SURGICAL PATHOLOGY SECTION C

The liver
Tumor-Like and Tumor Lesions of the Liver
1. Functional Anatomy of the Lobule and Gross Anatomy of Bile
Ducts
2. General Features of Liver and Biliary Lesions
3. Focal Nodular Hyperplasia (FNH)
4. Nodular Regenerative Hyperplasia (FRH)
5. Hepatic Adenoma
6. Hepatocellular Carcinoma
7. Hepatoblastoma
8. Extra-Hepatic Obstructions
9. Liver Abscess

FUNCTIONAL ANATOMY OF LOBULE

GENERAL FEATURES OF LIVER LESIONS

Patterns of hepatic injury
 When exposed to any injurious stimuli, the hepatocytes undergo
certain changes
 Irrespective of the cause 5 general responses are seen
 These changes may exist alone or in combination depending upon the
etiology
1.Degeneration and Intracellular accumulation
2.Necrosis and Apoptosis
3.Inflammation
4.Degeneration
5.Fibrosis

1. Degeneration and Intracellular accumulation

 The first change that takes place is the hydropic change
which is a reversible state

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SURGICAL PATHOLOGY SECTION C

2. Necrosis and Apoptosis

3. Inflammation
4. Degeneration
5. Fibrosis

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SURGICAL PATHOLOGY SECTION C

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Focal nodular hyperplasia

This can occur in any age group (3rd to 4th Decades)
and F>M (3:1 to 8:1)
Males (Related to Chronic Alcoholism)
Females (Related to Oral Contraceptives)
80% cases are asymptomatic.
Associated with other Pathological Findings:
(Particularly Vascular)
Hemangiomas
Telangiectasias of the Brain
Berry Aneurysm
Portal Vein Atresia
Astrocytoma and Meningiomas
Pathogenesis:
Exposure to Oral Contraceptives
Vascular Anomalies/Insults can cause
hyperplastic/regenerative response to localized
insults to liver parenchyma.

Nodular degenerative hyperplasia

This is a rare condition.
The Liver Parenchyma is transformed to
Regenerative, Non-Neoplastic Nodules.
This is not separated by Fibrous Septa.
Associated with other Clinical Findings:
Non-Cirrhotic Portal Hypertension
Autoimmune Diseases
Immunodeficiency
Hematologic Disorders
Drugs: Azathioprine, Didanosine, and Oxaliplatin.
Also with other Primary/Metastatic Tumors.
Pathology: Related to abnormalities of the portal
hepatic blood flow (Portal Venous Thrombosis)
localized areas of hypo and hyperperfusion.
Laboratory: Elevated Alkaline Phosphatase, GGT,
and Transaminases
Gross: It is nodular and resemble micronodular
cirrhosis.
Microscopic: Nodules of the hyperplastic
hepatocytes arranged in plates. The surrounding
Parenchymal Cells adjacent to the nodules
(centrilobular areas) compressed and atrophic.
Note: FIBROUS SEPTA/BRIDGING FIBROSIS IS
ABSENT.
Stain: Reticulin Stain
Gross Findings: Solitary Subscapsular gray-white,
solid mass and can be pedunculated. (Cut section)
there is a White Depressed Area of FIBROSIS
arranged in Stellate Configuration.
MRI Findings: Scar can be detected (Low Signal
Central Scar)
Microscopic:
Nodular appearance with Central Stellate Scar.
Patchy Ductular Reaction at the interface between
the fibrous septa and liver parenchyma.
Dysmorphic vesels
Poorly formed Fibrous Scar
Stain: (Used for distinguish from HCC)
Glutamine Synthase (GS) with Map like staining
pattern for FNH.
Reticulin Stain no loss of Staining for FNH

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Ductular Reaction: CK7, CK19, Neuronal Cell Highly correlated for MALIGNANT
Adhesion Molecule TRANSFORMATION
Males affected due use Androgen and Glycogenesis
Stain: (GS) and B-catenin expression
3. Inflammatory Telangiectatic Adenoma
- Most Common (40-50%)
4. Unclassified (<10%)
– Lacks molecular recognition and Rare
ER and PR Positivity (75% Cases)
Risk Malignant Transformation (5%) but M>F,
CTNNB1.
Can be confused with Well Differentiated
Carcinoma (GS, Heat Shock Protein 70/HSP70 stains
best to correct this)
Multiple tumors are seen mostly in HNF1 subtype.
(LIVER CELL ADENOMATOSIS)

