eMedicine Specialties > Pulmonology > Lung Tumors

Adenoma, Bronchial: Differential Diagnoses & Workup

Author: Charles W Van Way III, MD, The Ralph Ringo Coffey Professor and Chairman, Department of Surgery, University of Missouri-Kansas City; Chief, Department of Surgery, Truman Medical Center
Coauthor(s): Gerald L Early, MA, MD, BA, FACS, FCCP, Associate Professor, Department of Surgery, University of Missouri-Kansas City
Contributor Information and Disclosures

Updated: Nov 13, 2008

Differential Diagnoses

Histoplasmosis

Other Problems to Be Considered

Adenocarcinoma of the lung
Large cell lung cancer
Squamous cell lung cancer
Carcinoid
Mucoepidermoid carcinoma
Adenoid cystic carcinoma
Granuloma
Hamartoma
Metastatic cancer

Aspergillosis: This may occur in association with malignant disorders. Uncommonly, it accompanies benign carcinoid and can lead to a delay in diagnosis of the adenoma.

Recurrent lobar pneumonia: Consider primary endobronchial tumor as the etiology, especially in children.

Asthma: Asthma can be an early cause of misdiagnosis, a common error with obstructing tracheobronchial lesions.

Workup

Laboratory Studies

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

• Complete blood cell count
  • Not diagnostic but can help in differentiation of an infiltrate as a pneumonia
  • Useful to help quantify volume of hemoptysis associated with endobronchial lesions
• Electrolyte, BUN, creatinine, and calcium values: These values are not particularly helpful, but the results may assist in the evaluation of paraneoplastic involvement.
• Liver function tests: Results are insensitive as indicators of hepatic metastases.
• Arterial blood gas determination: This is useful for the detection of respiratory failure (eg, acidosis, hypercarbia, hypoxia).
• Sputum culture and cytology
  • Rarely helpful in diagnosing bronchial adenomas
  • Sensitivity of approximately 74% if central airways are involved
• Tumor markers
  • Corticotropin
  • Antidiuretic hormone
  • Calcitonin
  • Bombesin
  • Neuron-specific enolase
  • Serotonin
  • Synaptophysin
  • Note: 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.

Imaging Studies

• Chest radiography
• Films may demonstrate a nodule, mass, infiltrate, mediastinal or hilar lymphadenopathy, or pleural effusion.
• Findings may be due to bronchial obstruction.
• Radiological findings are frequently nondiagnostic.
• Oblique-view radiographs provide improved detectability of central lesions and may delineate an occult endobronchial component. 
• Computed tomography 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. 
• 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.
• Magnetic resonance imaging: 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 usually do not "light up" with PET-FDG scanning.
• 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).
• Nuclear imaging: This can include bone scanning when applicable.

Other Tests

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

Procedures

• Transbronchoscopic fine-needle aspiration
  • Fine-needle aspiration (FNA) biopsy of peripheral lesions may yield a basis for diagnosis, including revision of incorrect interpretations (eg, bronchial carcinoid misinterpreted as small cell carcinoma); therefore, histologic confirmation is the only definitive means of diagnosis.
  • FNA biopsy is a routine 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 usually is successful in localizing within and proximal to segmental orifices.
  • Accurate identification requires bronchial biopsy; biopsy should be performed.
  • 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 typical carcinoid tumors, 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 the carcinoid with mediastinal lymph node dissection provides excellent local control and 5-year survival.

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.
 
Tumorlets are foci of atypical hyperplastic bronchial epithelium. 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.

Staging

No correlation is shown to standard tumor, node, metastases (TNM) classifications. Most typical lesions are stage 1 tumors at presentation. More than 50% of atypical lesions are at stage 2 or 3 at presentation, with bronchopulmonary or mediastinal nodal involvement noted. Intraoperative biopsies of hilar and lobar nodal tissue and tissue in the involved bronchopulmonary segment, with frozen section analysis, are required.

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