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Abstract：
BACKGROUND: Acinic cell carcinoma (AciCC) of the breast is a rare subtype of breast cancer. It was considered a low-grade triple-negative breast cancer (TNBC) with the potential to progress or transform into a high-grade lesion because of the molecular similarities with conventional aggressive TNBC in several genetic studies. Microscopically, the coexistence of classical low-grade and high-grade triple-negative components in breast AciCC is not uncommon. However, there is a scarcity of research on the comparative histopathological and genetic aspects of both components.
METHODS: A 34-year-old woman with a nontender mass in the upper outer quadrant of the left breast was initially diagnosed with a malignant small round cell tumor (undifferentiated or poorly differentiated carcinoma) based on a preoperative biopsy, which was later identified as breast AciCC with a high-grade solid component. Left breast-conserving surgery with sentinel lymph node biopsy was performed. Microscopically, the breast AciCC consisted of a classical acinic component and a high-grade component. The latter demonstrated a solid sheet-like pattern characterized by large, round, pleomorphic or vesicular nuclei, prominent nucleoli, and frequent mitotic activities. Classical acinic architectures focally merged together to form solid nests and transited into high-grade areas. Remarkably, in the high-grade lesion, conventional immunochemical markers for breast AciCC, such as α1-antitrypsin (AAT), Lysozyme (LYS), Epithelial membrane antigen (EMA), S100 protein (S100), and cytokeratin (CK) were negative, whereas cell cycle protein D1 (cyclin D1) and vimentin showed diffuse expression. Next‑generation sequencing (NGS) revealed that 43.5% of variants were identical in both components. Furthermore, PAK5 mutation; copy number (CN) loss of CDH1, CHEK1, and MLH1; and CN gains of CDK6, HGF, and FOXP1 were identified in the high-grade lesion. The patient was treated with eight cycles of adjuvant chemotherapy (epirubicin combined with cyclophosphamide) and radiotherapy after surgery, and she is currently alive for 43 months with no metastases or recurrences.
CONCLUSIONS: This case demonstrates a comparative analysis of the histopathological and genetic characteristics of classical low-grade and high-grade components of AciCC within the same breast. This information may serve as a morphological and molecular basis for further investigation into the molecular mechanisms underlying high-grade lesions in breast AciCC.
METHODS: A 34-year-old woman with a nontender mass in the upper outer quadrant of the left breast was initially diagnosed with a malignant small round cell tumor (undifferentiated or poorly differentiated carcinoma) based on a preoperative biopsy, which was later identified as breast AciCC with a high-grade solid component. Left breast-conserving surgery with sentinel lymph node biopsy was performed. Microscopically, the breast AciCC consisted of a classical acinic component and a high-grade component. The latter demonstrated a solid sheet-like pattern characterized by large, round, pleomorphic or vesicular nuclei, prominent nucleoli, and frequent mitotic activities. Classical acinic architectures focally merged together to form solid nests and transited into high-grade areas. Remarkably, in the high-grade lesion, conventional immunochemical markers for breast AciCC, such as α1-antitrypsin (AAT), Lysozyme (LYS), Epithelial membrane antigen (EMA), S100 protein (S100), and cytokeratin (CK) were negative, whereas cell cycle protein D1 (cyclin D1) and vimentin showed diffuse expression. Next‑generation sequencing (NGS) revealed that 43.5% of variants were identical in both components. Furthermore, PAK5 mutation; copy number (CN) loss of CDH1, CHEK1, and MLH1; and CN gains of CDK6, HGF, and FOXP1 were identified in the high-grade lesion. The patient was treated with eight cycles of adjuvant chemotherapy (epirubicin combined with cyclophosphamide) and radiotherapy after surgery, and she is currently alive for 43 months with no metastases or recurrences.
CONCLUSIONS: This case demonstrates a comparative analysis of the histopathological and genetic characteristics of classical low-grade and high-grade components of AciCC within the same breast. This information may serve as a morphological and molecular basis for further investigation into the molecular mechanisms underlying high-grade lesions in breast AciCC.
摘要：
背景：乳腺腺泡细胞癌（AciCC）是一种罕见的乳腺癌亚型。由于在几项遗传研究中与常规侵袭性TNBC的分子相似性，它被认为是低级别三阴性乳腺癌（TNBC），有可能发展或转变为高级病变。微观上,乳腺AciCC中经典的低级别和高级三阴性成分共存并不少见。然而,缺乏对两种成分的比较组织病理学和遗传方面的研究。
方法：一名34岁的左乳外上象限无触痛性肿块的妇女，根据术前活检，最初被诊断为恶性小圆细胞肿瘤（未分化或低分化癌）。后来被鉴定为具有高级固体成分的乳腺AciCC。行左乳保乳手术伴前哨淋巴结活检。微观上,乳腺AciCC由经典的酸碱成分和高级成分组成。后者表现出坚固的片状图案，其特征是大，圆形,多形性或泡状核，突出的核仁，和频繁的有丝分裂活动。经典的acinic建筑集中融合在一起，形成坚固的巢穴，并过渡到高级区域。值得注意的是,在高级别病变中，乳腺AciCC的常规免疫化学标记物，如α1-抗胰蛋白酶（AAT），溶菌酶(LYS),上皮膜抗原(EMA),S100蛋白(S100),细胞角蛋白（CK）阴性，而细胞周期蛋白D1（cyclinD1）和波形蛋白表现为弥漫性表达。下一代测序（NGS）显示，43.5％的变体在两个组件中都是相同的。此外，PAK5突变；CDH1，CHEK1和MLH1的拷贝数（CN）丢失；以及CDK6，HGF，在高级别病变中发现了FOXP1。术后给予8个周期的辅助化疗（表柔比星联合环磷酰胺）和放疗，她目前存活43个月，没有转移或复发。
结论：该病例对同一乳腺内经典低度和高度的AciCC成分的组织病理学和遗传特征进行了比较分析。此信息可作为进一步研究乳腺AciCC高级病变的分子机制的形态学和分子基础。
方法：一名34岁的左乳外上象限无触痛性肿块的妇女，根据术前活检，最初被诊断为恶性小圆细胞肿瘤（未分化或低分化癌）。后来被鉴定为具有高级固体成分的乳腺AciCC。行左乳保乳手术伴前哨淋巴结活检。微观上,乳腺AciCC由经典的酸碱成分和高级成分组成。后者表现出坚固的片状图案，其特征是大，圆形,多形性或泡状核，突出的核仁，和频繁的有丝分裂活动。经典的acinic建筑集中融合在一起，形成坚固的巢穴，并过渡到高级区域。值得注意的是,在高级别病变中，乳腺AciCC的常规免疫化学标记物，如α1-抗胰蛋白酶（AAT），溶菌酶(LYS),上皮膜抗原(EMA),S100蛋白(S100),细胞角蛋白（CK）阴性，而细胞周期蛋白D1（cyclinD1）和波形蛋白表现为弥漫性表达。下一代测序（NGS）显示，43.5％的变体在两个组件中都是相同的。此外，PAK5突变；CDH1，CHEK1和MLH1的拷贝数（CN）丢失；以及CDK6，HGF，在高级别病变中发现了FOXP1。术后给予8个周期的辅助化疗（表柔比星联合环磷酰胺）和放疗，她目前存活43个月，没有转移或复发。
结论：该病例对同一乳腺内经典低度和高度的AciCC成分的组织病理学和遗传特征进行了比较分析。此信息可作为进一步研究乳腺AciCC高级病变的分子机制的形态学和分子基础。