Hepatocellular adenoma
True Adenomas in liver (RARE)
3rd-5th Decade of Life
F>M predilection (Due to OCP use, Anabolic-
Androgenic Steroid Therapy, & Carbamazepine
Therapy)
70% of the lesions are SOLITARY & usually on RIGHT
LOBE OF THE LIVER
Associated with Clinical Findings:
1. Glycogen Storage Diseases (Genetic)
2. Sex Hormone Disturbances in Children
Symptom: Symptomatic and cause Fatal
Intraperitoneal Hemorrhage.
Gross: Well demarcated but usually
unencapsulated, pale to yellow and CENTRAL SCAR
IS ABSEN

4 Major Groups based on Genotypic and Phenotypic

Characteristics:
1. Hepatocyte Nuclear Factor 1 alpha (HNF1) – 30-
50%
Associated with Steatosis, Insulin resistance
Stain: Liver Fatty Acid-Binding Protein (Negative)
2. CTNNB1 Mutations (10-15%)

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 SURGICAL PATHOLOGY
LIVER CELL CARCINOMA
(Hepatoma/Hepatocarcinoma)
 - 6th most common malignancy
 - 2nd most common cancer associated deaths
 - Highest incidence in areas with Hepatitis B & C
infections. (China)
 - Common in peak age 40-70 years.
 - M>F (2:1)
 Symptoms: Anorexia, Malaise, Abdominal Pains,
Ascites, and Liver Enlargement.
 Obstructive Signs: Due to Tumor Invasion in the
COMMON BILE DUCT.
 Serum Markers: AFP elevation (60%) and 40%
are normal if the tumor is small. (BUT THIS IS
NOT SPECIFIC TEST FOR HCC)
Associated and Predisposing Factors:
1. Hepatotropic Viruses (Hepatitis B & C)
- (Hepatitis B) 5-15X risk to develop HCC
- (Hepatitis C)15-20X risk to develop HCC
2. Alcoholic Liver Disease (15% risk)
3. NAFD (Develop HCC even without Cirrhosis)
4. Cirrhosis is present 80% Cases
5. Drugs: Thorium Dioxide Suspension
6. Aflatoxin B1 (Aspergillus flavus) – induces p53 mutations and
act synergistically to Hepatitis B
7. Oral Contraceptive - >5 years
Gross: Solitary Mass or Multiple Nodules, Can be or not
encapsulated.
Microscopic: Pattern can be Trabecular, Solid,
Pseudoglandular, and Multiple growth patterns (Acinar).
- Hepatic plates should be at least 3 cells thickness.
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SECTION C
Stains:
1. Reticulin Stains
2. Hep Par-1/Hepatocyte Specific Antibody (84% Sensitive)
Reacts with Urea Cycle (CPS-1)
3. Arginase-1 (96% Sensitive)
4. Glypican-3
5. Glutamine Synthase (GS) – enzyme role nitrogen metabolism
6. MOC-31 (Cholangiocarcinoma vs. HCC)
7. TTF-1
8. AFP (Insensitive Marker)
9. CD34 (Sinosodal Marker)
10. CK8/CK18 POSITIVE
11. CK7/CK20 NEGATIVE
Molecular Genetic Features: The direction is always toward to
CHRONIC HEPATOCYTE DAMAGE involvement that leads to
Cell Death and Regeneration (Leads to Genetic Instability and
Initiation of Carcinogenesis).
1. Wnt/Beta Catenin Pathways (Common)
2. TP53 Mutations (Aflatoxin & Hepatitis B)
3. ARID1 A and ARID2 genes (Hepatitis C) -> Chromatin
Remodeling.
4. Telomerase (TERT) Promotor Mutations
5. Methylation and Epigenetic Factors (p16 Suppression)
6. Proliferation Subclass (50%) – More aggressive behavior,
higher AFP, Moderate to Poor Differentiation of Cells.
7. Non-Proliferative Subclass – Resemble normal liver but
dominated by Wnt/Beta Catenin Pathway (Less Aggressive)
which better well differentiated cells with lower levels serum
AFP. (Hepatitis C and Alcoholic Liver Disease examples)
8. Grading System: EDMONDSON and STEINER 4 Tiered System
9. Portal Venous System: Involved 80% Cases (reach to the
Right Atrium Via Hepatic Vein and Inferior Vena Cava)
10. Extrahepatic Metastasis: Lungs, Abdominal Lymph Nodes,
and Bone
FACTORS AFFECTING PROGNOSIS
Stage : most important prognostic determinator
Size: ‘small’ tumors (from 2 to 5 cm in diameter – better
prognosis
Encapsulation
Number of tumors: single lesion – better survival
Portal vein involvement: adverse prognostic sign
Microscopic type: fibrolamellar – better prognosis
Microscopic features: vascular invasion, high nuclear
grade, and mitotic activity
Presence of cirrhosis: worsened prognosis
Serum AFP levels

