Alwaqfi Rofieda R, Samuelson Megan I, Guseva Natalya N, Ouyang Michelle, Bossler Aaron D, Ma Deqin
Department of Pathology, and.
Department of Radiology, University of Iowa Hospitals and Clinics, Iowa City, Iowa.
J Natl Compr Canc Netw. 2021 Sep 20;19(9):998-1004. doi: 10.6004/jnccn.2021.7058.
Recurrent GLI1 gene fusions have been recently described in a subset of soft tissue tumors showing a distinct monotonous epithelioid morphology with a rich capillary network and frequent S100 protein expression. Three different fusion partners-ACTB, MALAT1, and PTCH1-have been reported with the PTCH1-GLI1 fusion from 2 patients only, both with head and neck tumors. Herein, we report for the first time a PTCH1-GLI1 fusion in a primary ovarian tumor from a female patient aged 54 years who presented with a 21-cm right ovarian mass and mesenteric metastasis. The tumor was diagnosed as "favor malignant melanoma" based on histologic examination and extensive immunohistochemistry studies. The patient received 4 cycles of pembrolizumab and 2 cycles of trabectedin but developed multiple metastases. A next-generation sequencing-based assay detected a PTCH1-GLI1 fusion, which led to a revised pathologic diagnosis and a change of the patient's management. The patient was switched to the tyrosine kinase inhibitor (TKI) pazopanib to target the sonic hedgehog pathway. Her disease was stable 49 months post TKI therapy. Our case report is the first to show that a tumor with GLI1 oncogenic activation was sensitive to a TKI. The morphologic and immunohistochemistry similarities of our patient's tumor to other recently described tumors harboring GLI1 fusions suggest that these tumors may all belong to the same entity of GLI1 fusion-positive neoplasms and may be treated similarly.
最近在一部分软组织肿瘤中发现了复发性GLI1基因融合，这些肿瘤表现出独特的单调上皮样形态，伴有丰富的毛细血管网络且S100蛋白表达频繁。已报道了三种不同的融合伴侣——ACTB、MALAT1和PTCH1，其中PTCH1-GLI1融合仅在2例患者中出现，均为头颈部肿瘤。在此，我们首次报告了一名54岁女性患者原发性卵巢肿瘤中的PTCH1-GLI1融合，该患者表现为21厘米的右侧卵巢肿块并伴有肠系膜转移。根据组织学检查和广泛的免疫组化研究，该肿瘤被诊断为“倾向恶性黑色素瘤”。患者接受了4个周期的派姆单抗和2个周期的曲贝替定治疗，但出现了多处转移。基于二代测序的检测方法检测到了PTCH1-GLI1融合，这导致了病理诊断的修订以及患者治疗方案的改变。患者改用酪氨酸激酶抑制剂（TKI）帕唑帕尼以靶向音猬因子通路。TKI治疗49个月后她的病情稳定。我们的病例报告首次表明，具有GLI1致癌激活的肿瘤对TKI敏感。我们患者的肿瘤在形态学和免疫组化方面与其他最近描述的携带GLI1融合的肿瘤相似，这表明这些肿瘤可能都属于GLI1融合阳性肿瘤的同一实体，并且可能采用相似的治疗方法。
