Liver

, Haiyan Liu1 and Jun Zhang2



(1)
Department of Laboratory Medicine, Geisinger Health System, Danville, PA, USA

(2)
Department of Laboratory Medicine and Pathology, Mayo Clinic, Scottsdale, AZ, USA

 



Keywords
LiverHepatic abscessGranulomatous inflammationEchinococcal (hydatid) cystHepatocellular adenomaFocal nodular hyperplasiaCirrhosisRegenerative nodulesBile duct adenoma and hamartomaCavernous hemangiomaAngiomyolipomaLymphangiomaLymphangiomatosisInfantile hemangiomaMesenchymal hamartomaSolitary fibrous tumorHepatocellular carcinomaHepatocellular carcinomaFibrolamellar variantHepatoblastomaIntrahepatic cholangiocarcinomaCombined hepatocellular-cholangiocarcinomaAngiosarcomaEpithelioid hemangioendotheliomaInflammatory pseudotumorSolitary fibrous tumorEmbryonal (undifferentiated) sarcomaExtrarenal malignant rhabdoid tumorFollicular dendritic cell tumorSarcomaCarcinomaGastrointestinal stromal tumorLymphomaGerm cell tumorMetastasisNeuroendocrine tumorMelanomaLiver fatty acid-binding protein (L-FABP)Hepatocyte nuclear factor 1-alpha (HNF-1a)Serum amyloid A (SSA)/C-reactive protein (CRP)Beta-cateninGlutamine synthetase (GS)CK7CK20CD34ReticulinArginase-1HepPar-1Glypican-3Alpha-fetoproteinHeat-shock protein 70 (HSP70)ClusterinCD10p-CEAMOC31pVHLHMB45CD31ERGGATA3ERPAX8TTF1SOX10SALL4CDX2SATB2ATRX/DAXX



Summary of Pearls and Pitfalls





  • Fine needle aspiration (FNA) and small needle core biopsies of the liver under a guidance of computed tomography (CT) or ultrasound (US) are popular procedures to obtain a diagnosis from a mass lesion. It is a very useful approach in the diagnosis of malignant liver neoplasms, with sensitivity ranging from 75% to 94% and specificity ranging from 87% to 100%.


  • Approximately 95% of malignant liver tumors are metastasis, and the majority of other malignant tumors are hepatocellular carcinoma (HCC).


  • In order to obtain a definitive diagnosis, a cellblock preparation or thin needle core biopsy in conjunction with immunohistochemical (IHC) stains is strongly encouraged for every FNA of the liver.


  • FNA of the liver cannot differentiate among the benign lesions of hepatocellular adenoma (HCA), focal nodular hyperplasia, and regenerative nodule in cirrhosis .


  • Two important diagnostic issues are frequently encountered in the FNA of the liver. One is to differentiate well-differentiated HCC from benign/reactive hepatic lesion, and the other is to distinguish poorly differentiated HCC from cholangiocarcinoma or metastatic carcinomas or even sarcomas.


  • Glypican- 3, heat-shock protein 70 (HSP70 ), glutamine synthetase (GS ) , and clusterin are useful markers in diagnosing a well-differentiated HCC.


  • Alpha-fetoprotein (AFP ) is a specific, after exclusion of germ cell tumors and other tumors, but insensitive marker (about 25%) in the detection of HCC on tissue section.


  • Arginase-1 is a more specific marker than hepatocyte paraffin-1 (HepPar-1 ) in confirming a hepatocellular origin when working on a tumor of unknown origin.


  • Approximately 70% of intrahepatic cholangiocarcinomas (IHCCs) are positive for von Hippel-Lindau tumor suppressor gene protein (pVHL ); in contrast, metastatic adenocarcinomas, including those from the pancreas and extrahepatic biliary tract, are negative for pVHL.


  • Albumin by ribonucleic acid (RNA) in situ hybridization has been reported to be detectable in nearly 100% of HCCs and IHCCs and the majority of hepatoid carcinomas.


  • Vascular tumors of the liver tend to have a bloody and hypocellular smear; therefore, avoid calling a smear non-diagnostic before excluding a vascular tumor. Bland spindled endothelial cells may be mistaken for other mesenchymal lesions.