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 SURGICAL PATHOLOGY
Viral antigenemia
Use of progestational hormones: better prognosis
Sex and age: Females –better survival
CMYC amplification: unfavorable prognosis
Heat shock protein
P-glycoprotein
DEFINITIONS OF TNM
Many pathologists use a three-tiered system of well
(G1), moderately (G2), and poorly (G3) differentiated HCC,
ranging from a very close resemblance to normal liver in G1
tumors to pleomorphic tumors that may not resemble liver at
all in G3 neoplasms.
Higher grade does appear to correlate with worse
prognosis; however, when assessing grade on a needle biopsy
or FNA specimen, it is important to remember that grade may
be heterogeneous within the same tumor, and thus a single
small sample may not be representative of the overall grade.
The TNM staging system is widely used by pathologists
but is limited as it does not take into account important
clinical factors
A number of independent adverse prognostic factors have
been reported, including presence of cirrhosis, poor
performance status, presence of multiple tumors, significantly
elevated preoperative serum AFP (typically 200 ng/mL or
greater), vascular invasion, poorly differentiated histologic
grade, and tumor size.
In many series, patients with tumors less than 2–3 cm have
a significantly better prognosis.Some authors, however, have
not found size to be an important prognostic determinator.
Although some studies have shown that chronic viral
infection had no effect on prognosis, others have shown that
HBV and HCV infection are associated with worse outcomes. In
most series, age and gender have not been found to correlate
with prognosis.
HEPATOBLASTOMA
- The MOST COMMON Primary PEDIATRIC LIVER TUMOR.
- Diagnosed with 1st – 3 years of life.
- Isolated cases are seen older children and adults may occur.
- POORER PROGNOSIS in YOUNGER CHILDREN.
Congenital Associated Disorders:
1. Beckwith-Wiedemann Syndrome
2. Trisomy 18
3. Familial Colonic Polyposis
- Ectopic Sex Hormones are released from tumor –
VIRILIZATION
- FETAL & EMBRYONAL TYPE: AFP is expressed.
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SECTION C
- UNDIFFERENTIATED & MESENCHYMAL TYPES: AFP is
negative.
- Nuclear INI1 Staining
INTRA & EXTRA-HEPATIC OBSTRUCTIONS
1. Hepatic Venous Outflow Obstruction: (Primary Hepatic)
- Can be called as BUDD-CHIARI SYNDROME.
- Characterized based on the location, cause and the nature of
occlusive lesion.
- According to severity and duration:
a. Acute HVOO – dilation and congestion of the sinusoids
usually located at CENTRILOBULAR AREA this may cause
atrophy of the hepatocytes.
b. Chronic HVOO – CENTRILOBULAR NECROSIS.
2. Sinosoidal Obstruction Syndrome – Also called as VENO
OCCLUSIVE DISEASE.
- There is a fibrous occlusion of the small branches of the
hepatic vein less than 1.0 mm in diameter.
- The lesion of obstruction may cause circulatory compromise
of the centrilobular hepatocytes, fibrosis, venular narrowing,
and obstruction of the liver blood flow.
- Usually caused by TOXIN-MEDIATED INJURY to the
sinusoidal endothelial cells. (Pyrrolizidine alkaloids), and
Chemotherapeutic Agents.
- Related to patients underwent Bone marrow, Liver and Kidney
Transplants.
LIVER ABSCESS
- Past mostly affected are the Young Adults and cases mostly
AMOEBIC and PYLEPHLEBITIS.
- Older patients (ENTERIC BACTERIA & DIVERTICULOSIS)
- HIV Immuno-compromised Patients (TB)
- Neonatal Hepatic Abscess – RARE but a sign of SEPSIS
(misplaced central umbilical catheters)
Location: Usually Right Sided Lobe, Solitary, and Close to the
Liver Dome.
Other Predisposing Factors:
1. Liver Transplants
2. Diabetes
3. Alcoholism
4. History of Malignancy
Immuno-compromised Host – greater tendency for
MULTICENTRICITY
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GROSS: The necrotic center is usually odorless, pasty, 3. - PAS- Diastase Staining (REVEAL THICKENING OF THE
chocolate brown fluid. BASEMENT MEMBRAINE)
Superinfection: by bacteria can extend to 4. COMPLICATION: Cholangiocarcinoma (DUE TO BILIARY
pleuropulmonary structures , subphrenic spaces, DYSPLASIA)
peritoneal cavity and pericardial sac (less common)
BILIARY TRACT Imaging Studies of a Patient with Primary
1. Primary Biliary Cirrhosis Sclerosing Cholangitis
Magnetic resonance cholangiography shows focal dilatation
2. Primary Sclerosing Cholangitis
in some bile ducts (bright, broad areas) and stricturing of
3. Cholestasis others (thinning or absence).
4. Intra-Hepatic Bile Duct Carcinoma Endoscopic retrograde cholangiography of the same patient
5. Cystic Fibrosis shows nearly identical features as in A. The endoscope is
6. Cholangiocarcinoma visible, giving a sense of scale.

