Supplementary Material for: Clinicopathologic and Molecular Characteristics of and Diagnostic Dilemmas in Invasive Breast Carcinoma with Choriocarcinomatous Pattern apropos a New Case: A Literature Review with New Findings

Background: Invasive breast carcinoma with a choriocarcinomatous pattern (IBC-CP) is extremely rare, and its molecular basis is yet unclear. The choriocarcinomatous pattern is characterized by the biphasic arrangement of multinucleated syncytiotrophoblast-like cells around clusters of monotypic tumor cells in a hemorrhagic background, along with β-human chorionic gonadotropin (β-hCG) expression. The differentiation of IBC-CP from metastatic choriocarcinoma of the breast (MC-B) is difficult due to the histologic similarity. Methods: Based on a literature review and our own case, the clinicopathologic differences between IBC-CP patients (n = 17) and MC-B patients (n = 8) were analyzed. Moreover, in our case of IBC-CP, next-generation sequencing (NGS) comparative analysis was conducted for both choriocarcinomatous and invasive breast carcinoma (IBC) components. Results: Compared to the MC-B patients, the IBC-CP patients were older (p p = 0.001) and distant metastases (p = 0.005). Our case, a 49-year-old female patient, presented with masses in the right breast and axilla. Following neoadjuvant chemotherapy, a radical mastectomy found an 8.5-cm-sized tumor. Microscopically, multinucleated syncytiotrophoblast-like cells were observed around mononuclear tumor cells with hemorrhage and necrosis. Some tumor cells showed β-hCG immunopositivity, which was compatible with IBC-CP. NGS results showed a missense mutation in exon 5 of the TP53 gene in both the choriocarcinomatous and IBC components. Meanwhile, copy number loss in the PTEN gene was only identified in the choriocarcinomatous components. Conclusion: The present IBC-CP case is triple-negative breast cancer with TP53 mutation. The PTEN gene may be associated with choriocarcinomatous differentiation. Obtaining a medical history is mandatory to exclude metastatic lesions.

背景：伴绒毛膜癌样形态的浸润性乳腺癌（Invasive breast carcinoma with a choriocarcinomatous pattern, IBC-CP）极为罕见，其分子基础尚未明确。该亚型的绒毛膜癌样形态特征为：在出血性背景中，多核合体滋养细胞样细胞围绕单一型肿瘤细胞簇呈双相排列，且表达β-人绒毛膜促性腺激素（β-human chorionic gonadotropin, β-hCG）。由于二者组织学形态相似，将IBC-CP与乳腺转移性绒毛膜癌（Metastatic choriocarcinoma of the breast, MC-B）进行鉴别诊断存在一定难度。
方法：本研究结合文献复习与本院1例病例，对17例IBC-CP患者与8例MC-B患者的临床病理差异展开分析。此外，针对该例IBC-CP患者的绒毛膜癌样成分与浸润性乳腺癌（Invasive breast carcinoma, IBC）成分，开展了下一代测序（next-generation sequencing, NGS）对比分析。
结果：与MC-B患者相比，IBC-CP患者年龄更大（p=0.001）且伴远处转移（p=0.005）。本院1例49岁女性患者表现为右侧乳腺及腋窝肿物。新辅助化疗后，行根治性乳房切除术，术中见肿瘤大小为8.5cm。镜下可见单核肿瘤细胞周围存在多核合体滋养细胞样细胞，伴出血与坏死。部分肿瘤细胞呈β-hCG免疫阳性，符合IBC-CP的诊断。NGS结果显示，绒毛膜癌样成分与IBC成分均存在TP53基因第5外显子的错义突变。同时，仅在绒毛膜癌样成分中检测到PTEN基因的拷贝数缺失。
结论：本次报道的IBC-CP病例为伴TP53突变的三阴性乳腺癌。PTEN基因可能与绒毛膜癌样分化相关。采集完整病史以排除转移性病变为强制性要求。