Diseases of the Digestive System
Pathology Notes
Esophagus
Stomach
Colon
Liver
MBBS Pathology
🔴 Esophagus
Topics: Barrett Esophagus · Esophageal Carcinoma (SCC & AC)
- Hollow muscular tube from epiglottis → gastroesophageal (GE) junction
- Layers: Mucosa → Submucosa → Muscularis propria → Adventitia/Serosa
- Normal epithelium: Non-keratinized stratified squamous
- No goblet cells normally
Definition
Complication of chronic GERD — intestinal metaplasia of the esophageal squamous mucosa (replacement by columnar epithelium with goblet cells). It is a direct precursor of esophageal adenocarcinoma.
Who gets it
White males, 40–60 years; 10% of symptomatic GERD
Key Cell
Goblet cells with pale blue mucin vacuoles (defining feature)
Risk of AC
High-grade dysplasia → ≥10% progression to cancer
Progression Sequence (Important!)
GERD → Intestinal Metaplasia → Low-grade Dysplasia → High-grade Dysplasia → Intramucosal AC → Invasive AC
Gross / Endoscopic Appearance
- Red velvety mucosa (gastrointestinal-type) extending >1 cm above GE junction
- Granular zone visible on endoscopy
Diagnosis & Treatment
- Endoscopic biopsy showing intestinal metaplasia
- Periodic surveillance endoscopy for dysplasia
- High-grade dysplasia / intramucosal CA → esophagectomy, endoscopic mucosectomy, radiofrequency ablation
🧠 Quick Memory Hook
SCC = Smoking & Spirit (alcohol) | Stratified squamous → Superior/Middle third
AC = Acid reflux (GERD) → Barrett's | Adistal/Antrum → Adenocarcinoma
| Feature | SCC (Squamous Cell Carcinoma) | AC (Adenocarcinoma) |
|---|
| Frequency globally | 90% — more in underdeveloped regions (central China) | 10% but rising — more in Western countries (USA) |
| Predilection site | 50% middle third of esophagus | Distal third; involves gastric cardia |
| Risk factors | Alcohol, tobacco, hot beverages, caustic injury, achalasia, Plummer-Vinson syndrome, radiation, poverty | Barrett esophagus, chronic GERD |
| Demographics | Male, >50 years | White male |
| Histology | Nests of malignant cells; keratin pearls; intercellular bridges (desmosomes) | Mucin-producing back-to-back glands |
| Gross (advanced) | Polypoid / fungating; ulcerating; diffuse infiltrating | Bulky mass; ulceration; infiltration |
Microscopic ID — Well-differentiated SCC (Exam Favourite!)
- Keratin pearls — round, laminar keratinization
- Intercellular bridges (desmosomes) between cells
Early vs Advanced Esophageal Carcinoma
- Early SCC: confined to mucosa & submucosa → small gray-white plaquelike thickenings; carcinoma in situ
- Advanced SCC: extends beyond submucosa; 3 gross patterns — polypoid, ulcerated, infiltrative (causes strictures)
Spread of Esophageal Carcinoma
- Rich submucosal lymphatics → circumferential & longitudinal spread
- Upper 1/3: → cervical lymph nodes
- Middle 1/3: → mediastinal, paratracheal, tracheobronchial nodes
- Lower 1/3: → gastric and celiac nodes
- Local invasion → respiratory tree (pneumonia), aorta (fatal hemorrhage), mediastinum
Clinical Features
- Begins insidiously → dysphagia (solid → liquid), odynophagia
- Anorexia, weight loss, cachexia, debilitation
- Hemorrhage, sepsis, hoarseness, tracheoesophageal fistula → cough
- Diagnosis: endoscopy + biopsy
- Prognosis: 5-year survival ~10% — early detection is critical
📝 Exam Questions (from slides)
- Which morphology is found in Barrett esophagus? → Intestinal Metaplasia
- Keratin pearls + intercellular bridges = feature of? → Well-differentiated SCC
- Predilection sites of SCC and AC?
