Gen. and Systemic Pathology Course Description & Lab. Manual Vol. 2 (AY 2021-2022) - Protected43

ANGELES UNIVERSITY FOUNDATION
SCHOOL OF MEDICINE
Department of Pathology
GENERAL AND SYSTEMIC PATHOLOGY

COURSE DESCRIPTION
AND
LABORATORY MANUAL
Volume II
Academic Year 2021-2022
This Manual Belongs to KAMODIA DRASHTI

SAMIR
PATHOLOGY LABORATORY E-MANUAL
THE AUTHORS:
GONZALO B. ROMAN, JR., MD, FPSP

RICARDO E. ECLARIN, MD, FPSP
KATHRYNA LESLEY A. TAMAYO-AYRO, MD, FPSP
EMIL BRYAN M. GARCIA, MD, FPSP
VANESSA GRACE M. DE VILLA-ATIENZA, MD, DPSP
PIERRE GIVENCHY G. LAYSON, MD, DPSP
ELIZABETH JEREMMIE L. REYES-URSUA, MD, DPSP
TERENCE L MANUEL, MD, DPSP
JOED T. TICSE, MD, DPSP
OLIVIA VICTORIA M. CALAGUAS-BONDOC, MD
MEDICAL TECHNOLOGIST:
LOU GRACE T. MANALILI, RMT, DVM
ANGELES UNIVERSITY FOUNDATION | SCHOOL OF MEDICINE | DEPARTMENT OF PATHOLOGY II

This is provided only for educational purposes to facilitate virtual learning
discussions in lieu of traditional laboratory sessions.

No part of this e-manual may be shared,
reproduced in any form, or stored in any
retrieval system without prior written permission
from the AUF-SOM Department of Pathology.
TABLE OF CONTENTS
Page No.
TOPIC TOPIC Page No.
ANGELES UNIVERSITY FOUNDATION | SCHOOL OF MEDICINE | DEPARTMENT OF PATHOLOGY III

I. I. Respiratory PathologyPulmunary Pathology .................. 1

............................................................
Hematopathology
. Hematopathology
II. II ................................................................................... 20
Gastrointestinal Pathology
III.
III. Gastrointestinal Pathology ..................................................................... 39
IV. Liver Pathology
IV. Biliary Tract Pathology ............................................................................. 62
V. Biliary Pathology
V. Liver Pathology ........................................................................................ 67

VI. Dermatopathology
VII.VI. Dermatopathology ................................................................................. 76

Renal Pathology
VIII.VII. Endocrine PathologyEndocrine Pathology .................. 87

............................................................
IX. VIII. Bone and Joint PathologyRenal .................. 96

Pathology ....................................................................
Soft Tissue Pathology

X. IX. Male Reproductive Pathology
............................................................... 104
Male Reproductive Pathology

XI.
X. Bone and Joint Pathology ...................................................................... 111
XII. Breast Pathology

XI. Breast Pathology ...................................................................................... 115
XIII. Female Reproductive Pathology
XII. Head and Neck Pathology .................................................................... 137

XIV. Head and Neck Pathology
ANGELES UNIVERSITY FOUNDATION | SCHOOL OF MEDICINE | DEPARTMENT OF PATHOLOGY IV

XV. XIII. Female Reproductive Pathology .......................................................... 145

Neuropathology
XIV. Neuropathology ...................................................................................... 158
INTRODUCTION: The Discipline of Pathology
What is PATHOLOGY?
P athology is the study of how the organs and tissues of a healthy body change to
those of a sick person. It provides an understanding of the disease processes
encountered, their causes, and their clinical effects. In this way, pathology
constitutes a logical and scientific basis of medicine.
There are two general divisions of Pathology.

In General Pathology, we study cell adaptations, necrosis, neoplasia, inflammation,
vascular, fluid and clotting derangements, and immunologic disease at the cellular and tissue
levels. This will comprise most of the topics in the first semester.
In Systemic Pathology, we study these phenomena at the organ-system

level.
In both General and Systemic Pathology, we emphasize understanding etiology,
pathogenesis, and tissue changes primarily in terms of basic science (e.g., anatomy, biochemistry,
physiology and molecular biology).
In Clinical Medicine, you will understand further how disease affects humans as living
beings, with social and psychological consequences of illness.
In the hospital environment, the term pathology is used in a narrower sense to denote that
specialty of medicine concerned with the performance and interpretation of laboratory
procedures. It is also divided into:
(1) Clinical Pathology – is concerned with biochemical and microbiologic procedures

performed on blood, tissue fluids or other substances secreted or excreted by the body, such
as sputum, urine, and cerebrospinal fluid. The hospital clinical pathology laboratory is further
subdivided into many sections – clinical chemistry, microbiology, immunology, serology,
clinical microscopy, hematology and coagulation, and blood banking – to perform the many
specific kinds of procedures. The results of these laboratory procedures, when used in
conjunction with the clinical evaluation of the patient, facilitate diagnosis of specific disease.
(2) Anatomic Pathology – is a separate section – called histopathology. It considers structural

abnormalities of cells and tissues that can be detected by gross and microscopic examination
ANGELES UNIVERSITY FOUNDATION | SCHOOL OF MEDICINE | DEPARTMENT OF PATHOLOGY V

of tissues removed from the patient. In a hospital it is further subdivided into: surgical
pathology, cytology, hematopathology, and autopsy/forensic pathology.
The AUF-SOM Department of Pathology
GOALS:
1) To develop an understanding of the causes and mechanisms of disease and the associated
alterations of structure and function.
2) To develop skills of observation, interpretation, and integration needed to analyze human
disease. When provided with the clinical history, the anatomical lesions, and the
laboratory data of a patient, the students are expected to determine the most likely
diagnosis and explain the pathogenesis of the disease.
REQUIRED TEXTBOOK:
Robbins and Cotran Pathologic Basis of Disease – Kumar, Abbas, Aster; Elsevier Saunders,
latest edition.
Note: This is the official textbook and the reference used in our examinations. If there are any
questions, inquiries or doubts regarding certain topics, this textbook will serve as the final arbiter.
Other Helpful Textbooks:

1. Henry, J.B. Clinical Diagnosis and Management by Laboratory Methods. W.B.
Saunders, latest edition.
2. Rubin E and JL Farber, Pathology, Lippincott-Raven, latest edition.
3. Carol Mattson Porth, Pathophysiology: Concepts of Altered Health States,
Lippincott, latest edition.
ANGELES UNIVERSITY FOUNDATION | SCHOOL OF MEDICINE | DEPARTMENT OF PATHOLOGY VI

CHAPTER
ANGELES UNIVERSITY FOUNDATION | SCHOOL OF MEDICINE | DEPARTMENT OF PATHOLOGY 1

PULMONARY
PATHOLOGY

PULMONARY PATHOLOGY
LEARNING OBJECTIVES (Pulmonary Vascular Diseases)

At the end of the module, the student should be able to:
1. Organize and discuss features of pulmonary embolism in terms of clinical presentation,

associated conditions and predisposing factors, pathogenesis, gross and physiology,
complications, and clinical course-prognosis.
2. Compare pulmonary embolism caused thrombus, fat, air, bone marrow, amniotic fluid and talc in
terms of predisposing factors, incidence, and clinical course.
3. Organize and discuss features of secondary pulmonary hypertension in terms of clinical
presentations, predisposing conditions, pathogenesis, gross and microscopic morphology,
(including Heart-Edwards’s grading) effects of pulmonary vasculature and pulmonary
physiology, and clinical course-prognosis.
4. Compare the following disorders of pulmonary circulation:
a. primary pulmonary hypertension,
b. secondary pulmonary hypertension, and
c. pulmonary emboli and infarction on the basis of:
i. size and type of vessel involved
ii. laboratory and radiographic findings,
iii. predisposing diseases, and iv. clinical course-prognosis
5. Organize and discuss features of pulmonary edema and pulmonary congestion in terms of
etiologies, pathogenesis-mechanisms, and morphology.
LEARNING OBJECTIVES (Pulmonary Infections)
1. Define and use in context upper and lower respiratory tract infections. Compare
bronchopneumonia, lobar pneumonia and interstitial pneumonia with regards to predisposing
factors, pathogenesis, etiology, gross and microscopic morphology, clinical manifestation,
prognosis and treatment.
2. Organize and discuss community acquired acute pneumonias, community acquired atypical
pneumonias in the context of epidemiology, etiologic agents, predisposing factors, clinical
manifestation, complications, and prognosis.
3. Organize and discuss pulmonary tuberculosis in the context of classifications of types,
pathogenesis, gross and microscopic morphology, clinical course and complications.
4. Define and use in context lung abscess, nosocomial, aspiration and chronic pneumonias regarding
predisposing factors, pathogenesis, etiology, clinical manifestation, complications, and prognosis.

LEARNING OBJECTIVES (Tumors of the Lung)
1. Outline and discuss the etiology and pathogenesis of the lung carcinoma in terms of predisposing
factors and epidemiologic factors.
2. Organize and discuss the classification of lung tumors based on histologic types, clinical
presentation, histologic types, and clinical course prognosis.
3. Compare central and peripheral neoplasms of the lung in terms of clinical presentation,
radiographic presentation, histologic types, and clinical course prognosis.
4. Compare the following pulmonary tumors: a). Squamous cell carcinoma, b) adenocarcinoma, c).
small cell undifferentiated carcinoma, d). large cell carcinoma, e). bronchioloalveolar carcinoma
in terms of clinical presentation, incidence, predisposing factors, age-sex location of tumor, gross
and microscopic morphology, and clinical course.
5. Organize and discuss general features of bronchial carcinoid tumors, hamartomas, and metastatic
tumors regarding clinical presentation, morphology and clinical course.
6. Organize and discuss effects of the lung tumor spread, hormonal manifestations and
extrapulmonary manifestations of carcinoma of the lung.
7. Organize and apply TNM staging system of lung carcinoma in determining the prognosis of a
tumor.
LEARNING OBJECTIVES (Obstructive Pulmonary Disease)
1. Define and use in context atelectasis. Compare resorption atelectasis, compression atelectasis,
microatelectasis, and contraction atelectasis about predisposing factors, pathogenesis, and
etiology.
2. Organize and discuss the major types of obstructive pulmonary disease and the basic etiology of
obstructive pulmonary disease. Compare and discuss the etiologies and effects of airflow
obstruction that occur in lesions involving the larynx, major bronchi, bronchioles, alveoli and
alveolar septae.
3. Organize and discuss asthma in the context of classification of types, pathogenesis, gross and
microscopic morphology, and clinical course.
4. Compare and contrast non-atopic asthma and in the context of pathogenesis.
5. Compare and discuss panacinar(panlobular) emphysema, centricianar (centrolobular)emphysema
and distal acinar (paraseptal) emphysema in the context of definition, clinical presentation
including age and sex distribution, incidence, etiology, pathogenesis, gross and microscopic
morphology, physiologic changes, and clinical course-prognosis.

6. Define and use in context compensatory hyperinflation, senile hyperinflation, obstructive over
inflation, interstitial emphysema, bullous emphysema.
7. Organize and discuss features of different forms of bronchitis including definition, and clinical
course.
8. Organize and discuss chronic bronchitis regarding the morphologic basis of airway obstruction,
predisposing conditions, pathogenesis, gross and microscopic morphology, and clinical
presentation.
9. Define the Reid Index and discuss what constitutes a normal index and an index diagnostic of
chronic bronchitis.
10. Organize and discuss bronchiectasis in relation to definitions, predisposing conditions,
pathogenesis, organisms typically culture from bronchi, gross and microscopic morphology, and
clinical course-prognosis.
11. Compare and contrast chronic bronchitis and bronchiectasis on the basis of etiology,
pathogenesis, gross and microscopic morphology and clinical course.
12. Organize and discuss respiratory bronchiolitis of smokers (small airways disease) in terms of
pathogenesis, morphology, and clinical presentation.
13. Organize and discuss bronchiolitis obliterans in terms of etiology and morphology. Be able to
discuss the relationship of silo-filler’s disease to bronchiolitis obliterans.
14. Organize and discuss the pulmonary features of cystic fibrosis in terms of pulmonary
morphology, pulmonary pathogenesis, and pulmonary complications, including obstructive
changes and different infections and organisms.
LEARNING OBJECTIVES (Restrictive Pulmonary Disease)
1. Organize and discuss the basic classification of restrictive lung disease and general features in
terms of clinical presentation and pathogenesis.
2. Organize and discuss features of adult respiratory distress syndrome (diffuse alveolar damage) in
terms of clinical presentation, associated conditions, pathogenesis, gross and microscopic
morphology, complications, and clinical course.
3. Compare and discuss neonatal and adult type acute respiratory distress syndrome based on
predisposing factors, pathogenesis, morphology, complications, and clinical course.
4. Organize and discuss the major categories of chronic interstitial lung disease in terms of clinical
presentation and etiology.
5. Organize and discuss the features of idiopathic pulmonary fibrosis in terms of clinical
presentation, etiology, morphology, complications, and clinical course.
6. Organize and discuss the features of desquamative interstitial pneumonitis in terms of clinical

7. Organize and discuss features of sarcoidosis in terms of clinical presentation, etiology,

pathogenesis, morphology (lung, lymph nodes, skin, eyes, salivary gland, spleen, and liver),
complications, and clinical course-prognosis.
8. Organize and discuss features of lymphocytic interstitial pneumonia (LIP) in children and adults
in terms of clinical presentation, morphology, and clinical course.
9. Organize and discuss the features of desquamative interstitial pneumonitis in terms of clinical
10. Organize and discuss the features of hypersensitivity syndrome in terms of etiology, clinical
presentation, morphology, and clinical course. List etiologies of the following-Farmer’s lung,
Pigeon breeder’s lung, air conditioner lung, bagassosis and byssinosis.
11. Organize and discuss the features of PIE syndromes (pulmonary infiltrates with eosinophilia) in
terms of classifications, etiology and morphology. Describe the radiographic finding of Loffler
syndrome and clinical presentation of chronic eosinophilic pneumonia.
12. Organize and discuss features of bronchiolitis obliterans-organizing pneumonia in terms of
etiology and morphology.
13. Organize and compare features of the diffuse pulmonary hemorrhage syndromes (Goodpasture’s
syndrome, idiopathic pulmonary hemosiderosis, and Wagener’s Granulomatosis) in terms of the
clinical presentation, pathogenesis, morphology, and clinical course.
14. Compare features of idiopathic pulmonary hemosiderosis with Goodpasture’s syndrome in terms
of clinical presentation, pathogenesis and morphology.
15. Organize and discuss pulmonary alveolar proteinosis in terms of clinical presentation,
pathogenesis, associated conditions, and morphology.
16. List pulmonary manifestations in various systemic collagen vascular disorders, adverse
pulmonary therapeutic drug reactions, acute radiation, and chronic radiations.
17. Organize and discuss features of eosinophilic granuloma of lung in terms of clinical presentations
and morphology.
LEARNING OBJECTIVES (Pneumoconiosis)
1. Define and discuss the basic pathogenesis of pneumoconiosis.

2. Organize and discuss the common pneumoconiosis in terms of etiology, basic morphologic
pulmonary reactions, and common complications.
3. Organize and discuss features of coal workers pneumoconiosis in terms of occupational exposure,
pathogenesis, gross and microscopic morphology, complications, and clinical course. Compare
coal worker’s pneumoconiosis with simple or asymptomatic anthracosis. Define and discuss
Caplan’s syndrome in relation to coal workers pneumoconiosis, asbestosis, and silicosis.

4. Organize and discuss features of silicosis in terms of occupational exposure, pathogenesis, gross
and microscopic morphology, complications, and clinical course. Give examples of different
forms of silica and differentiate between silicoproteinosis and classic nodular silicosis.
5. Organize and discuss features of asbestosis-related diseases and asbestosis in terms of
occupational exposure, categories of asbestosis fibers, pathogenesis, gross and microscopic
morphology, complications, and clinical course.
6. Organize and discuss features of berylliosis in terms of occupational exposure, pathogenesis,
gross and microscopic morphology, complications, and clinical course.
7. Compare and contrast coal workers pneumoconiosis, silicosis, asbestosis and berylliosis in terms
of microscopic morphology, complications and disease processes the patients are predisposed to.
8. Define and use in context the following rare types of occupational lung diseases, such as farmer’s
lung, bagassosis, byssinosis, bird fancier’s lung and silicofancier’s disease.
LEARNING OBJECTIVES (Mediastinum and Pleura)
1. Organize and discuss different types of mediastinal tumors based on location in the anterior
mediastinum, superior mediastinum, posterior mediastinum, and middle mediastinum.
2. Compare thymoma, malignant thymoma and thymic carcinoma in terms of clinical presentation,
morphology, clinical course, and associated conditions and syndromes.
3. Define and list likely etiologies and expected effects on pulmonary function of the following: a).
hydrothorax, b). empyema, c). hemothorax, d). chylothorax, e). Tension pneumothorax, f).
Pleural adhesion, g). interstitial emphysema, h). Solitary fibrous tumor, and I). blebs.
4. Organize and discuss pleural fluid collections based on fluid type and common associations.
Organize and discuss appropriate diagnostic procedures for patients clinically suspected of having
pleural effusions.
5. Organize and discuss general features of malignant mesothelioma in terms of clinical
presentations, etiology, morphology, and clinical course-prognosis.
Case 1: Chronic Passive Congestion, Lung
History: A 50-year-old widower, jobless, had a history of easy fatigability for four

months prior to admission and later developed difficulty to breathing,

three- pillow orthpnea and bipedal edema. ECG and X-ray of chest show
enlargement of the left ventricular shadow. The patient died because of
digitoxin toxicity and an autopsy was done.
Gross: Both lungs are heavy, weighing 50 grams each. The lungs are boggy,
non-crepitant. There is oozing of frothy fluid on cut sections. Even the
bronchi and brochioles contain frothy fluid.
Microscopic: Sections show presence of pinkish granular material within the alveolar spaces.
Alveolar capillaries are engorged. Hemosiderin-laden macrophages called “heart
failure cells” are present. There is also mild fibrosis and thickening of the alveolar walls.
Draw and Label:

STUDY QUESTION:
1. What are heart failure cells? What is their clinical significance?
Heart Failure cells are also known as Hemosiderin-laden macrophages. These are
brown granules of hemosiderin from breakdown of RBCs which appear in the
macrophage cytoplasm. These macrophages are sometimes called "heart failure
cells" because of their association with pulmonary congestion with congestive heart
failure.

Case 2: Pulmonary Infarct
History: A 69-year-old obese female with history of deep vein varicosities

developed easy fatigability, chest pain and difficulty of breathing few
hours after a foot and leg massage from an ordinary spa.
Draw and Label:
The white arrows point to red

infarcts which are seen on
both sides of the lung

The red arrow points to

thromboembolic that is
occluding a pulmonary vessel

STUDY QUESTION:
1. What type of infarct is present? Give bases for your answer.
Red infarct is present
Due to:
• Blockade of pulmonary artery by small-medium sized thromboembolus that
is dislodged from the lower extremities during the massage and causes a
pulmonary infarct in which the patient manifests with chest pain, dyspnea
and easy fatigability
• This type of infarct is usually seen in loose spongy tissues like the lungs
where blood can collect in the infarcted zone
• Tissues with dual circulations that allow blood to flow from an unobstructed
parallel supply into a necrotic zone
Case 3: Bronchopneumonia with abscess
History: A 7-year-old female child had history of measles and later developed productive cough, high
grade fever with respiratory difficulty. The sputum is characterized initially as greenish
and mucoid and later became foul smelling, purulent to sanguinous. Chest X-ray showed
a cavitary lesion on the lower lobe. There was extension of the abscess to different parts
of the body, as evidenced by the autopsy.
Gross: The left is heavy, with grayish-white thickened pleura. On sections of the
upper lobe, there is a large mass measuring 4 cm. in greatest diameter containing yellow
viscid fluid. The neighboring parenchyma is compressed and atelectatic.
Microscopic: The area between the lung parenchyma and exudates shows numerous congested blood
vessels. The lung shows compression of the alveolar spaces. Within the alveolar spaces
are some large cells with brownish thickened with scattered black pigments. These are
macrophages with hemosiderin. Some alveolar septa are thickened with scattered black
pigments. There is a large focus of suppurative destruction of the lung parenchyma

within the central area of cavitation. This is pyogenic lung abscess that usually occurs
close in, or in contact to pleura. The abscess begins as a focus of inflammation followed
in time by central necrosis. At first, the enclosing wall is poorly defined, but with time
and progressive fibrosis, it becomes more discrete. The blood vessels around this lesion
are numerous and dilated.
Draw and Label
Lung with bronchopneumonia

showing patches of
consolidation

STUDY QUESTIONS:
1. Enumerate some of the pulmonary defense mechanisms.
 Filtration of the nasal cavity
 Mucociliary blanket
 Alveolar macrophages
2. Briefly discuss the pathogenesis of pulmonary infections.
Pulmonary infections happen when the host's local defense mechanisms fail or
when the host's systemic resistance is compromised. Loss or suppression of the
cough reflex as a result of anesthesia, neuromuscular disorders, etc.; mucociliary
apparatus dysfunction as a result of smoking, inhalation of toxic substances, and
even genetics; secretion accumulation as a result of pulmonary obstruction and
cystic fibrosis; interference with alveolar macrophage phagocytic and bactericidal
activities; and pulmonary congestion and edema are some other factors that affect
local defense mechanisms.
Inherited immunity defects and humoral immunodeficiency also increase the risk of
pulmonary infections. Germline mutations in MyD88, an adaptor for several Toll-

like receptors that is required for the activation of the transcription factor nuclear
factor kappa B, may also play a role.

