Clinicopathological Charts

Chart 1
Tubercular Lymphadenitis
Microscopic Features:
A granuloma is defined as a distinctive type of chronic
inflammation characterized by microscopic aggregation of
activated macrophages (that are transformed into
epithelium-like/epithelioid cells) with scattered
lymphocytes.
Older granulomas in addition show rim of fibroblasts and
connective tissue as the outermost layer. Structurally
granuloma consists of:
Granuloma:
Well circumscribed aggregates of:
• Histiocytes,
• Lymphocytes,
• Epitheloid histiocytes,
• Langhans’ giant cells,
• Fibroblasts,
• Caseation,
Introduction:
• Chronic Infectious Granulomatous Disease
Caused by:
• Mycobacterium tuberculosis
• Mycobacterium bovis
• Mycobacterium africanum
• Nontuberculous Mycobacteria
Transmission:
• Inhalation of droplets/dried residues from open
cases of pulm. TB
• Direct inoculation of abraded skin (laboratory
personnel)
• Ingestion – No pasteurized milk
Host Response
• Activation of Cell Medicated Immunity
• Pattern of Reaction-
- Primary Tuberculosis,
- Secondary Tuberculosis:
= Reinfection,
= Reactivation,
- Miliary Tuberculosis.
Chart 2
Osteoclastoma
Osteoclastoma
• Definition - Giant cell tumor is characterized by reactive
multinucleated osteoclast type giant cells randomly and
uniformly distributed in a background of neoplastic
mononuclear cells.
Clinical Features
• Age – 20 to 40 years
• Sex – Women
• Pain and arthritis like symptoms
• Microfractures and pathological fractures develop due to thinning of
the cotrtex
• Cell of Origin – Primitive stromal cells
 Pathogenesis – the neoplastic cells express high levels of
RANKL.
 They promote the proliferation of osteoclast precursors and
their differentiation into mature osteoclasts through RANK
expressed by these cells.
Radiological appearance
Morphology
 Site – Epiphysis
 Bones involved – Knee area, Lower
end of radius, humerus and fibula.
 Gross – Large tumor, clearly
circumscribed, frequent cystic change.
 Cut surface – Soft and red brown
without bone or calcification.
Microscopy
 Giant cells have as many as
100 benign nuclei. These cells
have very high acid
phosphatase activity.
 Stromal cells – mononuclear
cells, real tumor cells, cells
are plump, spindle-shaped or
round to oval cells with
numerous mitotic figures.
Microscopy
Chart 3
Wilms’ Tumour
Wilms tumour / Nephroblastoma
• Max Wilms – German surgeon
• Most common primary Renal tumor of childhood
• Highly malignant Primary Embroynal tumor
Age group:
• Most common between 2 and 5 years of age
• More than 95% occur below 10 years of age
Pathogenesis and Genetics

Mutations in genes responsible for

GENITOURINARY DEVELOPMENT

Gonads Kidney
Pathogenesis and Genetics

Mutations in genes responsible for

11p13 GENITOURINARY DEVELOPMENT

Chromosome
Gonads Kidney
Band

Short arm

Region
WT 1 (Wilms’ Tumor 1 gene)
Tumor suppressor gene

Mutation
(Deletion)

