Cutaneous metastasis of hepatocellular carcinoma diagnosed by fine needle aspiration cytology and Hep Par 1 immunopositivity

Abstract

Cutaneous metastasis of hepatocellular carcinoma (HCC) is very rare, accounting for less than 0.8% of all known cutaneous metastases and occurring in 2.7-3.4% of HCCs. With less than 50 such cases reported worldwide, most of which were diagnosed histologically on excised lesions, it can only be expected that diagnosis made on cytological features alone would be challenging. We report a case of cutaneous metastasis of HCC diagnosed based on cytological features and confirmed by Hep Par 1 immunopositivity of the cell block material. An 81-year-old man, who was known to have unresectable HCC, presented with a 1-month history of painless, left nasal alae mass. The mass measured 1.5 cm in diameter, and was multilobulated with a central necrosis. Fine needle aspiration of the mass was done. Smears were cellular, comprising of malignant cells in loose clusters and aggregates as well as singly dispersed. The malignant cells displayed moderate nuclear pleomorphism, occasional prominent nucleoli, and intranuclear pseudoinclusion. Cell block material demonstrated the trabeculae pattern of the malignant cells and Hep Par 1 immunopositivity. The final diagnosis of a metastatic cutaneous HCC was made. In conclusion, cutaneous HCC metastasis is rare and should be considered in the differential diagnosis in patients with a history of HCC presenting with suspicious skin lesion. In the right clinical setting, a confident diagnosis can be made in such cases by using the fine needle aspiration technique aided with immunopositivity for Hep Par 1 antibody of the aspirated material.

Cutaneous Metastases from Primary Liver Cancers: The Need for Knowledge and Differential Diagnosis

“…In fact, although the metastasis may have histological characteristics that lead to suspicion (bundles of hepatocyte-like cells with a solid-trabecular pattern, with pleomorphic nuclei and evident nucleoli), immunohistochemical investigations constitute a fundamental step to disentangle the various differential diagnoses. Among these, Hepar-1 constitutes a reference point, with a sensitivity and specificity index that is 82% to 95% [5], but in recent years Arginase-1 (Arg-1) and Glypicane-3 (Gly-3+) have also acquired a certain role [6]. Isa et al [5] describe in detail that to be considered effectively positive, the immunohistochemical staining must be strong, cytoplasmic, and granular in spite of a small part of malignant neoplasms that can focal, in an aberrant sense, express it.…”

“…Among these, Hepar-1 constitutes a reference point, with a sensitivity and specificity index that is 82% to 95% [5], but in recent years Arginase-1 (Arg-1) and Glypicane-3 (Gly-3+) have also acquired a certain role [6]. Isa et al [5] describe in detail that to be considered effectively positive, the immunohistochemical staining must be strong, cytoplasmic, and granular in spite of a small part of malignant neoplasms that can focal, in an aberrant sense, express it. Briefly, all this serves to allow a correct differential diagnosis with respect to primary malignant skin neoplasms (such as squamous cell carcinoma, melanoma and adnexal cutaneous neoplasm) and secondary non-hepatic skin neoplasms originating from organs such as lung, gastrointestinal tract, kidney, bladder, prostate, adrenal carcinoma and/or pancreatic carcinoids [5,6,[14][15][16][17][18][19].…”

“…Isa et al [5] describe in detail that to be considered effectively positive, the immunohistochemical staining must be strong, cytoplasmic, and granular in spite of a small part of malignant neoplasms that can focal, in an aberrant sense, express it. Briefly, all this serves to allow a correct differential diagnosis with respect to primary malignant skin neoplasms (such as squamous cell carcinoma, melanoma and adnexal cutaneous neoplasm) and secondary non-hepatic skin neoplasms originating from organs such as lung, gastrointestinal tract, kidney, bladder, prostate, adrenal carcinoma and/or pancreatic carcinoids [5,6,[14][15][16][17][18][19]. Hu SC et al [18] provide their experience related to a medical center in Taiwan in which they describe only 4 cases of skin metastases out of 1189 cases of HCC, equal to 0.34% of cases.…”

“…Primary liver cancer is globally the sixth most frequent cancer and the fourth leading cause of death from cancer. These cancers sometimes can metastasize to the skin; indeed, Hepatocarcinoma (HCC) metastasizes with a frequency ranging from 2.7% to 3.4% of all HCCs [5], and it may be the first sign of an underlying malignancy, with disease stages usually found to be advanced [6]. On the other hand, cholangiocarcinoma is a diverse group of epithelial cancers united by late diagnosis and poor outcomes [7]; cases of skin metastases of cholangiocarcinoma are extremely rare and, to date, about 35 cases have been reported in the literature [8].…”

Cutaneous metastasis of hepatocellular carcinoma following liver transplantation

“…Cutaneous hepatocellular carcinoma metastases occur in 2.7% to 3.4% of HCCs, but are extremely rare following orthotopic liver transplantation, with only three reported cases in the literature . Cutaneous HCC lesions may be the first sign of underlying malignancy or may be evidence of recurrence, but in all cases indicate advanced stage disease.…”