Xp11.2 translocation renal cell carcinoma occurring during pregnancy with a novel translocation involving chromosome 19: a case report with review of the literature

Abstract

The recently recognized renal cell carcinomas (RCCs) associated with Xp11.2 translocations (TFE3 transcription factor gene fusions) are rare tumors predominantly reported in children. They comprise at least one-third of pediatric RCCs and only few adult cases have been reported. Here, we present a case of Xp11.2 translocation RCC in 26-year-old pregnant female. Her routine antenatal ultrasonography accidentally found a complex cystic right renal mass. Further radiologic studies revealed unilocular cyst with multiple mural nodules at inferior pole of right kidney, which was suspicious for RCC. She underwent right radical nephrectomy at 15 weeks gestation. Macroscopically, the cystic tumor was well encapsulated with multiple friable mural nodules on its inner surface. Microscopically, the tumor consisted of clear and eosinophilic/oncocytic voluminous cells arranged in papillary, trabecular, and nested/alveolar patterns. Occasional hyaline nodules and numerous psammoma bodies were present.Immunohistochemically, the tumor showed strong nuclear positivity for TFE3. Epithelial membrane antigen, CD10, and E-cadherin were strongly positive. Cytokeratin AE1/AE3, cytokeratin CAM-5.2, calveolin, and parvalbumin were moderately positive. Cytokeratin 7, renal cell carcinoma antigen, and colloidal iron were focally weakly positive. BerEP4 and carbonic anhydrase IX were negative. Cytogenetically, the tumor harbored a novel variant translocation involving chromosomes X and 19, t(X;19)(p11.2;q13.1). Interphase FISH analysis performed on cultured and uncultured tumor cells using a dual-color break-apart DNA probe within the BCL3 gene on 19q13.3 was negative for the BCL3 gene rearrangement. She received no adjuvant therapy, delivered a normal term baby five months later, and is alive without evidence of disease 27 months after diagnosis and surgery. Unlike most recently reported Xp11.2 translocation RCCs in adult patients with aggressive clinical course, this adult case occurring during pregnancy with a novel translocation involving chromosome 19 followed an indolent clinical course.

Molecular heterogeneity of TFE3 activation in renal cell carcinomas

“…As there is evidence of further, as yet unrecognised fusion variants, the direct visualisation of the TFE3 split remains the method with the highest sensitivity for paraffin-embedded, clinical tissue samples. 7,17,21 Of the eight genetically verified Xp11 translocation renal cell carcinomas in both series, seven occurred in adult patients corresponding to an overall frequency of 0.75% Xp11-associated tumours in unselected (adult) cases. The average age of patients with Xp11 translocation renal cell carcinomas was 44 years, the oldest patient 75 years at diagnosis.…”

Usefulness of a break-apart FISH assay in the diagnosis of Xp11.2 translocation renal cell carcinoma

“…TFE3 FISH analysis showed a fused green and red signal (arrows) (c, f) (×1,000). One negative control clear cell RCC case (g) (H&E, ×200) showed negative TFE3 immunohistochemistry (h) (×200) and normal TFE3 FISH signals (arrows) (i) (×1,000) Although this tumor was initially known as RCC in pediatric patients, adult cases have been continuously reported [9,10,15,[19][20][21][22][23]. Furthermore, unusual morphologies mimicking other RCC subtypes have been found in some Xp11.2 translocation RCCs [11,15,16].…”

Molecular cytogenetic analysis for TFE3 rearrangement in Xp11.2 renal cell carcinoma and alveolar soft part sarcoma: validation and clinical experience with 75 cases

“…31 Therefore, the diagnosis of Xp11.2 renal cell carcinoma and alveolar soft part sarcoma requires genetic confirmation using a method such as FISH or RT-PCR to supplement histology and IHC results in diagnostically challenging cases. Owing to reports of Xp11.2 rearrangement in renal cell carcinoma with currently unknown partners, 9,34 and likely future discoveries of additional fusion variants, FISH for TFE3 rearrangement is the preferred method to RT-PCR as it does not require knowledge of the partner gene and is a highly sensitive method without the technical challenge of RNA degradation in formalin-fixed, paraffin-embedded tissue samples.…”

“…Reverse transcription PCR (RT-PCR) is technically challenging because of RNA degradation in paraffinembedded tissues and also requires knowledge of all partner genes, some of which are currently not established for Xp11.2 renal cell carcinoma. 9,34 Fluorescence in situ hybridization (FISH) does not necessitate knowledge of the fusion partners and is a highly sensitive method for analysis of paraffinembedded tissues. In response, we demonstrate through both validation and extensive clinical experience that a break-apart strategy probe set for TFE3, including a chromosome X centromere probe as a control and a TFE3/ASPSCR1 dual-color, singlefusion reflex probe set, is an excellent test to aid in the identification of tumors with Xp11.2 rearrangement.…”