Increased infections with intracellular microorganisms such as Mycobacterium and
Herpesviridae may result from cell-mediated immune defects, both congenital and
acquired.

3. Give example of microorganisms implicated in community acquired pneumonias.

Community-Acquired Bacterial Pneumonias
• Streptococcus pneumoniae
• Haemophilus influenzae
• Moraxella catarrhalis
• Staphylococcus aureus
• Klebsiella pneumoniae
• Legionella pneumophila
Community Acquired Viral Pneumonia

• Influenza virus
• Respiratory syncytial virus
• Human metapneumovirus
• Adenovirus
Case 4: Miliary Tuberculosis, Lung and liver
History: A 3-year-old child had on and off afternoon fever for many weeks without consultation.
One day prior to admission, she had convulsion with rigidity of neck and extremities. The
doctor’s impression was tuberculosis meningitis. She was placed under triple anti-Koch’s
therapy but nevertheless died.

Gross: The lung is slightly heavier than normal. The pleura is glistening and smooth. On sections,
there are small, hard lesions dispersed all over.
Microscopic: You can appreciate here very well the honey-comb appearance of the pulmonary
parenchyma. Dispersed are the so called tubercles. These tubercles are also known as
granuloma formations. Characteristics granulomas composed of phagocytic and
epithelioid cells surrounded by a zone of fibroblasts and lymphocytes are present. They
contain one or
more characteristics giant cells of Langhan’s type which are really large ones with
pinkish cytoplasm and numerous nuclei usually present in the center of the tubercle, the
amount being entirely dependent upon the sensitization of the patient and the virulence of
the organism.
Draw and Label


STUDY QUESTIONS:
1. Aside from tuberculous infection, what are other diseases that usually present as granulomatous
type of inflammation?
• Leprosy
• Syphilis
• Cat-scratch disease
• Histoplasmosis
• Blastomycosis
• Cryptococcosis
• Sarcoidosis
• Crohn’s Disease
2. What is military tuberculosis?
Miliary tuberculosis is a potentially fatal form of the disseminated disease due to

the hematogenous spread of tubercle bacilli to the lungs, and other organs. It
results in the formation of numerous, minute, yellow-white lesions (resembling
millet seeds) in distant organs. Miliary tuberculosis is most prominent in the liver,
bone marrow, spleen, adrenals, meninges, kidneys, fallopian tubes, and epididymis,
but could involve any organ.
Case 5: Adenocarcinoma, (Lung)
History: 55-year-old non-smoker developed chronic hacking cough nonproductive of sputum, with
weight loss and history of previous pulmonary infarct.
Gross: Lungs were heavy and weigh 680 grams each with multiple nodularities, both near the
trachea and near the pleura and measuring up to 3.5 cm in diameter. Cut sections show
grayish white solid surface.

Microscopic: Section shows cellular mass near tracheal region with malignant cells arrange in glandular
formation.
Draw and Label

STUDY QUESTIONS:
1. Enumerate some of the clinical and morphologic features of this tumor.
Adenocarcinomas are distinguished by tumor cell mucin production or glandular
differentiation. Acinar, lepidic, papillary, micropapillary, and solid are the various
growth patterns seen in adenocarcinomas. These tumors are smaller than squamous
cell cancers and are usually found on the periphery.
2 Types differentiated by morhphology:
• Adenocarcinoma microinvasive
o Tumor cells "crawl" along normal-appearing alveolar septa in a "lepidic"
pattern of spread.
o Has a minor invasive component that is linked to scarring
o Has better prognosis when compared to other invasive carcinomas of the
same size
• Adenocarcinomas with mucinous adenocarcinomas

o Spreads aerogenously which forms satellite tumors
o Surgery is less likely to cure these types of adenocarcinomas
o It can appear as a single nodule, multiple nodules, or a tumor that has
consolidated an entire lobe, mimicking lobar pneumonia.
Case 6: Small Cell Carcinima, (Lung)

History: 50-year-old male, executive with history of cigarette smoking (50 pack years), with
weight loss and Cushingoid features.
Gross: Right and left lung weigh 550 and 750 grams, respectively. The left is non-
crepitant with multiple nodularities at the hilum.
Microscopic: Sections shows small cells arranged in nest and ribbons filling up the alveolar space and
invading the stroma.
Draw and Label


STUDY QUESTIONS:
1. Enumerate paraneoplastic syndromes usually associated with small cell carcinomas and non-
small cell carcinomas:
Paraneoplastic syndromes associated with small cell carcinomas:
• Cushing Syndrome
• SIADH
Other paraneoplastic syndromes associated with non-small cell carcinoma
• Hypercalcemia
2. Why is there a need to classify lung carcinomas at least to non-small cell and small cell
carcinomas?
The correct classification of lung carcinomas as non-small cell or small cell carcinomas
is critical because it determines the patient's expected disease course, appropriate
treatment, and prognosis. Small cell carcinomas are the most aggressive lung tumors,
with the greatest potential for metastasis and a high likelihood of death.

Case 7: Squamous Cell Carcinoma
History: A 60-year-old male patient came in because of dyspnea that was noted
3 months prior to consultation. This was accompanied by loss of weight
and frequent productive cough. Physical examination revealed a
cachectic patient with respiratory distress. Chest X-ray revealed a
centrally located lung mass accompanied by pleural effusion in the right.
Gross: Both lungs are heavy and congested. Multiple nodulations are seen on the right lung.
Microscopic: Micro sections show groups of malignant squamous cells infiltrating the surrounding area.
Draw and Label


STUDY QUESTIONS:
1. Where is the usual location of this tumor type?
At the conducting zones or central parts of the lung (e.g., Right or Left bronchus)
2. This tumor is commonly seen in associated with what environmental hazard?

Tobacco exposure
3. What is the sex predilection of this tumor?
It is more common in males
Case 8: Adult Respiratory Distress Syndrome
History: A 45-year-old male jeepney driver survived a vehicular accident. He was

unconscious and confined at the ICU. In his stay at the ICU, he developed
worsening signs of respiratory failure. A chest X ray on the third day
revealed a complete “white out” of both of the lungs. Laboratory
evaluation showed severe hypoxemia. The patient deteriorated and died.
Gross: Autopsy findings show heavy lungs weighing 600 grams each. On cut
section there are signs of edema and congestion.
Microscopic: Sections disclose pulmonary edema and alveolar spaces partially covered with
eosinophillic material. Evidence of congestion and interstitial inflammation are also present.
Draw and Label

STUDY QUESTION:
1. Discuss briefly the pathophysiology of the above condition using a diagram.


Microscopic: Sections disclose collapsed pulmonary alveoli.
Draw and Label

Case 9: Atelectasis
History: This is a case of premature infant who suffered pulmonary distress few
minutes after delivery and died.
Gross: Autopsy findings show solid rubbery lungs.

STUDY QUESTIONS:
1. Define Atelectasis.
It is the collapse of a previously inflated lung which results to poorly aerated areas in the
pulmonary parenchyma
2. Enumerate and describe the different types of atelectasis.

Resorption atelectasis
• There is obstruction of an airway which is usually caused by excessive secretions

or exudates within small bronchi
• Mediastinum shifts toward the atelectatic lung
Compression atelectasis
• Significant volumes of fluids, tumor, or air accumulate within the pleural cavity
• Mediastinum shifts away from the atelectatic lung
Contraction atelectasis
• Focal or generalized pulmonary or pleural fibrosis prevents full lung expansion
Case 10: Anthracosis
History: A 45-year-old male driver died because of heart attack. The patient has

been lying in the City of Angeles since birth with a part time work in a
cement factory.
Gross: The lungs are heavy weighing 600 grams each. On cut sections there is
oozing of frothy fluid from the bronchial cut section. Incidental finding is
diffusely scattered blackish pigments.
Microscopic: The blacken pigments are seen mostly in alveolar septa engulfed by the
macrophages that contain this pigment in their cytoplasm.
Draw and Label
STUDY QUESTIONS:

1. Enumerate and give a brief description of the pathogenetic principles involved in

pneumoconiosis.
• Particle size
o Particles that are 1-5um in diameter are able to reach and deposit
on terminal airways and air sacs
• Tobacco smoking
o Worsens the effect of inhaled mineral dusts
• Activation of Inflammasome
o Activation results in the increased intensity and duration of local
response
• Particle uptake by epithelial cells

o Allows direct interactions with interstitial macrophages and
fibroblasts
• Particle solubility and cytotoxicity

o Small particles usually produce rapid onset acute inflammation.
While large particles resist dissolution and can remain within the ling
parenchyma for years
• Dust retention
o Impaired mucociliary clearance results in increased accumulation
of dust in the lungs
2. What is the role of asbestos in the development of pulmonary diseases? Enumerate asbestos-
related pulmonary diseases.
• Asbestos is a group of crystalline hydrated silicates that have been linked to

pulmonary fibrosis and cancer in various forms.
• Asbestos is both a tumor promoter and a tumor initiator.
• Asbestos fibers produce reactive free radicals, which preferentially reside in the
distal lung, near the pleura's mesothelial cells, which mediate some of the
cancerous effects.
• Asbestos fibers activate the inflammasome and stimulate the release of

proinflammatory factors and fibrogenic mediators once they have been

phagocytosed by macrophages.
Asbestos-related pulmonary diseases:
• Carcinoma of the lung (in smokers)
• Benign pleural effusions
• Asbestosis
• Parietal pleural plaques
• Diffuse pleural fibrosis
Microscopic: Sections show granulomas occupying the parietal pleura with focal caseation necrosis.
Draw and Label

Case 11: Chronic Granulomatous Inflammation, Pleura
History: A 52-year-old female with history of breast carcinoma and underwent

series of chemotherapy developed difficulty of breathing. CXR revealed
pleural effusion. Biopsy of the parietal pleura is done during tube
thoracostomy.
Case 12: Metastatic Carcinoma, Pleura, Demo Slide
History: A 70-year-old female with history of breast carcinoma 5 years ago suddenly complained
of easy fatigability and difficulty of breathing. CXR revealed pleural effusion. Biopsy
of the parietal pleura was done during tube thoracostomy.
Microscopic: Sections show neoplastic cells with a demoplastic stroma. The cells are polygonal with
attempts at glandular formation.
STUDY QUESTIONS:
1. Enumerate the different pathogenetic mechanisms of pleural effusions.
• Increased vascular permeability

• External penetrating wound that introduces pyogenic organisms into pleural
space
• Increased intrapleural negative pressure
2. Describe malignant mesothelioma including clinical and characteristic pathologic features.
• It is a diffuse pleural lesion that originates in the visceral or parietal pleura and
spreads throughout the pleural space, causing pleural effusion and thoracic
structures to invade directly. Asbestos bodies are found in greater numbers in a
patient's lung with mesothelioma, which is linked to a high level of asbestos
exposure.
• The lung is directly invaded, and metastatic spread to the hilar lymph nodes,
then to the liver and other distant organs, is common.

• Chest pain, dyspnea, and recurrent pleural effusions are all signs and
symptoms of malignant mesothelioma. Concurrent pulmonary asbestosis (fibrosis)
is present in a small percentage of cases.
3. Enumerate the usual tumors located in the different parts of the mediastinum.
• Anterior Mediastinum
o Lymphoma
o Thyroid lesions
o Thymoma
o Teratoma
o Parathyroid tumors
o Metastatic carcinoma
• Posterior Mediastinum
o Lymphoma
o Metastatic tumor
o Schwannoma
o Neurofibroma
• Middle Mediastinum
o Pericardial cyst
o Lymphoma
o Bronchogenic cyst

CHAPTER

HEMATOPATHOLOGY

HEMATOPATHOLOGY
Blood is probably the most versatile of all human body fluids. It delivers raw materials, oxygen
and nutrients to the millions of cells of the human body. The cells also empty their waste products into its
stream and then carry them to the kidneys and other organs of waste elimination. Blood also aids in
regulating water content, temperature and alkalinity of tissues. During a microbial assault, it serves as a
mechanized army, transporting white cells and antibodies to battle those infectious organisms. Quite
often, its factors or coagulation are called upon to help mend an abrasion, laceration or incision. All of
these, the blood accomplishes day in and day out, travelling through endless miles of arteries, capillaries
and veins.
The main organs of hematopoiesis are the bone marrow, liver, spleen, thymus and lymph nodes.
Most of the functions are shouldered by the bone marrow, but in period of stress, the liver, spleen, thymus
and lymph nodes may revert to their fetal function and show extramedullary hematopoiesis.
The specific gravity of whole blood ranges between 1.048 and 1.066 to 1.057 in males and 1.053
in females. The specific gravity of serum is 1.026 to 1.031. The pH of normal blood is 7.35 to 7.45 ( the
range compatible with life is 6.8 – 7.8).
The total volume of blood is approximately 30 ml/kg body weight. It composes of liquid plasma
in which are suspended erythrocytes (red blood cells), leukocytes (white blood cells) and thrombocytes
(platelets).
Total blood volume in terms of body weight is greater in males than in females, chiefly owing to
the higher red cell volume in male. The average values are 75.5 ml/kg. in males and 66.5 ml/kg in female
or a total of 5 to 6 liters or about 7 to 8% of body weight. Blood cells make up 45% by volume of whole
blood. Blood plasma which is composed of serum plus fibrinogen making up 55% of blood volume;
water makes 91 to 92% by weight of the plasma, and plasma protein 6 to 7 % by weight of plasma. The
plasma protein which are formed mainly in the liver, exert an osmotic pressure of 25 to 30 ml. of
mercury, are non-diffusible and important in regulating blood volume and the body’s fluid balance. The
plasma proteins are composed of:
(1) serum albumin (4%).
(2) serum globulin (2.7%).
alpha fraction – associated w/ the transport of bilirubin, lipids, & steroids beta fraction -
associated w/ the transport of iron & copper in plasma gamma fraction - associated with
the production of antibodies
(3) fibrinogen (0.3%) is the precursor of fibrin which forms the framework of blood
clot.

Also present in the plasma are regulatory and protective proteins, such as hormones, enzymes and
antibodies. Diffusible anabolic substances include inorganic material (0.9%) such as sodium chloride,
calcium, potassium, acid carbonate iodine, and iron. Also included in this category are nutritive organic
materials (such as amino acids, glucose, fats, cholesterol) all of which are foodstuffs in solution absorbed
from the gastrointestinal tract, plus respiratory gases (O 2 and CO2). Diffusible catabolic constituents
(such as urea, uric acid, xanthine, creatine, creatinine and ammonia) in plasma are products of tissue
activity that are transported from tissues to kidneys and skin for excretion.
LEARNING OBJECTIVES (Hematopoiesis)
1. Organize and discuss the stages of erythropoiesis in terms of morphology of each stage, stages in
which hemoglobin is produced, lifespan of reticulocytes and mature red blood cells, mechanisms
of degradation of senescent erythrocytes, and factors (vitamin, minerals, and hormones) which
influence erythropoiesis.
2. Define and use in context morphological terms used to describe abnormal red cell morphology
(see list of definitions).
3. Organize and discuss the stages of granulopoiesis in terms of morphology of each stage, time to
form and life span of mature granulocytes, basic functions of the different types of maturing
granulocytes and factors which influence granulopoiesis.
4. Define and use in context morphological terms used to describe abnormal granulocytic
morphology (see lists of definitions).
5. Organize and discuss the stages of development of lymphocytes, plasma cells and monocytes in
terms of morphology, life span of mature forms, functions of mature forms, and factors which
influence production.
6. Define and use in context morphological terms and to describe morphologic variants or abnormal
forms of lymphocytes and plasma cells.
7. Organize and discuss thrombocytopoiesis in terms of morphology of megakaryocytes, fate of
megakaryocytes, life span of platelets, factors which influence thrombocytopoiesis, and abnormal
morphologic forms of platelets and megakaryocytes.
8. Organize and discuss hematologic laboratory values that can be affected by an inflammatory
response in terms of effects on white blood cell counts, differential counts, red blood cell counts
(neutrophilia, lymphocytosis, monocytosis, eosinophilia basophilia, anemia, thrombocytosis), and
sedimentation rate.
LEARNING OBJECTIVES (Nutritional Anemia)

1. Organize and discuss features of iron deficiency anemia in terms of clinical presentation,
incidence, etiology and pathogenesis, marrow and peripheral blood morphology, laboratory
diagnostic criteria and clinical course.
2. Categorize and discuss features of megaloblastic anemias in terms of different etiologies,
pathogenesis, and bone-marrow-peripheral smear morphology.
3. Organize and discuss folate deficiency anemia in terms of associated risks, etiology,
pathogenesis, clinical presentation, laboratory diagnosis and clinical course.
4. Organize and discuss pernicious anemia in terms of associated risks, etiology, pathogenesis,
clinical presentation, laboratory diagnosis and clinical course.
5. Categorize and discuss laboratory test procedures used in the diagnosis of anemia. List normal
values and expected abnormal values of this laboratory test for the different types of anemia (i.e.
– iron deficiency, folic acid deficiency, megaloblastic anemia, anemia of chronic disease, and
aplastic anemia.
6. Compare and contrast anemia secondary to acute blood loss and chronic blood loss in terms of
etiology, pathophysiologic changes and clinicopathologic diagnosis.
7. Compare and discuss anemia of chronic disease, and aplastic anemia and in terms of definition,
associated risk-diseases, etiology, diagnosis, morphology, and clinical course.
8. Compare and differentiate iron deficiency anemia, megaloblastic anemia (folate and pernicious),
anemia of chronic disease, aplastic anemia, acute blood loss, and chronic blood loss, based on
clinicopathologic data.
LEARNING OBJECTIVES (Hemolytic Anemia)
1. Organize and discuss sickle cell anemia in terms of incidence, clinical features, etiology,
pathogenesis, morphology of bone marrow, peripheral smear and spleen, clinical presentation,
laboratory diagnosis and complications - clinical course.
2. Organize and discuss the thalassemia disorders in terms of genetics - molecular changes,
pathogenesis, clinical features, morphology of peripheral smear, spleen, liver, bone, and bone
marrow, laboratory diagnosis, and clinical coursecomplications.
3. Organize and discuss hereditary spherocytosis in terms of genetics, pathogenesis, clinical
presentation, morphology of peripheral smear and spleen, laboratory diagnosis and clinical
course-complications.
4. Compare and discuss G-6PD, paroxysmal nocturnal hemoglobinuria, mechanical hemolytic
anemia, and malaria in terms of clinical features, pathogenesis and laboratory diagnosis.

