Typical and atypical carcinoid tumours: analysis of the experience of the Spanish Multi-centric Study of Neuroendocrine Tumours of the Lung.

BACKGROUND: This study examines the experience of the Spanish Multi-centric Study of Neuroendocrine Tumours of the Lung with patients treated surgically for typical and atypical carcinoid tumours. METHODS: From 1980 to 2002, 661 patients were treated surgically for 569 typical carcinoid tumours and 92 atypical carcinoid tumours. Three hundred and four cases were studied retrospectively from 1980 to 1997 (261 typical carcinoid and 43 atypical carcinoid tumours); the other 357 new cases (308 typical carcinoid and 49 atypical carcinoid tumours) were collected prospectively from 1998 to 2002. Tumours were classified according the 1999 classification from the WHO and the International Association for the Study of Lung Cancer (IASLC). Several variables were reviewed in all patients. Univariate and multivariate statistical analyses were performed in order to determine whether clinical characteristics were associated with significant differences in survival. RESULTS: In the total of the patients, 5-year survival for different tumours was as follows: typical carcinoid: overall survival 97%; with nodal involvement 100%; atypical carcinoid: overall 78%; with nodal involvement 60%. A significant difference in survival was found between patients in the retrospective and prospective groups with atypical carcinoid and nodal involvement. The comparative analysis of several factors in typical and atypical carcinoid tumours showed a significant difference for mean age, tumour size, nodal involvement and distant metastases. CONCLUSION: Nodal involvement and histological sub-type appear as the most important factors influencing the prognosis. Adequate lung resection and systematic radical mediastinal lymphadenectomy should always be performed. Sleeve resection could be performed in central typical and atypical carcinoid tumours, avoiding pneumonectomy.     

Treatment of rectal carcinoid tumors

We investigated the treatment of 24 rectal carcinoid tumors from both the clinicopathologic and prognostic viewpoints. All tumors less than 2 cm in diameter had neither muscle layer invasion nor lymph node metastasis, except for an atypical carcinoid tumor that had both lymphatic permeation and intramural metastasis. One typical carcinoid tumor larger than 2 cm had both several lymphatic permeations and urinary bladder invasion. All cases had a good prognosis with no recurrence and no new metastases. For rectal carcinoid tumors less than 2 cm in diameter, local resection is sufficient, whereas radical operation is required for tumors larger than 2 cm in diameter. For atypical rectal carcinoid tumors, radical operation should be considered even if the diameter is less than 2 cm.     

Surgical treatment of bronchial carcinoid: report of seven cases

Seven patients with pulmonary carcinoid including three with typical carcinoid and four with atypical carcinoid were reported. There were 3 males and 4 females, with an age range of 37 to 80 years. All patients with typical carcinoid had pathological stage I. Of the patients with atypical carcinoid, one patient had stage I, two stage IIIA and one stage IIIB. All but two patients underwent lobectomy and mediastinal lymph node dissection. Bronchoplastic operation or right pneumonectomy were performed in the two patients. All but one patient underwent absolute or relative curative operation. Only one patient died on the 4th postoperative day. One patient with atypical carcinoid died of cancer recurrence 4 years after surgery. One patient died of breast cancer. One patient underwent surgery for metachronous multiple lung cancer, and he is doing well without recurrence. In conclusion, a limited operation is thought to be acceptable only in patients with typical carcinoid in a peripheral lesion without lymph node metastasis. Lobectomy and mediastinal lymph node dissection is necessary for the atypical carcinoid case.     

