Cui Wenjing, Yang Changwei, Ding Xiaochen, Liu Jiayan, Zhang Hongjuan, Xu Hong
Department of Pathology, State Key Laboratory of Cancer Biology, Xijing Hospital and School of Basic Medicine, Fourth Military Medical University, Xi'an, Shaanxi, China.
Department of Emergency Medicine, Xi'an Honghui Hospital, Xi'an, Shaanxi, China.
Diagn Cytopathol. 2025 Mar;53(3):E38-E45. doi: 10.1002/dc.25427. Epub 2024 Dec 5.
Primary breast large-cell neuroendocrine carcinoma (LCNEC)/squamous cell carcinoma (SCC), also referred to as mixed neuroendocrine/non-neuroendocrine neoplasms of the breast (Br-MiNENs), represents an exceedingly rare malignancy. We report the first case of primary breast LCNEC/SCC diagnosed via ultrasound-guided fine-needle aspiration (FNA) biopsy of the left supraclavicular and left internal mammary lymph nodes. The patient, a 40-year-old female, underwent a lumpectomy followed by breast-conserving surgery and was diagnosed with primary breast LCNEC. Notably, within merely four months following the breast-conserving surgery, PET-CT revealed lymph node enlargement, prompting the performance of FNA. FNA cytology of metastatic lymph nodes revealed two distinct tumor components, allowing for clear differentiation between LCNEC and SCC in the smear. The diagnosis was further corroborated by immunocytochemical (ICC) staining of the cell blocks. Subsequently, histopathological re-examination of the breast mass revealed occult SCC components comprising less than 1% of the tumor cells. Additionally, the case exhibited triple-negative breast cancer, with PIK3CA, TP53, RB1, and BCL2L11 mutations identified through next-generation sequencing (NGS). Br-MiNEN is exceedingly rare, and its cytological diagnosis poses significant challenges. It is recommended that a detailed and objective description of each tumor component and its proportion be provided. This report provides the first detailed description of the FNA cytology of LCNEC/SCC, thereby enhancing cytopathologists' comprehension of this tumor. Auxiliary studies, including ICC staining and molecular biology assays, are crucial for accurate diagnosis, therapy, and prognosis.
原发性乳腺大细胞神经内分泌癌（LCNEC）/鳞状细胞癌（SCC），也被称为乳腺混合性神经内分泌/非神经内分泌肿瘤（Br-MiNENs），是一种极其罕见的恶性肿瘤。我们报告首例通过超声引导下对左锁骨上和左乳内淋巴结进行细针穿刺（FNA）活检诊断的原发性乳腺LCNEC/SCC病例。该患者为一名40岁女性，接受了肿块切除术，随后进行了保乳手术，被诊断为原发性乳腺LCNEC。值得注意的是，在保乳手术后仅仅四个月，PET-CT显示淋巴结肿大，促使进行FNA。转移性淋巴结的FNA细胞学检查发现了两种不同的肿瘤成分，使得在涂片上能够清晰区分LCNEC和SCC。细胞块的免疫细胞化学（ICC）染色进一步证实了诊断。随后，对乳腺肿块进行组织病理学复查发现隐匿性SCC成分，其占肿瘤细胞不到1%。此外，该病例表现为三阴性乳腺癌，通过下一代测序（NGS）鉴定出PIK3CA、TP53、RB1和BCL2L11突变。Br-MiNEN极其罕见，其细胞学诊断面临重大挑战。建议提供每个肿瘤成分及其比例的详细客观描述。本报告首次详细描述了LCNEC/SCC的FNA细胞学，从而增强了细胞病理学家对这种肿瘤的理解。辅助研究，包括ICC染色和分子生物学检测，对于准确诊断、治疗和预后至关重要。
