liver pathgology.pptx

liver pathology

1. LIVER PATHOLOGY Moderator : Dr. Susmitha . S

2. Contents Introdution Normal anatomy & Histology Biopsy Viral hepatitis Steatosis and steatohepatitis Cirrhosis Vascular disorders Pigmentary disorders Drug/ toxin mediated injury Benign Epithelial tumors Malignant Epithelial tumors Mesenchymal tumors Metastatic tumors

3. LIVER Largest internal organ 1.4–1.6 kg (3.1–3.5 lb) R eddish brown soft organ with four lobes of unequal size and shape

4. Histologically units LOBULES Center of the lobule - CV Periphery of the lobule - PT Functionally, Divided into : 3 ZONES, based upon oxygen supply Zone 1- Encircles the PT where the oxygenated blood from hepatic arteries enters. Zone 3 is located around CV, where oxygenation is poor. Zone 2 is located in between. LIVER HISTOLOGY CV PT

5. Liver Biopsy Liver histopathology remains a mainstay in the diagnostic work-up of most liver diseases Biopsy remains the gold standard for the diagnosis of cellular rejection Adequacy of biopsy, Site of biopsy (is it from liver?), Architecture on low power; Assess inflammation (degree, type), Necrosis, fibrosis, tumor cells

6. Pattern Recognition Acute Hepatitis Chronic hepatitis Fatty liver disease Biliary Pathology Vascular Pathology Metabolic liver disease Architecture and fibrosis

7. STE A T OSIS

8. This liver is slightly enlarged Tense capsule P ale yellow seen both on external and cut surface FATTY CHANGE: GROSS

9. Initial microvesicular Macrovesicular droplets Fat cysts - coalescence and rupture Less often - lipogranulomas (Lymphocytes, macrophages and multinucleate giant Cells) FATTY CHANGE: MICRO

10. VIRAL HEPATITIS

11. Microscopy : Ballooning degeneration Spotty necrosis Predominantly sinusoidal and lobular mononuclear cell infiltrate (occasional neutrophils and eosinophils ) Kupffer cell hyperplasia Scattered apoptotic bodies Canalicular cholestasis Hepatocellular regeneration

12. Microscopy of CVH Predominantly portal tract inflammation Interface hepatitis Lobular acidophil bodies Mononuclear inflammatory cells, +/-plasma cells Portal-based lymphoid aggregates and lymphoid follicle formation Bile ductular proliferation Progressive fibrosis with eventual cirrhosis

13. VIRAL HEPATITIS: TRICHROME This trichrome stain demonstrates the collapse of the liver parenchyma with viral hepatitis. The blue-staining areas are the connective tissue of many portal tracts that have collapsed together.

14. Hepatitis A - mononuclear infiltrate rich in plasma cells Hepatitis B - “ground-glass” hepatocytes - cells with endoplasmic reticulum swollen by HBsAg Hepatitis C - shows lymphoid aggregates or fully formed lymphoid follicles

15. ALCOHOLIC HEPATITIS - Mallory's hyaline, neutrophils, necrosis of hepatocytes, collagen deposition, and fatty change

16. MALLORY'S HYALINE Rope like red hyaline material within hepatocytes also known as "alcoholic " hyaline , Mallory- Denk Bodies - chronic alcoholism aggregates of intermediate filaments in the cytoplasm resulting from hepatocyte injury.

17. CIRRHOSIS

18. CIRRHOSIS Diffuse nodulation of liver due to fibrous bands subdividing liver into regenerative nodules Nodules : > 3 mm - macronodular < less than 3 mm - Micronodular

19. M I CRONODULAR CIRRHOSIS The regenerative nodules - quite small, averaging < 3 mm in size CAUSES : Chronic Alcoholism – Most Common Wilson's disease Primary biliary cirrhosis Hemochromatosis.

20. MACRONODUL A R CIRRHOSIS CAUSES: Viral hepatitis (B or C) - most common cause Wilson's disease Alpha-1-antitrypsin deficiency

21. CIRRHOSIS: micro Regenerative nodules of hepatocytes are surrounded by fibrous connective tissue that bridges between portal tracts. Within this collagenous tissue are scattered lymphocytes as well as a proliferation of bile ducts.