Head and neck large cell neuroendocrine carcinoma should be separated from atypical carcinoid on the basis of different clinical features, overall survival, and pathogenesis

According to the 2005 World Health Organization classification of head and neck tumors, neuroendocrine tumors can be subdivided into typical carcinoid, atypical carcinoid, and small cell carcinoma. Similar tumors diagnosed as large cell neuroendocrine carcinomas (LCNECs) in the lung are diagnosed as atypical carcinoids in the head and neck region. We studied neuroendocrine tumors and analyzed whether LCNEC should be separated from atypical carcinoid in the head and neck region. Twenty-three cases of primary head and neck neuroendocrine tumors were included and subdivided into typical carcinoid, atypical carcinoid, and small cell carcinoma according to the 2005 World Health Organization guidelines, and then LCNECs were separated from atypical carcinoids according to modified criteria using the Ki-67-labeling index and mitotic count. Clinical information and survival data were obtained, and immunohistochemical studies for p53 were conducted. The 5-year survival rates for the 2 typical carcinoids, 7 atypical carcinoids, 7 LCNECs, and 7 small cell carcinomas were 100.0%, 83.3%, 21.4%, and 20.8%, respectively (P=0.032). The LCNEC patients were older (mean age, 61 vs. 41 y; P=0.038), more commonly in advanced stage (stages III and IV 100% vs. 28.6%, P=0.01), with a poorer prognosis (5-year survival 21.4% vs. 83.3%, P=0.03), and more commonly had tumors overexpressing p53 (85.7% vs. 0%, P=0.005) as compared with atypical carcinoid patients. LCNECs should be separated from atypical carcinoids as a new entity of neuroendocrine carcinoma in the head and neck region. The new classification may provide better risk stratification and useful information for proper treatment.     

Bronchial carcinoids: a review of 60 patients

Sixty patients with a bronchial carcinoid underwent surgical treatment. Preoperative fiberoptic bronchoscopy revealed a characteristic pink, smooth, bleeding tumor in 71.4% of the patients with a typical carcinoid and 16.7% of those with an atypical carcinoid (p less than 0.05). Eight pneumonectomies, seven bilobectomies, 34 lobectomies, three lobectomies with bronchoplasty, six bronchotomies with bronchoplasty, and two segmental resections were performed. All patients entered follow-up, and 47 were followed for more than 5 years. Ten-year survival was 89.6% for patients with a typical carcinoid and 60% for those with an atypical carcinoid. Ten-year survival was 88.1% for patients with carcinoids without lymph node involvement. All patients with lymph node involvement died within 5 years. Overall, 5 of the 8 patients having pneumonectomy died of acute cardiorespiratory failure. We conclude that a limited surgical resection with or without bronchoplasty and systematic lymphadenectomy is the procedure of choice in patients with typical carcinoids. On the other hand, atypical carcinoids are comparable to well-differentiated malignancies of the lung. Whenever possible, pneumonectomy should be avoided in favor of bronchial sleeve resection.     

Atypical pulmonary carcinoid tumor with abnormal elevation of serum gastrin-releasing peptide precursor: report of a case

We report a rare case of atypical pulmonary carcinoid tumor accompanied by elevation of serum gastrin-releasing peptide precursor (ProGRP). A 55-year-old male presented to our hospital with a history of bloody sputum. The level of serum ProGRP was elevated to 781 pg/ml (normal < 46 pg/ml). Chest computed tomography (CT) revealed a solitary pulmonary tumor in the left lower lobe with sub-carinal lymph node enlargement. Transbronchial lung biopsy showed a pulmonary carcinoid, therefore left lower lobectomy with mediastinal lymph node dissection was performed. ProGRP decreased to normal level 1 month after operation. Histopathological diagnosis showed an atypical pulmonary carcinoid tumor.     

A clinical study of resected bronchopulmonary carcinoids

19 surgically treated cases with bronchopulmonary carcinoid in our hospital were studied clinically, and we discussed the criteria of limited operation for typical carcinoid. 11 cases had typical carcinoid and 8 had atypical. All patients of typical type were alive with no recurrence. No lymph node metastasis was revealed in all cases of typical type. On the contrary, in cases of atypical type, 1 had n 2 disease and 1 had distant metastasis. The five survival rates of patients with typical carcinoid was 100%, and significantly better than that of patients with atypical, 27%. Therefore, patients with typical carcinoid can be cured by limited operation, but radical operation should be indicated for atypical carcinoid.     

