Recurrent YAP1::MAML2 fusions in “nodular necrotizing” variants of myxoinflammatory fibroblastic sarcoma: a comprehensive study of 7 cases

Myxoinflammatory fibroblastic sarcoma (MIFS) is a rare soft tissue tumor with a predilection for the distal extremities and a tendency for local recurrence. Morphologically, MIFS consists of spindle and bizarre epithelioid cells resembling virocytes embedded in a fibrous to myxoid stroma with an abu...

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Bibliographic Details
Published in:Modern pathology Vol. 35; no. 10; pp. 1398 - 1404
Main Authors: Perret, Raul, Tallegas, Matthias, Velasco, Valérie, Soubeyran, Isabelle, Coindre, Jean-Michel, Azmani, Rihab, Baud, Jessica, Bacle, Guillaume, De Pinieux, Gonzague, Le Loarer, François
Format: Journal Article
Language:English
Published: New York Elsevier Inc 01.10.2022
Nature Publishing Group US
Elsevier Limited
Subjects:
14/1
14/63
38/91
45/43
45/61
631/337/2019
692/308/53/2421
692/699/67/1798
Biopsy
Copy number
Cyclin D1
Cyclin D1 - genetics
DNA Copy Number Variations
Female
Fibrosarcoma - genetics
Humans
Inflammation
Keratin
Keratins
Laboratory Medicine
Male
Medicine
Medicine & Public Health
Metastases
Necrosis
Nucleoli
Pathology
Proto-Oncogene Proteins B-raf - genetics
RNA
Sarcoma
Skin Neoplasms
Soft Tissue Neoplasms - pathology
Stroma
Trans-Activators - genetics
Transcription Factors - genetics
Tumors
YAP-Signaling Proteins
Yes-associated protein
ISSN:0893-3952, 1530-0285, 1530-0285
Online Access:Get full text
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Description
Summary:Myxoinflammatory fibroblastic sarcoma (MIFS) is a rare soft tissue tumor with a predilection for the distal extremities and a tendency for local recurrence. Morphologically, MIFS consists of spindle and bizarre epithelioid cells resembling virocytes embedded in a fibrous to myxoid stroma with an abundant inflammatory infiltrate. Importantly, the molecular landscape of MIFS is wide and includes: VGLL3 amplification, BRAF fusion/amplification and OGA/TGFBR3 rearrangements. In this study, we describe a variant of MIFS showing a frequent nodular configuration associated with necrosis and recurrent YAP1::MAML2 fusions. The cohort consisted of 7 patients (4 females and 3 males) ranging in age from 21 to 71 years (median: 47 years). Two tumors (28%) occurred in acral locations while the remaining cases were more widely distributed (thigh, n = 2; arm, n = 1; neck; n = 1; chest-wall, n = 1). Tumor size ranged from 10 to 38 mm (median: 20 mm). Histologically, lesions frequently presented as nodules with central areas of necrosis, and were predominantly composed of sheets of epithelioid cells with large vesicular nuclei and prominent nucleoli (Reed-Sternberg-like cells or virocytes). The stroma was mostly fibrous and showed a polymorphous inflammatory infiltrate. Myxoid stromal changes were focally seen in one case, and pseudolipoblasts were absent. The immunophenotype was nonspecific, with only pan-keratin (AE1-AE3) and cyclin D1 expression in a subset of cases. RNA-Sequencing detected YAP1::MAML2 fusions in 3/7 cases; aCGH showed no significant gene copy number variations in 4 tested cases, and FISH analysis showed no VGLL3 amplification in 1 tested case. Follow-up was available for 6 cases, ranging from 7 to 63 months (median: 42 months). Local recurrence and metastasis were not seen and one tumor showed spontaneous regression following initial biopsy. In conclusion, we describe a novel variant of MIFS with distinctive clinicopathological and molecular features for which we propose the term “nodular necrotizing” MIFS.
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ISSN:0893-3952
1530-0285
1530-0285
DOI:10.1038/s41379-022-01096-6