Liver and intrahepatic bile duct - tumor
Last revised 9 April 2008
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Benign tumors/conditions: angiomyolipoma, benign cystic mesothelioma, bile duct adenoma, biliary adenofibroma, biliary cystadenoma, biliary cyst, biliary papillomatosis, extramedullary hematopoiesis, fatty change, focal nodular hyperplasia, glomangioma, hemangioma, hemangiomatosis, hepatic vascular malformation with capillary proliferation, hepatocellular adenoma, hereditary hemorrhagic telangiectasia, heterotopia, inflammatory myofibroblastic tumor, intraductal papillary neoplasms, leiomyoma, lipoma, lymphangioma, mesenchymal hamartoma, myelolipoma, nodular regenerative hyperplasia, paraganglioma, perivascular epithelioid cell tumor, pseudocyst, pseudolipoma, reactive bile ductule proliferation, solitary fibrous tumor, solitary necrotic nodules
Dysplasia: liver cell dysplasia, borderline nodule, macroregenerative nodule
Hepatocellular carcinoma: general, cytology, variants: clear cell, fibrolamellar, oncocytic, pleomorphic, sarcomatoid, sclerosing, small
Leukemia/lymphoma: leukemia, lymphoma-general, lymphoma-primary, secondary, lymphoma subtypes: Burkitt’s, CLL/SLL, diffuse large B cell, follicular, hepatosplenic alpha-beta, hepatosplenic gamma-delta, Hodgkin’s, lymphoplasmacytic, MALT, nodal CD8+ cytotoxic peripheral T cell, splenic margin zone
Other malignancies: angiosarcoma, biliary cystadenocarcinoma, carcinoid, carcinosarcoma, Castleman’s disease, cholangiocarcinoma, congenital primitive epithelial tumor, epithelial myoepithelial carcinoma, epithelioid hemangioendothelioma, Erdheim-Chester disease, fibrosarcoma, follicular dendritic cell, gastrointestinal stromal tumor, germ cell tumors, hepatoblastoma, infantile hemangioendothelioma, juvenile xanthogranuloma, Kaposi’s sarcoma, Langerhans cell histiocytosis, leiomyosarcoma, liposarcoma, lymphoepithelioma-like carcinoma, malignant fibrous histiocytoma, malignant histiocytosis, mastocytosis, metastases, mixed hepatocellular carcinoma-cholangiocarcinoma, neuroendocrine carcinoma, reactive lymphoid hyperplasia, rhabdomyosarcoma, squamous cell carcinoma, undifferentiated sarcoma
Miscellaneous: staging, frozen section, grossing, features to report
Go to Liver and intrahepatic bile ducts - Non-tumor
AJCC Cancer Staging Manual (6th Ed)
American Journal of Surgical Pathology (AJSP), Jan 1999 to Feb 2004
Archives of Pathology and Laboratory Medicine (Archives), Jan 1999 to Apr 2004
Human Pathology, Jan 1999 to Mar 2004
Modern Pathology, Jan 1999 to Mar 2004
Rosai, J: Ackerman’s Surgical Pathology (8th Ed); Mosby-Year Book, Inc., 1996
Sternberg, S: Diagnostic Surgical Pathology (3rd Ed); Lippincott Williams & Wilkins, 1999
USCAP short course: Mod Path 2000;13:679
Journal search terms: liver, hepatic
Please refer to these primary references for more detailed discussions
Benign tumors
<100 cases reported; often misdiagnosed
Mesenchymal tumor arising from perivascular epithelioid cells; also lymphangioleiomyomas, clear cell sugar tumors of lung, rare myomelanocytic tumors
Similar histologically to renal angiomyolipoma
Mean age 50 years, range 9-79 years; 80% women
Only 6-10% associated with tuberous sclerosis, these cases are associated with renal AML and may be multiple
Myoid and vascular components are clonal; adipose tissue component may be reactive
Case report of 15+ tumors in 46 year old woman without tuberous sclerosis (Mod Path 2002;15:167)
MRI image : multiple hypointense lesions
Gross: well circumscribed, solitary masses up to 20 cm, yellow-gray-white; necrosis present in larger tumors, background liver is normal
Gross images : multiple well circumscribed lesions
