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

Department of Pathology, The Johns Hopkins University, Baltimore, MD 21231-2140, USA.
American Journal of Surgical Pathology (Impact Factor: 5.15). 09/2007; 31(8):1149-60. DOI: 10.1097/PAS.0b013e318031ffff
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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.

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    • ". These translocations most frequently involve the TFE3 gene on locus Xp11.2 and less frequently involve the TFEB gene on locus 6p21 [7]. "
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    ABSTRACT: Introduction: Renal cell carcinoma (RCC) with t(6:11) (p21;q12) are extremely rare, fewer than 30 cases have been reported in literature. These tumors are characterized by specific chromosomal translocation involving TFEB, as against the more commonly known TFE3 (Xp11.2) translocation associated RCCs. The distinctive immnohistologic features are helpful in enabling a diagnosis of this rare tumor, otherwise diagnosed by fluorescence in situ hybridization assay, specific for detecting TFEB gene rearrangement. Presentation of case: Herein, we report a case of this rare tumor in a 11 years old boy, with the objective of highlighting distinctive light microscopic and immuno-phenotypic features of this rare sub-type of translocation associated renal cell carcinoma, otherwise diagnosed by fluorescence in situ hybridization technique. Morphologically tumor showed distinctive biphasic population of cells, large epitheloid cells with voluminous eosinophillic cytoplasm and smaller cells with much lesser amount of cytoplasm and small rounded nuclei. The smaller cells at places clustered around hyaline pink material forming "pseudorosettes". population. Immunohistochemically both types of tumor cells showed negativity for pan CK (cytokeratin), EMA (epitheleal membrane antigen) and TFE3 (transcription factor E3). HMB 45 (human melanoma black 45) and Melan- A /MART 1 (melanoma antigen recognized by T cells) were moderate to strongly expressed. Discussion: On review of literature, most RCCs with t(6;11) translocation have been reported to be negative for pan cytokeratins and EMA. Published literature also shows that the most distinctive immunohistochemical feature of t(6;11) translocation RCC is nuclear staining for TFEB protein. Immunostains for TFE3 have always been negative in the reported cases. It is noteworthy that immunoreactivity for melanocytic markers HMB45 and Melan A and immunonegativity for epithelial markers pan CK and EMA may lead to misdiagnosis of angiomyolipoma to the unwary. Conclusion: Knowledge of distinctive morphological and immuno-histochemical features of this tumor can help in establishing a diagnosis of this rare subset of translocation associated RCC on routine hematoxylin and eosin (H and E) staining and immunophenotyping.
    International Journal of Surgery Case Reports 12/2014; 24. DOI:10.1016/j.ijscr.2014.12.026
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    • "RCCs treated with partial nephrectomy have been found with no recurrence or metastasis in the limited studies available. In the studies by Argani et al (1/28 cases; 6-month follow-up) (16) and Komai et al (2/7 cases; 96- and 132-month follow-up, respectively) (17), Xp11.2 RCC patients with small tumors (<4 cm) and no symptoms were shown to have usually favorable outcomes subsequent to PN. More time is required to further observe this type of RCC, which may belong to a special subtype of Xp11.2 RCCs. "
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    ABSTRACT: The current study presents a case of Xp11.2 translocation renal cell carcinoma (Xp11.2 RCC) in a 30-year-old female. The patient was referred to The Affiliated Drum Tower Hospital of the Medical College of Nanjing University (Nanjing, Jiangsu, China) due to a right renal tumor without evident symptoms, which was found by a routine physical examination. A computed tomography (CT) scan indicated that the mass exhibited cystic and solid components. The patient underwent laparoscopic radiofrequency ablation-assisted enucleation. Immunohistochemistry revealed intense nuclear staining for transcription factor E3 protein in the cancer cells. The patient was diagnosed with Xp11.2 RCC. The urological and radiological outcomes remained satisfactory after >2.5 years of follow-up.
    Oncology letters 09/2014; 8(3):1237-1239. DOI:10.3892/ol.2014.2267 · 1.55 Impact Factor
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    • "Cette classification histologique est utilisée pour le diagnostic. Ces dernières années, l'apport de la cytogénétique a permis la reconnaissance de nouveaux sous-types de carcinomes rénaux comme le carcinome rénal avec translocation impliquant la région Xp11,2 (TFE3) [5] [6]. L'évaluation du pronostic individuel et la thérapeutique des patients atteints d'un carcinome rénal repose sur la prise en compte de facteurs cliniques (performans status), histopathologiques (type cellulaire, architecture tumorale, taille tumorale, stade TNM, grade nucléaire de Fuhrman) et biologiques. "
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    ABSTRACT: Renal carcinomas are histologically and prognostically heterogeneous. Genomic as well as chromosomal studies of these tumors have permitted a better comprehension of molecular mechanisms implicated in their development and progression. The most frequent histological subtypes are characterized by recurrent cytogenetic abnormalities, such as the loss of the chromosome 3 short arm involving a VHL gene copy in clear cell renal carcinomas, or trisomies 7 and 17 in papillary renal cell carcinomas. New histological subtypes like renal carcinomas associated with Xp11.2 translocations have also been individualized. Besides diagnosis, some chromosomal aberrations like the loss of a short arm of chromosome 9 in different renal carcinoma histological subtypes have a worse prognostic impact. The identification of chromosomal shuffles contributes in backing histological diagnosis and in precising the individual prognosis of patients. This review describes chromosomal abnormalities associated to renal carcinomas and their impact for an accurate classification of these tumors and the evaluation of their prognosis.
    Morphologie 03/2014; 98(320). DOI:10.1016/j.morpho.2014.02.006
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