乳腺化生性鳞状细胞癌临床病理特征及HER2表达情况分析

Clinicopathological features and HER2 expression of metaplastic squamous cell carcinoma of the breast

目的探讨乳腺化生性鳞状细胞癌(metaplastic squamous cell carcinoma,MSCC)的临床病理特点及HER2表达情况。方法回顾性分析华中科技大学同济医学院附属协和医院2010—2021年诊断的MSCC共47例,收集所有病例的临床病理资料,检测肿瘤细胞的免疫表型,分析患者的临床病理特征和预后。结果47例患者均为女性,单纯的鳞状细胞癌(pure squamous cell carcinoma,PSCC)25例,含有鳞状细胞癌成分的混合性化生性癌(mixed metaplastic carcinoma with squamous cell component,MMSC)22例。中位年龄54岁(29~84岁),肿块直径0.8~10.0 cm,平均3.3 cm,85.7%(24/28)病例的最大直径<5 cm,仅4例≥5 cm。89.5%的MMSC表现为实性肿块,而囊性变更常见于PSCC组(50%,P<0.05)。36.7%(11/30)患者在确诊时已存在淋巴结转移。在所有病例中鳞状细胞癌成分均完全或部分表达p63、p40及细胞角蛋白(CK)5/6,55.3%(26/47)为三阴性表型,HER2阳性患者共7例,6例为MMSC,显著高于PSCC组(1例),且差异有统计学意义(P<0.05)。其中1例MMSC中的浸润性导管癌HER22+/鳞状细胞癌HER20,但荧光原位杂交示浸润性导管癌阴性,鳞状细胞癌阳性。7例HER2阳性患者中,6例接受了抗HER2靶向治疗,其中2例在术前接受了联合抗HER2靶向治疗的新辅助化疗,1例达到病理完全缓解,1例部分缓解,残留肿瘤为鳞状细胞癌;随访9~26个月,4例无疾病进展,2例出现肺转移,1例出现局部复发。结论MSCC是一组异质性疾病,PSCC和MMSC可能是两种不同的疾病实体。大部分MSCC为三阴性,HER2阳性多见于含有浸润性导管癌成分的MMSC。部分HER2阳性MSCC患者接受抗HER2靶向治疗后可以达到完全缓解或长期无进展生存,但鳞状细胞癌成分对靶向治疗的敏感性可能要差于浸润性导管癌成分。

Objective To investigate the clinicopathological features and HER2 expression of metaplastic squamous cell carcinoma(MSCC)of the breast.Methods A total of 47 MSCC cases diagnosed in the Wuhan Union Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan,China from January 2010 to December 2021 were reviewed.The clinical information(including the follow-up data of HER2 positive patients)and pathological features were collected and analyzed.Results All of the patients were female.Among the 47 cases,25 were pure squamous cell carcinoma(PSCC)and 22 were mixed metaplastic carcinoma with squamous cell component(MMSC).The median age of the patients was 54 years(range,29-84 years).The maximum diameter of the mass ranged from 0.8 to 10.0 cm,with a mean value of 3.3 cm,85.7%(24/28)of the cases were smaller than 5 cm,and only 4 cases were larger than or equal to 5 cm.89.5%of the MMSC presented with a solid mass.Cystic changes were more commonly found in the PSCC group(50%,P<0.05)than the MMSC group.36.7%(11/30)of the patients had lymph node metastasis at the time of diagnosis.The squamous cell carcinoma component in all cases showed diffuse or patchy expression of p63,p40 and CK5/6.55.3%(26/47)of the cases showed triple-negative phenotype.Among the 7 HER2-positive patients,6 were MMSC group,which had a significantly higher rate of HER2-positivity than that in the PSCC group(1 case).In 1 MMSC case,immunohistochemistry showed HER22+in the invasive ductal carcinoma component and HER2 negativity(0)in the squamous cell carcinoma component,but HER2 FISH was negative in invasive ductal carcinoma and positive in squamous cell carcinoma component.Six HER2-positive MSCC patients received anti-HER2-targeted therapy,including two patients who received neoadjuvant chemotherapy combined with anti-HER2-targeted therapy before surgery.One patient achieved pathological complete remission,while the other achieved partial remission(the residual tumors were squamous cell carcinoma components).After 9-26 months of follow-up,four patients had no disease progression,two patients developed pulmonary metastases,and one patient showed local recurrence.Conclusions MSCC is a group of heterogeneous diseases.PSCC and MMSC may be two different entities.Most of the MSCC are triple-negative and HER2 positivity is more commonly seen in MMSC with invasive ductal carcinoma component.Some HER2-positive MSCC patients can achieve complete remission or long-term progression-free survival after receiving anti-HER2 targeted therapy,but the squamous cell carcinoma component may be less sensitive to targeted therapy than the invasive ductal carcinoma component.