Chest ACCP Career Connection
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Guest Access | Sign In via User Name/Password
This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF) Free
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Article Archive
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via ISI Web of Science (25)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Thomas, C. F.
Right arrow Articles by Jett, J. R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Thomas, C. F., Jr.
Right arrow Articles by Jett, J. R.
(Chest. 2001;119:1143-1150.)
© 2001 American College of Chest Physicians

Typical and Atypical Pulmonary Carcinoids*

Outcome in Patients Presenting With Regional Lymph Node Involvement

Charles F. Thomas, Jr., MD; Henry D. Tazelaar, MD, FCCP and James R. Jett, MD, FCCP

* From the Department of Medicine (Dr. Thomas), the Department of Anatomic Pathology (Dr. Tazelaar), and the Department of Oncology (Dr. Jett), Division of Pulmonary, Critical Care, and Internal Medicine, Mayo Clinic and Foundation, Rochester, MN.

Correspondence to: Charles F. Thomas, Jr., MD, Thoracic Diseases Research Unit, Guggenheim Bldg 696, Mayo Clinic and Foundation, Rochester, MN 55905; e-mail: thomas.charles{at}mayo.edu


   Abstract
TOP
 Abstract
Introduction
 Materials and Methods
 Results
 Discussion
 References
 
Study objective: Typical pulmonary carcinoid tumors are well-differentiated neuroendocrine tumors that are associated with good patient survival rates, while atypical carcinoid tumors are more aggressive and have worse patient survival rates. Because these tumors rarely involve the thoracic lymph nodes at presentation, it is currently unknown to what extent the presence of thoracic lymph node metastases at the time of diagnosis influences patient survival.

Methods: A computerized search of the medical records for pulmonary carcinoid tumor at the Mayo Clinic from 1976 to 1997 revealed 517 patients, from which we identified 36 patients with pulmonary carcinoid tumors involving regional thoracic lymph nodes but without distant disease. For each patient, we reviewed the tumor histology, stage, and outcome. In addition, because the histologic criteria for the diagnosis of carcinoid tumors had changed significantly during the time of the study, we reexamined all of the histologic specimens using the current World Health Organization (WHO) criteria for classifying pulmonary neuroendocrine tumors.

Results: After reclassification with the WHO criteria for neuroendocrine tumors, 23 patients had typical carcinoid tumors with thoracic lymph node involvement. At the last follow-up, 19 patients had no evidence of disease (NED), 2 patients had developed systemic metastases (SM) and are still alive, and 2 patients had died. Eleven patients had atypical carcinoid tumors with thoracic lymph node involvement. At the last follow-up, four patients had NED, seven patients had developed SM within a median time of 17 months, and six patients with SM died shortly thereafter (median survival time, 25.5 months), while one is still alive. Two patients had been reclassified with large cell neuroendocrine carcinoma at the time of this review; both of these patients had developed SM (at 4 months and 21 months after diagnosis) and had died (at 15 months and 21 months after diagnosis, respectively).

Conclusions: These data suggest that patients with atypical pulmonary carcinoid tumors with regional lymph node metastases have a high likelihood of developing recurrent disease if treated with surgical resection alone and have significantly worse outcome (p < 0.001) compared to those patients with typical carcinoid tumors with thoracic lymph node involvement.

Key Words: atypical carcinoid • bronchial carcinoid • survival


   Introduction
TOP
 Abstract
 Introduction
Materials and Methods
 Results
 Discussion
 References
 