Loss of function

Wilms’ Tumour
Pathogenesis and Genetics
• Majority – otherwise healthy
• Mutation in tumour suppressor genes - Wilms tumour associated genes
(WT1) and WT2.
• WT1 gene is located in the chromosome 11p13.
• Developmental syndromes
Pathogenesis and Genetics
Wilms’ tumor: Associated congenital syndromes
1. WAGR syndrome
2. Denys-Drash syndrome
3. Blackwith-Wiedmann syndrome.
WAGR syndrome
WT1 (Wilms’ tumor 1)
Wilms tumor
• Wilms tumor
Genitourinary malformations
• Aniridia
• Genital anomalies
• Mental Retardation PAX6
• It has germline deletions of Aniridia
11p13, region where Wilms Intellectual disability
(Mental retardation)
tumor associated gene (WT1)
is located.
Denys-Drash syndrome
• Wilms tumor
• Intersexual disorders
• Glomerulopathy
Associated with mutations of the WT1 gene
Beckwith-Wiedmann syndrome (BWS)
• Associated with Wilms’ tumor
and WT2 gene imprinting
abnormalities.
WT2
- Wilms tumor
- Organomegaly
- Macroglosia
- Hemihypertrophy
Wilms’ tumor - Gross
• 90% cases - Unilateral.
• 5–10% are bilateral which involve
either simultaneously (synchronous)
or one after the other
(metachronous).
• Large, single, round, well-
circumscribed.
• Cut section – Soft, bulging,
homogeneous, and tan to gray, Foci
of hemorrhage, cyst formation, and
necrosis may be seen.
Wilms’ Tumor - Microscopy
Tumor shows three major components, which resemble normal fetal tissue.
These cells attempt to recapitulate different stages of nephrogenesis.
The three types of cells are: (Triphasic Tumor)
1. Blastemal component: It consists of small, round to oval blue cells with
scanty cytoplasm. These cells are arranged in sheets, nests and trabeculae.
2. Immature stromal (mesenchymal) component: It consists of
undifferentiated fibroblast-like spindle cells. They may show smooth
muscle, skeletal muscle or fibroblast differentiation.
3. Immature epithelial component: Epithelial cells show differentiation in
the form of small abortive (embryonic) tubules or immature glomeruli.
Wilms’ Tumor - Microscopy
Wilms’ Tumor - Microscopy
Wilms’ Tumor - Microscopy
Clinical Features
• Abdominal mass, when large extends across the midline and down into the pelvis.
• Haematuria, pain in the abdomen, intestinal obstruction, and pulmonary
metastases
Spread
• Local spread to perirenal soft tissues.
• Lymphatics spread to regional lymph nodes.
• Hematogenous spread to Lungs, liver and peritoneum.
Prognosis
• Clinical parameter: Children younger than 2 years of age have a better prognosis.
• Histological parameter:
• Invasion of the renal capsule is associated with poor prognosis.
• Anaplasia indicates a poorer prognosis.
Chart 4
Chart 5
 Rhematic Fever and
Rheumatic Heart Diseases
Definition:
Rheumatic fever (RF) is an
• Acute
• Post-streptococcal
• Immune-mediated
• Multisystem inflammatory disease.
Etiology and Pathogenesis
• Post-streptococcal disease.
• Develops after a latent period of 2 to 6 weeks after an episode of
pharyngitis or tonsillitis by group A –hemolytic streptococci.
• Most often in children.
• Immunologically mediated disease:
• Streptococcal infection introduces the streptococcal antigens into the body
which activate both antibody and T-cell–mediated reactions against
streptococci.
Antibody-mediated reactions (type II
hypersensitivity reaction)
• Antibodies may be produced by B-lymphocytes against various
antigenic components of the Streptococcus.
• One of them produced against the M proteins of streptococci seems to
cross-react with certain similar self-antigens in the myocardial cells
and glycoproteins of the valves in the heart.
• This may be the mechanism for pancarditis in acute rheumatic fever.
T-cell–mediated reactions (type IV
hypersensitivity reaction):
• CD4+ T-cells are also activated by streptococcal antigens.
• These along with antibodies cross react with self-proteins in the heart.
• These reactions produce cytokines leading to activation of
macrophages, which are seen in lesions of rheumatic fever.
Incidence
• Age group: 5 to 15 years.
• Sex: Equally effected.
• Socioeconomic conditions
• Poor economy and overcrowding
• Rheumatic fever rarely follows infections by streptococci at other
sites, like skin.
 Valvular