22. PRIMARY BILIARY CIRRHOSIS A rare autoimmune disease (mostly of middle-aged women ) C haracterized by destruction of bile ductules within the triads of the liver. I ntense chronic inflammatory infiltrate L oss of bile ductules. Micronodular cirrhosis

23. PIGMENTARY DISORDERS OF THE LIVER

24. HEMOSIDEROSIS Hemosiderosis - accumulation of iron. The hepatocytes and Kupffer cells here are full of granular brown deposits of hemosiderin from accumulation of excess iron in the liver. H emochromatosis - used when organ dysfunction occurs. The iron accumulation may lead to a micronodular cirrhosis - " pigment" cirrhosis).

25. Iron stain highlights the periportal predominance of iron deposition seen in hemochromatosis . There are larger dark blue granules in the hepatocytes closer to the portal tracts.

26. HEREDITARY HEMOCHROMATOSIS (HHC): GROSS Dark brown - liver, the pancreas and lymph nodes -due to extensive iron deposition HHC results from a mutation involving the hemochromatosis gene (HFE) that leads to increased iron absorption from the gut .

27. LIPOFUSCIN PIGMENT -Pale golden brown finely granular pigment in nearly all hepatocytes is lipochrome (lipofuscin). -This is a "wear and tear" pigment from the accumulation of autophagolysosomes over time. - This pigment is of no real pathologic importance

28. CHOLESTASIS: MICRO accumulations of pigment - bile often this is due to extrahepatic biliary tract obstruction Bile may also accumulate in liver (called cholestasis) when there is hepatocyte injury.

29. INTRAHEPATIC LITHIASIS Small stone in an intrahepatic bile duct Produce a localized cholestasis, but the serum bilirubin is NOT increased, because there is plenty of non-obstructed liver to clear the bilirubin from the blood Serum Alkaline Phos is increased with biliary tract obstruction at any level

30. VASCULAR DISORDERS

31. CHRONIC PASSIVE CONGESTION "nutmeg" liver - chronic passive congestion of the liver. the dark red congested regions that represent accumulation of RBC's in centrilobular regions . This is usually due to a "RIGHT SIDED" heart failure.

32. CENTRILOBULAR NECROSIS If the passive congestion is pronounced, then there can be centrilobular necrosis, because the oxygenation in zone 3 of the hepatic lobule is decreased . The light brown pigment in the necrotic hepatocytes around the central vein is lipochrome.

33. CPC - CARDIAC CIRRHOSIS " cardiac cirrhosis " - fibrosis bridging between central zonal regions , T he portal tracts appear to be in the center of the reorganized lobule. U nlike a true cirrhosis, there is minimal nodular regeneration.

34. INFARCTION OF THE LIVER Infarcts are uncommon because the liver has two blood supplies-portal venous system and hepatic arterial system . The infarcts seen here are yellow, with geographic borders and surrounding hyperemia . About half of liver infarcts occur with arteritis, and the remaining half are due to a variety of causes.

35. ACETAMINOPHEN OVERDOSE There is extensive hepatocyte necrosis This pattern can be seen with a variety of hepatotoxins .

36. POLYCYSTIC KIDNEY DISEASE (P C KD) - POLYCYSTIC LIVER M anifest with renal failure beginning in middle age Sometimes the liver can be affected as well by polycystic change . Less commonly the pancreas is involved . These patients with DPKD can also have berry aneurysms in the cerebral arteries.

37. EXTRAHEPATIC BILIARY ATRESIA I nflammation with stricture of hepatic or common bile ducts. This leads to marked cholestasis with intrahepatic bile duct proliferation, fibrosis, and cirrhosis . Th e liver i s rock hard . The dark green color comes from formalin acting on bile pigments in the liver from marked cholestasis, turning bilrubin to biliverdin.

38. EXTRAHEPATIC BILIARY ATRESIA Micro scopy : N umerous brown-green bile plugs, B ile duct proliferation E xtensive fibrosis.

39. α-1-ANTITRYPSIN DEFICIENCY AAT deficiency - chronic obstructive pulmonary disease with panlobular emphysema. The periportal red hyaline globules seen with periodic acid-Schiff (PAS ) stain The globules are collections of alpha-1-antitrypsin not being excreted from hepatocytes . This may eventually lead to chronic hepatitis and cirrhosis .

