摘要

伴平滑肌瘤样间质的肾细胞癌（Renal cell carcinoma with leiomyomatous stroma 

，RCCLMS）是 WHO( 2016) 泌尿系统肿瘤2016版分类中肾细胞癌（Renal cell carcinoma，RCC)的暂定亚型。HE 染色显微镜下见平滑肌瘤样间质中，肿瘤边界清楚，呈管状、乳头状生长，胞质透明。RCCLMS在临床上罕见，截止目前为止，国内外报道的病例仅有104例。与其它类型的RCC相比，RCCLMS具有独特的组织学、免疫组织化学染色以及分子遗传学特点。本文就以上特点对RCCLMS进行简明阐述。

大体观察

与其它RCC类似，RCCLMS表现为肾脏实性包快，切面类似于子宫平滑肌瘤，灰白、实性、质韧，有时可见出血及坏死。

图1、RCCLMS切除标本。（a）新鲜标本；（b）福尔马林固定后的标本。

组织学表现

 RCCLMS特征性改变是两种不同的成分混合:上皮透明细胞肿瘤和明显的血管平滑肌瘤样的间质。肿瘤细胞大,胞质透明,胞膜清楚,核深染,位于细胞中央。细胞轻度多形,多呈管状排列,伴有局灶的乳头状和实性区域,部分病例可见坏死；间质成分为均一的梭形细胞成束状排列,见典型的成熟平滑肌细胞形态,与血管壁融合,极像软组织的血管平滑肌瘤,细胞缺乏非典型性、凝固性坏死和核分裂,这种平滑肌增生与肿瘤的上皮成分混合,围绕癌巢形成多结节样结构,在肿瘤周围尤其明显,构成上皮周围的真正包膜,血管平滑肌瘤样增生区的外侧伸入正常肾实质或呈片状间隔于肾周成熟脂肪组织岛之间。可见灶性黏液样变和玻璃样变,化生性骨化罕见。电子显微镜下可见瘤细胞边缘存在不规则的刷状缘及瘤细胞内丰富的线粒体。

图2、RCCLMS组织学改变。（A）肾脏上极结节，切面灰白、实性、质地硬，局部可见出血、坏死；（B和C）可见平滑肌瘤样间质；（D，E和F）肿瘤细胞排列成长管状穿梭于间质中。

图3、RCCLMS组织学改变。（A）肾脏下极结节，切面灰白、实性、质地硬，周围包绕肾脏实质；（B）左侧为正常肾组织，右侧为肿瘤组织，两者界限清晰；（C和D）肿瘤组织，瘤细胞呈圆形透明样，细胞质淡染；瘤细胞由梭形细胞组成的瘤巢包绕。

图4、RCCLMS电子显微镜改变。（A）瘤细胞周围的刷状缘；（B）瘤细胞胞质内的线粒体。

免疫组织化学染色

在RCCLMS中，CK7。CANH9，Vim，AMACR，EMA，SMA及CD10表达强阳性；HMB-45表达阴性。

图5、RCCLMS中免疫组织化学表达情况。

图6、RCCLMS中免疫组织化学染色。（A）CK7；（B）CD10；（C）Vimentin；（D）EMA

图7、RCCLMS中免疫组织化学染色。（A）SMA；（B）Caldesom；（C）HHF-35；（D）HMB-45。

分子遗传学改变

多数病例存在TSC1/TSC2，mTOR和TCEB1基因突变。

图8、RCCLMS基因突变位点。（A）TSC1；（B）TSC2；（C）mTOR；（D）TCEB1。

与其它类型RCC鉴别

1、透明细胞性肾癌（clear cell renal cell carcinoma，RCCC）RCCC存在VHL基因的缺失，且CK7不会呈现强阳性表达。RCCLMS中VHL基因的无改变，且CK7呈现强阳性表达。

2、乳头样透明细胞性肾癌（Clear cell-papillary renal cell carcinoma，CCPRCC）CCPRCC无明显的基因突变。肿瘤细胞呈乳头样、腺泡样排列。

图9、RCCLMS不存在VHL基因突变。

图片来源：

图片1源自于Martignoni G, Brunelli M, Segala D, et, al. Renal cell carcinoma with smooth muscle stroma lacks chromosome 3p and VHL alterations..Mod Pathol. 2014 ;27(5):765-74. doi: 10.1038/modpathol.2013. 

图片2源自于Shah RB, Stohr BA, Tu ZJ, et, al. "Renal Cell Carcinoma With Leiomyomatous Stroma" Harbor Somatic Mutations of TSC1, TSC2, MTOR, and/or ELOC (TCEB1): Clinicopathologic and Molecular Characterization of 18 Sporadic Tumors Supports a Distinct Entity. Am J Surg Pathol. 2020 ;44(5):571-581. doi: 10.1097/PAS.0000000000001422.