Pulmonary carcinoid tumors are malignant neoplasms that show neuroendocrine differentiation.1 2 3 Although the distinction between typical and atypical carcinoid tumors was first described by Engelbreth-Holm4 in 1944, it was not until 1972 that histologic criteria for separating these tumors were proposed by Arrigoni et al.5 In the intervening 25 years, numerous studies have continued to confirm that there is a spectrum of neuroendocrine-appearing tumors from the carcinoid tumorlet to small cell undifferentiated carcinoma. However, the distinction between typical carcinoids and more aggressive neuroendocrine neoplasms has been problematic, and several classification schemes have been proposed but none have been widely accepted or applied.6 7 8 The 1981 World Health Organization (WHO) classification of neuroendocrine neoplasms stated only that atypical carcinoid tumors had "increased mitotic activity, cellularity and could have necrosis."9 While this statement is true in general, strict criteria were not suggested. The most recent WHO classification has proposed more strict criteria for separating these two tumors, based on work by Travis et al.10 11 The new WHO classification (Table 1 ) also lays out criteria for large cell neuroendocrine carcinoma, a tumor that undoubtedly has, in the past, been included in at least some series of atypical carcinoid tumors.10


View this table:
[in this window]
[in a new window]

  		Table 1.. 1999 WHO Criteria for the Diagnosis of Neuroendocrine Tumors*

 
Typical pulmonary carcinoid tumors rarely metastasize and, in general, patients with these tumors have a good prognosis, with 5-year survival rates ranging from 87 to 100%. This is in contrast to patients with atypical carcinoid tumors, who have a greater tendency to have metastases and a 25 to 69% 5-year survival rate (Table 2 ).5 6 12 13 14 15 16 17 18 19 20 Although previous studies have reported the outcome of patients with typical and atypical carcinoid tumors, none have specifically investigated the subset of patients who have thoracic lymph node metastases at the time of surgical staging. It is uncertain whether the survival rate is significantly worse in this subset of patients and whether consideration of more aggressive management and follow-up is indicated for them. In this study, we retrospectively analyzed the clinical characteristics and survival rates of surgically treated patients with typical and atypical pulmonary carcinoid tumors who had thoracic lymph node metastases.


View this table:
[in this window]
[in a new window]

  		Table 2.. Comparison of 5-Year and 10-Year Survival Rates for Pulmonary Carcinoid Tumors*

 

   Materials and Methods
TOP
 Abstract
 Introduction
 Materials and Methods
Results
 Discussion
 References
 
A computerized search of the medical records at the Mayo Clinic from 1976 to 1997 revealed 517 patients with pulmonary carcinoid tumors, from which we identified 36 patients with pulmonary carcinoid tumors involving regional thoracic lymph nodes but without distant disease. The medical records of these 36 patients were reviewed, and the study population included only patients with pulmonary carcinoid tumors presenting with thoracic lymph node metastases at the time of surgical resection. This group was selected because we were specifically interested in the outcomes of patients with completely resected carcinoid tumors having regional lymph node metastases. Carcinoid tumor patients presenting with distant metastases or concurrent cancers were excluded from the study.

The histologic diagnosis of pulmonary carcinoid tumor was confirmed by review of all histologic sections by a single pathologist with special expertise in neuroendocrine tumors who was blinded to the initial diagnosis (ie, typical or atypical carcinoid tumor). Histologic sections were available for all 36 patients. Because the histologic criteria for the diagnosis of pulmonary carcinoid tumors changed significantly during the dates of this study, all tumors were classified on the basis of the newly proposed WHO classification scheme and were compared to the original diagnoses.10 The pathologic stage of disease using the TNM classification for non-small cell lung cancer also was confirmed.21 Two sets of survival curves were generated using the Kaplan-Meier method, one based on the original pathologic diagnosis and the second based on tumor classification according to the new WHO criteria.22


   Results
TOP
 Abstract
 Introduction
 Materials and Methods
 Results
Discussion
 References
 
