Presentation on theme: "Liver and Biliary Tract-Tumors"— Presentation transcript:
1Liver and Biliary Tract-Tumors Inga Gurevich, MD, PhDMay, 2008
2Liver - Benign Tumors and Tumor Like Conditions Focal nodular hyperplasiaLiver cell adenomaHemangioma (most common benign lesion)Mesenchymal hamartoma
3Focal nodular hyperplasia (FNH) Common (#2 liver tumor after hemangioma)Mass lesion of young (median age 38 years); some studies show female predominanceRepresents 2-10% of pediatric hepatic tumorsMay be associated with oral contraceptives (66-95% of cases), hepatic cavernous hemangioma (20%), glycogen storage disease type Ia, portal hypertensionTumors associated with oral contraceptives often have hemorrhage, necrosis, infarctionUsually an incidental finding; present in 1% of autopsiesXray: mass with central scar, centrifugal hypervascularity by angiography; CT and MRI are important,Treatment: excellent prognosis; discontinue oral contraceptives, if applicable; surgery if symptomatic, complications, compression of adjacent organs or lesion progression
4Focal nodular hyperplasia Well-demarcated, subcapsular, light brown to yellow ; bulging nodule, 70-80% solitary, up to 5 -10cm; has central gray-white stellate scar (unless < 1 cm) from which fibrous septa radiate to periphery and create multiple smaller nodules; hemorrhage, necrosis, infarction, bile staining often seen; larger tumors may have multiple scars; adjacent liver is normal
5Focal nodular hyperplasia Micro: Most tumors (80%) have the 3 classic features of abnormal architecture, bile ductular proliferation and malformed vessels. Non-classic forms lack either abnormal architecture or malformed vessels, and are divided into three types - (a) telangiectatic, (b) mixed hyperplastic and adenomatous or (c) atypia of large cellPositive stains: alpha-1-antitrypsinNegative stains: p53, CD143 (angiotensin I-converting enzyme: reduced expressionDD: Osler-Weber-Rendu disease, Budd-Chiari syndrome or cirrhosis (adjacent liver is not normal), fibrolamellar hepatocellular carcinoma (marked atypia of hepatocytes), hepatocellular adenoma (encapsulated, monoclonal)
6Focal nodular hyperplasia (FNH) There is a central gray-white, depressed stellate scar with fibrous septaradiating to the periphery. The central scar contains large vessels withfibromuscular hyperplasia +intense lymphocytic infiltrates and bile ductproliferation + normal hepatocytes with regeneration.
7Liver Cell Adenoma95% women, usually child-bearing age (very rare in children), history of 5+ years of oral contraceptives in 85% ; also associated with anabolic steroids (in men), anti-estrogens, Klinefelter’s syndromeAlso associated with glycogen storage disease types Ia and III, Fanconi’s anemia, familial adenomatous polyposis, familial diabetes mellitus, Hurler’s disease or tyrosinemia;Spontaneous2-4% of hepatic tumors in childrenSubcapsular tumors may rupture, particularly during pregnancyBenign, but may contain hepatocellular carcinoma or cause severe hemorrhage10% or lower risk of hepatocellular carcinoma if not resectedMust sample generously to rule out coexisting hepatocellular carcinoma
8Liver Cell AdenomaGross: solitary pale, yellow-tan, frequently bile-stained nodules, often subcapsular, cm, sharply demarcated or encapsulated; usually right lobe; usually no fibrous septa or central scar; adjacent liver is non-cirrhotic
9Liver Cell AdenomaNormal liver tissue with a portal tract is seen on the left. The hepatic adenoma is on the right and is composed of cells that closely resemble normal hepatocytes, but the neoplastic liver tissue has disorganized (portal tracts are absent) hepatocyte cords and does not contain a normal lobular architecture.
