中央坏死性乳腺癌的临床病理分析

Clinicopathologic study of centrally necrotizing carcinoma of breast

目的探讨中央坏死性乳腺癌的临床病理和免疫表型特征及其与基底细胞样型乳腺癌的关系。方法观察35例中央坏死性乳腺癌的临床病理特点，并采用ER、PR、HER2、CK8／18、高相对分子质量CK（3413E12）、CK5／6、CK14、CK17、平滑肌肌动蛋白（SMA）、p63、波形蛋白、表皮生长因子受体（EGFR）进行EnVision法免疫组织化学染色。结果35例患者的发病年龄为30—82岁，平均54．2岁。大体观察，肿物表现为边界较清楚的单中心结节，直径1．0～5．0cm，平均2．4cm。镜下，肿瘤中央有大片坏死或无细胞区，残留癌组织呈缎带状环绕在坏死区周围。中央坏死区表现为三种形态：24例主要由肿瘤性凝固性坏死组成，伴不同程度的纤维化或玻璃样变；8例以纤维化或瘢痕组织为主，见少量坏死癌组织残影；3例为梗死。周围残留癌组织32例为浸润性导管癌3级，3例为2级。20例伴有导管原位癌，5例伴有浸润性微乳头状癌，17例肿瘤周边见淋巴细胞浸润。31例中央坏死性乳腺癌中，基底细胞样标记（83．9％，26例）的阳性率明显高于肌上皮标记（38．7％，12例）。基底细胞样型所占比例（20例，64．5％）显著高于管腔A型（3例，9．7％）、管腔B型（3例，9．7％）、HER2过表达型（4例，12．9％）和不表达型（1例，3．2％）。20例基底细胞样型癌中，基底细胞样标记中CK5／6阳性18例，其余依次为CK17（8／10）、CK14（14／19）、EGFR（8／16）。10例获得随访资料，随访15～42个月，平均21．5个月。9例疾病进展（因乳腺癌复发、转移或死亡），中位无病生存和总生存时间分别为14．0和18．0个月。平均和中位疾病进展时间分别为16．6和13．0个月。结论中央坏死性乳腺癌具有独特的、容易识别的形态特点，大多显示基底细胞样免疫表型，预后差，是基底细胞样型乳腺癌的典型代表。

Objective To study the clinicopathologic features and immunophenotype of centrally necrotizing carcinoma （CNC） of breast ; and to study its relationship with basal-like breast cancer. Methods The clinical and pathologic characteristics of 35 cases of CNC were analyzed. Immunohistochemical study for estrogen receptor, progesterone receptor, HER2, CK8/18, 34βE12, CK5/6, CK14, CK17, smooth muscle aetin, p63, vimentin and epidermal growth factor receptor was performed using EnVision method. The surival information of 10 case were obtained. Results The age of patients with CNC ranged from 30 to 82 years （mean = 54. 2 years）. Macroseopically, all tumors were relatively circumscribed, with a mean diameter of 2.4 cm. Histologically, there was a prominent central, necrotic or acellular zone surrounded by a narrow rim of viable tumor cells. The central necrotic foci had the following morphologic patterns ： （ 1 ） coagulative tumor necrosis associated with various degree of fibrosis or hyaline degeneration （24 cases ）, （2） predominance of fibrous and scar tissue, with small amount of necrotic debris （8 cases） , and （3） infarction （3 cases）. The peripheral zone of tumor cells showed features of grade 3 invasive ductal carcinoma in 32 cases and grade 2 in 3 cases. Twenty cases of CNC were associated with ductal carcinoma in-situ. A component of invasive micropapillary carcinoma was identified in 5 cases. Peripheral lymphocytic infiltrates were seen in 17 cases. Immunohistochemical study of 31 cases showed that the expression rate of basal-like markers （83.9%, 26 cases） was higher than that of myoepithelial markers （ 38. 7%, 12 cases）. The percentage of basal-like subtype（64. 5% ,20 cases） was higher than luminal-A（9. 7% ,3 cases） ,luminal-B （9.7% ,3 cases）, HER2 over-expression （ 12. 9% , 4 cases） and null （3.2% , 1 case） subtypes. In 20 cases of basal-like carcinoma, the expression ratio of CK5/6 was highest amongst basal-like markers （18 cases）, the other markers ratios of CK17, CK14 and epidermal growth factor receptor were 8/10, 14/19 and 8/16, respectively. Follow-up data were available in 10 patients. The follow-up duration ranged from 15 to 42 months （mean =21.5 months）. The median disease-free and overall survivals were 14.0 and 18.0 months, respectively. Disease progression （as defined by the presence of recurrence, metastasis or tumor-related death） occurred in 9 patients. The mean and median time to disease progression was 16. 6 and 13.0 months, respectively. Conclusions CNC is a rare subtype of breast carcinoma and has distinctive, easily discernible morphologic features. The majority of CNC exhibits basal-like immunophenotype and carries a poor prognosis. CNC is the typical representative of basal-like breast cancer.