Ningbo Clinical Pathology Diagnosis Center, Ningbo, China.
Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China; Institute of Pathology, Fudan University, Shanghai, China.
Mod Pathol. 2024 May;37(5):100468. doi: 10.1016/j.modpat.2024.100468. Epub 2024 Mar 7.
Soft tissue neoplasms, harboring fusions between EWSR1 and FUS with genes encoding CREB transcription factors family (ATF1, CREB1, and CREM), are an emerging heterogeneous group of mesenchymal tumors that differ significantly in morphology, immunophenotypes, and behavior. Recently, EWSR1/FUS::CREB fusions have been recognized to define a group of aggressive neoplasms of epithelioid morphology with multiple growth patterns and a striking predilection for mesothelial-lined cavities. These neoplasms presenting as a primary neoplasm of intra-abdominal visceral organs are rare, which could elicit a wide range of differential diagnoses because of their diverse morphologies and immunohistochemical profiles. We report 3 cases of intra-abdominal epithelioid neoplasms with EWSR1::CREB fusions involving the kidney. This study included 2 female patients and 1 male patient, with age at presentation ranging from 17 to 61 years (mean: 32 years). All the patients underwent radical nephrectomy without adjunctive therapies. Grossly, the tumors were large, and all were solitary masses with sizes ranging from 5.6 to 30.0 cm (mean: 14.5 cm). Histologically, the neoplasms showed infiltrating and indistinct borders and were composed predominantly of monomorphic round-to-epithelioid cells with variable amounts of pale-to-clear cytoplasm, arranged in cords, nests, and sheets and embedded in a sclerotic hyalinized stroma with variable lymphoid cuffing either intermixed or at the periphery. Notably, a hemangiopericytomatous growth pattern was commonly seen. Nuclear atypia was mild, and mitotic activity was scarce. Immunohistochemically, all 3 cases were at least focally positive for epithelial membrane antigen and keratin AE1/AE3, with 2 tumors showing focal MUC4 expression and 1 case displaying diffuse CD34 and focal CAIX positivity. Targeted RNA sequencing identified EWSR1::CREM fusion in 2 cases and EWSR1::ATF1 fusion in 1 case. Subsequent fluorescence in situ hybridization analysis confirmed the RNA sequencing results. On follow-up, 1 patient developed multiple spinal bone metastases 5 months after the surgery while the other 2 patients were free of disease 9 and 120 months after diagnosis, respectively. Our findings demonstrate that intra-abdominal epithelioid neoplasms with EWSR1::CREB fusions may rarely occur primarily in the kidney and should be included in the differential diagnosis of primary renal epithelioid mesenchymal neoplasms.
软组织肿瘤中，EWSR1 和 FUS 与 CREB 转录因子家族（ATF1、CREB1 和 CREM）基因融合的肿瘤为一组新兴的具有显著形态学、免疫表型和行为差异的间叶性肿瘤。最近，已经认识到 EWSR1/FUS::CREB 融合定义了一组具有上皮样形态、多种生长模式和明显倾向于间皮衬里腔的侵袭性肿瘤。这些表现为腹腔内脏器原发性肿瘤的肿瘤较为罕见，由于其形态和免疫组化特征多样，可能会引起广泛的鉴别诊断。我们报告了 3 例累及肾脏的腹腔上皮样肿瘤伴 EWSR1::CREB 融合。该研究包括 2 例女性患者和 1 例男性患者，发病年龄 17 至 61 岁（平均：32 岁）。所有患者均接受了根治性肾切除术，未行辅助治疗。大体上，肿瘤较大，均为单发肿块，大小 5.6 至 30.0cm（平均：14.5cm）。组织学上，肿瘤呈浸润性，边界不清，主要由形态单一的圆形至上皮样细胞组成，伴有不同数量的淡染至透明细胞质，呈条索状、巢状和片状排列，嵌入伴不同程度淋巴细胞套的硬化性玻璃样基质中，或混合存在，或位于边缘。值得注意的是，常见到血管外皮细胞瘤样生长模式。核异型性轻微，有丝分裂活性稀少。免疫组化染色，所有 3 例均至少局灶性表达上皮膜抗原和角蛋白 AE1/AE3，2 例肿瘤局灶性表达 MUC4，1 例弥漫性表达 CD34 和局灶性表达 CAIX。靶向 RNA 测序在 2 例中发现 EWSR1::CREM 融合，在 1 例中发现 EWSR1::ATF1 融合。随后的荧光原位杂交分析证实了 RNA 测序结果。随访时，1 例患者术后 5 个月出现多发脊柱骨转移，另 2 例患者分别在诊断后 9 个月和 120 个月无疾病生存。我们的研究结果表明，腹腔上皮样肿瘤伴 EWSR1::CREB 融合罕见地发生于肾脏，应纳入原发性肾脏上皮样间充质肿瘤的鉴别诊断中。
