Department of Biopathology, Institut Bergonié, Comprehensive Cancer Center, F-33000, Bordeaux, France.
Department of Pathology, Hôpital Trousseau-CHU de Tours, Avenue de la République, 37170, Chambray-lès-Tours, France.
Mod Pathol. 2022 Oct;35(10):1398-1404. doi: 10.1038/s41379-022-01096-6. Epub 2022 May 11.
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.
黏液炎症性纤维母细胞肉瘤（MIFS）是一种罕见的软组织肿瘤，好发于四肢远端，具有局部复发倾向。形态学上，MIFS 由梭形和奇异上皮样细胞组成，类似于嵌入纤维黏液基质中的 virocyte，伴有丰富的炎症浸润。重要的是，MIFS 的分子谱很广泛，包括：VGLL3 扩增、BRAF 融合/扩增和 OGA/TGFBR3 重排。在本研究中，我们描述了一种具有频繁结节状形态的 MIFS 变体，其特征为坏死和 YAP1::MAML2 融合的频繁复发。该队列包括 7 名患者（4 名女性和 3 名男性），年龄 21 至 71 岁（中位数：47 岁）。2 例肿瘤（28%）发生在肢端部位，其余病例分布更为广泛（大腿，n=2；手臂，n=1；颈部，n=1；胸壁，n=1）。肿瘤大小为 10 至 38mm（中位数：20mm）。组织学上，病变常表现为结节状，中央有坏死区，主要由上皮样细胞组成，细胞核大而呈泡状，核仁明显（雷氏细胞样细胞或 virocyte）。基质主要为纤维状，伴有多形性炎症浸润。1 例病例可见局灶性黏液样基质改变，无假性脂肪细胞。免疫表型不具有特异性，仅在部分病例中表达泛角蛋白（AE1-AE3）和 cyclin D1。RNA 测序在 3/7 例中检测到 YAP1::MAML2 融合；在 4 例测试病例中，aCGH 未显示明显的基因拷贝数变异，在 1 例测试病例中未显示 VGLL3 扩增。6 例患者可获得随访，随访时间为 7 至 63 个月（中位数：42 个月）。未发现局部复发和转移，1 例肿瘤在初次活检后自发消退。总之，我们描述了一种具有独特临床病理和分子特征的 MIFS 新变体，我们提出了“结节性坏死性”MIFS 的术语。