Malignant carcinoid tumor in the papilla of Vater: case report and review of 25 cases reported in Japan

Carcinoid tumors in the papilla of Vater are rare. We describe a 48-year-old male who was diagnosed with a tumor consisting of atypical cells in the papilla of Vater. He underwent curative resection of the tumor by pancreatico-duodenectomy (PD), with dissection of the regional lymph nodes. Microscopic examination revealed a metastatic lymph node in the pancreatic region. Characteristic findings on histopathological and electron microscopic studies led to the final diagnosis of malignant carcinoid tumor. It is clear from the literature that carcinoid tumors in the papilla of Vater metastasize to the regional lymph nodes and the liver. However, it has been difficult to preoperatively diagnose carcinoid tumor in the papilla of Vater. Therefore, if we observe atypical cells in the papilla of Vater, malignant carcinoid tumor should be considered. If this tumor is suspected, PD or pylorus-preserving PD, together with dissection of the regional lymph nodes, at least along the hepatoduodenal ligament, should be considered as the treatment of first choice.     

Pulmonary Carcinoid Found in a Patient who Presented with Initial Symptoms of Brain Metastasis: Report of a Case

Although atypical pulmonary carcinoids frequently metastasize to regional lymph nodes, they rarely metastasize to the brain. We describe herein an extremely unusual case of a 52-year-old woman who presented with the symptoms of brain metastasis as the initial manifestation of an atypical pulmonary carcinoid. After control of the multiple metastatic brain lesions had been achieved by tumorectomy and stereotactic radiosurgery, a middle lobectomy of the right lung was performed to completely resect the primary pulmonary carcinoid. This aggressive surgical approach was successful in that it prolonged the survival of the patient and enhanced her quality of life. Received: November 25, 1999 / Accepted: January 9, 2001     

Atypical carcinoid of thymus associated with multiple endocrine neoplasia syndrome type 1

Thymic carcinoid associated with multiple endocrine neoplasia syndrome type 1 (MEN-1) is a rare tumor. We report a case of MEN-1-related thymic carcinoid. The patient reported herein had already been diagnosed with MEN-1 and was found to have a mediastinal mass. She underwent thymectomy with partial resection of the left innominate vein and lung. Histological examination revealed atypical carcinoid with infiltration. MEN-1 gene mutation was detected by employing the direct nucleotide sequencing method. Postoperative 2-fluoro-2-deoxyglucose positron emission tomography showed probable multiple metastases in the vertebrae and myocardium. However, she has been alive and asymptomatic for 2 years postoperatively. MEN-1-related thymic carcinoid is often insidious with a poor prognosis. We suggest chest computed tomography scan or magnetic resonance imaging for MEN-1 patients and serological or genetic screening for patients with thymic carcinoid to screen for MEN-1.     

Typical bronchopulmonary carcinoid tumors: a ramifying bronchial presentation with metastatic behavior

Bronchopulmonary typical carcinoid tumors (BTCT) are neuroendocrine neoplasms with histologic low grade characteristics considered benign. However, despite reassuring histologic classification, some of them demonstrate an aggressive nature and metastatic behavior. During a not yet concluded study aiming at establishing criteria to predict this metastatic behavior, three uncommon cases were observed. Metastasis occurred despite typical carcinoid microscopic features in 3 female patients of African origin presenting at macroscopic examination as ramifying bronchopulmonary typical carcinoid tumors following the bronchial tree. We suggest that clinical ramifying presentation may be related to metastatic behavior, even for bronchopulmonary typical carcinoid tumors not displaying histologic criteria for atypical carcinoid tumors.     

