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BSC SEM 4 UNIT 1 PATHOLOGY 2 & GENETICS

UNIT 1 Special Pathology:

Pathological changes in disease conditions of selected systems

  1. Kidneys and Urinary tract

Glomerulonephritis – Pathological Changes

Glomerulonephritis refers to a group of kidney diseases that cause inflammation of the glomeruli, the tiny filtering units in the kidneys. The pathological changes vary depending on whether the condition is acute, chronic, or rapidly progressive, but some common mechanisms underlie all types.


πŸ”¬ Pathophysiological Mechanisms:

  1. Immune Complex Deposition
    • Antigen-antibody complexes (from infections, autoimmune disorders) deposit in the glomerular basement membrane (GBM).
    • These immune complexes activate the complement system, attracting neutrophils and macrophages, causing inflammation and damage.
  2. Cellular Proliferation
    • Mesangial cells, endothelial cells, and epithelial cells proliferate in response to injury.
    • This causes glomerular enlargement and reduced filtration surface area.
  3. Increased Glomerular Permeability
    • Damage to the podocytes and GBM leads to leakage of proteins (proteinuria) and red blood cells (hematuria) into the urine.
  4. Thickening of Basement Membrane
    • Chronic inflammation causes fibrosis and scarring of the GBM, further impairing filtration.
  5. Crescent Formation (in Rapidly Progressive GN)
    • Severe injury leads to leakage of fibrin and inflammatory cells into Bowman’s space.
    • Forms crescents that compress the glomerulus and rapidly destroy renal function.
  6. Glomerulosclerosis
    • Over time, persistent inflammation and ischemia lead to hardening and scarring of the glomeruli (glomerulosclerosis), reducing kidney function.
  7. Tubulointerstitial Changes
    • As glomerular damage progresses, tubular atrophy, interstitial inflammation, and fibrosis occur, contributing to chronic kidney disease (CKD).

🩸 Clinical Correlation:

  • Hematuria (tea-colored or cola-colored urine)
  • Proteinuria
  • Edema (especially around eyes and ankles)
  • Hypertension
  • Reduced glomerular filtration rate (GFR)

πŸ§ͺ Histological Findings:

  • Hypercellular glomeruli (due to proliferation/infiltration)
  • Thickened capillary walls
  • Immune deposits (seen on immunofluorescence microscopy)
  • Crescents in Bowman’s space (in rapidly progressive types)
  • Fibrosis and glomerulosclerosis in chronic stages

Pyelonephritis – Pathological Changes

Pyelonephritis is an inflammation of the renal pelvis and the renal parenchyma, typically due to a bacterial infection. It may be acute or chronic, with distinct pathological features.


πŸ”¬ Pathophysiological Mechanisms:


πŸ”΄ Acute Pyelonephritis

  1. Bacterial Infection
    • Most commonly caused by Escherichia coli (E. coli).
    • Bacteria ascend from the lower urinary tract (bladder) to the kidney via the ureter.
  2. Inflammatory Response
    • Neutrophils infiltrate the renal interstitium and tubules.
    • Formation of pus (suppuration) and abscesses in the renal tissue.
  3. Tubular Damage
    • Infection leads to necrosis of tubular epithelium, causing tubular dysfunction.
    • Cast formation and shedding of epithelial cells seen in urine.
  4. Edema and Hyperemia
    • Kidneys become swollen, red, and congested due to vascular dilation and inflammatory exudate.

🟀 Chronic Pyelonephritis

  1. Repeated or Persistent Infection
    • Often associated with urinary tract obstruction, vesicoureteral reflux, or neurogenic bladder.
    • Leads to progressive renal damage.
  2. Interstitial Fibrosis and Tubular Atrophy
    • Ongoing inflammation causes scarring and fibrosis of the interstitial tissue.
    • Loss and atrophy of nephrons, especially tubules.
  3. Irregular Renal Scarring
    • Patchy, asymmetric scarring with cortical thinning.
    • Seen especially at upper and lower poles of the kidney.
  4. Glomerulosclerosis and Hyalinization
    • Chronic inflammation may lead to sclerosed glomeruli and hyalinized arterioles.
    • May progress to chronic kidney disease (CKD).

🩺 Clinical Correlation:

Acute PyelonephritisChronic Pyelonephritis
Sudden fever, chills, flank painOften asymptomatic or mild symptoms
Dysuria, urgency, frequencyPolyuria, nocturia, hypertension
Tenderness at costovertebral angleProgressive renal failure
Pus cells and bacteria in urineSmall, shrunken, scarred kidneys on imaging

πŸ§ͺ Histological Findings:

  • Acute:
    • Neutrophilic infiltration in interstitium and tubules
    • Microabscess formation
  • Chronic:
    • Interstitial fibrosis
    • Tubular atrophy and thyroidization (tubules resemble thyroid tissue)
    • Glomerulosclerosis

Renal Calculi – Pathological Changes

Renal calculi, also known as kidney stones, are solid crystalline masses formed in the kidneys from minerals and salts. These can obstruct urinary flow and cause tissue damage.


πŸ§ͺ Types of Renal Calculi:

  1. Calcium oxalate/calcium phosphate (most common)
  2. Struvite stones (infection-related)
  3. Uric acid stones
  4. Cystine stones (rare, genetic)

πŸ”¬ Pathophysiological Changes:


1. Supersaturation of Urine

  • High concentrations of stone-forming substances (e.g., calcium, oxalate, uric acid) in urine.
  • Leads to crystallization when these exceed their solubility.

2. Nucleation and Crystal Growth

  • Crystals start to form around a nucleus (tiny particle or existing damage).
  • Grow larger over time to form calculi.

3. Aggregation and Retention in Kidney

  • Crystals aggregate and get trapped in the renal tubules or calyces.
  • They attach to damaged epithelium or Randall’s plaques (calcium deposits at papillary tips).

4. Obstruction of Urinary Tract

  • Stone can block ureter, renal pelvis, or urethra.
  • Causes urinary stasis, hydronephrosis (dilation of renal pelvis), and increased pressure in kidneys.

5. Inflammation and Mucosal Injury

  • Stones cause irritation and erosion of the urinary tract lining.
  • Leads to hematuria (blood in urine), pain, and infection risk.

6. Secondary Infection (Especially in Struvite Stones)

  • Stones may harbor bacteria.
  • Promotes recurrent urinary tract infections (UTIs) and stone enlargement (staghorn calculi).

7. Ischemia and Renal Damage

  • Long-standing obstruction causes:
    • Compression of renal vasculature
    • Decreased blood flow (ischemia)
    • Atrophy and fibrosis of kidney tissue
    • Can lead to renal failure if untreated

🧬 Histological Findings:

  • Damaged tubular epithelium
  • Inflammatory cell infiltration
  • Calcium deposits within tubules
  • Areas of fibrosis and scarring

🩺 Clinical Correlation:

SymptomsFindings
Severe flank pain (renal colic)Hematuria (microscopic or visible)
Nausea, vomitingCrystals in urine (crystalluria)
Urinary urgency/frequencyImaging: X-ray, Ultrasound, CT scan
Fever (if infection present)Hydronephrosis on imaging

Cystitis – Pathological Changes

Cystitis refers to inflammation of the urinary bladder, most commonly due to a bacterial infection. It can be acute or chronic, and the pathological changes differ depending on the stage and cause of the condition.


🧫 Etiology (Common Causes):

  • Bacterial infection – most common cause (e.g., E. coli, Klebsiella, Proteus)
  • Chemical irritants (e.g., drugs, radiation, chemotherapy)
  • Catheter use
  • Urinary obstruction or stasis
  • Interstitial cystitis (non-infective, chronic bladder inflammation)

πŸ”¬ Pathological Changes

πŸ”΄ 1. Acute Cystitis

  1. Hyperemia of Mucosa
    • The bladder mucosa becomes red, swollen, and congested due to inflammation.
  2. Neutrophilic Infiltration
    • Neutrophils infiltrate the urothelium (bladder lining) and submucosa.
  3. Mucosal Ulceration
    • In severe cases, the epithelium becomes ulcerated, leading to bleeding and pain.
  4. Exudate Formation
    • Mucopurulent or hemorrhagic exudates (pus-like or bloody secretions) may be present in the bladder lumen.
  5. Edema and Tenderness
    • The bladder wall becomes edematous and painful, especially during urination.

🟀 2. Chronic Cystitis

  1. Lymphocytic and Plasma Cell Infiltration
    • The submucosa contains chronic inflammatory cells instead of neutrophils.
  2. Fibrosis and Thickening
    • The bladder wall becomes thickened and fibrotic, reducing bladder capacity.
  3. Urothelial Hyperplasia
    • Prolonged irritation causes thickening of the bladder epithelium.
  4. Granular or Follicular Cystitis
    • May see lymphoid follicles or granular mucosa on cystoscopy.
  5. Squamous Metaplasia (in severe, long-standing cases)
    • Normal transitional epithelium changes to squamous epithelium, which is more resistant to chronic irritation but increases cancer risk.

