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CYTOPATHOLOGY OF THE LIVER

23rd Annual Cytology Conference Pittsburgh PA

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

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Benign hepatocytes and endothelial cells, trabecular arrangement

Benign liver plates, granular cytoplasm, endothelial cells

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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

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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; 178:253-258

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

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RESECTION/TRANSPLANTATION

HCCs found earlier, smaller, greater resectability

Transplantation (Milan criteria): < 3cm or < 5cm

But false positive radiology > micronodular cirrhosis

Gender: M>F, 2:1 - 5:1

Prognosis: dismal unless resectable

FNA: 90+% sensitive ~100% specific

HCC geographic pattern

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HCC Bare nuclei

HCC Bare nuclei of HCC mimic lymphoma

HCC, geographic pattern and wrapping

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HCC, endothelial cell wrapping

HCC, bile plugs

HCC, transgressing vessels

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Pleomorphism and nuclear inclusions

Macronucleoli and endothelial cells

HCC, clear cell variant

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HCC, clear cell variant

Pleomorphic HCC, multinucleation

IMMUNOCHEMISTRY OLD AND NEW

(AFP) oncofetal antigen (

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HCC, positive Glypican 3

CHILDREN, ADOLESCENTS, YOUNG ADULTS

Usual HCC Especially with vertical transmission of Hepatitis B virus

Hepatoblastoma USA 0.2/100,000, 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

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Hepatoblastoma

Hepatoblastoma

Fibrolamellar HCC - LP

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Fibrolamellar HCC, HP

Fibrolamellar HCC carcinoma

OTHER PRIMARY LIVER TUMORS

Epithelial:

Intrahepatic cholangiocarcinoma

Mesenchymal:

EHEE Epithelioid

hemangio-endothelioma

Angiosarcoma

Kaposis sarcoma

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Full renal glomerulus in liver FNA

Benign ciliated hepatic foregut cyst

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Benign ciliated hepatic foregut cyst

Degenerated benign ciliated hepatic foregut cyst

Echinococcus granulosus, hydatid cyst,

full scolex

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E. granulosus, collarette of hooklets

E. granulosus, hydatid hooklets and capsule

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EMH: megakaryocytes

EMH, section

Benign hemangioma

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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

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Herpes hepatitis?

Pitfall 1

Pitfall 2 GI epithelium

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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

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Metastatic mucinous adenocarcinoma

Metastatic pancreatic adenoca, well differentiated

Metastatic colorectal ca, necrosis

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Metastatic colorectal

carcinoma

Metastatic adenoca, cytoplasmic vacuoles

Metastatic colonic ca, CEA

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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

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Neuroendocrine tumor, vascular core

Neuroendocrine tumor

Neuroendocrine carcinoma, small cell carcinoma

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Metastatic squamous cell

carcinoma, necrosis

Metastatic squamous cell carcinoma

Metastatic melanoma, melanotic

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Melanoma, single cells, INCI

Melanoma, S-100 immunostain

Metastatic GIST

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Metastatic GIST

Metastatic GIST, c-Kit

Non Hodgkins lymphoma

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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