Carcinoid tumour of the lung


A neuroendocrine tumour composed of uniform cells with finely granular cytoplasm


Carcinoids usually occur in young adults30. Rare cases are associated with MEN1 syndrome8,20.

Clinical features

The most common symptoms are cough and haemoptysis. Cushing's syndrome3 and ectopic ACTH production are rare. The carcinoid syndrome does not occur until there are widespread metastases.


Carcinoid tumours commonly present as incidental radiological findings. Typical carcinoids are usually central30. Atypical carcinoids are more often peripheral30.

Macroscopic appearances

Carcinoids are tan to yellow. Particularly central typical carcinoids often form a dumbbell with endobronchial and extra-bronchial lobes.


Cells are uniform with finely dispersed chromatin and inconspicuous nucleoli. If atypia occurs, it is not a reliable indicator of malignancy. In most cases they are polygonal but may be spindled13. There are clear cell11 and oncocytic variants. Cells may contain melanin12. The architecture varies from trabecular and organoid to papillary19, pseudoglandular or follicular. The stroma is usually highly vascular but may be hyalinised and may form cartilage or bone. Stromal amyloid may occur1,10. Sustentacular cells may be seen, particularly in typical carcinoids14.

There is an association with neuroendocrine hyperplasia and airway fibrosis18; rarely there are multiple carcinoids17.


See immunohistochemistry of malignant epithelial tumours of lung.



positive in >80% of cases



positive: may be focal in atypical carcinoids


positive: may be focal in atypical carcinoids


positive: may be focal in atypical carcinoids


positive: may be focal in atypical carcinoids


often positive23


positive in sustentacular cells3, 3/312


variable results21,26


Ki-67 expression is higher in atypical carcinoids than in typical carcinoids6.


Desmosomes and dense core granules are present. In pigmented cases, the sustentacular cells contain melanosomes12.

Molecular genetics

Rb expression is preserved in typical carcinoids5. There is an intermediate level of loss of Rb expression in atypical carcinoids5. Immunoreactivity for the Rb gene product has been proposed as differentiating carcinoids (typical and atypical, positive) from small and large cell neuroendocrine carcinomas7,15. Mutations of the MEN1 gene at 11q13 may occur in sporadic carcinoids8. Mutations of p53 are less common in carcinoids than in high grade neuroendocrine carcinomas22-24. LOH at 5q21 was correlates with poor survival in carcinoid tumours31.

Differential diagnosis


Resection with minimal but clear margins30.


At presentation, 10-15% of typical carcinoids have metastasized to regional lymph nodes: 40-50% of atypical carcinoids will have metastasized (20% stage II, 15% stage III and 10% stage IV, using the TNM staging)9.


5 year

10 year

Typical carcinoid



Atypical carcinoid



The presence of metastases predicts subsequent survival27:


5 year

10 year

Carcinoid without metastases



Carcinoid with metastases



For atypical carcinoids, female gender, a tumour larger than 3.5 cm, a higher stage and a mitotic rate of 6 to 10 per 2mm2 are associated with a worse prognosis4.


0 Tumours of the Lung, Pleura, Thymus and Heart. WHO Classification of Tumours. IARC Press 2004.

1 Al-Kaisi N, Abdul-Karim FW, Mendelsohn G, et al. Bronchial carcinoid tumor with amyloid stroma. Arch Pathol Lab Med 1988; 112:211-4

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3 Barbareschi M, Ferrero S, Frigo B, et al. Bronchial carcinoid with S-100 positive sustentacular cells. Tumori 1988; 74:705-11

4 Beasley MB, Thunnissen FB, Brambilla E, et al. Pulmonary atypical carcinoid: predictors of survival in 106 cases. Hum Pathol 2000; 31:1255-65

5 Beasley MB, Lantuejoul S, Abbondanzo S, et al. The P16/cyclin D1/Rb pathway in neuroendocrine tumors of the lung. Hum Pathol 2003; 34:136-42

6 Costes V, Marty-Ane C, Picot MC, et al. Typical and atypical bronchopulmonary carcinoid tumors: a clinicopathologic and KI-67-labeling study. Hum Pathol 1995; 26:740-5

