EWSR1 translocation in primary hyalinising clear cell carcinoma of the thymus.
ATF1
EWSR1
hyalinising clear cell carcinoma
thymic carcinoma
thymus
Journal
Histopathology
ISSN: 1365-2559
Titre abrégé: Histopathology
Pays: England
ID NLM: 7704136
Informations de publication
Date de publication:
Sep 2019
Sep 2019
Historique:
received:
30
01
2019
revised:
24
04
2019
accepted:
28
04
2019
pubmed:
6
5
2019
medline:
23
2
2020
entrez:
4
5
2019
Statut:
ppublish
Résumé
In thymic carcinomas, focal clear cell change is a frequent finding. In addition to a prominent, diffuse clear cell morphology, some of these carcinomas show an exuberant hyalinised extracellular matrix, and therefore probably represent a separate entity. However, a characteristic genomic alteration remains elusive. We hypothesised that, analogous to hyalinising clear cell carcinomas of the salivary gland, hyalinising clear cell carcinomas of the thymus might also harbour EWSR1 translocations. We identified nine archived cases of thymic carcinoma with focal clear cell features and two cases that showed remarkable hyalinised stroma and prominent, diffuse clear cell morphology. These two cases expressed p40 and were negative for Pax8, CD5, and CD117. Programmed death-ligand 1 was highly positive in one case (70%), and negative in the other one. EWSR1 translocation was identified in both cases of hyalinising clear cell carcinoma, and was absent in all nine carcinomas that showed clear cell features without substantial hyalinisation. In one of the EWSR1-translocated cases, a fusion between exon 13 and exon 6 of EWSR1 and ATF1, respectively was identified by next-generation sequencing. These findings suggest that the EWSR1 translocation and possibly the EWSR1-ATF1 fusion might be unifying genomic alterations for thymic clear cell carcinomas with prominent hyalinised stroma, for which we propose the term 'hyalinising clear cell carcinoma of the thymus'. Because the immunophenotype is unspecific, testing for the EWSR1 translocation might be helpful in discriminating this entity from other thymic neoplasms or metastases, in particular those with clear cell change.
Substances chimiques
EWSR1 protein, human
0
EWSR1-ATF1 fusion protein, human
0
Oncogene Proteins, Fusion
0
RNA-Binding Protein EWS
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
431-436Informations de copyright
© 2019 John Wiley & Sons Ltd.
Références
Wu J, Fang W, Chen G. The enlightenments from ITMIG Consensus on WHO histological classification of thymoma and thymic carcinoma: refined definitions, histological criteria, and reporting. J. Thorac. Dis. 2016; 8; 738-743.
Levine GD, Rosai J. Thymic hyperplasia and neoplasia: a review of current concepts. Hum. Pathol. 1978; 9; 495-515.
Snover DC, Levine GD, Rosai J. Thymic carcinoma. Five distinctive histological variants. Am. J. Surg. Pathol. 1982; 6; 451-470.
Hasserjian RP, Klimstra DS, Rosai J. Carcinoma of the thymus with clear-cell features. Report of eight cases and review of the literature. Am. J. Surg. Pathol. 1995; 19; 835-841.
Milchgrub S, Gnepp DR, Vuitch F, Delgado R, Albores-Saavedra J. Hyalinizing clear cell carcinoma of salivary gland. Am. J. Surg. Pathol. 1994; 18; 74-82.
Daniele L, Nikolarakos D, Keenan J, Schaefer N, Lam AK. Clear cell carcinoma, not otherwise specified/hyalinising clear cell carcinoma of the salivary gland: the current nomenclature, clinical/pathological characteristics and management. Crit. Rev. Oncol. Hematol. 2016; 102; 55-64.
Garcia JJ, Jin L, Jackson SB et al. Primary pulmonary hyalinizing clear cell carcinoma of bronchial submucosal gland origin. Hum. Pathol. 2015; 46; 471-475.
Shah AA, Mehrad M, Kelting SM, Lewis JS Jr, Stelow EB. An uncommon primary lung tumour: hyalinizing clear cell carcinoma, salivary gland-type. Histopathology 2015; 67; 274-276.