Thirty-six patients with pulmonary carcinoid tumors had thoracic lymph node involvement at the time of surgical resection and staging from 1976 to 1997. These included 15 men and 21 women with a mean age of 55.9 years (age range, 17 to 77 years). The original classification was 24 typical carcinoid tumors and 12 atypical carcinoid tumors (Table 3 ). Using the current criteria for classifying pulmonary neuroendocrine tumors, four patients originally receiving diagnoses of typical carcinoid tumors were reclassified as having atypical carcinoid tumors. In addition, three patients originally receiving diagnoses of atypical carcinoid tumor were reclassified as having typical carcinoid tumors, and two patients originally receiving diagnoses of atypical carcinoid tumors were reclassified as having large cell neuroendocrine carcinoma. Therefore, using the current WHO criteria, there were 23 patients with typical carcinoid tumors (10 men and 13 women; mean age, 52 years; age range, 17 to 74 years), 11 patients with atypical carcinoid tumors (4 men and 7 women; mean age, 63 years; age range, 34 to 77 years), and 2 patients with large cell neuroendocrine carcinoma (1 man, age, 68 years; 1 woman, age, 64 years; Table 3 ).


View this table:
[in this window]
[in a new window]

  		Table 3.. Demographics of the 36 Patients With Typical Carcinoid Tumors, Atypical Carcinoid Tumors, or Large Cell Neuroendocrine Carcinoma*

 
Typical carcinoid tumors had a mean mitotic rate of 0.19/2 mm2 (10 high-power fields) and, by definition, did not have necrosis. Three tumors, however, had foci of discohesive cells with somewhat pyknotic nuclei and condensed, shrunken-appearing cytoplasms in comparison to adjacent cells (Fig 1 ); but, because of a lack of karyorrhexis, associated eosinophilic debris, or apoptosis, such foci were not accepted as necrosis. All three patients are currently alive and without metastatic disease at a median time of 88 months.



View larger version (137K):
[in this window]
[in a new window]
[Download PPT slide]
  		Figure 1.. Typical carcinoid tumor with central (top, A) and peripheral (bottom, B) foci (arrows) of cell discohesion, nuclear hyperchromatism, pyknosis, and condensed cytoplasm. Such foci were not accepted as tumor necrosis (hematoxylin-eosin, original x 100 [top, A], original x 200 [bottom, B]).

 
Atypical carcinoid tumors had a mean mitotic rate of 1.78/2 mm2; 10 of 11 atypical carcinoid tumors also had foci of necrosis (Fig 2 ). Six tumors were classified as atypical carcinoid only on the basis of necrosis with a mitotic rate of < 2/2 mm2. Three patients from this subgroup are alive without evidence of metastases, one developed metastases 12 months after diagnosis but is still alive at 89 months, and two patients developed metastases and died. The two patients with large cell neuroendocrine carcinoma had foci of necrosis and mitotic rates of 19/2 mm2 and 32/2 mm2 (Fig 3 ).



View larger version (188K):
[in this window]
[in a new window]
[Download PPT slide]
  		Figure 2.. Atypical carcinoid tumor with focus of central necrosis (arrows; hematoxylin-eosin, original x 200).

 


View larger version (197K):
[in this window]
[in a new window]
[Download PPT slide]
  		Figure 3.. Large cell neuroendocrine carcinoma with numerous mitotic figures (arrows; hematoxylin-eosin, original x 100).

 
Among the 23 patients with typical pulmonary carcinoid tumors, 8 had stage IIA disease (T1N1M0), 6 had stage IIB disease (T2N1M0), and 9 had stage IIIA disease (T1N2M0 or T2N2M0). Nineteen patients (82.6%) had no evidence of disease (NED) at follow-up (median, 84 months after diagnosis; range, 12 to 242 months after diagnosis). Only two patients (8.7%) developed systemic metastases (SM) at 54 and 78 months after diagnosis. Both patients are currently alive. Two patients died (one at 29 months of unknown causes, and the other at 223 months of "natural causes" at age 93 years; Table 3 ).