PRIMARY BILIARY CIRRHOSIS (PBC) CHOLESTASIS

- This is an AUTOIMMINE DISEASE. 2 Types:
- Associated with OTHER AUTOIMMUNE DISEASES. 1. Features of Cholestatatic Liver Diseases (GENERAL)

- 10x F>M 2. Features of Cholestatatic Liver Diseases (INDIVIDUAL)

- Anti-mitochondrial Antibodies (AMAs) directed to
CHOLESTASIS – Marked reduction in the Bile Secretion and
(Multicomplex) E2/ M2 component of the Pyruvate
Bile Flow.
Dehydrogenase.

Clinical: Pruritus Functional secretory disturbance in HEPATIC PARENCHYMAL

Basic Lesion: Chronic, Nonsuppurative, destructive cholangitis CELLS
Complication: Cirrhosis b. Obstruction at the level of EXCRETORY PATHWAYS BILE
Microscopic: The Affected duct segments show Swelling and (PAPILLA OF VATER with CANALICULI)
Vacuolization, Nuclear Disarray, Infiltration of the lymphocytes Intrahepatic Cholestasis: Lesion is inside the liver parenchyma
and plasma cells. and intrahepatic bile ducts.
Difference between PBC vs. AIH: Extrahepatic Cholestasis: Lesion is outside the liver and
1. Plasma Cells in Portal Tracks: IgM affects the bile excretory system in the larger
- linked in Female, Serum Alkaline Phosphatase ducts/extrahepatic bile ducts.
2. Plasma Cells in the Autoimmune Hepatitis: IgG MIXED INTRA/EXTRAHEPATIC CHOLESTASIS:
- linked in More Alanine Aminotransferase 1. Neonatal Bile Duct Atresia
Gross: 2. Primary Sclerosing Cholangitis
Sagittal section demonstrates liver enlargement, nodularity
indicative of cirrhosis, and green discoloration due to COMPLETE CHOLESTASIS: Denotes a total arrest of Bile
cholestasis. Secretion with the retention of the following:
Primary biliary cirrhosis. A portal tract is markedly expanded 1. Bile Salts
by an infiltrate of lymphocytes and plasma cells surrounding a
2. Bilirubin
destructive granulomatous reaction centered on a bile duct
(the “florid duct lesion”)
INCOMPLETE CHOLESTASIS: Denotes a partial arrest of Bile
PRIMARY SCLEROSING CHOLANGITIS (PSC) Secretion with the retention of the following:
- This can cause Liver Cirrhosis 1. ONLY Bile Salts
- 1:100,000/year, F>M
(DUE TO DESTRUCTIVE DISEASES OF THE INTRAHEPATIC
DUCTS like PSC or PBC)
Associated with: Ischemic Injury (Arteriosclerosis of the Bile
Acute Cholestasis: This is Complete Cholestasis (DUE TO
Duct)
TOTAL FUNCTIONAL EXOCRINE SECRETORY FAILURE of the
Characterized: Inflammation, Stricture, Saccular Dilatation in
HEPATOCYTES)
the Biliary System.
- Drug Induced or Gallstone Obstruction
Microscopic:
Chronic Cholestasis: Cholestatic condition occurring weeks-
1. PORTAL TRACTS are primarily affected. Shows a pleomorphic
years. (Can be complete or incomplete type)
and fibro-obliterative cholangitis. “ONION-SKIN PERIDUCTAL
- Related Pancreatic Cancers
FIBROSIS.”
- Incomplete (PSC and PBC)
2. In chronic inflammation there is disappearance of the ducts
and replacement of FIBROUS SCAR
BILIRUBINOSTASIS: Relates with cholestasis