Micro: mature adipose tissue, smooth muscle cells and thick walled blood vessels with spindle cells radiating from walls; extramedullary hematopoiesis (40%); smooth muscle cells are epithelioid or spindled with clear or eosinophilic cytoplasm; mast cells common; occasional features are cellularity, nuclear pleomorphism with intranuclear inclusions, tumor giant cells; no/rare mitotic figures; unusual subtypes are oncocytic and trabecular
Micro images: H&E and stains
Micro images : low power, epithelioid tumor and smooth muscle actin
Positive stains: HMB45, MelanA/MART-1, microphthalmia transcription factor (50%), S100, smooth muscle actin, desmin, c-kit/CD117 (all cell types)
Negative stains: cytokeratin
EM: epithelioid myoid cells have premelanosomes, numerous mitochondria, abundant rough endoplasmic reticulum, glycogen, tight junctions and basal lamina, but no thick filaments
References: AJSP 2002;26:493 (c-kit staining), Archives 2002;126:49 (melanoma markers), AJSP 1999;23:34 (review)
Also called multilocular peritoneal inclusion cyst
Very rare in liver; elsewhere usually young women with local recurrence
Benign, indolent, slowly progressive, curable
Laboratory: elevated CA 19-9 in serum and cyst fluid
Case reports: 58 year old Italian man with elevated CA 19-9, multiple benign appearing liver cysts and single cysts in kidney and pancreas (Archives 2001;125:944), 51 year old woman (AJSP 2002;26:1523)
Treatment: excision, but may recur
Gross images: cyst before and after aspiration
Micro: well encapsulated, partially cystic, highly vascular; no cirrhosis; loose cords of tumor cells separated by medium to large vessels with walls of varying thickness; cystic spaces lined by tumor cells, either epithelioid or with hobnail appearance
Micro images: H&E, EM, CA 19-9, CEA, CA 125
Positive stains: CK 8/18 (CAM 5.2), calretinin, EMA, vimentin, estrogen receptor
DD: hydatid cyst, biliary cystadenoma, serous cystadenoma, cystic neoplasms
Incidental finding, although often confused with adenocarcinoma
Usually adults > 40 years old, no gender preference
Benign
Much less common than bile duct hamartoma
Gross: well-circumscribed but unencapsulated, firm, gray-white, tan, subcapsular nodules; 85% solitary; usually 5 mm or less but 7% are larger than 1 cm; may have central depression
Micro: compact network of simple tubular ducts or more complex tortuous arrangement, 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 invasion
Positive stains: mucin (intracytoplasmic), CEA, EMA, keratin, PAS highlights basement membrane
DD: cholangiocarcioma, adenocarcinoma
Atypical clear cell type
Rare; ages 25-64 years in 3 cases described
Incidental finding
Gross: 1 cm, subcapsular
Micro: bile duct tumor composed almost entirely of small nests and tubules of clear cells infiltrating hepatic parenchyma; small nests surrounded by PAS+ membrane (may represent tubular structures); well defined cytoplasmic borders, mild nuclear hyperchromasia, mild stromal sclerosis; no mitotic activity
Positive stains: CK7, EMA, CEA, p53, mucin (focal)
Negative stains: CK20, vimentin, HepPar1, chromogranin, Ki-67 (<10% positive)
DD: well differentiated adenocarcinoma, metastatic renal cell carcinoma, clear cell cholangiocarcinoma (larger, tubular pattern, desmoplastic stroma, more nuclear atypia and mitotic activity; similar immunostains results)
References: AJSP 2001;25:956
Extremely rare (< 5 reported cases)
Case report in 47 year old woman, AJSP 2003;27: 693
Appears to originate from interlobular or larger bile ducts
Benign behavior to date, but may be premalignant
Micro: (a) microcystic and tubular structures lined by low columnar/cuboidal epithelium and (b) dense fibrous stroma with spindle cells displaying mild nuclear pleomorphism; no/rare mitotic figures, no stromal invasion
Positive stains: epithelium - AE3, CAM5.2, CK 7, CK9, CEA, EMA, D10, p53
