Hepatocellular carcinoma in a cow: detection of tumor-infiltrating T lymphocytes implicated in anti-tumor immune response and partial spontaneous tumor regression

Hepatocellular carcinoma has been reported with some frequency in cattle. This report describes the morphological finding in a 12-year-old Holstein-Friesian dairy cow with spontaneous hepatocellular carcinoma. The cow that showed anorexia, emaciation, depression, and sluggish movement was culled and exhibited multiple tumor nodules (<20 mm diameter) in the liver on postmortem examination. On histopathology, the tumors revealed unencapsulated carcinomatous lesions consisting of a thick, compact, somewhat ambiguous trabecular to alveolar pattern of hepatoid tumor cells. The tumor cells showed anisocytosis and anisokaryosis, high mitotic index, and cytoplasmic deposition of bile pigments and periodic acid-Schiff (PAS)-positive granules, favoring a diagnosis of hepatocellular carcinoma. The tumor cells invaded the surrounding hepatic lobules but showed no metastatic spread to any extrahepatic sites. Numerous CD3+ T lymphocytes infiltrated prominently around and within the tumor cell nests. Necrotic or hemorrhagic foci were scattered throughout the tumor. Particularly in the central zone of many tumor nodules, necrotic foci and tumor cell nests associated with T lymphocytic infiltrates were surrounded and replaced, in part, by highly extensive sclerotic/fibrotic area, respectively. Diffuse infiltration of T lymphocytes was also observed in the sclerotic/fibrotic area. The findings observed in this hepatocellular carcinoma indicated that T lymphocytes played a critical role in the development of a local, anti-tumor, cellular immune response and contributed to the induction of T lymphocyte-fibroblast interaction that might have been implicated in the development of partial spontaneous regression of the cancer.