40. TUMORS OF THE LIVER & INTRAHEPATIC DUCTS

41. BENIGN EPITHELIAL TUMORS

42. FOCAL NODULAR HYPERPLASIA (FNH) Benign nonneoplastic hepatic lesion, Arising in a noncirrhotic liver parenchyma Most common in young adults May represent hyperplastic response to arterial malformation or other vascular anomaly

43. Gross : Well demarcated, Unencapsulated Solitary lesion Lighter in color than the surrounding liver parenchyma Subcapsular region Measure < 5 cm Cut surface : Central scar Radiating fibrous septa

44. Micro : Bland hepatocytes Surrounded by fibrous septa Artery branches Bile ductular reaction Variable amount of mixed inflammatory infiltrate Portal tracts are absent except at periphery

45. Hepatocytes - similar to those in the surrounding liver 1 - 2 cells thick Supported by an intact reticulin framework

46. FNH Positive stains: alpha-1-antitrypsin Negative stains: p53, CD143 (angiotensin I-converting enzyme: reduced expression DD: Budd-Chiari syndrome or cirrhosis (adjacent liver is not normal) Fibrolamellar hepatocellular carcinoma (marked atypia of hepatocytes) Hepatocellular adenoma (encapsulated, monoclonal) Peritumoral hyperplasia Mesenchymal hamartoma

47. GROSS: LIVER CELL ADE N OMA Solitary ( 70 % ), pale, yellow-tan bile-stained nodules , Often subcapsular, 10-30 cm , S harply demarcated Usually right lobe , Adjacent liver is noncirrhotic

48. LIVER CELL ADE N OMA: MICRO Sheets and cords 1-3 cells thick of normal appearing hepatocytes with variable glycogen P rominent “free floating” arterial vessels and draining veins throughout the tumor Intact reticulin framework No/rare mitotic figures No portal tracts, no central veins or connection with biliary system

49. LIVER CELL ADENOMA Positive stains: ER, PR Negative stains: p53 DD: HEPATOCELLULAR CARCINOMA (mitotic activity, atypia, trabecular growth, cell plates > 2 cells thick, vascular invasion, infiltrative, often different clinical features) FOCAL NODULAR HYPERPLASIA (central stellate scar and radiating fibrous septa)

50. BILE DUCT ADENOMA (Cholangioma ) 30% - incidental finding GROSS : Small, well-circumscribed but unencapsulated , firm , gray-white / tan , subcapsular nodule; 85 % solitary ; usually 5 mm or less

51. BDA: MICRO: Small tubules set in a fibrous stroma with lymphocytes Single layer of cuboidal cells ; possible mucin secretion ; no bile in the lumen Normal portal tracts often included

52. Biliary Hamartoma Within cirrhotic livers, most commonly seen chronic hepatitis C and alcohol-related liver disease single or multiple M icro : composed of bile duct structures that grow in an irregular inter-anastomosing fashion. duct structures have open lumens, associated with either a myxoid or fibrotic stroma

53. Intraductal papillary neoplasm of the bile ducts GROSS : Inner surface of ducts has velvety friable papillary growths / excrescences with masses filling dilated major bile ducts Masses are soft, friable, white-red-tan

54. Micro : M ultiple papillary tumors composed of fibrovascular cores L ined by columnar, pseudostratified, biliary-type cells with numerous cytoplasmic mucin vacuoles Ovarian stroma is absent Varying cytologic atypia and mitotic activity May have associated tubular adenocarcinoma with invasion

55. Differential diagnosis Mucinous cystic neoplasm Also a cystic hepatic lesion Lined by biliary type epithelium Has ovarian type stroma and Does not communicate with biliary lumen Cholangiocarcinoma May show areas of cystic degeneration Does not communicate with biliary lumen Simple cyst, simple hepatic cyst, Simple biliary cyst, bile duct cyst Lacks papillary projections

56. MALIGNANT TUMOR S

57. Hepatocellular Carcinoma GROSS Unifocal , multifocal or diffusely infiltrative soft tumor , P aler than normal tissue, may be green due to bile Extensive intrahepatic metastases are common Snakelike masses of tumor may involve the portal vein (35-80%), hepatic vein (20%) or inferior vena cava Hemorrhage and necrosis are common Occasionally tumor is pedunculated Liver usually cirrhotic, often enlarged

58. HEPATOCELLULAR CARCINOMA

59. HCC: MICRO Patterns: Trabecular (most common ) - 4+ cells surrounded by layer of flattened endothelial cells Pseudoglandular (acinar with proteinaceous material or bile in lumina) Solid and macrotrabecular Cells Polygonal with distinct cell membranes Higher N/C ratio Abundant granular eosinophilic cytoplasm Round nuclei with coarse chromatin and thickened nuclear membrane Prominent nucleoli

