Spontaneous pulmonary co-metastasis of hepatoblastoma arising within a hepatocellular carcinoma in an aged C57BL/6J mouse.

Murine hepatoblastoma (HB) is a rare spontaneous tumor with controversial histogenesis. It mainly occurs in aged males, frequently in close association with preexisting hepatocellular neoplasms. The present work describes a spontaneous HB arising within a hepatocellular carcinoma (HCC) in a 22-month-old male C57BL/6J mouse. The mouse also developed pulmonary co-metastases with either tumor components physically associated within the same metastatic foci. Microscopically, the HB consisted of a densely cellular neoplastic growth composed of palisades and perivascular pseudorosettes of poorly differentiated primitive cells, with a scant amount of cytoplasm, elongated hyperchromatic nuclei, and a high mitotic rate, whereas the hepatocellular carcinoma was composed of solid areas of neoplastic hepatocytes. Both in primary tumors and their metastases, β-catenin immunohistochemistry revealed a strong nucleocytoplasmic signal in HB cells, while neoplastic hepatocytes displayed a delicate membranous staining pattern. These findings suggest that the Wnt/β-catenin oncogenic pathway is upregulated in murine HB but not in the co-existing HCC, thus providing some insights into their divergent pathogenesis. Coexisting murine HB and HCC have been demonstrated to be completely distinct entities including origin, mutational landscape, and molecular profile. In this context, they might be regarded as collision tumors because of their intimate association, unique histologic features, and distinct immunohistochemical patterns. Nevertheless, the nature of their coevolution and progression to a co-metastatic phenotype reflects a close interdependence and support the overall idea that HB's origin and progression might be promoted by not otherwise specified paracrine stimuli provided by the concurrent hepatocellular tumor (the so called "interaction theory").