Answer: Clear cell adenocarcinoma

Histology: This TUR specimen shows a tumor composed of cells with clear cytoplasm. Most of the tumor is composed of solid nests of cells. Focally the tumor has a tubular and papillary configuration. Cytologically, there is significant variation in nuclear size with many of the cells having prominent nucleoli. Scattered mitotic figures are identifiable.

Discussion: This histology is typical of clear cell adenocarcinoma of the bladder. These tumors are also known as mesonephroid adenocarcinomas of the bladder. These tumors predominate in women and are very rare. More commonly one sees similar tumors occurring within the urethra. The major differential diagnosis is between the more common transitional cell carcinomas which on occasion may show striking clear cytoplasm. If one only had some of the solid nests of cells with clear cytoplasm, as seen in the current case, then a transitional cell carcinoma with clear cytoplasm would be a possible diagnosis. However, within almost all clear cell adenocarcinomas, one will at least focally find better differentiated areas showing tubular and papillary features which rules out transitional cell carcinoma. The presence of tubular and papillary architecture also brings into the differential diagnosis the entity nephrogenic adenoma. On a limited biopsy it may be very difficult in some cases to distinguish between nephrogenic adenoma and clear cell adenocarcinoma. Nephrogenic adenomas, however, lack clear cells, sheets of cells, and mitotic figures. Whereas nephrogenic adenomas may have atypia, it appears more degenerative in nature, occurring in vascular-like structures where the cells have a hobnail appearance. Although nephrogenic adenomas may on occasion be large and involve the muscle wall of the bladder, typically they are relatively small whereas clear cell adenocarcinomas are large destructive lesions. Also in the differential diagnosis are metastatic tumors to the bladder with clear cell morphology. The most common such tumor would be metastatic clear cell carcinoma of the kidney to the bladder. In addition to its rarity, clear cell carcinomas of the kidney typically have a nested appearance surrounded by a prominent delicate vasculature. Within clear cell carcinoma of the bladder, this vascular pattern is absent.

In the most recent series on this entity, some of these cases arose in the setting of endometriosis and other benign müllerian elements. Other cases had a minor component of transitional cell carcinoma associated with the clear cell adenocarcinoma. Consequently, some of these lesions appear to be of müllerian origin and in others, it may represent a peculiar form of gland differentiation in transitional cell carcinoma.