Negative stains: Alcian blue, vimentin, desmin
DD: von Meyenburg complex (smaller, usually multifocal, but similar staining pattern)
5% of all hepatic solitary cysts
95% occur in women, mean age 45 years (range 2-87 years)
84% are intrahepatic, also in common bile duct (6%), hepatic ducts (4%), cystic duct (4%), gallbladder (2%)
Associated with polycystic liver disease, abnormal hepatobiliary anatomy
Usually slow growing with good prognosis after surgical excision, although 25% have coexisting malignancy
Complications: intracystic hemorrhage, bacterial infection, rupture
Also associated with borderline or malignant lesions
Laboratory: elevated CA 19-9 (in cases with ovarian type stroma) and CEA in cyst fluid and serum
Xray: calcification in 20% (resemble echinococcal cyst)
Treatment: complete excision (rarely has delayed recurrence)
Case reports: Case of the Week #70, tumor arising from left hepatic duct (Archives 2001;125:1507), encased in smooth muscle tumor (AJSP 1999;23:854), 39 year old woman with abdominal pain (World J Gastroenterol 2006;12:6062)
Gross: encapsulated, solitary, mean 15 cm (range 3-28 cm), usually mucinous, multilocular by definition (locules have varied sizes); contains up to several liters of fluid; smooth inner surface with few trabeculations or polypoid cystic projections; rarely contains gallstones; nodules of solid tissue suggests malignancy
Gross images: large, smooth lined cyst
Micro: mucinous - lined by single layer of columnar-cuboidal mucinous epithelium with basal nuclei and apical mucin; spindle-cell ovarian type stroma only in women (resembles pancreatic mucinous cystic neoplasms); spindle cells may contain fat and smooth muscle; may have collagenous zone above stroma (resembling collagenous colitis); capsule composed of dense collagen with blood vessels, variable bile ducts; may have squamous or intestinal metaplasia, often neuroendocrine cells; may have dysplastic or borderline foci; may have ulceration with macrophages containing lipofuscin or hemosiderin, cholesterol clefts with foreign body giant cell reaction or calcification; no/rare atypia, no/rare mitotic figures
serous - lined by bland, flat to cuboidal cells with clear, glycogen-rich cytoplasm, no spindle cell stroma; no mucin; may represent hepatic metastasis from pancreatic serous cystadenocarcinoma
Micro images: image #1-low power; #2-low power; #3-high power; #4-high power; #5-high power; #6-high power; #7-high power; #8-CA19-9; #9-progesterone receptor
Positive stains: epithelial cells - cytokeratin, EMA, CEA, CA19-9; stromal cells - muscle specific actin, vimentin; usually ER and PR (Dig Dis Sci 2006;51:623)
DD: borderline tumors (have high grade dysplasia and complex architecture), invasive tumors (put through numerous sections to exclude)
Borderline
Tumors with high grade dysplasia with complex architecture
Micro: lined by cuboidal or biliary type epithelium; rarely squamous lined; thin fibrous wall
Rare, 50 cases reported
2/3 men, usually ages 40+ years
Multiple papillary adenomas extensively throughout intra- or extrahepatic biliary tract
Often recurs, 25% have malignant transformation, but only rare metastases (to lung)
Associated with Caroli’s disease, choledochal cyst, polyposis coli and ulcerative colitis
Most patients die within 3 years due to cholangitis and hepatic failure
Case report in 66 year old man with cirrhosis due to Hepatitis C and malignant transformation, Archives 2002;126:369
Treatment: difficult to treat because multifocal; liver transplant may be helpful
Gross: inner surface of ducts has velvety papillary growths with masses filling dilated ducts; masses are soft, friable, white-red-tan