图片3源自于Carlos Filipe Abrantes，Rui Caetano Oliveira，Luís Sepúlveda. A case of renal cell carcinoma with abundant smooth muscle (leiomyomatous) stroma and the differential diagnosis. Diagnostic Pathology. 2015;1; 28. doi: 10.17629/www.diagnosticpathology.eu-2015-1:28

图片4源自于Williamson SR, Hornick JL, Eble JN，et, al. Renal cell carcinoma with angioleiomyoma-like stroma and clear cell papillary renal cell carcinoma: exploring SDHB protein immunohistochemistry and the relationship to tuberous sclerosis complex. Hum Pathol. 2018 ;75:10-15. doi: 10.1016/j.humpath.2017.11.013.

图片5源自于Peckova K, Grossmann P, Bulimbasic S, et, al. Renal cell carcinoma with leiomyomatous stroma--further immunohistochemical and molecular genetic characteristics of unusual entity. Ann Diagn Pathol. 2014;18(5):291-6. doi: 10.1016/j.anndiagpath.2014.08.004.

图片6源自于Carlos Filipe Abrantes，Rui Caetano Oliveira，Luís Sepúlveda. A case of renal cell carcinoma with abundant smooth muscle (leiomyomatous) stroma and the differential diagnosis. Diagnostic Pathology. 2015;1; 28. doi: 10.17629/www.diagnosticpathology.eu-2015-1:28

图片7源自于Carlos Filipe Abrantes，Rui Caetano Oliveira，Luís Sepúlveda. A case of renal cell carcinoma with abundant smooth muscle (leiomyomatous) stroma and the differential diagnosis. Diagnostic Pathology. 2015;1; 28. doi: 10.17629/www.diagnosticpathology.eu-2015-1:28。

图片8源自于Chen YB, Mirsadraei L, Jayakumaran G, et, al. Somatic Mutations of TSC2 or MTOR Characterize a Morphologically Distinct Subset of Sporadic Renal Cell Carcinoma With Eosinophilic and Vacuolated Cytoplasm. Am J Surg Pathol. 2019 Jan;43(1):121-131. doi: 10.1097/PAS.0000000000001170.

图片9源自于Martignoni G, Brunelli M, Segala D, et, al. Renal cell carcinoma with smooth muscle stroma lacks chromosome 3p and VHL alterations..Mod Pathol. 2014 ;27(5):765-74. doi: 10.1038/modpathol.2013. 

参考文献

1.Martignoni G, Brunelli M, Segala D, et, al. Renal cell carcinoma with smooth muscle stroma lacks chromosome 3p and VHL alterations..Mod Pathol. 2014 ;27(5):765-74. doi: 10.1038/modpathol.2013. 

2.Shah RB, Stohr BA, Tu ZJ, et, al. "Renal Cell Carcinoma With Leiomyomatous Stroma"  Harbor Somatic Mutations of TSC1, TSC2, MTOR, and/or ELOC (TCEB1): Clinicopathologic and Molecular Characterization of 18 Sporadic Tumors Supports a Distinct Entity. Am J Surg Pathol. 2020 ;44(5):571-581. doi: 10.1097/PAS.0000000000001422.

3.Carlos Filipe Abrantes，Rui Caetano Oliveira，Luís Sepúlveda. A case of renal cell carcinoma with abundant smooth muscle (leiomyomatous) stroma and the differential diagnosis.  Diagnostic Pathology. 2015;1; 28. doi: 10.17629/www.diagnosticpathology.eu-2015-1:28

4.Williamson SR, Hornick JL, Eble JN，et, al. Renal cell carcinoma with angioleiomyoma-like stroma and clear cell papillary renal cell carcinoma: exploring SDHB protein immunohistochemistry and the relationship to tuberous sclerosis complex. Hum Pathol. 2018 ;75:10-15. doi: 10.1016/j.humpath.2017.11.013.

5.Peckova K, Grossmann P, Bulimbasic S, et, al. Renal cell carcinoma with leiomyomatous stroma--further immunohistochemical and molecular genetic characteristics of unusual entity. Ann Diagn Pathol. 2014;18(5):291-6. doi: 10.1016/j.anndiagpath.2014.08.004.

6.Chen YB, Mirsadraei L, Jayakumaran G, et, al. Somatic Mutations of TSC2 or MTOR Characterize a Morphologically Distinct Subset of Sporadic Renal Cell Carcinoma With Eosinophilic and Vacuolated Cytoplasm. Am J Surg Pathol. 2019 Jan;43(1):121-131. doi: