Physical Examination, Complementary Tests, and Functional Status Assessment

Symptoms in patients with bronchial carcinoid depend on the tumor size, site, and growth pattern. For instance, a small peripheral carcinoid may be an incidental finding, and a large central tumor may result in symptoms similar to those found in our patient: cough, hemoptysis (due to its hypervascularity), and obstructive pneumonia. Some patients may also have shortness of breath.¹ The diagnosis is often delayed, and patients may receive several courses of antibiotics, bronchodilators, or inhaled corticosteroids to treat recurrent pneumonia or suspected asthma. In one study, 14% of patients had been treated for asthma for up to 3 years before the tumor was discovered.² The wheezing noted in our patient was localized to the left hemithorax, reflecting focal airway obstruction, not bronchoconstriction. In fact, diffuse wheezing is rare in patients with carcinoids, regardless of tumor location, because only 1% to 5% of patients exhibit hormone-related symptoms such as carcinoid syndrome.^† In part, this reflects the low incidence of hepatic metastases—2% and 5%, respectively—for typical and atypical carcinoids.^2,3 In the setting of liver metastasis, however, more than 80% of patients have symptoms of carcinoid syndrome.¹ Bronchial and other extraintestinal carcinoids, whose bioactive products are not immediately cleared by the liver, may cause the syndrome in the absence of liver metastasis because of their direct access to the systemic circulation. However, bronchial carcinoids have low serotonin content because they often lack aromatic amino acid decarboxylase and cannot produce serotonin and its metabolites; they only occasionally secrete bioactive amines. Elevated plasma or urinary secretory product levels such as 5′-hydroxyindoleacetic acid (5′-HIAA) thus are rarely detected. Elevation of plasma chromogranin A^* is a relatively sensitive (≈75%) marker of bronchopulmonary carcinoids, but elevated levels are also seen in approximately 60% of patients with small cell carcinoma, and false-positive elevations can occur in renal impairment, in atrophic gastritis, and during proton pump inhibitor therapy.⁴ Measurement of its levels is considered useful only in following disease activity in the setting of advanced or metastatic carcinoid.⁵ No such serologic or urinary testing was performed in our patient before bronchoscopic intervention was provided.

With regard to radiographic studies, when the tumor is centrally located, as in our patient, bronchial obstruction may occur and atelectasis is noted (see Figure 2-1, C). Compared with chest x-ray, CT provides better resolution of tumor extent and location, as well as the presence or absence of mediastinal lymphadenopathy. High-resolution CT allows characterization of centrally located carcinoids, which may be purely intraluminal, exclusively extraluminal, or, more frequently, a mixture of intraluminal and extraluminal components (the “iceberg” lesion). In the setting of post obstructive pneumonia, a clear distinction between intraluminal and extraluminal extension can be properly made only after post obstructive debris and atelectasis have been removed.⁶ Tumor morphology impacts management because bronchoscopic treatments alone are considered by some investigators to be acceptable therapeutic alternatives for purely intraluminal typical carcinoids.⁶ Chest CT scan should be performed as part of nodal staging for carcinoid tumors. Atypical carcinoids have a higher recurrence rate and present more often with hilar or mediastinal nodal metastases (20% to 60% vs. 4% to 27%), when compared with typical carcinoids.¹ This patient had no evidence of mediastinal or hilar lymphadenopathy on CT scan; because atelectasis and pneumonia were present, it was unclear whether the tumor had an extraluminal component (e.g., mixed obstruction, iceberg lesion).

The bronchoscopic appearance of this patient’s carcinoid is classic: a pink to red vascular mass attached to the bronchus by a broad base. In one study, 41% of patients presented with evidence of bronchial obstruction.³ These lesions occasionally can create a ball-valve effect (see video on ExpertConsult.com) (Video I.2.1). The hypervascular pattern has raised concern for bleeding following bronchoscopic biopsy. Some authors report bleeding in a quarter to two thirds of their patients, and some advise against biopsy when carcinoid is suspected.^7–9 In a review of 587 biopsies by flexible and rigid bronchoscopy, significant hemorrhage was seen in 15 (2.6%) patients, but 11 (1.9%) of these patients did not require transfusion or emergency surgery. In four patients (0.7%), emergency thoracotomy was necessary to address the problem of massive uncontrollable hemorrhage.¹⁰ Other authors showed that biopsy is safe, significantly increases the diagnostic yield, and is not associated with significant hemorrhage.^3,11 It is wise to have electrocautery, argon plasma coagulation, or a laser readily available to control spontaneous or post biopsy hemorrhage if necessary (see video on ExpertConsult.com) (Video I.2.2).

Comorbidities

This patient had no signs or symptoms suggesting hormone-related disorders caused by carcinoid, such as Cushing’s syndrome, acromegaly, or typical or atypical carcinoid syndrome.*

Support System

The patient lived with her husband, who was very supportive. Both were willing to proceed with treatment for curative intent.

