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

Abstract

<b><i>Background:</i></b> 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. <b><i>Methods:</i></b> Based on a literature review and our own case, the clinicopathologic differences between IBC-CP patients (<i>n</i> = 17) and MC-B patients (<i>n</i> = 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. <b><i>Results:</i></b> Compared to the MC-B patients, the IBC-CP patients were older (<i>p</i> &#x3c; 0.001) and less frequently had past histories of gestational trophoblastic disease/pregnancy/abortion (<i>p</i> = 0.001) and distant metastases (<i>p</i> = 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 <i>TP53</i> gene in both the choriocarcinomatous and IBC components. Meanwhile, copy number loss in the <i>PTEN</i> gene was only identified in the choriocarcinomatous components. <b><i>Conclusion:</i></b> The present IBC-CP case is triple-negative breast cancer with <i>TP53</i> mutation. The <i>PTEN</i> gene may be associated with choriocarcinomatous differentiation. Obtaining a medical history is mandatory to exclude metastatic lesions.