Fine needle aspiration biopsy of the liver: Algorithmic approach and current issues in the diagnosis of hepatocellular carcinoma

Abstract

The role of fine needle aspiration biopsy (FNAB) in the evaluation of focal liver lesions has evolved. Guided FNAB is still useful to procure a tissue diagnosis if clinical, biochemical and radiologic findings are inconclusive. Major diagnostic issues include: (i) Distinction of benign hepatocellular nodular lesions from reactive hepatocytes, (ii) Distinction of well-differentiated hepatocellular carcinoma (WD-HCC) from benign hepatocellular nodular lesions, (iii) Distinction of poorly differentiated HCC from cholangiocarcinoma and metastatic carcinomas, (iv) Determination of histogenesis of malignant tumor, and (v) Determination of primary site of origin of malignant tumor. This review gives a general overview of hepatic FNAB; outlines an algorithmic approach to cytodiagnosis with emphasis on HCC, its variants and their mimics; and addresses current diagnostic issues. Close radiologic surveillance of high-risk cirrhotic patients has resulted in the increasing detection of smaller lesions with many subjected to biopsy for tissue characterization. The need for tissue confirmation in clinically obvious HCC is questioned due to risk of malignant seeding. When a biopsy is indicated, core needle biopsy is favored over FNAB. The inherent difficulty of distinguishing small/early HCC from benign hepatocellular nodular lesions has resulted in indeterminate reports. Changing concepts in the understanding of the biological behavior and morphologic evolution of HCC and its precursors; and the current lack of agreement on the morphologic criteria for distinguishing high-grade dysplastic lesions (with small cell change) from WD-HCC, have profound impact on nomenclature, cytohistologic interpretation and management. Optimization of hepatic FNAB to enhance the yield and accuracy of diagnoses requires close clinicopathologic correlation; combined cytohistologic approach; judicious use of ancillary tests; and skilled healthcare teams.

Figure 1

Normal and reactive hepatocytes: FNAB. Monolayered clusters of loosely-cohesive, well-defined, polygonal cells with ample dense, granular cytoplasm, round central nuclei and low nuclear-cytoplasmic ratio. Note the double-layered row of ductular epithelial cells with scanty cytoplasm (May-Grunwald-Giemsa).

Figure 2

Normal and reactive hepatocytes: FNAB. (A) Hepatocytes show dense granular cytoplasm, round central nuclei, well-delineated nuclear membrane, distinct nucleoli, granular chromatin and binucleation. Note polymorphism displayed by nonneoplastic hepatocytes. The cells contain brown granules of lipofuscin pigment in the cytoplasm (Papanicolaou). (B) Lipofuscin appears as black granules. The two elongated nuclei are likely to be Kupffer cells (May-Grunwald-Giemsa).

Figure 3

Hepatocytes with large cell change: FNAB. There is simultaneous nuclear and cell enlargement of the hepatocytes, thus maintaining the nuclear-cytoplasmic ratio of 1/3. Note mild nuclear atypia (Papanicolaou).

Figure 4

Naked eye inspection of hepatic aspirate. Uniformly granular pattern of spread of classic hepatocellular carcinoma. Note the regularly irregular tumor fragments which tend to be equidistant (Papanicolaou).

Figure 5

Well-differentiated hepatocellular carcinoma with trabecular and pseudoacinar patterns: FNAB. (A) Thick arborizing cords of malignant hepatocytes showing cellular monotony, increased nuclear-cytoplasmic ratio, and impression of nuclear crowding. The circular spaces among the cords represent pseudoacini (Papanicolaou). (B) Corresponding histologic section of the tumor shows trabecular-sinusoidal arrangement with pseudoacini. Note the uniformity of the tumor cells and cords 2 to 3 cells thick (H&E).

Figure 6

Moderately differentiated hepatocellular carcinoma: FNAB. Thick cords of malignant hepatocytes are wrapped by peripheral endothelium. They appear to be floating on transverse section view (Papanicolaou).

Figure 7

Moderately differentiated hepatocellular carcinoma with pseudoacinar pattern: FNAB. (A) Pseudoacini filled with bile which appears as dark brown blobs (Papanicolaou) (B) Bile appears black (May-Grunwald-Giemsa). (C) Corresponding histologic section of the tumor shows cystically dilated canaliculi filled with golden-brown bile and surrounded by polygonal cells with central nuclei (H&E).

Figure 8

Poorly differentiated hepatocellular carcinoma: FNAB. High-grade tumor shows marked pleomorphism but still retaining some hepatocytic characteristics (Papanicolaou).

Figure 9

Poorly differentiated hepatocellular carcinoma: FNAB. Atypical naked hepatocytic nuclei exhibit pleomorphism, thin nuclear membrane, nuclear contour irregularities, prominent nucleoli and multinucleation (Papanicolaou).

Figure 10

Fatty change: FNAB. Hepatocytes exhibit polymorphism and contain cytoplasmic fat vacuoles of varying sizes pushing nucleus to one side. Cytologic picture can mimic signet-ring cell adenocarcinoma (Papanicolaou).

Figure 11

Hepatocellular carcinoma: FNAB. The tumor cells stain positively for alpha-fetoprotein (Immunostain).

Figure 12

Hepatocellular carcinoma: Histology. Parts of the tumor show intense granular cytoplasmic reactivity with HepPar1 (Immunostain).