Typical and atypical carcinoids within the pulmonary APUD tumor spectrum

The behavior of pulmonary APUD tumors is not constant; management is controversial, and morphology has reached its limit as a tool for prognostic assessment and therapeutic planning. We have studied 24 patients with carcinoids; 17 patients with typical carcinoids presented with Stage I disease, but one patient later died most probably of small cell undifferentiated lung cancer (SCLC). Seven patients with atypical carcinoids included three with Stage III cancers, one patient with simultaneous bilateral carcinoids, and one patient with simultaneous adenocarcinoma. Of 17 patients with typical carcinoids, 16 or 92% are disease free or died of unrelated causes. Of seven patients with atypical carcinoids, five or 71% are disease free. Tumor doubling time of atypical carcinoids, was 79.6 months (45 to 120) or six times shorter than that of typical carcinoids (p less than 0.05). Two of the three deaths from cancer were probably from SCLC and one from a synchronous adenocarcinoma. Review of diagnostic material from 12 patients with SCLC who survived a mean of 41 months (24 to 134) showed that diagnosis had rested on cytology alone in four patients and that, in seven patients, the quality or extent of the original diagnostic material was adequate to make the diagnosis of a malignant tumor but inadequate to permit reclassification. Tumor cells from 11 patients with carcinoids (seven typical and four atypical) and 28 patients with SCLC had DNA measurement by image analysis. The mean DNA content of typical and atypical carcinoids and SCLC is 1.17, 1.25, and 1.94 respectively (p less than 0.001). These findings strongly suggest a relationship between DNA content and atypia or malignancy in APUD lung tumors. We conclude that there are at least two levels of virulence among carcinoids represented by typical and atypical carcinoids. The prognosis for treated Stage I typical and atypical carcinoids is excellent. When deaths occur, they are from systemic cancer. Current evidence indicates that DNA measurements by image analysis may help to discriminate levels of malignancy among APUD pulmonary cancers and thereby help to clarify therapeutic controversies.