The Surgical Spectrum of Pulmonary Neuroendocrine Neoplasms

doi:10.1378/chest.119.1.14

Chest

Volume 119, Issue 1, January 2001, Pages 14-18

https://doi.org/10.1378/chest.119.1.14 Get rights and content

Objectives:

The purpose of this study is to review ourexperience with the spectrum of neuroendocrine neoplasms of the lungwith emphasis on the histopathologic classification and surgicaltherapy of each class of neoplasm.

Design:

Thisretrospective review covers the entire spectrum of neuroendocrineneoplasms of the lung over an 11-year period (January 1985 to December1995) in a university hospital setting. Only patients who underwentsurgical resection were included in this review.

Patients:

During this period, a total of 77 patientsunderwent lung resection for the following neuroendocrine neoplasms: typical carcinoid (TC), 50 patients; atypical carcinoid (AC), 5patients; large cell neuroendocrine carcinoma (LCNEC), 9 patients; mixed large-small cell neuroendocrine carcinoma (LSNEC), 4 patients; orsmall cell neuroendocrine carcinoma (SCC), 9 patients. There were 37men (48.1%) and 40 women (51.9%) among the patients, with a mean ageof 57.9 years (range, 14 to 87 years).

Interventions:

Primary surgical resection consisted of the following procedures: 52lobectomies (67.5%); 10 pneumonectomies (13%); 13 limited resections(16.9%); 1 left main bronchus sleeve resection; and 1 carinalresection. Six patients had the following concomitant procedures: pericardiectomy, 2 patients; mediastinoscopy, 1 patient; chest wallresection, 1 patient; stapling blebs, 1 patient; and transdiaphragmaticliver biopsy, 1 patient. Four patients underwent bilobectomies, and two patients underwent multiple wedge resections.

Results:

The hospital mortality rate was 2.6% (2 of 77patients), and both patients died of pulmonary failure. Follow-up wasobtained in 62 of 77 patients (80.9%) for an average of 38.1 months(range, 2 to 132 months). There were a total of 13 deaths, and 8 weredisease-related (LCNEC, 4 deaths; SCC, 2 deaths; LSNEC, 1 death; and ACtumor, 1 death. The mean disease-free intervals for patientswith these neoplasms were the following: TC tumor, 41.3 months; ACtumor, 20 months; LCNEC, 20.4 months; LSNEC, 25 months; and SCC, 48months. The overall 3-year survival rate was 45.2% (28 of 62patients).

Conclusion:

This report will emphasize theclassification, surgical management, and treatment considerations ofpulmonary neuroendocrine neoplasms. Despite the poor overall prognosisin high-grade neuroendocrine tumors of the lung, surgery remains aviable adjunct in the early stages of thisdisease.

Section snippets

Materials and Methods

The purpose of our study is to review again the cases of allpatients who had undergone surgical resection for a neuroendocrineneoplasm over a 10-year period. We retrospectively reviewed the recordsof 77 patients who had undergone pulmonary resection for neuroendocrinetumors during an 11-year period from January 1985 to December 1995 onthe general thoracic surgery service of Emory University Hospitals. Only patients who had undergone resection were included in this study. Patients who were

Demographics

During the 11-year study period, 77 patients underwent thoracotomyfor resection of a pulmonary neuroendocrine tumor. Among thesepatients, there were 40 women (51.9%) and 37 men (48.1%). The averageage was 57.9 years (range, 14 to 87 years). Sixty patients (78%) had ahistory of tobacco abuse. Comorbid conditions included hypertension (53patients), coronary artery disease (31 patients), diabetes mellitus (23patients), and COPD (10 patients).

Presenting symptoms were invariably respiratory related,

Discussion

Since the original description of carcinoid tumors in1907,¹ the spectrum of pulmonary neuroendocrine tumors hascontinued to evolve. The vast majority of these tumors that areresectable are low-grade TC tumors. As the malignant features becomemore prominent, lymph node and distant metastases occur morefrequently. Certainly, the presence or absence of nodal involvement andhistology are the major determinants of survival.