60. Sinusoidal vessels surrounding tumor cells is important diagnostic feature Scanty stroma , from well differentiated to bizarre (often within same tumor )

61. HEPATOCELLULAR CARCINOMA

62. Differential diagnosis Hepatocellular adenoma : Neoplastic hepatocytes are not expanded on  reticulin  stain (no loss) Noncirrhotic background Intrahepatic cholangiocarcinoma : Discrete gland formation surrounded by desmoplastic stroma Negative for hepatocellular markers; positive for  CK7 Dysplastic nodule in cirrhosis : ~ 1 cm lesion Preserved portal tracts Metastatic neuroendocrine neoplasms : Positive staining for neuroendocrine markers while negative for hepatocellular markers Metastatic carcinomas Possible clinical history of prior malignancy Differing immunohistochemical profile

63. CLEAR CELL VARIANT - HCC Predominant appearance in 5-16% of cases, but some clear cells present in 20-40% of cases Tumor cells have prominent clear cytoplasm due to cytoplasmic fat or glycogen May need to hunt for typical HCC to rule out metastatic tumor Similar prognosis to classic tumor

64. FIBROLAMELLAR VARIANT- HCC GROSS : Single ( 75 %) Large (mean 13 cm) Hard Scirrhous Well-circumscribed Bulging White-brown tumor with fibrous bands throughout and central stellate scar Most cases involve left lobe, but may involve both lobes Variable bile staining, hemorrhage and necrosis

65. FIBROLAMELLAR VARIANT - HCC Micro: Nests , sheets or cords of well differentiated oncocytic cells in B ackground of dense, acellular collagen bundles T hat may contain small, thick-walled vessels Fibrotic tissue coalesces into central scar

66. Differential diagnosis Cholangiocarcinoma : Truly glandular, often conspicuous pleomorphism Focal nodular hyperplasia : Ductular reaction around central scar Lesional cells are not characteristically oncocytic Does not have the nuclear features of fibrolamellar carcinoma Hepatocellular carcinoma, sclerosing variant : No oncocytes , smaller tumor cells, pseudoglandular pattern common Metastatic carcinoma  with sclerotic stroma : Conspicuous pleomorphism Neuroendocrine tumors : Nuclear features are often not typical of fibrolamellar carcinoma Positive for neuroendocrine marker

67. ONCOCYTIC VARIANT -HCC Oncocytes are present in fibrolamellar variant and O ccasionally in classic hepatocellular carcinoma Rarely these cells predominate without fibrous stroma of fibrolamellar variant Cytoplasm is intensely eosinophilic with coarse granules

68. PLEOMORPHIC (GIANT CELL) VARIANT <1% of all hepatocellular carcinomas , A lthough 15% have some tumor giant cells Multinucleated tumor giant cells predominate , marked loss of cell cohesion

69. SARCOMATOID VARIANT - HCC 1-9 % of all HCC have prominent sarcomatoid pattern Diffuse collection of spindle cells resembling fibrosarcoma Classic HCC is also present; May have pleomorphic and osteoclast -like giant cells

70. Differential diagnosis Undifferentiated pleomorphic sarcoma  and  fibrosarcoma No area of classic HCC Immunohistochemistry (entirely negative for  pancytokeratin ) 2. Metastatic sarcomatoid carcinoma : Will not have area of classic HCC Usually multiple nodules Immunohistochemistry ( pancytokeratin +) Negative for hepatocellular markers,

71. SCLEROSING: HCC Micro: Fibrous septa separate trabecular cell plates but no lamellar fibrosis Cell plates 3 or more cells thick Tumor cells may have pseudoglandular (acinar) features compared to fibrolamellar variant Tumor cells are smaller Lack vesicular nuclei and prominent nucleoli Have less abundant and granular cytoplasm No apparent endothelial sinusoidal cells

72. CHOLANGIOCA RCINOMA Gross: Large, nonencapsulated , well demarcated, Firm, white-tan to gray Nodular intrahepatic mass More frequent in the right lobe of the liver Satellite nodules in 30% Noncirrhotic background liver in most cases

73. Grossly - 3 growth patterns Mass forming: hepatic parenchymal solid mass Periductal infiltrating: infiltrates along the portal tracts, causing bile duct strictures Intraductal growth: papillary or polypoid growth inside a dilated bile duct

