Abstract Introduction Distinguishing between primary lung adenocarcinoma and metastatic triple-negative breast cancer can be complex due to overlapping histologic and radiologic features. Immunohistochemistry plays a key role in defining tumor origin, which is crucial for guiding therapy. We present a case of a young woman with a history of TNBC who developed a right upper lobe pulmonary nodule with inconclusive IHC findings. Case Presentation A 30-year-old woman, previously diagnosed with left breast invasive ductal carcinoma, grade III, triple-negative (ER-, PR-, HER2-, Ki-67 75%), underwent quadrantectomy (Jul,2023) followed by adjuvant radiotherapy and chemotherapy. In April 2025, during oncologic follow-up, a right upper lobe pulmonary nodule (2.7 × 3.5 × 2.2 cm) with heterogeneous enhancement and central necrosis was detected on chest CT. No other metastatic lesions were identified. The patient underwent bilobectomy (right upper and middle lobes) and mediastinal lymphadenectomy. Histopathology revealed a moderately differentiated adenocarcinoma with central necrosis, but the primary site could not be determined. IHC demonstrated negativity for ER, PR, HER2, mammaglobin, GATA3, CDX2, CK7, CK20, and breast markers, with Ki-67 positivity (80%). The profile was compatible with either a primary lung adenocarcinoma or a metastatic carcinoma of breast origin. Mediastinal lymph node (station 4R) biopsy confirmed metastatic adenocarcinoma with necrosis. Given the patient’s prior TNBC history and lack of definitive pulmonary markers, a multidisciplinary tumor board favored the diagnosis of metastatic breast carcinoma. She initiated adjuvant chemotherapy with cisplatin and oral vinorelbine on October 3, 2025. Discussion This case underscores the diagnostic complexity of differentiating pulmonary adenocarcinoma from metastatic TNBC. Triple-negative tumors frequently lack organ-specific markers, complicating IHC interpretation. In our case, the absence of ER, PR, HER2, GATA3, and mammaglobin, along with high Ki-67, did not favor a typical lung adenocarcinoma pattern (TTF-1 or Napsin A positivity, which were also negative). Given the patient’s young age, prior history of aggressive TNBC, and isolated pulmonary lesion, the multidisciplinary consensus supported a diagnosis of metastatic breast carcinoma rather than a de novo primary lung adenocarcinoma. This decision directly influenced systemic therapy, emphasizing the importance of integrated evaluation involving pulmonology, thoracic surgery, oncology, and pathology. Conclusion In young women with a history of TNBC, solitary pulmonary nodules present a significant diagnostic challenge. When IHC is inconclusive, multidisciplinary discussion integrating clinical context, radiologic evolution, and prior tumor biology is essential. Accurate differentiation between primary lung cancer and metastatic breast carcinoma is critical to guide appropriate treatment and prognosis This abstract is funded by: none
Binda et al. (Fri,) studied this question.
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