  • When working on a spindle cell lesion, even if no lipomatous component is seen, an angiomyolipoma should be included in the differential diagnoses. The epithelioid variant of angiomyolipoma can mimic other tumors, such as HCC, clear cell renal cell carcinoma (RCC), adrenocortical carcinoma, and melanoma.


Liver Lesions, Neoplasms, and Tumors in the 2010 World Health Organization (WHO) Classification , Modified1






  • Normal/reactive liver


  • Infection



    • Hepatic abscess


    • Granulomatous inflammation


    • Echinococcal (hydatid) cyst


  • Benign neoplasms/lesions



    • HCA


    • Focal nodular hyperplasia


    • Cirrhosis


    • Regenerative nodules


    • Bile duct adenoma and hamartoma


    • Cavernous hemangioma


    • Angiomyolipoma (perivascular epithelioid cell tumor [PEComa])


    • Lymphangioma


    • Lymphangiomatosis


    • Infantile hemangioma


    • Mesenchymal hamartoma


    • Solitary fibrous tumor


  • Premalignant lesions



    • Intraductal papillary neoplasm with low-, intermediate-, or high-grade dysplasia


    • Mucinous cystic neoplasm with low-, intermediate-, or high-grade dysplasia


  • Malignant neoplasms



    • Hepatocellular carcinoma (HCC)


    • HCC, fibrolamellar variant


    • Hepatoblastoma


    • Intrahepatic cholangiocarcinoma (IHCC)


    • Combined hepatocellular-cholangiocarcinoma


    • Intraductal papillary neoplasm with an associated invasive carcinoma


    • Mucinous cystic neoplasm with an associated invasive carcinoma


    • Angiosarcoma


    • Epithelioid hemangioendothelioma


    • Other sarcomas


    • Germ cell tumors


    • Lymphomas


  • Rare primary lesions/tumors


  • Secondary tumors


Normal Cytology of the Liver



Hepatocytes (Figs. 7.1, 7.2, 7.3, 7.4, 7.5, 7.6, 7.7, and 7.8)




A333337_1_En_7_Fig1_HTML.jpg


Fig. 7.1
Normal hepatocytes with round and centrally located nuclei with prominent nucleoli (Diff-Quik)


A333337_1_En_7_Fig2_HTML.jpg


Fig. 7.2
Normal hepatocytes (Papanicolaou [Pap] stain)


A333337_1_En_7_Fig3_HTML.jpg


Fig. 7.3
Hepatocytes with steatosis


A333337_1_En_7_Fig4_HTML.jpg


Fig. 7.4
Hepatocytes with lipofuscin


A333337_1_En_7_Fig5_HTML.jpg


Fig. 7.5
Hepatocytes with bile (Diff-Quik)


A333337_1_En_7_Fig6_HTML.jpg


Fig. 7.6
Hepatocytes with bile (Pap stain)


A333337_1_En_7_Fig7_HTML.jpg


Fig. 7.7
Reactive hepatocytes with prominent nucleoli


A333337_1_En_7_Fig8_HTML.jpg


Fig. 7.8
Two-dimensional sheets of benign duct epithelium cells. The nuclei are round to ovoid, same size or slightly larger than one red blood cell, evenly distributed nuclear chromatin, smooth nuclear membranes, and indistinct nucleoli (Diff-Quik)




  • Large polygonal cells singly, in ribbons, or in large tissue fragments.


  • Round and centrally located nuclei with prominent nucleoli.


  • Binucleation and intranuclear inclusion are common.


  • Low nuclear-to-cytoplasmic ratio with abundant granular cytoplasm.


  • Pigments can be lipofuscin (Fig. 7.4), bile (Figs. 7.5 and 7.6) , or hemosiderin (Fig. 7.7).


Bile Duct Epithelial Cells






  • Two-dimensional sheets of variable sizes, with a scant amount of cytoplasm and poorly defined cytoplasmic borders.


  • The cell borders may be prominent, forming an orderly honeycomb appearance.


