Hepatocellular carcinoma with osteoclast‐like giant cells: Possibility of osteoclastogenesis by hepatocyte‐derived cells

Abstract

Giant cell tumor (GCT) of bone is a primary osteolytic tumor that is characterized by the formation of osteoclast-like giant cells. In addition to GCT of bone, extraskeletal GCT are known to be formed in several soft tissues. Giant cells in GCT of bone were suggested to be identical to osteoclasts, but the characterization of giant cells in extraskeletal GCT remains incomplete. In this study, a case of sarcomatoid hepatocellular carcinoma with osteoclast-like giant cells was analyzed. Immunohistochemistry revealed the expression of almost all markers of osteoclasts: tartrate-resistant acid phosphatase, CD68, CD51, CD54 and matrix metalloprotease-9, in osteoclast-like giant cells in the tumor. In situ hybridization revealed the expression of receptor activator of nuclear factor-kappa B (RANK) in the giant cells and receptor activator of nuclear factor-kappa B ligand (RANKL) in the tumor cells. The hepatic origin of the sarcomatoid hepatocellular carcinoma cells was confirmed by the expression of albumin. This is the first report suggesting that hepatocyte-derived cells possess the potential for osteoclastogenesis. In addition, these findings suggest that osteoclast-like cells in the hepatocellular carcinoma were formed by the same mechanism as osteoclastogenesis in bone.

A malignant hepatic tumour with osteoclast‐like giant cells

“…Sir: Tumours with an osteoclast‐like giant cell (OGC) component have been described in a wide variety of organs outside bone: most of them are now considered to be undifferentiated carcinomas with the potential for intratumoral osteoclastogenesis. Hepatic neoplasms with OGCs are quite uncommon 1 . Here, we report a case of undifferentiated carcinoma of the liver with an abundant component of OGC.…”

“…Only 10 cases of ‘primitive osteoclast‐like giant cell tumours’ have been described in the liver, most of them considered to be primitive undifferentiated carcinomas; despite the lack of epithelial differentiation, most of them have displayed phenotypic evidence of an epithelial lineage (Table 1). 1,3–11 …”

Gallbladder carcinoma with osteoclast-like giant cells

“…[1][2][3][4][5][6] These giant cells cut sections of the resected specimen showed that the tumor was widely extended through the gallbladder wall (6 cm maximum width), and had directly invaded the liver parenchyma (Fig. 3b).…”

Giant cell tumor-like lesion of the urinary bladder: a report of two cases and literature review; giant cell tumor or undifferentiated carcinoma?

“…Osteoclasts may also be seen in carcinomas of visceral organs, gastrointestinal stromal tumors and leiomyosarcomas [22-24]. These tumors should be clearly differentiated from tumors with typical morphological features of GCT accompanying to an in situ or invasive carcinoma to prevent an overdiagnosis of 'undifferentiated carcinoma'.…”