- How to define an early esophageal carcinoma?
- Precursor disease of AC? → Barrett Esophagus
🟠 Stomach — Gastritis
Topics: Acute Gastritis · H. pylori Gastritis · Autoimmune Gastritis · Chronic Atrophic Gastritis
- Regions: Cardia → Fundus → Corpus (body) → Antrum → Pylorus
- Superomedial = lesser curvature; Inferolateral = greater curvature
- Normal epithelium: uniform mucous (foveolar) cells WITHOUT goblet cells
- Simple tubular glands open at epithelial pits
Causes (multiple)
- Alcohol, NSAIDs, severe stress, systemic infections
- Uremia, bile reflux, portal hypertension, radiation, chemotherapy
- Ischemia & shock, mechanical trauma
Microscopy
- Mucosal edema + neutrophil infiltrate
- Concurrent erosion and hemorrhage visible
- Variants: diffusely hyperemic mucosa OR acute erosive gastritis
🧠 HP Virulence Factors — "FUAT"
Flagella | Urease | Adhesins | Toxins
4 Classic Microscopic Features (Warthin-Starry silver stain)
- A: Spiral-shaped HP bacilli in surface mucus (highlighted by silver stain)
- B: Intraepithelial & lamina propria neutrophils (prominent)
- C: Lymphoid aggregates with germinal centers + subepithelial plasma cells
- D: Intestinal metaplasia
Two Patterns of HP Gastritis
- Antral type: High acid production → risk for duodenal ulcer
- Pangastritis / Multifocal atrophy: Low acid secretion → risk for adenocarcinoma
HP-associated Diseases (4 key associations)
- Chronic gastritis
- Peptic ulcer disease (>70%)
- Gastric adenocarcinoma
- Gastric MALT lymphoma (HP-induced proliferation of lymphoid tissue)
Definition
Body-restricted (fundus/corpus) chronic atrophic gastritis associated with anti-parietal cell and anti-intrinsic factor antibodies
Acid
Achlorhydria (impaired acid secretion)
Hormones
↑ Gastrin (antral G-cell hyperplasia)
Vitamin
B12 deficiency → Pernicious Anemia
🧠 Why pernicious anemia?
Anti-intrinsic factor antibodies → no intrinsic factor → vitamin B12 cannot be absorbed in ileum → megaloblastic/pernicious anemia
- Glandular atrophy
- Intestinal metaplasia (strong association with gastric adenocarcinoma)
- Lymphocytes & plasma cells in lamina propria
- Dysplasia: back-to-back glands, gland-in-gland, dilated — cells with enlarged, stratified, hyperchromatic nuclei
📝 Exam Questions
- Four gastric diseases associated with HP? → Chronic gastritis, PUD, Adenocarcinoma, MALT lymphoma
- Microscopy of chronic HP gastritis? → A, B, C, D above
- Why does autoimmune gastritis → pernicious anemia? → Anti-IF antibody → no B12 absorption
🟡 Peptic Ulcer Disease (PUD)
Chronic mucosal ulceration from imbalance between protective & damaging forces
Main causes
HP infection (>70%) or NSAID use
Sites
Gastric antrum + proximal duodenum (1st part)
Mechanism
Hyperacidity + impaired mucosal defenses
Pathogenesis
Imbalance: Damaging forces (acid, pepsin, HP toxins, NSAIDs) > Mucosal defenses (mucus, bicarbonate, prostaglandins, blood flow, cell turnover)
- Usually solitary (>80%)
- Shape: round to oval
- "Punched-out" defect with sharp demarcation
- Flat and flush edges (vs raised edges in malignant ulcer)
- Clean, flat, smooth base
- Gastric folds radiating from ulcer
- Mucosal defect penetrates the muscularis propria
Duodenal Peptic Ulcer
Small, sharply punched-out. Margins NOT elevated. Ulcer base is clear.