10Liver Cell AdenomaMicro: sheets and cords 1-3 cells thick of normal appearing hepatocytes; no/rare mitotic figures; no portal tracts, no central veins ; intact reticulin framework; pseudoglands may be present; but no atypiaPositive stains: ER, PRNegative stains: p53DD: 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)
11Hemangioma Most common primary hepatic tumor Usually an incidental findingMore common in adults than children, 75% in women10% enlarge with follow-up, may be related to pregnancy or oral contraceptivesAssociated with multiple focal nodular hyperplasia syndromeGiant cavernous hemangiomas (> 4-10 cm) only rarely rupture
12HemangiomaGross: 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
13HemangiomaMicro: variably sized vascular spaces lined by flat endothelial cells and myxoid or fibrous stroma; large fibrous septa may trap bile ducts; variable thrombosis, calcification, increased fibrosis with age of lesion may obliterate lumen
14Mesenchymal Hamartoma Formerly called cavernous lymphangioadenomatoid tumor, cystic hamartoma, benign mesenchymoma75% are age 1 year or less (rarely adults), 60-70% male8% of pediatric liver tumorsUsually asymptomaticSerum AFP is usually normal or mildly elevatedRarely associated with undifferentiated sarcomaAdult cases are usually women with abdominal pain, more prominent fibrosis and a lesser myxoid component than childhood cases, usually no extramedullary hematopoiesisTreatment: excision, liver transplantation may be necessary
15Mesenchymal Hamartoma Gross: well circumscribed, solitary, 5-23 cm, 20% pedunculated, myxoid mass with fluid filled cysts; usually no necrosis, hemorrhage or calcification; interstitial deletion near 19q13.4
16Mesenchymal Hamartoma Micro: branching bile ducts without atypia in a loose, myxoid stroma with myofibroblast-like cellsdilated vessels and lymphatics;also normal appearing hepatocytes, thick walled veins, variable collagenbile ducts may have mesenchymal collars and are often cystically dilated
17Mesenchymal Hamartoma Positive stains: CK7, vimentin, smooth muscle actin, desmin, actinNegative stains: CK20Molecular: interstitial deletion near 19q13.4DD: bile duct adenoma (no hepatocyte islands) or cystadenoma (adults), bile duct hamartoma (usually multiple with fibrous background), infantile hemangioendothelioma (more vascular), embryonal sarcoma (marked cellularity and atypical cells)
19Hepatocellular carcinoma 85% of hepatic malignancies (30% in children); major cause of cancer death worldwide (20-40% in China, Japan, sub-Saharan African)Primary carcinomas are rare in North America, but more common in countries bordering Mediterranean Sea endemic for viral hepatitis; highest rates in Korea, Taiwan, southeast China, Mozambique;Higher rates in blacks vs. whites (4:1)Most are age 60+ years with cirrhosis or ages years without cirrhosis, occasionally are second tumors in Wilm’s tumor patientsRisk factors/causes: hepatitis B virus (HBV), cirrhosis (85% in West with HCC have cirrhosis, 3% with cirrhosis develop HCC annually), hepatitis C virus (HCV), alcohol abuse, aflatoxins, Thorotrast exposure, androgenic steroids, tyrosinemia
20Hepatocellular carcinoma Symptoms: abdominal pain, ascites, hepatomegaly, obstructive jaundice; also systemic manifestationsLaboratory: elevated serum AFP (70% sensitive), tumors arising in noncirrhotic liver (33%), tumors 2 cm or less (25%)Screening: recommended to use ultrasound and serum AFP in patients with chronic liver disease; leads to diagnosis of tumors 2 cm or lessOther causes of elevated serum AFP: yolk sac tumors of gonads, cirrhosis, massive liver necrosis, chronic hepatitis, normal pregnancy, fetal neural tube defects, hepatoblastoma5 year survival: 10% normally to 50% in tumors 5 cm or less with resection; death usually within 1 year from cachexia, GI bleed, liver failure, rupture of tumor (10%)Metastases: initially within liver, distant metastases late to lungs, bone, adrenal gland or porta hepatis lymph nodes