Our data are comparable to those previously reported in otherseries.⁹¹⁰¹¹¹²²¹

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Cited by (110)

Clinical Behavior of Combined Versus Pure High-Grade Neuroendocrine Carcinoma
2022, Clinical Lung Cancer
Citation Excerpt :
The histopathological and clinical similarities have led to proposals that LCNEC and SCLC should be reclassified as a single group, namely, high-grade NEC.6,7 So far, LCNEC and SCLC have been proven to have equivalent clinical behaviors in many previous reports.1,2,8,9 High-grade NEC often includes other histological subtypes.
The aim of this study was to investigate and compare the clinical behaviors of combined and pure high-grade neuroendocrine carcinoma (large-cell neuroendocrine carcinoma [LCNEC] and small-cell lung carcinoma [SCLC]).
Data of 132 patients who underwent complete resection for combined or pure high-grade neuroendocrine carcinoma (combined group, 67; pure group, 65) between January 2001 and December 2015 were retrospectively reviewed. The clinicopathological features were analyzed and compared, and the prognoses were assessed by performing the Kaplan–Meier method and Cox regression analysis.
The combined and pure groups had nearly equivalent clinicopathological characteristics, specifically, older males with smoking history, almost the same percentage of pleural/lymphatic/vascular invasion, and nearly the same recurrence rates and relapse patterns.
The combined group had prognosis equivalent to that of the pure group (5-year overall survival [OS] rates: 61.8% vs. 52.2%, respectively; P = .82 and 5-year recurrence-free survival [RFS] rates: 42.4% vs. 43.9%, respectively; P = .96), and this trend was identified in sub-analyses only for patients with LCNEC, SCLC, and the same pathological stage.
Multivariable Cox regression analysis in patients with high-grade neuroendocrine carcinoma revealed that vascular invasion and pathological stage were independent prognostic factors for OS; more importantly, combined and pure histologies were proven to have nearly equivalent associations with prognosis (hazard ratio, 0.96; 95% confidence interval, 0.22to 1.66; P = .96).
Combined high-grade neuroendocrine carcinoma had clinical behavior equivalent to those of pure high-grade neuroendocrine carcinoma, with similar clinicopathological characteristics.
Outcomes for Surgery in Large Cell Lung Neuroendocrine Cancer
2019, Journal of Thoracic Oncology
There are limited small, single-institution observational studies examining the role of surgery in large cell neuroendocrine cancer (LCNEC). We investigated the outcomes of surgery for stage I to IIIA LCNEC by using the National Cancer Database.
Patients with stage I to IIIA LCNEC were identified in the National Cancer Database (2004–2015) and grouped by treatment: definitive chemoradiation versus surgery. Overall survival, by stage, was the primary outcome. Outcomes of surgical patients were also compared with those of patients with SCLC or other non–small cell histotypes.
A total of 6092 patients met the criteria: 96%, 94%, 75%, and 62% of patients received an operation for stage I, II, IIIA, and cN2 disease, respectively. Complete resection was achieved in at least 85% of patients. The 5-year survival rates for patients undergoing an operation for stage I and II LCNEC were 50% and 45%, respectively. Surgical patients with stage IIIA and N2 disease had 36% and 32% 5-year survival rates, respectively. When compared with stereotactic body radiation in stage I disease and chemoradiation in patients with stage II to IIIA disease, surgery was associated with a survival benefit. Patients with LCNEC who underwent an operation generally experienced worse survival by stage than did those with adenocarcinoma but experienced improved survival compared with patients with SCLC. Perioperative chemotherapy was associated with improved survival for pathologic stage II to IIIA disease.
Surgery is associated with reasonable outcomes for stage I to IIA LCNEC, although survival is generally worse than for adenocarcinoma. Surgery should be offered to medically fit patients with both early and locally advanced LCNEC, with guideline-concordant induction or adjuvant therapy.
Neuroendocrine Tumors of the Lung Other Than Small Cell Lung Cancer
2018, IASLC Thoracic Oncology
Adjuvant Chemotherapy Does Not Confer Superior Survival in Patients With Atypical Carcinoid Tumors
2017, Annals of Thoracic Surgery
