Castleman Disease

Lymphoproliferative disorder characterized by large, benign, hyperplastic lymph nodes (localized form, pauci-symptomatic, and multicentric form).

Castleman Tumor; Angiofollicular Lymph Node Hyperplasia; Angiomatous Lymphoid Hamartoma; Lymphatic Hamartoma; Giant Lymph Node Hyperplasia; Giant Benign Lymphoma.

Named after B. Castleman, an American pathologist, who first described this condition in 1956.

Rare. Localized form is more frequent than the multicentric form.

Three histologic variants (plasma cell, hyaline-vascular and mixed) and two clinical variants (localized and multicentric) exist. The hyaline-vascular variant accounts for approximately 90% of the cases. The localized form is more common than the multicentric form.

The etiology of this disease has not been fully determined. Current knowledge suggests the multicentric plasma cell variant is highly associated with an infection by human herpes virus 8 (HHV-8). In addition, these patients also seem to have an increased risk of developing other HHV-8-associated malignancies, such as (extranodal) B-cell non-Hodgkin lymphomas, multiple myeloma, and Kaposi sarcoma. The localized plasma cell and the mixed variant of Castleman disease are frequently found in patients who have a history of lymphoma. Interleukin-6 overproduction, either endogenously or virally encoded, has been made responsible for uncontrolled plasma cell proliferation in these two variants.

Based on the characteristic lymph node histology and exclusion of other disorders resulting in lymph node swelling. The localized form is often asymptomatic or becomes symptomatic once the diameter of the lymph node is significant enough to cause local compression of important structures, such as airway, vessels, or nerves (resulting in pain). The multicentric form is always symptomatic because of high production of interleukin-6.

The localized variant of Castleman disease presents as a mass lesion. The mediastinum, abdomen, and neck are the sites most commonly affected. Lesions up to 16 cm in diameter have been reported. Constitutional symptoms are most commonly seen in the plasma cell and multicentric forms. Symptoms include asthenia, weight loss, fever, skin rash, hemolytic anemia, and/or hypergammaglobulinemia. Hepatomegaly and/or splenomegaly are present in approximately 75% of cases. In approximately 25% of patients, the disease may also present with features of PEP (plasma cell dyscrasia, endocrinopathy, polyneuropathy) syndrome. Amyloidosis has been described in a number of cases. Patients with multicentric disease are prone to infections and malignancies. Treatment is surgical excision where possible (localized variant). Surgery, steroids, and chemotherapy are mainly used for the multicentric variant, which has a poor prognosis. Paraneoplastic pemphigus vulgaris has been described in some patients suffering from Castleman disease. The disease in the pediatric population appears to have a more favorable course than in adults.

Preoperative assessment should attempt to determine the direct and systemic effects of the lesion(s). Assess mediastinal or thoracic masses (chest radiographs, computed tomography scanning, diagnostic bronchoscopy), and ask about positional stridor and dyspnea to determine the degree of tracheobronchial compression and cardiovascular involvement. Pulmonary function tests can be useful for adults, but are less sensitive (and more difficult to obtain) in the pediatric population. Evaluate for adverse effects of chemotherapy.

Loss of airway patency and/or cardiovascular collapse may occur on induction in patients with mediastinal masses. Preserve spontaneous ventilation or at least avoid neuromuscular blocking agents if signs of airway or vascular compression are present. In some cases, changing the patient's position (e.g., from supine to lateral decubitus or prone position) and/or rigid bronchoscopy have been used successfully to (at least partially) resolve airway compression. Another concern is the loss of sympathetic tone on induction resulting in cardiopulmonary collapse secondary to a significant drop in pulmonary and systemic venous return. Positive pressure ventilation in the case of airway collapse may be helpful, but its hemodynamic effects will result in further exacerbation of cardiac filling. Regional or local anesthetic techniques are recommended whenever possible.

Avoid neuromuscular blocking agents if signs of compression of the airway or major vessels are present. Adapted antibiotic therapy in case of immunosuppression may be required.

PEP Syndrome: A plasma cell dyscrasia (bone marrow disorder) that causes multisystem disorders, including neuropathy, organ overgrowth, endocrine dysfunctions, and skin changes.