CYTOPATHOLOGY OF THE LIVER Gladwyn Leiman

Transcription

1 23 rd Annual Cytology Conference Pittsburgh PA CYTOPATHOLOGY OF THE LIVER Gladwyn Leiman OUTLINE MICROSCOPY Normal constituents HCC and other primary liver tumors Selected important metastatic tumors Benign liver lesions DIDACTICS Indications, contras & complications Immunochemistry in liver FNA BENIGN CONSTITUENTS Macroscopically: intact formed cores visible Epithelial cells: - Hepatocytes, single and trabecular - Bile duct cells Mesenchymal cells: - Endothelial lining cells - Macrophages (Kupffer cells) - Fibroblasts 1

2 /3576/fulltext.php?bframe=figures.htm Benign hepatocytes and endothelial cells, trabecular arrangement Benign liver plates, granular cytoplasm, endothelial cells 2

3 Benign hepatocytes with pigment Benign bile duct cells INDICATIONS AND CONTRA-INDICATIONS Indication Solid liver mass or masses Contraindications Bleeding diathesis Suspected vascular tumors Diffuse liver disease eg cirrhosis Relative: Suspected Echinococcus/hydatid Relative IN SOME CENTERS, Suspected HCC 3

4 EFFICACY AND SAFETY Among the safest of all deep organ FNAS Sensitivity >90% - operator dependent Specificity ~100% - reader dependent Hemorrhage 10-20/100,000 often sub-capsular and contained FATALITIES: LIVER FNA 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 Smith EH: Radiol 1991; 178: NEEDLE TRACK SPREAD 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 NTS = 7 per 100,000 Some centers still choose not to sample apparently resectable HCCs pre-operatively 4

5 RESECTION/TRANSPLANTATION HCCs found earlier, smaller, greater resectability Transplantation (Milan criteria): < 3cm or < 5cm But false positive radiology <3cm Reports of higher recurrence rates with HCC after FNA (no needle gauge) Surgeons want clean field, thus refuse FNA 90+% world HCCs still inoperable FNA STILL FIRST LINE DIAGNOSTIC MODALITY HEPATOCELLULAR CARCINOMA (HCC) USA incidence: 22 nd ranking, 4/100,000 Major geographic variation (Africa, SE Asia) Hep-B, Hep C, aflatoxins, steroids Age: Africa 4 th decade, USA 7 th decade Macronodular >> micronodular cirrhosis Gender: M>F, 2:1-5:1 Prognosis: dismal unless resectable FNA: 90+% sensitive ~100% specific HCC geographic pattern 5

6 HCC Bare nuclei HCC Bare nuclei of HCC mimic lymphoma HCC, geographic pattern and wrapping 6

7 HCC, endothelial cell wrapping HCC, bile plugs HCC, transgressing vessels 7

8 Pleomorphism and nuclear inclusions Macronucleoli and endothelial cells HCC, clear cell variant 8

9 HCC, clear cell variant Pleomorphic HCC, multinucleation IMMUNOCHEMISTRY OLD AND NEW (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 9

10 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 10

11 Hepatoblastoma Hepatoblastoma Fibrolamellar HCC - LP 11

12 Fibrolamellar HCC, HP Fibrolamellar HCC carcinoma OTHER PRIMARY LIVER TUMORS Epithelial: Intrahepatic cholangiocarcinoma Mesenchymal: EHEE Epithelioid hemangio-endothelioma Angiosarcoma Kaposi s sarcoma 12

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14 Full renal glomerulus in liver FNA Benign ciliated hepatic foregut cyst 14

15 Benign ciliated hepatic foregut cyst Degenerated benign ciliated hepatic foregut cyst Echinococcus granulosus, hydatid cyst, full scolex 15

16 E. granulosus, collarette of hooklets E. granulosus, hydatid hooklets and capsule 16

17 EMH: megakaryocytes EMH, section Benign hemangioma 17

18 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 18

19 Pitfall 1 Herpes hepatitis? Pitfall 2 GI epithelium 19

20 Benign biliary cyst, no cytopathology example 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 Most common metastatic tumor type in the liver - Mainly lung & GI colorectal, pancreas - Breast and gynecologic sites - Others uncommon - prostate, head & neck Targeted immunochemistry usually required Clinical history can save thousands! Molecular markers increasingly important 20

21 Metastatic mucinous adenocarcinoma Metastatic pancreatic adenoca, well differentiated Metastatic colorectal ca, necrosis 21

22 Metastatic colorectal carcinoma Metastatic adenoca, cytoplasmic vacuoles Metastatic colonic ca, CEA 22

23 Metastatic duct carcinoma breast Metastatic breast cancer 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 SELECTED METASTASES OF NOTE Neuroendocrine tumors, small cell carcinoma Squamous cell carcinoma Melanoma Gastrointestinal stromal tumor Non-Hodgkins lymphoma 23

24 Neuroendocrine tumor, vascular core Neuroendocrine tumor Neuroendocrine carcinoma, small cell carcinoma 24

25 Metastatic squamous cell carcinoma, necrosis Metastatic squamous cell carcinoma Metastatic melanoma, melanotic 25

26 Melanoma, single cells, INCI Melanoma, S-100 immunostain Metastatic GIST 26

27 Metastatic GIST Metastatic GIST, c-kit Non Hodgkins lymphoma 27

28 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, p40 (+ve in squamous-cell ca) S100, HMB45, MART-1 (+ve in melanoma) COLLECT MATERIAL FOR MOLECULAR MARKERS! - lung, colon, melanoma, breast, gastro-esophageal 28