Abstract Background Small cell lung cancer (SCLC) is a high-grade neuroendocrine carcinoma that usually presents as a central hilar mass with mediastinal lymphadenopathy and positive thyroid transcription factor-1 (TTF-1) expression. Rarely, SCLC may arise without a visible lung mass and lack TTF-1 immunoreactivity, mimicking primary mediastinal neoplasms and delaying diagnosis. Case Presentation A 68-year-old woman, former 30 pack-year smoker with COPD on nocturnal oxygen, presented with 3 months of progressive dysphagia to solids then liquids, nasal regurgitation, pooled saliva, new daytime oxygen requirement, and 18-lb weight loss. Examination revealed a firm, immobile right supraclavicular node. CT neck/chest showed a 9.5 × 7×7 cm right inferior neck/superior mediastinal mass causing tracheoesophageal deviation and an 8 × 5.5 cm pericarinal mass narrowing the left mainstem bronchus, with bulky mediastinal and right supraclavicular adenopathy but no discrete lung mass. MRI brain and CT abdomen/pelvis showed no distant metastases, and radiology favored primary mediastinal lymphoma. Laboratory evaluation revealed mild anemia, thrombocytosis, elevated LDH, and persistent hyponatremia consistent with paraneoplastic SIADH. Because of severe dysphagia and aspiration risk, she underwent EGD/EUS with PEG placement. Right supraclavicular nodal core biopsy was chosen over mediastinal sampling due to airway deviation. Histology showed sheets of small cells with scant cytoplasm, finely granular chromatin, nuclear molding, high mitotic index, and necrosis. Immunohistochemistry was positive for INSM1, synaptophysin, and CAM5.2, negative for TTF-1 and lymphoid markers, consistent with high-grade neuroendocrine small cell carcinoma. With cervical nodal involvement beyond the hemithorax, the tumor was staged as extensive-stage SCLC. The patient was treated with carboplatin/etoposide and pegfilgrastim, with planned consolidative thoracic radiotherapy. Discussion This case illustrates an uncommon presentation of TTF-1-negative SCLC as a bulky mediastinal mass without a radiographically apparent lung primary, closely simulating primary mediastinal lymphoma. Although 85-90% of SCLCs are TTF-1 positive, up to 10-20% are negative, and TTF-1 negativity does not exclude pulmonary origin. Most reported mediastinal SCLC cases either have a visible lung mass or retain TTF-1 expression; to our knowledge, no prior report describes a TTF-1-negative SCLC presenting solely as a bulky mediastinal mass without a lung lesion. This case underscores the limitations of relying on TTF-1 and imaging alone and highlights the critical role of comprehensive histopathology and immunohistochemistry in distinguishing SCLC from lymphoma and other mediastinal tumors. This abstract is funded by: None
Elsawy et al. (Fri,) studied this question.