Answer: Metastatic hepatocellular carcinoma

Histology: The tumor is essentially one of eosinophilic polygonal cells, which show trabecular and cribriform growth patterns and a somewhat myxoid stroma. The cytoplasm is finely granular in its appearance, and cell borders are fairly well formed. Nuclei are generally round. On the initial round of immunohistochemical stains, the tumor labeled for CD138 (a marker of plasma cells) and not for cytokeratin AE1/3, which suggested the diagnosis of plasmacytoma. However, the tumor was negative for both kappa and lambda light chains. It did label for cytokeratin Cam 5.2 and polyclonal CEA (the latter in a canalicular pattern), and HepPar 1. These findings are diagnostic of metastatic hepatocellular carcinoma.

Discussion: While plasmacytoma was suggested by the immunoreactivity for CD138, it is important to recognize that CD138 (also known as syndecan-1, a cell surface heparin sulfate proteoglycan) also labels many carcinomas. Hence, while it is useful for separating plasma cell neoplasms from other lymphoproliferative disorders, it does not distinguish plasma cell neoplasia from epithelial neoplasia. The negative staining for both kappa and lambda argue strongly against a plasma cell neoplasm. Anaplastic large cell lymphoma would show more pleomorphic nuclei than the current case, would be more discohesive, and would not label for CD138, cytokeratin Cam 5.2, polyclonal CEA or HepPar 1. Similarly, melanoma would be more pleomorphic and less cohesive than the current case, and would label for S-100 and HMB 45.

The differential diagnosis for this case is in essence that of the eosinophilic polygonal cell tumor. Most common entities in this differential diagnosis are epithelial neoplasms, which have a granular pink cytoplasm due to abundant mitochondria. These oncocytic neoplasms include hepatocellular carcinoma, renal cell carcinoma, Hurthle cell carcinoma of the thyroid, and parathyroid carcinoma. Other pink cell carcinomas include adrenal cortical carcinoma and apocrine breast carcinoma. Other lesions in the differential include melanoma, plasmacytoma, Leydig cell tumor, alveolar soft part sarcoma, granular cell tumor, and rhabdomyoma. Among these lesions, hepatocellular carcinoma can be very difficult to diagnose when it is not suspected. This is because this tumor is frequently negative for cytokeratin AE1/3, which is used in screening for carcinomas, negative for EMA and negative for both cytokeratin 7 and cytokeratin 20. The most useful markers for this diagnosis include canalicular labeling with polyclonal CEA, which is about 80% sensitive and highly specific for the diagnosis, and the new HepPar 1 immunostain that recognizes a cytoplasmic but yet uncharacterized antigen. HepPar 1 is thought to be approximately 95 percent sensitive for the diagnosis of hepatocellular carcinoma, and is highly specific. Both of these markers, along with labeling for low molecular weight cytokeratin, were crucial in arriving at the correct diagnosis in this case.