Williamson Sean R, Hes Ondrej, Trpkov Kiril, Aggarwal Aditi, Satapathy Abhishek, Mishra Sourav, Sharma Shivani, Sangoi Ankur, Cheng Liang, Akgul Mahmut, Idrees Muhammad, Levin Albert, Sadasivan Sudha, San Miguel Fraile Pilar, Rogala Joanna, Comperat Eva, Berney Daniel M, Bulimbasic Stela, McKenney Jesse K, Jha Shilpy, Sampat Nakul Y, Mohanty Sambit K
Department of Pathology, Robert J. Tomsich Pathology and Laboratory Medicine Institute, Cleveland Clinic, Cleveland, Ohio, USA.
Department of Pathology, Faculty of Medicine in Pilsen, Charles University, Pilsen, Czech Republic.
Histopathology. 2023 Jan;82(2):296-304. doi: 10.1111/his.14816. Epub 2022 Oct 18.
Low-grade oncocytic tumour (LOT) of the kidney has recently emerged as a potential novel tumour type. Despite similarity to oncocytoma or eosinophilic chromophobe renal cell carcinoma, it shows diffuse keratin 7 immunohistochemistry (IHC) and negative KIT (CD117), which differs from both. We aimed to identify the molecular characteristics of these tumours. Seventeen tumours (one male, 16 female, nine previously published) fitting the original description of this entity (solid eosinophilic cell morphology, often with areas of tumour cells loosely stretched in oedematous stroma, and the above IHC features) were analysed with a next-generation sequencing panel of 324 cancer-associated genes from formalin-fixed, paraffin-embedded tissue. All tumours harboured at least one alteration in either TSC1 (n = 7, 41%), TSC2 (n = 2, 12%), MTOR (n = 5, 29%) or PIK3CA (n = 4, 24%). Four tumours harboured a second alteration, including two NF2, one each in conjunction with MTOR and TSC2 alterations, one PTEN with TSC1 alteration and one tumour with both MTOR and TSC1 alterations. No other renal cancer-related or recurring gene alterations were identified. In addition to the previously described IHC findings, 16 of 16 were positive for GATA3. Eleven patients with follow-up had no metastases or recurrent tumours. Recurrent tuberous sclerosis/MTOR pathway gene alterations in LOT support its consideration as a distinct morphological, immunohistochemical and genetic entity. PIK3CA is another pathway member that may be altered in these tumours. Further study will be necessary to determine whether tumour behaviour or syndromic associations differ from those of oncocytoma and chromophobe carcinoma, warranting different clinical consideration.
肾低度嗜酸细胞瘤（LOT）最近已成为一种潜在的新型肿瘤类型。尽管它与嗜酸细胞瘤或嗜酸性嫌色肾细胞癌相似，但它显示弥漫性细胞角蛋白7免疫组化（IHC）阳性且KIT（CD117）阴性，这与两者均不同。我们旨在确定这些肿瘤的分子特征。对17例符合该实体原始描述（实性嗜酸性细胞形态，通常有肿瘤细胞在水肿基质中松散伸展的区域，以及上述免疫组化特征）的肿瘤（1例男性，16例女性，9例先前已发表），使用来自福尔马林固定、石蜡包埋组织的324个癌症相关基因的二代测序panel进行分析。所有肿瘤在TSC1（n = 7，41%）、TSC2（n = 2，12%）、MTOR（n = 5，29%）或PIK3CA（n = 4，24%）中至少有一个改变。4例肿瘤有第二种改变，包括2例NF2，1例分别与MTOR和TSC2改变同时存在，1例PTEN与TSC1改变同时存在，1例肿瘤同时有MTOR和TSC1改变。未发现其他肾癌相关或复发性基因改变。除了先前描述的免疫组化结果外，16例中有16例GATA3阳性。11例有随访的患者无转移或复发性肿瘤。LOT中复发性结节性硬化症/MTOR通路基因改变支持将其视为一种独特的形态学、免疫组化和遗传学实体。PIK3CA是这些肿瘤中可能发生改变的另一个通路成员。有必要进一步研究以确定肿瘤行为或综合征关联是否与嗜酸细胞瘤和嫌色细胞癌不同，从而需要不同的临床考虑。