Endocarditis

Mural
Acute Myocarditis

Cardiac Pericarditis
Rheumatic
Fever
Changes in Mitral, Aortic,
Extracardiac Chronic
Tricuspid, Pulmonary Valve
Two major phases
1. Acute rheumatic fever: It frequently manifest as acute rheumatic
carditis.
2. Chronic rheumatic heart disease: Acute rheumatic carditis may
progress to chronic rheumatic heart disease (RHD). The deforming
fibrotic valvular lesions (mainly mitral stenosis)

• Old dictum is that “rheumatic fever licks the joint but bites the heart”.
Acute rheumatic heart disease
• Characterized by pancarditis
• Endocarditis
• Myocarditis
• Pericarditis
Rheumatic Endocarditis
Inflammation of the endocardium
• Valvular (valvular endocarditis)
• Mural endocardium (mural endocarditis).
Rheumatic Mural Endocarditis
• Most common as MacCallum’s patch
which is the region of endocardial
surface in the posterior wall of the left
atrium just above the posterior leaflet
of the mitral valve.
• MacCallum’s patch appears as a map-
like area of thickened, roughened and
wrinkled part of the endocardium
Aschoff nodules/Aschoff bodies
Aschoff body: It is spheroidal or fusiform characteristic lesion seen in
rheumatic disease.
• Size: About to 1 to 2 mm.
• Site: During acute RF, may be found in any of the three layers, in the
perivascular interstitial region of the heart
Formation of Aschoff body consists of 3 phases:
• Early/exudative phase:
• Intermediate/granulomatous phase
• Late/healed /final phase
Early/exudative phase:
• About 4th week of illness
• Initially, there is oedema of the connective tissue and increase in acid
mucopolysaccharide in the ground substance.
• Results in separation of the collagen fibres by accumulating ground
substance.
• Collagen fibres are fragmented and disintegrated and the affected
focus takes the appearance and staining characteristics of fibrin.
• Fibrinoid degeneration.
Intermediate/granulomatous phase:
• Granulomatous lesion, with a central fibrinoid focus associated with
lymphocytes (primarily T-cells), macrophages, Anitschkow cells
(pathognomonic for RF) and occasional plasma cells.
• Anitschkow cells are plump activated macrophages, which have
abundant cytoplasm. They have round-to-ovoid nuclei in which the
chromatin is disposed in a central, slender, wavy ribbon.
• Longitudinally cut - “caterpillar cells”
• On cross section – “owl-eye appearance”
• Aschoff giant cells.
Late/healed /final phase
• Aschoff body is replaced by a nodule of scar tissue.
• 12 to 16 weeks after the illness.
• The nodule becomes oval or fusiform in shape, about 200 μm wide
and 600 μm long.
• The Anitschkow cells in the nodule become spindle-shaped with
diminished cytoplasm and the nuclei stain solidly rather than showing
vesicular character.
• These cells tend to be arranged in a palisaded manner.
Rheumatic Valvular endocarditis:
• During acute rheumatic carditis, valve
leaflets become inflamed and edematous.
• All four valves may be affected, but left-
sided valves (mitral and aortic) are more
injured than do right sided valves
(tricuspid and pulmonary).
Rheumatic Valvular endocarditis:
• Inflammatory damage causes focal loss of endothelium and fibrin
deposits along the lines of closure of the valve leaflets or along the
tendinous cords.
• Overlying these deposits develop small (1–2 mm) nodular or warty
