目的：本研究旨在探讨ELOC(TCEB1)突变型肾细胞癌的临床病理和分子学特征。
方法：采用Sanger测序法评估32例最初诊断为肾透明细胞癌的CK7阳性和/或纤维肌瘤间质。其中,筛选4例ELOC(TCEB1)基因突变患者,收集其临床病理资料进行组织形态学观察,免疫组织化学染色，和后续行动，并对相关文献进行了综述。
结果：4例ELOC（TCEB1）突变患者均为男性，年龄在57至64岁之间（中位年龄：59岁）。肿瘤位于肾皮质,直径2-3.5厘米。横截面为灰黄色和灰褐色，固体和结节，并与周围组织清楚地划分。在4个病人中,3带有富含平滑肌的厚纤维假胶囊，并与周围的正常肾组织分离，其中2例显示局灶性侵入假胶囊，而1例患者没有包膜，但局灶性侵犯了周围的肾实质。肿瘤组织主要表现为细长或分枝酸性或管状结构，通常伴有散布的小囊性和局灶性簇状短乳头状结构。肿瘤细胞的细胞质丰富，轻度染色，核分级从1到2。所有患者均表现为间质疏松性水肿，2例患者显示少量散布的平滑肌束。4例患者均显示EMA,CA9,AMACR,和TCEB1表达，TCEB1主要位于细胞核内。Vimentin,在大多数情况下观察到CK7和CD10的表达；CD117，TFE3，HMB45和黑色素A在所有肿瘤中均未表达；Ki67的表达率为3％-8％。所有4例患者在ELOC(TCEB1)Y79C中均有点突变。随访24～93个月,平均49个月。到目前为止，他们都存活了下来，没有复发或转移。
结论：ELOC(TCEB1)-突变型肾细胞癌是一种罕见的肾细胞癌，这往往发生在中年和老年男性。这种肿瘤的主要特征是分支的肺泡或管状结构，簇状的短乳头，纤维肌瘤间质的存在，CK7、CA9、CD10和AMACR的表达。TCEB1核染色阳性可能是重要标志，Sanger测序法有助于该类RCC的诊断。大多数患者的肿瘤表现出低核级和惰性的临床行为，和一些肿瘤表现出高核等级和侵袭性的特点。
OBJECTIVE: This study aimed to investigate the clinicopathological and molecular characteristics of ELOC(TCEB1)-mutant renal cell carcinoma.
METHODS: Sanger sequencing was used to assess 32 cases originally diagnosed as clear cell renal cell carcinoma with CK7 positive and/or fibromyomatous stroma. Of these, 4 patients with ELOC(TCEB1) gene mutation were screened, and their clinicopathological data were collected for histomorphological observation, immunohistochemical staining, and follow-up, and relevant pieces of literature were reviewed.
RESULTS: The 4 patients with ELOC(TCEB1) mutations were all males and aged between 57 and 64 years (median age: 59 years old). The tumor was located in the renal cortex, with a diameter of 2-3.5 cm. The cross-section was grayish-yellow and grayish brown, solid and nodular, and clearly demarcated from the surrounding tissues. Of the 4 patients, 3 harbored a thick fibrous pseudocapsule rich in smooth muscle and were separated from the surrounding normal renal tissue, and 2 of them showed focal invasion into the pseudocapsule, whereas 1 patient had no capsule but had focal invasion into the surrounding renal parenchyma. The tumor tissues mainly exhibited elongated or branched aciniform or tubular structures, commonly accompanied by interspersed small cystic and focal clustered short papillary structures. The cytoplasm of the tumor cells was rich and lightly stained, and the nuclear grading ranged from 1 to 2. All patients showed loose edema in the stroma, and 2 patients showed a small number of interspersed smooth muscle bundles. All 4 patients showed EMA, CA9, AMACR, and TCEB1 expression, and TCEB1 was mainly located in the nucleus. Vimentin, CK7, and CD10 expressions were observed in most cases; CD117, TFE3, HMB45, and melanA were not expressed in all tumors; the expression rate of Ki67 was 3%- 8%. All 4 patients had a point mutation in ELOC(TCEB1) Y79C. The patients were followed up for 24-93 months (mean 49 months), and all of them survived to date without recurrence or metastasis.
CONCLUSIONS: ELOC(TCEB1)-mutant renal cell carcinoma is a rare type of renal cell carcinoma, which tends to occur in middle-aged and elderly men. The main characteristics of this tumor are the branching alveolar or tubular structure with clustered short papillae, presence of fibromyomatous stroma, and the expression of CK7, CA9, CD10, and AMACR. Positive TCEB1 nuclear staining may be an important marker and the Sanger sequencing method is helpful for the diagnosis of this type of RCC. Most patients harbor tumors exhibiting low nuclear grade and inert clinical behavior, and a few tumors exhibit high nuclear grade and aggressive characteristics.
