Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX.
Adv Anat Pathol. 2022 May 1;29(3):168-177. doi: 10.1097/PAP.0000000000000337.
Renal cell carcinoma (RCC) with fibromyomatous stroma (FMS) was included as an "emerging/provisional" entity in the 2016 World Health Organization (WHO) classification as a "RCC with (angio) leiomyomatous stroma." It has been debated whether RCCFMS represents a separate entity or a group of RCCs with overlapping morphologies. Accordingly, various names have been used to refer to the RCCs that exhibited clear cells and prominent smooth muscle and fibromatous stroma. Recent studies have demonstrated that RCCFMS indeed represents a distinct entity with subtle but distinguishable features that can be separated from other RCCs that exhibit clear cells, as well as tubulopapillary morphology and smooth muscle/fibromatous stroma, such as clear cell RCC and clear cell papillary RCC. Microscopically, the epithelial component forms tumor nodules composed of elongated and frequently branching tubules, lined by clear or mildly eosinophilic cells containing voluminous cytoplasm. Focal papillary morphology is also frequently present. Diffuse CK7 positivity is typical and is required for the diagnosis. Molecular analysis of these tumors demonstrated recurrent mutations involving the TSC/mTOR pathway. A subset of tumors with similar morphology has shown mutations involving ELOC (previously referred to as TCEB1), typically associated with monosomy 8. Finally, in addition to the more common RCCFMS that are sporadic, essentially identical tumors have been found in patients with tuberous sclerosis complex, suggesting the existence of hereditary and sporadic counterparts of this tumor. It is currently debated whether TSC/mTOR and ELOC mutated RCCFMS should be grouped together, based on their shared and overlapping morphology and common CK7 reactivity, despite the differing molecular alterations. This review outlines evidence supporting the recognition of RCCFMS as a novel subtype of RCC with morphologic, immunohistochemical, and molecular characteristics distinct from clear cell RCC and clear cell papillary RCC.
肾细胞癌（RCC）伴纤维平滑肌基质（FMS）被纳入 2016 年世界卫生组织（WHO）分类中的“新兴/暂定”实体，作为“伴（血管）平滑肌脂肪瘤样基质的 RCC”。关于 RCCFMS 是否代表一个独立实体或一组具有重叠形态的 RCC，一直存在争议。因此，各种名称被用来指代表现出明显的细胞和突出的平滑肌和纤维母性基质的 RCC。最近的研究表明，RCCFMS 确实代表了一个独特的实体，具有微妙但可区分的特征，可以与表现出明显的细胞、管状乳头状形态以及平滑肌/纤维母性基质的其他 RCC 区分开来，如透明细胞 RCC 和透明细胞乳头状 RCC。显微镜下，上皮成分形成由拉长且常分支的小管组成的肿瘤结节，由透明或轻度嗜酸性细胞组成，细胞含有丰富的细胞质。局灶性乳头状形态也经常存在。弥漫性 CK7 阳性是典型的，也是诊断所必需的。对这些肿瘤的分子分析显示，涉及 TSC/mTOR 通路的反复突变。具有相似形态的肿瘤亚组显示出涉及 ELOC（以前称为 TCEB1）的突变，通常与单体 8 相关。最后，除了更为常见的散发性 RCCFMS 外，在结节性硬化症患者中还发现了实质上相同的肿瘤，表明这种肿瘤存在遗传性和散发性对应物。目前，基于其共享和重叠的形态、共同的 CK7 反应性以及不同的分子改变，是否应将 TSC/mTOR 和 ELOC 突变的 RCCFMS 分组在一起存在争议。本综述概述了支持将 RCCFMS 确认为具有独特形态、免疫组织化学和分子特征的新型 RCC 亚型的证据，与透明细胞 RCC 和透明细胞乳头状 RCC 不同。