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CHOLATE STASIS: Accumulation of Bile Salts with HISTOLOGIC 

CHANGES. Poor prognostic factors:
- Due to membrane damaging effect of retained bile acids in • Lymphatic or intrahepatic metastases
the PERIPORTAL HEPATOCYTES. • Reduced keratin 903 expression may be a favorable
prognostic factor
Neonatal cholestasis
• Morphologic features Gross:
Lobular disarray
• Solitary, 7-10 cm,
Giant cell transformation of hepatocytes (unique
• multinodular or diffuse small nodules < 1 cm; gray-white and
feature)
firm;

• Often hepatomegaly and satellite nodules
Hepatocellular and canalicular cholestasis
Mononuclear infiltration of portal areas • No peripheral hyperemic zone seen in metastatic disease
Reactive changes in Kupffer cells • Rarely cirrhosis
Extramedullary hematopoiesis • Rarely bile stained, although may see bile
RISK FACTORS: CHOLANGIOCARCINOMA (EXTRAHEPATIC •
BILE DUCT) / BILE DUCT CARCINOMA • in periphery
Infection by liver flukes Clonorchis sinensis or Opisthorchis • May invade portal vein
viverrini
Primary sclerosing cholangitis Microcopic:
Hepatolithiasis • Mod to well diff adenoca with glandular and tubular
Fibropolycystic liver disease structures, mucin production and dense desmoplasia
Hepatitis B and C * • Epithelial cells are anaplastic, cuboidal to columnar with
non alcoholic fatty* eosinophilic cytoplasm and round central nuclei, tumor cells
NAFLD* are heterogeneous even within the same gland but resemble
bile duct cells, not hepatocytes
* Note: risk factors for CCA & HCC
CHOLANGIOCARCINOMA 
Klatskin tumor [American internist]: hilar tumor arising Positive stains:
at confluence of left and right hepatic ducts • Mucin (almost always)
Laboratory: Normal AFP, occasional hypercalcemia • CEA (cytoplasmic and luminal, not canalicular)
• CAM 5.2, AE1-AE3, keratin 903 (74%), CK7 (90-96%), CK19
CHOLANGIOCA (INTRAHEPATIC) (84%), CK20 (30-70%, more often positive in non-peripheral
Rarely associated with tumors), EMA, amylase, PTH-related peptide, p53 (10-94%),
neoplastic transformation of Von Meyenburg Negative stains: AFP
complexes Molecular: Kras mutations
Not associated with cirrhosis has a glandular appearance
Diagnosis of exclusion (must rule out metastatic - A liver CA may have both HCC & cholangiolar differentiation
adenocarcinoma) - DO NOT MAKE BILE, but the cells do make mucin, and they
Usually age 60+ years; no gender preference; but mean can be almost impossible to distinguish from mets Adenoca on
age 40 years in those with primary sclerosing cholangitis or biopsy or FNA.
chronic inflammatory bowel disease OTHER HEPATIC COMPLICATIONS IN
ORGAN TRANSPLANTATION
1. Preservation and Reperfusion Injury
2. Acute Allograft Rejection
3. Chronic Rejection
4. Graft vs. Host Disease

