Primary Large Cell Neuroendocrine Carcinoma of the Mediastinum

BACKGROUND: to present a rare case of primary neuroendocrine carcinoma of the mediastinum treated by multimodal therapy. METHODS: a 50-year-old man, non-smoker, with unremarkable past medical history, presented for asthenia, dyspnea and sub-sternal discomfort. A chest CT-scan showed a huge mass of 10,7x5,5x9,5cm in the anterosuperior mediastinum. The mass seems infiltrate both brachiocephalic veins, the superior vena cava, pericardium and both lungs (Fig.1a/b). PET-CT showed an intense hyperactivity of the mediastinal mass. CT-guided needle biopsy allows diagnosis of neuroendocrine carcinoma. After multisciplinary discussion, a multimodal approach was planned. The patient underwent 4 cycles of chemotherapy with cisplatin and gemcitabine. Since chest CT-scan showed a reduction of the tumor (7,4x5,6x9cm), a surgical resection was proposed. RESULTS: a median sternotomy was performed. On exploration, both lungs were marginally infiltrated. The pericardium was partially excised; the left anonymous vein was almost totally invaded by the tumor. The right anonymous vein was infiltrated at the confluence with the superior vena cava. After total caval clamping (clamping time: 27’), a partial section and reconstruction with bovine pericardium was performed (Fig.1c). The patient was discharged uneventfully on postoperative-day 9. The patient underwent 25 sessions of adjuvant radiotherapy. Currently, he’s free of disease after 30 months. Macroscopically the mass measured 9x8x3cm, looks whitish with tense-elastic consistency. Microscopically it showed clusters of small uniform cells, sometimes with cuboidal morphology, with nuclear pleomorphism and small nucleoli, arranged in trabeculae, nests and lobules and immersed in a hyaline stroma with foci of necrosis (Fig.2a). Perineural and vascular invasion were present. Immunohistochemistry showed the tumor cells were positive for chromogranin (Fig.2c), synaptophysin (Fig.2d), cytokeratins and negative for TTF1, FAP, PSA. The proliferation index Ki-67 was 10% (Fig.2b). Considering the radiological, morphological and immunophenotypic characteristics, the diagnosis was consistent with primary neuroendocrine carcinoma of the mediastinum. CONCLUSIONS: mid-term survival was achieved after aggressive multimodal therapy