Normal Morphology

Aspirate smears of normal liver typically show a polymorphous cell population dominated by hepatocyte s, occurring singly in short rows or small clusters and intermingling with scattered bile duct epithelial cells and sparse sinusoidal endothelial cells and Kupffer cells ( Fig. 45.1, A ). Normal hepatocytes are large, polygonal cells with abundant granular cytoplasm and a centrally placed, round nucleus with a well-delineated nuclear membrane, granular chromatin pattern, and distinct nucleolus. Hepatocytes normally exhibit variations in cell and nuclear size (i.e., sibling polymorphism). The nucleus-to-cytoplasm ratio (N : C ratio) is approximately 1 : 3. Bile duct epithelial cells are smaller than hepatocytes and appear as flat, monolayered, honeycomb sheets of glandular epithelium (see Fig. 45.1, B ). They may also reveal an on-edge picket-fence arrangement or small acinar structures. The cells have minimal pale cytoplasm and equidistant, round to oval, bland nuclei without nucleoli. Bile duct epithelium can be differentiated from bile ductular epithelium.

Normal hepatocytes and bile duct epithelium. A, The polygonal hepatocytes occur in narrow cords and exhibit mild polymorphism with ample granular cytoplasm; a central, round nucleus; well-delineated nuclear membrane; granular chromatin; and a distinct nucleolus. The nucleus-to-cytoplasm ratio is about 1 : 3. The small bile duct epithelial cluster consists of uniform cells with oval nuclei and indistinct cytoplasm (Papanicolaou stain). B, Bile duct epithelium from a larger duct displays a flat, monolayered, honeycomb sheet of glandular cells with nuclear palisading. The cells have minimal, pale cytoplasm and evenly spaced, regular, oval, bland nuclei without nucleoli (Papanicolaou stain).

Elongated endothelial cells and comma-shaped Kupffer cells are almost indistinguishable from each other, especially when they appear as nuclear streaks. The thickness of liver cords can be appreciated in large sheets of cells and in fragments of liver parenchyma by focusing on the nuclear streaks in different planes of magnification ( Fig. 45.2 ).

Normal liver parenchyma. A, Fragment of liver parenchyma with jagged edges shows narrow cords of hepatocytes, nuclear streaks, and a portal tract (Papanicolaou stain). B, Nuclear streaks represent Kupffer or endothelial cells sandwiched between hepatocytes and highlighting the narrow width of the cell cords (Papanicolaou stain).

Pigments

Lipofuscin is a fine, golden, granular, relatively nonrefractile pigment with Papanicolaou stain and is black with Giemsa stain ( Fig. 45.3 ). This predominantly perinuclear pigment is common in aspirates of adult livers, and its absence in the context of a mass lesion is considered suspicious for a hepatocellular neoplasm. One potential diagnostic pitfall is that lipofuscin stains similar to melanin with Fontana-Masson stain, and the sample may be mistaken for metastatic melanoma.

Lipofuscin pigment appears as nonrefractile, black granules located in the perinuclear cytoplasm of non-neoplastic hepatocytes (May-Grünwald-Giemsa stain).

Bile pigment varies in color, texture, size, and density, but it is best recognized by its coarse, irregular, rather amorphous, nonrefractile appearance. In Giemsa-stained preparations, bile appears as a purplish-black pigment within the cytoplasm of hepatocytes or as ropey strands within bile canaliculi ( Fig. 45.4 ). Hall stain may be used to confirm the pigment as bile.

Bile pigment is seen as purplish-black, ropey strands within bile canaliculi and a few black droplets within the cytoplasm of non-neoplastic hepatocytes in a patient with cholestasis (May-Grünwald-Giemsa stain).

Iron or hemosiderin may be present in hepatocytes, bile duct epithelial cells, and Kupffer cells as a coarse, golden-brown, refractile pigment with the Papanicolaou stain and brown-black with the Giemsa stain ( Fig. 45.5 ). Malignant hepatocytes typically lose their ability to retain iron. In the setting of hemochromatosis, Perl (Prussian blue) stain is a helpful ancillary tool to highlight nonstaining tumor cells.