Among the 11 patients with atypical carcinoid tumors, 3 had stage IIA disease (T1N1M0), 4 had stage IIB disease (T2N1M0), and 4 had stage IIIA disease (T2N2M0 or T3N1M0). Only four patients (36.4%) showed NED at the time of follow-up, while seven patients (63.6%) developed SM at a median time of 17 months after diagnosis (range, 2 to 57 months after diagnosis). Six patients with SM died within a median time of 25.5 months after the initial diagnosis (range, 2 to 123 months after diagnosis). One patient with SM is still alive at 89 months (Table 3) .

Both patients with large cell neuroendocrine carcinoma (one man, age 68 years; one woman, age 64 years) had stage IIIA disease (T1N2M0 or T2N2M0) and developed SM at 4 months and 21 months after receiving their diagnoses, respectively. Both patients died shortly thereafter, 15 months and 21 months, respectively, after the initial diagnoses (Table 3) .

Survival curves for the patients classified according to the original pathologic diagnosis and the diagnosis based on the new classification scheme are shown in Figure 4 . Although the number of patients in this study was too small to permit a meaningful statistical analysis between the two groups (old vs new classification), the new classification scheme does separate tumors that behave worse than the atypical carcinoid tumors, as previously classified.



View larger version (13K):
[in this window]
[in a new window]
[Download PPT slide]
  		Figure 4.. Figure 4 . Kaplan-Meier survival analysis of study patients using the Arrigoni criteria (top, A) or the current WHO classification (bottom, B).

 

   Discussion
TOP
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
References
 
Pulmonary carcinoid tumors comprise 1 to 2% of all lung malignancies.1 15 23 Historically called bronchial adenomas, they were thought to be benign tumors. The recognition of a more aggressive variety of carcinoid tumor, the atypical carcinoid, suggested that they might all be malignant.4 5 11 18 20 Currently, typical and atypical carcinoids are considered to be part of a spectrum of malignant neoplasms with neuroendocrine differentiation along with large cell neuroendocrine carcinoma and small cell carcinoma.10 11 18

In general, patients with typical carcinoids have good prognoses, with > 87% of patients surviving for 10 years. In contrast, approximately 25 to 69% of patients with atypical carcinoid tumors survive 5 years, and many develop widespread disease.5 6 12 13 14 15 16 17 18 19 20 Multivariate analyses from four studies12 15 18 20 suggest that pathologic stage and atypical histology are the most important factors affecting survival; however, not all studies have confirmed this. In a study of 93 patients with typical carcinoid tumors, the presence of lymph node metastases in 9 patients (all with N1 disease) did not have any prognostic significance. Eight patients survived a mean of 8 years, while one patient died of unrelated causes.17 In another report of 120 patients,19 there was insufficient information to allow any conclusions about the significance of either atypical features or lymph node metastases (only 7 patients had lymph node metastases). No prior studies specifically analyzed the subset of patients with typical or atypical pulmonary carcinoid tumors who presented with lymph nodal metastases at the time of surgical resection. As shown in Table 3 , we compare the survival data for patients with typical or atypical pulmonary carcinoid tumors presenting with lymph node metastases with a historical series of patients with pulmonary carcinoid tumors.

In the present study, patients with typical pulmonary carcinoid tumors with thoracic lymph node metastases did well after surgical resection alone. The overall survival rate was excellent, with only two patients (8.7%) developing systemic disease at a median time of 66 months after diagnosis and two patients dying. This is in contrast to patients with atypical pulmonary carcinoid tumors with thoracic lymph node metastases. When treated with surgical resection alone, most of these patients (63.6%) developed SM at a median time of 17 months after diagnosis. The majority of patients with SM (54.5%) died shortly thereafter (median time, 25.5 months after initial diagnosis).

