Review
Management of Carcinoid Tumors

https://doi.org/10.1016/j.athoracsur.2009.07.097Get rights and content

Primary bronchopulmonary carcinoids comprise a significant proportion of carcinoid tumors. The clinical presentation allows prediction of the diagnosis and cell type and directs evaluation and treatment. Young age, central tumor, and no nodal enlargement are highly suggestive of typical carcinoid. These patients require no further diagnostic or staging tests beyond chest computed tomography and bronchoscopy before resection using parenchyma-sparing techniques. All bronchopulmonary carcinoids are malignant (though indolent), and surgical intervention is the mainstay of treatment. Mediastinoscopy is suggested when there is moderate suspicion of atypical carcinoid (central cN1 or peripheral cN0), with lobectomy and lymphadenectomy if the mediastinal nodes are benign. For a high suspicion of atypical carcinoid (central cN2, peripheral cN1, 2), imaging for distant metastases and mediastinoscopy is suggested, with multimodality treatment for an atypical carcinoid with N2 involvement.

Section snippets

Classification

Carcinoid tumors are classified by pathologic features as typical carcinoid (TC; < 2 mitoses/2 mm2 of viable tumor) or atypical carcinoid (AC; 2 to 10 mitoses, necrosis, or architectural disruption) [1]. In 1998 the criterion for TC was changed from fewer than 5 to fewer than 2 mitoses/2 mm2 to enhance reproducibility and prognostic differentiation [1]. This resulted in reassignment of about 30% of carcinoids and better 10-year survival (87% vs 73% for TC and 35% vs 9% for AC) [1]. Overall, 16%

Clinical Presentation

Bronchopulmonary carcinoids have a wide age distribution (range, 4 to 86 years) [8, 9], with an equal gender distribution [2]. The late peak of the bimodal distribution is only partly explained by an increase in AC tumors in older patients [10, 11, 12, 13] (Fig 1) [14, 15, 16, 17, 18, 19]. The chance of AC is about 25% in patients aged older than 50 years and less than 10% in patients younger than 30 [14, 15, 16].

One-third of patients are asymptomatic (usually peripheral tumors); cough,

Paraneoplastic Syndromes

Carcinoid syndrome is seen at presentation in only 0.7% of patients (17 of 2496) with a bronchopulmonary carcinoid [9, 14, 16, 17, 18, 19, 20, 21, 22, 23, 27, 28, 29, 30, 31, 32, 33]. During follow-up, this syndrome, which consists of episodic flushing and diarrhea, will develop in another 2% to 5% [14, 28, 20, 34]. These patients almost always have increased urinary levels of the serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA) [20, 35, 36]. Patients with bronchopulmonary carcinoids

Imaging Studies

A chest computed tomography (CT) with intravenous contrast is essential for central tumors to visualize extrabronchial tumor, hilar nodes, adjacent vessels, and to distinguish tumor from atelectatic lung. Peripheral carcinoids are typically homogeneous, rounded, and sharply demarcated (not spiculated), and grow slowly. They usually occur deep within the lung parenchyma, making a wedge resection difficult. Node enlargement by CT has a false-positive rate of 20% to 40%, whereas the false-negative

Diagnostic Tests

Bronchoscopy of a central carcinoid typically reveals a smooth reddish-brown growth, often covered by mucosa. Mucoepidermoid tumors are 10 to 20 times less common but have a similar appearance (sometimes more tan/gray), location (lobar/segmental bronchi), and age distribution (often young adults) [8]. Primary NSCLC or SCLC typically appears irregular and friable.

Biopsy of a carcinoid is safe, with risks similar to bronchoscopy in general [2, 8], despite historical dogma to the contrary. Data on

General Aspects

A clinical diagnosis of carcinoid tumor can be made reliably without a tissue biopsy specimen in most patients with a central tumor (eg, a lobar or segmental endobronchial tumor in a patient aged <40). Only mucoepidermoid tumors have a similar clinical constellation. Fortunately, the evaluation and treatment approach is similar for mucoepidermoid and carcinoid tumors [8].

A clinical diagnosis is more difficult with a peripheral tumor. Peripheral carcinoids are usually round, sharply demarcated,

General Aspects

The mainstay of treatment of carcinoids is surgical resection. For TC tumors, excellent long-term survival is consistently seen (90% or higher survival at 5 and 10 years) [2]. Recurrence occurs in only 3% to 5%, and only 15% of deaths are due to carcinoid tumors [2]. For AC tumors, survival is clearly worse (about 70% at 5 years and 50% at 10 years) 25% experience recurrence, and most deaths are due to recurrence [2]. Almost all recurrences involve distant sites for both TC and AC [2].