21Hepatocellular carcinoma Favorable prognosis factors: low stage, encapsulation, single lesion, tumor size < 5 cm, fibrolamellar variant, no cirrhosis (independent of fibrolamellar subtype), no vascular invasion, negative surgical marginsPoor prognostic factors: microscopic vascular invasion, high nuclear grade (grade 3 of 3)Factors that are not prognostic: age, gender, HBV statusClassification: small (< 2 cm) or advanced (2 cm or more)Treatment: resection, transplantation
22Hepatocellular carcinoma Gross: unifocal, multifocal or diffusely infiltrative soft tumor, paler 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; liver usually cirrhotic, often enlarged
23Hepatocellular carcinoma Micro patterns aretrabecular (most common) with 4+ cells surrounded by layer of flattened endothelial cellssolid (compact)pseudoglandular (acinar with proteinaceous material or bile in lumina, may resemble thyroid follicles)pelioid, giant cellsarcomatoidclear cell pattern
24Hepatocellular carcinoma Well differentiated: thin plates (1-3 hepatocytes thick), cells smaller than normal, abnormal reticulin network; minimal nuclear atypia, nuclear density 2x normal liver; commonly fatty change and pseudoglands; may resemble hepatocyte adenoma; common pattern for small hepatocellular carcinomaModerately differentiated: trabecular pattern with 4+ cells thick; larger tumor cells than well differentiated HCC with more eosinophilic cytoplasm, distinct nucleoli, pseudoglands, bile, tumor giant cells; most common pattern in advanced HCCPoorly differentiated: Large tumor cells with hyperchromatic nuclei in compact growth pattern with rare trabeculae or bile; prominent pleomorphism, may have spindle cell or small cell areas; may not appear to be hepatocellular
25Hepatocellular carcinoma Note that this hepatocellular carcinoma is composed of liver cords that are much wider than the normal liver plate that is two cells thick. There is no discernable normal lobular architecture, though vascular structures are present.
26Hepatocellular carcinoma A, hepatocellular carcinoma, pseudoalveolar patternB,cholangiocarcinoma
27Hepatocellular carcinoma Positive stains: HepPar1 (80-90%, cytoplasmic and granular), polyclonal CEA in canalicular pattern (50-90%, in better differentiated tumors), AFP (15-70%, not in small tumors), alpha-1-antitrypsin (55-93%), CEA-Gold 5 (76%), albumin mRNA ISH, CD10 (52%), transferrin, copper (7-41%), CAM 5.2 (CK 8/18), Fas, Fas ligandNote: polyclonal CEA in canalicular pattern is specific for hepatocellular carcinoma ; monoclonal CEA is usually negativeNegative stains: AE1-AE3, CK7 (80%), CK13, CK19 (>90%), CK20, keratin 903 (>90%), EMA, monoclonal CEA (present in 0-10%), CD15, mucin (mucicarmine), MOC31, BerEP4Recommended panel: p-CEA or CEA-Gold 5 or (less recommended) CD10, HepPar-1, mucicarmine or MOC31Molecular: 50-92% hyperploid or aneuploid
28Hepatocellular carcinoma DD: metastatic hepatoid adenocarcinoma from stomach or lung (CK19+, CK20+, CK7-, HepPar1 negative, no cirrhosis)neuroendocrine tumors from pancreas or small bowel (similar trabecular pattern but smaller cells, inconspicuous nucleoli, stippled chromatin, no cirrhosis)poorly differentiated metastatic adenocarcinoma or cholangiocarcinoma (desmoplastic stroma, mucin+)renal cell carcinoma (RCC+, HepPar1-, biopsy may be from renal mass)Melanoma, angiosarcoma, epithelioid angiomyolipoma (spindle cell component, thick walled vessels, HMB45+, actin+, CK-)adenoma or macroregenerative nodule (no trabecular growth pattern, different clinical history, minimal atypia
29Hepatocellular carcinoma Hepatocellular carcinoma. A, hematoxylin and eosin stained section.B, cytoplasmic staining with Hepatocyte (40).