πŸ§ͺ Histological Findings:

TypeFindings
Acute CystitisNeutrophilic infiltration, edema, congestion, mucosal ulceration
Chronic CystitisLymphocytes, plasma cells, fibrosis, thickened wall, epithelial hyperplasia

🩺 Clinical Correlation:

SymptomExplanation
Burning urination (dysuria)Due to mucosal irritation
Frequency and urgencyInflamed bladder stimulates urination
Lower abdominal/pelvic painDue to inflammation and pressure
Hematuria (blood in urine)From ulceration or inflammation
Cloudy or foul-smelling urineDue to pus, bacteria
Fever (occasionally)More common if infection spreads

🧬 Renal Cell Carcinoma (RCC) – Pathological Changes

Renal Cell Carcinoma (RCC) is the most common malignant tumor of the kidney in adults, originating from the renal tubular epithelium. It is also called hypernephroma or adenocarcinoma of the kidney.


⚠️ Etiology / Risk Factors:

  • Smoking
  • Obesity
  • Hypertension
  • Chronic kidney disease
  • Genetic syndromes (e.g., von Hippel-Lindau disease)
  • Male gender, typically between 50–70 years of age

πŸ”¬ Pathological Changes (Gross & Microscopic)

πŸ”΄ 1. Origin and Growth

  • RCC arises from proximal convoluted tubule epithelial cells.
  • The tumor usually grows unilaterally (one kidney) and is solitary.
  • Located in the cortex of the kidney.

πŸ” 2. Gross Appearance

  • Golden-yellow color due to high lipid content.
  • Often has areas of:
    • Hemorrhage
    • Necrosis
    • Cystic degeneration
    • Calcification

πŸ”¬ 3. Histological Types (Subtypes of RCC)

TypeFeatures
Clear Cell RCC (most common)Cells have clear cytoplasm due to lipid and glycogen. Highly vascular.
Papillary RCCPapillary or tubular structures with foamy macrophages. Associated with trisomy 7, 17.
Chromophobe RCCPale eosinophilic cells with perinuclear halo. Better prognosis.

πŸ§ͺ 4. Invasion and Spread

  • RCC is known for early vascular invasion, especially into:
    • Renal vein
    • Inferior vena cava
  • Can also invade the pelvis and ureter, spreading via hematogenous route.

πŸ“ˆ 5. Metastasis

  • Common sites:
    • Lungs
    • Bones
    • Liver
    • Brain
  • Metastasis may occur before primary tumor is detected due to silent progression.

🧫 Microscopic Features (Clear Cell RCC):

  • Cells arranged in nests or tubules
  • Clear cytoplasm with distinct borders
  • Rich capillary network
  • Atypical nuclei, mitotic figures may be seen

🩺 Clinical Correlation – Classic Triad (seen in <10% cases):

SymptomExplanation
HematuriaDue to tumor invading renal vessels
Flank painFrom tumor mass or hemorrhage
Palpable massLarge or advanced tumor
Other features:
  • Fever
  • Weight loss
  • Hypertension (due to increased renin)
  • Polycythemia (due to ectopic erythropoietin production)
  • Paraneoplastic syndromes

πŸ” Imaging and Diagnosis:

  • Ultrasound, CT scan, MRI
  • Confirmed by histopathology after nephrectomy or biopsy

🚨 Acute Renal Failure (Acute Kidney Injury) – Pathological Changes

Acute Renal Failure (ARF) or AKI is a sudden and rapid decline in kidney function, leading to the accumulation of waste products, fluid, and electrolyte imbalances. It develops over hours to days.


πŸ“Š Types of AKI (based on the location of the cause):

TypeCause Origin
PrerenalDue to reduced blood flow to kidneys
Intrarenal (Intrinsic)Due to direct kidney tissue damage
PostrenalDue to obstruction of urine flow

πŸ”¬ Pathological Changes by Type


πŸŸ₯ 1. Prerenal AKI – Before the kidney

Cause: Hypoperfusion due to dehydration, shock, heart failure, blood loss.

Changes:

  • No structural damage initially
  • Prolonged hypoperfusion β†’ ischemic injury to tubules
  • Can progress to acute tubular necrosis (ATN) if not corrected

🧱 2. Intrarenal AKI – Within the kidney

Most common type = Acute Tubular Necrosis (ATN)

πŸ”Ή a. Ischemic ATN

  • Caused by prolonged hypotension or shock
  • Patchy necrosis of tubular epithelium (especially in proximal tubules & thick ascending limb)
  • Tubular basement membrane may remain intact

πŸ”Ή b. Nephrotoxic ATN

  • Caused by toxins (e.g., aminoglycosides, contrast dye, heavy metals)
  • Diffuse necrosis of proximal tubular cells
  • May see cellular debris and casts in tubules

Other Intrarenal Causes:

  • Glomerulonephritis – inflammation & damage to glomeruli
  • Interstitial nephritis – allergic/infective inflammation of interstitium

Common Pathological Changes in Intrarenal AKI:

  • Tubular epithelial cell necrosis
  • Loss of brush border
  • Cell shedding into tubule lumen β†’ obstruction
  • Back-leak of filtrate into the interstitium
  • Inflammatory infiltration and edema

🟨 3. Postrenal AKI – After the kidney

Cause: Obstruction (e.g., BPH, kidney stones, tumors, ureteral obstruction)

Changes:

  • Increased intratubular pressure
  • Hydronephrosis (dilation of renal pelvis & calyces)
  • Tubular atrophy and interstitial inflammation
  • Prolonged obstruction β†’ irreversible damage

🧬 Histological Features:

LocationPathology
Proximal TubulesLoss of brush border, cell swelling, necrosis
Tubule LumenCasts, sloughed cells, debris
InterstitiumEdema, inflammation
GlomeruliUsually intact in ATN unless glomerulonephritis is present

🩺 Clinical Correlation:

StageFeatures
Oliguric Phase↓ Urine output, ↑ BUN & creatinine, acidosis, hyperkalemia
Diuretic Phase↑ Urine output (but dilute), risk of dehydration, electrolyte loss
Recovery PhaseGradual normalization of renal function

πŸ“Œ Summary:

  • ARF/AKI involves sudden kidney dysfunction
  • Depending on the cause, it leads to tubular necrosis, inflammation, obstruction, or interstitial edema
  • Early detection and management can reverse damage, especially in prerenal and postrenal forms

πŸ’€ Chronic Renal Failure (CRF) / Chronic Kidney Disease (CKD)

Chronic Renal Failure is a progressive, irreversible decline in kidney function lasting more than 3 months. It leads to the accumulation of waste products, electrolyte imbalance, fluid overload, and hormonal dysfunction.


πŸ”¬ Pathological Changes in CRF

🧬 1. Nephron Loss

  • Primary event: Continuous damage to nephrons due to underlying disease (e.g., diabetes, hypertension, glomerulonephritis).
  • Remaining nephrons undergo hypertrophy and hyperfiltration to compensate β†’ over time, they burn out too.

🩸 2. Glomerular Changes

  • Glomerulosclerosis – scarring of glomeruli.
  • Reduced filtration surface β†’ ↓ GFR (Glomerular Filtration Rate).
  • Progressive loss of glomerular capillaries.

🧱 3. Tubulointerstitial Changes

  • Tubular atrophy – degeneration and loss of tubule structure.
  • Interstitial fibrosis – accumulation of extracellular matrix (scar tissue).
  • Inflammatory cell infiltration – especially lymphocytes and macrophages.
  • Leads to impaired reabsorption and secretion.

πŸ”„ 4. Vascular Changes

  • Arteriosclerosis – thickening of arterial walls β†’ ↓ blood flow.
  • Ischemia β†’ further tubular and glomerular damage.
  • Hyalinization of small vessels.

βš–οΈ 5. Systemic Effects (Multisystem Involvement)

System AffectedPathological Effects
HematologicAnemia (↓ Erythropoietin), Platelet dysfunction
SkeletalRenal osteodystrophy (↓ Vitamin D, ↑ PTH)
CardiovascularHypertension, LVH, Uremic pericarditis
NeurologicalUremic encephalopathy, peripheral neuropathy
GastrointestinalNausea, vomiting, uremic breath
SkinUremic frost, pruritus, dry skin

πŸ“‰ Stages of CRF (Based on GFR):

StageGFR (ml/min/1.73mΒ²)Description
1>90Normal GFR, kidney damage present
260–89Mild reduction
330–59Moderate reduction
415–29Severe reduction
5<15Kidney failure (End-stage renal disease – ESRD)

πŸ§ͺ Histological Findings:

  • Glomerulosclerosis
  • Tubular atrophy
  • Interstitial fibrosis
  • Arterial narrowing and hyalinization
  • Inflammatory infiltrates

🩺 Clinical Features:

ManifestationCause
Fatigue, weaknessAnemia, uremia
EdemaSalt & water retention
HypertensionRAAS activation, fluid overload
Bone painRenal osteodystrophy
Nausea, vomitingUremic toxins
Itching (pruritus)Accumulation of uremic waste in skin
Confusion, seizuresUremic encephalopathy (late stage)

πŸ”š Summary:

Chronic Renal Failure involves progressive nephron loss, fibrosis, and inflammation, eventually leading to end-stage renal disease (ESRD), where the kidneys can no longer sustain life without dialysis or transplantation.

. Male genital systems

🧬 Cryptorchidism – Pathological Changes

Cryptorchidism is a condition in which one or both testes fail to descend into the scrotal sac. Normally, the testes descend from the abdomen to the scrotum during fetal development, usually before birth. When this process is incomplete, the testes may remain in the abdomen, inguinal canal, or upper scrotum.


