Hirose Takeshi, Chang Hsin-Yi, Saoud Carla, Lefkowitz Robert A, Athanasian Edward, Antonescu Cristina R
Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
Genes Chromosomes Cancer. 2025 Jan;64(1):e70018. doi: 10.1002/gcc.70018.
Myxoinflammatory fibroblastic sarcoma (MIFS) is a rare, low-grade sarcoma affecting with predilection the acral soft tissues of middle-aged adults. Clinically, MIFS is associated with a high rate of local recurrence but infrequent distant metastases. The diagnosis remains challenging due to their wide histologic spectrum and overlap with reactive, benign, and low-grade malignant lesions. Moreover, a significant limitation is that molecular confirmation is achieved in only a subset of cases, due to its broad range of genetic alterations which requires a multiplatform approach. Thus, a definitive diagnosis, especially at nonacral sites and in molecularly negative cases, remains uncertain. Our goal was to perform a detailed clinicopathologic and molecular reappraisal of MIFS managed at a single tertiary cancer center with dedicated orthopedic oncology expertise. Additionally, we examined potential outcomes correlating with specific genetic alterations.
A cohort of 33 patients (12 males, 21 females, median age 52 years) was selected. Tumors were tested by FISH, Archer, and/or targeted NGS.
VGLL3 amplification was detected in 84%, BRAF fusions in 33% and combined TGFBR3/MGEA5 rearrangements in 32% of cases. Two novel fusions were detected, RRAGB::CCNB3 and FGFR1::ZBTB47. Other events included a YAP1::MAML2 fusion in two cases, one co-existing with a BRAF fusion. Overall, 8 (24%) patients recurred, 4 more than once, while 4 (12%) patients developed metastasis (3 locoregional, 1 pulmonary), all associated with VGLL3 gene amplification.
Positive margin status was associated with increased recurrence and reduced disease-free survival (DFS, p = 0.02). Moreover, it emphasizes the impact of multiplatform molecular testing in confirming the diagnosis. The lack of both local recurrence and metastatic potential outside VGLL3 amplifications requires further investigation.
黏液样炎性纤维母细胞肉瘤（MIFS）是一种罕见的低级别肉瘤，好发于中年成人的肢端软组织。临床上，MIFS局部复发率高，但远处转移不常见。由于其广泛的组织学谱以及与反应性、良性和低级别恶性病变的重叠，诊断仍然具有挑战性。此外，一个显著的局限性是，由于其广泛的基因改变需要多平台方法，只有一部分病例能够实现分子确诊。因此，明确诊断，尤其是在非肢端部位和分子检测阴性的病例中，仍然不确定。我们的目标是对一家拥有专门骨科肿瘤学专业知识的单一三级癌症中心管理的MIFS进行详细的临床病理和分子重新评估。此外，我们研究了与特定基因改变相关的潜在结果。
选取了33例患者（12例男性，21例女性，中位年龄52岁）。通过荧光原位杂交（FISH）、Archer检测和/或靶向二代测序（NGS）对肿瘤进行检测。
84%的病例检测到VGLL3扩增，33%检测到BRAF融合，32%检测到TGFBR3/MGEA5联合重排。检测到两种新的融合，RRAGB::CCNB3和FGFR1::ZBTB47。其他事件包括两例YAP1::MAML2融合，其中一例与BRAF融合共存。总体而言，8例（24%）患者复发，4例复发不止一次，而4例（12%）患者发生转移（3例局部区域转移，1例肺转移），均与VGLL3基因扩增相关。
切缘阳性状态与复发增加和无病生存期（DFS，p = 0.02）缩短相关。此外，它强调了多平台分子检测在确诊中的影响。除了VGLL3扩增外，缺乏局部复发和转移潜能需要进一步研究。
