Karamzadeh Dashti Nooshin, Bahrami Armita, Lee Seung J, Jenkins Sarah M, Rodriguez Fausto J, Folpe Andrew L, Boland Jennifer M
*Mayo Clinic, Rochester, MN †St Jude Children's Research Hospital, Memphis, TN ‡Johns Hopkins Hospital, Baltimore, MD.
Am J Surg Pathol. 2017 Nov;41(11):1532-1541. doi: 10.1097/PAS.0000000000000913.
Glomus tumors are rare mesenchymal neoplasms with a phenotype akin to the modified smooth muscle cells of the glomus body. Most are benign, but rare examples show malignant histologic characteristics and aggressive behavior. We recently encountered a malignant glomus tumor with BRAF V600E mutation. We sought to study a large cohort for this mutation, with particular attention to associated malignant histologic characteristics. Tumors were classified based on WHO criteria as benign, uncertain malignant potential (glomus tumors of uncertain malignant potential-GT-UMP), or malignant. Tumors were screened for BRAF V600E by immunohistochemistry, and positive staining was evaluated further by Sanger sequencing. A total of 102 glomus tumors were included and classified as benign (57, 56%), GT-UMP (15, 15%) and malignant (30, 29%). Tumors occurred in patients aged 8 to 89.9 years (median: 50.2), without sex predilection (55% men). Most occurred in the superficial soft tissue (84%) and upper extremities (55%). Six of 95 tested cases had BRAF V600E mutation (6%), including 0 of 57 benign tumors, 3 of 14 GT-UMP (21%), and 3 of 24 malignant tumors (12%). Follow-up was obtained for 59 cases (median: 75.7 mo, range: 7.8 to 268.5). Three of 11 malignant tumors (27%) had progressive disease: 1 with metastasis to brain and heart, 1 with enlarging residual disease, and 1 with recurrence. Two of 4 GT-UMP (50%) had progressive disease: 1 with metastasis to lung, and 1 with local recurrence (50%). Three of 44 benign tumors (7%) had local recurrence. Two of 5 patients with BRAF V600E had progression, including 1 GT-UMP with local recurrence and 1 malignant tumor with enlarging residual disease. In summary, BRAF V600E mutation was detected in 6% of glomus tumors, all of which were malignant or GT-UMP. This mutation may be associated with a malignant phenotype, although study of additional cases is needed. In patients with progressive disease, BRAF could be a promising therapeutic target.
血管球瘤是一种罕见的间叶组织肿瘤，其表型类似于血管球的改良平滑肌细胞。大多数为良性，但少数病例具有恶性组织学特征和侵袭性表现。我们最近遇到了一例具有BRAF V600E突变的恶性血管球瘤。我们试图对这一突变进行大样本队列研究，特别关注相关的恶性组织学特征。肿瘤根据世界卫生组织标准分为良性、恶性潜能不确定（恶性潜能不确定的血管球瘤-GT-UMP）或恶性。通过免疫组织化学对肿瘤进行BRAF V600E筛查，阳性染色进一步通过桑格测序进行评估。共纳入102例血管球瘤，分为良性（57例，56%）、GT-UMP（15例，15%）和恶性（30例，29%）。肿瘤发生于8至89.9岁的患者（中位年龄：50.2岁），无性别倾向（男性占55%）。大多数发生于浅表软组织（84%）和上肢（55%）。95例检测病例中有6例（6%）存在BRAF V600E突变，其中57例良性肿瘤中0例，14例GT-UMP中有3例（21%），24例恶性肿瘤中有3例（12%）。对59例进行了随访（中位随访时间：75.7个月，范围：7.8至268.5个月）。11例恶性肿瘤中有3例（27%）出现疾病进展：1例转移至脑和心脏，1例残留病灶增大，1例复发。4例GT-UMP中有2例（50%）出现疾病进展：1例转移至肺，1例局部复发（50%）。44例良性肿瘤中有3例（7%）出现局部复发。5例BRAF V600E突变患者中有2例出现疾病进展，包括1例GT-UMP局部复发和1例恶性肿瘤残留病灶增大。总之，6%的血管球瘤检测到BRAF V600E突变，所有这些均为恶性或GT-UMP。尽管需要更多病例研究，但该突变可能与恶性表型相关。在疾病进展的患者中，BRAF可能是一个有前景的治疗靶点。