7 Cagle PT, el-Naggar AK, Xu HJ, et al. Differential retinoblastoma protein expression in neuroendocrine tumors of the lung. Potential diagnostic implications. Am J Pathol 1997; 150:393-400

8 Debelenko LV, Brambilla E, Agarwal SK, et al. Identification of MEN1 gene mutations in sporadic carcinoid tumors of the lung. Hum Mol Genet 1997; 6:2285-90

9 Fink G, Krelbaum T, Yellin A, et al. Pulmonary carcinoid: presentation, diagnosis, and outcome in 142 cases in Israel and review of 640 cases from the literature. Chest 2001; 119:1647-51

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11 Gaffey MJ, Mills SE, Frierson HF, Jr., et al. Pulmonary clear cell carcinoid tumor: another entity in the differential diagnosis of pulmonary clear cell neoplasia. Am J Surg Pathol 1998; 22:1020-5

12 Gal AA, Koss MN, Hochholzer L, et al. Pigmented pulmonary carcinoid tumor. An immunohistochemical and ultrastructural study. Arch Pathol Lab Med 1993; 117:832-6

13 Fekete PS, Cohen C,DeRose PB Pulmonary spindle cell carcinoid. Needle aspiration biopsy, histologic and immunohistochemical findings. Acta Cytol 1990; 34:50-6

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15 Gouyer V, Gazzeri S, Brambilla E, et al. Loss of heterozygosity at the RB locus correlates with loss of RB protein in primary malignant neuro-endocrine lung carcinomas. Int J Cancer 1994; 58:818-24

16 Gaertner EM, Steinberg DM, Huber M, et al. Pulmonary and mediastinal glomus tumors--report of five cases including a pulmonary glomangiosarcoma: a clinicopathologic study with literature review. Am J Surg Pathol 2000; 24:1105-14

17 Miller MA, Mark GJ,Kanarek D Multiple peripheral pulmonary carcinoids and tumorlets of carcinoid type, with restrictive and obstructive lung disease. Am J Med 1978; 65:373-8

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19Mark EJ, Quay SC,Dickersin GR Papillary carcinoid tumor of the lung. Cancer 1981; 48:316-24

20Nakhoul F, Kerner H, Levin M, et al. Carcinoid tumor of the lung and type-1 multiple endocrine neoplasia associated with persistent hypercalcemia: a case report. Miner Electrolyte Metab 1994; 20:107-11

21Oliveira AM, Tazelaar HD, Myers JL, et al. Thyroid transcription factor-1 distinguishes metastatic pulmonary from well-differentiated neuroendocrine tumors of other sites. Am J Surg Pathol 2001; 25:815-9

22Onuki N, Wistuba, II, Travis WD, et al. Genetic changes in the spectrum of neuroendocrine lung tumors. Cancer 1999; 85:600-7

23Pelosi G, Fraggetta F, Sonzogni A, et al. CD99 immunoreactivity in gastrointestinal and pulmonary neuroendocrine tumours. Virchows Arch 2000; 437:270-4

24Przygodzki RM, Finkelstein SD, Langer JC, et al. Analysis of p53, K-ras-2, and C-raf-1 in pulmonary neuroendocrine tumors. Correlation with histological subtype and clinical outcome. Am J Pathol 1996; 148:1531-41

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26Sturm N, Rossi G, Lantuejoul S, et al. Expression of thyroid transcription factor-1 in the spectrum of neuroendocrine cell lung proliferations with special interest in carcinoids. Hum Pathol 2002; 33:175-82

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28Travis WD, Rush W, Flieder DB, et al. Survival analysis of 200 pulmonary neuroendocrine tumors with clarification of criteria for atypical carcinoid and its separation from typical carcinoid. Am J Surg Pathol 1998; 22:934-44

29Travis WD, Linnoila RI, Tsokos MG, et al. 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 1991; 15:529-53

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31 Onuki N, Wistuba, II, Travis WD, et al. Genetic changes in the spectrum of neuroendocrine lung tumors. Cancer 1999; 85:600-7

This page last revised 29.3.2005.

©SMUHT/PW Bishop