 PRESERVATION REPERFUSION INJURY

Poor prognosis PRI Associated POOR ALLOGRAFT OUTCOME:
Death w/in 6 mos; 5 yr survival in resectable cases is 30% 1. Hepatocellular ballooning
50-75% metastasize to regional lymph nodes, lungs, 2. Hepatocyte Dropout
vertebrae, adrenals, brain, elsewhere at autopsy 3. Associated with Bilirubinistasis
50% are metastatic to perihilar, peripancreatic and para-
aortic nodes

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ACUTE ALLOGRAFT REJECTION

Hepatic Allograft Rejection: this is an injury to the transplanted
liver cased by IMMUNOLOGIC REACTIONS of the HOST.
Types of Rejection:
1. Humoral Rejection (Hyperacute/Antibody Mediated)
- Rare
- Common in ABO Incompatible Donor
- C4d Immunostains help for the diagnosis

2. Acute Rejection (Cellular)

- Most common form
- Occurs usually at 1st - 3rd weeks after transplantation (7-
10days)
- CELL MEDIATED IMMUNE REACTION directed to Bile Duct
Epithelium and Endothelium of Portal and Centrilobular Veins.
CHRONIC REJECTION (DUCTOPENIC REJECTION)
Microscopic: Triad of portal infiltration, bile duct damage, and This is an immunologic injury to the allograft that is severe or
endotheliitis. (2 features may satisfy the diagnosis) persistent acute rejection that may lead to IRREVERSIBLE
Inflammation: Predominantly Lymphocytes DAMAGE of the bile ducts, arteries, and terminal hepatic veins.
(CENTRILOBULAR & PORTAL TRACTS AFFECTED)

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Clinical History: History of Acute Cellular rejection with

Progressive Cholestasis. Microscopic: Show an irregular profile, Epithelial Atypia,
Microscopic Features: Nuclear Pleomorphism, Cytoplasmic Vacoulation, Cell Necrosis,
Bile duct atrophy/pynknosis & Duct Destruction
Foam Cell Obliterative Arteriopathy
Bile Duct Loss >50% of the portal tracts
- Senescence related P21(WAF1/Cip1) protein increases with
damage and decreases during recovery.

GALL BLADDER
1. Cholelithiasis
2. Cholesterosis
3. Acute Cholecystitis
4. Chronic Cholecystitis
5. Carcinoma of the Gall Bladder

CHOLELITHIASIS
- This is one of the most common GIT Diseases worldwide
affecting F>M.

Formation and Risk of Gallstones are due to:

1. Body Weight

2. Childbearing

3. Estrogens

Other Conditions that Cholelithiasis are also involved:

1. Hemolysis

2. Crohn Disease

3. Congenital Anomalies in Biliary Tree

Gallstones (Stones) – formed based on the amount of

GRAFT VS. HOST DISEASE
Cholesterol.
- Bone Marrow Transplantation- causes Hepatic
a. Cholesterol (Mixed Type) (>80% Stones) – Cholesterol, Bile
Complications
Salts, & Phospholipids
Transplant Causing Injury are Associated to:
1. Pre-transplant conditioning regimens.
b. Pigment (Medical Condition Related DUE TO
2. Immunosuppression-Related Infections
HYPERBILIRUBINEMIA) – Calcium Bilirubinate, Phosphate, &
3. Graft vs. Host Disease (Depends on the timing of the
Carbonate
Transplant)
- 90 days post-transplant (Acute GVHD): Cholestasis and Bile Key for the Development Stones:
Duct Damage
(Cholesterol Crystal Aggregates & Mucin Proteins)
- <35 Days Post Transplant (Early) – Marked
1. Bile Supersaturation & Destabilization
Hepatocellular Apoptosis.
- Chronic GVHD Post Transplant - >3 months after 2. Gallbladder Hypomotility
transplantation.

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Other Types of Stones:

1. Brown Stone – Calcium Salts of Bilirubin and Palmitate.
2. Calcium Carbonate & Phospahate Stones
3. Brown-Green Stones – Associated with Infections (E-Coli
and Biliary Flukes)
Choledocholithiasis – can occur with or with out obstruction
but are secondary to Cholelithiasis.