Hemosiderin (iron) pigment appears as coarse, golden-brown, refractile granules within the cytoplasm of non-neoplastic hepatocytes (Papanicolaou stain).

Steatosis

Steatosis is common in the liver, and the examiner should be aware of focal fatty changes. Cytologically, fat may be a single, large, intracytoplasmic vacuole in a cell with an eccentric nucleus (i.e., macrovesicular steatosis) or multiple, small vacuoles in a cell with a central nucleus (i.e., microvesicular steatosis) ( Fig. 45.6 ). Fat is best appreciated in Giemsa-stained preparations, which often reveal abundant oil globules in the background as a result of ruptured hepatocytes.

Macrovesicular steatosis. Non-neoplastic hepatocytes show large, intracytoplasmic fat vacuoles pushing the nucleus to one side of the cell cytoplasm (Papanicolaou stain).

Infections

Liver abscess formations are suspected radiologically by the characteristic double target sign on CT scans. The most common is pyogenic abscess, in which case aspiration is performed for tissue confirmation, culture, and drainage. Smears are dominated by acute inflammatory cells and cellular debris ( Fig. 45.7 ). Cultures are helpful for identification of bacterial organisms. Special stains, such as Gram stain, are not usually helpful, but uniquely characteristic organisms may be readily identified on smears. For example, Actinomyces has sulfur granules ( Fig. 45.8 ).

Pyogenic abscess. Abundant neutrophils and cellular debris show golden-brown bile pigment (Papanicolaou stain).

Abscess caused by Actinomyces . The fibrillar, star-shaped sulfur granules are characteristic of this organism (Papanicolaou stain).

Smears from suspected fungal abscesses should be stained with Gomori methenamine silver and periodic acid–Schiff (PAS) stains. Amebic abscesses tend to be paucicellular with abundant amorphous granular debris, and trophozoites are rare. Necrotizing eosinophilic granulomas contain abundant eosinophils and possibly Charcot-Leyden crystals. Parasitic or fungal organisms should be sought ( Fig. 45.9 ).

Necrotizing eosinophilic granuloma. Neutrophils, eosinophils, and Charcot-Leyden crystals are evident (May-Grünwald-Giemsa stain).

A potential diagnostic pitfall is that necrotic tumors may be associated with fever, simulating abscesses clinically and radiologically; or they may become secondarily infected. If clinically warranted, aspiration cytology is recommended to avoid delay in instituting appropriate therapy.

Hydatid disease leads to cyst formation, which may become secondarily infected (see “ Cystic Lesions of the Liver ”). Echinococcosis is usually ruled out with clinical and imaging studies and the findings of a negative test result for specific echinococcal antibodies by serum enzyme immunosorbent assay performed before percutaneous needle aspiration. In the event that a hydatid cyst is aspirated, the pathologist should search for protoscolices or hooklets of Echinococcus granulosus in the fluid or pus ( Fig. 45.10 ).

Hydatid cyst. The fluid contains single refractile hooklets or, rarely, intact echinococcal protoscolices (May-Grünwald-Giemsa stain).

Granulomatous inflammation may be caused by fungal or acid-fast organisms, but the presence of granulomas is not necessarily diagnostic of an infection. Cytologically, granulomas are composed of clusters of epithelioid histiocytes that have oval to elongated, sometimes twisted nuclei and visible but indistinct cytoplasm. Multinucleated giant cells may be present ( Fig. 45.11 ). The characteristics of the necrotic background should also be evaluated. Gomori methenamine silver, PAS, and Ziehl-Neelsen stains may be performed on smears but are easier to perform on tissue sections.

Tuberculous granuloma. A multinucleated Langhans giant cell has a horseshoe-shaped arrangement of the nuclei (May-Grünwald-Giemsa stain).

