In 2015, the WHO proposed histopathological diagnostic criteria for LCNEC, which include the presence of neuroendocrine architecture (nests, trabeculae, rosettes, palisades), a high mitotic index (≥ 11 mitoses per 2 mm2 (10 HPF) with an average of 70 per 2 mm2 (10 HPF)), presence of necrosis, often in form of large areas, presence of large tumor cells with moderate to abundant cytoplasm, prominent nucleolus, and finally on the immunohistochemical level, one or more positive neuroendocrine markers in immunohistochemistry: synaptophysin, chromogranin, and CD56. This evidence concerns the gene SYP and large cell neuroendocrine carcinoma.