30Hepatocellular carcinoma Hepatocellular carcinoma stained with pCEA.A, canalicular pattern of staining.B, canalicular-membranous pattern of immunoreactivity (40 ).
31Hepatocellular carcinoma Hepatocellular carcinoma, focal positive staining with ά-fetoprotein
32Hepatocellular carcinoma A, hepatocellular carcinoma, negative staining with MOC31B, cholangiocarcinoma, positive staining with MOC31
33Hepatocellular carcinoma A, hepatocellular carcinoma, negative staining with MOC31B,cholangiocarcinoma, positive staining with MOC31
34Hepatocellular carcinoma A, hepatocellular carcinoma, canalicular pattern of staining with polyclonal carcinoembryonic antigen (pCEA)B, cholangiocarcinoma, positive cytoplasmic staining with pCEAC, cholangiocarcinoma, difficult pattern of pCEA to interpret with focal pattern resembling canalicular stainingD, hepatocellular carcinoma, luminal pattern of staining with pCEA
35Hepatocellular carcinoma Cytology: highly cellular, polygonal tumor cells with abundant eosinophilic cytoplasm, central hyperchromatic nuclei or variable prominent nucleoli; increased nuclear to cytoplasmic ratio; often naked tumor cell nuclei;
36Clear cell variant of hepatocellular carcinoma Hepatocellular clear cell carcinoma.A, low-power view of tumor, capsule, and normal nontumor parenchyma.B, medium-power view, macrotrabeculae.C, high-power view, sheets of tumor cells.D and E, high-power views, macrotrabeculae, sinusoids.
37Fibrolamellar Variant of Hepatocellular Carcinoma Young adults years, but 30-40% in patients are less than 20 years old, no gender preference1-5% of all hepatocellular carcinomaNot associated with hepatitis B virus, cirrhosis or metabolic abnormalities; pathogenesis unknownBetter prognosis than classic HCC; 5 years survival is 60%Metastasizes to abdominal lymph nodes, peritoneum, lungXray: central scar (similar to focal nodular hyperplasia); often calcified (uncommon with FNH)Laboratory: serum alpha fetoprotein elevated in only 10% vs. 60% of classic HCCGross: 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
38Fibrolamellar Variant of Hepatocellular Carcinoma This neoplasm is composed of big pink cells that form trabeculae. These trabeculae are separated by fibrous stroma
39Fibrolamellar Variant of Hepatocellular Carcinoma Positive stains: fibrinogen (pale bodies), copper, copper-binding protein, bile, alpha-1-antitrypsin, polyclonal CEA, CAM 5.2 (CK 8/18), CK7Negative stains: mucin (if present, call combined hepatocellular carcinoma-cholangiocarcinoma), alpha fetoproteinDD: focal nodular hyperplasia (usually 5 cm or less, fibrous stroma contain bile ductules and inflammatory cells, no bile staining grossly, no hepatocyte atypia), sclerosing variant of hepatocellular carcinoma (no oncocytes, smaller tumor cells, pseudoglandular pattern common), cholangiocarcinoma, adenosquamous carcinoma with sclerosis, metastatic carcinoma with sclerotic stroma, neuroendocrine tumors
40HepatoblastomaMost common primary liver tumor in children (50% of liver malignancies in children)90% occur by age 5 years, 70% by age 2 years2/3 maleAssociated with hemihypertrophy (Beckwith-Wiedemann syndrome), Wilm’s tumor, glycogen storage disease, familial colonic polyposis); not associated with cirrhosisSymptoms: variable virilization due to hCG production by multinucleated giant cellsLaboratory: elevated serum AFP in 75%Metastases to regional lymph nodes, lung, brain, adrenal glands, bone marrowTreatment: preoperative chemotherapy and surgery; resect lung metastases; liver transplant if unresectableLong term survival now 60-70%Prognostic factors: stage, age, sex; increase mitotic activity may confer poorer prognosis; presence of osteoid may confer favorable prognosis
41HepatoblastomaGross: tan-green, 70% solitary, well circumscribed, variable hemorrhage and cysts; mean 10 cm (range 3-20 cm), often partially encapsulated; may be calcified in prominent mesenchymal component
42HepatoblastomaThis neoplasm is composed of a mixture of two cell types. Some neoplastic hepatocytes are arranged in irregular laminae (fetal) while others grow in a more embryonal pattern.