The results of this study suggest that the accurate classification of pulmonary neuroendocrine tumors is essential to determining prognosis, but until recently there have been no widely accepted criteria with which to make a reproducible or clinically meaningful separation between the various tumor types. The new WHO classification scheme, based on the work of Travis and Sobin,10 utilizes a combination of mitotic activity and the presence of necrosis to separate typical carcinoid tumors from atypical carcinoid tumors. This study supports the clinical utility of the WHO classification, demonstrating differences in the Kaplan-Meier survival curves comparing the patients’ original diagnoses with the WHO classification (Fig 4) . Although our numbers are relatively small, they do suggest that carcinoid tumors with mitotic counts between 2/2 mm2 and 10/2 mm2 of viable tumor or coagulative necrosis behave in a more aggressive fashion than ordinary carcinoid tumors and that patients with those tumors that have a very high mitotic rate (>= 10/2 mm2) have the worst prognoses. Although much has been written about the difficulty in counting mitotic figures in several tumor systems, there are equally difficult problems with basing the classification scheme on such things as "cellularity and atypia."6 7 8 24 25 26 One problem encountered in this study was distinguishing between true coagulative necrosis and what might be called "incipient necrosis." This latter finding consisted of foci of cells with somewhat pyknotic nuclei and shrunken-appearing cytoplasm, in comparison to immediately adjacent cells, and cell discohesion without frank karyorrhexis, eosinophilic necrotic debris, or apoptosis (Fig 1) . Such foci were not counted as foci of coagulative necrosis and were not used to classify a tumor as an atypical carcinoid tumor. Because of the difficulty in evaluating small foci of necrosis and in counting mitotic figures on frozen sections, it may be very difficult in borderline cases to make a definitive diagnosis without examining the permanent sections. For intraoperative surgical management, however, a diagnosis of carcinoid tumor should be sufficient, and we reiterate the opinion of others that all such patients should be treated and staged similarly to other patients with lung cancer.

Finally, this study supports the significance of recognizing the existence of a high-grade non-small cell tumor with neuroendocrine differentiation (ie, large cell neuroendocrine carcinoma). Although there is debate regarding the significance of non-small cell carcinomas the neuroendocrine differentiation of which is only suggested by the presence of chromogranin A or synaptophysin identification immunohistochemically, tumors that appear to be neuroendocrine by light microscopy and that have a mitotic rate > 10/2 mm2 behave significantly worse than those with mitotic rates < 10/2 mm2.27 We identified two patients whose tumors were reclassified from atypical carcinoid tumor to large cell neuroendocrine carcinoma. Both patients with large cell neuroendocrine carcinoma developed systemic disease and died shortly after diagnosis (median time, 18 months after initial diagnosis).

We concur with others that all patients with any type of carcinoid tumor should be treated and staged similarly to other patients with malignant epithelial lung tumors. Because the majority of pulmonary carcinoid tumors occur centrally and involve the bronchial tree, lung preservation surgery (ie, bronchial sleeve resection) is recommended when possible.15 17 23 28 29 Tumors with greater involvement of the airway or ones that are located peripherally need more extensive surgery, ranging from lobectomy to pneumonectomy.15 17 30 Bronchoscopic removal is suboptimal treatment, because the tumors can extend submucosally and adequate resection is not achieved by removing the intraluminal component. However, a minority of patients have bronchial carcinoid tumors presenting as polypoid structures in the airway lumen, and in these rare cases bronchoscopic resection alone has been curative.31 Bronchoscopic resection does not, however, allow for lymph node staging, which the results of this study suggest is very important for prognostic information and may be beneficial in making therapeutic decisions.

Our data suggest that the subset of patients with atypical pulmonary carcinoid tumors and regional lymph node metastases have a high likelihood of developing recurrent disease if treated with surgical resection alone. Although there is a paucity of data available on the treatment of atypical pulmonary carcinoid tumors, previous studies32 33 34 35 have demonstrated a poor response to standard chemotherapy and radiation therapy. Currently, there is no standard therapy for treating atypical carcinoid tumors with any modality other than surgery. Further investigation is needed to determine the optimal treatment with chemotherapy, radiotherapy, or alternative promising new experimental agents.