Micro: dilated ducts contain multiple papillary tumors composed of fibrovascular cores lined by columnar, pseudostratified, biliary-type cells with numerous cytoplasmic mucin vacuoles; tumor may be solid or cribriform; varying cytologic atypia and mitotic activity; may have associated tubular adenocarcinoma with invasion
Micro images: fibrovascular cores and invasive disease (in case report above)
Usually asymptomatic or associated with anemia; rarely presents as a liver mass
Case report of 52 year old woman with 2.5 cm, 5 cm and 7 cm liver masses and normal serum AFP, Archives 2003;127:631
Treatment: radiation or hydroxyurea if symptomatic
Micro: erythroid precursors in sinusoids (resemble lymphocytes), myeloid precursors in portal tracts (resemble mixed portal infiltrate or eosinophils in neonates); also megakaryocytes within sinuses
Cytology images: Diff-Quick (2), Pap stain
Not neoplastic, but simulates lipomatous tumor
Associated with obesity, diabetes, alcohol abuse, dyslipidemia
Stable or regresses if underlying condition improves
Gross: subcapsular yellow-white foci, often multiple, up to 10 cm
Micro: diffuse or focal steatosis adjacent to unremarkable liver, may have foreign-body type granulomatous inflammation
Focal nodular hyperplasia (FNH)
Common (#2 liver tumor after hemangioma)
Mass lesion of young (median age 38 years); some studies show female predominance
Represents 2-10% of pediatric hepatic tumors
May be associated with oral contraceptives (66-95% of cases), hepatic cavernous hemangioma (20%), glycogen storage disease type Ia, portal hypertension
Tumors associated with oral contraceptives often have hemorrhage, necrosis, infarction
Usually an incidental finding; present in 1% of autopsies
May have abdominal discomfort, pain, anorexia or fatigue (Hepatobiliary Pancreat Dis Int. 2004;3:199)
May represent hyperplastic response to arterial malformation or other vascular anomaly; is NOT a neoplasm (Am J Gastroenterol 2006;101:2341)
Case reports: Case of the Week #88
Xray: mass with central scar, centrifugal hypervascularity by angiography; CT and MRI are important, but often cannot make a definite preoperative diagnosis (Hepatobiliary Pancreat Dis Int. 2007;6:52)
Treatment: excellent prognosis; adult women should discontinue oral contraceptives, if applicable; surgery if symptomatic, complications, compression of adjacent organs or lesion progression (Eur J Pediatr Surg 2006;16:235)
Gross: well-demarcated, subcapsular, light brown to yellow (lighter than surrounding liver); bulging nodule, 70-80% solitary, up to 5 cm; rarely > 10 cm; 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
Gross images: well circumscribed mass with central stellate scar #1; #2
Micro: hepatocyte nodules are surrounded by fibrous septa with large malformed arterial branches not accompanied by interlobular bile ducts or portal veins; septal margins have foci of intense lymphocytic infiltrates and marked bile duct proliferation with histologic changes of chronic cholestasis (Mallory’s hyaline, bile pigment, copper deposits, pseudoxanthomatous change), variable neutrophilic infiltration; ductules appear to arise from limiting plate; central scar contains central fibrous body with tortuous large vessels with fibromuscular hyperplasia and luminal narrowing; hepatic plates are 1-2 cells thick, similar to surrounding liver, but may be larger and paler with fat or glycogen; no atypia, no mitotic figures; telangiectatic variant has multiple dilated vascular channels in center of mass
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 cell (AJSP 1999;23:1441)
Telangiectatic FNH is considered by some to be a variant of hepatocellular adenoma (World J Gastroenterol 2007;13:2649)
Micro images: fibrous area with blood vessels and bile ductules #1; #2; #3; associated with fibrolamellar carcinoma; diagram of possible pathogenesis
Positive stains: alpha-1-antitrypsin
