Carcinoid Tumors

Carcinoids are typically less aggressive tumors.

They are usually arise from major bronchi or the trachea. Carcinoids are most often treated with surgical excision.

The patients have a high rate of survival, with 95% of patients alive after five years.

Patients are usually younger than 60 years of age, and commonly present with hemoptysis, cough, wheezing, and/or recurrent pneumonia.

Surgical resection is the treatment of choice because most carcinoids are resistant to both radiation and chemotherapy. Carcinoids need to be removed to prevent local complications such as bronchial obstruction.

Carcinoid tumors are usually covered with respiratory epithelium and have a heterogenous microscopic appearance with a trabecular, papillary, insular, solid, or spindle cell pattern.

They have uniform, polygonal cells, round nuclei, and a stippled chromatin pattern. Carcinoids have a well-vascularized stroma, which may result in significant bleeding with bronchoscopic biopsy.

The majority of carcinoids arise centrally and cause complete obstruction of the affected bronchus.

Therefore the majority of cases present with lobar or segmental collapse.

Infection and abcess formation may complicate the radiographic picture. Approximately 20% of carcinoids present as peripheral masses between 1-10 cm (average 4cm).

These soft tissue masses may calcify or ossify but this is a rare occurance.

Carcinoid tumors are recognized as low malignant potential neoplasms with biochemical, cytochemical and ultrastructural features of neuroendocrine cells. They represent 1-2% of lung neoplasms. They present most commonly in the 5th and 6th decades of life, but can occur in any age group. These tumors do not appear to share a relationship with smoking or exposure environmental agents.

Clinically, patients are either asymptomatic and detected incidentally by radiograph or are symptomatic, due to tumor growth, presenting with cough, wheezing, hemoptysis or obstructive pneumonia. The most frequent radiographic finding is a round or ovoid lobulated mass in the peripheral lung. Only rarely do patients present with the clinical manifestation of the carcinoid syndrome: diarrhea, flushing, right sided valvular lesions of the heart, bronchoconstriction and cyanosis, owing to the secretion of serotonin. Most of the lesions with functional secretory activity are of the argentaffinoma pattern.

Most bronchial carcinoids follow a relatively benign course without metastasis, making them amenable to resection. Surgical resection is the treatment of choice because most carcinoids are resistant to both radiation and chemotherapy. Carcinoids need to be removed to prevent local complications such as bronchial obstruction. The patients have a high rate of survival, with 95% of patients alive after five years.

The overall 5 to 10 year survival rates for typical carcinoids are 94 and 87%, respectively. Poor prognostic factors include advanced disease at presentation and lack of surgical treatment. It should be noted that a small subset (less than 10%) of carcinoid tumors which exhibit a more aggressive behavior, cytologic atypia, and necrosis, exists and are termed atypical carcinoids. Over 50% of atypical carcinoids recur within 2 years.

Gross Appearance

The majority of pulmonary carcinoids are 2-4 cm with approximately 80% located centrally and the remainder peripherally. They are most frequent in the lobar bronchi, probably because, this area has the highest concentration of neuroendocrine cells. Generally they appear as soft, polypoid masses covered with a smooth erythematous mucosa. Cut sections show the tumor to be well circumscribed and uniformly yellow-gray, with infrequent areas of hemorrhage or necrosis. Foci of calcification or ossification may be present. These tumors often project into the bronchial lumen, and the lung parenchyma distal to the tumor may demonstrate gray hepatization due to the development of postobstructive pneumonia.

Microscopic Features

Histologically carcinoids show neuroendocrine differentiation, which reflects their origin from the Kulchitsky cells of the bronchial mucosa. Architecturally, they form nests and chords surrounding a thin well-vascularized fibrous stroma, which may result in significant bleeding with bronchoscopic biopsy. Individual cells are characterized by their regularity, polygonal shape, central round nuclei with uniform chromatin, eosinophilic cytoplasm, minimal pleomorphism and infrequent mitoses. The tumor is generally covered by an intact mucosa. This finding tends to reduce the utility of sputum samples and bronchial washes and brushes for procuring diagnostic tissue. Peripheral carcinoids may exhibit a more spindled appearance, and immunohistochemical stains may be necessary to differentiate them from other spindle cell neoplasms.

Several different immunohistochemical stains and other special stains are can be useful in confirming the neuroendocrine differentiation of suspected carcinoid tumors. PAS-lead hematoxylin positive granules or intracytoplasmic immunoreactivity to neuron-specific enolase (NSE), synaptophysin and/or chromogranin are indicative of the neuroendocrine differentiation. These special studies are especially useful for making the diagnosis based on small biopsy specimens. Electron microscopy can also be employed to demonstrate neuroendocrine granules, although this is seldom performed due to the relative simplicity of immunohistochemical techniques.