HISTOPATHOLOGY LEC

PROFESSOR/S: Sir Mark D. Francisco

THIRD YEAR – 1ST SEMESTER | S.Y 2023 – 2024

I. PATHOLOGY LABORATORY
A. CLINICAL LABORATORY * Cancer can block a certain passage way OR mimic or
B. ANATOMICAL LABORATORY copy a certain production or secretion of hormones,
II. ROLE OF MEDICAL TECHNOLOGY enzymes, and substances in the body
III. FUNDAMENTALS OF HISTOLOGY ❖ Surgical Pathology vs. Cytological Pathology
A. NORMAL CELL STRUCTURE ➢ Surgical – tissue specimen
B. INTERCELLULAR COMMUNICATION ➢ Cytological – fluids, smears
C. TISSUES ❖ Histotechnician vs. Histotechnologist
IV. INTRODUCTION TO PATHOLOGY ➢ Histotechnician: Techniques, applications, or
V. PATHOLOGIST skills, support in the laboratory
VI. MODERN PATHOLOGY ➢ Histotechnologist: Analyst
VII. DIVISION OF PATHOLOGY
VIII. PROCEDURE III. FUNDAMENTALS OF HISTOLOGY
IX. 5 ASPECT OF SIGNIFICANT REPORT
X. QUALITY CONTROL A. Normal Cell Structure
◉ Cells – Dynamic structures existing in fluid
I. PATHOLOGY LABORATORY environment
• PATHOLOGY LABORATORY OR INSTITUTE OF o Has distance to prevent frictions and damages
PATHOLOGY
▪ Institute – Laboratory somehow is active in Cell Membrane
research; not just releasing results • Phospholipids, glycolipids, cholesterol, proteins, and
carbohydrates
A. Clinical Laboratory • Some with mucopolysaccharides or “glycocalyx”
o Plasma is more opaque than serum due to its • Proteins and glycoproteins — “antigens” or
fibrinogen content “receptors”
❖ Section in Clinical Laboratory • Microfilaments: contractile structures (cytoskeleton
1. Clinical Microscopy with actin subunits)
2. Serology • Microvilli: absorptive and secretory cells
3. Blood Banking
Functions of Cell Membrane:
B. Anatomical Laboratory 1. Selective permeability: (diffusion, sodium pump,
pinocytosis)
II. ROLE OF MEDICAL TECHNOLOGY 2. Holds membrane antigen
3. Cell receptors
❖ Histopathology Laboratory
➢ Preparation of slide Nucleus
➢ Working directly with the head of the laboratory • Nuclear chromatin (RNA and DNA) and nucleoli
(Pathologist) • Nuclear membrane: outer envelope (ribosomes and
➢ More of a support than an actual analyst endoplasmic reticulum)
❖ Histology vs. Histopathology • Nuclear chromatin: chromosomes (23 pairs, 46
➢ Histology – study everything that is normal chromosomes
➢ Histopathology – study abnormalities that leads ➢ autosomes: 22 pairs (44 chromosomes)
to disease ➢ sex chromosomes: 1 pair (XX female | XY male)
* Mutation is normal for survival
 CHAPTER 1: INTRODUCTION TO GENERAL PATHOLOGY

Cytosol ▪ Ion channels – for electrolytes exchange

▪ G-protein receptors – phosphorylating
• Gel-like ground substance where organelles are enzymes for metabolic and synthetic
suspended functions of cells

C. TISSUES
Organelles
• “little organs”
FOUR BASIC TYPES
▪ Cytoskeleton
▪ Mitochondria TISSUE CELL FUNCTION
▪ Ribosomes
▪ E. reticulum Epithelial Polyhedral cells Lining
▪ Golgi Apparatus Fixed and Support and
Connective
▪ Lysosome wandering cells protection
▪ Peroxisome
Elongated Contractile
Muscle
contractile cells movements
B. INTERCELLULAR COMMUNICATION
1. Intercellular Junction – “cell to cell contact” Elongated with
Transmission of
Nervous extremely fine
2. Molecular Interactions Between Cells – molecular nerve impulses
processes
or chemical agents/factors

