Combined hepatocellular carcinoma and osteoclast‐like giant cell tumor of the liver: Possible clue to histogenesis

Abstract

Hepatic giant cell tumor is extremely rare, and only five cases have been reported of overt hepatocellular carcinoma, thus its histogenesis is controversial. Herein is reported a case of simultaneous hepatocellular carcinoma and osteoclast-like giant cell tumor in a single tumor. A liver tumor was found in a 74-year-old woman. Histologically the tumor consisted of two distinct components: mononuclear and multinuclear giant cells with osteoclastic giant cells, and a conventional hepatocellular carcinoma. The boundary between the two components showed transitional features. Immunohistochemistry showed that the osteoclast-like giant cells were CD68 and vimentin positive, but cytokeratin and AFP negative, while spindle-shaped cells were positive only for vimentin. In a portion of the hepatocellular carcinoma the cells were cytokeratin-8 and AFP positive. Ki-67 positivity was 10% for the hepatocellular carcinoma, 60% for the spindle-shaped cells, and 0% for the giant cells. It is possible that the tumor might have had a hepatocellular carcinoma origin, given the more highly proliferative sarcomatous changes and reactive osteoclast-like cells. This case provides a clue to the histogenesis of hepatic giant cell tumors.

Sarcomatoid hepatocellular carcinoma with mixed osteoclast-like giant cells and chondroid differentiation

“…OGC in carcinomas are reported in many organs including the pancreas, breast, and thyroid; among them, the pancreas is predominant. 10 The incidence of OGC in liver cancer was reviewed in 2009 by Tanahashi et al, who summarized 15 earlier studies, of which one-third of 16 reports including their case reported the presence of overt HCC. 10 OGC in carcinoma are generally considered reactive histiocytic cells rather than true malignant tumor cells 10 because OGC react positively for CD68 and have a low Ki-67 index.…”

“… 10 The incidence of OGC in liver cancer was reviewed in 2009 by Tanahashi et al, who summarized 15 earlier studies, of which one-third of 16 reports including their case reported the presence of overt HCC. 10 OGC in carcinoma are generally considered reactive histiocytic cells rather than true malignant tumor cells 10 because OGC react positively for CD68 and have a low Ki-67 index. About histogenesis of OGC in liver, OGC in liver cancer had a similar expression of almost all osteoclast markers of bone: tartrate-resistant acid phosphatase, CD68, CD51, CD54, matrix metalloprotease-9, receptor activator of nuclear factor-kappa B (RANK), and RANK ligand (RANKL), suggesting that OGC in liver cancer had similar histogenesis of osteoclastogenesis in bone.…”

Hepatocellular Carcinoma with Osteoclast-Like Giant Cells: Report of the Seventh Case in the Literature

“…Since then, five additional cases have been reported. Its histology is represented by the combination of hepatocellular carcinoma and giant cell tumor of the liver [ 2 – 4 ]. The histogenesis is controversial although extraskeletal giant cell tumors may occur in the soft tissue of many organs such as pancreas, thyroid gland, and liver.…”

“…However, the characterization of the origin of giant cells in this kind of tumor remains incomplete. According to many reports, the osteoclast-like giant cells in tumors of organs other than the bone represent nonneoplastic histiocytes with stromal reaction, especially when this kind of cells was observed in a portion of a well-differentiated carcinoma [ 2 , 5 – 7 ]. In the liver, several cases of hepatocellular carcinoma with formation of osteoclast-like giant cells have been reported as an extremely rare variant of HCC, and the hepatocyte-derived tumor cells were suggested to induce osteoclast-like giant cells [ 8 – 12 ].…”

“…This type of tumor is very aggressive: in all the cases, the patients died of the disease, more often, within one month after the diagnosis [ 4 , 5 , 7 , 8 , 13 , 14 ]. Metastases have been observed in the vertebral bones and in the lung and are due to the sarcomatoid osteoclast-like component of the tumor [ 2 , 15 ]. No evidence of a favourable effect of adjuvant or neoadjuvant chemotherapy is available at the moment and surgery seems to represent the treatment of choice [ 2 , 5 , 6 , 13 ].…”