Inflammatory pseudotumors are potential clinical, radiologic, and cytohistologic pitfalls because they mimic tumors. They may be lymphoplasmacytic, fibrohistiocytic, xanthogranulomatous, or granulomatous in nature ( Fig. 45.12 ). Activated lymphoid cells may be mistaken for lymphomas, atypical reactive hepatocytes for HCC, atypical reactive biliary epithelium for adenocarcinoma, atypical reactive stroma for sarcoma, and foamy histiocytes for amebic trophozoites. Immunoglobulin G4 (IgG4)–related disease may rarely manifest as a fibroblastic mass with lymphoplasmacytic infiltrates, eosinophils, IgG4-positive plasma cells, dense fibrosis of large bile ducts, and obliterative phlebitis.

Lymphoplasmacytic-type inflammatory pseudotumor. A, Aspirate smears are dominated by lymphocytes and plasma cells, with occasional spindle-shaped fibroblasts and multinucleated foreign body giant cells (Papanicolaou stain). B, Cell block shows a heavy lymphoplasmacytic infiltrate with a granulation tissue background (hematoxylin and eosin stain).

Nodular hematopoiesis is a rare diagnostic pitfall. Hematopoietic cells (especially megakaryocytes) may mimic inflammatory or malignant cells when perceived out of context.

Bile Duct Cyst, Simple Hepatic Cyst, and Fibropolycystic Disease

In cases of bile duct cyst, simple hepatic cyst, and fibropolycystic disease, the fluid may contain isolated cells or scant strips or sheets of cuboidal to low columnar epithelium without cytologic atypia ( Fig. 45.13 ).

Solitary bile duct cyst. Flat honeycomb sheet of cuboidal epithelium with no cytologic atypia (Papanicolaou stain).

Ciliated Foregut Cyst

Aspirates of foregut cysts are characterized by ciliated columnar cells and detached ciliated tufts. The background usually contains amorphous debris and rare macrophages. The differential diagnosis includes cystic neoplasms.

Mucinous Cystic Neoplasm and Intraductal Papillary Neoplasm

Mucinous cystic neoplasms and intraductal papillary neoplasms have overlapping cytomorphologic features. The cytodiagnosis may indicate a benign cyst, papillary neoplasm, or adenocarcinoma. FNAB alone cannot differentiate the various types of hepatobiliary cysts. Generic terms such as cystic mucinous neoplasm or neoplastic mucinous cyst may be applied if imaging studies are not available for correlation.

Mucinous cystic neoplasms typically occur as single or multiloculated, mucinous, epithelial-lined cysts surrounded by ovarian-type stroma. The cyst fluid may be watery or viscous. Diagnostic aspirates likely contain degenerated cuboidal to columnar epithelial cells with bland nuclear features ( Fig. 45.14 ). The neoplastic epithelial cells may be arranged singly, on edge, in sheets, or as small papillary tufts. The background usually shows mucin with chronic inflammatory cells, histiocytes, and debris. The degree of cellularity varies and tends to increase with higher grades of intraepithelial neoplasia. Stromal components are not usually present. With malignant transformation, features of adenocarcinoma with or without mucin and cellular debris are often evident. The definitive diagnosis requires correlation with clinical information, imaging studies, and histopathologic confirmation of ovarian-type stroma surrounding the cyst. The cyst fluid may be assayed for carcinoembryonic antigen and CA 19-9 to distinguish neoplastic from non-neoplastic liver cysts ( Box 45.8 ).

Mucinous cystic neoplasm. Mucinous glandular epithelium and foamy histiocytes predominate the contents of this benign hepatic cyst (cell block, hematoxylin and eosin stain).

(From Sidawy MK, Syed ZA. The Liver in Fine Needle Aspiration Cytology: A Volume in the Foundations in Diagnostic Pathology . Edinburgh: Churchill Livingstone; 2007.)