🧠 Mnemonic: N-I-G-S (from surface to deep)
N = Necrosis (surface exudate)
I = Inflammation (neutrophils)
G = Granulation tissue (new blood vessels + fibroblasts)
S = Scar (fibrous tissue at base)
N
Necrosis — superficial fibrinopurulent exudate
I
Inflammation — neutrophilic infiltrate
G
Granulation tissue — vascular proliferation
S
Scar — fibrous tissue; hypertrophied nerve bundles; proliferative endoarteritis
Healing: crater fills with granulation → reepithelialization from margins → extensive fibrous scarring remains
| Feature | Benign (Peptic) | Malignant (Carcinoma) |
|---|
| Size | Small | Large |
| Shape | Regular (round/oval) | Irregular (volcano-like / crater) |
| Margin | Flat and flush | Raised, everted |
| Mucosal folds | Radiating from ulcer | Interrupted/destroyed |
| Ulcer bed | Clean, smooth or hemorrhagic | Shaggy, necrotic, or hemorrhagic |
Bleeding
Most common — iron deficiency anemia, hematemesis
Perforation
Peritonitis — surgical emergency
Pyloric Stenosis
Scarring → obstruction → projectile vomiting
Malignant transformation
Rare — gastric ulcer > duodenal ulcer
Clinical Features
- Chronic, recurring lesions
- Epigastric burning or aching pain
- Nausea, vomiting, bloating, belching
- Iron deficiency anemia, frank hemorrhage, or perforation
- Treatment: HP eradication, acid neutralization (PPIs/H2-blockers), surgery
🔴 Gastric Carcinoma
Second leading cause of cancer deaths worldwide — usually asymptomatic until late
Age/Sex
>50 years; males > females
Infection
H. pylori or EBV infection
Dietary
Nitrosamines, salted/smoked foods
Precursor
Intestinal metaplasia, chronic atrophic gastritis
Gene Mutations
- CDH1 — Diffuse type (E-cadherin loss)
- APC, β-catenin — Intestinal type
- TP53 — Both types
- HER2 (targetable)
Early Gastric Carcinoma (EGC)
- Confined to mucosa & submucosa regardless of lymph node status
- Most important prognostic feature = depth of invasion
- Generally good prognosis
Advanced Gastric Carcinoma — 3 Gross Patterns
- Exophytic (Polypoid/Fungating): Mushroom-like mass protruding into lumen; favored site = lesser curvature of antrum
- Ulcerated: Elevated mass with heaped-up everted borders + central ulceration
- Infiltrative (Linitis Plastica): Entire wall infiltrated → "leather bottle" appearance; diffuse rugal flattening
| Feature | Intestinal Type | Diffuse Type |
|---|
| HP association | Yes — via chronic gastritis → metaplasia | No |
| Histology | Malignant cells forming intestinal glands | Signet ring cells (no gland formation) |
| Signet ring cell | Absent | Large mucin vacuole pushes nucleus to periphery |
| Gross form | Exophytic, ulcerated | Infiltrative (linitis plastica) |
| Stroma | Desmoplastic reaction | Discohesive cells permeate wall |
Lymphatic
Left supraclavicular node (Virchow's node = Troisier sign)
Hematogenous
Liver (most common), lung, bone
Local invasion
Adjacent stomach wall, nearby organs
Transcoelomic
Peritoneal seeding; Krukenberg tumor
Krukenberg Tumor (Important!)
Intraperitoneal spread of gastric carcinoma to both ovaries in females. Gray-white masses up to 20 cm. Composed of signet-ring mucus-secreting cells.
