阑尾低级别黏液性肿瘤卵巢转移临床病理特点及免疫组化分析

Clinicopathological and immunohistochemical charactoristics of low-grade mucous appendiceal neoplasm with ovarian metastasis

目的 探讨阑尾低级别黏液性肿瘤(LAMN)卵巢转移的临床病理特点,提高临床及病理医师对此类病变的诊断及鉴别诊断认识。方法 对2008-04—2020-12山东第一医科大学附属青岛医院病理科诊治的6例LAMN卵巢转移进行回顾性研究,复习临床资料,复阅全部病理切片,并行免疫组化检查,同时选择17例卵巢原发性交界性黏液性肿瘤(MBOT)进行对照分析。结果 两者平均发病年龄及肿瘤大小均无明显差异,6例LAMN卵巢转移中,5例同时行阑尾切除,术后诊断LAMN;6例中4例呈双侧卵巢受累,2例右侧卵巢发生,4例显示黏液组织浸润卵巢被膜并呈外突结节性生长,5例出现腹膜假黏液瘤。形态学观察:肿瘤均呈多灶性生长,可见大小不一扩张囊腔,囊内壁以高柱状黏液性上皮为主,杯状细胞少见。免疫组织化学显示3例CK7局灶弱阳性,3例阴性,5例CK20弥漫强阳性,1例弱阳性,4例CDX2及SATB2均呈阳性表达;同时切除5例阑尾病例,均符合LAMN形态学特点,免疫标记CDX2及SATB2均呈强阳性。17例MBOT中,15例单侧卵巢发生,2例双侧发生,卵巢被膜均完整,未见黏液浸润。卵巢内可见单灶或多灶性黏液性囊腔,囊内壁覆轻/中度异型性黏液性上皮,杯状细胞易见,免疫组织化学显示:15例CK7呈弥漫性强阳性,5例CK20局灶阳性,17例中的4例及2例CDX2及SATB2呈弱阳性,其余呈阴性。结论 肿瘤发生部位、是否存在腹膜假黏液瘤、卵巢被膜有无浸润以及囊内壁上皮是否出现多灶性乳头状结构等形态是区分两者的主要临床特点,镜下判断要点除了依据是否出现黏液池,黏液上皮形态,是否出现杯状细胞及上皮下裂隙、是否存在黏液性肉芽肿等形态学特征外,黏液内脱落微小乳头簇以及固缩退变性上皮细胞聚集这两个特征,也可作为鉴别两者的附加形态学参数。免疫组织化学检查CK7、CK20、CDX2、SATB2等可作为两者鉴别诊断的一线抗体使用,但需注意后者可能在LAMN累及卵巢中失表达。同时,与畸胎瘤相关的卵巢黏液性肿瘤可表现为与LAMN累及卵巢相同的组织学和免疫组织化学特点,需注意鉴别。

Objective To investigate the clincopathological features of low-grade mucous appendiceal neoplasm(LAMN) with ovarian metastasis, which is crucial for clinicians and pathologists to more accurately diagnose the metastatic ovrian cancer. Methods Six patients with ovarian metastatic carcinomas of LAMN were retrospectively studied in Qingdao Hospital Affiliated to Shandong First Medical University from April 2008 to December 2020. The clinical data and all pathological slides were reviewed, and immunohistochemical staining was examined. 17 primary mucinous borderline ovary tumor(MBOT) cases were used as control. Results The average age and tumor size were similar between two groups. 5 of 6 cases of LAMN ovarian metastasis underwent appendectomy and were diagnosed as LAMN. In the 6 cases, 4 cases involved both ovaries and 2 cases involved the right ovary only. 4 of 6 cases showed mucin invasion of ovarian capsule with protruding nodules. Peritoneal pseudomyxoma was found in 5 of 6 patients. Morphologically, all tumors showed multifocal growth with dilated cysts of different sizes. The inner wall of the cysts was dominated by tall columnar mucinous epithelium, and goblet cells were rare. Immunohistochemical staining showed that 3 cases were weakly positive for CK7, and 3 cases were negative for CK7;5 cases were diffuse and strongly positive for CK20, and 1 case were weakly positive for CK20;4 cases wre positive for CDX2 and SATB2. The morphological chractoristic of the 5 cases undergoing appendectomy was the same as LAMN. CDX2 and SATB2 in the 5 cases were also strongly positive. Among the 17 cases of MBOT, 15 cases were unilateral and 2 cases were bilateral. The ovarian capsule was intact without mucus infiltration. Single or multifocal mucous cysts with mild to moderate atypical mucous epithelium were observed in the ovaries, and goblet cells were common. Immunohistochemically, diffusely strong positive for CK7 in 15 of 17 cases, and locally positive for CK20 in 5 of 17 cases were noted;4 and 2 in 17 cases were weakly positive for CDX2 and SATB2, respectively, and the others were negative. Conclusion Univariate regression analysis shows that the location of the tumor, peritoneal pseudomyxoma, infiltration of ovarian capsule, and multifocal papillary structures in cyst inner wall epithelium could be used to distinguish the two groups of ovrian cancer in practice. For microscopic examination, the shedding of tiny papillary clusters in the mucus and the aggregation of pyknotic degeneration epithelial cells also can be used as morphological parameters to distinguish the them besides the presence of mucous pool and the morphology of mucous epithelium including the presence of goblet cells, subepithelial fissures, and mucinous granuloma. CK7, CK20, CDX2 and SATB2 can be used as the primary panel of immunohistochemical examination, but it should be remembered that LAMN-involved ovaries may induce the loss of the latter proteins expression. And the teratoma-associated ovarian mucinous neoplasms may also show the same histological and immunohistochemical characteristics as LAMN-involved ovaries.