43HepatoblastomaEpithelial type (56%)Fetal pattern (31%): tumor cells in trabeculae 2-3 cells thick (resembling fetal liver), separated by sinusoids lined by CD34+ endothelial cells; tumor cells are same size or smaller than in non-neoplastic liver; distinct cell membranes, uniform, polyhedral, slightly higher nuclear/cytoplasmic ratio, inconspicuous nucleoli, may contain bile; minimal pleomorphism, no/rare mitotic figures;; no portal tracts, bile ducts or ductules; reduced reticulinEmbryonal pattern (19%): sheets, ribbons, rosettes, papillary patterns or trabeculae of variable thickness with immature appearance, discohesive small cells with poorly defined cell borders, basophilic cytoplasm, high N/C ratio, prominent nucleoli, coarse chromatin, increased mitotic figures; extramedullary hematopoiesis, necrosis and vascular lakes are common; no fat, glycogen or bileMacrotrabecular pattern (3%): frequent trabeculae > 10 cells thick throughout the tumor, variable cytologic featuresSmall cell undifferentiated pattern (3%): discohesive sheets of small uniform cells with minimal cytoplasm, indistinct cell borders, oval hyperchromatic nuclei, variable prominent nucleoli and increased mitotic figures; resembles small cell carcinoma at other sites; may have mucoid stroma, hyalinized septae; tumor cells are keratin+, bile-Mixed epithelial and mesenchymal type (44%)mixture of fetal/epithelial and mesenchymal cell types; teratoid (34%) or not (10%); mesenchymal component has spindle-oval cells with minimal cytoplasm, frequent osteoid, fibrous septa, myxoid zones, hemorrhage and necrosis; teratoid features are keratinized squamous epithelium, intestinal epithelial, skeletal muscle, mature bone and cartilage, melanin and neuroectodermal structures
44Epithelioid Hemangioendothelioma Malignant endothelium derived neoplasm with intermediate clinical course between hemangioma and angiosarcomaHepatic EH is considered a neoplasm of unpredictable malignant potential: the metastatic rate of hepatic EH was 27%, and 43% of the patients ultimately died of their disease.Mean age 47 years, but occurs at any age, 60% womenNo predisposing factorsFNA not recommended as even small biopsies can be misleading
45Epithelioid Hemangioendothelioma Most of the lobe is occupied by a ill-defined, mottled tumorous mass (arrowheads) corresponding to EH. Note a cavernous hemangioma (arrow).
46Epithelioid Hemangioendothelioma The tumor forms a relatively circumscribed mass with a prominent fibrous stoma with myxohyaline areas. In some areas, the tumor grows as strands and cords of cells. Here the tumor cells are rounded to slightly spindled. Some of the cells contain prominent intracytoplasmic vacuoles. In other areas the tumor cells line open channels filled with erythrocytes. Here the tumor cells are flat and lack tufting or pleomorphism.