Patient Preferences and Expectations

The patient had expressed fears of having lung cancer. She wanted clarification in terms of her diagnosis, prognosis, and follow-up after treatment. It was explained to her that bronchial carcinoid tumors are rare lung malignancies that rarely spread outside the chest.*^12,13 We were aware of data showing that the incidence of distant metastases at diagnosis for bronchopulmonary carcinoids is 5.5%¹⁴; that overall, 27.5% of bronchopulmonary carcinoids exhibit invasive growth or metastatic spread; and that the overall 5-year survival rate is 73.5%. Therefore we did not use the term benign tumor in our conversation with the patient.¹² Typical and atypical carcinoids, however, have different biologic behaviors and prognoses, causing them to be considered and reported as different tumors.² Typical carcinoids, as seen in this patient, usually have a good prognosis, with 5 year survival of 87% to 89%. Distant metastases from typical carcinoids may occur in approximately 10% of patients, even many years after radical resection of the primary tumor. Prolonged 10 year follow-up is therefore recommended. Atypical carcinoids are associated with 5 year survival of 44% to 78%.¹

Indications

In addition to being the procedure of choice to obtain a preoperative histologic diagnosis, bronchoscopy can be therapeutic in some cases when a polypoid exophytic tumor is entirely intraluminal. However, endobronchial resection with Nd : YAG laser is not considered curative for the vast majority of patients with central lesions, because most tumors extend into or through the wall of the bronchus. Bronchoscopic resection may be considered in the following clinical scenarios:

Figure 2-3 A, Right middle lobe typical carcinoid in a nonoperable elderly patient with significant cardiac comorbidities. B, Lateral and medial segments of the middle lobe bronchus are patent immediately after neodymium-doped yttrium aluminum garnet (Nd : YAG) laser–assisted bronchoscopic resection, with subsequent recurrence on follow-up bronchoscopy.

Contraindications

No contraindications to rigid bronchoscopy are known.

Expected Results

Bronchoscopic resection alone may provide prolonged recurrence-free survival for highly selected patients with a purely exophytic endoluminal bronchial carcinoid.^6,18–21 These patients present with a polypoid (exophytic) intraluminal tumor, good visualization of the distal tumor margin (usually less than 2 cm in extent), and no evidence of bronchial wall involvement or suspicious lymphadenopathy by high-resolution CT. In the largest series of 72 patients treated with this approach (57 typical and 15 atypical carcinoids), initial bronchoscopic management resulted in complete tumor eradication in 33 patients (46%). Surgery was required in 37 patients (including 11 of the 15 with atypical carcinoids)—2 for delayed recurrence at 9 and 10 years. At a median follow-up of 65 months, 66 patients (92%) remained alive, and only 1 of the deaths was tumor related.⁶

Team Experience

Rigid bronchoscopy with Nd : YAG laser resection is frequently performed in our referral center by a team of doctors and nurses experienced in managing critical central airway obstruction and hemoptysis. The goal of the operating team when this type of laser is used should be to remove unwanted tissue (tumor) with adequate hemostasis and minimum destruction of adjacent healthy tissue. Accurate removal of diseased tissue depends on the surgeon’s ability to visualize tissues and feel and control the shape and size of target tissues in three dimensions. Thus experience is important because complete and clear visualization of the treated area, ensuring hemostasis and minimization of adjacent laser-induced thermal injury, requires skillful operation of the rigid bronchoscope and knowledge of laser physics and laser-tissue interaction. For example, in a patient with mid-left mainstem bronchial carcinoid (Figure 2-4), the goal is precise removal of the lesion with minimal thermal trauma to the normal adjacent mucosa. Resection may be achieved in ways other than vaporization or widespread coagulation of blood vessels. Power density should be employed in ways that avoid damaging surrounding tissues to minimize interference, with consideration for future bronchoplastic procedures. If the tumor is completely removed, some investigators have suggested applying low-power density laser energy to residual bronchial surfaces to ablate and presumably kill residual tumor cells. Deep mucosal biopsies are warranted after a complete resection to ascertain the absence of disease.

Figure 2-4 A, Typical bronchial carcinoid completely obstructing the mid-left mainstem bronchus. B, After laser resection, the base of implantation is seen extending for 1 cm along the medial wall of the left main bronchus (arrow). Because this patient’s high-resolution computed tomography (HRCT) scan showed no extraluminal disease and distal airways were patent, this patient was referred for a bronchoplastic intervention.

Risk-Benefit Analysis

Open surgical resection is the preferred treatment approach for patients whose overall medical condition and pulmonary reserve will tolerate it. For patients whose condition does not permit complete resection, and for exceptional cases in which the lesion is entirely intraluminal, bronchoscopic resection may be an alternative.⁶ Our patient had post obstructive pneumonia, so we opted for initial bronchoscopic treatment to restore airway patency to the left lower lobe.

Therapeutic Alternatives