5. Compare and discuss warm and cold antibody immunohemolytic anemias in terms of etiology,
pathogenesis, associated risks-diseases, laboratory diagnosis and complications.
6. Categorize and discuss laboratory test procedures used in the diagnosis of hemolytic anemias.
List normal values and expected abnormal values of these laboratory test for the different types of
hemolytic anemias (sickle cell anemia, beta thalassemia, alpha thalassemia, G-6PD, PNH,
hereditary spherocytosis, immunohemolytic anemias, malaria, and hemolytic anemia secondary
to mechanical trauma.
7. Compare and discuss iron deficiency anemia, megaloblastic anemia, sickle cell anemia,
thalassemia, aplastic anemia, hereditary spherocytosis, and anemia of acute blood loss in terms of
etiology-pathogenesis, clinical manifestations and laboratory features. Be able to differentiate
these diseases based on clinicopathologic data.
LEARNING OBJECTIVES (White Blood Cell Disorder)
1. Organize, discuss and differentiate acute lymphoblastic and myelogenous leukemia in terms of
incidence, cytogenetics, morphology, clinical presentation, laboratory diagnosis and prognosis.
2. Describe the FAB (French-American-British) classification of acute myeloblastic leukemias
(MO-M7) in terms of class-nomenclature, incidence and general features of each type.
3. Organize, discuss and differentiate chronic lymphocytic and myeloid leukemia in terms of
incidence, clinical feature, genetics, associated conditions, morphology-peripheral blood and
bone-marrow, laboratory diagnosis and clinical course – prognosis.
4. Define and list the major etiologic influence and pathogenesis of the following terms -
leukopenia, leukemoid reaction, neutropenia (relative and absolute) lymphocytosis (absolute and
relative), left shift, atypical lymphocytes, eosinophilia, monocytosis, basophilia, and
leukoerythroblastic reaction.
5. Organize and discuss general features of myelodysplastic syndromes in terms of clinical
presentation, etiology, genetics, morphology of peripheral blood-bone marrow, laboratory
diagnosis & clinical course-prognosis.
6. Organize and differentiate the major types of myelodysplastic syndromes (FAB classification)
based on clinicopathologic data.
7. Define and classify the myeloproliferative disorders.
8. Organize and discuss the different myeloproliferative disorders in terms of incidence, clinical
presentation, genetics, pathogenesis, morphology-peripheral blood and bone marrow, laboratory
diagnosis and clinical course-prognosis.
9. Compare and discuss myeloid metaplasia with myelofibrosis and myelopathic anemia in terms of
predisposing factors, etiology and pathogenesis, laboratory diagnosis and clinical course.

10. Compare and discuss polycythemia vera, relative polycythemia, and secondary polycythemia in
terms of etiology, diagnosis, and clinical course-complications. Be able to differentiate these
processes from clinicopathologic data.
11. Organize and differentiate myeloproliferative disorder (CML, polycythemia vera, myeloid
metaplasia and essential thrombocythemia) from each other and corresponding acute leukemias
(AML, M6, M7) based on clinicopathologic data.
12. Categorize and discuss the different types of plasma cell dyscrasias in terms of definitions and
clinical presentation.
13. Organize and discuss multiple myeloma in terms of clinical presentation, etiology,
clinicopathologic diagnosis, clinical course with complications and prognosis.
14. Organize and discuss Waldenstrom macroglobulinemia in terms of clinical presentation,
morphology with immunophenotyping, associated conditions, complications, and clinical course-
prognosis.
15. Compare and discuss plasmacytoma, monoclonal gammopathy of uncertain significance (MGUS)
and heavy chain disease in terms of incidence, clinical presentation, clinicopathologic diagnosis,
and clinical course. Be able to differentiate these disease processes from each other and from
multiple myeloma based on clinicopathologic data.
16. Organize and discuss the different laboratory procedures used in the clinicopathologic diagnosis
of the different plasma cell dyscrasias. List benign and malignant etiologies of monoclonal
gammopathies.
LEARNING OBJECTIVES (Lymph Node Pathology)
1. Differentiate a reactive lymph node from a neoplastic process.

2. Enumerate and describe the different patterns of a reactive lymph node.
3. Organize and discuss the general features of non-Hodgkin’s lymphomas in terms of incidence,
immunophenotyping (T vs. B cells), morphologic patterns (diffuse vs. follicular), classification
and grading (Working Formulation), laboratory methods of diagnosis, clinical course-prognosis,
and likelihood of a leukemic phase.
4. Organize and discuss small lymphocytic lymphoma, follicular lymphoma, and diffuse large cell
lymphoma in terms of incidence associated risk-conditions, age and sex distribution, morphology
with immunophenotyping, clinical presentation, laboratory diagnosis and clinical course-
prognosis.
5. Organize and discuss lymphoblastic lymphoma, and Burkitt’s lymphoma (small noncleaved) in
terms of incidence-age/sex distribution, associated risks, morphology with immunophenotyping,
clinical presentation, laboratory diagnosis and clinical course-prognosis.
6. Organize and discuss Hodgkin’s Disease in terms of classification incidence of each type, clinical
presentation, etiology, pathogenesis, morphology of the four types, and laboratory diagnosis.

7. Define and discuss the staging of Non-Hodgkin’s lymphomas and Hodgkin’s lymphomas.
8. Compare and discuss clinical differences between Hodgkin’s and Non-Hodgkin’s lymphomas.
9. List benign and malignant etiologies of lymphadenopathy and splenomegaly.
10. Organize and discuss mantle cell lymphoma, MALToma, peripheral T-cell lymphoma, adult T-
cell lymphoma, and cutaneous T-cell lymphomas in terms of definitions and clinicopathologic
presentation.
LEARNING OBJECTIVES (Platelet and Coagulation)
1. Organize and discuss thrombocytopenia in terms of different mechanisms with differential

diagnosis, clinical features, bone marrow morphology and laboratory features.
2. Organize and discuss thrombocytosis in terms of diagnosis and differential diagnosis.
3. Organize and discuss inherited disorders of platelets secondary to surface membrane
abnormalities (Glanzmann’s thrombasthenia, chediak-Higashi syndrome, Bernard-Soulier’s
disease, and von Willebrand’s Disease) in terms of definition, genetics, and laboratory features
including platelet aggregation patterns. Be able to differentiate these disease processes based on
clinicopathologic data
4. Categorize and discuss acquired disorders of platelet function in terms of etiology and
pathogenesis.
5. Develop a systematic approach to the evaluation of a patient suspected to have a platelet disorder.
6. Organize and discuss idiopathic thrombocytopenic purpura (ITP) in terms of definition,
pathogenesis, clinical features, morphology, and clinicopathologic diagnosis.
7. Organize and discuss features of hemostasis in terms of the intrinsic pathway, extrinsic pathway,
the final common pathway, fibrin formation and fibrinolysis, protein C/protein S pathway, role of
platelets, the role of vascular integrity and factors which regulate hemostasis.
8. Organize and discuss the laboratory diagnostic procedures used to approach a patient with
bleeding disorders, a patient with thrombotic disorders.
9. Organize and discuss the different hemophilias in terms of different types, genetics, clinical
presentation, laboratory diagnosis, and clinical course.
10. Organize and discuss the von Willebrand disease in terms of different types, genetics, clinical
presentation, laboratory diagnosis, and clinical course.
11. Organize and discuss bleeding abnormalities secondary to vitamin K deficiency in terms of
etiologies, clinical presentation, pathogenesis, and laboratory diagnosis.
12. Organize and discuss coagulopathies seen in liver disease in terms of pathogenesis, laboratory
diagnosis, and clinical course.

13. Organize and discuss disseminated intravascular coagulopathy (DIC) in terms of etiologies,
clinical presentation, pathogenesis morphologic features, laboratory diagnosis, clinical course,
and complications.
14. Organize and discuss coagulopathies associated with systemic lupus erythematosus in terms of
clinical presentation, pathogenesis, laboratory diagnosis and clinical course.
15. Differentiate the following disease processes based on clinicopathologic data:
a). von Willebrand;s disease vs. hemophilia vs. ITP vs DIC
b). ITP vs. myeloproliferative processes vs. myelodysplastic processes vs. myelophthistic
anemia
c). liver disease coagulopathies vs. DIC vs. ITP vs. SLE coagulopathy
Case 1: Anisopoikilocytosis
Peripheral smear of a 62-year-old female patient with chronic renal disease and anemia.
Draw and Label:

STUDY QUESTION:
1. Describe the red cells in the peripheral smear. Give examples of conditions where you
can encounter this kind of smear.
• Here we can see a peripheral blood smear of red blood cells of different shapes and sizes. We can also
observe red blood cells with increased central pallor
• Conditions:
o Iron-deficiency anemia
o Hereditary spherocytosis
o Thalassemia
o Folate and vitamin B-12 deficiency
Case 2: Reticulocytes, New Methylene Blue Stain,
This smear was taken from a 7-year-old male with history of hemolytic anemia.
Draw and Label:

STUDY QUESTION:
1. What are reticulocytes? What is the clinical significance of an elevated reticulocyte count?
• Immature red blood cells produced in the bone marrow and released into the bloodstream in
the form of reticulocytes are erythrocytes that mature in a matter of days. An increase in
reticulocytes can be a sign of a bone marrow erythropoiesis defect or a response to clinical
conditions like hemolytic anemias and blood loss.
Case 3: Hypochromic Microcytic red cells,
This peripheral smear was taken from a 10-year-old male with history of anemia.
Draw and Label:

STUDY QUESTION:
1. Give the expected red cell indices usually seen in patient with this type of anemia (use
descriptive term rather than values).
RED CELL INDICES:

• MCV - Decreased MCV which results to Microcytic cells
• MCH - Decreased MCH
• MCHC - Decreased MCHC which results to Hypochromic cells
2. Give one clinical condition where you can encounter this type of red cells.
• Iron deficiency anemia

Case 4: Target Cells

This is a peripheral smear of a 7-year-old female with thalassemia.
Draw and Label:
STUDY QUESTIONS:
1. Name all RED CELL INCLUSIONS and give the clinical conditions where you encounter them:
• Cabot rings - present in megaloblastic anemia and myelofibrosis
• Pappenheimer bodies - seen post splenectomy and in lead poisoning
• Basophilic stippling - seen in hemoglobinopathies and heavy metal
poisoning
• HbH bodies - present on supravital staining in HbH disease such as alpha
thalassemia major.
• Howell-jolly bodies - asplenia

• Heinz bodies - present on supravital staining in oxidative hemolysis
Case 5: Acute Myelogenous Leukemia (AML)
History: A 25-year-old male was admitted because of complaints of profuse nose

bleeding with easy bruisibility of the extremities on slight trauma. Physical
examination showed ecchymosis on his arms and thighs. Spleen and liver
were not palpable.
Microscopic: Peripheral smear showed:

Myeloblasts - 80 %
Progranulocytes - 7%
Myelocytes - 10 %
Segmenters - 1%
Lymphocytes - 3%
STUDY QUESTION:
1. Enumerate at least three clinical features of acute leukemia and briefly describe the
pathophysiology.
 Bleeding from the gums.

 Bone pain.
 Fever.

Case 6: Chronic Monocytic Leukemia
History: A 70-year-old male, for the previous 10 days, had complained of

increasingly severe dizziness, shortness of breath and weakness.
Microscopic: Peripheral smear showed:

Monoblasts - 30%
Promonocytes - 10%
Monocytes - 30%
Segmenters - 20%
Lymphocytes - 10%
STUDY QUESTIONS:
1. Differentiate this type of leukemia from the myelogenous type.
CMML is different to chronic myeloid leukaemia (CML). CML affects the myeloid cells in the
blood and bone marrow, while CMML affects a specific myeloid cell called a monocyte, which
helps to fight infections.
2. In what organs do leukemic cells show striking changes?

lymph nodes, spleen, and brain.
3. Massive splenomegaly is usually associated with what types of leukemias?
Chronic myelogenous leukemia
Case 7: Chronic Lymphocytic Leukemia
Draw and Label:

STUDY QUESTION:
1. Differentiate this type of leukemia from its acute component.
AML and CML are blood and bone marrow cancers that affect the same lines of white
blood cells. AML comes on suddenly as very immature cells crowd out normal cells in
the bone marrow. CML comes on more slowly, with the CML cells growing out of
control.
Case 8: Leukocytosis with Shift to the Left
Draw and Label:

STUDY QUESTION:
1. Define leukemoid reaction. Differentiate it from leukemia.
Leukaemia is the cancer of blood or bone marrow. Leukemoid reaction is an
increase in the number of WBC that mimic leukmia and it is not a sign of
malignancy. In the leukemoid reaction, the neutrophils are mature and not clonally
derived.
Case 9: TB of the Lymph Node
History: 20-year-old female with anterior cervical lymphadenopathy. Excision

biopsy was done.
Gross: The lymph nodes are enlarged and measure 2 x 2.0 x 1.0 cm.
Microscopic: Section shows chronic granulomatous lesion with scattered Langhan's giant cells.
Draw and Label:

STUDY QUESTIONS:
1. Give the expected gross appearance of the lymph node.
Cheesy tan to white appearance

CHAPTER
GASTROINTESTINAL
PATHOLOGY

GASTROINTESTINAL TRACT
The digestive system is composed of several specialized organs and tissues whose collective functions are
the ingestion, digestion and absorption of nutrients and the disposal of associated wastes. It consists of a single
unbranched tube, which runs from the mouth to the anus, and several specialized glandular structures, which
produce the digestive fluids and deliver them to the alimentary canal via their own respective ducts.
The structure of the gastrointestinal tract follows a generally uniform plan throughout its length – mucosal
lining, submucosal, muscularis and serosa, with minimal variations (either absence of one layer or presence of
additional layer) in some specific parts.
The esophagus is lined by stratified squamous epithelium and its submucosa contains alveolar mucus
glands. At the junction of the esophagus where it joins the stomach, the lining epithelium changes abruptly to
columnar epithelium, which contains secretory cells such as chief cells – pepsin, parietal cells – hydrochloric acid
and mucous cells.
Absorption predominantly takes place in the mucosa of the small intestines. The mucosa is thrown into
minute fingerlike projections called villi. Each division of the small intestines has its own histologic peculiarities.
The duodenum contains submucosal tubuloalveolar glands, called Brunner’s glands; the jejunum has rounded villi;
and the ileum showed club-shaped villi and submucosal Payer’s patches.
The colon’s principal role is the absorption of water from digestive wastes and the production of mucus. It
contains goblet cells. It is divided into the cecum, ascending colon, transverse colon, descending colon, sigmoid
and the rectum and anus. The vermiform appendix appears as an extension from the cecum.
Material can be obtained from the digestive tract for cytologic or histologic studies as well as chemical
analysis of the gastric juices and glandular secretions. Exfoliative cytology studies can be performed in the mouth
by simple scraping of the buccal mucosa and from other parts of the gastrointestinal tract by washing or brushing or
both through fiberoptic instruments. Biopsy of mucosal lesions can also be done through this noninvasive
procedure. All tissues removed from the gastrointestinal tract must be submitted to the laboratory for pathological
studies.
The pathology of the gastrointestinal tract varies from congenital anomalies to inflammatory, infectious
and neoplastic process. This section of your manual will provide you an overview of the most common pathology
we encounter in clinical practice. A good correlation of what you see in the laboratory, both the microscopic
sections and the gross, with the possible clinical signs and symptoms will help you understand the disease process
as a whole.

LEARNING OBJECTIVES (Esophagus)
1. Define and discuss general features of hiatal hernia, Achalasia, Mallory-Weiss syndrome, and
varices in terms of clinical presentation, morphology, and clinical course.
2. Organize and discuss reflux esophagitis in terms of clinical presentation, etiologypathogenesis,
morphology, and clinical course.
3. Organize and discuss Barrett’s esophagus in terms of clinical presentation, etiology-pathogenesis,
morphology, and complication-clinical course.
4. Organize and discuss esophageal carcinoma in terms of clinical presentation, etiology, (risk
factors) pathogenic morphology, and prognosis-clinical course.
5. Compare squamous cell carcinoma and adenocarcinoma of the esophagus in terms of risk factors,
microscopic morphology, and clinical presentation.
6. Define and discuss esophageal stenosis, esophageal atresia, mucosal webs, and esophageal
diverticula in regard to clinical presentation and morphology.
LEARNING OBJECTIVES (Stomach)
1. Organize and discuss general features of congenital gastric anomalies (pyloric stenosis,
diaphragmatic hernia, and gastric heterotopia) in terms of incidence, clinical presentation, and
pathologic morphology.
2. Organize and discuss acute and chronic gastritis in terms of etiology, pathogenesis, morphology,
clinical presentation, and clinical course.
3. Organize and discuss peptic ulcers and stress ulcers in terms of etiologypathogenesis, clinical
presentation, pathologic morphology, and clinical course.
4. Organize and discuss general features of gastric polyp (hyperplastic polyp, fundic gland polyp
and adenomatous polyps) in terms of incidence, pathogenesis, and malignant potential.
5. Organize and discuss gastric carcinoma in terms of risk factors, epidemiology, pathogenesis,
tumor classification, gross and microscopic morphology, clinical presentation, and clinical
course prognosis.
6. Compare and discuss benign gastric ulcers and ulcerated gastric carcinomas in terms of age and
sex, location of lesion, gross and microscopic morphology, and clinical presentation. Be able to
differentiate these from clinicopathologic presentation.

7. Compare and discuss clinical presentation, morphologic features, and clinical course-prognosis of
the following: a). gastric lymphoma, b). gastric leiomyoma (gastrointestinal stromal tumor), and
c). gastric leiomyosarcoma.
LEARNING OBJECTIVES (Small and Large Intestines and Vermiform Appendix – Non
Neoplastic)
1. Organize and discuss inflammatory bowel disease (IBD) in terms of etiology and pathogenesis
(hereditary, infectious, immune dysfunction).
2. Organize and discuss Crohn’s Disease in terms of etiology, epidemiology, pathogenesis,
morphology, clinical presentation, clinical course, prognosis, and complications.
3. Organize and discuss ulcerative colitis in terms of etiology, epidemiology, pathogenesis,
morphology, clinical presentation, clinical course, prognosis, and complications.
4. Compare, contrast, and discuss ulcerative colitis and Crohn’s Disease in terms of clinical
presentation, pathogenesis, gross and microscopic morphology, and clinical course.
5. Compare, contrast, and discuss Crohn’s Disease of the small intestine and Crohn’s Disease of the
colon in terms of morphology and clinical features. Be able to differentiate the 2 diseases
clinicopathologically.
6. Organize and discuss features of Hirschsprung’s disease in terms of clinical presentation,
pathogenesis, morphology, and clinical course.
7. Organize and discuss infectious enterocolitis in terms of epidemiology, etiology (viral, bacterial,
mycobacterial, and fungal), clinical presentation, pathogenesis, morphology, and clinical course.
8. Compare and discuss viral, bacterial, and parasitic enterocolitis in terms of epidemiology,
pathogenesis, morphology, and clinical features.
9. Organize and discuss pseudomembranous colitis in terms of clinical presentation, etiology-
pathogenesis, morphology, diagnosis, and clinical course.
10. Differentiate the following infectious process when provided a typical case history or
epidemiologic case presentation: viral enterocolitis, staphylococcal enterocolitis, shigellosis,
salmonella enterocolitis, E. coli enterocolitis, cholera, typhoid fever, campylobacter enterocolitis,
yersinia enterocolitis, clostridium enterocolitis (difficile, botulinum and perfringens), tuberculous
enterocolitis and amebic enterocolitis.
11. Compare the pathogenesis and effects on stool formation of secretory diarrhea, osmotic diarrhea,
exudative enterocolitis, malabsorption and deranged motility.
12. Compare and discuss bacterial infection caused by preformed toxins, toxigenic organisms and
enteroinvasive organisms regarding type of organisms (genes and species) and pathogenesis.

13. Differentiate the following types of infection colitis/enteritis based on clinical data: Viral,
Staphylococcal, Salmonella, E. coli, Shigella, Campylobacter, and Clostridium difficile.
14. Organize and discuss general features of malabsorption syndromes in terms of basic
pathogenesis, major diseases that produce malabsorption, and clinical features.
15. Classify and discuss disease processes which produce malabsorption in terms of etiology-
pathogenesis (defective digestion, mucosal cell abnormalities, reduced mucosal surface,
lymphatic obstruction, infectious, and iatrogenic).
16. Organize and discuss celiac sprue in terms of clinical presentation, pathogenesis, morphology,
clinical course, diagnosis, and complications.
17. Organize and discuss tropical sprue in terms of etiology, epidemiology, morphology, and clinical
presentation, and associated conditions.
18. Organize and discuss Whipple Disease in terms of etiology, morphology, clinical presentation,
diagnosis, and clinical course.
19. Compare and discuss celiac sprue, tropical sprue, and Whipple’s Disease based on etiology,
morphology, clinical presentation including age distribution, diagnosis, and complications. Be
able to differentiate these diseases based on clinical pathologic information.
LEARNING OBJECTIVES (Small and Large Intestines and Vermiform Appendix – Neoplastic)
1. Organize and discuss features of small intestinal adenomas, gastrointestinal stromal tumors
(GIST), and adenocarcinoma in terms of clinical presentation, site of tumors, morphology, and
clinical course.
2. Organize and discuss different types of non-neoplastic and neoplastic polyps in terms of clinical
presentation, morphology, pre-malignant features, and metastatic potential of polyps with
carcinoma in situ, intramucosal carcinoma and invasive carcinoma.
3. Organize and discuss the different familial polyposis syndromes regarding pathogenesis-genetics,
morphology and types of polyps produced, associated disease processes and malignant potential.
4. Organize and discuss the concept of colorectal carcinogenesis in terms of the adenoma-carcinoma
sequence and molecular basis.
5. Organize and discuss features of carcinoma of the colon and rectum based on incidence,
epidemiology, etiology and pathogenesis, clinical presentation, gross and microscopic
morphology, clinical course, and prognosis including prognostic indicators (staging).
6. Compare and discuss features of right sided colon cancers and left sided colon cancers in terms of
clinical presentation, morphology, and prognosis.
7. Organize and discuss features of carcinoid tumors in terms of clinical presentations, sites of
tumors, morphology, clinical diagnosis, and clinical courseprognosis.

