卵巢高钙血症型小细胞癌的临床病理特征及SMARCA4失表达的诊断意义

Small cell carcinoma of ovary, hypercalcemic type： analysis of clinicopathologic characteristics and the diagnostic utility of loss expression of SMARCA4 protein

目的探讨卵巢高钙血症型小细胞癌（SCCOHT）的临床病理特征，明确SMARCA4在SCCOI-IT中的表达情况及其诊断意义。方法回顾性复习5例SCCOI-IT的临床资料及组织学形态，采用免疫组织化学染色EnVision法检测SMARCA4蛋白在SCCOHT及240例卵巢和腹膜其他原发恶性肿瘤中的表达情况。结果本组患者的平均年龄和中位年龄分别为30岁和28岁。患者均以腹痛、腹胀、盆腔包块为主诉就诊，其中3例伴随血清钙升高。肿瘤最大径13．5—22．0cm。5例患者手术时均已发生卵巢外扩散。镜下见肿瘤细胞主要为胞质稀少、染色质凝块状的小细胞，呈弥漫片状、巢团状、梁状、条索状排列，其中4例可以观察到散在分布的滤泡样结构，3例观察到数量不等的胞质嗜酸性的大细胞，1例可观察到梭形细胞呈片巢状分布，2例伴有水肿、黏液变性和玻璃样变的间质。免疫组织化学染色结果显示，SMARCA4在4／5的SCCOHT病例失表达，而在卵巢其他恶性肿瘤及腹膜高级别浆液性癌中仅有6．3％（15／240）的失表达，其中包括卵巢未分化癌（1／5）、高级别浆液性癌（4．6％，5／109）、子宫内膜样癌（7．7％，2／26）、透明细胞癌（1／9）、黏液性癌（1／5）、混合性癌（4．9％，3／61）、癌肉瘤（1／9）和腹膜高级别浆液性癌（1／9），而幼年型颗粒细胞瘤病例中未见失表达。结论SCCOHT作为一种少见的恶性肿瘤，易被误诊为其他类型的小细胞肿瘤。SMARCA4蛋白失表达对于SCCOHT的诊断和鉴别诊断具有潜在的临床应用价值。

Objective To study the clinicopathologic features of small cell carcinoma of ovary, hypercalcemic type （SCCOHT） and to evaluate the diagnostic significance of loss of SMARCA4 expression. Methods The clinicopathologie characteristics of 5 cases of SCCOHT were reviewed. The expression of SMARCA4 protein was detected by immunohistochemistry in the cases of SCCOHT and 240 cases of other primary malignant tumors of ovary and peritoneum. Results The mean and medium age of these patients was 30 years and 28 years, respectively. The presenting symptoms included abdominal pain, distention and a pelvic mass. Hypercalcemia was found in 3 patients. The maximum diameter of tumors ranged from 13.5 to 22.0 cm. Extraovarian spread was demonstrated in all of the patients on presentation. Histologically, the tumors were composed of closely packed small round cells with scanty cytoplasm, hyperchromatic nuclei and irregular chromatin clumps. The tumor cells grew in sheets, nests, cords or trabecular pattern. Follicle-like spaces were observed in 4 cases. Three of the tumors contained large cells with abundant eosinophilic cytoplasm. Spindle cell morphology was found in 1 case. There were 2 cases with myxoid or hyaline stroma. Four out of five of SCCOHT cases showed loss of SMARCA4 protein while only 6.3% （15/240） of the other primary malignant tumors of ovary and peritoneum ,including undifferentiated carcinoma （1/5） , high-grade serous carcinoma （4.6% , 5/109 ）, endometrioid carcinoma （ 7.7%, 2/26 ）, clear cell carcinoma （ 1/9）, mucinous carcinoma （ 1/5 ） , mixed carcinoma （ 4. 9% , 3/61 ） , carcinosarcoma （ 1/9 ） and high-grade serous carcinoma of peritoneum （1/9）, were negative. Conclusions SCCOI-IT is a rare malignant tumor and often misdiagnosed as other types of ovarian small cell tumor. Loss expression of SMARCA4 protein is characteristic and facilitates the diagnosis and differential diagnosis of SCCOHT.