Metachronous Metastatic Invasive Breast Carcinoma and Metastatic Small Cell Carcinoma Clinically and Radiologically Favoured to Be of Pulmonary Origin: A Case Report

Background

In patients with metastatic breast carcinoma, newly identified visceral or pulmonary lesions may represent progression of the known malignancy or, less commonly, a distinct second primary tumor. Histopathological and immunohistochemical evaluation is therefore essential for establishing tumor lineage and guiding treatment. Case Presentation: We report the case of a 46-year-old woman diagnosed in 2021 with metastatic hormone receptor-positive/HER2-negative breast carcinoma, presenting with a left breast mass and multiple osteolytic bone metastases. Histopathological examination demonstrated invasive breast carcinoma of no special type, with 98% estrogen receptor expression, 98% progesterone receptor expression, a Ki-67 proliferation index of 15%, and negative HER2 status. She received palliative radiotherapy for painful bone metastases and systemic treatment with letrozole and ribociclib. Five years later, she was evaluated for newly detected liver lesions. Positron emission tomography-computed tomography also demonstrated a metabolically active right centrohilar pulmonary lesion, although a primary lung tumor could not be definitively distinguished radiologically from nodal disease. Liver biopsy revealed a high-grade small-cell neuroendocrine carcinoma with positivity for TTF-1, chromogranin, synaptophysin, and CD56, a Ki-67 proliferation index of 85%, and negative GATA3 expression. These findings, together with the clinical and radiological features, favored a pulmonary origin. The patient was subsequently treated with cisplatin, etoposide, and atezolizumab.