Bronchial carcinoid tumors: nodal status and long-term survival after resection

BACKGROUND: Bronchial carcinoid tumors show a favorable outcome. We sought to determinate the variables influencing the long-term survival of patients treated for bronchial carcinoid tumors. METHODS: We conducted a retrospective single institutional review of 163 patients surgically treated from January 1990 to April 2002. According to 1999 World Health Organization criteria, cases were segregated into typical (<2 mitoses per 2 mm, no necrosis) and atypical carcinoids (2 to 10 mitoses per 2 mm or necrosis). RESULTS: There were 86 men and 77 women with a mean age of 49.5 +/- 11 years. Symptoms were present in 89 patients (54.6%). Operations included 145 formal lung resections (89%), 9 wedge resections (5.52%), 8 sleeve lobectomies (4.9%), and 1 segmental resection (0.61%) plus radical mediastinal lymphadenectomy in all cases. No operative mortality was reported. Histologic examination showed 121 (74.2%) typical carcinoids (107 N0 and 14 N1), and 42 (25.8%) atypical carcinoids (15 N0, 18 N1, 9 N2). All patients were included in a follow-up (median, 54 months; mean, 58 months; range, 4 to 150 months), which included total body computed tomographic scan and bronchoscopy every year. Overall 5-year survival was 90.3% with a mean survival time of 139 months (95% confidence interval, 133 to 145). In N0 patients with either typical or atypical carcinoid tumors, no disease-related mortality was reported (100% 5-year survival). In N1 patients, 5-year survival was 90.0% for those with typical carcinoids, and 78.8% for those with atypical carcinoids (p = 0.394). In atypical carcinoids with N2 disease, 5-year survival was 22.2%. CONCLUSIONS: Prognosis in bronchial carcinoid tumors is more related to nodal status than to histologic subtype. In N0 and N1 patients no statistical significant difference has been found between typical and atypical subtype. However, N2 bronchial carcinoid tumors show a dismal prognosis.     

Esophageal Cancer with a Synchronous Multiple Carcinoid of the Duodenal Bulb

Carcinoid tumors of the duodenum are relatively rare. Although they were considered benign lesions, they are now classified malignant, occasionally with poor prognosis. We report a case of esophageal cancer with a synchronous multiple carcinoid of the duodenal bulb. An upper endoscopy visualized with esophageal scan disclosed a stenotic lesion in the lower esophagus and revealed multiple 4-–5-mm-diameter masses which were on the fore wall of the duodenal bulb. The postoperative pathology report confirmed the diagnosis of esophageal squamous cancer and duodenal bulb carcinoid.     

Bronchial carcinoid arising in intralobar bronchopulmonary sequestration with vascular supply from the left gastric artery. Case report

We report the unique case of a large, nonmetastasizing bronchial carcinoid tumor that arose within an intralobar bronchopulmonary sequestration in a 45-year-old man. The vascular supply to the sequestrated area within the left lower lobe as well as to the carcinoid tumor originated from atypical branches of the left gastric artery and the thoracic aorta. A left lower lobe lobectomy was performed. Histologically, a typical carcinoid tumor without lymph node metastases was found (T2 N0 M0). Seven years postoperatively, the patient is without signs of recurrence.     

Gastric carcinoid and gastric carcinoma. Morphologic correlates of survival

The clinical and histologic material of 140 patients with gastric carcinoma resected more than 5 years previously was examined and 10 tumors with a previous diagnosis of adenocarcinoma showed atypical carcinoid differentiation. The clinical extent of tumors in this carcinoid group was similar to that of the ordinary gastric adenocarcinoma. The 5-year survival was 15% in patients with adenocarcinoma and 70% in those with carcinoid (P less than 0.01 by chi 2 test). These findings indicate the need to distinguish atypical carcinoids from ordinary gastric adenocarcinoma. The most commonly encountered histologic feature suggesting carcinoid, and leading to confirmatory histochemical studies, was found to be regular interlacing trabeculae of tumor and fibrovascular stroma.     

Bronchial carcinoid tumor arising from an intralobar bronchopulmonary sequestration

We report a rare case of a 38-year-old woman with a bronchial carcinoid tumor arising from an intralobar bronchopulmonary sequestration. The vascular supply to the sequestered left lower lobe originated from the descending thoracic aorta. A left lower lobe lobectomy was performed. The findings of the pathological examination revealed an atypical carcinoid tumor that was immunopositive for chromogranin and synaptophysin. At the 3-year follow-up examination, the patient was healthy.     

Pulmonary carcinoid tumors--ten years experience

Pulmonary carcinoid tumors are rare, accounting for as many as 2% of all pulmonary neoplasms and for 10% of carcinoid tumors overall. Previously classified as bronchial adenomas, actually are classified as neuroendocrine tumors. They have a subclassification into typical classed as low-grade malignant neoplasm and atypical more aggressive, with more potential to cause local invasion. In this paper, the authors report a retrospective study of 25 patients, who had the diagnosis of pulmonary carcinoid tumors and had been operated between January of 1994 and August of 2004. We conclude that this tumors must be considered malignant in the surgical approach.     

