Perivascular Epithelioid Cell Tumors (PEComas) Harboring TFE3 Gene Rearrangements Lack the TSC2 Alterations Characteristic of Conventional PEComas

*Brigham & Women's Hospital Boston, MA †Department of Pathology, Emory University, Atlanta, GA ‡Department of Pathology, University of Verona, Verona, Italy §The Johns Hopkins Hospital Baltimore, MD.
The American journal of surgical pathology (Impact Factor: 5.15). 03/2012; 36(5):783-4. DOI: 10.1097/PAS.0b013e31824a8a37
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Available from: Izabela Malinowska
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    • "TFE3 rearrangements are also present in alveolar soft part sarcoma, certain pediatric renal cancers and a subset of PEComas [15-18]. The use of an antibody against the C-terminal portion of TFE3 seems to be a useful diagnostic tool in all rearranged tumors [10,19], but one has to be aware of an unspecific staining pattern [17] as we found in a proportion of cases with WWTR1-CAMTA1 fusion. "
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    ABSTRACT: Epithelioid hemangioendothelioma is a malignant, often indolent vascular tumor which occurs at various anatomic sites. Based on a reciprocal translocation t (1;3)(p36;q25), a consistent WWTR1-CAMTA1 fusion gene has been found. An alternate YAP1-TFE3 fusion has been detected in a small and distinct subset of cases. Methods: Thirty-nine tumors, from 24 females and 15 males with an age range 9-85 years, were located in soft tissue (head and neck [8], trunk [5], upper extremities [3], lower extremities [2], mediastinal [1], and paratesticular [1]), lymph node (1), breast (1), skin (2), bone (6), lung (7), and liver (2). The cases were investigated using a panel of immunohistochemical markers. The aforementioned fusion-genes were examined using RT-PCR and/or FISH in order to validate their diagnostic value. Results: Follow-up available for 17 patients ranged from 3 months to 7 years (median interval 1.5 years). Eleven patients were alive without disease, 2 patients were alive with disease after 1.5 and 2 years, respectively. Four patients died of disease after 4 months (n = 1), 5 months (n = 2), and 1.5 years (n = 1). The size, known for 30 lesions, was >3 cm in 9 of them. Histologically, all lesions had classical features, at least focally. Four tumors counted >3 mitoses/50 HPF. Immunohistochemically, all cases tested stained positive for ERG (21), FLI1 (5) and CD31 (39). CD34 and D2-40 positivity was seen in 81% and 71% of the examined cases, respectively. 11/35 cases expressed pan-keratin and 6/20 cases CK8.18. TFE3 showed a nuclear reaction in 21/24 cases, irrespective of TFE3 rearrangement. Molecular genetically, 35/35 cases revealed one of the fusion genes by FISH and/or RT-PCR with WWTR1-CAMTA1 in 33 cases and YAP1-TFE3 in 2 cases. Conclusions: These results demonstrate the high diagnostic value of FISH and RT-PCR in detecting the fusion genes of EHE. The immunohistochemical utility of TFE3 appears questionable in this study.
    Full-text · Article · Jul 2014 · Diagnostic Pathology
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    • "This raises the possibility that melanotic Xp11 TRC and Xp11RCC are closely related, although in the majority of cases to date the gene fusion partner of TFE3 has not been described [2]. TFE3-rearranged PEComas that exhibit strong TFE positivity and minimal desmin and actin positivity have also recently been described [14]. Therefore, TFE3-rearranged PEComa should be carefully considered as a diagnostic possibility in tumors with histologic features that overlap with melanotic Xp11 TRC. "
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    ABSTRACT: Melanotic Xp11 translocation renal cancer is a rare tumor belonging to the family of microphthalmia-associated transcription factor (MiTF)/transcription factor E (TFE) neoplasms. This tumor family also includes alveolar soft part sarcoma, perivascular epithelioid cell neoplasms, Xp11 translocation renal cell carcinoma, and melanoma. To date, six confirmed melanotic Xp11 translocation cancers (five renal, one ovarian) have been reported in the literature.Case Report: Here, we report the clinical, histologic, immunohistochemical, and molecular features of a unique melanotic Xp11 translocation renal cancer arising in a 34-year old African-American female. Histologically, the tumor was composed of epithelioid tumor cells arranged in a nested pattern. The cells had clear to eosinophilic granular cytoplasm, vesicular nuclear chromatin, and prominent nucleoli. Multifocal intracytoplasmic deposits of granular brown melanin pigment were identified and confirmed by Fontana-Masson stain. An unusual histologic feature, not previously reported in melanotic Xp11 translocation renal cancer, was a sarcoid-like granulomatous reaction consisting of tight epithelioid granulomas with lymphocytic cuffing, numerous giant cells, and calcifications. Nuclear transcription factor E3 expression was identified by immunohistochemistry and TFE3 rearrangement was confirmed by fluorescence in situ hybridization. Additional immunohistochemical findings included immunoreactivity for HMB45, cathepsin K, and progesterone receptor; negative staining was seen with actin, desmin, cytokeratins, epithelial membrane antigen, CD10, vimentin, and PAX-8. The patient is currently free of disease, two years following initial clinicoradiologic presentation and twenty-two months following partial nephrectomy without additional therapy. This report further expands the spectrum of morphologic and clinical findings previously described in melanotic Xp11 translocation renal cancer, a distinctive tumor showing overlapping features between Xp11 translocation renal cell carcinoma, melanoma, and perivascular epithelioid cell neoplasms.Virtual slides: The virtual slide(s) for this article can be found here:
    Full-text · Article · Apr 2014 · Diagnostic Pathology
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    ABSTRACT: Perivascular epithelioid cell tumors (PEComas) are mesenchymal tumors composed of histologically, immunohistochemically, ultrastructurally, and genetically distinctive cells. PEComas have been described in different organs and are considered ubiquitous tumors. In this review we discuss recent informations related to PEComas in the genitourinary tract.
    No preview · Article · Feb 2007 · Advances in Anatomic Pathology
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