Renal cell carcinoma in a 33-year-old male with an unusual morphology and an aggressive clinical course: possible Xp11.2 translocation.

Sir, Xp11.2 translocation-TFE3 renal cell carcinomas, a recently classified distinct subtype, usually affect young patients. They are defined by at least five different translocations involving the Xp11.2 chromosome, all of which result from gene fusions involving the TFE3 gene, and whose morphology and biological behaviour are not widely recognised as yet. They are rare tumours, with approximately 35 reports in the international medical literature. Although, thus far, only limited data are available, they are believed to be rather indolent, even when diagnosed at advanced stages. We present a case of a 33-year-old male with a renal cell carcinoma (RCC) bearing an Xp11.2 translocation, suggested by histology and confirmed by immunohistochemistry (IHC), with an aggressive clinical course. He presented with worsening chronic lower back pain for 2 months. Computed tomography (CT) scan showed an inferior right kidney mass measuring 8.2 cm, and metastatic micronodules in the lumbar spine and right lung. A CT-guided fine needle aspiration (FNA) biopsy of this mass was obtained, and the cytological analysis revealed abundantly cellular aspirate with numerous dyscohesive clusters of malignant epithelial cells, many of which were arranged in papillary clusters with central hyalinised fibrovascular core (Fig. 1A). There was a small amount of necrosis and dense metachromatic extracellular matrix (arrow, Fig. 1B) in the background. The tumour cells were large with abundant granular finely vacuolated cytoplasm and discrete cell borders, imparting a predominantly clear cell appearance (Fig. 1C). The nuclei were enlarged with mild contour irregularities, fine chromatin, and had prominent central macronucleoli (Fig. 1D). Mitotic figures were not readily identified, and psammoma bodies were absent. Immunocytochemical studies performed on the cell block sample showed tumour cells that were positive for RCC marker, CD10, vimentin, and TFE3, and negative for TTF-1, cytokeratin (CK) 7, and CK20 (not shown). A right radical nephrectomy and regional lymphadenectomy were performed, and revealed a circumscribed nodular 8.2 cm tumour in the inferior right kidney. A L3-L5 kyphoplasty and bone biopsy with fiducial placement was also performed. Histology of the renal tumour and bone metastasis (Fig. 2) showed carcinomatous proliferation arranged in papillary (Fig. 2A), trabecular and nested patterns. The tumour cells were large with irregular nuclei and conspicuous nucleoli. The cytoplasm was usually clear with well-defined limits, and the stroma was fibrous and contained hyaline nodules and psammoma bodies (Fig. 2B) in the nested areas. Metastatic renal cell carcinoma was present in one renal hilar lymph node (Fig. 2C), which measured 3.8 cm in its greatest dimension and was completely replaced by neoplastic cells with extracapsular extension. The L3-L5 bone biopsy revealed a similar carcinomatous proliferation to the renal tumour (Fig. 2D). IHC staining performed on histological sections of renal tumour and bone metastasis (Fig. 3) revealed that the neoplastic cells expressed pancytokeratin, vimentin (Fig. 3C), epithelial membrane antigen (EMA; focal), E-cadherin, alpha-methylacyl CoA-racemase (AMACR), BerEP4 (focal), RCC marker (patchy), and CD10 (patchy) (Fig. 3D). The neoplastic cell expression of CK7 was weak and very focal. The neoplastic cells did not express c-kit, HMB-45, or Melan-A. Ki-67 proliferative index of the neoplastic cells was approximately 20%. The histological features of psammoma bodies and hyaline nodules raised the possibility of renal cell carcinoma associated with an Xp11.2 translocation. IHC nuclear staining for TFE3 was