74. Micro: Moderate to well differentiated adeno ca G landular and tubular structures , M ucin production and dense desmoplasia Epithelial cells are anaplastic, cuboidal to columnar with eosinophilic cytoplasm and round central nuclei , T umor cells are heterogeneous even within the same gland but resemble bile duct cells, not hepatocytes Multicentricity and perineural invasion are common

75. HEPATOBLASTOMA Malignant primary hepatic blastomatous tumor Most frequent liver tumor in children 1 - 1.5 cases per million 80 - 90% between 5 months to 6 years old Slight male predominance

76. Gross : Single or multinodular Well defined boundaries Tan-brown cut surface Undifferentiated subtypes have a variegated appearance Necrosis and hemorrhage are present in posttreatment specimens Osteoid may be present- firm and gritty

77. Fetal pattern Small to medium sized cells Thin trabeculae or nests Resembling hepatocytes of fetal liver Clear or finely granular cytoplasm Small round nucleus with indistinct nucleolus Foci of extramedullary hematopoiesis are usually present Low mitotic activity, Referred to as well differentiated hepatoblastoma

78. Embryonal pattern Resembles liver at 6 - 8 weeks of gestation Solid nests or glandular / acinar morphology Papillae and pseudorosettes Dark and granular cytoplasm without glycogen or lipids Enlarged nuclei with coarse chromatin, Resembling blastemal cells Extramedullary hematopoiesis - absent Increased mitotic activity

79. Small cell undifferentiated pattern Small, round blue tumor Solid sheets of discohesive small cells Abundant mitoses, apoptosis and necrosis

80. Cholangioblastic pattern Small ducts within or around hepatocellular component s Mesenchymal pattern Mature and immature fibrous tissue Osteoid or osteoid -like tissue Hyaline cartilage Small subset may exhibit teratoid features: endodermal , neuroectodermal (neuronal cells, glial tissue, melanin producing cells) and complex tissue (striated muscle)

81. MESENCHYMAL TUMORS

82. HEMANGIOMA: GROSS Gross: solitary (70-90%), usually 2-4 cm, although tumors up to 20 cm are overrepresented in studies of excisions Soft, red-purple, well circumscribed Subcapsular or deep Collapse when sectioned as blood oozes out

83. HEMANGIOMA: MICRO Micro: Variably sized vascular spaces L ined by flat endothelial cells and F ibrous stroma

84. Epithelioid hemangioendothelioma Low grade Malignant endothelial neoplasm  GROSS : Poorly circumscribed, firm, white-tan mass Variable size, up to 18 cm

85. MICROSCOPY Cords, strands or small nests of large endothelial cells with abundant eosinophilic cytoplasm Embedded in a myxohyaline stroma Tumor cells have vesicular, round to oval, sometimes indented nuclei Intracytoplasmic , round, clear vacuoles representing small vascular lumina , May contain erythrocytes

86. Peliosis Hepatis P e l i o s i s h e p atis r e p r e s e n ts b l oo d - f i ll ed c y s ts i n t h e h e p atic pa r e n c h y m a c e r ta i n dr u g s , pa r t i c u l a r l y a n a b o l i c s t e r o i ds, h i gh - d o s e or al c o n t r a c e p t i v e , or azathioprine in patients with solid organ t r a n s p l a n ts , T B , I MM U N O C O M P R O M ISE D M o s t c a s es o f p e l i o s i s a r e det e c t e d incidentally, b u t r u p t u r e , i n t r a p e r i t o n eal h e m o r r h ag e , a n d death h a v e b ee n r e p o r ted. P e l i o s i s m a y r eg r e s s o n s to p p i n g h or m o n e o r dr u g c a u s i n g t h e l e s i o n . M/E blood-filled cystic spaces, separated by c o r d s o f n or m a l o r c o m p r e s s e d h e p atoc y t e s , d i s t r i b u te d r a n d o m ly i n l i v e r pa r e n c h y m a

87. METASTASES TO THE LIVER Numerous mass lesions that are of variable size Larger ones demonstrate central necrosis

88. METASTATIC CARCINOMA Microscopically, metastatic infiltrating ductal carcinoma from breast is seen on the right, with normal liver parenchyma on the left.

89. REFERNCES : Mills SE , Carter D ,Sternberg diagnostic pathology , 4 th edition , Lipincott Williams and wilkins . Rosai J,Rosai and Ackerman surgical pathology, 9 th edition Differential diagnosis in surgicalpathology ,3 rd edition Robbins and cotran , Pathologic basis of disease. Internet sources

90. THANK YOU