Mladenovic Andrea, Harik Lara R, Deeb Kristin K, Genega Elizabeth M, Saeed Faisal, Gandhi Jatin S
Department of Pathology and Laboratory Medicine, Emory University, School of Medicine, Atlanta, GA, 30322, USA.
Department of Pathology and Laboratory Medicine, Emory University, School of Medicine, Atlanta, GA, 30322, USA.
Hum Pathol. 2025 Apr;158:105783. doi: 10.1016/j.humpath.2025.105783. Epub 2025 May 6.
Translocation renal cell carcinoma (tRCC) are morphologically distinct tumors having an underlying disease defining molecular alterations (commonly TFE3/TFEB gene alterations). Their occurrence in the setting of end stage renal disease (ESRD) has been rarely reported. This study was undertaken to assess the occurrence of TFE3/TFEB altered RCCs in ESRD setting at our institution.
By retrospective review, we searched our pathology database for tRCC in ESRD setting over a 14-year period. We analyzed and documented the clinical, histopathological, immunohistochemical, and molecular findings in these tumors.
Out of 223 patients of ESRD associated with RCCs, we found 4 cases of molecularly confirmed TFE3/TFEB-altered RCCs. Three of four patients were on pharmacologic immunosuppression (2 for underlying SLE and 1 for prior liver transplant). The ages ranged from 36 to 74 years (median 48 years) with an equal sex ratio. Tumors were solitary and ranged in size from 1.3 to 4.7 cm (median 2 cm). All four cases were confined to the kidney (pT1) and did not exhibit any necrosis, small vessel invasion, or sarcomatoid/rhabdoid features. The tumors exhibited characteristic morphology (solid, nested and papillary architectures with clear and eosinophilic cytoplasm in TFE3-rearranged RCCs, and biphasic morphology with basement membrane-like material in TFEB-altered RCCs). On immunohistochemistry, tumors consistently expressed cathepsin-K (3/3) & Melan-A (3/3). On molecular studies one case was confirmed via FISH study (TFEB gene rearrangement) and three cases were confirmed via RNA fusionplex (PRCC::TFE3, MED15::TFE3 and MALAT1::TFEB fusion transcripts). The median follow-up was 13 months (range 10-95 months), none of the 4 patients had any local or metastatic recurrences. One patient died of other comorbidities. Background kidney in all 4 patients exhibited variable features of ESRD.
TFE3/TFEB-altered RCCs are rarely encountered in ESRD. Morphological and immunohistochemical findings of tRCC in ESRD replicate those found in sporadic settings. To the best of our knowledge, our study is the first to identify TFEB-rearranged RCCs in an ESRD setting.
易位性肾细胞癌（tRCC）是形态学上独特的肿瘤，具有定义潜在疾病的分子改变（通常为TFE3/TFEB基因改变）。其在终末期肾病（ESRD）患者中的发生情况鲜有报道。本研究旨在评估我院ESRD患者中TFE3/TFEB改变的肾细胞癌的发生情况。
通过回顾性研究，我们在病理数据库中搜索了14年间ESRD患者中的tRCC。我们分析并记录了这些肿瘤的临床、组织病理学、免疫组织化学和分子学特征。
在223例合并肾细胞癌的ESRD患者中，我们发现4例经分子学确诊的TFE3/TFEB改变的肾细胞癌。4例患者中有3例正在接受药物免疫抑制治疗（2例因潜在的系统性红斑狼疮，1例因既往肝移植）。年龄范围为36至74岁（中位年龄48岁），男女比例相等。肿瘤均为单发，大小从1.3至4.7厘米不等（中位大小2厘米）。所有4例肿瘤均局限于肾脏（pT1），未表现出任何坏死、小血管侵犯或肉瘤样/横纹肌样特征。肿瘤表现出特征性形态（TFE3重排的肾细胞癌呈实性、巢状和乳头状结构，细胞质透明且嗜酸性，TFEB改变的肾细胞癌呈双相形态，伴有基底膜样物质）。免疫组织化学检查显示，肿瘤均持续表达组织蛋白酶K（3/3）和Melan-A（3/3）。分子学研究中，1例通过荧光原位杂交（FISH）研究确诊（TFEB基因重排），3例通过RNA融合检测（PRCC::TFE3、MED15::TFE3和MALAT1::TFEB融合转录本）确诊。中位随访时间为13个月（范围10 - 95个月），4例患者均无局部或远处复发。1例患者死于其他合并症。所有4例患者的背景肾脏均表现出ESRD的不同特征。
ESRD患者中很少遇到TFE3/TFEB改变的肾细胞癌。ESRD中tRCC的形态学和免疫组织化学特征与散发性病例中发现的特征相似。据我们所知，我们的研究是首次在ESRD患者中鉴定出TFEB重排的肾细胞癌。