Negative stains: p53, CD143 (angiotensin I-converting enzyme: reduced expression, AJSP 2004;28:84)
DD: 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), peritumoral hyperplasia (Archives 2000;124:1105)
References: Radiographics 2004;24:3, eMedicine
Multiple focal nodular hyperplasia syndrome
Multiple FNH lesions plus one other lesion: either hepatic hemangioma, arterial dysplasia, Klippel-Trenaunay-Weber syndrome, brain telangiectasia, berry aneurysm, astrocytoma or meningioma
Micro: often telangiectatic variant with multiple dilated vascular channels in center of mass
Rare, <10 cases reported
Type of glomus tumor (neoplasm of glomus apparatus) with prominent vascular structures
Case report in 57 year old man with flank pain and 3 cm liver mass, Archives 2004;128:e46
Xray images: hypervascular mass
Micro: small to medium branched vessels with stroma containing small, round regular cells with sharply outlined round/oval nuclei
Micro images: small bland tumor cells in vascular network, smooth muscle actin and CD34
Positive stains: vimentin, smooth muscle actin, CD34, calponin (focal)
Negative stains: desmin, S100, chromogranin, CD117
Most common primary hepatic tumor
Usually an incidental finding, found in 1% of routine autopsies and 20% of autopsies with extensive investigation
More common in adults than children, 75% in women, who are more likely symptomatic
10% enlarge with follow-up, may be related to pregnancy or oral contraceptives
Associated with multiple focal nodular hyperplasia syndrome
Giant cavernous hemangiomas (> 4-10 cm) only rarely rupture
Fibrotic tumors may be precursor of solitary necrotic nodules
Solitary capillary hemangiomas are extremely rare
Treatment: excision or observation (may involute)
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
Gross images: well circumscribed mass
Micro: variably sized vascular spaces lined by flat endothelial cells and myxoid or fibrous stroma; large fibrous septa may trap bile ducts; variable thrombosis, calcification, phleboliths; increased fibrosis with age of lesion may obliterate lumen
Micro images: cavernous hemangioma #1, #2
Positive stains: elastin and trichrome may expose vessels in old fibrous lesions
DD: peliosis hepatis (no fibrous septa), hereditary hemorrhagic telangiectasia (aberrant portal vessels, dilated vascular channels within portal tracts), hemangiomatosis, infantile hemangioendothelioma (atypia present, although not necessarily everywhere)
Also called diffuse hemangiomatosis
Rare disease of adults
May also affect lung and bone
Gross: nodules may replace entire liver
Micro: numerous small, poorly circumscribed, hemangiomatosis nodules in portal tracts, may become sclerosed
Hepatic vascular malformation with capillary proliferation
Usually symptomatic at birth
Congenital vascular malformation
Does not regress spontaneously
Symptoms: abdominal mass or distention, cardiomegaly, congestive heart failure, anemia, thrombocytopenia, DIC, fever, jaundice, elevated serum AFP
Treatment: lobectomy; good outcome
Gross: single large mass, mean 8 cm, range 5-11 cm; central infarction and hemorrhage is common
Micro: outer dilated vessels lined by flattened endothelium and loose myxoid stroma; central infarction and hemorrhage
DD: infantile hemangioendothelioma (GLUT1+, Hum Path 2004;35:200)
Also called liver cell adenoma
Arises in normal or nearly normal liver in patients with abnormal hormonal or metabolic condition
95% women, usually child-bearing age (very rare in children), history of 5+ years of oral contraceptives in 85% (occasionally regress after discontinuation); also associated with anabolic steroids (in men), anti-estrogens, Klinefelter’s syndrome or other abnormal secretion of sex steroids
Also associated with glycogen storage disease types Ia and III, Fanconi’s anemia, familial adenomatous polyposis, familial diabetes mellitus, Hurler’s disease or tyrosinemia; also spontaneous
2-4% of hepatic tumors in children
Subcapsular tumors may rupture, particularly during pregnancy
Benign, but may contain hepatocellular carcinoma or cause severe hemorrhage
10% or lower risk of hepatocellular carcinoma if not resected; definite risk in young men with glycogen storage disease type Ia
Must sample generously to rule out coexisting hepatocellular carcinoma
May contain hepatic progenitor cells, AJSP 2001;25:1388
Laboratory: normal liver function tests, may have elevated alpha fetoprotein
Hepatocellular adenomatosis: 10+ tumors
Treatment: excision
Case reports: tumor in 9 year old girl with later fibrolamellar carcinoma (Archives 2004;128:222)
Gross: solitary (70%, anabolic steroid related more often multiple), pale, yellow-tan (different from surrounding liver), frequently bile-stained nodules, often subcapsular, 10-30 cm, sharply demarcated or encapsulated; usually right lobe, may be pedunculated (10%); may have hemorrhagic, necrotic or infarcted foci; usually no fibrous septa or central scar; adjacent liver is noncirrhotic
Gross images: well circumscribed lesion #1, #2
Micro: sheets and cords 1-3 cells thick of normal appearing hepatocytes with variable glycogen; no/rare mitotic figures; no portal tracts, no central veins or connection with biliary system but see prominent “free floating” arterial vessels and draining veins throughout the tumor; intact reticulin framework; pseudoglands may be present; may have cytoplasmic globules (PAS+, diastase resistant, alpha-1-antitrypsin+, AFP-), 10% have multinucleation, but no atypia, no prominent nucleoli, no intranuclear vacuoles, no/rare mitotic figures, no angiolymphatic invasion, no/rare extramedullary hematopoiesis, no epithelioid granulomas, no decreased reticulin framework; degenerative changes include dilated sinusoids, blood filled (pelioid) spaces, myxoid stroma, focal necrosis, infarction, hematoma; rarely contains abundant fat, oncocytic changes, Mallory’s hyaline, granulomatous inflammation
Micro images: adenoma #1, #2 in 14 year old (figures a-d), ER and PR
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)
References: Hum Path 2002;33:852 (childhood tumors with beta catenin abnormalities)
Atypical hepatocellular adenoma
Androgen related tumors that regress with androgen withdrawal
Only rarely metastasize
Micro: marked pleomorphism with prominent nucleoli and extensive pseudoglands, resembling hepatocellular carcinoma, but no trabecular pattern, low N/C ratio, no vascular invasion
DD: hepatocellular carcinoma (elevated serum AFP, cirrhosis, vascular invasion, high N/C ratio, trabecular pattern), focal nodular hyperplasia (central scar), hepatoblastoma (elevated serum AFP, age < 3 years, no metabolic disease, light and dark cytoplasmic pattern, small cell size)
Pigmented liver cell adenoma
Black pigment present
Case reports in 2 men without Dubin-Johnson syndrome, AJSP 2000;24:1429
Micro: pigment granules are larger and darker than lipofuscin; no portal tracts, bile ducts or ductules within the tumor
Positive stains: Masson-Fontana (for melanin and Dubin-Johnson pigment)
DD: well differentiated hepatocellular carcinoma
Hereditary hemorrhagic telangiectasia
Also called Osler-Weber-Rendu syndrome
Autosomal dominant; systemic fibrovascular dysplasia; prevalence of 10-20 per 100,000 population
Caused by HHT1 (encodes endoglin on #9, expressed in central vein endothelium of normal liver) and HHT2 (encodes activin receptor-like kinase 1 / ALK1 on #12)
Hemorrhage, telangiectasia and arteriovenous malformations of vessels in skin, mucous membranes, lung, liver (up to 33%), CNS
Usually asymptomatic
May have hepatic vascular shunts that may cause high output congestive heart failure, portovenous shunts that cause hepatic encephalopathy or arterioportal shunts that cause portal hypertension
Case reports: 56 year old woman with pulmonary hypertension and intractable pulmonary bleeding (due to pulmonary capillary hemangiomatosis) and GI bleeding, Hum Path 2004;35:266
Gross: telangiectatic lesions throughout the liver
Gross images: dilated and thickened hepatic artery branches
Micro: focal sinusoidal ectasia, abnormal direct communications between hepatic arterial branches and ectatic sinusoids (AV shunts), frequent and large communications between portal and central veins through ectatic sinusoids (portovenous shunts)
Micro images: dilated arteries, vein and sinusoids, three dimensional reconstruction
References: Archives 2001;125:1219
Usually from pancreas, adrenal gland or spleen
Pancreas: 4% of autopsies, usually within large and medium sized portal tracts; acinar cells but no islets
Adrenal gland rests: rare, may be confused with renal cell carcinoma or other clear cell carcinomas
Heterotopic liver is not connected to main liver; is found in gallbladder, spleen, pancreas, umbilicus, adrenal gland, small intestine, lesser omentum, lung
Inflammatory myofibroblastic tumor
Also called inflammatory pseudotumor
Uncommon
Mean 37 years but all ages, 75% male
Associated with occlusive phlebitis and chronic cholangitis
Rarely associated with sarcoma or follicular dendritic cell tumor
In extrapulmonary tumors, recurs locally in 25%; 8% metastasize
Symptoms: fever, upper abdominal pain
Treatment: excision, occasionally regresses spontaneously
Gross: well circumscribed, solitary (70%), 1-25 cm, variegated cut surface, may extend into vena cava or soft tissue
Micro: plasma cells, lymphocytes, neutrophils, macrophages, mast cells and myofibroblast-like spindled cells in varying amounts, in whorled, fibrotic stroma; occasional myxoid areas, minimal vascular component; minimal pleomorphism, no/rare mitotic activity; rarely is highly cellular or has mitotic activity (often in children)
Positive stains: vimentin (>90%), smooth muscle actin (80%), muscle specific actin (80%), desmin (40%), CD68 (40%), pankeratin (30%), p53 (30%), ALK1
Negative stains: S100, CD21, myoglobin
DD: sclerosing hemangioma, leiomyoma, solitary fibrous tumor, follicular dendritic cell tumors (CD21+, CD35+), Hodgkin’s lymphoma (stromal cells CD15+, CD30+), organizing abscess, postoperative spindle cell nodule, spindle cell carcinoma or sarcoma
Intraductal papillary neoplasms of biliary tract
Uncommon
Solitary or may spread along biliary tree to cystic duct or duodenal papilla
May resemble intrapapillary mucinous neoplasms of pancreas as both arise within a dilated duct system and demonstrate predominantly intraductal growth
Risk factor for cholangiocarcinoma, biliary obstruction, recurring ascending cholangitis
Often are carcinomas
Micro: papillary fronds with fine vascular cores; epithelial cells are either biliary type or have gastric or intestinal differentiation with goblet cells and Paneth cells; production of extracellular intraductal mucin less common than pancreatic IPMNs
Borderline tumors: mild to moderate nuclear atypia and nuclear pseudostratification limited to basal 2/3 of the epithelium
Carcinomas: severe cytological atypia, loss of nuclear polarity or architectural cribriforming / papillary fusion is present
Negative stains: p53, CK20
Molecular: Kras activating mutations (29%), 18q- (31%) but no loss of DPC4
References: Hum Path 2003;34:902, Hum Path 2002;33:503 (stains)
Solitary nodule that may resemble metastatic well differentiated leiomyosarcoma
May be associated with HIV, EBV
Rare, usually incidental finding
Gross: solitary, 1-20 cm
Micro: mature fat or brown fat (hibernoma)
DD: angiomyolipoma, focal fatty change