Large cell neuroendocrine carcinomas (LCNEC) express one or more of the neuroendocrine markers – chromogranin, synaptophysin, NCAM/CD56 and others. NCAM/CD56 is highly sensitive but less specific for LCNEC. TTF-1 is positive in about 50% of cases. Napsin A expression is seen only in rare cases. LCNEC is positive for pancytokeratin, low molecular weight cytokeratins, and CK7. Squamous cell carcinoma-related markers such as CK5/6 and p40 are usually negative. Ki-67 labeling index is high, usually between 40% and 80%. CD117 (positive in 70% cases) is an indicator of adverse prognosis. The image shows chromatin diffusion and encrustation of DNA from the necrotic tumor cells onto the vessel wall. It is referred to as Azzopardi effect.