Distinctive Nested Glomoid Neoplasm Clinicopathologic Analysis of 20 Cases of a Mesenchymal Neoplasm With Frequent GLI1 Alterations and Indolent Behavior
Distinctive Nested Glomoid Neoplasm Clinicopathologic Analysis of 20 Cases of a Mesenchymal Neoplasm With Frequent GLI1 Alterations and Indolent Behavior
复制标题
DOI：
10.1097/pas.0000000000001979
复制
发表时间：
2023-01-01
影响因子：
5.6
通讯作者：
Fletcher, Christopher D. M.
中科院分区：
文献类型：
--
作者：
Papke, David J.;Dickson, Brendan C.;Fletcher, Christopher D. M.
最近，人们已经认识到，一个子集的原发性软组织肿瘤与GLI 1基因的改变表现出巢状结构，可以模仿血管球瘤或分化良好的神经内分泌肿瘤。在这里，我们报告了一系列的20个这样的肿瘤，我们暂时称之为“独特的巢状血管球样肿瘤。“11名患者（55%）为女性，9名为男性。就诊时的中位年龄为41.5岁（范围：先天性至74岁）。解剖分布广泛，身体部位包括躯干（7个肿瘤）、下肢（5个）、舌（4个）、上肢（3个）和颈部（1个）。除舌部肿瘤外，深部软组织肿瘤10例（62%），皮下组织肿瘤6例（38%）。肿瘤大小范围为0.9 - 11.1 cm（中位数：3 cm）。独特的巢状血管球样肿瘤由圆形到卵圆形细胞巢组成，细胞质稀少，淡嗜酸性，核单形，染色质呈泡状，核仁小。巢被突出的毛细血管网包围，它们位于由不规则的厚纤维隔膜分隔的大小叶内。在18个可评估邻近非肿瘤组织的肿瘤中，16个肿瘤（89%）中确定了肿瘤细胞的血管周围增殖。8个肿瘤（40%）至少局灶性存在微囊性结构，5个肿瘤（25%）至少局灶性存在粘液样间质。7个肿瘤（35%）显示透明细胞特征。通过免疫组织化学，一些肿瘤表达MDM 2（7/15; 47%）、S100（5/19; 26%）、STAT 6（2/5; 20%）和AE 1/AE 3（1/5; 20%）。肿瘤很少表达泛角蛋白（1/10; 10%）或CAM 5.2（1/10），所有肿瘤均为β-连环蛋白（12例肿瘤）、嗜铬粒蛋白（12例）、突触素（11例）、上皮膜抗原（10例）、结蛋白（10例）、平滑肌肌动蛋白（9例）、INSM 1（7例）和CD 34（6例）阴性。对7个肿瘤进行了GLI 1断裂荧光原位杂交，对15个肿瘤进行了下一代测序（10个仅进行DNA测序，1个仅进行RNA测序，4个同时进行DNA和RNA测序）。发现16个肿瘤（包括所有15个通过下一代测序检测的肿瘤和另外1个仅通过荧光原位杂交检测的病例）存在GLI 1基因改变：10个存在GLI 1基因重排（3个ACTB：：GLI 1，2个PTCH 1：：GLI 1，1个HNRNPA 1：：GLI 1，1个NEAT 1：：GLI 1，1个TXNIP：：GLI 1，2个未确定的融合伴侣），6个存在GLI 1扩增。10例患者（50%;范围：3个月至10年;中位数：6.4年）进行了临床随访，其中8例随访时间>1年。3例患者（30%）出现局部复发（间隔3个月至10年）。没有发生远处转移或死于疾病。总的来说，我们的研究结果支持这样的观点，即GLI 1改变的软组织肿瘤的一个子集是惰性的，形态学上独特的巢状血管球样肿瘤，不应该被归类为肉瘤。
Recently, it has been recognized that a subset of primary soft tissue neoplasms with GLI1 gene alterations exhibit nested architecture and can mimic glomus tumors or well-differentiated neuroendocrine tumors. Here, we report a series of 20 such neoplasms, which we have provisionally termed "distinctive nested glomoid neoplasm." Eleven patients (55%) were female and 9 were male. The median age at presentation was 41.5 years (range: congenital to 74 y). The anatomic distribution was wide, with body sites including the trunk (7 tumors), lower extremity (5), tongue (4), upper extremity (3), and neck (1). Excluding tumors of the tongue, 10 tumors (62%) arose in deep soft tissue and 6 (38%) arose primarily in the subcutis. Tumor size ranged from 0.9 to 11.1 cm (median: 3 cm). Distinctive nested glomoid neoplasms are composed of nests of round-to-ovoid cells with scant, palely eosinophilic cytoplasm and monomorphic nuclei with vesicular chromatin and small nucleoli. The nests are invested by prominent capillary networks, and they are situated within large lobules separated by irregular, thick fibrous septa. Among 18 tumors for which adjacent non-neoplastic tissue could be assessed, perivascular proliferation of tumor cells was identified in 16 tumors (89%). Microcystic architecture was present at least focally in 8 tumors (40%), and myxoid stroma was identified at least focally in 5 (25%). Seven tumors (35%) showed clear cell features. By immunohistochemistry, some tumors expressed MDM2 (7/15; 47%), S100 (5 of 19; 26%), STAT6 (2 of 5; 20%), and AE1/AE3 (1/5; 20%). Tumors rarely expressed pan-keratin (1/10; 10%) or CAM5.2 (1/10), and all tumors were negative for beta-catenin (12 tumors), chromogranin (12), synaptophysin (11), epithelial membrane antigen (10), desmin (10), smooth muscle actin (9), INSM1 (7), and CD34 (6). GLI1 break-apart fluorescence in situ hybridization was performed on 7 tumors, and next-generation sequencing was performed on 15 tumors (10 DNA sequencing only, 1 RNA sequencing only, 4 both DNA and RNA sequencing). Sixteen tumors, including all 15 tested by next-generation sequencing and an additional case tested by fluorescence in situ hybridization only, were found to harbor GLI1 gene alterations: 10 harbored GLI1 gene rearrangements (3 ACTB::GLI1, 2 PTCH1::GLI1, 1 HNRNPA1::GLI1, 1 NEAT1::GLI1, 1 TXNIP::GLI1, 2 undetermined fusion partners), and 6 harbored GLI1 amplification. Clinical follow-up was available for 10 patients (50%; range: 3 mo to 10 y; median: 6.4 y), including 8 with >1 year of follow-up. Three patients (30%) experienced local recurrence (at intervals of 3 mo to 10 y). None developed distant metastases or died of disease as yet. Overall, our findings support the notion that a subset of GLI1-altered soft tissue neoplasms are indolent, morphologically distinctive nested glomoid neoplasms that should not be classified as sarcomas.