Biliary intraductal papillary neoplasm is a fusiform or cystic (unilocular or multilocular) luminal dilation in communication with the biliary tract. The affected intrahepatic bile ducts are typically filled with a noninvasive papillary or villous biliary neoplasm covering delicate fibrovascular stalks, and mucin may be seen. Aspirates are typically hypercellular, comprising broad and often double-layered sheets of ductal cuboidal or columnar epithelium with a distinctive three-dimensional, complex-branching papillary configuration ( Fig. 45.15 ). The sheets of cells do not form a honeycomb pattern but are crowded. Phenotypes include pancreaticobiliary, intestinal, gastric, and oncocytic forms. The epithelium shows intracytoplasmic mucin vacuoles and occasional signet ring cells. The nuclei show variable abnormalities. Psammoma bodies may be identified. Intraductal papillary neoplasm with associated invasive carcinoma has the highest degree of cellularity and pleomorphism ( Box 45.9 ).

Biliary intraductal papillary neoplasm. A, Delicate, branching, finger-like fibrovascular stalks are lined by three-dimensional, double-layered (crowded) sheets of cuboidal epithelium (Papanicolaou stain). B, Histologic section shows a complex branching papillary tumor, which would have been located within a cystically dilated duct (hematoxylin and eosin stain).

Metastases

Metastatic papillary carcinomas of the pancreas and ovary can simulate intraductal papillary neoplasms. Smears may contain numerous finger-like fibrovascular stalks lined by cuboidal or columnar epithelium with cytologic atypia.

Non-neoplastic Cysts

Aspirates of non-neoplastic cysts typically reveal an abundant amount of turbid, brown fluid with inflammatory cells, macrophages, fibrin, debris, and bile or hematoidin pigment. The fluid lacks lining epithelial cells but may contain benign cells from surrounding liver parenchyma. The differential diagnosis includes inflammatory/infectious cysts, cystic hematomas, as well as true cysts and cystic neoplasms. Secondary bacterial infection may produce cyst fluid that contains abundant neutrophils and proteinaceous background debris. However, the presence of a neoplastic lining epithelium or background mucin excludes the diagnosis of a non-neoplastic cyst.

Neoplastic Cysts and Tumor-like Lesions

Cavernous Hemangioma

Cavernous hemangiomas are usually asymptomatic, and they are usually diagnosed incidentally during the workup for other conditions, such as during the process of staging a malignancy, and they can be difficult to distinguish from metastasis radiologically. Hemorrhagic aspirates are often considered unsatisfactory. The nondiagnostic appearance of blood with loose rather than dense fibrous connective tissue and few or no background hepatocytes raises the possibility of a hemangioma in the proper clinical setting ( Fig 45.16 ). Histologic material is crucial in establishing a specific diagnosis ( Box 45.10 ).

Cavernous hemangioma. A, Scanty clumps of loose fibrous connective tissue are seen in the blood (May-Grünwald-Giemsa stain). B, Histologic section shows large, irregular, interconnecting endothelial-lined vascular spaces separated by loose connective tissue septa (hematoxylin and eosin stain).

Box 45.10

Cavernous Hemangioma

• •
  

  Bloody with scant cellularity on smears

  
  
• •
  

  Loose connective tissue; usually few to no hepatocytes

  
  
• •
  

  Smears commonly nondiagnostic; specific diagnosis depends more on cell block pattern

Mesenchymal Hamartoma

Aspirates of mesenchymal hamartomas are obtained mainly in the pediatric population, with rare exceptions, and usually show clusters of epithelial and mesenchymal or spindle-shaped cells with bland-appearing nuclei admixed with loose connective tissue ( Fig 45.17 ). However, aspiration cytology rarely enables a definitive diagnosis, and because hepatoblastomas or malignant mesenchymal tumors are difficult to exclude confidently, cytology is of limited value ( Box 45.11 ).

Mesenchymal hamartoma. A, Clusters of epithelial and spindle-shaped mesenchymal cells with bland nuclei are held together by myxoid matrix material (May-Grünwald-Giemsa stain). B, Histologic section shows lobulated islands of loose myxoid matrix containing misshapen ductal structures and mesenchymal cells (Masson trichrome stain).