   Acknowledgements
 
We thank Darrell R. Schroeder from the Mayo Clinic Section of Biostatistics for performing the statistical analysis in this study.


   Footnotes
 
Abbreviations: NED = no evidence of disease; SM = systemic metastases; WHO = World Health Organization

Received for publication July 28, 2000. Accepted for publication October 17, 2000.


   References
TOP
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 References
 

  1. Davila, DG, Dunn, WF, Tazelaar, HD, et al (1993) Bronchial carcinoid tumors. Mayo Clin Proc 68,795-803[ISI][Medline]
  2. Sheppard, MN (1991) Neuroendocrine differentiation in lung tumours. Thorax 46,843-850[ISI][Medline]
  3. Vuitch, F, Sekido, Y, Fong, K, et al (1997) Neuroendocrine tumors of the lung: pathology and molecular biology. Chest Surg Clin North Am 7,21-47[Medline]
  4. Engelbreth-Holm, J (1944) Benign bronchial adenomas. Acta Chir Scand 90,383-409
  5. Arrigoni, MG, Woolner, LB, Bernatz, PE (1972) Atypical carcinoid tumors of the lung. Thorac Cardiovasc Surg 64,413-421
  6. Mills, SE, Cooper, PH, Walker, AN, et al (1982) Atypical carcinoid tumor of the lung: a clinicopathologic study of 17 cases. Am J Surg Pathol 6,643-654[ISI][Medline]
  7. Gould, VE, Linnoila, RI, Memoli, VA, et al (1983) Neuroendocrine cells and neuroendocrine neoplasms of the lung. Pathol Annu 18,287-330
  8. Warren, WH, Gould, VE, Faber, LP, et al (1985) Neuroendocrine neoplasms of the bronchopulmonary tract: a classification of the spectrum of carcinoid to small cell carcinoma and intervening variants. Thorac Cardiovasc Surg 89,819-825
  9. . World Health Organization. (1981) Histologic typing of lung tumours. Tumori 67,253-272[ISI][Medline]
  10. Travis, WD, Sobin, LH (1999) Histologic typing of lung and pleural tumours: international histologic classification of tumours (No. 1). Springer-Verlag New York, NY.
  11. Travis, WD, Linnoila, RI, Tsokos, MG, et al (1991) Neuroendocrine tumors of the lung with proposed criteria for large-cell neuroendocrine carcinoma: an ultrastructural, immunohistochemical, and flow cytometric study of 35 cases. Am J Surg Pathol 15,529-553[ISI][Medline]
  12. McCaughan, BC, Martini, N, Bains, MS (1985) Bronchial carcinoids: review of 124 cases. Thorac Cardiovasc Surg 89,8-17
  13. Akiba, T, Naruke, T, Kondo, H, et al (1992) Carcinoid tumor of the lung: clinicopathological study of 32 cases. Jpn J Clin Oncol 22,92-95
  14. Attar, S, Miller, JE, Hankins, J, et al (1985) Bronchial adenoma: a review of 51 patients. Ann Thorac Surg 40,126-132[Abstract]
  15. Harpole, DH, Jr, Feldman, JM, Buchanan, S, et al (1992) Bronchial carcinoid tumors: a retrospective analysis of 126 patients. Ann Thorac Surg 54,50-54[Abstract]
  16. Torre, M, Barberis, M, Barbieri, B, et al (1989) Typical and atypical bronchial carcinoids. Respir Med 83,305-308[ISI][Medline]
  17. Schreurs, AJ, Westermann, CJ, van den Bosch, JM, et al (1992) A twenty-five-year follow-up of ninety-three resected typical carcinoid tumors of the lung. Thorac Cardiovasc Surg 104,1470-1475
  18. Travis, WD, Rush, W, Flieder, DB, et al (1998) Survival analysis of 200 pulmonary neuroendocrine tumors with clarification of criteria for atypical carcinoid and its separation from typical carcinoid. Am J Surg Pathol 22,934-944[CrossRef][ISI][Medline]
