Hepatocellular Carcinoma with Small Cell Histology: A Rare Mimic of Metastatic Tumors Involving the Liver

Hepatocellular Carcinoma (HCC) is the most common primary liver cancer, and the sixth most common human cancer overall. The incidence of HCC is increasing as the prevalence of chronic liver disease increases. HCC is associated with a poor prognosis frequently due to delayed diagnosis and its propensity for angioinvasion. Therefore, timely diagnosis of HCC is crucial for patient outcomes. Among the major histologic variants of HCC are clear cell, lymphoepithelial, steatohepatic, scirrhous, and fibrolamellar. However, HCC with small cell histology (HCCSC) is extremely rare and remains a challenging diagnosis as it can mimic other entities including neuroendocrine tumors, poorly differentiated carcinoma, and others. Two cases of HCCSC encountered as outside consultation cases are reported here. These were initially misdiagnosed as “metastatic neuroendocrine tumor” and “poorly differentiated carcinoma” on core biopsies at outside institutions. Tumors composed of uniformly small, round to polygonal cells with limited to medium amount of slightly eosinophilic, finely granular cytoplasm were seen on H&E. Tumor cells showed pseudoglandular/tubular, trabecular, and solid growth pattern. Equivocal synaptophysin labeling was detected in the first case, while other endocrine markers are negative. Additional immunohistochemistry at our institute was positive for glypican-3 and heppar-1; P-CEA and CD10 highlighted a canalicular pattern, while reticulin illustrated thickened hepatic plates. Radiological and laboratory studies supported the diagnosis of HCCSC. These cases highlight the importance of astute evaluation of H&E sections and dedicated ancillary investigation in reaching a timely and correct diagnosis of HCCSC.