Bronchial Adenoma Workup

Updated: Sep 19, 2019
  • Author: Charles W Van Way, III, MD; Chief Editor: Zab Mosenifar, MD, FACP, FCCP  more...
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Workup

Approach Considerations

No single investigative method is adequate to diagnose bronchial tumors in all patients, but most tumors are detectable. Radiographic and procedural techniques are usually required to locate lesions.

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Laboratory Studies

Laboratory studies include the following:

  • Complete blood cell count (CBC) - Results are not diagnostic but can help in differentiation of an infiltrate as a pneumonia; it is useful to help quantify volume of hemoptysis associated with endobronchial lesions.
  • Serum electrolytes, BUN, creatinine, and calcium - Results may assist in the evaluation of paraneoplastic involvement.
  • Liver function tests - Results are insensitive as indicators of hepatic metastases. 
  • Arterial blood gases - Results are useful for the detection of respiratory failure (eg, acidosis, hypercarbia, hypoxia).
  • Sputum culture and cytology  - These are rarely helpful in diagnosing bronchial adenomas.

Tumor markers

Tumor markers include the following:

  • Corticotropin
  • Antidiuretic hormone
  • Calcitonin
  • Bombesin
  • Neuron-specific enolase
  • Serotonin
  • Synaptophysin

All the above-mentioned markers also can be identified in small cell lung cancer; therefore, their presence offers no diagnostic value in distinguishing between these 2 tumor types.

Biochemical testing

Neither blood screening nor urine screening for serotonin or 5-hydroxyindoleacetic acid is of diagnostic value, unless carcinoid syndrome is clinically present. If it is, the presence of these biochemical abnormalities portends a more adverse prognosis.

Immunohistochemical staining

This may help detect differences in secretory products between typical carcinoids and others.

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Imaging Studies

Chest radiography

Radiological findings are frequently nondiagnostic. Films may demonstrate a nodule, mass, infiltrate or atelectasis, mediastinal or hilar lymphadenopathy, or pleural effusion. Findings may be due to bronchial obstruction. Oblique-view radiographs provide improved detectability of central lesions and may delineate an occult endobronchial component.

Chest radiograph findings are normal in about 5% of patients with bronchopulmonary carcinoid. 

MECs are generally well circumscribed, round, oval or lobulated masses. Signs of bronchial stenosis or obstruction are frequent. [2]

CT scanning

CT scanning is the best imaging modality.  Upon nodule discovery, obtain 10-mm CT cuts through the chest and upper abdomen. Fine cuts (eg, 1- to 2-mm) should be obtained through nodules, looking for calcifications. Tracheobronchial obstruction is suggested by compression of structures in close proximity to the trachea on the chest CT scan. Three-dimensional reconstruction may aid in localization of endobronchial tumors.

CT scanning further delineates endobronchial and parenchymal tumor components. Prior to the development of CT scanning, tomography and bronchography were used to delineate endobronchial obstruction and bronchiectasis distal to the mass. CT scanning supplants both of these tests; neither is currently indicated.

Central lesions are observed as well-defined masses that narrow, deform, or obstruct adjacent airways. Diffuse punctuate calcifications are observed in 30% of cases and are characteristic but not diagnostic of carcinoid.

Peripheral parenchymal atelectasis or bronchiectasis is common. Peripherally located lesions are contiguous with the airway. They are typically described as rounded, homogenous, sharply demarcated, and slow-growing. Despite their peripheral location these lesions are often buried deep within the parenchyma, making wedge resection difficult.

Typical carcinoid is marked by homogeneous contrast enhancement; atypical carcinoid is associated with less contrast enhancement and frequent irregular contours; regional adenopathy is common.

Stromal osseous metaplasia due to tumor-induced necrosis of bronchial cartilage is observed on CT scans as intratumoral calcification.