vegetations, called verrucae. These verrucae are firmly attached and do
not get dislodged. This is in contrast to friable detachable vegetations
of infective endocarditis.
Rheumatic Pericarditis
• Inflammation of the pericardium is known as pericarditis.
• Fibrinous pericarditis.
• Bread-and-butter pericarditis
• Clinically, It gives a friction rub, and it never causes constrictive
pericarditis.
Myocarditis
• Inflammation of the myocardium is known as myocarditis.
• Nonspecific myocarditis during acute RF may cause dilation of heart.
Microscopically, myocardium may show lymphocytes and
macrophages or Aschoff bodies.
Chronic changes
Valves Affected
• Mitral valve alone: It is the most
commonly (65–70% of cases) and
severely affected valve in chronic
rheumatic disease.
• Mitral valve along with the aortic valve
in another 25% of cases.
• Tricuspid and pulmonary valve are
rarely involved.
1. Changes in mitral valve
• Thickening of valve leaflet:
• Fusion of commissures: Healing of rheumatic lesions along the lines
of closure leads to formation of fibrous adhesions/ bridging of
valvular commissuresresult in a rigid and partially fused stenotic
valve.
• Characteristic appearance of a fish mouth” (or “buttonhole”) when
viewed from the ventricular aspect
Consequences of mitral stenosis
• Left atrium progressively dilates favor mural thrombi in the
appendage or along the wall.
• Thrombi can dislodge embolize.
• Chronic venous congestion in the lungs.
• Pulmonary hypertension -- right ventricular hypertrophy and
right-sided heart failure.
• Left ventricle is normal in isolated pure mitral stenosis
Changes in aortic valve
• This is the second most commonly involved valve in rheumatic heart
disease.
• Diffuse fibrous thickening of the cusps and fusion of the commissures
cause aortic stenosis.
• The cusps may become calcified as the patient ages, resulting in
stenosis and insufficiency.
• Tricuspid valve: In cases of recurrent RF, the tricuspid valve may be
deformed, always in association with mitral and aortic lesions.
• Pulmonary valve: It is rarely affected.
Extracardiac Lesions
1. Migratory polyarthritis:
• Usual presentation in acute
rheumatic fever and is
accompanied by fever.
• One large joint becomes painful
and swollen, which then subsides
and another joint gets involved
for a period of days.
2. Subcutaneous nodules:
• Seen in children
• Oval to spheroidal, painless and
measure about 0.5 to 2 cm in
diameter.
• Attached to tendons or ligaments
and are usually located at the
extensor aspect of wrist, elbows,
ankles or knees.
• Microscopically, they appear like
a giant Aschoff body.
3. Erythema marginatum
• These skin lesions are non-itchy
reddish rashes showing
characteristic bathing suit pattern
of distribution.
4. Sydenham's chorea or Saint Vitus’ dance
• It is a neurologic disorder with
involuntary rapid, jerky,
purposeless movements of trunks
and extremities
Complications of Chronic Rheumatic
Heart Disease
1. Infective endocarditis
2. Mural thrombi: Mitral stenosis
3. Thromboemboli
4. Congestive heart failure
5. Adhesive pericarditis
6. Arrhythmias (particularly atrial fibrillation)
Clinical Features
Laboratory Findings
• Serological tests: The antibodies to one or more streptococcal enzymes can
be detected in the sera of most patients with RF.
These include:
• Antistreptolysin O (ASO)
• DNase B
• Antihyaluronidase.