8. Organize and discuss clinical features of the carcinoid syndrome and other endocrine syndromes
which may be produced by carcinoid tumors (Zollinger-
Ellison syndrome, Cushing syndrome and hypoglycemia).
Organize and be able to discuss features of gastrointestinal lymphomas based on associated
conditions, clinical presentation, morphology and clinical courseprognosis.
9. List and discuss features of mesenchymal tumors of the gastrointestinal tract (leiomyoma,
leiomyosarcoma, submucosal lipomas, gastrointestinal stromal tumors (GIST) and Kaposi
sarcoma) in terms of clinical features, morphology, and biologic behavior.
10. Organize and discuss features of epithelial appendiceal tumors and nonneoplastic tumorous
appendiceal processes in terms of clinical presentation, morphology, and complications-
prognosis.
Exercise 1:
Draw the five types of esophageal atresia and tracheoesophageal fistula. Give a short description of each.
- EAs with and without tracheal fistulas have been classified into five types: (1) EA with
distal tracheoesophageal fistula (TEF), (2) EA without TEF, (3) EA with proximal TEF,
(4) EA with proximal and distal fistula, and (5) isolated TEF (H type).
- Type A = pure esophageal atresia; type B = esophageal atresia with proximal
tracheoesophageal fistula; type C = esophageal atresia with distal tracheoesophageal
fistula; type D = esophageal atresia with proximal and distal tracheoesophageal fistula;
type E = H-type tracheoesophageal fistula without esophageal atresia.
Exercise 2:
Differentiate the two types of hiatal hernia.
- There are two main types of hiatal hernias: sliding and paraesophageal (next to the
esophagus).
Case 1: Reflux esophagitis
Esophageal biopsy from a 47-year-old alcoholic.
Microscopic: Sections show stratified squamous epithelium with underlying stroma

infiltrated by chronic inflammatory cells and eosinophils.

Draw and Label
STUDY QUESTION:
1. Enumerate the major causative factors involved in GERD.
● Alcohol and Tobacco use

● Obesity
● Central Nervous System Depressant
● Hiatal Hernia
● Delayed Gastric emptying
● Increased Gastric volume
● Transient lower esophageal sphincter relaxation
● Increase intra-abdominal pressure

Case 2: Barrett’s Esophagitis
History: 47-year-old male executive experience heart burn. Esophagogastro-

duodenoscopy with biopsy of esophagus was performed.
Gross: Specimen consists of few pieces of tan white, irregular shaped soft to
rubbery tissues with an aggregate measurement of 0.4 x 0.4 x 0.3 cm.
Microscopic: Section shows fragment of tissues lined by stratified squamous epithelium

blending laterally and underneath with glandular epithelium with occasional
goblet cells. Chronic inflammatory cells are noted in the stroma. No dysplastic changes
seen.
Draw and Label

STUDY QUESTION:
1. Give the two criteria required for the diagnosis of Barrett’s esophagus.
● Barrett esophagus can be identified only through endoscopy and
biopsy.
● Endoscopy: metaplastic columnar mucosa above GEJ
● Microscopy: intestinal-type metaplasia of the squamous
esophageal epithelium (diagnostic of Barrett esophagus
2. Define Barret’s metaplasia. Is this premalignant?
a. Barrett’s metaplasia: change in typical cell shape due to prolonged

periods of exposure to acidity
b. Stratified Squamous → Columnar
c. It is premalignant in the sense that it may progress to high grade dysplasia
and eventually to intramucosal/invasive adenocarcinoma
Case 3: Squamous Cell Carcinoma

History: Endoscopic biopsy of an esophageal mass from a 62-year-old male smoker with difficulty of
swallowing.
Microscopic: Microsections showed nests of neoplastic squamous cells with focal keratin pearl
formation.
Draw and Label
STUDY QUESTION:
1. Give one factor associated with the development of this tumor and briefly discuss its
pathophysiology:
a. alcohol and tobacco use (synergistic)
b. In situ squamous dysplasia → small, gray-white, plaque-like thickenings →
tumor masses that may be polypoid, or exophytic, and protrude into and

obstruct the lumen → Tumors invade surrounding structures → dysphagia,

odynophagia (pain on swallowing)
Case Study: Acute Upper GI Bleeding
A 48-year-old accountant presented to the Emergency Room with 2 hours history of nausea and vomiting
of large amount of bloody material. He did not have any past history of gastrointestinal bleeding or
peptic ulcer disease. He reported taking ibuprofen (NSAID’s) for leg pain. The patient admits to a
history of alcohol abuse and cigarette smoking. Physical examination revealed a malnourished man in
acute distress. His supine blood pressure was 90/40 and his pulse is 120/min. His scleras were icteric
and there were spider angiomata on the chest. The liver and spleen were enlarged. The abdominal
examination revealed moderate distention, shifting dullness, and hyperactive bowel sounds.
1. What is the cause of the bleeding?

a. Varices c. Acute gastritis
b. Peptic ulcer d. All of the above
2. Mallory-Weiss syndrome occurs in a patient who is vomiting or retching violently and then starts
to vomit blood. The cause is:
a. Alcohol induced injury
b. Steroid-induced ulcer
c. Tear near esophagogastric junction
d. Tear near gastroduodenal junction

Case 4: Gastric Ulcer
History: 55-year-old male executive frequently expresses epigastric pain associated with nausea and
vomiting.
Gross: Specimen consists of few pieces of creamy white, irregular shaped soft tissues with an
aggregate measurement of 0.5 x 0.4 x 0.3 cm.
Microscopic: Section shows gastric tissues lined by tall columnar epithelium with ulcer.
The base of the ulcer shows fibrosis, granulation tissue with acute and chronic
inflammation.
Draw and Label

STUDY QUESTIONS:
1. Tabulate the differences of a benign and malignant ulcer.
2. Use a diagram to explain the pathophysiology of Peptic Ulcer Disease.

Case 5: Helicobacter pylori
Gastric biopsy of a 55-year-old female patient with history of chronic gastritis.
Draw and Label

STUDY QUESTIONS:
1. Enumerate the different specialized traits of H. pylori that allow it to flourish in the gastric
mucosa.
● Flagella - allow the bacteria to be motile in viscous mucus
● Urease - generates ammonia from endogenous urea and thereby
elevates local gastric pH and enhances bacterial survival
● Adhesins - enhance bacterial adherence to surface foveolar cells
● Toxins - cytotoxin-associated gene A (CagA)
2. Describe the two patterns of H. pylori gastritis.

 Pan-gastritis - affects the entire stomach lining, including both the antral and oxyntic mucosa of
the antrum (lower portion of the stomach) and fundus (upper portion of the stomach).
● Antral-predominant gastritis - a long-standing H. pylori gastritis may progress to
involve the gastric body and fundus which may result in atrophic gastritis with
reduced parietal cell mass and intestinal metaplasia The loss of parietal cells
leads to reduced acid secretion that, in turn, stimulates gastrin production.
Case 6: Amoebic Ulcer (Colon)

(Review previous exercise)
Draw and Label

STUDY QUESTIONS:

1. What is the most common site in the gastrointestinal tract affected by Entamoeba hystolitica?
○ Colon
2. What type of diarrhea is caused by Amoeba?
○ Dysentery
3. Enumerate the main properties of bacteria in the pathogenesis of enterocolitis.

Case 7: Intestinal Infarct, Gross
History: A 65- year-old male was brought to the ER due to left lower quadrant pain
4 hours PTA and several loose stools containing bright red blood. The

patient had a chronic history of hypertension, angina and congestive heart failure and had been
taking digoxin and hydrochlorothiazide. Physical examination showed BP of 100/70 mmHg, PR
104/min and temperature 100.5 ºF. PE of the chest was unremarkable. The abdomen revealed
increased bowel sounds and tenderness over the left lower quadrant. There was no muscle
guarding or rebound tenderness. A rectal examination revealed red bloody stool. Complete blood
count revealed hemoglobin - 14.5 g% and the white blood count - 12,800 with 81 polys, 15
lymphocytes, 3 monocytes and 1 eosinophil.
STUDY QUESTION:
1. Is the bleeding from upper or lower GI tract?
○ The bleeding is from lower GI tract
Case continuation
The patient was stabilized but continued to bleed. Physical examination at this time showed increasing
tenderness and guarding of abdomen and a gastrointestinal consultation was sought. A flexible
sigmoidoscopy was performed followed by biopsy. The patient was immediately referred to the surgeon.
Draw and Label:

STUDY QUESTIONS (continuation):

2. What is the diagnosis?
○ Intestinal infarct
3. What portion of the large intestines is at greatest risk of this type of pathology?
○ Descending and sigmoid colon
4. Discuss the differential diagnosis of this type of GI bleeding.
● CMV Infection ● Chronic Leukemia ● Radiation Enterocolitis
5. Differentiate the two phases of ischemic injury.

● Hypoxic Injury ○ Occurs at onset of vascular compromise ○ Epithelial cells lining the
intestine and relatively resistant to transient hypoxia ● Reperfusion Injury ○ Initiated by
restoration of blood supply and this is where the greatest damage occurs ○ Involves free
radical production, neutrophil infiltration and inflammatory mediator release
6. Enumerate at least three predisposing factors for ischemia.

● Smoking ● Atherosclerosis ● Age ● COPD ● Heart problems ● Medications ● Blood clotting

problems ● Illegal drug use
Case 8: Chronic Granulomatous Inflammation, Colon/Omentum

(Review previous exercise) Draw and
Label:
STUDY QUESTIONS:
1. How is tuberculosis of the intestines acquired?
It can be acquired via reactivation of latent TB infection or by ingestion of tuberculous

mycobacteria such as ingesting unpasteurized milk or uncooked meat.
2. In a tabular form, differentiate Crohn disease of the small intestines and large intestines from
ulcerative colitis. Focus only on the major differences.


Case 9: Diverticulitis
History: 42-year-old male with chronic history of lower abdominal discomfort and
alternating diarrhea and constipation suddenly presented with acute left
sided abdominal pain.
Gross: The specimen is a sigmoid colon with flash-like out-pouchings measuring

1.0 cm. to 1.5 cm. in greatest diameter with accompanying serosal fibrinoid
exudates.
Microscopic: Section showed a thin colonic wall with atrophic mucosa and attenuated muscularis
propria. Acute inflammation is also present.
Draw and Label:

STUDY QUESTIONS:
1. Differentiate congenital (Meckel’s diverticulum) from acquired diverticulum.

2. Give the two factors that are important in the genesis of diverticula.
○ Increased intraluminal pressure ○ Defects in the wall of the colon
Case 10: Acute Appendicitis, Slide and Gross

Draw and Label

STUDY QUESTION:
1. What is the histologic criterion for diagnosis of acute appendicitis?

○ Neutrophilic infiltration of muscularis propria
Case 11: Hemorrhoids

Draw and Label:


STUDY QUESTION:
1. Give two predisposing factors in the development of hemorrhoids.
○ Straining at defecation (eg. in constipation) ○ Venous stasis of pregnancy ○ Portal

hypertension
2. What venous plexuses are involved in hemorrhoids?

○ Venous plexus at the anorectal junction
Case 12: Tubular / Tubulovillous adenoma
History: 44-year-old asymptomatic male underwent colonoscopy.

Endoscopic findings showed sessile and pedunculated polyps at the

sigmoid region measuring 0.2 cm. and 1.0 cm. respectively.
Microscopic: Section shows polypoid lesions composed of tubular glands with a central
fibrovascular stroma. The other polyp showed a predominant villous component.
Draw and Label
STUDY QUESTIONS:
1. Enumerate the three features of an adenomatous polyp that are correlated with the risk to develop
malignancy.
● Size of the polyps (greatest for lesions over 2cm) ● Familial adenomatous polyposis with
multiple tubular adenomas ● High-grade dysplasia

2. In tabular form, define and differentiate the following: hyperplastic polyps, hamartomatous
polyps, and Peutz-Jeghers polyps

Case 13: Adenocarcinoma, Colon Slide
History: 66-year-old male with history of weight loss and rectal mass on endoscopy.
Gross: Anterior resection specimen showed a partially obstructing rectosigmoid mass

measuring 3.5 cm. in greatest diameter with focal superficial ulcerations. Sections showed an
infiltrative mass up to the peri-colic fat.
Microscopic: Section from the mass shows malignant irregular glands invading up to the
peri-colic fat.
Draw and Label


STUDY QUESTIONS:
1. Enumerate the two pathogenetic pathways for the development of colonic carcinoma. In what
ways are these two pathways different?
○ The combination of molecular events that lead to colonic adenocarcinoma is heterogeneous and
includes genetic and epigenetic abnormalities. ○ two genetic pathways have been described: the
APC/β-catenin pathway, which is activated in the classic adenoma-carcinoma sequence, and the
MSI pathway, which is associated with defects in DNA mismatch repair and accumulation of
mutations in microsatellite repeat regions of the genome. ○ Both pathways involve the stepwise
accumulation of multiple mutations, but differ in the genes involved and the mechanisms by
which mutations occur
2. What is the most frequently observed activated oncogene in adenomas and colon carcinomas?
○ APC ○ TP53 ○ KRAS

CHAPTER

BILIARY TRACT
PATHOLOGY

Exercise 1: Biliary Stone

By means of a diagrammatic representation, draw the pathogenesis of cholelithiasis.
STUDY QUESTIONS:
1. Differentiate cholesterol from pigment gallstones.
Cholesterol stones only form in the gallbladder and range in purity from 100 percent to
50 percent cholesterol. Pure cholesterol stones are pale yellow, round to ovoid, and
have a finely granular, hard external surface with a glistening radiating crystalline
palisade when transection is performed. Pigment gallstones, on the other hand, range
in color from brown to black. Brown pigment stones are found in infected large bile
ducts and black pigment stones are found in sterile gallbladder bile.

2. What are the risk factors for the formation of cholesterol and pigment stones?
Cholesterol stones:
• Demography: North and South Americans, Native Americans, Mexican

Americans and Northern Europeans
• Advancing Age
• Inborn Disorders of Bile Acid Metabolism
• Female Sex Hormones
• Obesity
• Metabolic Syndrome
• Rapid Weight Reduction
• Gallbladder Stasis
• Syndromes of Hyperlipidemia
Pigment stones:
• Living in rural areas
• Asian
• Biliary Infection
• Chronic Hemolytic Anemia
• GI Disorders: Ileal Disease, Ileal Resection or Cystic Fibrosis with Pancreatic
Insufficiency

Exercise 2: Chronic Cholecystitis

Draw and Label
STUDY QUESTIONS:
1. What is chronic cholecystitis? Differentiate it from the acute forms.
Chronic cholecystitis lacks the dramatic appearance of acute cholecystitis and is
characterized by recurrent attacks of steady epigastric or right upper quadrant pain.
Nausea, vomiting, and a fatty food intolerance are common side effects.

2. What are Rokitansky-Aschoff sinuses?

These are outpouchings of the mucosal epithelium through the wall.
3. Define Hydrops of the gallbladder.
Atrophic, chronically obstructed gallbladder that contains clear secretions in a

condition of overdistended gallbladder without inflammation.
Case 1: Biliary Cirrhosis
History: 56-year-old female with history of gallstone disease developed deepening jaundice later on
developed signs and symptoms of portal hypertension. Antimitochondrial antibody is negative.
Gross: The liver is atrophic and nodular weighing 500 grams. It is bile stained with pseudolobules seen
on cut section.
Microscopic: Section shows hepatocyte and disarrangement of liver architecture. Extra and intra
hepatic cholestasis is present. There's proliferation of fibro-connective tissue.

Draw and Label:
STUDY QUESTIONS:
1. What is the antibody characteristic of primary biliary cirrhosis?
The level of serum immunoglobulins, particularly IgM, has increased. Antimitochondrial

antibodies are present in over 95% of patients.

2. What part of the liver architecture is initially involved in this disease?
The cells that line the bile ducts inside the liver are attacked by the immune system.
Chronic inflammation, damage, and scarring result as a result of this.
Exercise 3: Pancreatitis
Draw and Label:

STUDY QUESTION:
1. List down the most common cause of Acute Pancreatitis.
• Excessive alcohol intake
• Genetic factors
• Medications
• Ischemia
• Metabolic disorders leading to hypercalcemia
• Traumatic injuries
• Pancreatic duct obstruction
CHAPTER

LIVER PATHOLOGY

DISEASES OF THE LIVER
The liver is situated under the right diaphragm in the lower part of the right rib cage. The left lobe of the
liver is in the epigastrium and is therefore not protected by the rib cage. The normal liver is firm and has a
smooth surface.
The liver parenchyma is divided into functional units called lobules. Each lobule is 1-2 mm in diameter
and is made up of a mazelike arrangement of interconnected plates of hepatocytes separated by
endothelium lined sinusoids. The liver cell plates are arranged radially around the central vein; the liver
cells that surround a portal tract comprise the limiting plate. Liver cell plates are normally one hepatocyte
in thickness. Individual hepatocytes are large, with a central round nucleus, a prominent nucleolus, and
abundant granular cytoplasm.
The liver cells are separated from the sinusoids by a narrow space (space of Disse) that contains
connective tissue and represents the scant interstitial compartment of the liver. Specialized cells of the
macrophage system (Kupffer cells) are present in the sinusoids scattered among the endothelial cells.
The normal liver has a huge reserve functional capacity. When the liver is normal, about 80% of it can be
removed without compromising function. The liver has synthetic, excretory, and metabolic functions.
The liver is the source of plasma albumin, many plasma globulins, including a1-antitrypsin, and many
proteins of the coagulation cascade. Many substances are excreted by the liver in bile. The liver plays a
central role in the metabolism of fat, carbohydrates, and protein and in detoxification.
Case 1: Central Hemorrhagic Necrosis With Passive Congestion, Liver
History: 58-year-old male, smoker with history of chronic obstructive lung disease had
hepatomegaly and distended anterior jugular pulses.
Gross: Liver specimen shows alternately yellow and red color with nut-meg like appearance.
Microscopic: Section shows liver tissue with central hemorrhagic necrosis with peripheral fatty change.
Draw and Label

STUDY QUESTIONS:
1. Give the different types of liver necrosis and give one example each.