⚠️ Sites of Undescended Testes:

  • Abdominal cavity (most severe)
  • Inguinal canal (most common)
  • Pre-scrotal or high scrotal position

πŸ”¬ Pathological Changes in Cryptorchidism

1. Histological Changes in the Undescended Testis:

ChangeDescription
πŸ”Ή Germ cell atrophyEarly loss of germ cells due to abnormal temperature
πŸ”Ή Sertoli cell-only tubulesSeminiferous tubules lack germ cells
πŸ”Ή Thickened basement membraneDegenerative changes in tubules
πŸ”Ή Fibrosis of interstitiumScarring replaces normal parenchyma
πŸ”Ή Leydig cell hyperplasiaIncreased Leydig cells due to disrupted hormonal feedback

2. Functional Impairment

  • Impaired spermatogenesis due to high intra-abdominal temperature (which is ~2–3Β°C higher than scrotal temperature)
  • Infertility especially if both testes are undescended and untreated
  • Endocrine function may be preserved in mild/unilateral cases

3. Risk of Malignancy

  • Increased risk (up to 4–10 times) of developing testicular cancer, especially seminoma
  • Risk remains even after surgical correction, but is reduced if corrected early (before 1–2 years of age)

4. Testicular Torsion & Trauma

  • Undescended testes are more prone to torsion (twisting of the spermatic cord) and trauma, particularly when located in the inguinal canal

5. Atrophy and Hypoplasia

  • Affected testis is usually smaller, softer, and atrophic compared to normal
  • May remain non-functional if not surgically corrected in time

πŸ“Έ Microscopic Features:

  • Loss of germinal epithelium
  • Small, hyalinized seminiferous tubules
  • Increased interstitial fibrosis
  • Few or absent spermatogonia
  • Prominent Leydig cells

🩺 Clinical Correlation:

FeatureExplanation
Empty scrotal sacMost obvious sign of cryptorchidism
InfertilityDue to impaired spermatogenesis
Increased cancer riskEspecially seminoma in abdominal testis
Testicular torsion/traumaDue to abnormal position

πŸ› οΈ Management Note:

  • Orchiopexy (surgical correction) recommended before 12–18 months of age
  • Early intervention preserves fertility and reduces cancer risk

🧬 Testicular Atrophy – Pathological Changes

Testicular atrophy refers to the shrinkage and loss of function of the testes. It can be unilateral or bilateral, and is often associated with reduced fertility or hormonal imbalance.


πŸ§ͺ Causes of Testicular Atrophy:

CategoryExamples
πŸ”₯ InflammatoryMumps orchitis, chronic epididymo-orchitis
πŸ”€ HormonalHypogonadism (primary or secondary), low FSH/LH
πŸ’Š Drugs/ToxinsAlcohol, chemotherapy, steroids
πŸ’’ VascularTesticular torsion, varicocele
🧬 Congenital/GeneticKlinefelter syndrome, cryptorchidism
🦠 InfectiousHIV, tuberculosis
πŸ› οΈ Trauma/RadiationTesticular injury or irradiation

πŸ”¬ Pathological Changes in Testicular Atrophy:

1. Shrinkage of Testicular Parenchyma

  • The testis becomes smaller, softer, and lighter in weight.

2. Tubular Changes (Seminiferous Tubules)

Pathological FeatureExplanation
Tubular atrophyThinning and collapse of seminiferous tubules
Germ cell lossEarly and progressive disappearance of spermatogenic cells
Sertoli cell-only patternOnly Sertoli cells remain in the tubules
Thickened basement membraneDue to fibrosis and degeneration

3. Interstitial Changes

  • Fibrosis of interstitial tissue
  • Loss of Leydig cells (↓ testosterone production)
  • In some cases: Leydig cell hyperplasia (compensatory)

4. Sclerosis and Hyalinization

  • Tubular walls become hyalinized (glassy appearance)
  • Peritubular fibrosis – collagen deposition around tubules
  • Loss of normal vascularity

5. Secondary Changes

  • Infertility due to loss of spermatogenesis
  • Hypogonadism (↓ testosterone) β†’ reduced libido, muscle mass, energy
  • Elevated FSH/LH in primary testicular failure (feedback response)

πŸ” Histological Features:

  • Small, atrophic seminiferous tubules
  • Loss of germ cells
  • Prominent Sertoli cells lining empty tubules
  • Fibrotic interstitial spaces
  • Thickened basement membranes

🩺 Clinical Correlation:

FeatureClinical Presentation
Decreased testicular sizeMost visible sign
InfertilityDue to absence of sperm
Low libido, erectile issuesIf testosterone is low
Soft or firm testesSoft = loss of tissue; Firm = fibrosis
May be asymptomaticEspecially if unilateral or gradual onset

πŸ› οΈ Management Depends on Cause:

  • Hormonal therapy for hypogonadism
  • Treat underlying infection/inflammation
  • Orchiopexy for undescended testis (if early)
  • Avoidance of toxins or drugs

πŸ”¬ Prostatic Hyperplasia (Benign Prostatic Hyperplasia – BPH)

Prostatic Hyperplasia is a non-cancerous enlargement of the prostate gland, commonly seen in older men, especially over age 50. It primarily affects the transition zone of the prostate (around the urethra) and can obstruct urine flow.


πŸ“Š Etiology & Risk Factors:

  • Hormonal imbalance: Increased dihydrotestosterone (DHT) and estrogen
  • Aging
  • Genetic predisposition
  • Androgen sensitivity

πŸ”¬ Pathological Changes in BPH

1. Glandular and Stromal Hyperplasia

  • Proliferation of both epithelial (glandular) and stromal (fibromuscular) cells
  • Results in formation of nodules, especially in the periurethral region (transition zone)

2. Nodular Enlargement

  • Multiple nodules of varying sizes compress the prostatic urethra
  • Leads to urinary outflow obstruction

3. Glandular Changes

  • Glands become dilated and lined by two layers:
    • Inner columnar epithelial cells
    • Outer basal cells
  • May contain corpora amylacea (proteinaceous concretions)

4. Stromal Changes

  • Increased smooth muscle and fibrous tissue
  • Fibromuscular nodules form due to proliferation of stromal elements

5. Compression of Urethra

  • Leads to narrowing of the prostatic urethra
  • Causes difficulty in urination (lower urinary tract symptoms)

6. Secondary Changes in Bladder and Kidneys

  • Bladder wall hypertrophy
  • Trabeculated bladder (due to chronic obstruction)
  • Hydronephrosis and renal damage in severe, untreated cases

πŸ§ͺ Histological Features:

FeatureDescription
Nodular hyperplasiaMultiple nodules in transition zone
Glandular componentCrowded, dilated glands with papillary infoldings
Two-layered epitheliumInner columnar + outer basal cells
Stromal componentProliferation of smooth muscle and fibrous tissue
Corpora amylaceaEosinophilic secretions in gland lumens

🩺 Clinical Correlation:

SymptomCause
Frequency and urgencyIncomplete bladder emptying
Hesitancy and weak streamUrethral compression
NocturiaBladder irritation
Incomplete voidingObstructed outflow
Acute urinary retentionSudden obstruction
Secondary UTIStasis of urine

πŸ› οΈ Management:

  • Medical: Ξ±-blockers, 5Ξ±-reductase inhibitors (e.g., finasteride)
  • Surgical: TURP (Transurethral Resection of Prostate) in severe cases

πŸ” Summary:

BPH is caused by hormonal-induced proliferation of glandular and stromal tissue in the prostate, leading to nodular enlargement and urinary outflow obstruction, but not a precancerous condition.

🧬 Carcinoma Penis – Pathological Changes

Penile carcinoma is a malignant tumor of the skin and mucosa of the penis, most commonly affecting the glans penis, prepuce (foreskin), or coronal sulcus. It is most often a squamous cell carcinoma (SCC).


⚠️ Risk Factors:

  • Poor hygiene
  • Phimosis (tight foreskin)
  • Chronic inflammation or smegma accumulation
  • Human papillomavirus (HPV) – especially types 16, 18
  • Smoking
  • Multiple sexual partners
  • Lack of circumcision

πŸ”¬ Pathological Changes

1. Origin

  • Arises from squamous epithelium of the glans, prepuce, or penile shaft.
  • Often begins as a precancerous lesion like leukoplakia, erythroplasia of Queyrat (in situ carcinoma), or Bowen’s disease.

