pulmonary carcinoid tumor
Sunday 2 May 2004
Bronchopulmonary Carcinoid Tumors, bronchial carcinoid tumor
JRC:4122 : Pulmonary carcinoid tumor.
JRC:4124 : Pulmonary carcinoid tumor.
JRC:4127 : Pulmonary carcinoid tumor.
JRC:4131 : Pulmonary carcinoid tumor.
JRC:4135 : Pulmonary carcinoid tumor.
JRC:4136 : Pulmonary carcinoid tumor.
JRC:413 : Pulmonary carcinoid tumor.
JRC:6147 : Pulmonary carcinoid tumor.
JRC:6159 : Pulmonary atypical carcinoid tumor.
Definition: Bronchial carcinoids are uncommon, low grade, slow growing, malignant neoplasms comprising 5% of all primary lung cancers and originally called as bronchial adenomas.
Bronchial carcinoids are neoplasms of bronchial endocrine or APUD cells derived from primitive gut.
Bronchial carcinoids are thought to arise from neuroendocrine / Kulchitsky’s cells located in bronchial mucosa. They range from low-grade typical carcinoids to more aggressive atypical carcinoids.
They account for 5% of all primary lung cancers.
In a recent review of data from the SEER registry, Modlin et al. demonstrated annual incidence rates of bronchial carcinoids of 0.52 and 0.89 per 100,000 population in white males and females, respectively (the corresponding values for black males and females were somewhat higher, at 0.39 and 0.57, respectively).
Pulmonary carcinoid tumors are thought to arise from Kulchitsky cells disseminated throughout the bronchopulmonary mucosa.
They are slow growing tumors which affect two persons per million per year. The age range is wide from teenagers to old age.
There is no relationship to smoking, environmental, inhalation of carcinogens or radiation. There is slight female predominance.
Bronchial carcinoids usually arise from a main or segmental bronchus. Occasionaly the tumor arises in the peripheral lung.
Histologically it is composed of aggregates of small cells with dark central nuclei and pale cytoplasm in a vascular stroma.
So-called atypical carcinoid tumors show increased mitotic activity, irregular nuclei and prominent nucleoli with areas of tissue necrosis.
This histology of atypical carcinoids is responsible for there aggressive behaviour. Occasionally amyloid material or bone may be laid down in stroma of carcinoid tumor.
According to site of origin, carcinoids are divided into fore gut, mid gut and hind gut tumors. According to histology they are classified as typical or atypical carcinoids.
Cushing’s and carcinoid syndromes are rare (1%) with bronchial carcinoids.
Though these tumors share certain morphologic and biochemical characteristics, confusion has plagued reasonable attempts to devise a classification system for these tumors.
In 2004, the WHO devised a new classification for bronchopulmonary carcinoids based on a spectrum of clinicopathologic entities ranging from hyperplastic neuroendocrine cell lesions (carcinoid tumorlets, diffuse idiopathic pulmonary neuroendocrine cell hyperplasia [DIPNECH]) to high-grade NETs (small cell carcinoma and large cell neuroendocrine carcinoma).
Pulmonary neuroendocrine cell hyperplasia and tumorlets (typical carcinoid tumors that measure 5 mm in greatest dimension and extend beyond the basement membrane) represent perhaps the earliest manifestations of neuroendocrine disease in the bronchopulmonary system.
The 2004 WHO classification of lung tumors applies the term DIPNECH to a proliferation of scattered single cells, small nodules (neuroendocrine bodies), or linear proliferations of pulmonary neuroendocrine cells confined to the bronchial and bronchiolar epithelium.
The clinical relevance of these lesions is controversial. Initially identified in the clinical context of chronic pulmonary diseases like obliterative bronchiolitis, bronchiectasis, and idiopathic pulmonary fibrosis, carcinoid tumorlets were thought to represent benign hyperplastic lesions of little clinical relevance.
However, recent data suggest the potential malignant nature of these lesions, as carcinoid tumorlets have been demonstrated in association with typical carcinoid tumors of the bronchopulmonary system and with lymph node metastases.
Representing nearly two thirds of pulmonary carcinoids, well-differentiated NETs of the lungs and bronchi (typical carcinoids) are composed of cytologically bland cells that exhibit minor cellular atypia and rare mitoses.
Based on the 2004 WHO classification, these tumors must demonstrate fewer than two mitoses per 10 high power fields (10HPF), lack necrosis, and be >5 mm.
