Departments of Pathology.
Oncology, Johns Hopkins University School of Medicine, Baltimore, MD.
Am J Surg Pathol. 2021 Apr 1;45(4):450-462. doi: 10.1097/PAS.0000000000001629.
Our recent study of early-onset unclassified eosinophilic renal cell carcinoma (RCC) demonstrated that two third of cases could be reclassified by performing a limited number of immunohistochemistry stains. Following the same approach, we aimed to investigate what proportion of adult unclassified RCC could be reclassified. We identified 79 cases. The mean age at presentation was 58 years (range, 29 to 84 y). Tumors were grouped based on their predominant morphologic features as oncocytic (n=23); papillary (n=22); clear cell (n=22); mucinous tubular and spindle cell (MTSC; n=5); rhabdoid (n=4); or lacking a dominant pattern (n=3). By reviewing the morphologic features and performing ancillary studies, we were able to reclassify 10 cases (13%). Four cases were positive for CK20 and showed morphologic features consistent with eosinophilic solid and cystic RCC. Four cases were reclassified as MTSC based on VSTM2A expression by RNA in situ hybridization. One case was negative for SDHB and reclassified as succinate dehydrogenase-deficient RCC. None of the cases showed loss of expression of fumarate hydratase. One case was diffusely positive for CK7 and negative for CD117 and reclassified as a low-grade oncocytic tumor. Four cases were positive for both cathepsin-K and TFE3 by immunohistochemistry, although fluorescence in situ hybridization failed to identify rearrangement in either TFE3 or TFEB genes. Of the tumors that remained unclassified, those with oncocytic features were less likely to be a high grade (odds ratio [OR]=0.22, P=0.013) or advanced stage (OR=0.19, P=0.039) and were more common in women (OR=3.4, P=0.05) compared with those without oncocytic features. Tumors with rhabdoid morphology were associated with advanced stage (relative risk=3.6, P=0.009), while tumors with clear cell or papillary features had a wide range of grades and stages at presentation. In summary, the most frequent reclassified entity is eosinophilic solid and cystic RCC. Investigation of expression of succinate dehydrogenase or fumarate hydratase in individuals older than 35 years with unclassifiable tumors is low yield in the absence of specific morphologic features. A subset of MTSC without well-developed morphologic features can be reclassified by using RNA-ISH for VSTM2A. Recognition of more-recently described RCC subtypes allows for their distinction from the unclassified subtype and improves the prognostic information provided.
我们最近对早发性未分类嗜酸粒细胞性肾细胞癌（RCC）的研究表明，通过进行有限数量的免疫组织化学染色，可将三分之二的病例重新分类。按照同样的方法，我们旨在研究有多少成人未分类的 RCC 可以重新分类。我们鉴定了 79 例病例。发病时的平均年龄为 58 岁（范围 29 至 84 岁）。肿瘤根据其主要形态特征分为嗜酸粒细胞性（n=23）；乳头状（n=22）；透明细胞（n=22）；黏液管状和梭形细胞（MTSC；n=5）；横纹肌样（n=4）；或缺乏主导模式（n=3）。通过回顾形态特征并进行辅助研究，我们能够重新分类 10 例（13%）。4 例 CK20 阳性，表现为嗜酸粒细胞性实性和囊性 RCC 的形态特征。4 例基于 RNA 原位杂交的 VSTM2A 表达被重新分类为 MTSC。1 例 SDHB 阴性，被重新分类为琥珀酸脱氢酶缺陷型 RCC。没有任何病例表现出延胡索酸水合酶表达缺失。1 例 CK7 弥漫阳性，CD117 阴性，被重新分类为低级别嗜酸粒细胞性肿瘤。4 例 cathepsin-K 和 TFE3 的免疫组织化学染色均为阳性，尽管荧光原位杂交未能在 TFE3 或 TFEB 基因中发现重排。在未分类的肿瘤中，具有嗜酸粒细胞特征的肿瘤更不可能为高级别（比值比 [OR]=0.22，P=0.013）或晚期（OR=0.19，P=0.039），且在女性中更为常见（OR=3.4，P=0.05），而不具有嗜酸粒细胞特征的肿瘤则不常见。具有横纹肌样形态的肿瘤与晚期相关（相对风险=3.6，P=0.009），而具有透明细胞或乳头状特征的肿瘤在发病时具有广泛的分级和分期。总之，最常见的重新分类实体是嗜酸粒细胞性实性和囊性 RCC。在缺乏特定形态特征的情况下，在年龄大于 35 岁的无分类肿瘤患者中检查琥珀酸脱氢酶或延胡索酸水合酶的表达，其检出率较低。一组形态特征不发达的 MTSC 可以通过使用 VSTM2A 的 RNA-ISH 进行重新分类。认识到最近描述的 RCC 亚型可以将其与未分类的亚型区分开来，并提高提供的预后信息。