2. Macroscopic Appearance

  • Ulcerative, exophytic (fungating), or nodular mass
  • May appear as:
    • A non-healing ulcer
    • A hard indurated growth
    • A cauliflower-like mass
  • Often foul-smelling due to secondary infection

3. Microscopic / Histological Features

FeatureDescription
Squamous cell carcinomaMalignant squamous epithelial cells invading underlying tissues
Keratin pearlsRounded eosinophilic structures seen in well-differentiated SCC
Cellular atypiaEnlarged, pleomorphic, hyperchromatic nuclei
InvasionTumor invades dermis, corpus spongiosum, corpus cavernosum
Lymphovascular invasionMay be present in aggressive tumors
Inflammatory infiltrateLymphocytes, plasma cells in stroma

4. Lymph Node Spread

  • Commonly spreads to inguinal lymph nodes
  • Later may spread to pelvic lymph nodes
  • Lymph node involvement is an important prognostic factor

🩺 Clinical Features:

Symptom/SignCause/Explanation
Penile lump or ulcerPrimary tumor
Foul-smelling dischargeSecondary infection or necrosis
Bleeding or painTumor invasion
Inguinal lymphadenopathyRegional metastasis
Difficulty retracting foreskinDue to phimosis or tumor mass

πŸ” Precancerous Lesions:

ConditionDescription
LeukoplakiaWhite plaque-like lesion
Bowen’s DiseaseSCC in situ on shaft or scrotum
Erythroplasia of QueyratSCC in situ on glans/prepuce

πŸ› οΈ Management:

  • Surgical excision (partial or total penectomy)
  • Inguinal lymph node dissection (if nodes are involved)
  • Radiotherapy or chemotherapy in selected cases
  • Early detection = better prognosis

🚩 Prognosis:

  • Good if detected early and limited to glans/prepuce
  • Poorer if there is deep invasion or lymph node metastasis

🧬 Carcinoma Prostate – Pathological Changes

Prostate carcinoma is a malignant tumor that arises most commonly from the glandular epithelium of the prostate. It is typically an adenocarcinoma and is the most common cancer in elderly men.


⚠️ Risk Factors:

  • Age > 50 years
  • Family history of prostate cancer
  • High-fat diet
  • Hormonal imbalance (androgens like testosterone)
  • African descent
  • Genetic mutations (BRCA2, HOXB13, etc.)

πŸ”¬ Pathological Changes in Prostate Cancer

1. Origin and Site

  • Arises from the posterior peripheral zone of the prostate (unlike BPH, which affects the central/transitional zone).
  • Often multifocal and asymmetrical.

2. Gross Pathology

  • Hard, irregular, gritty nodule in the posterior prostate.
  • In advanced stages, the prostate becomes enlarged, firm, and distorted.

3. Microscopic (Histological) Features

FeatureDescription
AdenocarcinomaMost common type (95%)
Small, crowded glandsLined by single layer of malignant cuboidal/columnar cells
Loss of basal cell layerImportant diagnostic clue
Perineural invasionCancer cells invade around nerves – common finding
Prominent nucleoliWithin malignant nuclei
Cribriform patternsFused glandular structures (in high-grade tumors)

4. Gleason Grading System

  • Used to assess tumor differentiation and prognosis.
  • Ranges from Grade 1 (well-differentiated) to Grade 5 (poorly differentiated).
  • Gleason Score = Sum of the two most common patterns (2–10).

5. Patterns of Spread

RouteSites Affected
Local invasionSeminal vesicles, bladder, rectum
LymphaticPelvic lymph nodes
HematogenousBones (especially vertebrae, pelvis), lungs

🩺 Clinical Features

FeatureCause/Mechanism
Often asymptomatic earlyTumor in peripheral zone
Urinary symptoms (late)Frequency, hesitancy, weak stream
Bone painDue to metastasis (especially to spine)
HematuriaInvasion into bladder
Weight loss, fatigueAdvanced/metastatic disease

πŸ§ͺ Laboratory and Diagnostic Findings

TestResult
Serum PSA (Prostate-Specific Antigen)Elevated in most cases (>4 ng/mL)
Digital Rectal Exam (DRE)Hard, irregular prostate
Biopsy (TRUS-guided)Confirms adenocarcinoma
ImagingMRI, bone scan for metastasis

πŸ› οΈ Management

  • Active surveillance (in low-risk cases)
  • Surgery: Radical prostatectomy
  • Radiation therapy
  • Hormonal therapy: Androgen deprivation (LHRH analogs, antiandrogens)
  • Chemotherapy (in advanced cases)

πŸ“Œ Summary:

  • Prostate cancer is a slow-growing adenocarcinoma that starts in the peripheral zone.
  • Shows microscopic glandular patterns, loss of basal layer, and may show perineural invasion.
  • Commonly metastasizes to bones and is monitored using PSA levels.

. Female genital system

🧬 Carcinoma Cervix – Pathological Changes

Carcinoma of the cervix is a malignant tumor arising from the epithelial lining of the cervix, most commonly the squamocolumnar junction (transformation zone). It is one of the most common cancers in women, especially in developing countries.


⚠️ Major Risk Factors:

  • Persistent HPV infection (especially types 16, 18)
  • Early onset of sexual activity
  • Multiple sexual partners
  • Poor genital hygiene
  • Smoking
  • Long-term use of oral contraceptives
  • Immunosuppression (e.g., HIV)
  • Lack of regular Pap smear screening

πŸ”¬ Pathological Changes in Cervical Cancer

1. Precancerous Lesions (Cervical Intraepithelial Neoplasia – CIN)

CIN GradeHistological Changes
CIN I (Mild dysplasia)Abnormal cells in lower 1/3 of epithelium
CIN II (Moderate dysplasia)Abnormal cells in lower 2/3
CIN III (Severe dysplasia/CIS)Full-thickness dysplasia (Carcinoma in situ)
  • If untreated, CIN III may progress to invasive carcinoma over years.

2. Invasive Carcinoma

The most common type is Squamous Cell Carcinoma (SCC) (80–90%).
Others include Adenocarcinoma, Adenosquamous, and Neuroendocrine carcinomas.

a. Microscopic Features of SCC:

  • Malignant squamous epithelial cells invading the stroma
  • Keratin pearls and intercellular bridges (well-differentiated)
  • Nuclear pleomorphism, hyperchromasia, increased mitotic activity
  • Loss of basement membrane integrity (a key sign of invasion)

b. Invasive Adenocarcinoma:

  • Arises from endocervical glands
  • Glandular structures with atypical columnar cells, mucin production, and stromal invasion

3. Macroscopic (Gross) Appearance:

  • Begins as an exophytic growth, ulcer, or fungating mass on the cervix
  • May also be infiltrative or nodular
  • Can extend to the vaginal fornices, uterus, bladder, and rectum

4. Local Spread and Metastasis:

Spread TypeCommon Sites Affected
Local invasionUterus, vagina, parametrium, bladder, rectum
Lymphatic spreadPelvic lymph nodes (iliac, obturator)
Distant metastasisLungs, liver, bones (in advanced stages)

πŸ§ͺ Histological Features Summary:

  • Dysplastic to malignant epithelial changes
  • Invasion beyond basement membrane into stroma
  • Inflammatory cell infiltration
  • Keratin production in SCC
  • Gland formation in adenocarcinoma

🩺 Clinical Features:

Symptom/SignCause
Post-coital bleedingFragile neoplastic vessels in cervix
Foul-smelling vaginal dischargeNecrosis and infection of tumor tissue
Pelvic painTumor invasion of surrounding structures
Irregular menstruationEndometrial involvement
Urinary or rectal symptomsAdvanced disease invading bladder/rectum

🧬 Screening and Diagnosis:

  • Pap smear – detects pre-cancerous changes
  • HPV DNA testing
  • Colposcopy and biopsy – for definitive diagnosis
  • Staging – via imaging and pelvic exam (FIGO staging)

πŸ› οΈ Management:

  • Pre-invasive (CIN): Cryotherapy, LEEP, laser ablation
  • Early invasive: Surgery (radical hysterectomy)
  • Advanced cases: Radiation + chemotherapy (cisplatin-based)

πŸ” Summary:

Cervical carcinoma is caused primarily by high-risk HPV infection. It progresses from dysplasia (CIN) to invasive cancer, showing clear histological features like basement membrane invasion, keratin pearls, or glandular patterns, with local and distant spread if untreated.

🧬 Carcinoma of Endometrium – Pathological Changes

Endometrial carcinoma is a malignant tumor arising from the lining of the uterus (endometrium). It is the most common gynecological cancer in postmenopausal women.


⚠️ Risk Factors (Mainly due to unopposed estrogen exposure):

  • Obesity
  • Early menarche / late menopause
  • Nulliparity (no childbirth)
  • Estrogen therapy (without progesterone)
  • Polycystic ovarian syndrome (PCOS)
  • Endometrial hyperplasia
  • Diabetes mellitus, hypertension
  • Tamoxifen therapy
  • Lynch syndrome (hereditary non-polyposis colorectal cancer – HNPCC)

πŸ”¬ Types of Endometrial Carcinoma

TypeDescription
Type I (Endometrioid type)Most common (~80%), estrogen-dependent, usually arises from endometrial hyperplasia, seen in perimenopausal/postmenopausal women, better prognosis
Type II (Non-endometrioid/serous type)Estrogen-independent, arises from atrophic endometrium, usually in older women, aggressive, poor prognosis

πŸ”¬ Pathological Changes

1. Gross Appearance:

  • Polypoid, fungating, or diffuse thickening of the endometrium
  • May fill the uterine cavity and invade the myometrium

2. Microscopic (Histological) Features

a. Type I (Endometrioid Adenocarcinoma):

  • Glandular pattern resembling normal endometrium
  • Crowded back-to-back glands
  • Minimal to moderate nuclear atypia
  • Invasion into myometrium is key feature of malignancy
  • Often associated with endometrial hyperplasia

b. Type II (Serous Papillary / Clear Cell Carcinoma):

  • Papillary or solid growth patterns
  • High-grade nuclei, marked atypia
  • Psammoma bodies may be present
  • Frequent myometrial invasion and lymphovascular spread

3. Myometrial Invasion

  • Depth of invasion into the myometrium is a key prognostic factor
  • Deep invasion β†’ higher risk of metastasis

4. Lymphovascular Spread

  • Tumor may invade lymphatic vessels
  • Spreads to pelvic and para-aortic lymph nodes
  • Hematogenous spread to lungs, liver, bones in advanced cases

🩺 Clinical Features

SymptomExplanation
Postmenopausal bleedingMost common early sign
Pelvic pain or pressureIn advanced disease
Watery or bloody vaginal dischargeDue to tumor breakdown
Enlarged uterusIn large or advanced tumors

πŸ§ͺ Diagnosis

  • Transvaginal ultrasound: Thickened endometrium (>4 mm in postmenopausal women)
  • Endometrial biopsy / D&C: For histological confirmation
  • Hysteroscopy: Direct visualization
  • Imaging: MRI/CT for staging

πŸ“‰ Staging (FIGO System)

StageDescription
ILimited to uterus
IIInvolves cervix
IIIBeyond uterus (adnexa, vagina, nodes)
IVDistant metastasis (bladder, bowel, distant organs)

πŸ› οΈ Management

Stage/DiseaseTreatment
Early stageSurgical removal (TAH + BSO – Total abdominal hysterectomy + bilateral salpingo-oophorectomy)
AdvancedSurgery + Radiotherapy and/or Chemotherapy
Hormone receptor positiveProgestin therapy (for fertility preservation or recurrence)

πŸ” Summary

Endometrial carcinoma arises from the endometrial lining, often due to unopposed estrogen. It shows glandular proliferation, nuclear atypia, and myometrial invasion. Early detection via postmenopausal bleeding can lead to excellent prognosis, especially in Type I cancers.

🌸 Uterine Fibroids (Leiomyomas) – Pathological Changes

Uterine fibroids are benign (non-cancerous) tumors of the smooth muscle of the uterus (myometrium). They are the most common tumor of the female reproductive tract, especially during reproductive years.


⚠️ Risk Factors:

  • Women of reproductive age (30–50 years)
  • Estrogen and progesterone sensitive – grow during pregnancy, shrink after menopause
  • Early menarche, obesity, nulliparity
  • Family history of fibroids
  • African descent (higher risk)

πŸ“Š Types of Uterine Fibroids (by location):

TypeLocation
IntramuralWithin the muscular wall of the uterus
SubmucosalBeneath the endometrial lining, projecting into the cavity
SubserosalBeneath the outer uterine layer, projecting outward
PedunculatedAttached to the uterus by a stalk (can be submucosal or subserosal)

πŸ”¬ Pathological Changes

1. Gross Appearance

  • Well-circumscribed, round, firm nodules
  • White or gray cut surface with whorled (spiral) pattern
  • May be single or multiple
  • Degenerative changes occur in large or long-standing fibroids

2. Histological Features

FeatureDescription
Smooth muscle cellsUniform spindle-shaped cells arranged in fascicles
No nuclear atypiaCells look benign (no malignant features)
Low mitotic activityCell division is minimal
Dense collagenInterspersed between muscle bundles
Whorled architectureCharacteristic pattern seen under microscope

3. Degenerative Changes (Common in large fibroids):

TypeDescription
Hyaline degenerationMost common; glassy, pink appearance
Cystic degenerationFluid-filled spaces form
Red (carneous) degenerationHemorrhagic infarction (often in pregnancy)
CalcificationCommon in postmenopausal women
Fatty or myxoid changeRare

🩺 Clinical Features

SymptomExplanation
Menorrhagia (heavy bleeding)Especially in submucosal fibroids
Pelvic pain or pressureDue to mass effect or degeneration
Urinary frequencyPressure on bladder
ConstipationPressure on rectum
Infertility or miscarriageInterference with implantation or fetal growth
Abdominal massFirm, irregular enlargement

πŸ§ͺ Diagnosis

  • Pelvic examination: Enlarged, irregular uterus
  • Ultrasound: Confirms size, number, and location
  • MRI: Used in complex or large cases
  • Hysteroscopy: For submucosal fibroids

πŸ› οΈ Management

Treatment OptionIndication
ObservationAsymptomatic, small fibroids
Hormonal therapyGnRH agonists (to shrink fibroids temporarily)
MyomectomySurgical removal (preserves uterus – good for fertility)
HysterectomyDefinitive treatment in symptomatic women not desiring future pregnancy
Uterine artery embolizationBlocks blood supply to fibroid – causes shrinkage

🌸 Vesicular Mole (Hydatidiform Mole) – Pathological Changes

A vesicular mole is an abnormal pregnancy caused by proliferation of trophoblastic tissue and swelling (hydropic degeneration) of chorionic villi. It is classified under gestational trophoblastic diseases (GTD) and can be either benign (molar pregnancy) or premalignant.


🧬 Types of Vesicular Mole:

TypeFeatures
Complete MoleNo fetal tissue, all villi are swollen, 46,XX or 46,XY (paternal origin only)
Partial MoleSome fetal tissue present, mixed normal and abnormal villi, triploid (69,XXY or 69,XXX)

πŸ”¬ Pathological Changes

1. Gross Appearance:

  • Uterus contains multiple translucent, grape-like vesicles (hydropic villi)
  • Vesicles vary in size and may fill or distend the uterus
  • In a complete mole, there is no fetus; in a partial mole, there may be fetal parts

2. Microscopic (Histological) Features

🟣 Complete Mole:

  • Diffuse swelling (hydropic change) of all chorionic villi
  • Circumferential trophoblastic proliferation (both cytotrophoblast and syncytiotrophoblast)
  • No fetal tissue
  • Avascular villi (no fetal blood vessels)

🟑 Partial Mole:

  • Focal swelling of some villi (others may be normal)
  • Focal and irregular trophoblastic proliferation
  • Fetal tissue or red blood cells may be seen in vessels
  • Triploid karyotype

3. Molecular/Genetic Basis:

Mole TypeGenetic Origin
Complete MoleFertilization of an empty ovum by one sperm (duplicates – 46,XX) or two sperms (46,XY)
Partial MoleFertilization of a normal ovum by two sperms – resulting in triploidy (69,XXY)

πŸ§ͺ Other Pathological Features:

  • Extensive villous edema
  • Trophoblastic atypia – nuclear enlargement, hyperchromasia
  • Absence of fetal blood vessels in complete mole
  • In some cases, invasion into myometrium (invasive mole)
  • Risk of progression to choriocarcinoma (especially with complete mole)

🩺 Clinical Features:

Symptom/SignExplanation
Vaginal bleedingDue to abnormal trophoblast invasion
Uterus larger than gestational ageExcessive villous growth
Hyperemesis gravidarumElevated hCG levels
Early-onset preeclampsiaBefore 20 weeks – suspicious for mole
Absence of fetal heart soundsIn complete mole
Passage of grape-like vesiclesCharacteristic of molar pregnancy

πŸ§ͺ Laboratory Findings:

  • Very high Ξ²-hCG levels (much higher than normal pregnancy)
  • Ultrasound: “Snowstorm” or “cluster of grapes” appearance
  • No gestational sac or fetus (in complete mole)

πŸ› οΈ Management:

  • Uterine evacuation by suction curettage
  • Monitor Ξ²-hCG levels post-evacuation weekly until undetectable
  • Avoid pregnancy for 6–12 months
  • Chemotherapy (e.g., methotrexate) if persistent GTD or choriocarcinoma develops

⚠️ Complications:

  • Persistent gestational trophoblastic disease
  • Invasive mole
  • Choriocarcinoma
  • Uterine rupture (rare)
  • Anemia, hyperthyroidism (due to cross-reactivity with TSH receptors)

🧬 Choriocarcinoma – Pathological Changes

Choriocarcinoma is a highly malignant tumor arising from the trophoblastic tissue of the placenta. It can occur after a molar pregnancy, normal pregnancy, abortion, or ectopic pregnancy.