CT is highly accurate in the assessment of ACC tumor location, extra luminal extensions, carinal involvement and distant metastasis. ACC appears as a focal mass in the trachea or main bronchi with a smooth border as it arises from submucosa. It may involve more than half of the airway circumference. This tumor can also be differentiated from MEC because of its frequent extra-luminal extension. Lymphadenopathy and distant metastases are uncommon and the local recurrence is most common. [8]

The majority of MECs arise from bronchial glands in the lumen of a main, lobar, or segmental bronchus, and CT findings are similar to those of bronchial carcinoid tumors. [2]

MRI

This is probably most often used when CT scan findings are equivocal.

Positron emission tomography

The positron emission tomography (PET) tracer F-18-fluorodeoxyglucose (FDG) has been used to detect bronchogenic carcinoma. Because of their low metabolic rate, carcinoid tumors may not consistently "light up" with PET-FDG scanning. Sensitivities range from 14-100%. Thus, the reliability of a positive or negative test result is unknown and, therefore, the routine use of PET scans is discouraged.

Radiolabeled peptides

Because carcinoid tumors, like other neuroendocrine tumors, may contain somatostatin receptors, the radiolabeled peptides may be useful. The 2 reported to be of greatest merit are [(111In0-DPTA(0)] octreotide (Octreoscan, Mallinckrodt; Petten, The Netherlands) and 99m technetium Tc depreotide single-photon emission CT scanning (NeoTect, Diatide; Londonderry, NH). However, about one third of carcinoid tumors are somatostatin-negative whereas the rest are weakly positive and, thus, difficult to distinguish from inflammation.

Furthermore, octreotide scan results are positive in almost all patients with lung cancer (NSCLC and SCLC), pneumonia, and lymphoma. Therefore, given the relatively high cost and low clinical yield, routine use of octreotide scanning is not recommended in bronchopulmonary carcinoid.

Nuclear imaging

This can include bone scanning when applicable.

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Other Tests

Spirometry

Peak expiratory flow is a good bedside detector of significant airflow obstruction. Flow volume loops indicate truncation of the expiratory limb.

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Procedures

Fine-needle aspiration

Fine-needle aspiration (FNA) biopsy of peripheral lesions may yield a diagnosis, including revision of incorrect interpretations (eg, bronchial carcinoid misinterpreted as small cell carcinoma).

FNA biopsy may be part of the bronchoscopic examination of submucosal lesions. Frozen section examination of FNA biopsy specimens may be misleading because of the tumors' similarity to small cell carcinoma. Permanent hematoxylin and eosin preparations usually lead to the correct diagnosis, although confusion regarding atypical carcinoid still may lead to an inaccurate diagnosis.

Bronchoscopy

Eighty percent of bronchial adenomas are visible under bronchoscopy, which is usually successful in localizing within and proximal to segmental orifices. See the images below.

Bronchoscopy: Carcinoid tumor (Left Lower Lobe - A Bronchoscopy: Carcinoid tumor (Left Lower Lobe - Anteromedial Basal)
Bronchoscopy: Carcinoid tumor (Left Lower Lobe - A Bronchoscopy: Carcinoid tumor (Left Lower Lobe - Anteromedial Basal)

Flexible bronchoscopy represents the main diagnostic tool for MECs, because it allows direct visualization of the lesions and biopsies, although extraluminal or peripheral lesions cannot be assessed. [4] Typical appearance is that of a smooth, reddish-brown lesion often covered by mucosa. Accurate identification requires bronchial biopsy; biopsy should be performed. [4]

Bleeding can occur, but reports of massive hemorrhage associated with biopsy are exaggerated. Most episodes of postbronchoscopy hemorrhage have followed attempts at partial or complete removal rather than simple biopsy. The submucosal location necessitates a biopsy deeper than usual. Dilute epinephrine is a helpful adjunct to prevent bleeding. General anesthesia and rigid bronchoscopy may be required for airway control if persistent hemorrhage occurs following fiberoptic bronchoscopy.

Bronchoscopy should be performed in all candidates for a bronchoplastic procedure in order to precisely define the limits of the planned bronchial resection.

