Top

Published in:

01-10-2021 | Fluorescence in Situ Hybridization | Brief Report

Clear cell tumor with melanocytic differentiation and MITF-CREM translocation: a novel entity similar to clear cell sarcoma

Authors: Arnaud de la Fouchardiere, Daniel Pissaloux, Franck Tirode, John Hanna

Published in: Virchows Archiv | Issue 4/2021

Abstract

The presence of melanocytic differentiation in tumors of non-melanocyte origin is uncommon and is typically associated with the overexpression of MITF, the master regulator of melanin synthesis, or another member of the MIT/TFE3 family. In clear cell sarcoma, the presence of either an EWSR1-ATF1 or EWSR1-CREB1 translocation-derived fusion protein is thought to drive melanocytic differentiation by directly stimulating the expression of MITF. Here, we describe a clear cell neoplasm with melanocytic differentiation that is characterized by a novel MITF-CREM gene fusion. CREM is the third member of the ATF1/CREB1/CREM family, and the nature of the MITF-CREM fusion appears analogous to the EWSR1-ATF1 and EWSR1-CREB1 fusions. Thus, this MITF-CREM-rearranged clear cell tumor represents a novel entity with morphologic, immunohistochemical, and molecular similarity to clear cell sarcoma.

Bertolotto C, Abbe P, Hemesath TJ, Bille K, Fisher DE, Ortonne JP, Ballotti R (1998) Microphthalmia gene product as a signal transducer in cAMP-induced differentiation of melanocytes. J Cell Biol 142(3):827–835CrossRef

Price ER, Horstmann MA, Wells AG, Weilbaecher KN, Takemoto CM, Landis MW, Fisher DE (1998) Alpha-melanocyte-stimulating hormone signaling regulates expression of microphthalmia, a gene deficient in Waardenburg syndrome. J Biol Chem 273(49):33042–33047CrossRef

Kawakami A, Fisher DE (2017) The master role of microphthalmia-associated transcription factor in melanocyte and melanoma biology. Lab Investig 97(6):649–656CrossRef

Garraway LA, Widlund HR, Rubin MA, Getz G, Berger AJ, Ramaswamy S, Beroukhim R, Milner DA, Granter SR, Du J, Lee C, Wagner SN, Li C, Golub TR, Rimm DL, Meyerson ML, Fisher DE, Sellers WR (2005) Integrative genomic analyses identify MITF as a lineage survival oncogene amplified in malignant melanoma. Nature. 436(7047):117–122CrossRef

Thway K, Fisher C (2012) Tumors with EWSR1-CREB1 and EWSR1-ATF1 fusions: the current status. Am J Surg Pathol 36(7):e1–e11CrossRef

Granter SR, Weilbaecher KN, Quigley C, Fletcher CD, Fisher DE (2001) Clear cell sarcoma shows immunoreactivity for microphthalmia transcription factor: further evidence for melanocytic differentiation. Mod Pathol 14(1):6–9CrossRef

Davis IJ, Kim JJ, Ozsolak F, Widlund HR, Rozenblatt-Rosen O, Granter SR, Du J, Fletcher JA, Denny CT, Lessnick SL, Linehan WM, Kung AL, Fisher DE (2006) Oncogenic MITF dysregulation in clear cell sarcoma: defining the MiT family of human cancers. Cancer Cell 9(6):473–484CrossRef

Russell-Goldman E, Lindeman NI, Laga AC, Hanna J (2020) Morphologic, immunohistochemical, and molecular distinction between fibroepithelioma of Pinkus and “fenestrated” basal cell carcinoma. Am J Dermatopathol 42(7):513–520CrossRef

Cellier L, Perron E, Pissaloux D, Karanian M, Haddad V, Alberti L, de la Fouchardière A (2018) Cutaneous melanocytoma with CRTC1-TRIM11 fusion: report of 5 cases resembling clear cell sarcoma. Am J Surg Pathol 42(3):382–391CrossRef

10.

Ko JS, Wang L, Billings SD, Pissaloux D, Tirode F, Berry R, De La Fouchardiere A (2019) CRTC1-TRIM11 fusion defined melanocytic tumors: a series of four cases. J Cutan Pathol 46(11):810–818CrossRef

11.

Kao YC, Sung YS, Zhang L, Chen CL, Vaiyapuri S, Rosenblum MK, Antonescu CR (2017) EWSR1 fusions with CREB family transcription factors define a novel myxoid mesenchymal tumor with predilection for intracranial location. Am J Surg Pathol 41(4):482–490CrossRef

12.

Chapman E, Skalova A, Ptakova N, Martinek P, Goytain A, Tucker T, Xiong W, Leader M, Kudlow BA, Haimes JD, Hayes MM, Bohus P, Miesbauerova M, Lee CH, Ng TL (2018) Molecular profiling of hyalinizing clear cell carcinomas revealed a subset of tumors harboring a novel EWSR1-CREM fusion: report of 3 cases. Am J Surg Pathol 42(9):1182–1189CrossRef

13.

Yoshida A, Wakai S, Ryo E, Miyata K, Miyazawa M, Yoshida KI, Motoi T, Ogawa C, Iwata S, Kobayashi E, Watanabe SI, Kawai A, Mori T (2019) Expanding the phenotypic spectrum of mesenchymal tumors harboring the EWSR1-CREM fusion. Am J Surg Pathol 43(12):1622–1630CrossRef

Title: Clear cell tumor with melanocytic differentiation and MITF-CREM translocation: a novel entity similar to clear cell sarcoma
Authors: Arnaud de la Fouchardiere
Daniel Pissaloux
Franck Tirode
John Hanna
Publication date: 01-10-2021
Publisher: Springer Berlin Heidelberg
Keywords: Fluorescence in Situ Hybridization
Clear-Cell Sarcoma
Published in: Virchows Archiv / Issue 4/2021
Print ISSN: 0945-6317
Electronic ISSN: 1432-2307
DOI: https://doi.org/10.1007/s00428-021-03027-3

At a glance: The STEP trials

Springer Medicine

Clear cell tumor with melanocytic differentiation and MITF-CREM translocation: a novel entity similar to clear cell sarcoma

Abstract

At a glance: The STEP trials

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 4/2021

Prognostic relevance and putative histogenetic role of cytokeratin 7 and MUC5AC expression in Crohn’s disease-associated small bowel carcinoma

Keratin 7 expression in hepatic cholestatic diseases

Micronodular thymic carcinoma with lymphoid hyperplasia: relevance of immunohistochemistry with a small panel of antibodies for diagnosis—a RYTHMIC study

An immunohistochemical panel of insulin-like growth factor II mRNA-binding protein 3 (IMP3), enhancer of zeste homolog 2 (EZH2), and p53 is useful for a diagnosis in bile duct biopsy

Correction to: Keratin 7 expression in hepatic cholestatic diseases

In this issue