Clinical Features & Prognosis
- Usually asymptomatic until late
- Weight loss, anorexia, early satiety, dysphagia, epigastric pain
- Occult bleeding, iron deficiency anemia
- Prognostic indicators: depth of invasion, nodal/distant metastasis, local invasion
📝 Exam Questions
- Routes of metastasis of gastric carcinoma? → Lymphatic, hematogenous, direct, transcoelomic
- What is Krukenberg tumor? → Bilateral ovarian metastasis from gastric carcinoma (signet ring cells)
- What is "linitis plastica"? → Diffuse infiltrative gastric carcinoma → leather bottle appearance
- What is a signet ring cell? → Large mucin vacuole pushing nucleus to periphery
- How to identify early gastric carcinoma? → Confined to mucosa/submucosa regardless of LN status
🟢 Large Intestine — Adenomas & Adenocarcinoma
Most common GI malignancy; arises from adenoma → carcinoma sequence
- Straight crypts — no villi (unlike small intestine)
- Simple columnar epithelium: absorptive cells + goblet cells
- Crypts aligned perpendicular to muscularis mucosae → "rack of test tubes" appearance
- Thin lamina propria surrounds crypts
Key Facts
- Most common & clinically important neoplastic polyps
- Present in ~50% of adults by age 50 in Western countries
- Screening colonoscopy starts at 45 years
- Size: 0.3–10 cm; can be pedunculated or sessile
- Velvety texture, bumpy surface
- Size is most important risk factor for malignancy
3 Histologic Types
- Tubular adenoma — small, pedunculated; crowded/disorganized tubular glands
- Villous adenoma — sessile; cauliflower-like; long slender projections like SI villi; highest malignant potential
- Tubulovillous — mixed
Sessile Serrated Adenoma
Lined by goblet cells WITHOUT typical dysplasia. Distinguished from hyperplastic polyp by involvement of the crypts.
Low-grade Dysplasia (Most Adenomas)
Relatively uniform, elongated hyperchromatic nuclei; pseudostratification; maintains polarity; apical slightly basophilic cytoplasm; inconspicuous nucleoli.
Gene
APC gene mutation (autosomal dominant)
Polyp count
500–2500 adenomas; minimum 100 for diagnosis
Age of onset
Adolescence or early adulthood
Cancer risk
100% by midlife without colectomy; colon cancer before 30 years
Treatment
Prophylactic colectomy is mandatory
Epidemiology & Etiology
- Most common malignancy of the GI tract
- >50 years; peak 60–70 y; males slightly more than females
- Geographic disparities — common in United States
- Dietary factors (high fat, low fiber)
3 Molecular Pathways
- APC/β-catenin pathway — increased Wnt signaling (FAP)
- Microsatellite instability pathway — defects in DNA mismatch repair (Lynch syndrome)
- CpG island hypermethylation phenotype — MLH1 inactivation
Gross Appearance — Predilection Sites
- Most common: rectum & sigmoid colon
- Right-sided (cecum/ascending): polypoid/exophytic mass → lumen is wide → obstruction uncommon → presents as anemia/fatigue
- Left-sided (descending/sigmoid): annular, circumferential (napkin-ring) → constricts lumen → changes in bowel habits, cramping
- Malignant ulcers with raised everted edges
Histology
- Adenocarcinoma accounts for 90% of colorectal carcinoma
- Irregularly distributed tubular structures in desmoplastic stroma
- Complex cribriform architecture; intraluminal necrotic debris
- Mucinous adenocarcinoma: extracellular mucin pools + signet ring cells → translucent, gelatinous → poor prognosis
Metastasis
- Lymph node → subcapsular sinus glandular structures
- Lung → solitary subpleural nodule
- Liver → large masses with central necrosis
- Invasive adenocarcinoma: malignant glands infiltrating muscle wall
Clinical Features — Right vs Left Sided
| Right-sided (Cecum/Ascending) | Left-sided (Descending/Sigmoid/Rectum) |
|---|
| Fatigue, weakness, iron deficiency anemia | Occult bleeding, changes in bowel habits |
| Exophytic growth; large lumen → no obstruction | Cramping, left lower-quadrant discomfort |
| Polypoid mass | Annular constricting lesion |
Prognostic Factors
- Depth of invasion (most important)
- Presence/absence of LN or distant organ metastases
- Histologic patterns
📝 Exam Questions
- What is FAP? → APC mutation; >100 adenomas; 100% cancer risk by midlife
- Predilection sites of colonic carcinoma? → Rectum & sigmoid colon
- Differences between right-sided and left-sided colon carcinoma?