  • The nuclei are round to ovoid, the same size or slightly larger than one red blood cell, evenly distributed nuclear chromatin, smooth nuclear membranes, and indistinct nucleoli (Fig. 7.9a, b).

    A333337_1_En_7_Fig9_HTML.jpg


    Fig. 7.9
    (a, b) Benign duct cell s and hepatocytes on Diff-Quik (a) and Pap stain (b)


Hepatic Abscess



Cytological Features





  • Numerous acute inflammatory cells and necrotic debris as shown in Fig. 7.10.

    A333337_1_En_7_Fig10_HTML.jpg


    Fig. 7.10
    Hepatic abscess with acute inflammatory cells and necrotic debris


  • Culture is needed.


  • Cellblock preparation for special stains.


Differential Diagnosis





  • Bacteria, amoeba, fungus, or neoplasms


Granulomatous Inflammation



Cytological Features





  • Aggregates of epithelioid histiocytes, multinucleated giant cells, and chronic inflammatory cells with or without necrosis, as shown in Fig. 7.11

    A333337_1_En_7_Fig11_HTML.jpg


    Fig. 7.11
    Granulomatous inflammation


Histology





  • Aggregates of epithelioid histiocytes, multinucleated giant cells, and chronic inflammatory cells with or without necrosis


Differential Diagnosis





  • Infection, such as tuberculosis, fungus, parasites


  • Sarcoidosis


  • Reaction to foreign materials


  • Neoplasms, Hodgkin’s lymphoma, T-cell lymphoma, and seminoma


Echinococcal (Hydatid) Cyst



Clinical Features





  • Anaphylactic shock has been reported as an occasional complication of the FNA.


Cytological Features (Fig. 7.12)





  • Fragments of the laminated membrane

    A333337_1_En_7_Fig12_HTML.jpg


    Fig. 7.12
    Hydatid cyst showing hooks


  • Scolices


  • Hooklets


Hepatocellular Adenoma



Clinical Features





  • Young female, usually under age 30.


  • Long-term use of oral contraceptives or androgenic steroids.


  • Other nonhormonal risk factors such as glycogenosis type 1 and 3, galactosemia, familial polyposis coli, obesity, etc.


  • Sizes are variable from microscopic focus to 20 cm .


Cytological Features





  • Normal-appearing or mildly atypical hepatocytes, singly or in groups or sheets (Fig. 7.13a–c)

    A333337_1_En_7_Fig13_HTML.jpg


    Fig. 7.13
    (a–c) HCA with benign hepatocytes and no ductal cells on an FNA smear (a), on cellblock (b), and reticulin showing hepatocytes of 1–2 cells in thickness (c)


  • Normal nuclear-to-cytoplasmic ratio with abundant granular cytoplasm


  • Decreased numbers or lack of bile duct epithelial cells


Histology





  • Benign hepatocytes arranged in plates, one or two cells thick (Fig. 7.14a–d).

    A333337_1_En_7_Fig14_HTML.gif


    Fig. 7.14
    (a–d) HCA showing hepatocytes arranged in layers of one to two cells in thickness and absence of portal tracts (a–c) and reticulin highlighting hepatocytes of 1–2 cells in thickness (d)


  • Absence of portal tracts with presence of isolated arteries.


  • Tumoral hepatocytes may show steatotic, clear, or pigmented cytoplasm.


  • Focal pseudoglandular formation can be seen.


  • Minimal nuclear atypia and no mitosis.


  • Biopsy of adjacent nontumoral liver to determine the presence of absence of cirrhosis is important.


  • HCA has been recently subclassified into several groups: hepatocyte nuclear factor 1-alpha (HNF-1a )-inactivated HCA (35–40%), beta-catenin-activated HCA (10–15%), inflammatory HCA (>50%), and unclassified HCA (<10%).


  • Beta-catenin-activated HCA has an increased risk of malignant transformation .


Immunohistochemistry



  • A panel of IHC markers including liver fatty acid-binding protein (L-FABP ), HNF-1a , serum amyloid A (SSA) /C-reactive protein (CRP ), beta-catenin, and GS has been reported to be useful in this subclassification. The immunoreactivity to each IHC marker for each subtype of HCA is summarized in Table 7.1.


