Pancsa Tamás, Klubíčková Natálie, Dashti Nooshin K, Machado Isidro, Llombart-Bosch Antonio, Linos Konstantinos, Mosaieby Elaheh, Vaněček Tomáš, Maňáková Lenka, Michal Michal, Michal Michael
Bioptical Laboratory, Ltd., Plzen, Czech Republic.
Department of Pathology, Charles University, Faculty of Medicine in Plzen, Plzen, Czech Republic.
Virchows Arch. 2025 Apr;486(4):751-757. doi: 10.1007/s00428-024-03998-z. Epub 2024 Dec 17.
Pathogenic alterations, namely, fusions and amplifications, of the GLI1 gene have been identified in various mesenchymal tumors, including pericytoma with t(7;12), plexiform fibromyxoma, gastroblastoma, and other malignant mesenchymal neoplasms arising in the soft tissues, as well as in various visceral organs. However, only three cases of GLI1-rearranged renal tumors have been reported to date, comprising two low-grade spindle cell tumors with GLI1::FOXO4 fusion along with one GLI1-rearranged case with an unknown fusion partner. In this study, we analyzed three cases with GLI1::FOXO4 fusion and overlapping morphology. One of the cases was reported previously, but an extended clinical and immunohistochemical information is provided. The studied cases occurred in 2 female and 1 male patients aged 35, 55, and 62 years (mean 51 years). All three tumors affected the renal parenchyma and grew as unencapsulated but well-circumscribed solid masses containing occasional entrapped and dilated renal tubules. The tumor cells were organized in cords, nests, or fascicles, had a round to spindled shape, and exhibited only mild nuclear atypia and minimal mitotic activity. They had a sparse eosinophilic to clear cytoplasm and were embedded in myxocollagenous stroma. Immunohistochemically, all cases expressed GLI1 (albeit with variable intensity) and harbored GLI1::FOXO4 fusion. All three patients were treated solely by complete surgical excision. Case 1 was alive with unknown disease status, case 2 was alive without evidence of disease, and case 3 died of unrelated causes. Our study doubles the number of reported cases with GLI1::FOXO4 fusion. The so far absolute predilection of this fusion for renal tumors, coupled with the absence of reports of other GLI1 fusions in tumors of the kidney, might indicate the potential existence of a distinct renal subtype with morphological features similar to other GLI1-altered tumors. All four reported cases had an uneventful follow-up which, together with their low-grade morphological features, suggests that these tumors might have a favorable prognosis.
在各种间叶性肿瘤中已鉴定出GLI1基因的致病性改变，即融合和扩增，这些肿瘤包括伴有t(7;12)的血管周细胞瘤、丛状纤维黏液瘤、胃母细胞瘤以及发生于软组织和各种内脏器官的其他恶性间叶性肿瘤。然而，迄今为止仅报道了3例GLI1重排的肾肿瘤，包括2例伴有GLI1::FOXO4融合的低级别梭形细胞瘤以及1例融合伴侣未知的GLI1重排病例。在本研究中，我们分析了3例具有GLI1::FOXO4融合且形态学特征重叠的病例。其中1例先前已有报道，但提供了扩展的临床和免疫组化信息。所研究的病例发生在2名女性和1名男性患者中，年龄分别为35岁、55岁和62岁（平均51岁）。所有3例肿瘤均累及肾实质，呈无包膜但边界清楚的实性肿块生长，偶见包绕和扩张的肾小管。肿瘤细胞呈条索状、巢状或束状排列，形状从圆形到梭形，仅表现出轻度核异型性和极少的有丝分裂活性。它们具有稀疏的嗜酸性至清亮的细胞质，包埋于黏液胶原性间质中。免疫组化显示，所有病例均表达GLI1（尽管强度不同）并存在GLI1::FOXO4融合。所有3例患者均仅接受了完整的手术切除。病例1存活，疾病状态未知；病例2存活，无疾病证据；病例3死于无关原因。我们的研究使报道的伴有GLI1::FOXO4融合的病例数量增加了一倍。迄今为止，这种融合在肾肿瘤中具有绝对偏好，且肾肿瘤中未报道其他GLI1融合，这可能表明存在一种形态学特征与其他GLI1改变的肿瘤相似的独特肾亚型。所有4例报道病例的随访过程均顺利，连同其低级别形态学特征表明这些肿瘤可能预后良好。