2. Give the most common antecedent cause of this lesion.
Right-sided heart failure
3. The different morphologic patterns of hepatic injury are:
Ballooning degeneration
Feathery degeneration
Microvesicular steatosis
Macrovesicular steatosis
Apoptosis
Inflammation
Case 2: Alcoholic Cirrhosis
History: A 50-year-old male alcoholic, had the habit of consuming a bottle of "Ginebra"
everyday. He had complained of abdominal pain, anorexia, nausea and abdominal
enlargement. He consulted his physician who noted ascites, jaundice and evidence
of portal hypertension. Patient died of massive upper gastrointestinal bleeding

secondary to ruptured esophageal varices. An autopsy was done.
Gross: The liver weighs 500 grams, contracted and is yellow-orange and diffusely
nodular. There are multiple nodules on the surface as well on cut section. The
nodules vary from 0.1 to 0.5 cm.
Microscopic: In this slide, the normal architecture of the liver is distorted with bands
of fibrosis connective tissue joining the portal area of the central vein
(portal - central fibrosis) and portal area with another portal area
(portal - portal fibrosis) forming pseudolobules
(lobules without central vein or disarray venous architecture). There is fatty change
of hepatocytes.
Draw and Label


STUDY QUESTIONS:
1.
What is CIRRHOSIS? Give the criteria for the diagnosis of cirrhosis. Explain each and briefly
discuss the pathogenesis of cirrhosis.
Cirrhosis
- widespread disruption of normal liver structure by fibrosis with the formation of regenerative nodules
caused by various chronic passive congestion and conditions affecting
the liver.
- It is a condition marked by diffuse remodeling of the liver into parenchymal nodules surrounded by fibrous
bands and variable degree of vascular shunting
CRITERIA FOR THE DIAGNOSIS OF CIRRHOSIS
- Bridging of Fibrous Septa
- Delicate bands or broad scars that link the portal tracts with one another and some with terminal hepatic
veins. FIbrosis is the key feature of progressive damage due to it’s dynamic
collagen deposition that remodel normal liver structure
- Parenchymal nodules
- Hepatocytes surrounded by fibrosis with varying diameters from very small to very large. The nodularities
result from the on-going cycle of regeneration and scarring
- Disruption of architecture of the entire lung
- Parenchymal injury and fibrosis are diffused extending all throughout.
2. Name agents or conditions/infections causing cirrhosis.
Chronic hepatitis B
Chronic hepatitis C
Nonalcoholic fatty liver
disease
Alcoholic liver disease
Metabolic diseases

3. In alcoholic cirrhosis, give the pathognomonic morphologic changes that it can be differentiated
from post necrotic cirrhosis.
ALCOHOLIC CIRRHOSIS Morphologic changes:

- Nodular pattern: Normal lobular architecture is
replaced by nodular structure.
- Fibrous septa: Thick septa dividing the nodules
- Hepatic parenchyma: Slow proliferation of
surviving hepatocytes forms nodules
- Duct proliferation
POST NECROTIC CIRRHOSIS Morphologic changes:

- Nodular pattern: Normal lobular architecture is replaced by nodular
structure larger than those in alcoholic cirrhosis
- Fibrous septa: Thick septa dividing the nodules
- Hepatic parenchyma: Proliferation of surviving hepatocytes forms
nodules
4. Why is there ascites in late stages of cirrhosis?
▷ Portal hypertension causes splanchnic vasodilation, and activation of the reninangiotensin-aldosterone

system, further resulting in renal sodium retention. ▷ Kidney function worsens as portal hypertension rises
and fluid accumulates in the abdomen ▷ As the liver struggles to manage this fluid, it is forced into the
abdominal cavity, resulting in ascites ▷ The primary cause of portal hypertension in cirrhosis is an increase
in intrahepatic vascular resistance due to massive structural changes associated with fibrosis and increased
vascular tone in the hepatic microcirculation. ▷ As portal hypertension develops, the formation of
collateral vessels and arterial vasodilation progress, which results in increased blood flow to the portal
circulation. Eventually the hyperdynamic circulatory syndrome develops (characterized by increased
cardiac output and heart rate, and decreased systemic vascular resistance with low arterial blood pressure),
leading to ascites.

STUDY QUESTIONS:
1.
Case 3: Chronic Active Hepatitis
History: 50-year-old female came in because of deepening jaundice.

She had history of contacting hepatitis B virus infection
10 years ago and had an on and off jaundice and abdominal pain.
Gross: The liver weighs 2,000 grams. It has smooth surface.
Microscopic: The morphologic changes include inflammatory reaction mostly lymphocytes and plasma
cells in the portal triad and spilling out of the liver parenchyma. Periportal fibrosis is also
evident and assumes a maple leaf-like appearance. Necrosis of hepatocyte is confluent
(bridging necrosis).
Draw and Label

Tabulate the differences between chronic persistent hepatitis and chronic active hepatitis.

STUDY QUESTIONS:
1.
2. What are the different serum markers for Hepatitis B and their respective clinical significance?
3. In tabular form, name the various hepatitis viruses and differentiate them according to:

Case 4: Hepatocellular Carcinoma
History: 50-year-old male with history of being rejected as blood donor developed
hepatomegaly upper gastrointestinal bleeding asterexis and caput medusae. SGOT
and SGPT were 500 and 620 IU respectively.
Gross: Liver weighs 2,000 grams with multiple nodules on cut surface and a big mass with

STUDY QUESTIONS:
1.
greenish cut surface and measuring 8 cm. in diameter.
Microscopic: Section shows malignant cells arranged in cords and trabecula and some infiltrating the
stroma. The background shows cirrhotic changes.
Draw and Label
Differentiate Hepatocarcinoma from Cholangiocarcinoma based on morphology.
HEPATOCARCINOMA CHOLANGIOCARCINOMA

2. What are the two types of primary carcinoma of the liver?
HEPATOCELLULAR CARCINOMA
INTRAHEPATIC CHOLANGIOCARCINOMA
3. Give three major predisposing factors associated with hepatocellular carcinoma.
o Chronic viral hepatitis o Metabolic diseases o Alcoholic liver disease

STUDY QUESTIONS:
1.
4. What is the role of cirrhosis in the development of hepatocellular carcinoma?

Hepatocellular carcinoma occur in the setting of chronic liver disease with cirrhosis
CHAPTER

DERMATOPATHOLOGY

SKIN
Dermatologic pathology is presented in this section in a very simplified manner. We stress skin
neoplasms, including carcinoma and malignant melanoma, and common skin infections. Only those
dermatologic diseases that have characteristic clinicopathologic features and that are encountered
commonly are discussed.
Case 1: Intradermal Nevus
History: A gray brown mass was excised from the base of the nose of a 35-year-
old
female.
Gross: A n elliptical skin measuring 2.0 x 0.6 cm.
Microscopic: Microscopic examination discloses nests of nevus cells located

predominantly in the papillary dermis. The nevus cells are more or less uniform looking
with no atypical changes or mitotic figures seen. Melanin pigments are seen. The
overlying stratified squamous epithelium is practically unremarkable.
Draw and Label

STUDY QUESTIONS: Draw schematically the following:
Intradermal Nevus Junctional Nevus Compound Nevus


Case 2: Melanoma
History: A 44-year-old, farmer noted a change in the appearance of his mole on his cheeks. He
had the mole on his cheeks for as long as he can remember. It started to be itchy at first,
which made him to scratch it often. He later noted a change in color and an increase in
size. He was advised by a friend to consult a doctor. Excision was done.
Gross: The specimen consists of an elliptical skin measuring 4.0 x 4.0 x 1.0 cm. There is a
central nodule averaging 1.0 cm. with irregular borders. It shows light to dark brown
discoloration.
Microscopic: Nests of malignant nevus cells are seen in the dermis and on the dermoepidermal junction.
Some mitotic figures are also seen.
Draw and label

STUDY QUESTIONS:
1. What are the clinical warning signs of a melanoma?
• Asymmetry
• Borders - irregular
• Color - variegated
• Diameter - increasing
• Evolution or change in appearance
2. Discuss the value of the “vertical growth phase vs. horizontal growth phase in a melanoma.

Case 3: Basal Cell Carcinoma
History: 64-year-old with a chronic ulcerating wound on left pinnae. Excision

biopsy was done.
Microscopic: Microsections show nest of basaloid cells with peripheral palisading. These nests are seen
invading the dermis.
Draw and Label: (Compare the slide with squamous cell carcinoma)
Basal Cell Carcinoma Squamous Cell Carcinoma

STUDY QUESTIONS:
1. Differentiate basal cell carcinoma from squamous cell carcinoma. Tabulate your answer. What is
the clinical behavior of basal cell carcinoma?
2. Give the usual location in the lips of squamous cell carcinoma and basal cell carcinoma.
• Squamous ce carcinoma is commonly found in the lower lip.
• Basa ce carcinoma is more common on the outer cutaneous part of the ip than on
the vermillion, but it can also occur on the upper lip.

CHAPTER

ENDOCRINE
PATHOLOGY

ENDOCRINE PATHOLOGY
Case 1: Nodular Adenomatous Goiter, Demo slide
History: A 30-year-old female complaining of anterior neck mass for several years.
Gross: The left thyroid lobe is enlarged measuring 5.0 cm. x 4.0 x 2.0 cm.
Microscopic: Section shows vari-sized follicles filled with colloid materials.
Draw and Label:

STUDY QUESTIONS:
1. Discuss the pathogenesis of endemic goiter.
 Endemic goiter occurs in geographic areas where the soil, water,

 and food soppy contain low levelsof iodine.
 The lack of iodine leads to decreased synthesis of thyroid hormone and
 a compensatory increase in TM, leading A follicular cell hypertrophy
 and hyperplasia and qoiroroos enlargement.

Case 2: Thyroid Hyperplasia
History: 24-year-old female with hand tremors, palpitations and anterior bulging of
the eyeball. The neck is enlarged.
Gross: The thyroid glands are enlarged with aggregate weight of 100 grams.
Both are meaty and homogenous tan brown surface.
Microscopic: Section shows hyperplastic thyroid follicles lined by cuboidal to tall

columnar cells.
Draw and Label

STUDY QUESTIONS:
1. Give the usual etiopathogenesis of this lesion.
- Increased thyroglobulin synthesis
- Increased iodination
- Thyroid gland hyperplasia
- Graves disease

2. What is the etiopathogenesis of exophthalmos in this patient?
- Opthalmopathy
- Auto antibody binding a thyro TSH receptor expressed on orbital fibrocytes leading to
production of inflammatory cytokines
3. Give the hormones that are increased in this patient and their clinical consequences.
- Immunoglobulin G (IgG) against TSH-receptor leads to increased thyroid function and

growth. Patients will often present with symptoms of hyperthyroidism and diffuse goiter.
Case 3: Hashimoto's Thyroiditis
History: 34-year-old from Baguio with anterior neck mass and signs of
hyperthyroidism.
Gross: Enlarged thyroid tissue weighing 75 grams each with meaty tan brown
homogenous surface.
Microscopic: Section shows thyroid tissue with effaced architecture by numerous

lymphocytes with tendency to form germinal follicles.
Draw and Label


STUDY QUESTIONS:
1. What is the etiopathogenesis of this lesion?
Hashimoto thyroiditis is caused by a breakdown in self-tolerance to thyroid autoantigens. This is

exemplified by the presence of circulating autoantibodies against thyroglobulin and thyroid
peroxidase in the vast majority of patients. The inciting events have not been elucidated, but
possibilities include abnormalities of regulatory T cells (Tregs), or exposure of normally
sequestered thyroid antigens. Similar to other autoimmune diseases, Hashimoto thyroiditis
predisposition has a strong genetic component. Increased susceptibility is associated with
polymorphisms in several immune regulation–associated genes, such as cytotoxic T lymphocyte–
associated antigen-4 (CTLA4), protein tyrosine phosphatase-22 (PTPN22), and interleukin-2
receptor α chain (IL2RA), all of which encode regulators of T-cell responses. The genetic
associations support the idea that breakdown in immune tolerance is a common pathophysiologic
theme for many autoimmune diseases, more than one of which can coexist in the same individual.
2. What are the characteristic histologic findings of this thyroid disorder?

Case 4: Papillary Carcinoma of the Thyroid
History: 60-year-old female with anterior neck mass.
Gross: The thyroid glands are moderately enlarged and firm. Cut sections
showed nodules with whitish papillary specks.
Microscopic: Section shows anaplastic thyroid follicles lined by cell with ground glass nuclei.
Papillary architecture is also prominent.
Draw and Label

STUDY QUESTIONS:
1. Differentiate:

2. What is a psammoma body?

Psammoma bodies are concentrically calcified structures which are often present, usually within
cores of papillae. These structures are almost never found in follicular and medullary carcinomas,
and they are a strong indication that the lesion is a papillary carcinoma when present in the fine-
needle aspiration material.
3. What are the histologic features of this tumor?
• Branching papillae - having a fibrovascular stalk covered by single to multiple layers of

cuboidal epithelial cells. • Nuclei with finely dispersed chromatin and an optically clear or empty
appearance, giving rise to ground glass or orphan eye nuclei • Invaginations of the nuclear membrane may

give rise to appearance of nuclear inclusion (pseudo inclusions) • Psammoma bodies - concentrically
calcified structures are usually present within the cores of papillae
Exercise 1: Follicular Carcinoma, Demo slide
Draw and Label

STUDY QUESTION:
Exercise 2: Diabetic Nephropathy

Draw and Label

STUDY QUESTIONS:
1. Discuss the pathogenesis of Diabetes Mellitus.
Type 1 diabetes (T1D) is an autoimmune disease characterized by pancreatic β-cell

destruction and an absolute deficiency of insulin (autoantibodies are markers of beta cell
autoimmunity in type 1 diabetes: islet cell antibodies (ICA, against cytoplasmic proteins in
the beta cell), antibodies to glutamic acid decarboxylase (GAD-65), insulin autoantibodies
(IAA), and IA-2A, to protein tyrosine phosphatase). Type 2 diabetes (T2D) is caused by a
combination of peripheral resistance to insulin action and a secretory response by pancreatic β
cells that is inadequate to overcome insulin resistance (interplay of genetic and environmental
factors and a pro-inflammatory state. Unlike T1D, there is no evidence of an autoimmune
basis.) Diabetes Mellitus refers to the metabolic disorder characterized by chronic
hyperglycemia.with disturbance of carbohydrate, fat and protein metabolism May result from
the following: Reduced insulin secretion Decrease glucose use by the body Increase glucose
production
2. What are the different cell types seen in the Islet of Langerhans?
● Alpha Cells ● Beta Cells ● Delta cells ● PP cells ● Epsilon cells

3. What are the hormones secreted by each?
4. Differentiate Type I and II DM.


CHAPTER

RENAL PATHOLOGY

RENAL AND LOWER URINARY TRACT
The kidneys are located in the retroperitoneum and weigh 130-150 g each. The surface is smooth
and invested in a capsule, which in turn is surrounded by perinephric fat and Gerota’s fascia.
The anatomic unit of the kidney is the nephron, which is composed of the glomerulus, proximal
convoluted tubule, loop of Henle, distal convoluted tubule, and collecting tubule. Each kidney contains
approximately 1 million nephrons.
The glomerulus is composed of: (1) an afferent and efferent arteriole; (2) intervening capillaries lined by
endothelial cells (glomerular tuft); (3) the outer surface of the capillaries, which is covered by epithelial
cells (podocytes), continous with the epithelium of Bowman’s space and the proximal tubules; (4) the
mesangium, composed of mesangial cells and matrix; and (5) the basement membrane.
Case 2: Chronic Pyelonephritis
History: noted. A 50-year-old male complaining of frequent dysuria. Fever was also
Gross: A small kidney with granular surface measures 3.5 x 3.0 x 2.6 cm.
Microscopic: The kidney shows tubules filled with pinkish and colloid like materials. There
are scattered inflammatory cell seen.
Draw and Label


STUDY QUESTIONS:
1. Differentiate pyelonephritis from hydronephrosis.

Case 3: Acute Tubular Necrosis
History: Kidney section from a 45-year-old male with a history of hypovolemic

shock secondary to vehicular accident. Patient manifested oliguria post
operatively and eventually died.
Gross: The kidneys show normal size. The outer surface is gray white with
granular surface.
Microscopic: Some tubules show focal necrosis with apoptosis. In areas, dilated tubules
are seen.
Draw and Label

STUDY QUESTIONS:
1. Define Acute Tubular Necrosis.

2. Differentiate ischemic from toxic type of ATN. Tabulate your answer.

Case 4: Rapidly Progressive Glomerulenpritis
History: being A 35-year-old male suddenly developed oliguria with reddish urine while
work up for a possible renal problem. He is hypertensive with bipel edema.
Gross: The kidneys are bigger than usual with focal hemorrhages on the outer
surface.
Microscopic: The glomeruli are obliterated with crescent shape mass in the Bowmans
capsules.
Draw and Label


CHAPTER
MALE GENITAL TRACT

PATHOLOGY

MALE GENITAL TRACT
The most important diseases of the male genital system are the highly malignant tumors, which occur in
the prostate glands and in the testis. Cancer of the prostate glands affects middle aged and elderly men,
often presents late such that the tumor is already well advanced when medical advice is sought, and can
be difficult to treat. One main problem is that the tumor spreads to bone, particularly the vertebrae.
Tumors of the testis occur in young and middle aged men, usually presenting as a painless intrascrotal
swelling. The most common tumors are derived from germ cells and are highly malignant, although
recent advances in tumor monitoring and the use of chemotherapy have greatly improved the prognosis.
Case 1: Tuberculosis of Testis
History: A 24-year-old male, complained of non-tender testicular swelling of 1 month

duration.
Gross: The testis measures 4.5 x 2.7 x 2.0 cm. It is tan and soft. Cut section
shows a cheesy like material on one area.
Draw and Label

STUDY QUESTIONS:
1. How would you diagnose this case clinically?
2. What is the usual route of infection? Compare it with that of syphilis.
3. Was the surgeon justified in removing the testis? Please explain.

Case 2: Benign Prostatic Hyperplasia (BPH)
History: A 64-year-old male complained of urinary hesitancy, dribbling, and vague lumbar pain.
IVP was done and showed dilated ureter up to renal pelvis. The prostate was removed
by TUR.
Gross: The specimen consists of several tan, irregularly shaped, rubbery tissue with an aggregate
measurement of 8 x 7 x 6.5 cm.
Microscopic: Microsections disclose prostatic tissues with proliferation of glands and the fibromuscular
stroma.
Draw and Label

STUDY QUESTIONS:
1. What will happen if you just leave it alone?

2. What are the prostatic elements that can undergo hyperplasia?

Case 3: Testicular Atrophy
History: This came from a 10-year-old male patient with undescended testis.
Draw and Label
STUDY QUESTIONS:
1. What are the usual atrophic changes affecting the scrotal testes?

PATHOLOGY LABORATORY E-MANUA
2. Why is there atrophy in Klinefelter's syndrome?
3. In what other conditions do you usually see testicular atrophy?
Case 4: Prostatic Carcinoma
History: A 69-year-old male patient underwent transurethral prostatectomy because of difficulty

of urination. On rectal examination, the prostate gland was enlarged and hard with
nodulations. PSA value was 125 mg/L.
This is the slide of his prostatic chips specimen.
Draw and Label

STUDY QUESTIONS:

Case 5: Seminoma
History: A 20-year-old male patient underwent orchiectomy because of an enlarging testis of 3

months duration. Lately, it was accompanied by dragging sensation and pain. On physical
examination, the left testis was enlarged measuring up to 8 cm. in diameter.
Transillumination was negative and ultrasound was done which revealed a partially cystic

and partially solid testicular mass. This is the orchiectomy specimen.
Draw and Label

STUDY QUESTIONS:
1. List down differential diagnosis of “scrotal enlargement”.
2. What is “transillumination” test? Give its clinical significance.
3. Is this tumor radiosentitive? What other testicular tumors do you know?


PATHOLOGY LABORATORY E-MANU
CHAPTER
BONE & JOINT PATHOLOGY

BONE AND JOINT PATHOLOGY
The skeleton is composed of flat bones and long tubular bones. Flat bones such as the skull,
sternum, and pelvic bones develop from fibrous tissue (through intramembranous ossification), whereas
long tubular bones increase in length at a line of cartilage present near the growing bone ends known as
the epiphyseal plate or growth plate. Anatomic regions of long bones relate to the growth plate and include
the epiphysis, which is the region between the growth plate and the nearest joint; the diaphysis, which is
the shaft region of the bone between the two growth plates; and the metaphysis, which is the region of
bone adjacent to the growth plate on the diaphyseal side. The metaphysis is the area where new bone is
laid down during growth, and in children, it represents the most vascular and most metabolically active
region of the bone. For this reason, the metaphysical region is the area most susceptible to infections and
neoplasm formation in childhood.
All bones are composed of an outer (cortical) shell of compact bone and an inner meshwork of
cancellous bone composed of bony trabeculae separated by vascular connective tissue, which contains fat
and bone marrow. Both cortical and cancellous bone are composed of bone cells embedded in a
mineralized matrix. The main bone cells are osteoblasts, which secrete matrix protein, and osteoclasts,
which resorb bone. The matrix of bone (called osteoid) is composed mainly of type I collagen. Other
collagen types, other proteins such as osteocalcin and osteonectin (which may play a role in mineralization
of the matrix), and glycoproteins complete the structure of bone matrix. The mineral phase of bone is
composed predominantly of calcium hydroxyapatite with smaller amounts of calcium phosphate.
The main functions of bone are to act as a hard protective shell for vital structures (e.g., skull, rib
cage, pelvis), to provide support for the trunk and limbs, and to permit movement by the action of muscles
attached to the bones. The long tubular bones of the limbs are ideal for their function because they are light
and have high tensile strength. Bone mineral also acts as a massive reservoir for calcium and phosphorus.
Case 1: Osteochondroma
History: 17-year-old female with bony outgrowth in the proximal femur.
Gross: Mushroom shaped bony lesion with smooth external surface measuring 4 x 3 x 1.0 cms.
Microscopic: Section shows polypoid lesion with cartilage capped, osteoid seam and marrow
elements.
Draw and Label

STUDY QUESTIONS:
1. Describe an osteochondroma based on the following:

2. Is this lesion congenital or neoplastic?
Case 2: Osteogenic Sarcoma
History: 15-year-old male with enlargement of the right knee and inability to step on the right foot.
Gross: Mass is present in the knee region measuring 10 x 8 x 5 cms. which is intramedullary in
location with cortical erosion.
Microscopic: Section shows malignant cells arranged in nest with malignant osteoid.
Draw and Label

STUDY QUESTIONS:
1. Differentiate osteoid osteoma from osteoblastoma.