⚠️ Key Characteristics:

  • Aggressive and rapidly spreading
  • Produces very high levels of Ξ²-hCG
  • Highly vascular and hemorrhagic
  • Tends to metastasize earlyβ€”especially to lungs and brain

πŸ”¬ Pathological Changes

1. Gross Appearance

  • Soft, bulky, and hemorrhagic mass
  • Often with areas of necrosis and blood clots
  • Usually found in the uterus, but can also appear at metastatic sites (lung, liver, brain)

2. Microscopic (Histological) Features

FeatureDescription
No chorionic villiDistinguishes it from hydatidiform mole
Sheets of malignant trophoblastsMade up of two cell types:
– CytotrophoblastsMononuclear, clear cytoplasm, defined borders
– SyncytiotrophoblastsMultinucleated, eosinophilic cytoplasm, irregular shapes
Hemorrhage and necrosisProminent in tumor areas due to vascular invasion
Vascular invasionTumor invades blood vessels β†’ rapid hematogenous spread

3. Origin & Associations

SituationFrequency of Choriocarcinoma
After complete mole50%
After abortion or miscarriage25%
After normal pregnancy22–25%
After ectopic pregnancyRare

4. Spread of Tumor

RouteCommon Sites Affected
HematogenousLungs (most common), liver, brain, vagina
LymphaticLess common than hematogenous route

🩺 Clinical Features

Symptom/SignExplanation
Irregular vaginal bleedingTumor invades uterine wall and vessels
Very high Ξ²-hCG levelsSecreted by syncytiotrophoblasts
Cough, hemoptysisLung metastasis
Neurological symptomsBrain metastasis (e.g., headache, seizures)
Uterine enlargementSoft, hemorrhagic mass inside uterus

πŸ§ͺ Laboratory and Imaging Findings

  • Ξ²-hCG: Markedly elevated (>100,000 mIU/mL)
  • Chest X-ray/CT: Detects lung metastases (“cannonball” metastases)
  • Pelvic ultrasound: May show intrauterine mass, but no fetus
  • Histopathology: Confirms diagnosis with absence of chorionic villi and presence of two trophoblast cell types

πŸ› οΈ Management

TreatmentNotes
ChemotherapyHighly effective – Methotrexate or multi-drug regimen (e.g., EMA-CO)
Surgery (rare)Hysterectomy for resistant or non-responsive cases
Monitor Ξ²-hCGUntil undetectable and then for 6–12 months
Avoid pregnancyDuring follow-up to ensure accurate Ξ²-hCG tracking

βœ… Prognosis

TypePrognosis
Gestational choriocarcinomaExcellent with chemo
Non-gestational (germ cell origin)Poorer prognosis

πŸ” Summary

Choriocarcinoma is a highly malignant tumor of trophoblastic origin, usually following a molar or normal pregnancy, characterized by absence of chorionic villi, high Ξ²-hCG levels, trophoblastic cell proliferation, hemorrhage, and early widespread metastasis, but is often curable with chemotherapy.

Breast

🧬 Fibrocystic Changes – Pathological Changes

Fibrocystic changes (also called fibrocystic breast disease or fibrocystic condition) are non-cancerous (benign) changes in the breast tissue. They are the most common breast condition in women of reproductive age, especially between 30–50 years.

These changes are hormone-related (estrogen and progesterone) and often fluctuate with the menstrual cycle.


πŸ” Overview of the Condition:

  • Not a true disease but a collection of benign histological changes
  • May involve fibrosis, cyst formation, ductal hyperplasia, or epithelial changes
  • Usually bilateral and associated with pain, tenderness, and lumpiness, especially before menstruation

πŸ”¬ Pathological Changes in Fibrocystic Disease

1. Cyst Formation

  • Dilatation of breast ducts β†’ formation of fluid-filled cysts
  • Cysts may be small (microcysts) or large (macrocysts)
  • Lined by flattened or apocrine metaplastic epithelium
  • Contents may be blue-green (“blue-dome cysts” on gross examination)

2. Fibrosis

  • Rupture of cysts β†’ leakage of fluid into surrounding stroma
  • Leads to chronic inflammation and fibrosis
  • Makes the breast feel firm, nodular, or rope-like

3. Epithelial Hyperplasia

  • Proliferation of ductal epithelial cells
  • Can be:
    • Usual (simple) hyperplasia: Benign, no atypia
    • Atypical hyperplasia: Cells show mild nuclear atypia, increased risk of developing breast cancer

4. Apocrine Metaplasia

  • Epithelial cells undergo apocrine change (eosinophilic granular cytoplasm, round nuclei)
  • Common and benign

5. Sclerosing Adenosis

  • Increased number of acini (glandular structures) compressed by fibrous tissue
  • Mimics carcinoma on physical exam or imaging but is benign

πŸ“Έ Histological Features Summary:

FeatureDescription
CystsDilated ducts filled with fluid
FibrosisDense collagen in stroma
Ductal hyperplasiaIncreased layers of epithelial cells
Apocrine metaplasiaGranular, eosinophilic cytoplasm in lining cells
Atypical hyperplasiaCellular atypia and architectural distortion

🩺 Clinical Features:

Symptom/SignExplanation
Breast lumpinessDue to fibrosis and cyst formation
Cyclical breast pain (mastalgia)Worsens before menstruation
TendernessEspecially in upper outer quadrants
Fluctuating size of lumpsRelated to hormonal cycle
Often bilateralIn contrast to many tumors

πŸ“‹ Classification of Changes by Cancer Risk:

Type of ChangeCancer Risk
Non-proliferative (cysts, fibrosis, apocrine metaplasia)No increased risk
Proliferative without atypia (usual hyperplasia, sclerosing adenosis)Slight increase
Proliferative with atypia (atypical ductal/lobular hyperplasia)Moderate to high risk (~4–5x)

πŸ§ͺ Diagnosis:

  • Breast examination
  • Ultrasound/mammography: May show dense, cystic, or fibrotic areas
  • Fine-needle aspiration or biopsy: To rule out malignancy
  • Cyst fluid analysis (if needed)

πŸ› οΈ Management:

ApproachIndication
ReassuranceIn simple, non-suspicious cases
Supportive therapyPain relief, proper bra support
Hormonal modulationFor severe symptoms (e.g., OCPs)
Cyst aspirationIf large, painful cyst
Biopsy/surgical removalIf atypia or suspicious lesion

🌿 Fibroadenoma – Pathological Changes

Fibroadenoma is a benign (non-cancerous), solid breast tumor that most commonly occurs in young women, typically between 15–35 years of age. It arises from the stromal (connective) and epithelial (ductal) elements of the breast, hence the name fibro- (fibrous tissue) + adenoma (glandular tumor).


πŸ”¬ Pathogenesis

  • Hormone-sensitive tumor (especially estrogen)
  • Commonly enlarges during pregnancy or menstrual cycle, and may regress after menopause
  • Arises from terminal duct-lobular unit of the breast

πŸ§ͺ Pathological Features

πŸ”Έ 1. Gross Appearance

  • Well-circumscribed, oval or round, rubbery, mobile mass (“breast mouse”)
  • Non-tender, usually painless
  • Size typically ranges from 1–3 cm, but may be larger (giant fibroadenoma)

πŸ”Έ 2. Microscopic (Histological) Features

Fibroadenoma is a biphasic tumor (has two components):

ComponentFeatures
Stromal (fibrous)Proliferation of fibrous connective tissue
Epithelial (glandular)Proliferation of ducts and glandular epithelium

There are two growth patterns:

πŸ”Ή a. Pericanalicular Pattern:

  • Fibrous tissue surrounds and compresses the ducts
  • Ducts remain round or oval

πŸ”Ή b. Intracanalicular Pattern:

  • Fibrous tissue invades and distorts ducts, creating slit-like spaces

Most fibroadenomas show a mixture of both patterns.


πŸ”Έ 3. Cellular Details:

  • Ducts lined by two layers: inner epithelial and outer myoepithelial cells (important to distinguish from malignancy)
  • No cellular atypia or mitosis
  • Stroma may be myxoid or hyalinized

🩺 Clinical Features

FeatureDescription
Painless breast lumpFirm, mobile, well-defined
Common in young womenAges 15–35 years
Increases with estrogenMay grow during pregnancy or hormone therapy
Regresses postmenopauseHormone-dependent

🧬 Variants of Fibroadenoma

VariantFeature
Giant fibroadenomaVery large (>5 cm), common in adolescents
Juvenile fibroadenomaRapidly growing, seen in teenagers
Complex fibroadenomaContains cysts, sclerosing adenosis, or epithelial hyperplasia; slightly ↑ cancer risk

πŸ§ͺ Diagnosis

  • Clinical examination
  • Ultrasound (especially in young women)
  • Mammography (in older women)
  • Fine-needle aspiration (FNA) or core biopsy to confirm diagnosis

πŸ› οΈ Management

ApproachIndication
ObservationSmall, asymptomatic fibroadenoma
Surgical excisionLarge, symptomatic, or growing mass
Cryoablation or laser therapyMinimally invasive alternatives
Regular follow-upTo monitor any changes or growth

βœ… Prognosis

  • Excellent – benign tumor
  • No risk of metastasis
  • Slight increase in cancer risk only in complex fibroadenomas

πŸŽ—οΈ Carcinoma of the Breast – Pathological Changes

Breast carcinoma is a malignant tumor that arises most commonly from the epithelial lining of the ducts or lobules of the breast. It is the most common cancer in women worldwide and a leading cause of cancer-related deaths.


⚠️ Risk Factors:

  • Female sex, increasing age
  • Family history (BRCA1, BRCA2 mutations)
  • Early menarche / late menopause
  • Nulliparity, late first pregnancy
  • Hormone replacement therapy
  • Obesity, alcohol, radiation exposure
  • Prolonged estrogen exposure

🧬 Types of Breast Carcinoma

A. Non-Invasive (In Situ) Carcinomas

πŸ”Έ Confined within the ducts or lobules; no stromal invasion

TypeFeatures
Ductal Carcinoma in Situ (DCIS)Arises in ducts, may show comedo necrosis, calcifications, or cribriform patterns
Lobular Carcinoma in Situ (LCIS)Arises in lobules, often multifocal and bilateral, marker for future invasive cancer

B. Invasive (Infiltrating) Carcinomas

πŸ”Έ Invade surrounding stroma, fat, lymphatics, and may metastasize.