🟤 Liver — Patterns of Hepatic Injury
Foundation for understanding all liver diseases
- Divided into lobules — plates of hepatocytes separated by sinusoids
- Hepatocyte plates radiate around central vein
- Peripheral portal tracts: connective tissue + hepatic artery + portal vein + bile duct + lymphatics
- Dual blood supply: portal vein (60–70%) + hepatic artery
Ballooning Degeneration
Marked cell enlargement; irregularly clumped cytoplasm; large clear spaces — serious damage
Steatosis (Fatty Change)
Fat droplets accumulate as clear vacuoles; micro- or macrovesicular
Feathery Degeneration
Retained biliary material → fine, foamy appearance in hepatocytes & bile ducts
Apoptosis
Acidophilic bodies (Councilman bodies): Shrunken, pyknotic, intensely eosinophilic hepatocytes with or without fragmented nucleus
Spotty
Spotty/Focal necrosis: Single or a few hepatocytes; with inflammatory infiltration; scattered in lobules
Piecemeal
Piecemeal/Interface necrosis: Hepatocyte necrosis at interface between periportal parenchyma & inflamed portal tracts
Bridging
Bridging necrosis: Contiguous necrosis spanning portal-to-portal, portal-to-central, or central-to-central — seen in moderate/severe chronic hepatitis → can progress to cirrhosis
Massive
Massive/Submassive necrosis: Large confluent areas → hepatic failure
📝 Exam Questions
- Types of degeneration in liver injury? → Ballooning, Steatosis, Feathery
- Patterns of necrosis in irreversible hepatic injury? → Spotty, Piecemeal, Bridging, Submassive/Massive
- Define "acidophilic body"? → Shrunken, pyknotic, eosinophilic apoptotic hepatocyte
🔵 Viral Hepatitis
Group of hepatotropic viruses: Hepatitis A, B, C, D, E
| Virus | Transmission | Chronicity | Special Features |
|---|
| HAV | Fecal-oral (water/food) | No chronic disease; rarely fulminant (0.1%) | Self-limited; no carrier state |
| HBV | Blood, birth (vertical) | Yes → cirrhosis, HCC | Ground-glass hepatocytes; carrier state; 5 outcomes |
| HCV | Blood | Yes — hallmark: persistent infection | Chronic hepatitis, cirrhosis, HCC; steatosis; lymphoid aggregates; bile duct injury |
| HDV | Blood (needs HBV) | Only with HBV co-infection | Defective virus |
| HEV | Fecal-oral | No (except immunocompromised) | High mortality in pregnant women (20%); epidemic; equatorial regions |
🧠 Summary Mnemonic
A & E = Acutely (fecal-oral) |
B = Blood & Birth |
C = Chronic, Cirrhosis |
D = Defective (needs B) |
E = Equatorial Epidemic, pregnant women (20% mortality) |
B & C → HCC
- Carrier state: Harbors & transmits organism; no symptoms; anti-viral antibodies present
- Asymptomatic infection: Elevated serum aminotransferases; antiviral antibodies
- Acute hepatitis: Incubation → preicteric phase → icteric phase → convalescence
- Chronic hepatitis: >6 months of disease
- Fulminant hepatitis: Massive liver necrosis → acute liver failure
5 Outcomes of HBV Infection
- Acute hepatitis → recovery + virus clearance
- Nonprogressive chronic hepatitis
- Progressive chronic disease → cirrhosis
- Fulminant hepatitis + massive liver necrosis
- Asymptomatic "healthy" carrier state
- Disruption of lobular architecture
- Inflammatory cells in sinusoids
- Apoptotic cells (acidophilic bodies)
- Ballooning degeneration of hepatocytes
- Mild portal mononuclear infiltration (minimal compared to chronic)
Defining Feature
Dense, prominent portal mononuclear infiltrates (vs minimal in acute hepatitis)
- Bridging necrosis and fibrosis
- Interface hepatitis (piecemeal necrosis)
- Ductular reactions (extensive in late-stage)
Chronic HCV — Specific Hallmarks
- Steatosis
- Lymphoid aggregates with germinal centers
- Bile duct injury
