Carcinoid tumour of the lung

Definition

A neuroendocrine tumour composed of uniform cells with finely granular cytoplasm

• Typical carcinoid: less than 2 mitoses per 2 mm3 and lacking necrosis28

• Atypical carcinoid: 2 to 10 mitoses per 2 mm3 or foci of necrosis28. Atypical carcinoids account for about 15% of all carcinoids.25

Epidemiology

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.

Radiology

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.

Histopathology

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.

Immunohistochemistry

See immunohistochemistry of malignant epithelial tumours of lung.

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

Ultrastructure

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

• Other neuroendocrine tumours:

  • Tumourlets are only differentiated from typical carcinoids by size, being less than 5 mm in diameter.

  • Sufficient material for a mitotic count to differentiate typical from atypical carcinoid often requires a surgical specimen.

  • Carcinoid tumours metastatic from the gastrointestinal tract.

  • LCNEC: mitotic count greater than 10 / 2 mm3 (usually much higher)29

  • small cell carcinoma: mitotic count greater than 10 /2 mm3 (usually much higher)29

• Pseudoglandular pattern:

  • adenocarcinoma: show more atypia

  • mucoepidermoid carcinoma: negative for neuroendocrine markers, positive for mucin

  • adenoid cystic carcinoma: negative for neuroendocrine markers

• Organoid carcinoid:

  • Paraganglioma: also contain S-100 positive sustentacular cells3 but are negative for cytokeratin

  • Glomus tumour: positive for SMA and negative for neuroendocrine markers16

• Spindle cell carcinoid:

  • smooth muscle tumours

• Papillary carcinoid19:

  • sclerosing haemangioma: negative for neuroendocrine markers

• Metastatic breast carcinoma

• Cribriform pattern: metastatic prostatic carcinoma2: positive for PSA, negative for neuroendocrine markers

Management

Resection with minimal but clear margins30.

Prognosis

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.

The presence of metastases predicts subsequent survival27:

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.

References

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

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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

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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

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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

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This page last revised 29.3.2005.

©SMUHT/PW Bishop