47Epithelioid Hemangioendothelioma Positive stains: factor VIII related antigen and CD34 for vacuoles, CD31, trichrome and elastic stains accentuate obliteration of hepatic venules and hepatic vein branches, NSEEM: Weibel-Palade bodies, intermediate filamentsDD: signet ring adenocarcinoma, scirrhous cholangiocarcinoma, sclerotic hepatocellular carcinoma, sclerosed hemangioma (well circumscribed, no venous invasion, no atypia), leiomyosarcoma, chondrosarcoma, metastatic tumor from lung or elsewhere, angiosarcoma (different stroma, more atypia)
48AngiosarcomaRare (10-30 annual cases in US), but most common hepatic primary sarcoma in adults (2% of all primary liver tumors)75% men, usually age 50+ years; rare in childrenCauses: 25-42% associated with exposure to vinyl chloride, arsenic, Thorotrast (thorium dioxide) or androgen steroids; rarely associated with copper sulfate, estrogenic steroids, phenelzine, radiotherapy, chemotherapy, hereditary hemochromatosisPatients with exposure to vinyl chloride or Thorotrast may have synchronous cholangiocarcinoma or hepatocellular carcinomaMost patients die within 6 months from hepatic failure, intraabdominal bleeding; metastasizes widely, often to lung
49AngiosarcomaGross: multicentric, diffusely infiltrative, hemorrhagic and gray-white solid nodules with blood filled cavitiesMicro: tumor composed of infiltrative, freely anastomosing vascular channels; tumor cells grow along sinusoids adjacent to hepatic cords; frequent mitotic activity; also epithelioid cells with abundant cytoplasm and prominent nucleoliPositive stains: CD34, CD31, factor VIII related antigenDD: reactive disorders, hepatocellular carcinoma, Kaposi’s sarcoma , peliosis hepatis, epithelioid hemangioendothelioma
50AngiosarcomaFigure 1. FNA specimen showing spindle cells with fine cytoplasmic processes and vascular lumen (microacinar) formationFigure 2. FNA specimen showing focally prominent intracytoplasmic vacuoles Figure 3. FNA specimen demonstrating an intracytoplasmic lumen containing fragmented red blood cell by-products, which stained densely basophilic)Figure 4. Discohesive anastomosing vascular channels lined by plump malignant spindle cells.
51Undifferentiated Sarcoma Also called embryonal sarcoma, malignant mesenchymoma, mesenchymal sarcomaUsually ages 6-10 years, rare in adults, 10% of pediatric hepatic tumors (#3 after hepatoblastoma and hepatocellular carcinoma)Often aneuploidAppears to be a primitive mesenchymal neoplasm with possible foci of differentiated sarcomaPresents with abdominal mass, fever, pain, normal serum AFPMost patients die within 2 years due to direct extension; often metastasizes to lung, pleura, peritoneumTreatment: complete resection
52Undifferentiated sarcoma Gross: cm, solitary, well-demarcated, soft tumor with cystic, gelatinous, hemorrhagic and necrotic fociMicro: variably cellular tumor with anaplastic, spindled / oval cells with hyaline globules and ill-defined borders within pseudocapsule; nuclei have stippled chromatin, inconspicuous nucleoli; variably myxoid stroma with numerous thin-walled veins
54Bile Duct AdenomaIncidental finding, although often confused with adenocarcinomaUsually adults > 40 years old, no gender preferenceBenignGross: well-circumscribed but unencapsulated, firm, gray-white, tan, subcapsular nodulesMicro: simple tubular ducts with small or indistinct lumina; epithelium has abundant cytoplasm and pale nuclei compared to interlobular bile ducts in adjacent liver; variable fibrous stroma, granulomas, calcification, inflammatory cells; usually no cystic change, no cytoplasmic or intraluminal bile, no atypia, no mitotic figures, no angiolymphatic invasionPositive stains: mucin (intracytoplasmic), CEA, EMA, keratin, PAS highlights basement membraneDD: cholangiocarcioma, adenocarcinoma