Endoscopic CO2 laser surgery for an atypical carcinoid tumor of the epiglottis masquerading as a supraglottic cyst

BACKGROUND: Atypical carcinoid tumor is a neuroendocrine tumor; its occurrence in the larynx is uncommon, and clinical manifestations are rare. We report an unusual case of atypical carcinoid tumor of the epiglottis mimicking a supraglottic retention cyst. METHODS: A 44-year-old woman complained of an intermittent globus sensation of the throat of 2 years' duration. A 1.0- x 0.8-cm cystic lesion was found over the tip of the epiglottis. A supraglottic retention cyst was initially diagnosed, and the patient was treated medically. Her symptoms persisted, so we performed a laryngoscopic biopsy, which suggested an atypical carcinoid tumor. RESULTS: Transoral endoscopic CO2 laser surgery and bilateral elective neck dissection were subsequently performed. The 2-year follow-up did not reveal any locoregional recurrence or distant metastasis. CONCLUSIONS: This aggressive neoplasm may cause only a few, unremarkable symptoms and masquerade as a supraglottic cyst. Endoscopic CO2 laser surgery can be used to resect this uncommon tumor, with oncologically sound results and without surgical morbidity.     

Cervical Approach for Resection of a Pedunculated Giant Atypical Lipomatous Tumor of the Esophagus

We describe how we removed a giant pedunculated atypical lipomatous tumor, arising in the cervical to upper thoracic esophagus and occupying a region extending from the cervical to the middle thoracic esophagus, through a cervical esophagotomy without thoracotomy or laparotomy. We suggest that if the base of the tumor is located in the cervical portion of the esophagus, and if the tumor is not aggressive, the cervical approach is best, irrespective of the size of the tumor.     

Long-term outcome after resection for bronchial carcinoid tumors.

OBJECTIVES: We sought to determine the long-term survival of patients treated for bronchial carcinoid tumors and whether lesser resections have had an effect on outcomes. METHODS: We conducted a retrospective, multi-institutional review of patients treated surgically for primary bronchial carcinoid tumors since 1980. Operative approach, pathologic stage, histology, surgical complications, tumor recurrence, and long-term survival were assessed. RESULTS: There were 50 men and 89 women with a mean age of 52.2+/-17.4 and 58.9+/-13.3 years, respectively (P=0.021). Men were more likely to be current or former smokers than were women. Operations included lobectomy or bilobectomy in 110, pneumonectomy in four, wedge resection in 22, and bronchial sleeve resection only in three patients; resection was performed thoracoscopically in six patients. One patient died postoperatively. Stages were I, 121; II, nine; III, six; and IV, three. Typical carcinoid tumors were stage I in 100 and more advanced (stages II-IV) in nine, whereas atypical carcinoid tumors were stage I in 18 and more advanced in eight (P=0. 002). Median follow-up was 43 months (range 1-149) during which 21 (15%) patients died (four from recurrent cancer) and 19 patients (14%) were lost to follow-up. Recurrent cancer developed in 2/98 patients with typical and 5/25 patients with atypical subtypes (P<0. 001; log-rank test). The likelihood of recurrence was related to histological subtype (relative risk 7.9 for atypical carcinoid; 95% confidence interval 1.4-43.5). Five-year survival was 88% for stage I patients and was 70% for patients with more advanced stages. When stratified by stage, survival was related to age (relative risk=1.9 for a 10 year increase in age; 95% confidence interval 1.2-2.9) and possibly to the histological subtype, but not to patient gender, year of operation, or type of operation performed. CONCLUSIONS: Either major lung resection or wedge resection is appropriate treatment for patients with early stage typical bronchial carcinoid tumors. Survival is favorable for early stage tumors regardless of histological subtype. Local recurrence is more common among patients with atypical subtypes, suggesting that a formal resection may improve long-term outcome.