Xp11 Translocation Renal Cell Carcinoma in Adults: Expanded Clinical, Pathologic, and Genetic Spectrum

Abstract

The recently recognized Xp11 translocation renal cell carcinomas (RCCs), all of which bear gene fusions involving the TFE3 transcription factor gene, comprise at least one-third of pediatric RCC. Only rare adult cases have been reported, without detailed pathologic analysis. We identified and analyzed 28 Xp11 translocation RCC in patients over the age of 20 years. All cases were confirmed by TFE3 immunohistochemistry, a sensitive and specific marker of neoplasms with TFE3 gene fusions, which can be applied to archival material. Three cases were also confirmed genetically. Patients ranged from ages 22 to 78 years, with a strong female predominance (F:M=22:6). These cancers tended to present at advanced stage; 14 of 28 presented at stage 4, whereas lymph nodes were involved by metastatic carcinoma in 11 of 13 cases in which they were resected. Previously not described and distinctive clinical presentations included dense tumor calcifications such that the tumor mimicked renal lithiasis, and obstruction of the renal pelvis promoting extensive obscuring xanthogranulomatous pyelonephritis. Previously unreported morphologic variants included tumor giant cells, fascicles of spindle cells, and a biphasic appearance that simulated the RCC characterized by a t(6;11)(p21;q12) chromosome translocation. One case harbored a novel variant translocation, t(X;3)(p11;q23). Five of 6 patients with 1 or more years of follow-up developed hematogenous metastases, with 2 dying within 1 year of diagnosis. Xp11 translocation RCC can occur in adults, and may be aggressive cancers that require morphologic distinction from clear cell and papillary RCC. Although they may be uncommon on a percentage basis, given the vast predominance of RCC in adults compared with children, adult Xp11 translocation RCC may well outnumber their pediatric counterparts.

Cathepsin-K immunoreactivity distinguishes MiTF/TFE family renal translocation carcinomas from other renal carcinomas

“…All the cases had been earlier reported and cytogenetically confirmed. 2,3,5,[12][13][14][15][16][17] Seven cases harbored the translocation t(6;11)(p21;q12), which results in an Alpha-TFEB gene fusion and all showed confirmatory TFEB nuclear immunoreactivity as described earlier. 5 Ten cases had translocations involving Xp11.2, and all ten of these renal cell carcinomas showed confirmatory TFE3 nuclear immunoreactivity as described earlier.…”

“…13 The PRCC-TFE3 renal carcinomas showed a more nested compact architecture. Psammoma bodies were rare or absent in these tumors.…”

“…6 Five cases showed the t(X;1)(p11.2;q21) resulting in the PRCC-TFE3 gene fusion; three cases showed the t(X;1)(p11.2;p34), resulting in the PSF-TFE3 fusion gene; one case showed the t(X;17)(p11.2;q25), resulting in the ASPL-TFE3 fusion gene and one case showed the novel t(X;3)(p11;q23). 13 For eight cases (cases 1, 2, 6-8, 10-12), five 1.4 mm diameter cores from the paraffin blocks of each case were used to create tissue microarrays for immunohistochemical analysis. These tissue microarrays also included six clear cell renal cell carcinomas and five papillary renal cell carcinomas.…”

Molecular heterogeneity of TFE3 activation in renal cell carcinomas

“…Initially described in children and designated as 'juvenile papillary renal cell carcinoma', there today is increasing evidence that these uncommon neoplasms also occur in adults although their true incidence and clinical peculiarities have not been evaluated in detail. 18,19 To systematically analyse the role of TFE3 alterations in unselected renal cell carcinomas, we have combined TFE3 immunohistochemistry with molecular analyses of the underlying genomic alterations. In a series of 876 well-characterised renal cell carcinomas, immunohistochemistry revealed that the vast majority (91%) of tumours showed no TFE3 expression at all, whereas the remaining 9% exhibited varying cytoplasmic or nuclear staining patterns.…”

Renal cell carcinoma with novel VCL–ALK fusion: new representative of ALK-associated tumor spectrum

“…Thus, although tumor karyotypes were not available, cases 4 ( Figure 1f) and 5 (Figure 1g), originally diagnosed as papillary renal carcinomas in 2002, could have in fact represented Xp11.2 translocation-associated carcinomas. Case 6 also demonstrated morphological (Figure 1h) and some immunohistochemical (Table 3) features assigned to the Xp11.2 translocationassociated carcinoma, 31 but lacked expression of TFE3 and TFEB and was, therefore, diagnosed as a renal cell carcinoma, indeterminate subtype. Immunohistochemical analyses using two anti-VCL antibodies were positive in cases 1 through 5, which is consistent with a collecting duct origin of these neoplasms.…”