An expanded immunohistochemical profile of osteoclast-rich undifferentiated carcinoma of the urinary tract

Abstract

Osteoclast-rich undifferentiated carcinoma of the urinary tract (ORUCUT) is a rare tumor composed of ovoid to spindle-shaped mononuclear cells with intermixed or focally clustered osteoclast-like giant cells. Previous studies have demonstrated that the mononuclear cells are neoplastic cells, while the giant cells are reactive cells of histiocytic lineage. The association between these tumors and classic urothelial carcinomas suggest that the mononuclear cells are derived from urothelial cells; however, no studies have been conducted to assess the immunohistochemical profile of ORUCUT with more specific urothelial markers. This study identified 21 cases of ORUCUT and performed immunohistochemistry for GATA3, uroplakin II, and thrombomodulin along with pancytokeratin (AE1/3) on all cases. Mononuclear cells stained positive in 20 cases (95%) for GATA3 and 19 cases (90%) for thrombomodulin. None of the mononuclear cells were positive for uroplakin II and only three cases showed focal positivity for AE1/3. The osteoclast-like giant cells were negative for GATA3, uroplakin II, thrombomodulin, and AE1/3, providing additional support to a reactive origin for these cells. Additionally, 15 cases (71%) were associated with either in situ or invasive urothelial carcinoma. This study provides an expanded immunohistochemical profile for ORUCUT and more definitively supports a urothelial origin for this tumor.

Variants and new entities of bladder cancer

“…Similar to other organs, undifferentiated bladder carcinoma shows three different morphological expressions: undifferentiated carcinomas of the bladder with rhabdoid features, undifferentiated carcinoma NOS and osteoclast‐rich undifferentiated carcinoma (Figure ) …”

“…Recognisable conventional urothelial carcinoma or urothelial carcinoma in situ is invariably present in most cases, at least focally. Cases described in the literature tend to show poor outcomes (Figure ) …”

“…Similar to other organs, undifferentiated bladder carcinoma shows three different morphological expressions: undifferentiated carcinomas of the bladder with rhabdoid features, undifferentiated carcinoma NOS and osteoclast-rich undifferentiated carcinoma (Figure 7). 92,93,104,105,106 A rare and aggressive disease, undifferentiated carcinoma NOS of the urinary bladder refers to carcinomas that are composed of sheets or isolated undifferentiated cells with no specific pattern of differentiation identifying it as urothelial, squamous, adenocarcinoma or any other recognised category of bladder carcinoma. 92 Immunohistochemical staining demonstrates positivity, at least focally, with cytokeratin.…”

“…Cases described in the literature tend to show poor outcomes (Figure 7). 93,106 Occasionally, an undifferentiated carcinoma may be seen with focal conventional urothelial carcinoma, a finding useful in the final characterisation of the neoplasia together with the finding of urothelial lineage by immunohistochemistry using GATA3 or S100P.…”

Bone Remodeling and the Role of TRAF3 in Osteoclastic Bone Resorption

“…Mesenchymal cells in these soft tissue lesions express RANKL and M-CSF ( 42 ), which presumably attract osteoclast precursors from the bloodstream and induce their differentiation into osteoclasts. Osteoclasts can also be observed, sometimes in large numbers, in a small percentage of primary carcinomas ( 43 , 44 ), including breast, lung, pancreas, and bladder, and in some soft tissue sarcomas, but the molecular mechanisms that induce their formation in these lesions are unknown. Macrophages, like osteoclasts, are derived from myeloid precursors and can comprise up to 40% of the cells in malignant tumors.…”