Acute phase reactants

• Raised ESR
• C-reactive protein.
Chart 6
HepatoCellular Carcinoma
Clinical features:
• 6th M/C common malignancy
• >40 yrs- peak at 70 yrs
• M>F (4:1 to 8:1)
• Anorexia, malaise, Abdominal pain/ abdominal mass, Ascitis

Can be associated with hypoglycaemia, hypercholesterolemia,

hypercalcemia, carcinoid syndrome.

AFP- increased (70%sensitive)

Risk Factors
• HBV- 5-15 times risk of HCC
• HCV- 15-20 times risk of HCC
• Alcohol use- 15%
• Alcoholic liver disease
• Non alcoholic fatty liver disease
• Metabolic syndrome- Obesity, DM, dyspilidemia, insulin resistence
• Drugs- thorium dioxide (Thorotrast)- radiographic contrast medium
• Aflatoxin- metabolic product of fungus Aspergillus flavus
Gross

• Single mass/ multiple nodules/

diffuse infiltrative
• May be paler than the
surrounding tissue
• Variegated appearance
Multicentric in the background of cirrhosis
Microscopy: 3 Patterns
• Trabecular, plate-like or sinusoidal
• Pseudoglandular, adenoid or acinar
• Compact, solid or scirrhous

Cytological features
• Hepatic or liver-like
• Pleomorphic cells
• Cell plate thickness>3cell
• Scant stroma, unpaired vessels
• Lack of portal tracts
• Loss of reticulin network
Microtrabecular growth pattern with 3-4 cell thick hepato cellular cord/plates, nuclear atypia and
absence of portal tracts.
Polygonal tumor cells with distinct cell membrane, enlarged nuclei, high N/C ratio and prominent
nucleoli and dilated bile canaliculi surrounded by hepatocytes.
Presence of endothelial cells lining the sinudoids surrounding the enlarged hepatocellular
cords/plates
Chart 7
Fibroadenoma - Breast
NORMAL BREAST
Fibroadenoma
• Most common benign tumor of the female breast.
• Age group: Mostly occur in females between 20 to 30 years.
• Origin: Arise from intralobular stroma.
• Clinical presentation: Young women usually present with a palpable
and freely movable mass
Microscopy
• Composed of a mixture of duct-like structures and fibrous connective
tissue.
Duct-like structures:
• Ducts may be either simple and round or elongate and branching.
• Epithelium lining the ducts ranges from the double layer of epithelium
of normal lobules to varying degrees of hyperplasia.
Fibrous connective tissue stroma:
• Constitutes most of the tumor
• Stroma is delicate, cellular, often myxoid and resembles normal
intralobular stroma.
FIBROADENOMA
Classification:
According to the microscopic appearance:
Pericanalicular:
• In this type, regular round or oval glandular configuration of the
glands is maintained. The epithelium forms ducts with patent lumen,
because the surrounding stroma proliferates circumferentially around
them.
Intracanalicular
• It is a misnomer in which the connective tissue invaginates into the
glandular spaces, so that it appears to be within them.
• The proliferated ducts are compressed and distorted by, fibrous tissue
reducing them to form curvilinear slits.
Chart 8
Squamous Cell Carcinoma -
Lung
• Most lung cancers develop as multistep process by accumulation of
oncogenic “driver” mutations.
• This causes neoplastic transformation of pulmonary epithelial cells
from a premalignant lesion to frank cancer after a number of years.
• Exposures to various carcinogens produce sequential genetic
alterations and epigenetic changes that result in the loss of normal
control of cell growth which eventually produce neoplasms.
Inactivation of tumor suppressor gene:
• Chromosome deletions involves tumor suppressor loci and involve 3p,
9p (site of the CDKN2A gene), and 17p (site of the TP53 gene).
Activation of oncogenes:
• Amplification of FGFR1 and MET: Many squamous cell carcinomas
have amplification of FGFR1, a gene encoding the fibroblast growth
factor receptor tyrosine kinase.
• Translocations: e.g. ALK, ROS1 and RET.
Diagnosis
• Sputum cytology
• Fiberoptic bronchoscopy
• Bronchial lavage, washings and brushings
• Radiological examination of chest
• FNAC
• Bronchoscopic biopsy.
Squamous cell carcinoma-LUNG
SCC- LUNG
Chart 9
Minimal Change Disease
(Nephrotic Syndrome)
Relevant Features
• Albumin ++++
• Hyaline Cast
• Lipid Cast
• S. Cholesterol increased – (Excreted in urine)
• Albumin Reduced
Light Microscopy findings
• Glomeruli: Appear normal by light microscopy.
• Tubules: The cytoplasm of epithelial cells lining the proximal
tubules contains lipid vacuoles and glassy (hyaline) protein
droplets (hence, the historical term lipoid nephrosis for this
disease). These are due to the tubular reabsorption of
lipoproteins passing through damaged glomeruli.
• Interstitium: May show mild edema.
• Blood vessels: Appear normal.
Electron Microscopy
• GBM appears normal without any electron-dense deposit.
• Changes in the visceral epithelial cells: Most characteristic feature is
uniform and diffuse effacement of foot processes in the visceral
epithelial cells. This change wrongly called as “fusion” of foot
processes. The cytoplasm shows vacuolization and swelling.