2. Give four histologic types of this lesion. Give the particular radiologic finding.

3. Give the age groups that are most commonly affected.
75% of cases occur before 20 years old. Smaller percentage occurs in older adults.

CHAPTER
BREAST PATHOLOGY

PATHOLOGY OF THE BREAST
Each breast develops from the epidermal milk line, an embryonic ridge of tissue between the upper and
lower limb buds. The two symmetrical ridges normally atrophy except in the thoracic region, where two thickenings
develop into the nipples. Cords of cells grow downward from the nipple, developing lumens to form the ducts of the
breast. This degree of development occurs in both sexes during fetal life.
At puberty, under the influence of female sex hormones, the female breast develops further. Outpouchings
arise from the terminal ducts that branch extensively into the lobules of the breast. The adult female breast is
composed of five to ten segments, each draining at the nipple by a separate lactiferous duct.
In the nonpregnant breast, the parenchyma represents only about 10% of the volume. Much of the breast
enlargement that occurs at puberty is due to an increase in the amount of fibroadipose stroma, which is also directed
by the female sex hormones. Histologically, the normal nonpregnant breast is composed of breast lobule units,
comprising approximately 10-20 acini around a terminal ductile. Lobular units are separated from one another by
abundant fibroadipose stroma.
The breast responds cyclically to menstruation. During the preovulatory phase, estrogen causes the glands
and ducts to undergo mild dilation and hypertrophy. During the postovulatory phase, progesterone causes stromal
proliferation and edema. These changes may result in mild enlargement of the breast toward the end of the cycle.
During pregnancy, there is marked hyperplasia of the glands that displaces the fibroadipose stroma of the
breast. Enlargement of the breast occurs in the third trimester and becomes prominent during lactation. Secretion of
colostrum, the first milk, begins in the third trimester of pregnancy. The lactating breast is composed of closely
packed dilated glands with little intervening stroma. After lactation, the glands atrophy to level that approaches the
prepregnant state.
After menopause, glands, ducts and adipose tissues atrophy further, causing progressive shrinkage in breast
size.
Case 1: Fibroadenoma
History: An 18-year-old female, single, presented a mass on her left breast, while bathing. She
consulted a doctor and a surgical excision was done.
Gross: The tissue submitted is a light brown, firm, nodular tissue measuring 4 x 3 x 2 cms. On
sections, it is gritty, grayish white with small slit-like structures. The tissue bulges on cut

sections.
Microscopic: Sections showed prominent proliferation of glandular and stromal components. The glands and ducts
are small to round to occasionally irregularly distended due to the actively proliferating
pericollagenous stroma. The lining cells are tall columnar with intact myoepithelial cells.
Epitheliosis is prominent.
Draw and Label
STUDY QUESTION:
1. Describe a fibroadenoma. Differentiate it from Phyllodes tumor?

Case 2: Fibrocystic Change
History: 36-year-old female with movable mass on the left breast on the upper outer quadrant. The
mass is occasionally painful especially during her menstrual period.
Gross: Well circumscribed gray white mass measuring 3.0 c 2.0 x. 2.0 cm. It has a gray white,
smooth outer surface. Cut section shows cystic spaces measuring from 0.2 to 0.5 cm with
clear watery onset.
Microscopic: Cystic ducts and acinic are seen lined epithelial cells with hyperplasia and apocrine change. They are
supported by a fibrous stroma.
Draw and Label

STUDY QUESTIONS:
1. What fibrocystic change is significantly associated with increased risk for carcinoma?
2. Differentiate the various morphologic fibrocystic changes in the breast.

IV. FINE NEEDLE ASPIRATION BIOPSY
TECHNIQUES OF ASPIRATION AND SMEAR PREPARATION
Introduction
This laboratory exercise aims to provide an overview of the various aspects of the aspiration technique, such as
indications for use, patient preparation, and possible side effects.
The main objectives of aspiration biopsy are to distinguish benign from malignant lesions and to classify
neoplasms and other pathologic processes. Well-prepared representative material is necessary for these objectives
to be consistently achieved. The quality of the material plays a crucial role in avoiding this problem.
EQUIPMENT
Needles
Ordinary disposable hypodermic needles with long bevels are well suited for aspiration. The needles may vary in
size from 22 to 27 gauge (outer diameter from 0.65 to 0.5 mm), depending on the location and organ to be
aspirated.

Syringes and Syringe Holders
Slip tip disposable syringes are recommended because of the ease of removing and reattaching the needle.
A syringe holder can be used when a free hand is needed to stabilize the palpable target during sampling. Most
syringe holders are reusable and are durable. The syringe holder should hold the syringe firmly, should be
comfortable to hold and easy to clean, and should not slip easily out of position. It should allow for removal of the
needle and retraction of the plunger, without removing the syringe from the holder.
A syringe holder that fits a 10-ml rather than a 20-ml syringe is easier to handle. The shorter 10-ml syringe
decreases the distance between the hand and target, making sampling easier. There is no significant advantage to
the larger syringe, since a small amount of suction (a vacuum of 1-2 ml) is sufficient to obtain the sample. A 20-ml
syringe may be more convenient when aspirating cysts containing fluid volumes in excess of 10-ml. However, in
the case of a large cyst that exceeds the capacity of the syringe, the needle tip can remain within the cyst while the
full syringe is removed and replaced by an empty one. This procedure can be repeated as often as necessary until
all of the fluid is evacuated.
PATIENT SELECTION
In general, any palpable mass can be evaluated by the aspiration technique. With ultrasound guidance,
fluoroscopy, and computed tomography, most deeply seated lesions can also be sampled.
Patient Preparation
For most aspiration and procedures, the only patient preparation needed is an explanation of the procedure
and a discussion of possible side effects. Local anesthesia is rarely required, as the discomfort caused by its
application is about the same as that of the aspiration. Furthermore, when very small targets are sampled, the
injected anesthetic may make it more difficult to feel the mass and consequently position the needle correctly.
Local anesthesia is more often employed when sampling deeply seated targets with the aid of computed
tomography or ultrasonic guidance. These procedures tend to be more painful than aspiration of superficial targets
for several reasons: (1) the needle has to travel a longer distance; (2) several attempts may be needed to position
the needle correctly; and (3) the needle tip must often pass through muscle, which is especially sensitive to needle
sticks.
Basic Aspiration Technique
The basic principles described in this section are applicable to aspiration biopsies of all organ sites.
When the lesion is composed of solid tissue, the needle tip functions as a cutting instrument: As it is moved back
and forth through the tissue, tiny tissue fragments become dislodged and collect inside the needle. When suction is
added to this procedure, the previously dislodged fragments are sucked into the needle and tip of the attached
syringe. Except for fluids, the aspirate should not reach the barrel of the syringe.

Requirements for obtaining adequate samples via aspiration biopsy include target immobilization and proper
needle tip placement and movement. The following protocol is suggested when sampling palpable lesions:
1. Palpation of the Target
Carefully palpate the target, assessing its size and its distance from the overlying skin surface.
These determinations govern the placement of the needle tip. In small lesions ( < 1cm), it is generally
desirable to aim for the center of the lesion. In very large lesions (> 5 cm), there may be central necrosis,
and thus, the peripheral part is more likely to yield diagnostic material. In mediumsized lesions (2-4 cm),
it is often advantageous to collect samples from two different areas: one to the side of the center and
another one in the mirrorimage position of the first aspiration. Two different areas are thus sampled,
yielding a more representative harvest. In addition, the second sample is extracted from an area not
previously disturbed by the needle, hence, decreasing the likelihood of contamination with blood.
2. Immobilization of the Target
In order to collect an adequate sample, it is important that the target should not move with the
needle. It is particularly important to immobilize lesions with dense stroma in order to facilitate
penetration of the needle tip into the target. Lesions over 3 cm in diameter can be held in place with the
thumb and forefinger. Smaller lesions (1-2.5 cm) can be more effectively immobilized between the
forefinger and middle finger. Very small lesions (<1 cm) are often difficult to stabilize and sample. To
immobilize these small targets, palpate them with the tips of the forefinger and middle finger held tightly
together. Push the target as far as possible in one direction in the subcutaneous space. Then, without
lifting the fingertips, retract the overlying skin. The pressure will cause the lesion to “pop-up” under the
skin surface in front of the fingertips.
3. Insertion of the Needle
Once the target has been secured, pick up the previously assembled aspiration instrument, insert
the needle tip into the target, and apply suction. Retracting the syringe plunger to the 1- to 2- ml mark is
sufficient; however, more suction should not alter the outcome.
4. Aspiration Procedure
Once suction has been applied, move the needle tip back and forth within the boundaries of the
target. In order to collect sufficient material for at least two smears, the needle should be moved
back and forth frequently, up to 15-20 times. It is best to move the needle in approximately the
same plane.
5. Withdrawal of the Needle

After collection of the sample, release the suction before withdrawing the needle. This allows the
collected material to stay within the needle and syringe tip. If suction is maintained while withdrawing the
needle, the collected material will be sucked into the syringe barrel and will be difficult to expel. After the
needle is withdrawn from the lesion, remove the needle from the syringe and pull back on the plunger.
Then, reattach the needle and expel the material onto a glass slide by pushing the plunger swiftly
through the syringe. In order to avoid splattering, the tip of the needle should rest on the slide with the
bevel pointing down.
6. Changing the Direction of the Needle
Occasionally, a significant change in the direction of the needle path may be desired while
sampling. In this event, the needle tip should be withdrawn from the target while remaining under the
skin. The angle of the needle is changed before the needle is reintroduced into the target. Suction need
not be released. If the needle is not withdrawn before changing direction, the target may merely be
pushed to the side and the intended redirection of the needle tip will not be accomplished. The patient
may also experience additional discomfort and bleeding.
ASPIRATION WITHOUT A SYRINGE
Zajdela et al. (1987) described a sampling technique that uses a thin needle without suction. The target is
identified and immobilized as described above. Then the needle, held by the hub, is placed within the target and
moved back and forth to collect small fragments of tissue. The fragments find their way into the needle by
capillary action. The main advantage of this technique is the ease with which the needle can be accurately
positioned in the target; the needle is easier to manipulate by itself than when attached to a syringe. This simple
technique also often enhances the differences in consistency between lesion tissue and the surrounding normal
tissue. In addition, sampling without suction may reduce the amount of blood when sampling highly vascular
lesions or organs. Obviously, the volume of the harvested material is usually smaller when compared with that of
procedures that apply suction. However, the smaller volume may be more representative of the lesion.
Sampling without suction may be especially useful in very small targets, in the thyroid, and in other sites with
abundant blood supplies. This technique is not recommended for aspirating cystic lesions filled with fluid unless
a syringe barrel without the plunger is attached to collect the excess fluid.
BASIC SMEAR PREPARATION TECHNIQUES
The goal of smear preparation is to allow optimal distribution of well-preserved cells and small tissue fragments on
the slide.
One-Step Technique
The basic one-step smearing technique (Abele et a l., 1985) is designed to process a harvest consisting of 1 or 2
droplets of semisolid tissue material. A small amount of blood (1 or 2 drops) may also be included. The
nondominant hand steadies the needle as the needle tip, bevel down, is touched to the frosted ( proximal) end of a

clean slide. The harvest (or part of it) is expelled onto the slide in the form of a droplet. Next, the slide is picked
up at its frosted end between the thumb and forefinger of the nondominant hand. The other fingers are used to
create a steady platform beneath the slide. A clean slide is then held by its frosted end in the dominant hand . Its
lower long edge is placed against the first slide at a 45-90 o angle proximal to the droplet. This top edge of the slide
is then lowered until it touches and then covers the droplet and the two slides are flush . At this point, the
material is spread in one smooth, rapid motion by pulling the top slide along the entire length of the bottom
slide.
As soon as the smear has been made, the first (bottom) slide should be fixed. Any delay in fixation will result
in air-drying artifacts. The second (top) slide used for smear preparation usually contains no diagnostic material
and can be reused to make several smears from the same harvest.
An alternative method of smear preparation is t o put a clean slide on top of the slide holding the expelled
material and then to pull the two slides apart sideways. Another variant of smear preparation involves placing
a second slide over the slide holding the aspirated material and then lifting it straight up. These two
techniques are easier to master than the one-step technique.
FIXATION AND STAINING OF ASPIRATED MATERIAL
The most commonly used stains for smears of aspirated material are the Papanicolaou, Hematoxylin-Eosin,
and Romanowsky-type stains, such as MayGruenwald-Giemsa, Wright-Giemsa, and Diff-Quick.
The Papanicolaou stain requires immediate fixation in alcohol before the smears start to dry. Ethanol (95%)
is most commonly used; methanol in a 70-95% solution also produces good results. Smears intended for
Romanowsky-type stains are air-dried before the staining procedure and can be stored indefinitely in their
unstained state.

Of the Romanowsky-type stains, May-Gruenwald-Giemsa and Wright-Giemsa applied by immersion appear

to yield the best results. The Diff-Quick and WrightGiemsa stains, when applied by automatic stainer, often
fail to penetrate sufficiently into cell clusters.
A rapid staining technique is valuable for a preliminary evaluation of material before releasing the patient.
Several options are available, including a fast version of the Papanicolaou method, the hematoxylin-eosin
stain designed for frozen sections, Diff-Quick or May-Gruenwald-Giemsa stains with the time reduced to 2
min. for each staining step, and toluidine blue, which is by far the fastest. Briefly, the smear is immersed
in alcohol for 15 sec. One to 2 drops of toluidine blue solution are applied to the smear, which is wet
mounted with a coverslip. After allowing the stain to penetrate for 10-15 sec, the slide is turned over onto
a paper towel with the coverslip in place, and excess stain is removed by applying by applying pressure to
the slide.
FAILURE TO OBTAIN A REPRESENTATIVE SAMPLE:

WHY IT OCCURS AND HOW TO CORRECT IT
Excess Blood
A specimen diluted with a substantial amount of blood is likely to be inadequate

for diagnosis. There are several ways to reduce the amount of blood. The first sampling of an area is the most
likely to yield a good specimen and it should be carefully planned. In subsequent samples, the amount of blood
is likely to increase substantially. If the mass is 1.5 cm or larger in diameter, sampling of two or more areas
should be considered. In this way, it is often possible to obtain two optimal samples. Bleeding is reduced if the
direction of the needle is not changed when the tip is inside the target.
When sampling highly vascular organs such as the thyroid gland, it may be impossible to avoid aspirating
substantial amounts of blood in spite of good technique. The number of needle excursions in these
circumstances should be limited to four or five. If blood starts to appear the procedure should be terminated and
the needle withdrawn. The sampling technique without suction, describe above, is often effective in targets with
an abundant blood supply. Additionally, in cases where a substantial amount of blood is present, special
smearing techniques designed to concentrate the tissue fragments can be used.
INSUFFICIENT OR NONREPRSENTATIVE MATERIAL
1. Incorrect needle placement. For instance, if the needle is placed at a 45 o angle overlying a 1-cm mass
situated 0.5 cm under the skin surface, the needle tip will not enter the mass . When choosing an angle
other than 90o, the needle tip must be placed in a manner that will allow it to penetrate the lesion.
2. Incorrect needle placement include inserting the needle tip too deeply or too superficially. In this
situation, it is often very helpful to use the needle tip as a sensitive indicator of changes in consistency.
When the needle enters an area of increased resistance, it is likely that the tip is correctly positioned for
sampling.

3. The target is not completely immobilized. Sampling may then be hampered by the target’s moving back
and forth with the needle tip. To prevent this, firm pressure may be used; the fingers holding the target
should be very close to it.
4. A target composed predominantly of dense, connective tissue stroma, may also present sampling
problem. In this case, as the needle penetrates the target, the consistency of the target resembles that of
rubber. It is often difficult to make a 22- or 23-gauge needle travel back and forth through such a target.
These targets often contain a relatively scant epithelial component and frequently yield a “dry tap” or a
very scanty cell harvest. Fibrocystic change in the breast is an example of a lesion that can have these
characteristics,
FAILURE TO PRODUCE WELL-PRESERVED MATERIAL:
Common problems and how to correct them
Air-drying artifacts occur when alcohol fixation is delayed even for a few seconds. Specimens with scanty
cellularity are especially sensitive to drying. In order to avoid air-drying, the container with the fixative should
be at hand and ready to use. The decision on whether or not to fix a smear in alcohol should be made before
the smear preparation has been completed. The inspection of the slide should be delayed until after initial brief
fixation. If spray fixatives are preferred, an assistant should be ready to apply the fixative as soon as the smear
preparation has been completed.
Blood clotting is a common problem. It distorts the architecture of cell clusters and may obscure microscopic
detail. In order to avoid clotting, the aspiration technique must be fairly rapid. When clotting occurs during
smear preparation, alcohol fixation is generally preferable to air-drying because it allows better visualization of
the cells in the sample.
Crush artifact is another problem that usually has one of two causes. First, crushing occurs when too
much pressure is applied to the material during smear preparation. The second cause of crushing is a faulty
smear preparation technique using two slides at a slight angle instead of parallel ( flush) with each other.
The result is scraping rather than smearing of the harvest. Crush artifact may also occur if the sliding movement
begins with the slides parallel to each other, but the top slide is angled before the smear is completed. This
results in a satisfactory smear at the top end of the slid but crushed cells and decreased cellularity at the bottom.
If single cells and clusters of cells overlap to the extent that they interfer with interpretation, insufficient pressure
may have been applied during smearing. This is a much less common problem then excessive pressure.
Difficulty in separating fluid from tissue fragments when using the two-step technique occurs when the bottom
slide is insufficiently tilted toward the frosted end. This tilt must be maintained throughout the procedure.

CELL CHARACTERISTICS
Table 1-2 Summarizes the principal morphologic differences between benign and malignant cells.
These general characteristics of cells may vary from organ to organ. The relationships of cells to each other and
their cytoplasmic and nuclear characteristics in benign tissues and in cancer that are of diagnostic significance are
briefly summarized in the following sections.
Table 1 – 2. PRINCIPAL MORPHOLOGIC DIFFERENCES BETWEEN NORMAL CELLS AND

CANCER CELLS*
BENIGN CELLS CANCER CELLS

Variable within physiologic limits Variable beyond physiologic
Cell size
limits
Variable within physiologic limits
Cell shape and depends on tissue type Abnormal shapes frequent
Variable within limits of cell Significant variability

Nuclear size
cycle (anisonucleosis)
Generally spherical or kidney Aberrations of shape and
Nuclear shape
shaped configuration
Chromatin texture Finely granular texture, Coarsely granular texture,
(nondividing nucleus) “transparent” opaque
Hyperchromasia Rare Common
Multinucleation Not characteristic Not characteristic
Enlarged, of irregular
Small, regular in shape, limited
Nucleoli configuration, increased in
in number
number
Excellent (except in lymph
Adhesiveness nodes, spleen, bone marrow) Poor
No conclusive evidence of
Cell junctions According to tissue type
abnormalities
Mitotic rate
As needed for replacement Elevated
Bipolar

Mitoses Aberrant forms

Placement of mitoses in
Basal layer only Not confined to basal layer
epithelium
Cell cycle duration 16-22 hr Normal or longer
* Modified from Koss (1992)
BENIGN TISSUES
Ducts and Acini

Tissues containing ducts and glands, such as the breast, the prostate, the salivary glands and the pancreas, are
among the targets most often aspirated. The following features must be emphasized:
1. There is a generally good adherence of cells, forming flat sheets or clusters.
2. The cell borders are well demarcated, with formation of the “honeycomb” pattern, often accompanied by
evenly distributed, centrally located nuclei.
3. The nuclei are of uniform size, with fine chromatic structure and absence of molding.
4. The nucleoli are absent or small.
5. Myoepithelial cells in the form of small, dark, spindly nuclei within and outside clusters are often present.
BENIGN EPITHELIAL STRUCTURES
Histology Cytology
A. Acini

B. Ducts
C. Multilayered Epithelium
Figure 1-1.
Comparison of histologic patterns with cytologic patterns in aspirates of some benign tissues.
A. ACINI
Left: Schematic presentation of a cross section of a gland acinus with myoepithelial cells surrounding
glandular cells.

