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> < 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.

Non‐small cell lung carcinoma with ectopic gonadotropin production: A case report and review of the literature

“…2 Ectopic secretion of trophoblastic hormones, namely hCG, by nontrophoblastic tumors is extremely rare but has been identified in men and women with lung, breast, renal, brain, and other neoplasms. [4][5][6][7][8][9][10][11][12][13][14][15] Marked serum hCG elevation due to ectopic production of hCG by lung cancer is extremely rare and has been the subject of case reports and small series in the literature. [4][5][6][7]9 Excessive hCG can mimic ectopic pregnancy or trophoblastic tumors in younger female patients 9 and can lead to gynecomastia in men and vaginal bleeding in postmenopausal women.…”

Morphological and molecular pathological features of the breast carcinoma with choriocarcinomatous features: A case report and a literature review

“…Anti-HER2 targeted therapy may be effective for both tumor components. BCCF is a highly malignant tumor of the breast and shows aggressive behavior in most cases with many patients presenting with lymph nodes and distant metastasis ( 4 – 16 ). Current therapeutic strategies for BCCF mainly consist of endocrine therapy, surgery, and chemotherapy ( 6 , 8 , 22 ).…”

“…The median age of the patients was 51.5 years (range, 31-71 years). Most tumors were in the right breast and all cases were positive for HCG antibodies in IHC studies (4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16).…”

“…Anti-HER2 targeted therapy may be effective for both tumor components. BCCF is a highly malignant tumor of the breast and shows aggressive behavior in most cases with many patients presenting with lymph nodes and distant metastasis (4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16).…”

“…Breast carcinoma with choriocarcinomatous features (BCCF) is a rare variant of breast carcinoma and was first reported by Saigo and Rosen in 1981 ( 4 ). To date, a total of 19 cases of BCCF have been reported ( 4 – 16 ). Here, we reported the morphological and molecular pathological features of a 55-year-old woman with BCCF and review the previous literature about BCCF.…”