  19. Vadasz, P, Palffy, G, Egervary, M, et al (1993) Diagnosis and treatment of bronchial carcinoid tumors: clinical and pathological review of 120 operated patients. Eur J Cardiothorac Surg 7,8-11[Abstract]
  20. Gould, PM, Bonner, JA, Sawyer, TE, et al (1998) Bronchial carcinoid tumors: importance of prognostic factors that influence patterns of recurrence and overall survival. Radiology 208,181-185[Abstract/Free Full Text]
  21. Mountain, CF (1997) Revisions in the International System for Staging Lung Cancer. Chest 111,1710-1717[Abstract/Free Full Text]
  22. Kaplan, E, Meier, P (1958) Nonparametric estimation from incomplete observations. J Am Stat Assoc 53,457-481[CrossRef][ISI]
  23. Rocco, G, Deschamps, C (1997) Cylindroma, carcinoid tumors, and mucoepidermoid carcinoma. Semin Respir Crit Care Med 18,333-340
  24. van Diest, PJ, Baak, JP, Matze-Cok, P, et al (1992) Reproducibility of mitosis counting in 2,469 breast cancer specimens: results from the Multicenter Morphometric Mammary Carcinoma Project. Hum Pathol 23,603-607[CrossRef][ISI][Medline]
  25. Silverberg, SG (1976) Reproducibility of the mitosis count in the histologic diagnosis of smooth muscle tumors of the uterus. Hum Pathol 7,451-454[ISI][Medline]
  26. Mills, SE, Bova, GS, Wick, MR, et al (1989) Leiomyosarcoma of the urinary bladder: a clinicopathologic and immunohistochemical study of 15 cases. Am J Surg Pathol 13,480-489[ISI][Medline]
  27. Schleusener, JT, Tazelaar, HD, Jung, SH, et al (1996) Neuroendocrine differentiation is an independent prognostic factor in chemotherapy-treated non-small cell lung carcinoma. Cancer 77,1284-1291[CrossRef][ISI][Medline]
  28. Cerfolio, RJ, Deschamps, C, Allen, MS, et al (1996) Mainstem bronchial sleeve resection with pulmonary preservation. Ann Thorac Surg 61,1458-1462[Abstract/Free Full Text]
  29. Kawahara, K, Shiraishi, T, Okabayashi, K, et al (1995) A new approach for bronchoplastic procedures in the treatment of bronchial carcinoid tumors. Thorac Cardiovasc Surg 43,290-292[ISI][Medline]
  30. Chughtai, TS, Morin, JE, Sheiner, NM, et al (1997) Bronchial carcinoid: twenty years’ experience defines a selective surgical approach. Surgery 122,801-808[CrossRef][ISI][Medline]
  31. Sutedja, TG, Schreurs, AJ, Vanderschueren, RG, et al (1995) Bronchoscopic therapy in patients with intraluminal typical bronchial carcinoid. Chest 107,556-558[Abstract/Free Full Text]
  32. Moertel, CG, Hanley, JA (1979) Combination chemotherapy trials in metastatic carcinoid tumor and the malignant carcinoid syndrome. Cancer Clin Trials 2,327-334[Medline]
  33. Jodrell, DI, Smith, IE (1990) Carboplatin in the treatment of metastatic carcinoid tumours and paraganglioma: a phase II study. Cancer Chemother Pharmacol 26,62-64[ISI][Medline]
  34. Saltz, L, Lauwers, G, Wiseberg, J, et al (1993) A phase II trial of carboplatin in patients with advanced APUD tumors. Cancer 72,619-622[CrossRef][ISI][Medline]
  35. Chakravarthy, A, Abrams, RA (1995) Radiation therapy in the management of patients with malignant carcinoid tumors. Cancer 75,1386-1390[CrossRef][ISI][Medline]



This article has been cited by other articles:


