Video Microscopy Tutorial 8 Common and Uncommon Lesions of the Liver Gladwyn Leiman, MD There are no disclosures necessary.
Common and Uncommon Lesions in Liver FNA Gladwyn Leiman University of Vermont and Fletcher Allen Health Care Conflict of interest No financial disclosures Outline MICROSCOPY Usual and unusual benign findings Primary liver tumors Selected important metastatic tumors DIDACTICS Indications, contras & complications A word on immunochemistry in liver FNA 1
Benign Liver Aspirates Macroscopically: intact formed cores visible Epithelial cells: Hepatocytes, single and trabecular Bile duct cells Mesenchymal cells: Endothelial lining cells Macrophages (Kupffer cells) Fibroblasts Benign hepatocytes and endothelial cells, trabecular arrangement 2
Benign hepatocytes Benign liver plates, granular cytoplasm, endothelial cells Benign hepatocytes with pigment 3
Benign bile duct cells Full renal glomerulus in liver FNA Full renal glomerulus in liver FNA 4
Benign ciliated hepatic foregut cyst Benign ciliated hepatic foregut cyst Degenerated benign ciliated hepatic foregut cyst 5
E. granulosus, hydatid cyst, full scolex E. granulosus, collarette of hooklets E. granulosus, hydatid hooklets and capsule 6
Echinococcus granulosus life cycle dog, sheep, man EMH - Megakaryocytes EMH: megakaryocytes 7
EMH, section Papanicolaou rigid fragments Bile duct seen Glypican 3 negative Fibrous tissue Focal nodular hyperplasia Benign hemangioma 8
Benign hemangioma Benign hemangioma Benign hepatic adenoma: Young females on OCs Radiological mass lesion Liver cells appear normal, lie singly No bile duct cells Rare endothelial cells, no wrapping GPC3 negative 9
Benign Lesions Benign liver and renal structures Benign ciliated hepatic foregut cyst Parasitic cyst: Echinococcus granulosus Extramedullary hematopoiesis (EMH) Focal nodular hyperplasia Benign cavernous hemangioma Benign hepatic adenoma Not shown: Liver abscess, biliary cystadenoma Beware G I elements in endoscopic samples, next 3 slides! Herpes hepatitis? Pitfall 1 Pitfall 2 GI epithelium, slides 30-31 10
Benign biliary cyst, no cytopathology example Indications and contraindications Indication Solid liver mass or masses Contraindications Bleeding diathesis Suspected vascular tumors Diffuse liver disease eg cirrhosis Relative: Suspected hydatid cyst Relative IN SOME CENTERS, Suspected HCC 11
Fatalities ascribed to Liver FNA Smith EH: Radiol 1991; 178:253 258 21 deaths, 17 hemorrhage using 19 gauge 11 deaths, using 21 gauge or smaller 4 vascular: hemangioma 2, angiosarcoma 2 5 hemorrhage: HCC 2, met ca 3 1 sepsis 1 carcinoid crisis Needle track spread (NTS) All reports show successful resection of NT and subcutaneous deposits No fatalities in this group, irrespective of gauge No survival differences with or without NTS Hemorrhage = 6 31 per 100,000 liver FNA (Smith) NTS = 7 per 100,000 (Smith) Some centers still choose not to sample apparently resectable HCCs pre operatively Resection, transplantation issues HCCs found earlier, smaller, resectability Transplantation possible (Milan criteria: single tumors < 5cm, multiple tumors <3cm) Reports of higher recurrence rates with HCC after FNA (no needle gauge) Surgeons want clean field & refuse FNA But also false positive radiology <3cm 90+% world HCCs still inoperable Liver FNA still first line diagnostic modality 12
Hepatocellular carcinoma Hepatocellular Carcinoma (HCC) Major geographic variation (Africa, SE Asia) Hep B, Hep C, aflatoxins, steroids Macronodular >> micronodular cirrhosis Age: Africa 4 th decade, USA 7 th decade Gender: M>F, 2:1 to 5:1 Prognosis: dismal unless resectable USA incidence: 22 nd ranking, 4/100,000 FNA: 90+% sensitive ~100% specific HCC geographic pattern 13
HCC Bare nuclei HCC Bare nuclei of HCC mimic lymphoma HCC, geographic pattern and wrapping 14