- Bridging fibrosis with dense mononuclear infiltration
HBV-Specific Finding
Ground-glass hepatocytes: Abundant finely granular pink cytoplasmic inclusions (HBsAg) on H&E — confirmed by immunostaining
Serologic Evidence of Chronic Hepatitis
- ↑ ALT, AST, bilirubin
- ↓ Albumin
- Prolonged prothrombin time (PT)
Gross
Shrunken, limp liver; wrinkled capsule; muddy red, mushy necrotic areas
Microscopy
- Massive necrosis
- Stromal collapse
- Bile duct hyperplasia
- Numerous Kupffer cells
Subacute Hepatic Necrosis
More protracted (weeks–months); both massive necrosis + regenerative hyperplasia
📝 Exam Questions
- Ground-glass hepatocytes = typical finding in? → Chronic HBV infection
- Histologic hallmarks of chronic HCV? → Steatosis, lymphoid aggregates, bile duct injury, bridging fibrosis
- Etiology & morphology of fulminant hepatitis? → HAV/HBV/HEV; massive necrosis, stromal collapse
- Histologic changes of acute viral hepatitis? → Ballooning, acidophilic bodies, lobular disruption
🟤 Liver Cirrhosis
Diffuse transformation of the entire liver — irreversible end-stage of many liver diseases
Definition
Diffuse transformation of the entire liver into regenerative parenchymal nodules surrounded by fibrous bands
Alcohol
Chronic alcoholism (micronodular)
Metabolic
NAFLD/MASLD, metabolic diseases
Biliary
Primary biliary cirrhosis, PSC
Inherited
Hereditary hemochromatosis, Wilson's
1
Bridging fibrous septa — delicate bands OR broad scars connecting portal tracts and central veins
2
Parenchymal nodules — various sizes; encircled by fibrotic bands; contain proliferating hepatocytes
3
Disruption of architecture of the entire liver (diffuse, not focal)
| Type | Nodule Size | Fibrous Bands | Common Cause |
|---|
| Micronodular | <3 mm; small, uniform, yellow nodules | Uniform and delicate | Alcoholic cirrhosis |
| Macronodular | >3 mm; large, irregular | Broad scars | Chronic viral hepatitis |
| Mixed | Both | Variable | Multiple causes |
- Hepatic cords: disorganized
- Hepatocytes: regeneration + degeneration (steatosis) + focal necrosis
- Abnormal central veins
- Fibrous bands contain: inflammatory cells + proliferating bile ducts (ductular reaction)
4 Major Consequences of Portal Hypertension
- Ascites — excess fluid in peritoneal cavity (increased transudation across peritoneal membrane)
- Portosystemic shunts — esophageal varices (life-threatening bleed), caput medusae, hemorrhoids
- Congestive splenomegaly
- (leads to hypersplenism)
Jaundice
Yellow skin/sclera — bilirubin retention & cholestasis
Hypoalbuminemia
Impaired synthesis → peripheral edema, ascites
Coagulopathy
↓ Coagulation factors → spontaneous bleeding, bruising
Hyperestrogenemia
↓ Estrogen clearance → spider angiomas, palmar erythema, gynecomastia, hypogonadism
Hyperammonemia
↓ Urea cycle → hepatic encephalopathy
Hepatorenal syndrome
Kidney failure due to circulatory dysfunction
📝 Exam Questions
- Define cirrhosis? → Diffuse transformation of entire liver into regenerative nodules surrounded by fibrous bands
- 3 main histologic characteristics? → Bridging septa + Parenchymal nodules + Disrupted architecture
- Main clinical features? → Portal hypertension + Hepatic failure
🔴 Primary Liver Carcinoma
HCC (hepatocytes), Intrahepatic Cholangiocarcinoma (bile ductulus), Mixed
Etiology / Risk Factors
- HBV and HCV — most common setting (chronic liver disease)
- Alcohol and Aflatoxins (from Aspergillus in moldy grains)
- Cirrhosis (regardless of cause)
- Hereditary hemochromatosis, metabolic syndrome, MASLD
- Gene mutations: β-catenin, TERT, TP53
- Male predominance 3:1–8:1
Small Liver Carcinoma (Definition — Exam Important!)