55Biliary Cystadenoma 5% of all hepatic solitary cysts 95% occur in women, mean age 45 years84% are intrahepatic,Associated with polycystic liver disease, abnormal hepatobiliary anatomyUsually slow growing with good prognosis after surgical excision, although 25% have coexisting malignancyComplications: intracystic hemorrhage, bacterial infection, ruptureAlso associated with borderline or malignant lesionsLaboratory: elevated CA 19-9 (in cases with ovarian type stroma) and CEA in cyst fluid and serumXray: calcification in 20% (resemble echinococcal cyst)
56Biliary CystadenomaGross: encapsulated, solitary, mean 15 cm), usually mucinous, multilocular by definition); contains up to several liters of fluid; smooth inner surfaceMicro: mucinous - lined by single layer of columnar-cuboidal mucinous epithelium with basal nuclei and apical mucin; serous - lined by bland, flat to cuboidal cells with clear, glycogen-rich cytoplasm, no spindle cell stroma
57Biliary Cystadenocarcinoma <100 cases reportedUsually ages 50+ years; equal gender frequencyUsually mucinous, often associated with cystadenomaTumors more indolent in women with ovarian-like stroma, more aggressive in menMay have intraabdominal dissemination as terminal eventCysts represent dilated intrahepatic bile ducts invaded by tumor cellsSurvival: 50% at 4 years, better prognosis if spindle-cell stroma
58Biliary Cystadenocarcinoma Left hepatic lobe (lateral segment) is replaced by multiple cystic lesions (large arrows) and a solid lesion (arrow heads). The largest cyst is 4 cm in diameter. The cysts are mucinous. Intrahepatic biliary tree of the right lobe also shows significant dilatation (small arrows).
59Biliary Cystadenocarcinoma Micro: papillary or tubulopapillary neoplasm of malignant cells lining fibrovascular cores that project into cystic cavities malignant diagnosis is based on stromal invasion
60Cholangiocarcinoma (intrahepatic) Also called bile duct carcinoma10% of primary liver cancersHigh prevalence in southeast and eastern Asia10-20% are associated with cholangitis due to autosomal dominant polycystic disease, congenitally dilated hepatic ducts (Caroli’s disease), congenital hepatic fibrosis, infection by liver flukes, Thorotrast, anabolic steroids, intrahepatic lithiasis (5-10% of these patients), primary sclerosing cholangitis (7-42% of these patients)Diagnosis of exclusion (must rule out metastatic adenocarcinoma)Usually age 60+ years; no gender preferenceLaboratory: normal AFPPoor prognosis; death usually within 6 months50-75% metastasize to regional lymph nodes, lungs, vertebrae, adrenals, brain, elsewhere at autopsy
61Cholangiocarcinoma (intrahepatic) Gross: solitary, 7-10 cm, multinodular or diffuse small nodules < 1 cm; gray-white and firm; often hepatomegaly and satellite nodules; rarely cirrhosis; rarely bile stained; may invade portal vein
63Cholangiocarcinoma (intrahepatic) The carcinoma has a glandular appearance that is most consistent with cholangiocarcinoma. Cholangiocarcinomas do not make bile, but the cells do make mucin, and they can be almost impossible to distinguish from metastatic adenocarcinoma on biopsy or fine needle aspirate.
64Cholangiocarcinoma (intrahepatic) 54-year-old woman, history of common duct stricture. Adenocarcinoma (x200). Note marked nuclear crowding, nucleomegaly, anisonucleosis, hyperchromasia and prominent nucleoli.
65Cholangiocarcinoma (intrahepatic) Positive stains: mucin (almost always), CEA (cytoplasmic and luminal, not canalicular), keratin 903 (74%), CK7 (90-96%), CK19 (84%), CK20 (30-70%)Negative stains: AFPMolecular: Kras mutationsDD: metastatic adenocarcinoma from pancreas, extrahepatic biliary tree, breast, colon (CK7-/CK20+ [strong]) or gallbladder (must exclude based on clinical and radiographic findings); hepatocellular carcinoma with ductular differentiation, epithelioid hemangioendothelioma (vascular markers+, mucin-), benign bile duct proliferations (smaller, no atypia, incidental)
66Cholangiocarcinoma (intrahepatic) Immunostains demonstrate that the tumor cells are diffusely CK7 positive, partially CK20 positive; and PSA, as well as Heppar-1 negative in support of a pancreato-biliary origin. Mucin stain is focally positive.