Mirrizi Syndrome – Impacted cystic duct stone causes edema

and compression and obstruction of common hepatic duct.
Internal Biliary Fistulas – 90% occur at the area: (Due to the
Inflammatory Adhesions between Affected Billiary Tree and
Adjacent Organ)
1. DUODENUM & GALLBLADDER

2. GALLBLADDER & COLON

3. CYSTIC BILE DUCT & DUODENUM

MIRRIZI SYNDROME

ACUTE CHOLELITHIASIS
Clinical Symptoms: Pain in the RIGHT UPPER QUADRANT,
NAUSEA & VOMITING, FEVER.
Three Types of Acute Cholecystitis:
1. Calculous (90%) – due to chemical/ischemic and or due to
impacted stone in the cystic duct.

2. Acalculous (10%) – Serious medical condition such cardiac

Hydrops – Caused by impaction gallstone to cystic duct. surgery , TPN, Sepsis
Obstruction at Common Bile Duct or Ampulla – Can cause
severe colicky pain and Obstructive Jaundice. 3. Emphysematous (Acute gaseous Cholecystitis) – Common in
diabetics infecting gas-forming types.

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 SURGICAL PATHOLOGY SECTION C

GROSS:
1. Angry Red Color, Large and Distended, Hemorrhagic External
Surface.

2. Foci of gangrene perforation.

3. Edema and fibrin within the gallbladder wall (MUCOSAL

ULCERATION & FIBRINOINFLAMMATORY EXUDATE)

CHOLESTEROSIS
-Accumulation of LIPDS WITHIN THE MACROPHAGES IN THE
LAMINA PROPRIA.
GROSS: Linear Yellow Streaks in the MUSCOSAL RIDGES
(STRAWBERRY BLADDER)
Associated Findings:
1. Cholesterol Stones
2. Cholesterol Polyps

CHRONIC CHOLECYSTITIS
- May or may not suffered pain.
GROSS: Enlarged, Shrunken, of Normal Size and Adhesions are ADENOCARCINOMA OF THE GALLBLADDER
seen. STONE are present 95% cases. - This is the most common 80-95% of BILIARY CANCERS.
MICROSCOPIC: - Affects F>M(3-4:1) and occurs >50% in at age 50 years.
1. MONONUCLEAR INFILTRATION (Lymphocytes and Plasma Associated cases risk to develop this cancer:
Cells) 1. Cholescystoenteric Fistula
2. FIBROSIS 2. Porcelein Gallbladder Carcinoma
3. ROKITANSKY-ASCHOF SINUSES – lined by columnar or 3. Segmental Adenomyosis
cuboidal epithelium and may contain bile stones. 4. Gardner Syndrome
5. Anomalous connection Common Bile Duct and Pancreatic
Duct

CLINICAL SIGN: Elevated Alkaline Phosphatase

GROSS: Diffuse (70%) growing or nodular, polypoid, or
papillary mass (30%). Some are not so apparent in gross
specimens and MICROSCOPIC EXAMINATION IS IMPORTANT.

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 SURGICAL PATHOLOGY SECTION C

LOCATION:
1. Fundus (70-80%)
2. Body (1/3 or 10%)
3. Neck (10%)

Calculi: Stones may be present (80-90%)

WITH MARKED FIBROSIS OF THE WALL (PREEXISTING
CHRONIC CHOLECYSTITIS).
MICROSCOPIC:
1. ADENOCARCINOMA (90%) – PANCREATOBILIARY TYPE
2. MICROPAPILLARY TYPE – Aggressive Behavior.
3. ADENOSQUAMOUS TYPE (Squamous component should be
25-99%)
4. PURE SQUAMMOUS CARCINOMA
5. MUCINOUS ADENOCARCINOMA – 50% Extracellular Mucin
6. SIGNET RING CELLS (Advanced Presentation)
7. CLEAR CELL VARIANT

Molecular Aberration:
1. KRAS mutation (60%)
2. TP53 Mutation (50%) – High Grade Tumor Types
3. Loss of Histidine (EARLY SIGNS)

SPREAD & METASTASIS: (ALL HALF THE PATIENTS ALREADY

HAVE THIS AT THE TIME SURGEY)
1. LIVER INVASION DIRECTLY (COMMON)
2. STOMACH & DUODENUM INVASION
3. OVARIAN METASTASIS with STIMULATION OF PRIMARY
OVARIAN IS RISK

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I am the master of my faith: I am the captain of my soul