- Single nodule <3 cm OR ≤2 nodules with total diameter <3 cm
- Clean border; no hemorrhage/necrosis within nodule
- With or without cirrhosis
- Clinically asymptomatic but serum AFP may be positive
Advanced HCC — 3 Gross Patterns
- Unifocal massive tumor — single large mass
- Multifocal — widely distributed nodules of variable size
- Diffusely infiltrative — permeating entire liver
Greenish cast (contains bile); satellite nodules = intrahepatic spread or multicentric origin
Histologic Features of HCC
- Multiple growth patterns in same tumor:
- Trabecular (most common) — hepatocyte plates ≥3 cells thick
- Pseudoglandular — gland-like spaces
- Solid
- Sinusoidal vessels surrounding tumor cells — important diagnostic feature
- Scant stroma
- Frequent portal venule invasion
- Wide range of differentiation (well → poorly differentiated)
Clinical Features
- Ill-defined upper-abdominal pain, malaise, fatigue, weight loss, abdominal mass
- Jaundice, fever, GI/variceal bleeding (occasional)
- Elevated serum α-fetoprotein (AFP) in 50% of advanced HCC
- Treatment: surgery, ablation, liver transplantation, kinase inhibitors
- 5-year survival of large tumors: extremely low
Favorable Prognostic Factors
- Low stage, encapsulation, single lesion, tumor <5 cm
- Fibrolamellar variant, no cirrhosis, no vascular invasion
- Negative surgical margins, low serum AFP
- 5-year survival: 10% normally → up to 50% with resection (tumors ≤5 cm)
Spread & Metastasis
- Portal venous system involved in ~80% of HCC
- Initially intrahepatic spread
- Extrahepatic: lungs (most common), abdominal lymph nodes, bone
Etiology
- Liver flukes, chronic inflammatory bile duct disease (PSC)
- Hepatolithiasis (intrahepatic stones)
- Fibropolycystic liver disease
- HBV, HCV, MASLD
Key Features
- Occurs in non-cirrhotic liver (unlike HCC)
- Markedly desmoplastic → extremely firm and gritty tumor
- Resembles adenocarcinoma from other organs
- Tubular glandular structures in dense sclerotic stroma
- Difficult to distinguish from metastatic adenocarcinoma
- Areas with intermediate phenotype between HCC and cholangiocarcinoma
- "Collision tumor" — separate areas of each
- IHC: Hepar-1 identifies hepatocyte-origin (HCC); CK-19 identifies bile ductulus-origin (CCA)
📝 Exam Questions
- HCC originates from? → Hepatocytes
- Main etiology of HCC? → HBV, HCV, cirrhosis, alcohol, aflatoxins
- Histologic patterns of HCC? → Trabecular, pseudoglandular, solid
- 3 gross patterns? → Unifocal massive, multifocal, diffusely infiltrative
- Define small liver carcinoma? → Single nodule <3 cm OR ≤2 nodules <3 cm total; clinically asymptomatic
- Favorable prognostic factors? → Low stage, encapsulated, single <5 cm, no cirrhosis, no vascular invasion