    Table 7.1.
    Summary of useful IHC markers in subclassification of HCA








































    Markers/diagnosis
    HNF-1a -inactivated HCA
    Beta-catenin-activated HCA
    Inflam-matory HCA
    Unclassified HCA

    L-FABP

    −
    +
    +
    +

    GS

    −
    +
    −
    −

    Beta-catenin (N+)
    −
    +
    −
    −

    SAA/CRP
    −
    −
    +
    −


    Note: N nuclear


Differential Diagnosis





  • Normal liver


  • Focal nodular hyperplasia


  • Regenerative nodules


  • Cirrhosis


Focal Nodular Hyperplasia



Clinical Features





  • Nodule usually contains a central scar.


Cytological Features





  • Normal-appearing or mildly atypical hepatocytes in singly or in groups or sheets


  • Normal nuclear-to-cytoplasmic ratio with abundant granular cytoplasm


  • Increased numbers of bile duct epithelial cells


Histology





  • Benign hepatocellular nodules arranged in plates no more than two cells thick (Figs. 7.15a–d and 7.16a–d).

    A333337_1_En_7_Fig15_HTML.jpg


    Fig. 7.15
    (a–d) Focal nodular hyperplasia with benign hepatocytes arranged in layers of less than two cells in thickness, lack of portal tract, stromal inflammatory infiltrate, and ductular reaction on a core biopsy


    A333337_1_En_7_Fig16_HTML.jpg


    Fig. 7.16
    (a–d) Focal nodular hyperplasia with benign hepatocytes arranged in layers of less than two cells in thickness, lack of portal tract, stromal inflammatory infiltrate, and ductular reaction on a resection specimen. Note the reticulin stain (c) and trichrome stain (d)


  • Central scar containing one or more large dystrophic vessels and many small arterioles.


  • Portal-like structures with arteries only, absence of veins or bile ducts.


  • Stromal inflammatory infiltration, cholate stasis, and ductular reaction at the parenchymal-stromal interface.


  • Cytokeratin (CK)7 highlights the prominent ductular reaction.


  • Sinusoids adjacent to arteries are lined by cluster of differentiation (CD)34-positive endothelium .


Differential Diagnosis





  • Normal liver


  • HCA


  • Regenerative nodules


  • Cirrhosis


Bile Duct Adenoma/Hamartoma



Clinical Features





  • Usually multiple small nodules


Cytological Features





  • Hypocellular specimen with increased numbers of benign to mildly atypical bile duct epithelial cells


  • Normal hepatocytes


Histology (Fig. 7.17a, b)





  • Bile duct adenoma is characterized by a proliferation of normal-appearing small bile ducts surrounded by connective tissue with entrapped portal tract forming a nodule or multiple nodules, usually in a subcapsular location. Nuclear atypia, mitosis, and intraluminal bile are usually absent.

    A333337_1_En_7_Fig17_HTML.jpg


    Fig. 7.17
    (a, b) Bile duct adenoma


  • Hamartoma is formed by a proliferation of bile ducts in anastomotic channels containing bile in a fibrotic stroma .


Differential Diagnosis





  • Cirrhosis


  • Focal nodular hyperplasia


  • Cholangiocarcinoma


  • Metastatic well-differentiated adenocarcinoma


Angiomyolipoma (PEComa)



Clinical Features





  • Most common benign tumor of the kidney


Cytological Features (Figs. 7.18 and 7.19)





  • Cluster of spindle cells or epithelioid smooth muscle cells.

    A333337_1_En_7_Fig18_HTML.jpg


    Fig. 7.18
    Angiomyolipoma with spindle cells and fat cells


    A333337_1_En_7_Fig19_HTML.jpg


    Fig. 7.19
    Angiomyolipoma on cellblock section


  • Adipocytes.


  • Thickened wall blood vessels.


  • The ratio of the above three components is variable from one case to another.


  • Extramedullary hematopoiesis.


Histology





  • Smooth muscle proliferation admixed with various proportions of adipose tissue and thick-walled hyalinized blood vessels.


