Malignant undifferentiated epithelioid neoplasms with MAML2 rearrangements: A clinicopathologic study of seven cases demonstrating a heterogenous entity Journal Article
| Authors: | Dermawan, J. K.; DiNapoli, S. E.; Sukhadia, P.; Mullaney, K. A.; Gladdy, R.; Healey, J. H.; Agaimy, A.; Cleven, A. H.; Suurmeijer, A. J. H.; Dickson, B. C.; Antonescu, C. R. |
| Article Title: | Malignant undifferentiated epithelioid neoplasms with MAML2 rearrangements: A clinicopathologic study of seven cases demonstrating a heterogenous entity |
| Abstract: | Among mesenchymal tumors, MAML2 gene rearrangements have been described in a subset of composite hemangioendothelioma and myxoinflammatory fibroblastic sarcoma (MIFS). However, we have recently encountered MAML2-related fusions in a group of seven undifferentiated malignant epithelioid neoplasms that do not fit well to any established pathologic entities. The patients included five males and two female, aged 41–71 years old (median 65 years). The tumors involved the deep soft tissue of extremities (hip, knee, arm, hand), abdominal wall, and the retroperitoneum. Microscopically, the tumors consisted of solid sheets of atypical epithelioid to histiocytoid cells with abundant cytoplasm. Prominent mitotic activity and necrosis were present in 4 cases. In 3 cases, the cells displayed hyperchromatic nuclei or conspicuous macronucleoli, and were admixed with background histiocytoid cells and a lymphoplasmacytic infiltrate. By immunohistochemistry (IHC), the neoplastic cells had a nonspecific phenotype. On targeted RNA sequencing, MAML2 was the 3′ partner and fused to YAP1 (4 cases), ARHGAP42 (2 cases), and ENDOD1 (1 case). Two cases with YAP1::MAML2 harbored concurrent RAF kinase fusions (RBMS3::RAF1 and AGK::BRAF, respectively). In 2 cases with targeted DNA sequencing, mutations in TP53, RB1 and PTEN were detected in 1 case, and PDGFRB mutations, CCNE1 amplifications and CDKN2A/2B deletion were detected in another case, which showed strong and diffuse PDGFRB expression by IHC. Of the 4 cases with detailed clinical history (median follow-up period 8 months), three developed distant metastatic disease (one of which died of disease); one case remained free of disease 3 years following surgical excision. In conclusion, we describe a heterogeneous series of MAML2-rearranged undifferentiated malignant epithelioid neoplasms, a subset of which may overlap with a recently described MIFS variant with YAP1::MAML2 fusions, further expanding the clinicopathologic spectrum of mesenchymal neoplasms with recurrent MAML2 gene rearrangements. © 2022 Wiley Periodicals LLC. |
| Keywords: | immunohistochemistry; adult; clinical article; protein expression; aged; middle aged; unclassified drug; gene deletion; genetics; mortality; microscopy; anamnesis; raf protein; adjuvant therapy; cancer radiotherapy; disease free survival; follow up; antineoplastic agent; mitosis; phenotype; metabolism; tumor localization; cell infiltration; cohort analysis; genetic variability; transcription factor; tumor biopsy; necrosis; protein p53; tumor marker; distant metastasis; transcription factors; docetaxel; soft tissue; rna; plasma cell; dna; gene rearrangement; fibrosarcoma; transactivator protein; phosphatidylinositol 3,4,5 trisphosphate 3 phosphatase; tumor cell; gene fusion; knee; cytoplasm; guanosine triphosphatase activating protein; trans-activators; histiocyte; cyclin dependent kinase inhibitor 2a; endonuclease; retinoblastoma protein; lymphocyte; yap1; transcription factor yap1; b raf kinase; epithelioid sarcoma; soft tissue neoplasms; soft tissue tumor; abdominal wall; retroperitoneum; regulator protein; platelet derived growth factor beta receptor; receptor, platelet-derived growth factor beta; hand; fibromyxosarcoma; epithelioid; wide excision; cyclin dependent kinase inhibitor 2b; arm; myxoinflammatory fibroblastic sarcoma; hip; decitabine; dna sequencing; humans; human; male; female; article; rna sequencing; macronucleus; undifferentiated sarcoma; biomarkers, tumor; maml2 gene; maml2; epithelioid histiocyte; maml2 protein, human; maml2 protein |
| Journal Title: | Genes Chromosomes and Cancer |
| Volume: | 62 |
| Issue: | 4 |
| ISSN: | 1045-2257 |
| Publisher: | Wiley Periodicals, Inc |
| Date Published: | 2023-04-01 |
| Start Page: | 191 |
| End Page: | 201 |
| Language: | English |
| DOI: | 10.1002/gcc.23102 |
| PUBMED: | 36344258 |
| PROVIDER: | scopus |
| PMCID: | PMC9908836 |
| DOI/URL: | |
| Notes: | Article -- MSK Cancer Center Support Grant (P30 CA008748) acknowledged in PubMed and PDF -- MSK corresponding author is Cristina Antonescu -- Export Date: 1 March 2023 -- Source: Scopus |
Altmetric
Citation Impact
BMJ Impact Analytics
Related MSK Work