Box 45.11

Mesenchymal Hamartoma

• •
  

  Hypocellular smears

  
  
• •
  

  Spindle-shaped cells with bland nuclei

  
  
• •
  

  Loose myxoid matrix with bile ductlike epithelial clusters

  
  
• •
  

  Cytology of limited value in establishing a definitive diagnosis

Undifferentiated Embryonal Sarcoma

Although most undifferentiated embryonal sarcomas appear ultrasonographically as solid lesions, CT and MRI imaging may detect a low-attenuation mass with a cystic appearance. Most cystic structures result from liquefactive necrosis and blood clots; however, true cystic spaces may also occur. Aspirates recapitulate the histologic pattern of the tumor. Smears are usually composed of spindle cells and myxoid tissue, intermixed with pleomorphic cells ranging from small round cells to larger multinucleated giant cells. Giant cells have bizarre nuclei and massively deranged chromatin structure. They contain intracytoplasmic vacuoles and are AFP negative, PAS positive, but diastase-resistant hyaline globules ( Fig. 45.18 ); extracellular globules may also be present. Immunostaining for α ₁ -antitrypsin, α ₁ -antichymotrypsin, and carcinoembryonic antigen is positive in tumor cells. The cytologic differential diagnoses include rhabdomyosarcoma , hepatoblastoma, undifferentiated pleomorphic sarcoma, NOS (so-called malignant fibrous histiocytoma), and poorly differentiated HCC ( Box 45.12 ).

Undifferentiated embryonal sarcoma. A, Smears are composed of anaplastic and multinucleated tumor giant cells displaying bizarre nuclei and a deranged chromatin structure (Papanicolaou stain). B, Tumor cells may also contain periodic acid–Schiff (PAS)–positive, diastase-resistant intracytoplasmic globules (PAS with diastase digestion).

Box 45.12

Undifferentiated Embryonal Sarcoma

• •
  

  Hypercellular smears

  
  
• •
  

  Large, pleomorphic anaplastic cells with multinucleated giant cells and atypical spindle cells

  
  
• •
  

  Intracytoplasmic globules: periodic acid–Schiff positive, diastase resistant

Benign Hepatocellular Nodules

Benign hepatocellular nodules, which can be non-neoplastic or neoplastic, such as focal fatty changes, large regenerative nodules, dysplastic nodules, focal nodular hyperplasia, and hepatocellular adenomas, are discussed together because they share common cytologic features, including fatty changes ( Box 45.13 ). Unfortunately, it is not always possible to distinguish these entities on the basis of smear cytology alone. They all can mimic well-differentiated HCC.

A focal fatty change may simulate a mass lesion radiologically. Aspirates are composed of a polymorphous population of enlarged, fat-laden, non-neoplastic hepatocytes intermingled with bile duct epithelial clusters. Oil globules may be seen in the background on air-dried smears.

Aspirates from large regenerative nodules are similar to those from cirrhosis, in which a polymorphous liver parenchymal population shows evidence of hyperplasia and hepatocellular-interface restoration (i.e., bile ductular epithelium and stromal fragments). Hyperplastic hepatocytes occur in two-cell-thick cords and exhibit slight polymorphism and binucleated forms. Normal bile duct epithelial clusters should be differentiated from bile ductular epithelial cells, which appear as curved, narrow, double-stranded rows of cells with overlapping, dark, oval nuclei; scant or absent cytoplasm; and a high N : C ratio. Nuclear disarray may be disconcerting. Ductules can be seen emanating from the jagged edges of sizeable parenchymal fragments ( Fig. 45.19 ). Stroma may be seen in the background. The presence of ductules should raise the diagnostic threshold for a malignant process.

Large regenerative nodule. Reactive hepatocytes in irregularly shaped clusters are associated with a curved bile ductule emanating from the hepatocellular-stromal interface. The ductule consists of a double row of closely apposed, overlapping, small, darkly stained, oval nuclei with absent cytoplasm (May-Grünwald-Giemsa stain).