  • Smooth muscle cells can be spindled or epithelioid. The epithelioid cells can have clear or oncocytic cytoplasm.


Immunohistochemistry



  • Positive for smooth muscle actin (SMA), human melanoma black 45 (HMB45 ), and melanoma antigen recognized by T cells-1 (Mart-1)


  • Can be positive for CD117 and desmin


  • Usually negative for S100


Differential Diagnosis





  • HCC


  • RCC


  • Adrenocortical carcinoma


  • Sarcoma


  • Carcinoma


  • Granulomatous inflammation


Hemangioma



Clinical Features





  • The most common benign neoplasm of the liver


  • Reported in up to 20% of autopsy studies


  • More common in young adult females


  • May increase in size or even rupture during pregnancy


Cytological Features (Figs. 7.20, 7.21, and 7.22)





  • Bloody sample with low cellularity and normal hepatocytes in the background

    A333337_1_En_7_Fig20_HTML.jpg


    Fig. 7.20
    Hemangioma with few benign elongated spindle cells


    A333337_1_En_7_Fig21_HTML.jpg


    Fig. 7.21
    Hemangioma with small cluster of three-dimensional coiled elongated spindle cells


    A333337_1_En_7_Fig22_HTML.jpg


    Fig. 7.22
    Tissue section of hemangiom a


  • Scattered, isolated cytologically bland spindle cells


  • Small clusters of three-dimensional coiled elongated spindle cells


Histology





  • Most benign vascular tumors are cavernous hemangioma s.


  • Various-sized blood-filled vascular channels lined by a single layer of flat endothelial cells separated by fibrous septa of various thicknesses.


Differential Diagnosis





  • Spindle cell tumor if a highly cellular sample is obtained


  • Granulomatous inflammation


  • Lymphangioma and lymphangiomatosis


Hepatocellular Carcinoma (HCC)



Clinical Features





  • Over 90% of primary malignant tumors of the liver are HCCs.


  • Can be solitary or multiple nodules or even a diffuse infiltrate.


  • Serum AFP is not a very sensitive or specific marker.


  • Frequently associated with cirrhosis .


  • Fibrolamellar-type HCC is not associated with cirrhosis ; mean age of patients is 23; normal serum AFP .


Cytological Features for Well-Differentiated HCC (Figs. 7.23, 7.24, 7.25, 7.26, 7.27, 7.28, 7.29, 7.30, 7.31, 7.32, 7.33, 7.34, 7.35, 7.36, 7.37, 7.38, 7.39, 7.40, and 7.41a–d)





  • Hypercellular samples with many single cells, thick cores, nets, and sheets.

    A333337_1_En_7_Fig23_HTML.jpg


    Fig. 7.23
    Hypercellular smears of HCC , low power; hypercellular samples with many single cells, thick cores, nets, and sheets


    A333337_1_En_7_Fig24_HTML.jpg


    Fig. 7.24
    Well-differentiated HCC with trabeculae (Diff-Quik)


    A333337_1_En_7_Fig25_HTML.jpg


    Fig. 7.25
    Well-differentiated HCC with trabeculae (Pap stain)


    A333337_1_En_7_Fig26_HTML.jpg


    Fig. 7.26
    Well-differentiated HCC with bile


    A333337_1_En_7_Fig27_HTML.jpg


    Fig. 7.27
    Well-differentiated with high nuclear-to-cytoplasmic ratio (Pap stain)


    A333337_1_En_7_Fig28_HTML.jpg


    Fig. 7.28
    Numerous naked nuclei


    A333337_1_En_7_Fig29_HTML.jpg


    Fig. 7.29
    Well-differentiated with pseudoglandular formation (Pap stain)


    A333337_1_En_7_Fig30_HTML.jpg


    Fig. 7.30
    Tissue with pseudoglands


    A333337_1_En_7_Fig31_HTML.jpg


    Fig. 7.31
    Well-differentiated HCC; CD34 highlighting the trabecular growth pattern


    A333337_1_En_7_Fig32_HTML.jpg


    Fig. 7.32
    Well-differentiated HCC; polyclonal CEA showing canalicular staining pattern