Nodal

Endobronchial Resection for Typical Carcinoids

Earlier reports of endobronchial removal of carcinoids demonstrated frequent recurrence (87% of 30 patients with follow-up) [14, 17, 20, 21, 26]. However, a retrospective study in 1995 reported no recurrences in 5 patients (follow-up of 2 to 21 years) and no residual tumor at surgical resection after initial endobronchial removal in 6 patients [60]. In prospective studies, complete resection was achieved in about 50% of selected patients, with recurrence in 5% (5 of 59, median follow-up of 8

References (67)

  • P.L. Filosso et al.

    Bronchial carcinoid tumors: surgical management and long-term outcome

    J Thorac Cardiovasc Surg

    (2002)
  • F. Rea et al.

    Bronchial carcinoids: a review of 60 patients

    Ann Thorac Surg

    (1989)
  • T.R. Todd et al.

    Bronchial carcinoid tumors: twenty years' experience

    J Thorac Cardiovasc Surg

    (1980)
  • G. Cardillo et al.

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

    Ann Thorac Surg

    (2004)
  • S. Attar et al.

    Bronchial adenoma: a review of 51 patients

    Ann Thorac Surg

    (1985)
  • D. Davila et al.

    Bronchial carcinoid tumors

    Mayo Clin Proc

    (1993)
  • C. Ricci et al.

    Carcinoid syndrome in bronchial adenoma

    Am J Surg

    (1973)
  • D.H. Harpole et al.

    Bronchial carcinoid tumors: a retrospective analysis of 126 patients

    Ann Thorac Surg

    (1992)
  • H.I. Pass et al.

    Management of the ectopic ACTH syndrome due to thoracic carcinoids

    Ann Thorac Surg

    (1990)
  • J.B. Shrager et al.

    Bronchopulmonary carcinoid tumors associated with Cushing's syndrome: a more aggressive variant of typical carcinoid

    J Thorac Cardiovasc Surg

    (1997)
  • C.E. Daniels et al.

    The utility of fluorodeoxyglucose positron emission tomography in the evaluation of carcinoid tumors presenting as pulmonary nodules

    Chest

    (2007)
  • T.C. Mineo et al.

    Relevance of lymph node micrometastases in radically resected endobronchial carcinoid tumors

    Ann Thorac Surg

    (2005)
  • M. Mezzetti et al.

    Assessment of outcomes in typical and atypical carcinoids according to latest WHO classification

    Ann Thorac Surg

    (2003)
  • M.C. Aubry et al.

    Significance of multiple carcinoid tumors and tumorlets in surgical lung specimens: analysis of 28 patients

    Chest

    (2007)
  • W. Travis et al.

    The IASLC lung cancer staging project: proposals for staging of carcinoid tumors of the lung

    J Thorac Oncol

    (2008)
  • P. Ferolla et al.

    Tumorlets, multicentric carcinoids, lymph-nodal metasases, and long-term behavior in bronchial carcinoids

    J Thorac Oncol

    (2009)
  • L.J. Wirth et al.

    Outcome of patients with pulmonary carcinoid tumors receiving chemotherapy or chemoradiotherapy

    Lung Cancer

    (2004)
  • T. Åberg et al.

    The choice of operation for bronchial carcinoids

    Ann Thorac Surg

    (1981)
  • T.G. Sutedja et al.

    Bronchoscopic therapy in patients with intraluminal typical bronchial carcinoid

    Chest

    (1995)
  • H. Luckraz et al.

    Long-term outcome of bronchoscopically resected endobronchial typical carcinoid tumors

    J Thorac Cardiovasc Surg

    (2006)
  • H.A.P. Brokx et al.

    Initial bronchoscopic treatment for patients with intraluminal bronchial carcinoids

    J Thorac Cardiovasc Surg

    (2007)
  • D. Granberg et al.

    Experience in treatment of metastatic pulmonary carcinoid tumors

    Ann Oncol

    (2001)
  • B. Kaplan et al.

    Outcomes and patterns of failure in bronchial carcinoid tumors

    Int J Radiat Oncol Biol Phys

    (2003)
  • Cited by (155)

    • Neuroendocrine neoplasms of the lung

      2022, Practical Pulmonary Pathology: A Diagnostic Approach
    View all citing articles on Scopus
    View full text