Molecular-genetic analysis is essential for accurate classification of renal carcinoma resembling Xp11.2 translocation carcinoma

Abstract

Xp11.2-translocation renal carcinoma (TRCC) is suspected when a renal carcinoma occurs in young patients, patients with a prior history of exposure to chemotherapy and when the neoplasm has morphological features suggestive of that entity. We retrieved 20 renal tumours (from 17,500 archival cases) of which morphology arose suspicion for TRCC. In nine cases, TFE3 translocation was confirmed by fluorescence in situ hybridisation analysis. In 9 of the remaining 11 TRCC-like cases (7 male, 4 female, aged 22-84 years), material was available for further study. The morphological spectrum was diverse. Six tumours showed a mixture of cells with eosinophilic or clear cytoplasm in tubular, acinar and papillary architecture. One case was high grade with epithelioid, spindle cell and sarcomatoid areas. Another showed tubular, solid, and papillary areas and foci containing spindle cells reminiscent of mucinous tubular and spindle cell carcinoma. The third showed dyscohesive nests of large epithelioid and histiocytoid cells in a background of dense lymphoplasmacytic infiltrate. By immunohistochemistry, keratin AE1/AE3 was diffusely positive in three tumours, while CK7 strongly stained one tumour and another focally and weakly. CD10 and Pax8 were expressed by eight, AMACR and vimentin by seven, CA-IX by four and TFE3 and cathepsin K by two tumours. Of the two TFE3-positive tumours, one showed polysomy of chromosome 7 and the other of 17; they were VHL normal and diagnosed as unclassifiable RCC. Of the seven TFE3-negative tumours, three showed polysomy of 7/17 and VHL abnormality and were diagnosed as combined clear cell RCC/papillary RCC. One TFE3-negative tumour with normal 7/17 but LOH 3p (VHL abnormality) was diagnosed as clear cell RCC. One TFE3-negative tumour with polysomy 7/17 but normal VHL was diagnosed as papillary RCC, and two with normal chromosomes 7/17 and VHL gene were considered unclassifiable. As morphological features and IHC are heterogeneous, TRCC-like renal tumours can only be sub-classified accurately by multi-parameter molecular-genetic analysis.

New and emerging renal entities: a perspective post‐WHO 2016 classification

“…Cases with LOH at 3p and polysomy of chromosomes 7 and 17 may show an aberrant chromosomal numerical pattern, which is observed within the spectrum of clear cell RCC. 118,119 There were also other more subtle genetic changes, which were also considered to be consistent with the clear cell RCC genetic patterns described in some large studies. 120 In our view, the presence of emperipolesis does not represent an independent adverse prognostic feature in a clear cell RCC.…”

“…Most of the tumours showed VHL abnormalities, but, in two cases that showed LOH at 3p, there was also polysomy of chromosomes 7 and 17. Cases with LOH at 3p and polysomy of chromosomes 7 and 17 may show an aberrant chromosomal numerical pattern, which is observed within the spectrum of clear cell RCC . There were also other more subtle genetic changes, which were also considered to be consistent with the clear cell RCC genetic patterns described in some large studies …”

TFE3 translocation and protein expression in renal cell carcinoma are correlated with poor prognosis

“…In female patients, a positive result included a fused green–red signal pair and an additional pair of split signals (Figure A). In male patients, a positive result included only a single pair of separate green and red signals (Figure B) …”

“…In male patients, a positive result included only a single pair of separate green and red signals ( Figure 2B). 5,19…”

Molecular Genetics of Renal Cell Tumors: A Practical Diagnostic Approach

“…Although TFE3 translocation RCCs can show a diverse morphologic spectrum, certain morphologic features (i.e., high-grade cells with abundant clear/eosinophilic cytoplasm and papillary/nested architecture; psammomatous calcifications) can be suggestive of this entity. Immunohistochemical analysis may not be sufficient to confirm the diagnosis of TFE3 translocation RCC, and that in some cases further molecular genetic testing maybe indicated [85]. Fluorescence in situ hybridization (FISH) testing is usually used to confirm the diagnosis.…”