TYPES OF COVERING EPITHELIA

Intercellular Junction
CELL LOCATION FUNCTION
1. Occluding Junction (Zonula occludens)
➢ Below the luminal margins of adjacent cells ▪ Movement of
2. Adhering Junctions (Zonula adherens) mesoderm
➢ Below the occluding zones, contact with actin Simple Blood vessels, ▪ active
microfilaments Squamous cardiac linings transport
3. Desmosomes (Macula densa) ▪ secretion in
➢ Tiny adhesion plates, numerous in epidermis mesothelium
4. Gap Junctions (Nexus)
➢ Lateral surfaces of epithelial cells Simple Ovary and thyroid ▪ Covering
Cuboidal gland ▪ Secretion
Molecular Interactions Between Cells
▪ Protection
• chemical agents/molecular agents or factors (need Simple Intestine and ▪ Lubrication
something to mediate) Columnar gallbladder ▪ Absorption
1. Cell adhesion molecules (CAMs) ▪ Secretion
o chemicals mediating interactions
o ECM - extracellular matrix interactions ▪ Protection
o Important in: fertilization, embryogenesis, tissue Pseudostratifie Nasal cavity, ▪ Secretion
repair, hemostasis, apoptosis and inflammation d trachea, bronchi ▪ ciliated
o Examples: Integrins, Cadherins, Selectins, transport
Immunoglobulin, CD44 (leukocyte-endothelial
interactions) Stratified ▪ Prevention of
Squamous Epidermis water loss
2. Cytokines Keratinized ▪ Protection
o Peptides
o Activation of immune system Mouth, larynx,
o Examples: Interferons (IFN), Interleukins (IL), Stratified ▪ Prevention of
esophagus,
Tumor necrosis factor group (TNF), Squamous water loss
vagina, anal
Transforming growth factor (TGF), Colony Nonkeratinized ▪ Protection
canal
stimulating factor (CSF), Growth factors
3. Cell membrane receptors Stratified Sweat glands, Protection,
o proteins, glycoproteins or lipoproteins Cuboidal ovarian follicles secretion
o Examples:
▪ Enzyme-linked receptors – control of cell Transitional Bladder, ureters, Protection,
growth

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 CHAPTER 1: INTRODUCTION TO GENERAL PATHOLOGY

• Practice of Medicine vs. Pathology

renal calyces distensibility
➢ Medicine – process of treating a patient
➢ Pathology – diagnostic procedure to detect a
Stratified Conjunctiva Protection
disease from patient
Columnar
Cornelius Celsus
TYPES OF CONNECTIVE TISSUE • “Four cardinal signs of Inflammation”
➢ Rubor (redness)
Loose Connective Tissues
General Type ➢ Tumor (swelling)
Dense Connective Tissues
➢ Calor (heat)
Cartilage ➢ Dolor (pain)
• Hyaline - present in the ➢ Loss of function
trachea
• Fibrous - Intervertebral disk
• Elastic - Blood vessels Anton Van Leeuwenhoek
• Microscope
Bone
• Histological Stain (saffron-muscle)
• Cancellous
Special Type • Compact o Staining a tissue specimen
o Saffron is a red stain used for muscle
Blood o We stain specimens to make them more visible
• RBC
and detailed
• WBC (differential count)
• Platelets
Marcello Malpighi
Lymph • Father of Histology
Hematopoietic Tissues
• Study capillaries of the skin