Hepatocellular atypia, such as large cell and small cell changes (e.g., dysplasia), are considered neoplastic precursor lesions and may be detected in aspirates from cirrhotic livers. Hepatocytes with large cell changes show corresponding cellular and nuclear enlargement and mild nuclear atypia; but the normal N : C ratio (i.e., one to three or less) is maintained ( Fig. 45.20 ). Hepatocytes with small cell changes are small and monotonous, with a subtle increase in the N : C ratio. The nuclear size is similar to that of normal hepatocytes, but there is less cytoplasm, imparting an impression of nuclear crowding ( Fig. 45.21 ).

Hepatocytes with large cell changes. There is cell and nuclear enlargement. The nucleus-to-cytoplasm ratio is maintained at about 1 : 3. Compare with normal hepatocytes in the bottom right side of the image (May-Grünwald-Giemsa stain).

Hepatocytes with small cell changes. Monotonous, small hepatocytes exhibit decreased cytoplasm, an increased nucleus to cytoplasm ratio, and an impression of nuclear crowding. Compare with two clusters of normal hepatocytes in the vicinity (Papanicolaou stain).

Aspirates of low-grade dysplastic nodules show hepatocytes that exhibit large cell changes, whereas those from high-grade dysplastic nodules show hepatocytes with small cell changes. Dysplastic hepatocytes tend to occur singly or in narrow cords, usually one to two cells thick. Transgressing endothelium is not a feature. It is almost impossible to distinguish a small cell change from a well-differentiated or early HCC. The key to recognizing a large cell change as benign is the sporadic placement of these cells in a background of otherwise reactive-appearing hepatocytes and accompanied by bile ductal or ductular epithelium and stroma. Availability of histologic material for immunohistochemistry is invaluable.

Patients with cirrhosis without iron overload can accumulate iron within regenerative or dysplastic nodules, which are called siderotic nodules . Siderotic dysplastic nodules are considered to be premalignant, whereas siderotic regenerative nodules are a marker for severe viral or alcoholic cirrhosis. Iron-free foci in patients with genetic hemochromatosis are likely to be malignant.

Focal nodular hyperplasia is characterized by a proliferation of hepatocytes surrounding a central scar containing blood vessels and bile ducts. A brisk ductular reaction is often seen at the hepatocellular-stromal interface. Aspirates typically contain a polymorphous population of cells, but this varies. Hyperplastic hepatocytes abound in one- to two-cell-thick cords. Bile duct epithelium is usually evident ( Fig. 45.22 ). The presence of ductular epithelium supports the benign nature of this lesion, but this feature can be mistaken for adenocarcinoma if it is the dominant component of the aspirate. A possible diagnostic pitfall is mistaking reactive stroma for a spindle cell neoplasm. A characteristic geographic immunostaining pattern is seen with the use of glutamine synthetase. Without radiologic demonstration of a central scar, it may not be possible to differentiate focal nodular hyperplasia from large regenerative nodules on smear cytology, because both show features of regeneration.

Focal nodular hyperplasia. A, Hyperplastic hepatocytes are present with ductules, which are represented by small, darkly stained, oval nuclei, emanating from the hepatocellular-stromal interface (Papanicolaou stain). B, Histologic section shows a brisk ductular reaction at the hepatocellular-stromal interface from the edge of a central scar (hematoxylin and eosin stain).

Aspirates of a hepatocellular adenoma are hypercellular and typically contain well-differentiated hepatocytes occurring in one- to two-cell-thick cords ( Fig. 45.23 ). There is no significant atypia. Transgressing endothelium is common, but peripheral endothelium is lacking. The tumor cells are polygonal and have moderate granular cytoplasm. Some cells display fatty or clear cell changes and bile or lipofuscin pigment. Bile duct epithelium is absent. The reticulin framework is usually well preserved. CD34, which highlights capillarization of the sinusoids in HCC, can also positively stain adenomas, particularly in the periseptal areas. This may be a diagnostic pitfall in assessing small, fragmented liver core specimens and cell block preparations. Glypican 3 staining should be focal and weak at best. The diagnosis requires clinical correlation. Chapter 55 provides more information on immunohistochemical markers of adenomas in tissue sections.

