Atypical carcinoid tumour of the lung: a study of 33 cases with prognostic features

Atypical carcinoids of the lung (well-differentiated neuroendocrine carcinomas) are rare tumours of uncertain prognosis. We have studied 33 cases--male to female ratio 2:1, age range 22-75 years, mean 55 years, 80% smokers, 15 peripheral and 18 central, tumour size 1.2-9.5 cm. Microscopically they had a nesting/insular, trabecular or lobular pattern. Nuclear morphology was variable, round cells, large cells and spindle cells being identified with small cell areas in five tumours. Mitotic activity varied from 4 to 80 per 1.52 mm2. Areas of necrosis were seen in all tumours. All 33 tumours were cytokeratin positive (AE1/AE3 and CAM5.2), 32 were positive for neuron-specific enolase, synaptophysin and chromogranin A. Electronmicroscopy showed dense core granules in 29 available cases. Nineteen cases were stage I, nine stage II, four stage III and one stage IV. Follow-up information was available for 22 cases. Size, location, stage and large cell/small cell morphology were important prognostic indicators. Large tumour size, large cell or mixed large cell/small cell morphology, peripheral localization and advanced stage were adverse prognostic indicators. Mitotic activity and the presence of necrosis did not appear to influence stage or behaviour.