TYPES OF TISSUES Giovanni Morgagni

Cardiac - Involuntary movement
Muscle Smooth - Involuntary movement
Skeletal - Voluntary movement
• Central Nervous System
• Peripheral Nervous System
Nervous
• Sensory: Eyes, Ears, Nose, Touch,
Tongue
IV. INTRODUCTION TO PATHOLOGY
◉ PATHOLOGY – medical science and practice
concerned with all aspects of the diseases
• Religious belief: disease was the outcome of curse
from God
• Evolved from Anatomy, Medicine, and Surgery
• Hippocrates – “Father of Medicine”
➢ study of patient’s symptoms and describe
methods of diagnosis
V. PATHOLOGIST
• Clinicopathologic Correlation (CPC) – importance
of correlating what you can see from the patient to
the result of the lab
• Cause, lesions, symptoms, and outcome of disease
Percival Pott
• Chimney Soot (carcinogenic)
• Discovered some factors that cause cancer
John Hunter
• Pathologic Anatomy
• He explained the changes in structure that can lead
to pathologic changes
Richard Bright
• Glomerulonephritis (Bright’s disease)
• Organ: Kidney
• Glomerulus function: filtration

◉ PATHOLOGIST – Diagnosticians of disease Thomas Addison

◉ DIAGNOSTICIAN – professional who is dealing with • Adrenal insufficiency (Addison’s disease)
procedures to diagnose diseases
• Cortisol – main hormone insufficient in the adrenal
William Osler gland

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 CHAPTER 1: INTRODUCTION TO GENERAL PATHOLOGY

• Stress hormone – common name for cortisol

VI. MODERN PATHOLOGY
Thomas Hodgkin • Study of Diseases at Molecular Level (DNA & RNA)
• Liver and Spleen enlargement (Hodgkin’s disease) • Diagnosis and Treatment:
➢ Genetic Disorders – early detection
Carl von Rokitansky ➢ Immunology – immune response
• Autopsy ➢ Cancer – research and special cases
❖ Watson and Crick: DNA structure
Paul Ehrlich ❖ Barbara McClintock: DNA flexibility and dynamism
• Gram staining bacteria (Bacterial Stains) ❖ Tijo and Levan: Chromosomes
❖ Kary Mullis: PCR “xeroxing”
Robert Koch
• He introduces the use of Methylene blue (bacilli) p53
(Bacterial Stains) • Example of tumor suppressor genes
o Located in ch.17 (together with genes of BRCA1
Christian Gram and Her-2/neu)
• Improved Paul Ehrlich’s stain (Bacterial Stains) o Gene product (protein) normally results in cell
cycle arrest and induces apoptosis (programmed
May-Grunwald cell death)
• Romanowsky – stain peripheral blood film (eosin • Upon mutation: loss of function mutation >
and methylene blue) cancer
-Colon cancer, Brain cancer, Lung cancer, Liver
Robert Feulgen cancer
• Foundation of cytochemistry and histochemistry • Carcinogens causing mutations in p53:
▪ Aflatoxin B
Rudolf Virchow - Potent hepatocarcinogen (common in China
• Etiology of embolism and Africa)
• Embolism – blockage - Causes mutations of p53 gene leading to liver
cancer
Julius Cohnheim ▪ Smoking
• Concept of frozen section - Causes mutations in p53 gene leading to lung
• Processing of fresh tissue cancer
• No fixatives or preservatives; no use of formalin
1996 – Ian Wilmut
Ruska and Lorries • “Dolly”
• Electron Microscope • Era of mammalian cloning
• Advantage: already computerized and smaller • From an adult somatic cell

George Papanicolaou 1998 - Era of Stem Cell Research

• Father of Exfoliative Cytology • Treatment: Alzheimer’s disease – Insulin
• Exfoliation – cells that are shredded and removed Production
from the external lining of the skin ❖ Sources:
• PAP Smear ➢ Embryonic stem cell
➢ Adult stem cell
* Symptoms: more subjective (what is being said by the
patient)
* Sign: less subjective (what can be observed)

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 CHAPTER 1: INTRODUCTION TO GENERAL PATHOLOGY

1969 - In Situ Hybridization 2020 – mRNA COVID 19 Vaccines

• Labeled probe to detect and localize RNA and DNA
sequences
• Probe – from reagent; target DNA is from sample
• Procedure:
1. Denaturation – remove the natural structure of
DNA
2. Hybridization – if the 2 DNA is related to each
other there will be binding (hybrid – combination)
3. Probe Detection – indication: flashing of the
probe
4. Analysis – positive (flashing); negative (no
flashing)

❖ Understanding the virus that causes COVID-19.

