Answer: Small cell carcinoma associated with non-invasive urothelial carcinoma with glandular differentiation

Histology: The majority of this tumor consists of large nests and sheets of cells that at low magnification have a very basophilic appearance. At higher magnification, the tumor consists of cells with high nuclear to cytoplasmic ratio, nuclear molding, indistinct nucleoli, numerous mitotic figures, and numerous apoptotic bodies. Areas in the tumor show geographic necrosis. Focally, the tumor shows a papillary configuration. In areas the tumor is lined by high grade papillary urothelial carcinoma. Other areas of the papillae are lined by pseudostratfied columnar epithelium with apical cytoplasm.

Discussion: The infiltrating tumor in this lesion is typical of small cell carcinoma. It is indistinguishable from small cell carcinoma seen at other sites such as the lung. The unusual aspect of this lesion is the exophytic papillary component. While some areas are typical of high grade papillary urothelial carcinoma, other areas have atypical glandular epithelium as the lining. In a prior series from Hopkins, the term “in situ adenocarcinoma” was utilized for these lesions analogous to noninvasive malignant glandular lesions found in other sites. However, this term is controversial for the lesions shown here as some experts consider that by definition “in situ adenocarcinoma” should be restricted for a lesion originating from glandular cells (i.e. in the bladder from cystitis glandularis). The co-existence of CIS and/or high grade noninvasive urothelial carcinoma typically found with non-invasive urothelial carcinoma with glandular differentiation favors that this lesion represents divergent differentiation of urothelial carcinoma. In support of this, is that none of our cases in our studies subsequently developed invasive adenocarcinoma. However, 50% eventually developed invasive bladder cancers. This is a higher rate of progression than that have been reported following de novo CIS. Of the nine patients in our study that did develop invasive tumors, 2 had small cell carcinoma and 2 had poorly-differentiated urothelial carcinomas that widely metastasized. The remaining 5 had invasive urothelial carcinomas. That noninvasive urothelial carcinoma with glandular differentiation is associated with these high-grade invasive tumors indicates that this intraepithelial lesion should be considered at least and possible more worrisome than CIS. There is an increased association of non-invasive urothelial carcinoma with glandular differentiation with small cell carcinoma, as seen in this case.

Reference(s):
– Miller JS, Epstein JI. Non-invasive urothelial carcinoma of the bladder with glandular differentiation: report of 24 cases. Am J Surg Pathol (Aug); 33: 1241-1248, 2009.