Although the use of adjuvant chemotherapy in patients with pathologically node-positive (pN+) atypical carcinoid tumor of the lung is an accepted practice, controversy exists about its use in pathologically node-negative (pN0) patients. Our aim was to determine whether a survival advantage exists in patients receiving chemotherapy postoperatively for pN0 or pN+ atypical carcinoid tumors of the lung.
Adult patients treated with lobectomy or pneumonectomy for pulmonary atypical carcinoid tumor were identified using the National Cancer Data Base, 2006 to 2011. Propensity scoring (4:1 nearest neighbor algorithm) and survival analysis were used to examine the association between adjuvant chemotherapy and pN+ versus pN0 atypical carcinoid tumors.
Of the total 581 patients identified with a diagnosis of atypical carcinoid of the lung, 363 (62.5%) were found to be node negative at the time of operation and 218 (37.5%) had node-positive disease. Adjuvant chemotherapy was used in 15 patients (4.1%) with pN0 disease and 89 patients (40.8%) with pN+ disease. Unadjusted survival, at 12 and 60 months, was similar between pN+ patients who were treated with adjuvant chemotherapy versus patients who received operation alone (adjuvant chemotherapy: 98.9% at 12 months and 47.9% at 60 months versus operation alone: 98.4% and 12 months and 67.1% at 60 months, p = 0.46) and for propensity-matched pN0 (adjuvant chemotherapy: 86.7% at 12 months and 73.3% at 60 months versus operation alone: 87.9% at 12 months and 72.3% at 60 months, p = 0.54).
In a national-level analysis, the use of adjuvant chemotherapy postoperatively in patients with pN+ and pN0 disease conferred no survival advantage; further study is needed to determine proper chemotherapy use for these patients.
A Single-Institution Analysis of the Surgical Management of Pulmonary Large Cell Neuroendocrine Carcinomas
2016, Annals of Thoracic Surgery
Large cell neuroendocrine carcinoma (LCNEC) is an uncommon tumor of the lung and represents approximately 3% of all lung cancers. LCNEC displays biological behaviors resembling those of small cell lung carcinomas and features of high-grade neuroendocrine tumors. LCNEC of the lung are considered aggressive. Reported prognoses are heterogeneous, and the optimum treatment remains undefined.
We conducted a retrospective study of all patients who were treated for LCNEC in our Department of Thoracic Surgery between May 2005 and December 2013. Primary outcomes of interest were patient survival and prognostic factors. Kaplan-Meier analysis was performed to determine the significant predictors of overall survival.
Within the prescribed period, 127 patients were treated for LCNEC, and 125 underwent surgical resection with curative intent. Induction chemotherapy or radiochemotherapy was given to 9 patients, and 63 patients received postoperative chemotherapy. Complete resection was achieved in 99.2%. The overall 1-, 3- and 5-year survival rates were 83.7%, 63.2%, and 53.8% of all patients, and the 5-year survival in patients at stages I, II, and III was 64.5%, 40%, and 29.7%. There was a significant survival difference at 5 years between pT1/2 (58.5%) and pT3 tumors (22.4%; p = 0.043) and for patients with lymphatic involvement (L0 vs L1, p = 0.001; pN1 or pN2 vs pN0, p = 0.04).
Surgical treatment can achieve satisfactory results in early tumor stages, which are comparable with other non-small cell lung cancers, with a low perioperative mortality rate.
Controversial tumors in pediatric surgical oncology
2014, Current Problems in Surgery

View all citing articles on Scopus

: Presented at the XIX World Congress of Diseases of the Chest and at the64th Annual International Scientific Assembly of the American Collegeof Chest Physicians, Toronto, Canada, November 10, 1998.

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Chest

Clinical InvestigationsSURGERYThe Surgical Spectrum of Pulmonary Neuroendocrine Neoplasms

Objectives:

Design:

Patients:

Interventions:

Results:

Conclusion:

Section snippets

Materials and Methods

Demographics

Discussion

J Thorac Cardiovasc Surg

Surgery

J Thorac Cardiovasc Surg

Lancet

Chest

J Thorac Cardiovasc Surg

Chest

J Thorac Cardiovasc Surg

J Thorac Cardiovasc Surg

Hum Pathol

Karzinoide Tumoren des Dunndarms

Frankf Z Pathol

Revised classification of neuroendocrine tumors of the lung, pancreas and gut

Digestion

Historical background and natural history of carcinoids

Digestion

Clinical Investigations
SURGERY
The Surgical Spectrum of Pulmonary Neuroendocrine Neoplasms