A distinctive translocation carcinoma of the kidney; "rosette forming," t(6;11), HMB45-positive renal tumor: a histomorphologic, immunohistochemical, ultrastructural, and molecular genetic study of 4 cases.

To date, only a few cases of "rosette forming t(6;11), HMB45-positive renal carcinoma" have been published. In this article, we contribute further data on 4 cases of this rare entity. Patients were 3 women and 1 man with an age range of 20 to 54 years (median, 23 years). Follow-up (range, 3-5 years; median, 4 years) did not reveal any metastatic events or recurrences. All tumors were well circumscribed and mostly encapsulated with homogeneous gray to tan cut surfaces. No necrosis was seen. All tumors displayed a solid or solid/alveolar architecture and contained occasionally long and branching tubular structures composed of discohesive neoplastic cells and pseudorosettes. The presence of pseudorosettes was a constant finding, but the number of pseudorosettes varied significantly among cases. All cases displayed focal immunoreactivity for the melanocytic marker HMB45, cathepsin K, and vimentin. Melan A, tyrosinase, cytokeratins, CD10, and microphthalmia transcription factor were each positive in 3 of 4 cases. On ultrastructural examination, numerous electron-dense secretory cytoplasmic granules with some resemblance to melanosomes were identified. The pseudorosettes were composed of reduplicated basement membrane material surrounded by small lymphocyte-like neoplastic cells. Using reverse transcription polymerase chain reaction, 2 tumors were positive for the Alpha-TFEB fusion transcript. The presence of the translocation t(6;11)(Alpha-TFEB) was confirmed in 2 analyzed cases. No von Hippel-Lindau tumor suppressor gene mutation, promotor methylation or loss of heterozygosity of 3p was found. Losses of part of chromosome 1 and chromosome 22 were found in one case.

Renal oncocytoma with and without intravascular extension into the branches of renal vein have the same morphological, immunohistochemical and genetic features.

We attempted to investigate the clinicopathological correlation of renal oncocytoma (RO) with renal vein extension. We identified seven ROs with extension into the branches of renal vein. The age of seven patients ranged from 61 to 82 years. Five cases were identified; incidentally, two patients had gross hematuria. After surgery, all patients were alive and free of tumors with follow-up of 1 to 5 years (mean=3.6). Oncocytomas measured from 2.2 to 7.5 cm. Renal vein extension was grossly suspected in 5/7 cases and histologically confirmed in all seven cases. Tumor cells were positive for cytokeratins, mitochondrial antigen, epithelial membrane antigen, and parvalbumin; 5/7 tumors were focally positive for cluster of differentiation 117. Ultrastructurally, the cytoplasm was packed by mitochondria. Molecular genetic analysis did not detect abnormal numbers of chromosomes 1, 2, 6, 7, 10, 17, and XY by fluorescence in situ hybridization, loss of heterozygosity on 3p, and mutation of Von Hippel-Lindau gene in all cases. Array comparative genomic hybridization analysis of two cases did not show any major genetic changes. Conclusions are: (1) renal oncocytomas may have intravascular extension to the branches of the renal vein; (2) renal oncocytomas with intravascular extension to the branches of the renal vein have the same morphological, immunohistochemical, and cytogenetic findings as have their counterparts without evidence of intravascular invasion; (3) the absence of metastases suggests an overall benign behavior of this tumor, but this has to be substantiated by further studies with a long-term follow-up; (4) in a renal tumor with granular cytoplasm showing renal vein extension, it is necessary to carefully exclude renal cell carcinomas (RCC) such as chromophobe RCC, oncocytic variant of papillary RCC, and granular variant of clear cell RCC.