Answer: Osteoclast rich undifferentiated carcinoma of urinary bladder

Histology: A striking morphologic feature of the tumor is the presence of multinucleated osteoclast like giant cells accompanying the neoplastic mononuclear ovoid to spindle cells. The mononuclear undifferentiated ovoid cells can focally acquire a “rhabdoid” or signet ring morphology. In other portions, the neoplastic cells are separated by a myxoid extracellular matrix acquiring a chondroid appearance. The richly vascularized stroma may contain areas of erythrocytes extravasation and occasional large blood lakes. Mitotic figures are common in the mononuclear cells but not in the multinucleated giant cell population. Large areas of necrosis are usually present. Tongue-like infiltrative growth pattern may also be encountered. Sarcomatoid component has been encountered in other examples of this lesion. When present, associated non invasive papillary or in-situ urothelial carcinoma are helpful clues to establish the urothelial nature of this unusual variant. The multinucleated giant cells are immunoreactive for CD68, vimentin, tartrate-resistant acid phosphatase, á1- antitrypsin, LCA, osteoclast markers such as CD51 and CD56, and negative to epithelial markers. Mononuclear cells show focal staining for epithelial markers (cytokeratins AE-1/AE-3, Cam 5.2, CK7 and/or EMA) but can also express CD68, smooth muscle actin, S-100 and p53.

Discussion: Osteoclast rich undifferentiated carcinoma is a very rare aggressive variant of urothelial carcinoma. It is predominantly seen in elderly men. Terminology, histogenesis, and biologic behavior of these tumors remain controversial. In the largest series reported to date by Baydar et al., six cases were reported. Patients were all males and with the exception of one patients, all were elderly (range 65-82). Three tumors were from bladder and the remaining three from the renal pelvis. Tumor size ranged from 5-11 cm. all patients had associated urothelial carcinoma in situ and/or high-grade papillary urothelial carcinoma. Four of the five patients with available follow up were dead of disease within 15 months of diagnosis. In the same study, the osteoclastic/histiocytic nature of the multinucleated cells was supported by their reactivity for CD68, LCA and CD51. The osteoclasts were therefore considered part of the host response mounted toward the neoplastic mononuclear cells.

Osteoclast rich undifferentiated carcinoma is more likely to present with advanced stage disease. Stage by stage however, its outcome is comparable to usual invasive urothelial carcinoma. A rare report on the cytologic features of the lesion in fine needle aspiration material from a metastatic site are on record.

The differential diagnosis include: Pleomorphic giant cell urothelial carcinoma, sarcomatoid carcinoma and high grade infiltrating urothelial carcinoma with syncytiotrophoblastic giant cells. In pleomorphic giant cell urothelial carcinoma, the giant cells are epithelial in nature and are part of the neoplastic population thus lacking the expression of osteoclast markers (CD51 and CD56). Sarcomatoid carcinoma of urothelial or prostatic origin will express p63 and or high molecular weight cytokeratin (CK903). Finally, HCG immunostain will label synciotrophoblasts in high grade infiltrating urothelial carcinoma with syncytiotrophoblastic giant cells.

Reference(s):
– Baydar D, Amin MB, Epstein JI. Osteoclast-rich undifferentiated carcinomas of the urinary tract. Mod Pathol. 2006 Feb;19(2):161-71.
– Bui MM, Purohit CN, Hakam A. Fine needle aspiration biopsy of an
osteoclast-rich undifferentiated urothelial carcinoma: A cytology case report and review of the literature. Cytojournal. 2010 Sep 17;7:18. PubMed PMID: 20976205; PubMed Central PMCID: PMC2955341.
– Castelino-Prabhu S, Ali SZ. Osteoclast-rich undifferentiated carcinoma of the
urinary tract: cytologic findings and literature review. Diagn Cytopathol. 2010
May;38(5):364-7. Review. PubMed PMID: 19894256