➢ Coronaviruses, like the one that causes COVID-
19, are named for the crown-like spikes on their
surface, called spike proteins. These spike
proteins are ideal target for vaccines

❖ What is mRNA?
1972 – Recombinant DNA Technique
➢ Messenger RNA, or mRNA, is genetic material
• Restriction enzymes to cut and paste bits of DNA
that tells your body how to make proteins
• By producing a product that is much better

❖ What is in the vaccine?

2003 – Human Genome Project (HGP)
• Genetic Blueprint ➢ The vaccine is made of mRNA wrapped in a
• Treatment and prevention of incurable diseases coating that makes delivery easy and keeps the
body from damaging it

❖ How does the vaccine work?

➢ The mRNA in the vaccine teaches your cells how
to make copies of the spike protein. If you are
exposed to the real virus later, your body will
recognize it and know how to fight it off.

▪ Old method of developing vaccines: you need to get

the attenuated/weakened/dead virus and inject it into
the human being

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 CHAPTER 1: INTRODUCTION TO GENERAL PATHOLOGY

◉ Gross and Microscopic Pathology

- Direct tissue examination
◉ Clinical Pathology
➢ Hematology
➢ Clinical Chemistry
➢ Immunology and Serology
➢ Microbiology
➢ Geographic Pathology
➢ Medical Genetics
▪ COVID-19 mRNA vaccines give instructions for our ➢ Molecular Pathology
cells to make a harmless piece of what is called the ◉ Anatomic Pathology
“spike protein”. The spike protein is found on the - Histopathology, Pathologic anatomy or Morbid
surface of the virus that causes COVID-19. anatomy
❖ 3 Main Subdivisions:
Terminologies 1. Surgical Pathology – Study of tissue
◉ Patient – person affected by disease removed from living body
◉ Lesions – changes in tissues and cells produced by 2. Forensic Pathology and Autopsy
disease - Removed postmortem (study) and
◉ Pathologic Changes – can be seen through: medicolegal
1. Gross or Macroscopic – direct analysis of the - The dead tech the living
specimen collected 3. Cytopathology – Exfoliative cytology and
2. Microscopic – analysis of the specimen through FNAC (Fine Needle Aspiration Cytology)
the microscopic confirmatory - Aspirate something using needle in a
◉ Causal Factors - “why of disease” etiology certain portion
◉Pathogenesis - how of disease
◉ Diagnosis - what is wrong VIII. PROCEDURE IN DIAGNOSTIC PATHOLOGY
◉ Prognosis - what is going to happen
◉ Treatment - what can be done 1. Request form
◉ Prevention - what should be done to avoid 2. Tissue accession - fixed or unfixed
complications and spread • Microwave technology – to shorten the time
of processing
• Fixed – submerged in 10% formalin
• Unfixed – fresh (frozen section)
3. Gross Examination - tissue cutting, gross
description, tissue selection
• tissue photography, radiography
4. Special Step – Calcified tissues
• Decalcification – removing of hydroxyapatite
crystals from the bone sample to make it
soft
• Calcium – component that makes the bone
VII. DIVISION OF PATHOLOGY hard
• Special step because not all specimens are
◉ General Pathology – general principles of disease
bony samples
- Complex study of cell injury and repair
5. 18 Hours overnight processing
◉ Systematic Pathology - disease of specific organ
and body systems

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VIII. 5 ASPECTS OF SIGNIFICANT REPORT

1) History – demographics of the patient

2) Precise gross description – description of the
specimen being submitted
3) Brief microscopic findings – findings of the
pathologist after analyzing the slide
4) Morphologic diagnosis
▪ SNOMED - Scientific Nomenclature in
Medicine/Code)
▪ codes much easier for reporting
▪ International Classification of Disease (ICD)
5) Additional comments in some cases

IX. QUALITY CONTROL

• Detect inadequacies – all result must be accurate

and precise
• Updating procedures
• Improvement of final reports
• Internal Quality Control – self check every day
before you run the result
• External Quality Control

to be continued on next discussion………

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