t(6;11) renal cell carcinoma: a study of seven cases including two with aggressive behavior, and utility of CD68 (PG-M1) in the differential diagnosis with pure epithelioid PEComa/epithelioid angiomyolipoma

Abstract

Renal cell carcinomas with t(6;11) chromosome translocation involving the TFEB gene are indolent neoplasms which often occur in young patients. In this study, we report seven cases of renal cell carcinoma with TFEB rearrangement, two of whom had histologically proven metastasis. Patients (4F, 3M) ranged in age from 19 to 55 years (mean 37). One patient developed paratracheal and pleural metastases 24 months after surgery and died of disease after 46 months; another one recurred with neoplastic nodules in the perinephric fat and pelvic soft tissue. Histologically, either cytological or architectural appearance was peculiar in each case whereas one tumor displayed the typical biphasic morphology. By immunohistochemistry, all tumors labelled for cathepsin K, Melan-A and CD68 (KP1 clone). HMB45 and PAX8 staining were detected in six of seven tumors. All tumors were negative for CD68 (PG-M1 clone), CKAE1-AE3, CK7, CAIX, and AMACR. Seven pure epithelioid PEComa/epithelioid angiomyolipomas, used as control, were positive for cathepsin K, melanocytic markers, and CD68 (PG-M1 and KP1) and negative for PAX8. Fluorescence in situ hybridization results showed the presence of TFEB gene translocation in all t(6;11) renal cell carcinomas with a high frequency of split TFEB fluorescent signals (mean 74%). In the primary and metastatic samples of the two aggressive tumors, increased gene copy number was observed (3-5 fluorescent signals per neoplastic nuclei) with a concomitant increased number of CEP6. Review of the literature revealed older age and larger tumor size as correlating with aggressive behavior in these neoplasms. In conclusion, we present the clinical, morphological and molecular features of seven t(6;11) renal cell carcinomas, two with histologically demonstrated metastasis. We report the high frequency of split signals by FISH in tumors with t(6;11) chromosomal rearrangement and the occurrence of TFEB gene copy number gains in the aggressive cases, analyzing either the primary or metastatic tumor. Finally, we demonstrate the usefulness of CD68 (PG-M1) immunohistochemical staining in distinguishing t(6;11) renal cell carcinoma from pure epithelioid PEComa/epithelioid angiomyolipoma.

NEAT1-TFE3 and KAT6A-TFE3 renal cell carcinomas, new members of MiT family translocation renal cell carcinoma

“…The tumor cells are frequently positive for melanocytic markers with negative or low expression of cytokeratins, which distinguishes them from other renal cell carcinoma subtypes [6, 14]. Renal cell carcinomas with MALAT1 (Alpha)-TFEB /t(6;11) are biphasic neoplasms composed of nested larger epithelioid cells with eosinophilic and vacuolated/clear cytoplasm and smaller cells surrounding basement membrane material [1, 20, 21]. The NEAT1-TFE3 renal cell carcinoma case reported here demonstrated a similar phenotype with an alveolar/nested growth pattern and only focal papillary architecture.…”

MiT Family Translocation Renal Cell Carcinoma: from the Early Descriptions to the Current Knowledge

“…Papillary and tubulocystic architectures, clear cell and oncocytoma-like features, and diffuse hyalinization with thick-walled blood vessels are some of the unusual pathological features described [1]. The cells typically show nucleolar grade G2 and G3 by ISUP/WHO 2016 [42].…”

“…The wide spectrum of morphology results in several differential diagnoses including Xp11 translocation renal cell carcinoma, pure epithelioid PEComa/epithelioid angiomyolipoma, and other more common types of renal cell carcinoma [46,47,48]. Among them, pure epithelioid PEComa/epithelioid angiomyolipoma is the most challenging diagnosis in clinical practice [42]. Indeed, the two entities share the immunohistochemical expression of melanogenesis markers and cathepsin K, and both are often negative for cytokeratin.…”

Late local, peritoneal and systemic recurrence of renal angiomyolipoma: A case report

“…The majority of EAML cases display membranous and cytoplasmic staining of E-cadherin, whereas classic AML cases demonstrate cytoplasmic staining alone (20). Moreover, in diagnostically challenging cases, staining for CD68 (PG-M1) (21) and PNL2 (22) may be helpful in distinguishing renal EAML form other renal tumors.…”