Cytokeratin-positive Malignant Tumor in the Abdomen With EWSR1/FUS-CREB Fusion: A Clinicopathologic Study of 8 Cases.
Abdominal Neoplasms
/ chemistry
Adolescent
Adult
Aged
Biomarkers, Tumor
/ analysis
Cyclic AMP Response Element Modulator
/ genetics
Gene Fusion
Genetic Predisposition to Disease
Histiocytoma, Malignant Fibrous
/ chemistry
Humans
Immunohistochemistry
In Situ Hybridization, Fluorescence
Keratins
/ analysis
Male
Mesothelioma, Malignant
/ chemistry
Middle Aged
Oncogene Proteins, Fusion
/ genetics
Phenotype
RNA-Binding Protein FUS
/ genetics
RNA-Seq
Treatment Outcome
Young Adult
Journal
The American journal of surgical pathology
ISSN: 1532-0979
Titre abrégé: Am J Surg Pathol
Pays: United States
ID NLM: 7707904
Informations de publication
Date de publication:
01 01 2022
01 01 2022
Historique:
pubmed:
29
5
2021
medline:
15
2
2022
entrez:
28
5
2021
Statut:
ppublish
Résumé
ATF1, CREB1, and CREM, which encode the CREB family of transcription factors, are fused with EWSR1 or FUS in human neoplasms, such as angiomatoid fibrous histiocytoma. EWSR1/FUS-CREB fusions have recently been reported in a group of malignant epithelioid tumors with a predilection to the peritoneal cavity and frequent cytokeratin expression. Here, we studied 8 cytokeratin-positive abdominal malignancies with these fusions for further characterization. The tumors affected males (15 to 76 y old) and presented as intra-abdominal masses with concurrent or subsequent peritoneal dissemination, ascites, and/or metastases to the liver or lymph nodes. Four patients died of the disease within 18 to 140 months. Cases 1 to 5 showed multinodular growth of monomorphic epithelioid cells with focal serous cysts. Lymphoplasmacytic infiltration was prominent and was associated with systemic inflammatory symptoms. Two patients suffered from membranous nephropathy with nephrosis. The tumors displayed partly overlapping phenotypes with malignant mesothelioma, including diffuse strong expression of AE1/AE3 and WT1 and membranous positivity of sialylated HEG1, although calretinin was negative. Case 6 showed similar histology to cases 1 to 5, but expressed smooth muscle actin diffusely, lacked WT1 and HEG1, and harbored prominent pseudoangiomatous spaces. Cases 7 and 8 displayed dense growth of small oval to short spindle cells, with occasional molding and minor swirling, superficially resembling small cell carcinoma. Lymphoplasmacytic infiltration was not observed. The tumors were positive for AE1/AE3 and CD34 (focal), whereas calretinin, WT1, and HEG1 were negative. The detected fusions were FUS-CREM (n=4), EWSR1-ATF1 (n=2), EWSR1-CREB1 (n=1), and EWSR1-CREM (n=1). We confirmed the prior observation that these tumors do not fit perfectly with known entities and provided additional novel clinicopathologic information. The tumors require wider recognition because of more aggressive behavior than angiomatoid fibrous histiocytoma despite similar genetics, and potential misdiagnosis as unrelated diseases, such as neuroendocrine neoplasms.
Identifiants
pubmed: 34049318
doi: 10.1097/PAS.0000000000001742
pii: 00000478-202201000-00022
doi:
Substances chimiques
Biomarkers, Tumor
0
CREM protein, human
0
EWSR1-ATF1 fusion protein, human
0
EWSR1-CREB1 fusion protein, human
0
FUS protein, human
0
Oncogene Proteins, Fusion
0
RNA-Binding Protein FUS
0
Cyclic AMP Response Element Modulator
135844-64-3
Keratins
68238-35-7
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
134-146Informations de copyright
Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.
Déclaration de conflit d'intérêts
Conflicts of Interest and Source of Funding: Supported in part by JSPS Grant-in-Aid for Young Scientists 18K15108 (A.Y.). The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article.
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