Home page
 ChestHome page
R. L. Young, J. D. Mitchell, C. Cool, and S. P. Nana-Sinkam
Wheezing and Exertional Dyspnea in a 25-Year-Old Mountaineer
Chest, March 1, 2008; 133(3): 820 - 825.
[Full Text] [PDF]

Home page
 Eur. J. Cardiothorac. Surg.Home page
F. Rea, G. Rizzardi, A. Zuin, G. Marulli, S. Nicotra, R. Bulf, M. Schiavon, and F. Sartori
Outcome and surgical strategy in bronchial carcinoid tumors: single institution experience with 252 patients
Eur. J. Cardiothorac. Surg., February 1, 2007; 31(2): 186 - 191.
[Abstract] [Full Text] [PDF]

Home page
 Eur. J. Cardiothorac. Surg.Home page
M. Garcia-Yuste, J. M. Matilla, A. Cueto, J. M. R. Paniagua, G. Ramos, M. A. Canizares, I. Muguruza, and Members of the Spanish Multi-centric Study of Neur
Typical and atypical carcinoid tumours: analysis of the experience of the Spanish Multi-centric Study of Neuroendocrine Tumours of the Lung
Eur. J. Cardiothorac. Surg., February 1, 2007; 31(2): 192 - 197.
[Abstract] [Full Text] [PDF]

Home page
 J. Thorac. Cardiovasc. Surg.Home page
B. D. Kozower, R. Jarrett, S. Bhalla, and G. A. Patterson
Clinical-pathologic conference in general thoracic surgery: Carinal resection for endobronchial grade I neuroendocrine carcinoma.
J. Thorac. Cardiovasc. Surg., November 1, 2006; 132(5): 1219 - 1222.
[Full Text] [PDF]

Home page
 Ann. Thorac. Surg.Home page
T. C. Mineo, G. Guggino, D. Mineo, G. Vanni, and V. Ambrogi
Relevance of Lymph Node Micrometastases in Radically Resected Endobronchial Carcinoid Tumors
Ann. Thorac. Surg., August 1, 2005; 80(2): 428 - 432.
[Abstract] [Full Text] [PDF]

Home page
 Eur. J. Cardiothorac. Surg.Home page
A. Terzi, A. Lonardoni, B. Feil, I. Spilimbergo, G. Falezza, and F. Calabro
Bronchoplastic procedures for central carcinoid tumors: clinical experience
Eur. J. Cardiothorac. Surg., December 1, 2004; 26(6): 1196 - 1199.
[Abstract] [Full Text] [PDF]

Home page
 Ann. Thorac. Surg.Home page
G. Cardillo, F. Sera, M. Di Martino, P. Graziano, R. Giunti, L. Carbone, F. Facciolo, and M. Martelli
Bronchial carcinoid tumors: nodal status and long-term survival after resection
Ann. Thorac. Surg., May 1, 2004; 77(5): 1781 - 1785.
[Abstract] [Full Text] [PDF]

Home page
 Ann. Thorac. Surg.Home page
M. Mezzetti, F. Raveglia, T. Panigalli, L. Giuliani, F. Lo Giudice, S. Meda, and S. Conforti
Assessment of outcomes in typical and atypical carcinoids according to latest WHO classification
Ann. Thorac. Surg., December 1, 2003; 76(6): 1838 - 1842.
[Abstract] [Full Text] [PDF]

Home page
 Ann. Surg. Oncol.Home page
R. Hage, A. B. de la Riviere, C.A. Seldenrijk, and J.M. M. van den Bosch
Update in Pulmonary Carcinoid Tumors: A Review Article
Ann. Surg. Oncol., July 1, 2003; 10(6): 697 - 704.
[Abstract] [Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF) Free
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Article Archive
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via ISI Web of Science (25)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Thomas, C. F.
Right arrow Articles by Jett, J. R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Thomas, C. F., Jr.
Right arrow Articles by Jett, J. R.

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS