Adult-Onset Xp11.2 Translocations/TFE3 Gene Fusions Renal Cell Carcinoma: Clinico-Pathological Features of 69 Cases
A Panizo, I de Torres, JJ Sola, J Pardo. Clinica Universidad de Navarra, Pamplona, Spain; Hospital Vall de Hebron, Barcelona, Spain
Background: The recently recognized renal cell carcinomas (RCC) associated with Xp11.2 translocations (TFE3 gene fusions) are rare tumors predominantly described in children, and only rare adult cases have been reported. The aim of our study was to evaluate the clinical and pathological features of 69 Xp11.2 translocations RCC in adult patients.
Design: We identified 69 TFE3 RCC in adults (over the age of 20 yrs.). All cases were confirmed by TFE3 IHC, and two cases were also confirmed genetically. Morphological, IHC, and flow-cytometry (FC) features, clinical data and follow-up were assessed.
Results: The patients were 46 males and 23 females (mean age 54 yrs.; range 20-77 yrs.). Mean tumor size was 7.4 cm. 38 tumors were in the right kidney and 31 in the left. TNM stage at diagnosis was pT1 (n= 21), pT2 (n= 9), pT3 (n= 36), pT4 (n= 3), pN+ (n=12), and pM+ (n= 23). Five histological patterns were found: solid/tubular, alveolar, pseudopapillary, true papillary, and multicystic. Tumors were composed of clear (40%), eosinophilic (15%) or mixed cells (45%). In some cases we found tumor spindle cells, tumor giant multinucleated cells, and bone metaplasia. The Fuhrman grade was: 2 (16 %), 3 (67%), and 4 (17%). IHC study showed that all cases strongly expressed TFE3, CD10, and P504s. Variable positivity for pan-CK, vimentin, EMA, and RCC antigen was also noted. Three cases were positive for Melan-A/MART1. None of the tumors expressed CK7, HMW CK, and CD117. From 11 tumors studied by FC, 6 were diploid, 3 aneuploid, and 2 multiploid. Two cases contained ASPL/TFE3 gene fusion. Follow-up was available for 57 cases (median 21.9 months; range 1 to 208 months): 13 patients were alive without disease, 24 patients were alive with metastasis, and 20 died of the disease. Locations of distant metastasis were: liver (n= 17), lung (n= 30), bone (n= 20), retroperitoneum (n=23), mediastinum (n=18), central nervous system (n= 6), and others (n= 5).
Conclusions: Xp11.2 translocations RCC occur in adults, and males were affected more frequently. Tumors exhibited heterogeneous morphology rendering this characteristic unreliable for identification. We recommend evaluating the TFE3 IHC expression in adult renal tumors with multiple morphologies or unclassified RCC. The IHC profile (TFE3+, CD10+, P504s+, and CK7-) is helpful for the diagnosis. Overall, Xp11.2 translocations RCC were frequently associated with an advanced stage, distant metastasis at presentation and an aggressive clinical course.
Category: Genitourinary (including renal tumors)
Tuesday, March 23, 2010 9:30 AM
Poster Session III # 152, Tuesday Morning