    A333337_1_En_7_Fig33_HTML.jpg


    Fig. 7.33
    (a, b) Well-differentiated HCC on tissue sections


    A333337_1_En_7_Fig34_HTML.jpg


    Fig. 7.34
    Well-differentiated HCC; lack of reticulin stain


    A333337_1_En_7_Fig35_HTML.jpg


    Fig. 7.35
    Well-differentiated HCC; positive for glypican- 3


    A333337_1_En_7_Fig36_HTML.jpg


    Fig. 7.36
    (a–f) Moderately differentiated HCC with pseudoglandular formation on (a) and (b). Note the loss of reticulin in the tumor cells (c), CD34 (d), CD10 (e), and polyclonal CEA (f)


    A333337_1_En_7_Fig37_HTML.jpg


    Fig. 7.37
    Poorly differentiated HCC showing marked nuclear atypia with giant cells, spindle cells, and atypical mitoses and many pleomorphic naked nuclei


    A333337_1_En_7_Fig38_HTML.jpg


    Fig. 7.38
    Poorly differentiated HCC (Pap stain)


    A333337_1_En_7_Fig39_HTML.jpg


    Fig. 7.39
    Poorly differentiated HCC on cellblock


    A333337_1_En_7_Fig40_HTML.jpg


    Fig. 7.40
    AFP positivity on cellblock


    A333337_1_En_7_Fig41_HTML.jpg


    Fig. 7.41
    (a–d) Poorly differentiated HCC on core biopsy specimen (a), CD34 (b), arginase-1 (c), and glypican-3 (d)


  • Hepatocytes more than three cell layers thick wrapped by spindle-shaped endothelial cells are the key to a final diagnosis.


  • Pseudoglandular formation with bile is another diagnostic feature.


  • Many naked, large/pleomorphic nuclei.


  • Hepatocytes with high nuclear-to-cytoplasmic ratio, large nuclei, prominent nuclei, and intranuclear inclusions.


  • Clear cell changes.


  • Steatosis.


  • Fibrolamellar HCC .


Histology





  • Architectural patterns: Trabecular pattern, pseudoglandular or acinar pattern, and compact/solid pattern


  • Cytological variants: Pleomorphic cells, clear cells, fatty changes, spindle cells


Immunohistochemistry and Special Stains



  • Arginase-1 is positive in both benign and neoplastic liver tissues. It is the most sensitive and specific marker available to identify hepatocellular origin when working on tumor of unknown primary.


  • HepPar1 is similar to arginase-1 with a lower specificity. It can be positive in other carcinomas.


  • Glypican- 3 is expressed in fetal liver, reactivated in about 80% of HCCs, including a small HCC and poorly differentiated HCC, and usually negative in normal liver, cirrhosis , benign hepatic lesions, and dysplastic nodules.


  • GS is frequently positive in HCC (defined as positive in >10% of tumor cells).


  • HSP70 is upregulated in HCCs, including early HCC (defined as positive in at least 10% of tumor cells), but usually negative in normal hepatocytes and expressed in bile ducts (as an internal positive control) .


  • Glypican- 3, GS , and HSP70 can serve as a diagnostic panel in the workup of a difficult case.


  • Clusterin has been reported to be overexpressed in HCC.


  • AFP is positive in only about 25% of HCC cases.


  • CD34 highlights neovascular spaces/sinusoidal capillarization; usually no immunoreactivity seen in normal liver and benign hepatic lesions; some immunoreactivity can be seen in the peripheral portion of a cirrhotic nodule.


  • CD10 and polyclonal carcinoembryonic antigen (CEA) show a canalicular staining pattern.


  • Albumin by RNA in situ hybridization .


Differential Diagnosis for Well-Differentiated HCC





  • Regenerative nodules in cirrhosis


  • Focal nodular hyperplasia


  • HCA


Cytological Features for Moderate and Poorly Differentiated HCC





  • Hypercellular samples with many singles, thick cores, nets, and sheets


  • Marked nuclear atypia with giant cells, spindle cells, and atypical mitoses


  • Many pleomorphic naked nuclei


Differential Diagnosis for Moderately and Poorly Differentiated HCC





  • Cholangiocarcinoma


  • Metastatic carcinoma


  • Table 7.2 summarizes some useful markers in the distinction between HCC and IHCC.


