Zheng Yan, Tang Huaxiao, Liu Qian, Zhang Yujie, Zhao Peng, Zhang Shukun, Wang Chengqin
Shandong Probincial Key Medical and Health Laboratory of Geriatric Gastrointestinal Tumor Pathology; Department of Pathology, Weihai Municipal Hospital, Cheeloo College of Medicine, Shandong University, Weihai, China.
Department of Pathology, the Affiliated Weihai Second Municipal Hospital of Qingdao University, Weihai, China.
Diagn Pathol. 2025 May 28;20(1):68. doi: 10.1186/s13000-025-01650-1.
Primary mucinous cystadenocarcinoma of the breast (BMCA) is a rare neoplasm with few reports in the literature. Its molecular characteristics, prognosis, and treatment protocols are not well understood, and there is a lack of consensus concerning the optimal management of this condition.
Four cases of clinical and pathological data were collected from 2018 to 2024. Next generation sequencing with a 654 cancer-associated gene panel was utilized to detect gene mutations. Immunohistochemistry was carried out to evaluate protein expression levels.
Firstly, we combined clinical imaging examinations and IHC to exclude the possibility of metastasis from ovarian or pancreatic origins. BMCA was composed of cystically dilated ducts lined by tall columnar mucin-containing epithelium. The morphological spectrum of MCA varied from MCA alone to MCA combined with carcinoma in situ (CIS) to MCA associated with invasive ductal carcinoma (IDC). ER/PR/HER2 and CK20 were all negative, while CK7 and GATA3 were positive by IHC in four cases. Although the prognosis of the other three patients was favorable during the follow-up periods of 13, 10, and 3 months, respectively, case 2# experienced a recurrence of the primary focus after 42 months. No lymphatic metastasis was identified in cases 1-4#. In addition, next-generation sequencing (NGS) identified 17 mutated genes and 25 mutation sites in four cases. TP53, PIK3CA, AKT, PTEN, and RB1 were the highest frequency mutated genes. Given that AKT mutations typically refer to AKT1(E17K) rather than AKT2 or AKT3, AKT protein expression was detected only in Case 2# (AKT1, E17K). PTEN protein was expressed in case 4# (corresponded to missense mutation), loss of PTEN expression were corresponding with splicing mutation in case1#. In brief, AKT and PTEN protein expression could be corresponded to gene mutation in a certain extent. However, PIK3CA protein expression was positive in Case 2# but negative in Case 1#, which did not fully accordance with the NGS-detected missense mutations. No associated germline variations were detected. Additionally, neither PDL-1 expression nor microsatellite instability-high (MSI-H) status was identified.
The tumorigenesis and development of BMCA may be regulated to the PI3K/AKT pathway. Consequently, a comprehensive genetic analysis of more cases could elucidate the molecular mechanisms underlying this rare tumor.
原发性乳腺黏液性囊腺癌（BMCA）是一种罕见的肿瘤，文献报道较少。其分子特征、预后和治疗方案尚不清楚，对于该疾病的最佳管理缺乏共识。
收集2018年至2024年4例临床和病理资料。利用包含654个癌症相关基因的二代测序检测基因突变。进行免疫组织化学以评估蛋白表达水平。
首先，我们结合临床影像学检查和免疫组化排除了卵巢或胰腺来源转移的可能性。BMCA由内衬高柱状含黏液上皮的囊性扩张导管组成。黏液性囊腺癌（MCA）的形态谱从单纯MCA到MCA合并原位癌（CIS）再到MCA合并浸润性导管癌（IDC）不等。4例患者免疫组化显示ER/PR/HER2和CK20均为阴性，而CK7和GATA3为阳性。尽管其他3例患者在分别为13个月、10个月和3个月的随访期内预后良好，但2#病例在42个月后出现原发病灶复发。1 - 4#病例均未发现淋巴转移。此外，二代测序（NGS）在4例中鉴定出17个突变基因和25个突变位点。TP53、PIK3CA、AKT、PTEN和RB1是突变频率最高的基因。鉴于AKT突变通常指AKT1（E17K）而非AKT2或AKT3，仅在2#病例中检测到AKT蛋白表达（AKT1，E17K）。4#病例中表达PTEN蛋白（对应错义突变），1#病例中PTEN表达缺失与剪接突变相对应。简而言之，AKT和PTEN蛋白表达在一定程度上可与基因突变相对应。然而，2#病例中PIK3CA蛋白表达为阳性，而1#病例中为阴性，这与NGS检测到的错义突变并不完全一致。未检测到相关的胚系变异。此外，未发现PDL - 1表达或微卫星高度不稳定（MSI - H）状态。
BMCA的发生发展可能受PI3K/AKT途径调控。因此，对更多病例进行全面的基因分析可能阐明这种罕见肿瘤的分子机制。