Right: In smears whole acini appear as sharply outlined, cohesive, multilayered clusters of cells of
even sizes. The myoepithelial cells (MEC) may either be found within the squashed acini or
appear as dispersed, comma-shaped, dark nuclei outside of the cell clusters. Fragments of
acini appear as small cell clusters with sharply demarcated cell borders forming a
honeycomb pattern. The myoepithelial cells are seen either outside or within these cell
clusters.
B. DUCTS
Left: Schematic presentation of a cross section of a duct with MEC.
Right: In smears t he ducts appear as flat epithelial structures in a honeycomb pattern or as detached
fragments in which the cells are arrayed in parallel rows. Depending on the caliber of the
duct, the cells are either cuboidal or columnar in shape. The MEC are seen either within or
outside of cell clusters.
C. MULTILAYERED EPITHELIUM
Left: Schematic presentation of histology
Right: The presentation in smears depends on the type of the epithelium. The cells may either form
cohesive clusters or appear singly. The size of the individual cells depends on the level of the
epithelial maturation. Superficial squamous or urothelial cells are significantly larger than cells
from the deeper layers.
MULTILAYERED EPITHELIA
The principal characteristics of aspirated multilayered eptithelia are shown in Figure 1-1C. Squamous
epithelium or the urothelium (transitional epithelium), when aspirated, sheds well-demarcated cells either
singly or in small clusters. The following features must be emphasized:
1. The cells vary in size, depending on their derivation; cells from superficial layers are generally larger
and have a more abundant cytoplasm than cells from deeper layers.

2. The nuclei are uniform in size and have finely granular chromatin. Nucleoli are generally not visible.
Note that the nuclei of superficial squamous cells tend to be pyknotic. Superficial urothelial cells
are often multinucleated, and the individual nuclei may be large and contain nucleoli.
MALIGNANT TUMORS
Adenocarcinomas
Figure 1-2A,B summarizes the principal cytologic features of adenocarcinomas. The presentation depends on
the degree of differentiation, but in general, adenocarcinomas share certain common characteristics.
1. There is formation of large, three-dimensional cell clusters, composed of several layers of superimposed
cells. Monolayered clusters (sheets) may also occur in well-differentiated tumors.
2. In papillary adenocarcinomas the clusters tend to be spherical or oval and may show palisading of
peripheral cells.
3. Individual tumor cells, which are almost invariably present, may have a cuboidal or columnar
configuration, with clear or vacuolated cytoplasm.
4. The nuclei, while large, show only moderate hyperchromasia and a moderately coarse arrangement of
chromatin. Large, sometimes multiple, nucleoli are common. The nuclei may show variability in size.
In clusters, adjacent nuclei may fit into each other’s contour, a feature described as nuclear molding.
5. Products of cell secretion include intra- or extracellular mucus and large intracytoplasmic vacuoles.
Psammoma bodies or concentric proteinaceous structures that are commonly calcified may be observed in a
variety of papillary carcinomas.
Solid Carcinomas
The main cytologic features of solidly growing carcinomas are shown in Figure 1-3. The following
must be emphasized:
1. The cancer cells are more likely to appear singly than in clusters.
2. The cell clusters have no particular structural arrangement and may be mono- or multilayered.
3. The individual cells are of variable shape and configuration and, in squamous carcinomas, may be very
bizarre.
4. In some tumors, notably the epidermoid and urothelial cancers, the cytoplasm of individual cells is sharply
demarcated. In squamous carcinoma the cytoplasm may show marked eosinophilia suggestive of keratin
formation. The keratin formation may be sufficiently abundant to change the affected cells into an
anucleated squame or a “ghost cell”. In other tumors the cell borders are often indistinct and, in clusters,
cannot be identified.

5. The nuclei are markedly enlarged and hyperchromatic and have a very coarse chromatin pattern. Nuclear
molding is common. Large nucleoli may be present, particularly in poorly differentiated cancer cells.
ADENOCARCINOMAS
GLAND FORMING
Histology Cytology

Figure 1-2. Comparison of histologic and cytologic patterns in aspirates of adenocarcinoma.
Top: Gland forming carcinomas. The cancer cells form irregular clusters with many detached cuboidal or
columnar cells. Cytoplasmic vacuoles may be observed. In some tumors the cancer cells form rosette-like clusters
(arrowhead).
Bottom: Papillary carcinomas are characterized by multilayered spherical or oval (“papillary”) clusters of cancer
cells.
SOLID CARCINOMAS
Histology Cytology
Figure 1-3. Comparison of histologic and cytologic patterns in aspirates of solid carcinomas. The
cancer cells are either dispersed or form small clusters. This tumor type is usually easily identified
in
smears.

REPORTING OF CYTOLOGY
Cytopathologic diagnoses of FNA material include:
1. POSITIVE FOR MALIGNANT CELLS- cells show conclusive evidence of malignancy. If possible, the
lesion type and the differentiation are specified.
2. NO MALIGNANT CELLS SEEN - if an adequate number of well-preserved benign epithelial cells occur
in the sample.
3. ATYPICAL/INDETERMINATE/ SUGGESTIVE OF MALIGNANCY/SUSPICIOUS
FOR
MALIGNANT CELLS - the cellular findings in the material are not diagnostic. This designation can be
followed with a description of the smear and further classification if possible. These cytologic findings
must then be correlated with the clinical impression and imaging characteristics to determine the next step
in the evaluation of the lesion.
If there are significant number of atypical but inconclusive for malignancy, the report falls into the
suggestive of malignancy category, and the FNA should be followed by excisional biopsy or a
confirmatory frozen section before definitive therapy is attempted.
4. UNSATISFACTORY – It is used when no or only minimal epithelial cellular material is obtained.
Specimens whose cellular material is obscured by blood, inflammatory cells, or necrotic debris are also less
ideal. Air-drying artifact can also distort a specimen to render it insufficient for interpretation.

CHAPTER
HEAD & NECK PATHOLOGY

HEAD AND NECK
Case 1: Retinoblastoma
Draw and Label
STUDY QUESTIONS:
1. List down the most common clinical presentation of this tumor.
2. How will you approach a child with this tumor in order for you to arrive at the correct diagnosis?

3. Give the preferred mode of management of this case. What is the prognosis?
Case 2: Squamous Cell Carcinoma (Lower Lips)
History: 59-year-old male pipe smoker, with a 1.5 cm. cauliflower mass on the lower lip. Excision biopsy was done.
Microscopic: The microscopic picture is that of nests and sheets of epithelial cells with enlarged,
hyperchromatic nuclei and eosinophilic cytoplasm. Keratin pearls are noted.
Draw and Label
STUDY QUESTIONS:
1. How did Broder grade squamous cell carcinoma? Give the differentiation of the tumor.

2. The genesis of squamous cell carcinoma of the oral cavity and tongue is closely linked to what
environmental factors?
3. Tumors with best prognosis are found in what part of the head and neck? What about tumors with worst
prognosis?
Case 3: Pleomorphic Adenoma

History: 27-year-old male, with larged mass just anterior to the right external ear. Excision biopsy
was done.
Microscopic: Examination disclosed glands of various shapes and sizes. Some of

the lumen of the glands are cystically dilated, some are slit-like; others are compressed forming a
very cellular pattern. In other areas, myxoid stroma are also seen.
Draw and Label
STUDY QUESTIONS:
1. Why does this tumor usually recur after operation?
2. What are the different salivary glands? Where are malignant tumors more common?
3. What is the most common malignant tumor of the salivary gland? In what specific gland is this tumor
commonly found?
4. What is the term used when a carcinoma arises from a pleomorphic adenoma?

Case 4: Warthin's Tumor
History: A 39-year-old female complaining of right infraauricular mass.

Biopsy was done.
Gross: A gray brown, rubbery and ovoid mass measuring 5.0 x 3.5 x 3.0 cm.
Microscopic: Microsections disclose lymphoid aggregate with overlying epithelium composed of large oxyphilic
cells.
Draw and Label
STUDY QUESTIONS:
1. What is the cell of origin of the tumor?

2. Give the other name of this tumor.
Case 5: Nasal Polyps
History: A 25 -year-old male complaining of recurrent post nasal drip.
Gross: Several fragments of light brown soft tissues measuring

3.0 x 2.5 x 1.4 cm. in aggregate.
Microscopic: Microsections disclose mucin secreting glands with dense eosinophilic cell infiltrates.
Draw and Label
STUDY QUESTIONS:
1. Is this a true neoplasm?
2.
What is the most common condition that precipitates the development of this lesion?

Case 6: Nasophagyngeal Carcinoma
History: A 69-year-old male patient who complained of frequent nose bleeding.

On rhinoscopy, a polypoid mass was noted at the right nasopharynx. Biopsy was done.
Draw and Label
CHAPTER

GYNECOLOGIC
PATHOLOGY

FEMALE GENITAL TRACT
Gynecology and obstetrics represent a large proportion of medical practice, and many medical centers
have dedicated a large area to this specialty.
Many infections of the female reproductive system are sexually transmitted. Neoplasms are important diseases of
the female reproductive system as well. The recognition of epithelial dysplasia of the cervix by cervical smears
was the beginning of the use of cytology in the detection of cancer.
Case 1: Chronic Cervicitis With Squamous Metaplasia
History: This came from a 50-year-old female patient who was operated because of uterine leiomyoma. The
slide was a section taken from the uterine cervix.
Draw and Label
Here is a gross specimen of the cervix from healthy to the chronic stage of cervicitis.
normal cervix with a smooth, glistening mucosal surface. There is a small rim of vaginal cuff from
this hysterectomy specimen. The cervical os is small and round, typical for a nulliparous woman.
The os will have a fish-mouth shape after one or more pregnancies.

This is chronic cervicitis at the transformation zone of the cervix. Shown are the presence of
Small round dark lymphocytes in the submucosa, and also hemorrhage. A dense infiltrate of
lymphocyte in histology is a sign of chronic cervicitis. Chronic cervicitis is quite common.
STUDY QUESTIONS:
1. What is the possible consequence of glycogen uptake in the cervical mucosa?
Glycogen provides a substrate for various endogenous vaginal aerobes and anaerobes,
particularly lactobacilli. Lactobacilli produce lactic acid, which maintains the vaginal pH below 4.5,
suppressing the growth of other saprophytic and pathogenic organisms.
2. What are the causes of squamous metaplasia?
 Chronic irritation (IUD)

 Chemical irritants
 Inflammation with cell destruction
 Endocrine changes at the beginning of, during, and after reproductive age.

Case 2: High Grade Squamous Intraepithelial Lesion (HSIL) or CIN3
History: This came from a 48-year-old female patient who has an abnormal pap smear report.
Draw and Label
This is cellular dysplasia in the uterine cervix. The normal cervical squamous epithelium has become
transformed to a more disorderly growth pattern, or dysplastic epithelium. The abnormal squamous cells
in HSIL are darker and larger than the squamous cells normally found in the cervix This is farther down
the road toward neoplasia, but dysplasia is still a potentially reversible process.
STUDY QUESTIONS:
1. In what portion of the cervix is SIL (Squamous Intraepithelial Lesion) usually located?
A squamous intraepithelial lesion (SIL) is an area of abnormal tissue on the skin inside of your body. It can affect the
cervix, vagina, vulva, anus, penis or back of the throat.

Most cervical intraepithelial lesions commonly arise from the transformation zone (squamocolumnar junction) /
squamous epithelial cells of the external lining of the cervix.
2. What are the different cell types usually seen in pap smear? Describe each.
 Superficial squamous cells

o Polygonal with abundant eosinophilic cytoplasm
o Matures in the ectocervix
o Pyknotic nuclei, N:C ratio is low
o Most mature
o Predominant in non-pregnant reproductive age women
 Intermediate squamous cells

o Cytoplasm is generally bluish/cyanophilic,
thin and transparent
o Nuclei is round but not as pyknotic as
superficial cells, fine and dispersed granular chromatin
o Approx. twice the size of parabasal cells
o Predominant in pregnant women
o Cytoplasm become angular, irregular, and
folded as cell enlarges
 Parabasal cells
○ smallest epithelial cell
○ larger nuclei
○ Finely granular chromatin
○ no visible nucleolus
○ largest N:C ratio
○ most immature cell in the ectocervix
○ predominant in menopausal women
 Basal cells
o Small round to oval
o Dense cyanophilic cytoplasm
o Large nucleus, fine reticular chromatin, small nucleoli
 Endocervical cells
o Columnar
o Abundant vacuolated cytoplasm
o Eccentrically placed vesicular
nuclei, inconspicuous nucleoli
 Cells arranged in strips giving a picket fence appearance or in sheets resembling honeycomb

Case 3: Squamous Cell Carcinoma, cervix
History: A 50-year-old female with irregular vaginal spotting associated with

leukorrhea.
Gross: The specimen from a 4 quadrant cervical punch biopsy consists of 4 brownish irregularly
shaped tissue fragments measuring up to 0.7 cm. in their greatest dimension.
Microscopic: Sections show cords of stratified squamous epithelial lining composed of polygonal - shaped tumor
cells with moderately pleomorphic and hyperchromatic nuclei. The moderately fibrous stroma
shows many inflammatory cells with focal necrosis and hemorrhage.
Draw and Label
Sections show cords of stratified squamous epithelial lining composed of polygonal - shaped tumor cells
with moderately pleomorphic and hyperchromatic nuclei. The moderately fibrous stroma shows many
inflammatory cells with focal necrosis and hemorrhage.

At high magnification, nests of neoplastic squamous cells are invaded through a chronically inflamed
stroma. This cancer is well-differentiated, as evidenced by keratin pearls. However, most cervical
squamous carcinomas are non-keratinizing
STUDY QUESTIONS:
1. What is the role of HPV in carcinoma of the cervix?
A. High-risk HPVs (HPV 16 & HPV 18) - most important factor in the development of cervical CA
> HPV 16: 60%
> HPV 18: 10%
B. HPV infects immature cells but can replicate in mature cells
> E7 → Rb, p21 and p27 inactivation → cell proliferation
> E6 → p53 inactivation and activation of telomerase → cellular immortality
C. Physical state of the virus
2. What are the risk factors associated with cervical carcinoma?

 HPV infection-linked features: multiple sexual partners, early age of first intercourse, history of
venereal disease
 Smoking
 HIV infection

Case 4: Endometrial Hyperplasia without Atypia (Simple Hyperplasia)
History: A 45-year-old female patient underwent diagnostic curettage because of prolonged

vaginal bleeding.
Draw and Label
The prominent folds of endometrium in this uterus opened to reveal the endometrial
cavity are an example of hyperplasia. Cells forming both the endometrial glands and the
stroma have increased in number. As a result, the size of the endometrium has
increased. This increase is physiologic with a normal menstrual cycle.
The endometrial cavity is opened to reveal lush fronds of hyperplastic endometrium.

Endometrial hyperplasia usually results with conditions of prolonged estrogen excess and can
lead to metrorrhagia (uterine bleeding at irregular intervals), menorrhagia (excessive bleeding
with menstrual periods), or menometrorrhagia.

 Highly proliferative glands in stroma

 Glands are enlarged and irregular with columnar cells
STUDY QUESTIONS:
1. What are the causes of Abnormal Uterine Bleeding in the adolescence and menopausal stages?
ABNORMAL UTERINE BLEEDING

Can be caused by well-defined pathologic conditions
- chronic endometritis,
- endometrial polyps,
- submucosal leiomyomas, or
- endometrial neoplasms
It most commonly stems from hormonal disturbances that produce

dysfunctional uterine bleeding.
Causes of Abnormal Uterine Bleeding:
a. Adolescence: Anovulatory cycle, coagulation disorders

b. Perimenopausal: DUB, Anovulatory cycle, Anatomic lesions
c. Postmenopausal: Endometrial atrophy, Anatomic lesions

ANOVULATORY CYCLE
 The most frequent cause of dysfunctional uterine bleeding which results from hormonal imbalances
 Most common at menarche and in perimenopausal period
ENDOMETRIAL ATROPHY
 Uterine lining may become too thin
 Low levels of estrogen
2. What is Dysfunctional Uterine Bleeding?
Dysfunctional uterine bleeding
 Uterine bleeding that lacks an underlying structural abnormality.

 This commonly results from any hormonal disturbances and disturbances in normal cyclical proliferation,
differentiation, and shedding of the endometrium

Case 5: Adenocarcinoma, endometrium
History: A 58-year-old woman consulted because of irregular vaginal bleeding and excessive
leukorrhea for the past month.
Gross: The specimen from the D & C consists of several brownish irregularly shaped soft
tissues fragments with moderate amount of blood clots, measuring 2 x 2 cm. in their
aggregate dimension.
Microscopic: Sections show several irregular tumor glands lined by tall columnar cells with slightly
pleomorphic and vesicular nuclei with small nucleoli. Occasional intraluminal
necrotic debris and hemorrhage is seen. The stroma is scanty with few inflammatory
cells, with focal areas of necrosis and hemorrhage.
Draw and Label
This adenocarcinoma of the endometrium is more obvious. Irregular masses of white

tumor are seen occupying most of the interior of this uterus that has been opened
anteriorly. The cervix is at the bottom of the picture. This enlarged uterus was no doubt

palpable on physical examination. Such a neoplasm may often present with abnormal
bleeding.
The endometrial adenocarcinoma in the polyp at the left is moderately differentiated, as

a glandular structure can still be discerned. Note the hyperchromatism and
pleomorphism of the cells, compared to the underlying endometrium with cystic atrophy
at the right.
STUDY QUESTIONS:
1. Discuss briefly the pathogenesis of endometrial carcinoma.
PATHOGENESIS:
 Uninterrupted endometrial proliferation
 Hormonally stimulated by endogenous or exogenous estrogen unopposed by progesterone or
progestins
 Progressing through states of simple to complex forms of endometrial hyperplasia (EH).
Atypical premalignant lesions (EIN) → Endometrioid carcinoma

o Stromal and/or myometrial invasion
o PTEN mutations
o KRAS2 mutations
o Microsatellite instability caused by mismatch repair (MMR) defects, and near-diploid
karyotype
Others:
o Insulin resistance
o Hyperandrogenemia

2. Name other causes of abnormal uterine bleeding in the postmenopausal age group.
 Atrophic vaginitis
 Endometrial atrophy
 Endometrial hyperplasia
 Endometrial polyps
 Submucosal leiomyomas
Exercise 3: Mucinous Cystadenocarcinoma
Draw and Label

STUDY QUESTIONS:
1. What is pseudomyxoma peritonei?

2. Classify tumors of the ovary based on their tissue of origin.
3. What are the most common benign and malignant tumors of the ovary?