    Table 7.2.
    Useful markers in the distinction between HCC and IHCC




























    Marker
    HCC
    IHCC

    CK7

    Negative or focally +
    +

    Arginase-1

    + (90%)
    –

    MOC31

    –
    +

    pVHL

    –
    + (70%)


    Note: MOC31  – EpCAM/epithelial specific antigen


Variants of HCC



Fibrolamellar Variant (Figs. 7.42, 7.43, 7.44, and 7.45)






  • Accounts for 0.5–9.0% of HCCs in various studies.

    A333337_1_En_7_Fig42_HTML.jpg


    Fig. 7.42
    Fibrolamellar HCC


    A333337_1_En_7_Fig43_HTML.jpg


    Fig. 7.43
    Fibrolamellar HCC – intracytoplasmic pale body


    A333337_1_En_7_Fig44_HTML.jpg


    Fig. 7.44
    Fibrolamellar HCC – intranuclear inclusion


    A333337_1_En_7_Fig45_HTML.jpg


    Fig. 7.45
    Fibrolamellar HCC tissue section


  • More common in North America and European countries.


  • Most frequently occurs in patients aged 35 years or younger with a peak at age 25.


  • Non-cirrhotic background.


  • Central scar in radiologic finding and gross examination.


  • Nests and bands of large polygonal tumor cells with abundant, granular oncocytic cytoplasm, large vesicular nuclei, and prominent nucleoli, in a distinctive lamellar fibrotic background.


  • Pseudoglandular formation and cytoplasmic “pale bodies” or “hyaline bodies” can be seen.


  • CK7 is frequently positive.


  • Better prognosis than typical HCC .


Scirrhous HCC






  • Accounts for 5% of HCCs.


  • Marked fibrotic background, sinusoid-like blood space, and atrophic tumor trabeculae.


  • Better prognosis than typical HCCs has been reported.


Clear Cell HCC and Sarcomatoid HCC






  • Clear cell HCC (Figs. 7.46a, b, 7.47, and 7.48)

    A333337_1_En_7_Fig46_HTML.jpg


    Fig. 7.46
    (a, b) Clear cell HCC on the smear (a, DQ; and b, Pap stain)


    A333337_1_En_7_Fig47_HTML.jpg


    Fig. 7.47
    Clear cell HCC on small core biopsy


    A333337_1_En_7_Fig48_HTML.jpg


    Fig. 7.48
    Clear cell HCC positive for arginase-1


Lymphoepithelioma-Like Carcinoma






  • A very rare type of HCC


  • Epstein-Barr virus (EBV)-positive


Intrahepatic Cholangiocarcinoma (IHCC)



Clinical Features





  • Second most common primary malignant tumor of the liver


  • Accounting for 5–15% in various study series


  • Arising from any portion of intrahepatic biliary tree except the right and left hepatic ducts (usually referred to as hilar cholangiocarcinoma or “Klatskin tumor”)


  • May be associated with sclerosing cholangitis, inflammatory bowel disease, Caroli disease, parasitic infection, hepatolithiasis, non-biliary cirrhosis including hepatitis C, alcoholic liver disease, human immunodeficiency virus (HIV), and diabetic mellitus


  • Radiologic findings similar to HCC


Cytological Features (Fig. 7.49a, b)





  • Single and crowded groups of atypical epithelial cells

    A333337_1_En_7_Fig49_HTML.jpg


    Fig. 7.49
    (a, b) Cholangiocarcinoma  – single and crowded groups of atypical epithelial cell nuclear enlargement, loss of nuclear polarity, and variation in nuclear sizes


  • Nuclear enlargement, loss of nuclear polarity, and variation in nuclear sizes


  • Nuclear contour irregularities, high nuclear-to-cytoplasmic ratio, and mitoses

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Jan 30, 2018 | Posted by in PATHOLOGY & LABORATORY MEDICINE | Comments Off on Liver

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