Hepatocellular adenoma. The hypercellular smear contains narrow cords (as many as three cells thick) of hepatocytes displaying mild sibling polymorphism but without significant cytologic atypia (Papanicolaou stain).

A nodule-in-nodule lesion occurs when an HCC subnodule develops within a parent dysplastic or regenerative nodule. Representative FNAB samples may be a problem because of the focality of proliferative clones within these nodules. Classic aspirates reveal more than one population of lesional hepatocytes, including malignant hepatocytes and dysplastic or hyperplastic hepatocytes in the background ( Fig. 45.24 ). The presence of biliary epithelial cells varies.

The nodule-in-nodule lesion is composed of a well-differentiated hepatocellular carcinoma arising within a large regenerative nodule. Notice the two populations of hepatocytes. Well-defined malignant hepatocytes from the subnodule exhibit mild pleomorphism, dense cytoplasm, and an increased nucleus-to-cytoplasm ratio. They are located among pale, hyperplastic hepatocytes with a normal nucleus-to-cytoplasm ratio from the parent nodule (Papanicolaou stain).

Hepatocellular Carcinoma

HCCs exhibit marked heterogeneity in differentiation, histologic patterns (i.e., trabecular-sinusoidal, pseudoacinar, and solid types), and cell morphology. The World Health Organization (WHO) classification of HCC lists the classic type, several variants, and special types. Sampling limitations of the FNAB technique and cytohistologic challenges in the face of this diversity are recognized. Most tumors show relatively good hepatic preservation and obvious malignant features. However, diagnostic dilemmas exist at both ends of the spectrum—cytologic features of malignancy are lacking at the well-differentiated end and resemblance to hepatocytes is lacking at the poorly differentiated end. The cytomorphologic features of HCC are summarized in Box 45.14 . The cytologic nuclear grading of HCC into well-, moderately, and poorly differentiated is outlined in Boxes 45.15 through 45.17 .

Box 45.16

Well-Differentiated Hepatocellular Carcinoma

• •
  

  On low-power microscopy, the smear pattern shows trails of smooth-edged, arborizing clusters of thickened trabeculae with peripheral endothelium (pathognomonic)

  
  
• •
  

  On low power, the smear pattern shows many loosely cohesive sheets of hepatocytes with transgressing vessels (highly suspect finding)

  
  
• •
  

  Monotonous, uniform hepatocytic cell population with subtle malignant features

  
  
• •
  

  Pseudoacinar formation in cell clusters

  
  
• •
  

  Nucleus-to-cytoplasm ratio higher than in normal hepatocytes (>1 to 3)

  
  
• •
  

  Macroeosinophilic nucleoli

  
  
• •
  

  Reduced number of binucleated cells

  
  
• •
  

  Background free of bile duct epithelial cells

  
  
• •
  

  Reticulin stain demonstrates loss of the normal one- to two-cell-thick hepatic cord architecture

  
  
• •
  

  Iron stain fails to stain tumor cells in hemochromatosis

  
  
• •
  

  α-Fetoprotein is helpful if positive but often is not

  
  
• •
  

  Novel markers, such as glypican 3, glutamine synthetase, and heat shock protein 70, are helpful if two of three show positivity

Only gold members can continue reading. Log In or Register to continue

Share this:

• Click to share on Twitter (Opens in new window)
• Click to share on Facebook (Opens in new window)

Related posts:

Systemic Illnesses Involving the Gastrointestinal Tract Polyps of the Esophagus Epithelial Neoplasms of the Stomach Epithelial Neoplasms of the Large Intestine Mesenchymal Tumors of the Gastrointestinal Tract Fatty Liver Disease

Stay updated, free articles. Join our Telegram channel

Join