Jeffus SK, Gardner JM, Steliga MA, Shah AA, Stelow EB, Arnaoutakis K. Hyalinizing clear cell carcinoma of the lung: case report and review of the literature. Am. J. Clin. Pathol. 2017; 148; 73-80.
Deenik W, Mooi WJ, Rutgers EJ, Peterse JL, Hart AA, Kroon BB. Clear cell sarcoma (malignant melanoma) of soft parts: a clinicopathologic study of 30 cases. Cancer 1999; 86; 969-975.
Enzinger FM. Clear-cell sarcoma of tendons and aponeuroses. An analysis of 21 cases. Cancer 1965; 18; 1163-1174.
Antonescu CR, Katabi N, Zhang L et al. EWSR1-ATF1 fusion is a novel and consistent finding in hyalinizing clear-cell carcinoma of salivary gland. Genes Chromosomes Cancer 2011; 50; 559-570.
Bridge JA, Borek DA, Neff JR. Huntrakoon M. Chromosomal abnormalities in clear cell sarcoma. Implications for histogenesis. Am. J. Clin. Pathol. 1990; 93; 26-31.
Thway K, Fisher C. Tumors with EWSR1-CREB1 and EWSR1-ATF1 fusions: the current status. Am. J. Surg. Pathol. 2012; 36; e1-e11.
Zucman J, Delattre O, Desmaze C et al. EWS and ATF-1 gene fusion induced by t(12;22) translocation in malignant melanoma of soft parts. Nat. Genet. 1993; 4; 341-345.
Huang J, Ahmad U, Antonicelli A et al. Development of the International Thymic Malignancy Interest Group international database: an unprecedented resource for the study of a rare group of tumors. J. Thorac. Oncol. 2014; 9; 1573-1578.
Hallor KH, Micci F, Meis-Kindblom JM et al. Fusion genes in angiomatoid fibrous histiocytoma. Cancer Lett. 2007; 251; 158-163.
Flucke U, Mentzel T, Verdijk MA et al. EWSR1-ATF1 chimeric transcript in a myoepithelial tumor of soft tissue: a case report. Hum. Pathol. 2012; 43; 764-768.
Radovich M, Pickering CR, Felau I et al. The integrated genomic landscape of thymic epithelial tumors. Cancer Cell 2018; 33; 244-258.
Petrini I, Meltzer PS, Kim IK et al. A specific missense mutation in GTF2I occurs at high frequency in thymic epithelial tumors. Nat. Genet. 2014; 46; 844-849.
Schirosi L, Nannini N, Nicoli D et al. Activating c-KIT mutations in a subset of thymic carcinoma and response to different c-KIT inhibitors. Ann. Oncol. 2012; 23; 2409-2414.
Hishima T, Fukayama M, Fujisawa M et al. CD5 expression in thymic carcinoma. Am. J. Pathol. 1994; 145; 268-275.
Comin CE, Novelli L, Tornaboni D, Messerini L. Clear cell sarcoma of the ileum: report of a case and review of literature. Virchows Arch. 2007; 451; 839-845.
Hisaoka M, Ishida T, Kuo TT et al. Clear cell sarcoma of soft tissue: a clinicopathologic, immunohistochemical, and molecular analysis of 33 cases. Am. J. Surg. Pathol. 2008; 32; 452-460.
Martignoni G, Brunelli M, Segala D et al. Renal cell carcinoma with smooth muscle stroma lacks chromosome 3p and VHL alterations. Mod. Pathol. 2014; 27; 765-774.
Perrino CM, Grignon DJ, Williamson SR, Idrees MT, Eble JN, Cheng L. Morphological spectrum of renal cell carcinoma, unclassified: an analysis of 136 cases. Histopathology 2018; 72; 305-319.
O’Sullivan-Mejia ED, Massey HD, Faquin WC, Powers CN. Hyalinizing clear cell carcinoma: report of eight cases and a review of literature. Head Neck Pathol. 2009; 3; 179-185.
Solar AA, Schmidt BL, Jordan RC. Hyalinizing clear cell carcinoma: case series and comprehensive review of the literature. Cancer 2009; 115; 75-83.