TypeFeatures
Invasive Ductal Carcinoma (IDC)Most common (~70–80%), hard, irregular mass, desmoplastic stroma
Invasive Lobular Carcinoma~10%, single-file pattern of tumor cells, bilateral/multifocal tendency
Medullary CarcinomaSoft, well-circumscribed, prominent lymphocytes, better prognosis
Mucinous (Colloid) CarcinomaTumor cells in mucin pools, older women, slow-growing
Inflammatory CarcinomaAggressive, peau d’orange appearance, dermal lymphatic invasion
Paget’s Disease of NippleDCIS cells invade nipple epithelium; crusting, itching nipple lesion

πŸ”¬ Pathological Changes

1. Gross Appearance

  • Hard, irregular mass, often in the upper outer quadrant
  • May be fixed to skin or chest wall
  • Retraction of nipple or skin dimpling
  • Inflammatory type β†’ swollen, red breast with peau d’orange

2. Microscopic Features

FeatureDescription
Malignant epithelial cellsIrregular, pleomorphic nuclei, high N/C ratio
Invasion of stromaBreaks through basement membrane
DesmoplasiaDense fibrous tissue reaction (firm feel)
Mitotic figuresIncreased cell division
Lymphovascular invasionCommon in aggressive types
Single-file cells (in lobular type)Classic feature of lobular carcinoma

πŸ§ͺ Molecular Subtypes (Based on Receptor Status)

SubtypeReceptorsPrognosis
Luminal AER+/PR+, HER2–Best prognosis
Luminal BER+/PR+, HER2+Moderate prognosis
HER2-enrichedER–, PR–, HER2+Aggressive
Triple-negativeER–, PR–, HER2–Poor prognosis, aggressive

🩺 Clinical Features

FeatureExplanation
Painless, hard breast lumpMost common presentation
Skin dimpling, nipple retractionTumor invasion of Cooper’s ligaments
Nipple discharge or eczemaIn Paget’s disease
Peau d’orangeLymphatic blockage by tumor cells
Axillary lymphadenopathyCommon first site of metastasis

🌍 Spread of Tumor

RouteSites Affected
LymphaticAxillary β†’ supraclavicular nodes
HematogenousBones, lungs, liver, brain
Local invasionSkin, muscle, chest wall

πŸ§ͺ Investigations

  • Mammography: Detects microcalcifications
  • Ultrasound/MRI
  • FNAC / Core biopsy: Histological diagnosis
  • IHC for receptor status: ER, PR, HER2
  • Staging: TNM system (Tumor, Node, Metastasis)

πŸ› οΈ Management

Treatment ModalityUsed For
SurgeryLumpectomy or mastectomy
RadiotherapyAfter breast-conserving surgery
ChemotherapyFor high-grade or advanced tumors
Hormonal therapyTamoxifen (ER+), Aromatase inhibitors
Targeted therapyTrastuzumab (HER2+ tumors)

βœ… Prognostic Factors

Good PrognosisPoor Prognosis
Small tumor sizeLarge tumor
Negative lymph nodesNode involvement
ER/PR positiveTriple negative
Low-grade tumorHigh mitotic index, necrosis

. Central nervous system

🧠 Meningitis – Pathological Changes

Meningitis is an inflammation of the meninges, the protective membranes covering the brain and spinal cord. It can be acute or chronic, and is usually caused by bacteria, viruses, fungi, or tuberculosis.


πŸ“Š Types of Meningitis and Their Causes

TypeCommon Causes
Acute Bacterial MeningitisStreptococcus pneumoniae, Neisseria meningitidis, Haemophilus influenzae, E. coli
Viral (Aseptic) MeningitisEnteroviruses, HSV, mumps virus
Tuberculous MeningitisMycobacterium tuberculosis
Fungal MeningitisCryptococcus neoformans (especially in immunocompromised)

πŸ”¬ Pathological Changes in Meningitis (by type)


πŸŸ₯ 1. Acute Pyogenic (Bacterial) Meningitis

a. Gross Changes

  • Cloudy, opaque meninges
  • Purulent exudate on surface of brain, especially over convexities and base
  • Congested blood vessels

b. Microscopic Features

  • Neutrophilic infiltration in the subarachnoid space
  • Inflammation of leptomeninges (pia + arachnoid mater)
  • Fibrinous exudate, bacteria seen on Gram stain
  • Vasculitis, thrombosis of vessels β†’ infarction
  • May involve ventricles (ventriculitis)

c. Complications

  • Hydrocephalus (due to blocked CSF flow)
  • Cerebral edema
  • Seizures, cranial nerve palsies
  • Abscess formation

🟧 2. Viral (Aseptic) Meningitis

a. Gross Changes

  • Meninges appear normal or slightly congested

b. Microscopic Features

  • Lymphocytic infiltration of meninges
  • Mild edema of brain tissue
  • No pus formation
  • No fibrin deposition

c. Prognosis

  • Generally self-limiting with full recovery

🟫 3. Tuberculous Meningitis

a. Gross Changes

  • Thick gelatinous exudate at the base of the brain
  • Involves cranial nerves and blood vessels

b. Microscopic Features

  • Granulomatous inflammation with:
    • Epithelioid cells
    • Langhans giant cells
    • Caseous necrosis
  • Lymphocytes and plasma cells in CSF
  • Vasculitis of arteries β†’ infarction
  • May lead to hydrocephalus

c. Complications

  • Fibrosis, adhesions, hydrocephalus
  • Cranial nerve damage

🟀 4. Fungal Meningitis (e.g., Cryptococcal)

a. Seen in immunocompromised (HIV/AIDS)

  • Minimal inflammation
  • Clear gelatinous appearance of meninges

b. Microscopy

  • Capsulated yeast cells (e.g., Cryptococcus) in CSF
  • May be seen with India Ink stain
  • Mild mononuclear infiltration

πŸ§ͺ CSF Findings (Key for Diagnosis)

TypeAppearanceCellsProteinGlucosePressure
BacterialTurbidNeutrophils ↑↑↑↓↓↑
ViralClearLymphocytes ↑Normal/↑NormalNormal/↑
TBCobweb clotLymphocytes ↑↑↓↑
FungalClear/slightly hazyLymphocytes ↑↑↓/Normal↑

🩺 Clinical Features of Meningitis

Sign/SymptomCause
Headache, feverInflammatory response
Neck stiffness (nuchal rigidity)Meningeal irritation
Vomiting, photophobiaRaised intracranial pressure
Seizures, altered sensoriumCerebral irritation or inflammation
Kernig’s/Brudzinski’s signSpecific signs of meningeal irritation

πŸ› οΈ Complications (Especially in bacterial/TB meningitis)

  • Hydrocephalus
  • Seizures
  • Hearing loss (CN VIII involvement)
  • Brain abscess
  • Death, if untreated

πŸ” Summary

Meningitis is an inflammatory condition of the meninges caused by various pathogens.

  • Bacterial: Acute, neutrophilic response with pus and high fatality
  • Viral: Lymphocytic, milder course
  • Tuberculous: Chronic granulomatous inflammation
  • Fungal: Subtle, seen in immunocompromised patients
    Early diagnosis via CSF analysis, and prompt treatment are crucial.

🧠 Encephalitis – Pathological Changes

Encephalitis is an inflammation of the brain parenchyma, usually caused by viral infections. It is a potentially life-threatening condition that affects the neurons, glial cells, and blood vessels of the brain.


⚠️ Common Causes of Encephalitis

Cause TypeExamples
Viral (most common)Herpes Simplex Virus (HSV-1), Enteroviruses, Japanese Encephalitis virus, Rabies virus, Cytomegalovirus (CMV), Epstein-Barr Virus (EBV), HIV
AutoimmuneAutoimmune encephalitis (e.g., anti-NMDA receptor encephalitis)
Post-infectiousAcute disseminated encephalomyelitis (ADEM)

πŸ”¬ Pathological Changes in Encephalitis

1. Gross Changes

  • Swollen brain with flattening of gyri and narrowing of sulci
  • Edematous and congested brain tissue
  • Petechial hemorrhages in severe cases
  • Softening of brain tissue (malacia)

2. Microscopic (Histological) Features

FeatureDescription
Perivascular cuffingLymphocytes and plasma cells accumulate around blood vessels
Neuronal degenerationNeurons show swelling, shrinkage, or necrosis
Microglial nodulesSmall clusters of activated microglia around damaged neurons
NeuronophagiaPhagocytosis of injured neurons by microglia
EdemaSwelling of brain tissue, leading to increased intracranial pressure
Glial reaction (gliosis)Proliferation of astrocytes in response to injury

3. Virus-Specific Features

VirusUnique Pathological Features
Herpes Simplex Virus (HSV-1)Necrosis and hemorrhage in temporal lobes, Cowdry type A inclusion bodies
Rabies virusNegri bodies in neurons (esp. hippocampus, Purkinje cells)
Japanese EncephalitisInflammation, microglial nodules, neuronophagia in thalamus and basal ganglia
HIVHIV encephalitis, multinucleated giant cells, microglial activation

🩺 Clinical Features of Encephalitis

FeatureExplanation
High-grade feverDue to infection/inflammation
Altered mental statusDrowsiness, confusion, disorientation
SeizuresDue to neuronal irritation or cortical involvement
Headache, vomitingDue to raised intracranial pressure
Focal neurological signsParalysis, speech issues, visual disturbances
Neck stiffnessSometimes present (may mimic meningitis)
Behavioral changesEspecially in HSV encephalitis (affecting temporal lobes)

πŸ§ͺ Diagnosis

InvestigationFinding
CSF analysisClear fluid, lymphocytic pleocytosis, ↑ protein, normal glucose
MRI/CT BrainEdema, hemorrhage, especially in temporal lobes (HSV)
EEGAbnormal electrical activity
PCR for viral DNA/RNAConfirms viral cause (e.g., HSV, JE virus)
Serological testsAntibodies to specific viruses

πŸ› οΈ Management

ApproachDetails
Antiviral therapyAcyclovir for HSV encephalitis
Supportive careFluids, fever control, oxygen, seizure management
CorticosteroidsIn autoimmune encephalitis or severe inflammation
Management of complicationsE.g., cerebral edema, respiratory failure

πŸ” Summary

Encephalitis is an inflammatory condition of the brain, often viral in origin, showing perivascular inflammation, neuronal destruction, microglial activation, and cerebral edema. It presents with fever, altered consciousness, seizures, and may lead to coma or death if untreated. Prompt diagnosis and antiviral therapy are critical.