HCC, endothelial cell wrapping HCC, more wrapping HCC, bile plugs 15
HCC, transgressing vessels Intact malignant hepatocytes and bare nuclei Pleomorphism and nuclear inclusions 16
Polygonal hepatocytes and pale nuclei Macronucleoli and endothelial cells HCC, clear cell variant 17
HCC, clear cell variant Pleomorphic HCC, multinucleation Immunochemistry: New antibodies (AFP) oncofetal antigen (<30%) pcea canalicular 77% CD10 canalicular 80% CD34 endothelial, sinusoidal 90% HepPar1 hepatocytes, cytoplasm 75% Arginase1 hepatocytes, cytoplasm 80% Glypican3 oncofetal, cytoplasmic 90% malignant hepatocytes only 18
HCC, positive Glypican 3 Children, Adolescents, Young Adults Usual HCC Especially with vertical transmission of Hepatitis B virus Hepatoblastoma USA 0.2/100,000, <5yrs, M>F, Fetal, embryonal, macrotrabecular, small cell undifferentiated Mixed epithelial and mesenchymal, + teratoid features Fibrolamellar variant HCC Age 2 35, mean 23, F>M, better prognosis Large polygonal cells separated by fibrosis Hepatoblastoma 19
Hepatoblastoma Hepatoblastoma Fibrolamellar HCC - LP 20
Fibrolamellar HCC, HP Fibrolamellar HCC carcinoma Other primary malignant liver tumors no slides Epithelial: Intrahepatic cholangiocarcinoma: Adenocarcinoma, NOS Mesenchymal: Epithelioid hemangioendothelioma Angiosarcoma 21
Liver FNA: Metastatic tumors Far exceed primary tumors in FNA Any tumor may ultimately involve liver Often a prior history, diagnosis and slides Liver mass may be initial manifestation Sampling liver may be safer than primary Liver involvement no longer untreatable Recourse to immunochemistry required Adenocarcinoma The most common metastatic tumor type in the liver Mainly lung & GI colorectal, pancreas Breast and gynecologic sites Others uncommon ie prostate, head & neck Targeted immunochemistry essential Clinical history can save thousands! Metastatic mucinous adenocarcinoma 22
Metastatic pancreatic adenoca, well differentiated Metastatic colorectal ca, necrosis Metastatic adenoca, palisading 23
Metastatic adenoca, less differentiated Metastatic adenoca, cytoplasmic vacuoles Metastatic colorectal carcinoma 24
Metastatic colonic ca, CEA Metastatic duct carcinoma breast Cholangiocarcinoma, intrahepatic -Clinical, radiologic, endoscopic data more useful than immunochemistry -Can be very well differentiated, desmoplastic and mucin-producing -Positive for CK7, CEA, MOC31,MUC 4 -Neg TTF1, CK20, p53 25
Other selected metastases of note Neuroendocrine tumors, small cell carcinoma Squamous cell carcinoma Melanoma Gastrointestinal stromal tumor Non Hodgkins lymphoma Neuroendocrine tumor, vascular core Neuroendocrine tumor, size cf hepatocytes 26
Neuroendocrine tumor, size cf rbcs, chromatin Neuroendocrine tumor Neuroendocrine carcinoma, small cell carcinoma 27
Neuroendocrine carcinoma, small cell carcinoma Small cell ca with CGA Metastatic squamous cell carcinoma, necrosis 28
Metastatic squamous cell carcinoma Metastatic melanoma, melanotic Melanoma, amelanotic, mimics HCC 29
Melanoma, single intact cells Melanoma, single cells, INCI Melanoma, S-100 immunostain 30
Metastatic GIST Metastatic GIST Metastatic GIST, c-kit 31
Non Hodgkins lymphoma involving liver Best antibodies in liver FNA Glypican 3, HepPar1, Arginase (+ve in HCC) CK 7, CK 20 profile ( ve in HCC) CDX 2 (+ve in GI primaries) TTF 1 (+ve for lung adenoca, NETs) TTF 1 (also +ve in hepatocyte cytoplasm) CD 56, SYN, CGA (+ve in NETs) p63 (+ve in squamous cell ca) S100, HMB45 (+ve in melanoma) We no longer use pcea, AFP, CD34 for HCC Be careful out there! 32
Special thanks Dr Pamela Michelow University of the Witwatersrand, Johannesburg, South Africa for finding selected cases shown Dr Liron Pantanowitz Baystate Medical Center MA, Tufts for the glass slide example of hepatic adenoma Thank you! 33