If the endoscopist is not prepared to deal with airway bleeding, biopsy should be deferred until the patient has been sent to an appropriate facility.

Thoracentesis

This can aid in diagnosis via cytological studies that confirm other diagnoses in the differential.

Thoracentesis can also be therapeutic when large pleural effusions cause respiratory insufficiency

Ultrasound guidance may be helpful when dealing with small effusions.

Mediastinoscopy

It is of little value in preoperative nodal staging in bronchial adenomas, unless mediastinal involvement is suspected.

It should be reserved for atypical carcinoid or for when evidence of mediastinal involvement is seen with CT scanning.

Even with mediastinal node involvement, resection of a carcinoid with mediastinal lymph node dissection provides excellent local control and 5-year survival.

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Histologic Findings

Carcinoids originate from bronchial epithelial stem cells and are not of neural crest origin. Grossly, they appear as soft, highly vascularized, and pink-to-purplish tumors. They are usually covered by intact epithelium, which occasionally has squamous metaplasia, and ulceration can be present. Carcinoids usually are sessile, but they can be polypoid. They may penetrate the bronchial wall and occasionally may show parenchymal or peribronchial nodal extension.

Microscopically, the cells are uniform and round-to-polygonal; however, when they are located peripherally, a spindle shape predominates. The cellular arrangement usually involves small clusters, interlacing cords, or both, separated by well-vascularized connective tissue. Nuclei are small and oval, and finely granular chromatin with abundant eosinophilic cytoplasm is observed. Typical carcinoids, or Kulchitsky cell type I neuroendocrine tumors, have less than 2 mitoses per 2 mm2 and they lack necrosis.

Atypical carcinoids, or Kulchitsky cell type II neuroendocrine tumors, have carcinoid morphology with 2-10 mitoses per 2 mm2 or necrosis. They exhibit malignant histologic features and aggressive behavior. They exhibit pleomorphism, more mitotic activity, nuclear abnormalities, prominent nucleoli with peripheral palisading, and necrosis.

Kulchitsky type III cells are thought to be the cells of origin of small cell carcinoma.

A rare, pigmented, melanocytic variety of carcinoid has been described and is differentiated from melanoma.

An oncocytic type is a rare subtype of typical lesions with mixed cellular content, including typical carcinoid cells and large eosinophilic oncocytes. True oncocytic differentiation occurs.

Adenoid cystic carcinomas are slow-growing tumors with the propensity for submucosal invasion, perineural invasion, and distant metastasis. Numerous prominent mitochondria and serous secretory granules can be observed with electron microscopy.

Mucoepidermoid tumors are characterized by a mixture of mucus-producing, glandular and squamous epithelial cells, as well as intermediate cells with both properties at various percentages, and by various growth patterns such as cystic, papillary, and solid structures. [2]  Low grade malignant tumors have mostly cystic components and mild cytologic atypia . Microscopic invasion into pulmonary parenchyma and metastasis to regional lymph nodes is unusual. High grade tumors presents areas of solid growth, with atypia, mitotic activity and necrosis, and may be difficult to distinguish from lung adenosquamous carcinomas. Regional lymph node involvement is more frequent in these tumors.

Tumorlets are foci of atypical hyperplastic bronchial epithelium less than 5 mm in diameter that appear histologically similar to carcinoid. These lesions are more commonly seen in middle-aged or older individuals with chronic pulmonary pathology. They are usually an incidental finding in a resected specimen or are found during an autopsy. These lesions, present in 7-10% of patients with pulmonary carcinoid, do not represent metastasis and should not alter treatment planning.

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Staging

Bronchopulmonary carcinoids are staged according to the AJCC TNM staging classification used for lung cancer. Size, nodal involvement, and presence of metastases have all been shown to be significant predictors of survival. Nodal status becomes particularly important given the relatively smaller size of carcinoid tumors when compared to NSCLC. About 90% of typical carcinoids are pN0 (Stage I) at presentation, as are about 60% of atypical carcinoids.

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