🧠 Stroke – Pathological Changes

A stroke (also known as cerebrovascular accident – CVA) is a sudden loss of brain function caused by interruption of blood supply to the brain. This leads to neuronal injury, inflammation, and tissue death. Strokes can be ischemic or hemorrhagic, and the pathological changes vary accordingly.


πŸ”„ Types of Stroke

TypeDescription
Ischemic StrokeCaused by blockage of a cerebral artery (80–85% of all strokes)
Hemorrhagic StrokeCaused by rupture of a blood vessel leading to bleeding into brain tissue (15–20%)

πŸ”¬ Pathological Changes in Stroke


🟨 1. Ischemic Stroke (Cerebral Infarction)

Caused by thrombosis or embolism β†’ reduced oxygen and glucose β†’ cell death

a. Gross Pathology:

  • Affected area becomes pale and soft in early stages
  • Over time, it becomes edematous, then liquefies (liquefactive necrosis)
  • Later, cystic cavities form due to tissue breakdown

b. Microscopic Changes (Time-dependent)

Time After InfarctChanges Seen
0–12 hoursNeuronal injury: “red neurons” (shrunken, eosinophilic neurons), edema
12–24 hoursNeutrophil infiltration
1–3 daysDense neutrophilic infiltration, beginning necrosis
3–7 daysMacrophages (microglia) remove debris
1–2 weeksLiquefaction, gliosis, vascular proliferation
>2 weeksCyst formation, reactive astrocytosis (gliotic scar)

πŸŸ₯ 2. Hemorrhagic Stroke

Caused by rupture of a blood vessel (commonly due to hypertension, aneurysm)

a. Gross Pathology:

  • Fresh blood in the brain parenchyma or subarachnoid space
  • Surrounding edema and tissue compression

b. Microscopic Features:

  • RBCs in brain tissue
  • Disruption of neurons and glial cells
  • Macrophages engulf blood cells (hemosiderin-laden macrophages)
  • Later: gliosis and scarring

c. Types of Hemorrhagic Stroke:

TypeSite
Intracerebral hemorrhageBasal ganglia, thalamus, pons, cerebellum
Subarachnoid hemorrhageCircle of Willis (due to aneurysm rupture)

πŸ§ͺ Key Pathological Features Summary

FeatureIschemic StrokeHemorrhagic Stroke
CauseArterial occlusionVessel rupture
Tissue DamagePale, soft, infarcted areaBlood-filled spaces, edema
Cell deathLiquefactive necrosisPressure damage + necrosis
Inflammatory responseNeutrophils β†’ macrophagesMacrophages, RBCs, gliosis
HealingCyst formation, gliosisHemosiderin deposits, gliosis

🩺 Clinical Features

SymptomExplanation
Sudden weakness/paralysisMotor cortex involvement
Slurred speech (aphasia)Dominant hemisphere lesion
Loss of consciousnessBrainstem or massive hemorrhage
Headache, vomitingCommon in hemorrhagic stroke
Visual disturbancesOccipital lobe involvement

πŸ› οΈ Diagnosis and Imaging

  • CT Scan: To differentiate ischemic vs. hemorrhagic stroke (bleeding appears bright)
  • MRI: More sensitive for early ischemic changes
  • Angiography: For aneurysms or vessel occlusion
  • Blood tests, ECG, carotid Doppler: For underlying causes

πŸ” Summary

A stroke leads to tissue damage due to interrupted blood flow or bleeding.

  • In ischemic stroke, the brain undergoes liquefactive necrosis, inflammatory infiltration, and later gliosis.
  • In hemorrhagic stroke, blood accumulation causes neuronal destruction, pressure effects, and edema.

Time is brain – early diagnosis and treatment can limit permanent damage.

🧠 Tumors of the Central Nervous System (CNS) – Pathological Changes

CNS tumors are abnormal growths within the brain or spinal cord. They can be benign or malignant, primary or secondary (metastatic), and may arise from neurons, glial cells, meninges, or other components.


πŸ”„ Classification of CNS Tumors

(Based on WHO & tissue origin)

πŸ”Ή I. Glial Cell Tumors (Gliomas)

(Arise from supporting glial cells)

TypeCell of OriginFeatures
AstrocytomaAstrocytesMost common glioma; graded I–IV
Glioblastoma multiforme (GBM)High-grade astrocytoma (Grade IV)Aggressive, necrosis, hemorrhage
OligodendrogliomaOligodendrocytesSlow-growing, calcifications, “fried-egg” cells
EpendymomaEpendymal cellsCommon in 4th ventricle (kids), spinal cord (adults)

πŸ”Ή II. Neuronal Tumors

TypeFeatures
MedulloblastomaMalignant cerebellar tumor (children), primitive neuroectodermal tumor (PNET), spreads via CSF
GangliogliomaContains both mature neurons and glial cells, usually benign

πŸ”Ή III. Meningeal Tumors

TypeFeatures
MeningiomaArises from arachnoid cap cells, usually benign, extra-axial (outside brain tissue), may compress brain

πŸ”Ή IV. Nerve Sheath Tumors

TypeFeatures
SchwannomaArises from Schwann cells (CN VIII – acoustic neuroma), well-circumscribed, spindle cells
NeurofibromaMixed tumor of Schwann cells and fibroblasts, associated with neurofibromatosis

πŸ”Ή V. Secondary (Metastatic) Tumors

  • Most common CNS tumors in adults
  • Common primaries: lung, breast, melanoma, kidney, GI tract
  • Usually multiple, located at gray-white matter junction

πŸ”¬ Pathological Features of Common CNS Tumors


🧠 1. Glioblastoma Multiforme (Grade IV Astrocytoma)

FeatureDescription
GrossIrregular, necrotic, hemorrhagic mass with infiltrative borders
MicroscopyPseudopalisading necrosis, endothelial proliferation, anaplastic cells
PrognosisPoor – survival <1 year

🧠 2. Meningioma

FeatureDescription
GrossWell-circumscribed, firm, attached to dura
MicroscopyWhorled pattern, psammoma bodies (calcifications)
Often estrogen-sensitiveMore common in females

🧠 3. Oligodendroglioma

FeatureDescription
GrossGray mass with calcifications
Microscopy“Fried-egg” appearance of cells, delicate capillary network
PrognosisRelatively better than GBM

🧠 4. Ependymoma

FeatureDescription
Location4th ventricle (children), spinal canal (adults)
MicroscopyPerivascular pseudorosettes, true rosettes
CSF spread possibleMay block CSF β†’ hydrocephalus

🧠 5. Medulloblastoma

FeatureDescription
PopulationChildren, cerebellum
MicroscopySmall round blue cells, Homer-Wright rosettes
AggressiveSpreads via CSF – drop metastases in spinal cord

πŸ“Š General Pathological Features of CNS Tumors

  • Mass effect: Pressure on adjacent brain tissue β†’ headache, vomiting, papilledema
  • Edema: Due to disrupted blood-brain barrier
  • Necrosis & hemorrhage: Common in high-grade tumors (e.g., GBM)
  • Infiltration vs. compression:
    • Malignant tumors (gliomas) infiltrate
    • Benign tumors (meningioma) compress

πŸ§ͺ Diagnosis Tools

  • MRI with contrast – gold standard
  • CT scan – quick for hemorrhage or calcification
  • Biopsy – definitive diagnosis
  • CSF analysis – for medulloblastoma or ependymoma (if spinal spread suspected)

πŸ› οΈ Treatment Options

MethodUsed For
Surgical excisionFirst-line for accessible tumors
RadiotherapyEspecially for malignant/inoperable tumors
ChemotherapyUsed in GBM, medulloblastoma
Targeted therapiesBased on genetic mutations (e.g., IDH, MGMT status in gliomas)

πŸ” Summary

CNS tumors include a wide range of benign and malignant neoplasms. Gliomas (especially glioblastoma) are the most common malignant primary brain tumors. Meningiomas and schwannomas are usually benign.
Pathological changes include cellular atypia, necrosis, vascular proliferation, and infiltrative growth, depending on the tumor type.

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Categorized as BSC SEM 4 PATHOLOGY 2 & GENETICS, Uncategorised