To analyse clinical and biomolecular prognostic factors associated with the surgical approach and the outcome of 247 patients affected by primary atypical carcinoids (ACs) of the lung in a multi-institutional experience. We retrospectively evaluated clinical data and pathological tissue samples collected from 247 patients of 10 Thoracic Surgery Units from different geographical areas of our country. All patients were divided into four groups according to surgical procedure: sub-lobar resections (SURG1), lobar resections (SURG2), tracheobronchoplastic procedures (SURG3) and pneumonectomies (SURG4). Overall survival analysis was performed using the Kaplan–Meier method and log-rank test. Survival was calculated from the date of surgery to the last date of follow-up or death. The parameters evaluated included age, gender, smoking habits, laterality, type of surgery, 7th edition of TNM staging, mitosis Ki-67 (MIB1), multifocal forms, tumourlets, type of lymphadenectomy and neo/adjuvant therapy. For multivariate analysis, a Cox regression model was used with a forward stepwise selection of covariates. Two hundred and forty-seven patients (124 females and 123 males; range 10–84, median 60 years) underwent surgical resection for AC in the last 30 years as follows: n = 38 patients in SURG1, 181 in SURG2, 15 in SURG3 and 14 in SURG4. A smoking history was present in 136 of 247 (55%) patients. The median follow-up period was 98.7 (range 11.2–369.9) months. The overall survival probability analysis of the AC was 86.7% at 5 years, 72.4% at 10 years, 64.4% at 15 years and 58.1% at 20 years. Neuroendocrine multicentric forms were detected in 12 of 247 patients (4.8%; 1 of 12 pts) during the follow-up (range 11.2–200.4, median 98.7 months) and 33.4% had recurrence of disease. There were no significant differences between gender, tumour location and type of surgery at the multivariate analysis. Age [P < 0.001, hazard ratio (HR) 0.60; confidence interval (CI) 0.32–1.12], smoking habits (P = 0.002; HR 0.43, 95% CI 0.23–0.80) and lymph nodal metastatic involvement (P = 0.008; HR 0.46, 95% CI 0.26–0.82) were all significant at multivariate analysis. ACs of the lung are malignant neuroendocrine tumours with a worst outcome in patients over 70 years and in smokers. With the exception of pneumonectomy, the extent of resection does not seem to affect survival and should be accompanied preferably by lymphadenectomy. Pathological staging, along with a mitotic index more than Ki-67 (MIB1), appears to be the most significant prognostic factor at the univariate analysis.

This report reviews the pattern of neuroendocrine (NE) differentiation, lymph-node involvement, extension of surgery, and survival in 125 NE lung tumor patients. Standard diagnostic workup included CT scan, bronchoscopy, bronchial biopsy or Fine Needle Aspiration Biopsy, (111)In-pentetreotide scan (OctreoScan) and mediastinoscopy in selected patients. NE differentiation was assessed based on the morphology and immunohistochemical reactivity for pan-neuroendocrine markers NSE, CGA, and Synaptophysin. For small cell carcinoma (SCC), only clinical stage I and II patients underwent surgery. Several different surgical procedures were utilized, from limited resections to lobectomy, pneumonectomy, and bronchoplastic procedures. Survival was assessed using Kaplan-Meyer method at 5 years. There were 79 typical carcinoid (TC), eight atypical carcinoid (AC), 18 large cell carcinoma (LCC) and 20 SCC patients. Mean age at diagnosis was 54.6+/-15.2 (ranges from 16 to 77 years) for TC, 68.5+/-9.1 (range 53-81) for AC, 68.7+/-4.6 (range 58-77) for LCC, 64.6+/-7.9 (range 48-82) for SCC. Male/female ratio was 1/1 for TC and AC, 2.6/1 for LCC and 9/1 for SCC. Lymph-node involvement was present in 14% of TC, 0% of AC, 31.5% of LCC, and 45% of SCC. Cancer specific survival was 96% for TC, 87.5% for AC, 37.5% for LCC, and 30% for SCC at 5 years from surgery. Presenting symptoms were invariably of respiratory-related. None had the carcinoid syndrome. History of tobacco abuse ranged from 46% for TC to 100% in SCC. Survival ranged from a minimum of 1 month for SCC to a maximum of 168 months with no evidence of disease for TC. Synchronous multicentric forms were found in 14% of TC. Twenty-one percent (4/19) of the patients with SCC treated by induction therapy and surgery, and in few cases by surgery and adjuvant chemotherapy are alive without the evidence of the disease for 5 years. Due to the high percentage of lymph-node involvement and multicentric forms found in our series lobectomy with radical lymph-node dissection appears, in our opinion, the most appropriate surgical treatment in well-differentiated forms, while more limited resection appears sub-optimal. Also, due to the finding of recurrences many years after surgery, the follow-up must be accurate and protracted in this subgroup. Only Small Cell Lung Carcinoma patients in clinical stage I and II underwent surgery with good long-term results.