They usually present as perihilar masses in the fifth decade of life and demonstrate a relatively indolent disease course; however, some patients may present with recurrent pneumonia, cough, hemoptysis, and chest pain.
Ectopic secretion of biologically active hormones is not uncommon, as these tumors may secrete corticotrophin and growth hormone with relative frequency; however, carcinoid syndrome occurs in < 5% of patients with these tumors because of the relative paucity of serotonin secretion.
Metastases from typical pulmonary carcinoids have been reported in approximately 12% of cases, and the overall survival rate is thought to be >90%.
Approximately one third of bronchopulmonary carcinoids are atypical tumors, intermediate grade NETs whose pathologic criteria depend on the presence of carcinoid morphology and at least one of the following: (a) necrosis or (b) 2–10 mitoses per 10HPF.
Unlike typical pulmonary carcinoids, atypical carcinoids usually occur in the periphery of the lungs of older patients. Their clinical course is aggressive, with a relatively high incidence of mediastinal lymph node metastases (>50%) and an abbreviated 5-year survival rate of only 40%–75%.
Central bronchial carcinoids
The centrally located carcinoids cause partial / complete bronchial obstruction. This leads to symptoms such as cough , wheeze, infections, atelectasis.
Central bronchial carcinoids manifests as an endobronchial nodule or hilar/ perihilar mass with a close anatomic relationship to the bronchus.
Peripheral bronchial carcinoids
Peripheral bronchial carcinoids appear as solitary nodules. Peripheral carcinoids are usually asymptomatic.
Typical carcinoid tumors
Typical carcinoids are more common (90%), perihilar in location, show indolent course, have less tendency to metastasize and calcify in 25% of cases. Five-year survival rate is more than 90%.
Chest radiograph is abnormal in 75% to 90% of cases. Peripheral carcinoids may present as simple peripheral pulmonary nodule. Central hilar / perihilar mass with or without atelectasis, bronchieatasis, mucoid impaction or consolidation can be seen. The majorities of bronchial carcinoids arise in the large bronchi and cause partial or complete obstruction.
Computed tomography discloses small tumors that are occult on plain radiographs. The appearance differs from carcinoma in that the bronchus may widen slightly as it approaches the mass.
The most frequent presentation is hilar / perihilar , well circumscribed , rounded or ovoid mass which may have a notched or lobulated contour.
It ranges in size from 2 to 5 cm. Non-spherical lesions are oriented parallel to the axis of adjacent major bronchi or pulmonary artery.
Calcification is uncommon in peripheral bronchial carcinoids as compared to central variety. Because carcinoids have a rich vascular stroma , they show homogeneous enhancement.
Lymphadenopathy and distant metastasis are also less common with peripheral bronchial carcinoids.
atypical bronchial carcinoid tumor (7180964)
Atypical carcinoids are peripheral in location, larger than typical carcinoids, aggressive in nature with tendency to metastasize in 30% to 50% of cases. Calcification is uncommon in atypical peripherally located carcinoid.
On contrary to typical carcinoids, atypical bronchial carcinoid tumors have different histologocal features that suggest aggressive nature with worse prognosis.
Carcinoid tumors should be removed surgically. Tumors confined to bronchus are treated by sleeve resection. Other tumors may require lobectomy or pneumonectomy.
After surgery the prognosis is very good with ten years survival rate upto 90%. In present case patient refused surgery resulting in poorer outcome. Liver metastases if present are treated by arterial embolisation.
Symptoms of carcinoid syndrome are treated with serotonin antagonists. Radiotherapy and chemotherapy can be used as adjuvant to destroy tumor cells and reduce the tumor bulk.
Surgical resection is the preferred treatment of bronchopulmonary carcinoid tumors in those patients with adequate functional pulmonary reserve.
In patients with relatively small ( < 2 cm), localized tumors of the peripheral lung parenchyma, conservative resection via a wedge or segmental resection has been shown to result in low recurrence rates and excellent long-term survival.
Tumors with extensive central bronchopulmonary involvement, those with large peripheral parenchymal involvement (>2 cm), and atypical carcinoids may require more extensive surgical resection with a lobectomy or pneumonectomy.
Given the significance of nodal involvement in long-term prognostic models of pulmonary carcinoid disease, recent data have demonstrated an advantage to systematic radical mediastinal lymphadenectomy in all patients at the time of initial treatment.
Atypical carcinoid tumor of the lung. A clinicopathologic study of 17 cases. Mills SE, Cooper PH, Walker AN, Kron IL. Am J Surg Pathol. 1982 Oct;6(7):643-54. PMID: 7180964