Case 7: Mature Cystic Teratoma (Dermoid Cyst), Ovary
History: 20-year-old female with abdominal mass.
Gross: The specimen consists of a cystic ovary with smooth brownish - white external
surface, measuring 10 x 5 x 5 cm. Cut sections reveal a cyst filled with sebaceous
material and hair.
Microscopic: Microsections showed a cyst lined by a stratified squamous epithelium with underlying
mucous, apocrine, and sebaceous glands. The wall is fibrous with few adipose cells.
Draw and Label


STUDY QUESTIONS:
1. Differentiate mature from immature teratoma based on the following:

2. What is the karyotype of mature cystic teratoma?

3. What is monodermal teratoma? Give one example.

CHAPTER
NEUROPATHOLOGY


CENTRAL NERVOUS SYSTEM I
Infections of the nervous system are classified according to the infected tissue into (1) meningeal
infections (meningitis), which may involve the dura primarily (pachymeningitis) or the pia-arachnoid
(leptomeningitis); and (2) infections of the cerebral and spinal parenchyma (encephalitis or myelitis). In
many cases, both the meninges and the brain parenchyma are affected to varying degree
(meningoencephalitis).
CENTRAL NERVOUS SYSTEM II
Intracranial and spinal neoplasms may be primary or metastatic; in most autopsy series, metastatic
tumors are more common. Primary intracranial tumors number about 13,000 new cases per year in the
United States and represent about 2% of deaths from malignant neoplasms. They are the second most
common group of neoplasms in children, after leukemia and lymphoma, if considered as one group.
Taken overall, 65% of primary intracranial neoplasm are of glial origin (gliomas), 10% meningiomas,
10% acoustic schwannomas, 5% medulloblastomas and 10% others. Primary malignant lymphomas of
the CNS have recently increased in frequency because they are common in patients with AIDS. Tumors
of the neurons per se are extremely uncommon except in childhood ( e.g. Medulloblastoma).
Case 1: Tuberculous Meningitis
History: A 5 -year-old female with history neck rigidity, vomiting, and headache.
Gross: Autopsy specimen of the brain shows shaggy and dull meninges
with multiple gray-white nodularities noted at the basal portion.
Microscopic: Section shows nodules with central caseation necrosis rimmed by

granulomatous infiltrates.
Draw and Label

Here is another example of an acute meningitis from bacterial infection. Note how the
sulci are obscured by the exudate. A sample of cerebrospinal fluid (CSF) can be
obtained via lumbar puncture, if there is no papilledema to indicate the intracranial
pressure is too high to safely perform this procedure. The CSF in such cases typically
has a low glucose, high protein, and a high cell count with many PMN's. A gram stain
should be done to aid in identification of bacterial organisms. The lactate
dehydrogenase (LD) is increased with bacterial meningitis but not with viral meningitis.
Microscopically, a neutrophilic exudate is seen involving the meninges at the left,

with prominent dilated vessels. There is edema and focal inflammation (extending down
via the Virchow-Robin space) in the cortex to the right. This acute meningitis is typical
for bacterial infection.
This edema can lead to herniation and death. Resolution of infection may be followed by
adhesive arachnoiditis with obliteration of subarachnoid space leading to obstructive
hydrocephalus.

Microscopically, a gram stain reveals gram negative diplococci within a neutrophil,

typical for Neisseria meningitidis. Gram stain and culture can be performed on
cerebrospinal fluid obtained via lumbar puncture.
STUDY QUESTIONS:
1. What are the routes of infection to the CNS?
4 Principal routes of infection to the CNS:

 Hematogenous spread - most common route
 Direct implantation- mostly from trauma or meningomyelocele
 Local extension- from infected adjacent structures
 Transport along peripheral nervous system- seen in rabies and Herpes zoster
 Respiratory tract - most common source of entry of microorganisms
2. Give the clinical signs of increased intracranial pressure.
 Headache
 Blurred vision
 Feeling less alert than usual
 Vomiting
 Changes in your behavior
 Weakness or problems with moving or talking
 Lack of energy or sleepiness

3. What are the possible complications that may arise from meningitis?
The most serious complications of chronic tuberculous meningitis are arachnoid fibrosis producing hydrocephalus
and obliterative endarteritis producing arterial occlusion and brain infarction.
4. Give the typical CSF findings in this patient.
 Pleocytosis- mononuclear cells or mixture of neutrophils and mononuclear cells

 Elevated protein concentration
 Moderately reduced or normal glucose
5. How would a patient with this condition die? Explain.
If left untreated, it can be fatal.

 Waterhouse-Friderichsen Syndrome
o Caused by meningitis-associated septicemia and hemorrhagic infarction of the adrenal glands

Exercise 1: Viral Encephalitis
Draw and Label
The hemorrhages seen here in the temporal lobe are due to Herpes simplex virus
infection. Viral infections produce mononuclear cell infiltrates microscopically.
Microscopical examination in the acute phase shows meningeal and perivascular mononuclear
cells (white arrow), activated microglia (black arrow), microglial nodules, and intranuclear
inclusions.
Virchow–Robbin space of vessels in affected areas is expanded by lymphocytes, histiocytes,

and fewer plasma cells.
A perivascular cuffing of inflammatory cells (mainly lymphocytes and plasma cells) in the brain.

STUDY QUESTIONS:
1. Give the more common virus in our country that can cause this?
 Japanese encephalitis
2. How does the virus cause damage?

Viral encephalitis is a parenchymal infection of the brain almost invariably associated with meningeal inflammation
(meningoencephalitis) and sometimes with simultaneous involvement of the spinal cord (encephalomyelitis).
HSV-1
 Inferior and medial regions of the temporal lobes
 Orbital gyri of the frontal lobes
 Necrotizing and often hemorrhagic
 Perivascular inflammatory infiltrates
 Cowdry type A intranuclear viral inclusions
Exercise 2: Rabies
STUDY QUESTIONS:
1. What is the reason behind the practice of observing the dog after it bit a person?
An animal or a dog that have bitten someone are quarantined for 10 days under observation to
see if they develop signs of rabies.
Studies have shown that dogs, cats, and ferrets only shed the rabies virus in their saliva for a
short period of time (usually 4 to 5 days) before they develop symptoms. If the animal has not
developed symptoms by the tenth day after the exposure then the animal would not have been
shedding the virus at the time of the exposure.
The signs, symptoms, and outcome of rabies in animals can vary. Symptoms in animals are
often similar to those in humans. These include early nonspecific symptoms, acute neurologic
symptoms, and ultimately death.
2. What is the reason for the 10 days duration of observation?

If the rabies virus was in the animal’s saliva at the time of the bite, it means the virus has
already reached the animal’s brain.
Within three or four days the animal will begin to develop brain damage. The brain damage
would lead to the death of the animal within the 10 day period
 3-4 days: brain damage and start acting strange
 10 day period: brain damage leading to death
PICTURE DISCUSSION
Case 1: Bacterial Meningitis
A 70-year-old man has a 2-day history of worsening generalized headache and increasing obtundation. He
now complains of stiffness in his neck.
PE Findings:
BP 130/85 mm Hg T 38.7°C PR 85/minute RR 23/minute
Pertinent Laboratory Results:

WBC count of 16,850/microliter

Blood glucose- 88 mg/dL

CSF glucose- 32 mg/dL
CSF protein- 146 mg/dL
CSF total cell count- 3800 WBCs (95% PMNs and 5 % mononuclears)
Photomicrographs shall be posted on line.
STUDY QUESTIONS:
1. Describe the gross and microscopic findings
A thick layer of suppurative exudate covers the brain surface and thickens the leptomeninges.
The meningeal vessels are engorged and stand out prominently. The anatomic distribution of
the exudate varies; in H. influenzae meningitis, for example, it is usually basal, whereas in
pneumococcal meningitis it is often densest over the cerebral convexities near the sagittal sinus.
From the areas of greatest accumulation, tracts of pus follow along blood vessels on the surface
of the brain. When the meningitis is fulminant, the inflammation may extend to the ventricles,
producing ventriculitis. The ventricles may also be the portal for CSF involvement by blood-
borne infections because the choroid plexus lacks a blood-brain barrier.

A neutrophilic exudate is seen involving the meninges at the left, with prominent
dilated vessels. There is edema and focal inflammation (extending down via the
Virchow-Robin space) in the cortex to the right. This acute meningitis is typical for
bacterial infection. This edema can lead to herniation and death. Resolution of infection
may be followed by adhesive arachnoiditis with obliteration of subarachnoid space
leading to obstructive hydrocephalus.
2. Discuss the pathogenesis.

3. Give your differential diagnosis.
 Viral meningitis
 Drug-induced aseptic meningitis
 Paraneoplastic syndrome
 Subdural empyema
 Subarachnoid hemorrhage
 Stroke
 Delirium tremens
 Brain abscess
 Paravertebral or epidural abscess
4. What long-term complication may develop in this patient?
 Waterhouse-Frederichsen Syndrome
0. Result from meningitis-associated septicemia and hemorrhagic infarction of the adrenal
glands
 Hydrocephalus (in some patients)
 Arterial or venous infarcts
 Abducens palsy
 Deafness
 Subdural empyema
 Increased intracranial pressure (ICP)
 Brain abscess, Brain herniation, Brain herniation
 Systemic complication

Case 2: Psammomatous Meningioma
History: A 49-year-old female, complained of frequent headaches. A CT scan showed a tumor in the
region of the pre-central gyrus. On surgery, an ovoid, grayish white mass was noted
attached to the meninges overlying the pre-central gyrus. The mass was removed.
Gross: The mass measures 1.5 x 1.5 x. 1.0 cm. It is well circumscribed, rubbery, grayish white and
has a solid cut surface.
Microscopic: The tumor is cellular with syncitial (whorls), fibroblastic and transitional patterns seen.
Numerous psammoma bodies are noted.
Draw and Label
Well circumscribed dural-based meningioma with a bulging tan-pink coarsely granular

appearance that may exert mass effect upon the underlying brain parenchyma. Focal areas of
hemorrhage are noted in the upper left corner. The peak incidence of meningiomas is seen in
the elderly (6th & 7th decades). They are slow-growing dural-based tumors.

Meningothelial cells are packed together in fascicles, whorls, and syncytia. The nuclei
are bland and occasionally inconspicuous nucleoli can be noted. Mitotic figures are
absent.
High power view of meningothelial meningioma syncytia. The cells look monomorphic.
Nuclei are round to ovoid harboring fine chromatin and inconspicuous nucleoli.
Scattered lymphocytes can be noted in the background.
STUDY QUESTIONS:
1. What are the calcified bodies seen in this slide?
Psammoma bodies
 concentric rings of calcification deposited over pre-existing whorls
2. What is the cell of origin of these tumors? Are these benign or malignant?
Meningiomas are predominantly benign tumors of adults that arise from the meningothelial cells of the arachnoid
and are usually attached to the dura.
Meningiomas may be found along any of the external surfaces of the brain as well as within the ventricular system,
where they arise from the stromal arachnoid cells of the choroid plexus.
Case 3: Astrocytoma, Grade III

History: A 74 -year-old male, with an intracranial space occupying lesion.
Gross: The mass is tan, soft, poorly circumscribed measuring 1.7 x 1.5 x 1.2 cm.
Microscopic: The tumor is very cellular with proliferation of astrocytes. They exhibit nuclear
pleomorphism and hyperchromasia. Also noted are prominent vascular channels and
endothelial proliferation. Areas of hemorrhages are seen.
Draw and Label
The tumor is very cellular with proliferation of astrocytes. They exhibit nuclear pleomorphism
and hyperchromasia. Also noted are prominent vascular channels and endothelial proliferation.
Areas of hemorrhages are seen.
STUDY QUESTIONS:
1. Why is this lesion not a glioblastoma multiforme?
 It originates from a specific glial cell namely the star-shaped astrocytes.
 Glioblastoma multiforme (WHO grade IV) are cytologically highly pleomorphic, and constituent
cells vary greatly in size and shape, with large bizarre nuclei and multinucleated cells.
 Mitotic activity is high
 Vascular proliferation with characteristic pseudopalisading necrosis or with serpentine
pattern
2. What is the unifying histologic feature of astrocytoma?
 Diffuse astrocytoma : Hypercellular, elongated or irregular hyperchromatic nuclei

 Anaplastic astrocytoma : Hypercellular (more dense); readily detectable mitotic activity

 Glioblastomas: variation in the appearance of the tumor from region to region is characteristic; some areas
are firm and gray-white, while others are soft and yellow due to necrosis or red due to hemorrhage and
hypervascularity
3. Give 2 microscopic characteristics of the lesion, which make us think more of an anaplastic
astrocytoma than benign astrocytoma.
 More densely cellular and have greater nuclear pleomorphism

 Mitotic figures are often observed.
PICTURE DISCUSSION
Case 1: Glioblastoma Multiforme (WHO IV)
A 53-year-old woman has a grand mal seizure. Her CSF values reveal a total protein of 117 mg/dL,
normal glucose, and 3 WBCs/uL, with no microorganisms by Gram stain. A large right cerebral mass is
resected as shown.
Photomicrographs shall be posted.
STUDY QUESTIONS:

 Soft infiltrating mass on the left side and there is presence of necrosis and hemorrhage
 Vascular with prominent areas of necrosis and hemorrhage
Glioblastomas display hypercellularity, greater nuclear pleomorphism and

hyperchromasia, and increased mitotic activity - all of which can be seen here. The
background has a fibrillary appearance.
Higher magnification showing nuclear pseudopalisading - aggregation of tumor cells

around the periphery of the necrotic areas.

Glioblastoma (WHO Grade IV) : “Glioblastoma multiforme
3. Explain the CSF findings.
 Total Protein = 117 mg/dL

o Increased permeability of the BBB
o Decreased resorption of the arachnoid villi
o Mechanical obstruction of the CSF flow caused by the tumor
 Normal Glucose
 3 WBCs/uL = within normal levels
 No microorganisms found in Gram Stain
4. What genetic alterations can be present?
 Most primary are IDH-wild type

 Gain of chromosome 7
 Loss of chromosome 10
 TERT promoter mutations
 EGFR gene amplification

Case 2: Hemorrhagic Infarct
A 77-year-old man with past medical history significant only for poorly controlled hypertension develops
loss of consciousness. He develops bilateral “blown” pupils and becomes unresponsive.
STUDY QUESTIONS:
Here is a cerebral infarct from an arterial embolus, which often leads to a hemorrhagic
appearance. There is edema which obscures the structures. The acutely edematous infarcted
tissue may produce a mass effect. Note the decrease in size of the ventricle on the left with shift
of the midline.

The neurons are the most sensitive cells to anoxic injury. Seen here are red neurons which are
dying as a result of hypoxia. One of the most sensitive areas in the brain to hypoxic injury is the
hippocampus, as seen below.
2. Discuss the pathogenesis.

Secondary hemorrhage can occur from ischemia-reperfusion injury following spontaneous or
therapeutic dissolution or fragmentation of the intravascular occlusive material
This process secondary hemorrhagic transformation and leading to a hemorrhagic infarct
develops if the causative ischemic event lasts long enough to damage small blood vessels in the
affected area.
The resulting reperfusion hemorrhages are largely petechial in nature, but may be multiple or
even confluent
3. Give your differential diagnosis.
 Ischemic stroke
o Ischemic stroke is due to reduced/ loss of blood supply because of either obstruction due to
embolism or a thrombus
 Hemorrhagic stroke
o Occurs in a background of hypertension causing a rupture of a blood vessel
4. What long-term complication may develop in this patient?
 Muscle weakness
 Decreased sensation
 Thinking difficulties
 Difficulty swallowing or talking
 Loss of bladder or bowel control
 Loss of vision
 Seizures

 Mental health challenges such as depression
Case 3: Alzheimer’s
A 77-year-old man with a history of progressive withdrawal and apathy is found on formal examination to
have severe short-term memory loss and is unoriented to place or time. No focal neurologic signs were
noted.
Photomicrographs shall be posted on line.
STUDY QUESTIONS:
1. Describe the gross and microscopic findings.

The cerebral atrophy seen here mainly in the frontal and parietal regions is characterized by narrowed
gyri along with widened sulci. The atrophy seen here was due to dementia of the Alzheimer type
(Alzheimer disease) marked by progressive loss of higher mental function.
This is a neurofibrillary "tangle" of Alzheimer's disease. The tangle appears as long pink filaments (Tau
Filaments) in the cytoplasm. They are composed of cytoskeletal intermediate filaments. This tangles are
usually seen in neurodegenerative diseases
Alzheimer’s Disease
3. What are possible gene mutations associated with this pathology?

 Single-gene mutations associated with early- onset Alzheimer’s disease
o Amyloid precursor protein (APP) on chromosome 21
o Presenilin 1 (PSEN1) on chromosome 14
o Presenilin 2 (PSEN2) on chromosome 1
 These mutations lead to a gain of function, such that the γ-secretase complex generates
increased amounts of Aβ, particularly Aβ42
 Other genetic risk factors
o Apolipoprotein E (ApoE) on chromosome 19; three alleles exist (ε2, ε3, and ε4); dosage
of the ε4 allele increases the risk of AD and lowers the age of onset of the disease

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ANGELES UNIVERSITY FOUNDATION

GENERAL AND SYSTEMIC PATHOLOGY

Academic Year 2021-2022

This Manual Belongs to KAMODIA DRASHTI

GONZALO B. ROMAN, JR., MD, FPSP

LOU GRACE T. MANALILI, RMT, DVM

ANGELES UNIVERSITY FOUNDATION | SCHOOL OF MEDICINE | DEPARTMENT OF PATHOLOGY II

This is provided only for educational purposes to facilitate virtual learning

discussions in lieu of traditional laboratory sessions.

ANGELES UNIVERSITY FOUNDATION | SCHOOL OF MEDICINE | DEPARTMENT OF PATHOLOGY III

I. I. Respiratory PathologyPulmunary Pathology .................. 1

V. Liver Pathology ........................................................................................ 67

VII.VI. Dermatopathology ................................................................................. 76

VIII.VII. Endocrine PathologyEndocrine Pathology .................. 87

IX. VIII. Bone and Joint PathologyRenal .................. 96

Soft Tissue Pathology

Male Reproductive Pathology

XII. Breast Pathology

XIII. Female Reproductive Pathology

XII. Head and Neck Pathology .................................................................... 137

ANGELES UNIVERSITY FOUNDATION | SCHOOL OF MEDICINE | DEPARTMENT OF PATHOLOGY IV

XV. XIII. Female Reproductive Pathology .......................................................... 145

INTRODUCTION: The Discipline of Pathology

There are two general divisions of Pathology.

In Systemic Pathology, we study these phenomena at the organ-system

(1) Clinical Pathology – is concerned with biochemical and microbiologic procedures

(2) Anatomic Pathology – is a separate section – called histopathology. It considers structural

ANGELES UNIVERSITY FOUNDATION | SCHOOL OF MEDICINE | DEPARTMENT OF PATHOLOGY V

The AUF-SOM Department of Pathology

Other Helpful Textbooks:

ANGELES UNIVERSITY FOUNDATION | SCHOOL OF MEDICINE | DEPARTMENT OF PATHOLOGY VI

ANGELES UNIVERSITY FOUNDATION | SCHOOL OF MEDICINE | DEPARTMENT OF PATHOLOGY 1

ANGELES UNIVERSITY FOUNDATION | SCHOOL OF MEDICINE | DEPARTMENT OF PATHOLOGY 2

LEARNING OBJECTIVES (Pulmonary Vascular Diseases)

ANGELES UNIVERSITY FOUNDATION | SCHOOL OF MEDICINE | DEPARTMENT OF PATHOLOGY 3

At the end of the module, the student should be able to:

1. Organize and discuss features of pulmonary embolism in terms of clinical presentation,

LEARNING OBJECTIVES (Pulmonary Infections)

At the end of the module, the student should be able to:

ANGELES UNIVERSITY FOUNDATION | SCHOOL OF MEDICINE | DEPARTMENT OF PATHOLOGY 4

LEARNING OBJECTIVES (Tumors of the Lung)

At the end of the module, the student should be able to:

LEARNING OBJECTIVES (Obstructive Pulmonary Disease)

At the end of the module, the student should be able to:

ANGELES UNIVERSITY FOUNDATION | SCHOOL OF MEDICINE | DEPARTMENT OF PATHOLOGY 5

LEARNING OBJECTIVES (Restrictive Pulmonary Disease)

At the end of the module, the student should be able to:

ANGELES UNIVERSITY FOUNDATION | SCHOOL OF MEDICINE | DEPARTMENT OF PATHOLOGY 6

7. Organize and discuss features of sarcoidosis in terms of clinical presentation, etiology,

LEARNING OBJECTIVES (Pneumoconiosis)

At the end of the module, the student should be able to:

1. Define and discuss the basic pathogenesis of pneumoconiosis.

ANGELES UNIVERSITY FOUNDATION | SCHOOL OF MEDICINE | DEPARTMENT OF PATHOLOGY 7

LEARNING OBJECTIVES (Mediastinum and Pleura)

At the end of the module, the student should be able to:

Case 1: Chronic Passive Congestion, Lung

ANGELES UNIVERSITY FOUNDATION | SCHOOL OF MEDICINE | DEPARTMENT OF PATHOLOGY 8

months prior to admission and later developed difficulty to breathing,

Draw and Label:

ANGELES UNIVERSITY FOUNDATION | SCHOOL OF MEDICINE | DEPARTMENT OF PATHOLOGY 9

ANGELES UNIVERSITY FOUNDATION | SCHOOL OF MEDICINE | DEPARTMENT OF PATHOLOGY 10

Case 2: Pulmonary Infarct