Pediatric Mesothelioma With ALK Fusions: A Molecular and Pathologic Study of 5 Cases.
Abdominal Neoplasms
/ enzymology
Adolescent
Anaplastic Lymphoma Kinase
/ genetics
Biomarkers, Tumor
/ analysis
Child
Female
Gene Fusion
Gene Rearrangement
Genetic Predisposition to Disease
Humans
Immunohistochemistry
Male
Mesothelioma
/ enzymology
Molecular Diagnostic Techniques
Testicular Neoplasms
/ enzymology
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 05 2021
01 05 2021
Historique:
pubmed:
6
1
2021
medline:
11
5
2021
entrez:
5
1
2021
Statut:
ppublish
Résumé
Pediatric mesotheliomas are rare and their pathogenesis remains undefined. In this study, we report 5 cases of malignant mesothelioma in children, characterized by fusions involving the anaplastic lymphoma kinase (ALK) gene. Four cases occurred in females involving the abdominal cavity and were characterized by a pure epithelioid morphology. The fifth arose in the tunica vaginalis of a 15-year-old male and displayed a biphasic epithelioid-sarcomatoid phenotype. All cases demonstrated the classic morphologic and immunohistochemical features of malignant mesothelioma, including tubulopapillary architecture and cuboidal epithelioid cells with eosinophilic cytoplasm and uniform nuclei with vesicular chromatin. Immunohistochemically, all cases showed labeling for ALK, cytokeratins, WT1, and calretinin, while lacking expression of adenocarcinoma immunomarkers. Four cases demonstrated weak-moderate labeling for PAX8 protein, which resulted in diagnostic challenges with primary peritoneal serous carcinoma. The ALK genetic abnormalities were investigated by a combination of molecular methods. Archer FusionPlex was performed in 2 cases, showing fusions between ALK with either STRN or TPM1 genes, resulting in a transcript that retained the ALK kinase domain. One case was further studied by DNA targeted sequencing, but no additional genetic alterations were observed. In 1 case, cytogenetic analysis showed the presence of a t(2;15)(p23;q22) and fluorescence in situ hybridization confirmed the ALK gene break-apart. In the remaining 2 cases, ALK gene rearrangements were demonstrated by fluorescence in situ hybridization. Unlike adult mesotheliomas, which are tightly linked to asbestos exposure, often show loss of BAP1 expression and have complex karyotypes, ALK-rearranged mesothelioma appears to be similar to other fusion-positive mesotheliomas, such as those harboring EWSR1/FUS-ATF1 fusions, sharing significant morphologic overlap, occurring in young patients and displaying a simple, translocation-driven genetic profile.
Identifiants
pubmed: 33399341
doi: 10.1097/PAS.0000000000001656
pii: 00000478-202105000-00006
pmc: PMC8035308
mid: NIHMS1654364
doi:
Substances chimiques
Biomarkers, Tumor
0
ALK protein, human
EC 2.7.10.1
Anaplastic Lymphoma Kinase
EC 2.7.10.1
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
653-661Subventions
Organisme : NCI NIH HHS
ID : P30 CA008748
Pays : United States
Organisme : NCI NIH HHS
ID : P50 CA140146
Pays : United States
Organisme : NCI NIH HHS
ID : P50 CA217694
Pays : United States
Informations 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 P50 CA217694 (C.R.A.), P50 CA140146 (C.R.A.), P30 CA008748 (C.R.A.), Cycle for Survival (C.R.A.), Kristin Ann Carr Foundation (C.R.A.), Dahan Translocation Carcinoma Fund (P.A.). 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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