神经肌肉脉络膜瘤(NMC)是一种周围神经畸形,通常与纤维瘤病(NMC-DTF)相关,模仿散发性纤维瘤病(DTF)。散发性DTF通常是保守管理的,但其临床行为各不相同。CTNNB1突变亚型在散发性DTF中具有预后价值。我们以前已经在NMC中发现了CTNNB1突变,和3个配对的NMC-DTF,但NMC-DTF的临床行为知之甚少。
评估NMC-DTF患者以确定(1)NMC-DTF中的CTNNB1突变亚型,和(2)相关的临床行为和对治疗的反应。
临床回顾,成像,NMC和NMC-DTF患者的病理特征,和分子检测CTNNB1突变。
在7例坐骨神经NMC患者中(中位年龄:18岁),NMC-DTF(平均大小10.7cm)在NMC活检(N=5)或自发(N=2)后不久出现:6个NMC-DTF具有CTNNB1p.S45X突变,1个NMC-DTF具有p.T41A突变。所有患者的CTNNB1-p。S45突变的NMC-DTF在广泛的局部切除或主动监测后出现局部进展,包括一个远端异时NMC-DTF。无患者自发性疾病稳定。辅助放疗或全身治疗后,4例(6例)患者实现疾病稳定.一名患者在索拉非尼治疗后进展。
NMC-DTF经常含有CTNNB1p.S45突变,表现得很积极,并且需要辅助治疗来稳定疾病。我们现在单独使用成像来诊断NMC,并常规监测受NMC影响的神经段以识别早期NMC-DTF。与零星的DTF相比,对于NMC-DTF的最佳疾病管理,可能需要尽早采用系统治疗策略.
Neuromuscular choristoma (NMC) is a peripheral nerve malformation frequently associated with a fibromatosis (NMC-DTF) that mimics sporadic desmoid-type fibromatosis (DTF). Sporadic DTF is often managed conservatively but its clinical behavior varies. CTNNB1 mutational subtypes in sporadic DTF have prognostic value. We have previously identified CTNNB1 mutations in NMC, and 3 paired NMC-DTF but the clinical behavior of NMC-DTF is poorly understood.
To evaluate patients with NMC-DTF to determine (1) CTNNB1 mutational subtypes in NMC-DTF, and (2) associated clinical behavior and response to treatment.
Retrospective review of clinical, imaging, and pathologic features of patients with NMC and NMC-DTF, and molecular testing for CTNNB1 mutations.
Among 7 patients with NMC of the sciatic nerve (median age: 18 yr), NMC-DTF (mean size 10.7 cm) developed shortly following NMC biopsy (N = 5) or spontaneously (N = 2): 6 NMC-DTF had CTNNB1 p.S45X mutations and 1 NMC-DTF had a p.T41A mutation. All patients with CTNNB1-p.S45-mutated NMC-DTF developed local progression after wide local excision or active surveillance, including one distal metachronous NMC-DTF. No patient had spontaneous disease stabilization. Following adjuvant radiation or systemic therapy, disease stabilization was achieved in 4 (of 6) patients. One patient progressed on sorafenib treatment.
NMC-DTF frequently contain CTNNB1 p.S45 mutations, behave aggressively, and require adjuvant therapies for disease stabilization. We now use imaging alone to diagnose NMC, and routinely surveille the NMC-affected nerve segment to identify early NMC-DTF. In contrast to sporadic DTF, earlier adoption of systemic therapeutic strategies may be required for optimal disease management of NMC-DTF.