Castleman's disease: three case reports and a review of the literature

Ear, Nose & Throat Journal, July, 2007 by James L. Newlon, Marion Couch, Joseph Brennan

Abstract

Castleman's disease is a rare lymphoproliferative disorder that is easily misdiagnosed. When it occurs in the head/neck and thorax, it can pose a diagnostic dilemma because of its lack of any specific presenting characteristics and distinguishing radiographic features. An accurate histopathologic diagnosis and careful staging are crucial to planning treatment. The highly vascular nature of the tumor makes surgical management challenging, and it warrants preoperative embolization whenever possible. We report 3 cases of Castleman's disease that involved the head/neck and thorax. We also review the presenting clinical features of Castleman's disease, its histopathologic characteristics, and the diagnostic and treatment challenges that it poses.

Introduction

Castleman's disease is a rare lymphoproliferative disorder that presents with or without constitutional symptoms. Many terms have been used over the years to describe this entity, including giant lymph node hyperplasia, angiomatous lymphoid hamartoma, benign giant lymphoma, and follicular lymphoreticuloma.

The entity was first described in 1956 by Castleman et al as a benign, localized enlargement of hyperplastic lymph nodes. (1) In 1970, Flendrig reported that this disorder has two separate histologic features. (2) Based on these features, Keller et al in 1972 subclassified Castleman's disease into two types: hyaline-vascular andplasma-cell. (3) In addition, some patients have a mixed variant.

Clinically, Castleman's disease can be either localized or multicentric. The localized form is more common:

* Approximately 90% of cases of the localized form are of the hyaline-vascular type. Patients present with a solitary mass, and their disease typically follows a benign course. (4)

* Most cases of the multicentric form are of the plasmacell type. Patients present with a systemic illness that manifests as disseminated lymph nodes, constitutional symptoms (e.g., fatigue, fever, weight loss, and sweats), autoimmune abnormalities, recurrent infections, and laboratory abnormalities (e.g., anemia, hypoalbuminemia, hypergammaglobulinemia, and an increased erythrocyte sedimentation rate). The multicentric form is aggressive and often culminates in death secondary to infectious complications or malignancy (e.g., lymphoma, Kaposi's sarcoma, or follicular dendritic cell sarcoma); malignancies have been reported to arise in as many as 32% of patients with multicentric Castleman's disease. (3-5)

Both the hyaline-vascular and plasma-cell types of Castleman's disease are usually accompanied by a systemic inflammatory response. The clinical course may also be complicated by acquired systemic amyloidosis. Following tumor resection, amyloid deposits and systemic inflammation regress.(6)

Multicentric Castleman's disease in the absence of human immunodeficiency virus (HIV) infection is associated with non-Hodgkin's lymphoma. Hodgkin's disease may occur with the localized form of the plasma-cell type of Castleman's disease, usually in the same region. (7) In HIV-positive patients, multicentric Castleman's disease is associated with human herpesvirus type 8 (HHV8), which is a Kaposi's-sarcoma-associated herpesvirus. In one study, the incidence of Kaposi's-sarcoma-associated, HHV8-related non-Hodgkin's lymphoma in a cohort of HIV-positive patients with multicentric Castleman's disease was 15-fold higher than the incidence in the general HIV-positive population. (8)

The most common location of Castleman's disease is the thorax; the neck is the second most common site, although only about 70 such cases have been reported (table 1). (9) The disease appears to have a predilection for men, and it usually occurs in the third through fifth decades of life (the youngest reported patient was diagnosed at 6 weeks of age). (5, 10-11) The incidence of Castleman's disease is low in the pediatric population; when it does occur, these patients appear to have a more favorable outcome than do adults. (12)

Collectively, we were involved in the treatment of 3 patients with Castleman's disease. Patients 1 and 2 were treated at Wilford Hall Medical Center in San Antonio, Texas, by two of the authors (J.L.N. and J.B.), and patient 3 was treated at The Johns Hopkins Hospital in Baltimore by the third author (M.C.). All 3 patients had the localized form and the hyaline-vascular type of Castleman's disease as determined by surgical lymph node biopsy. Follow-ups were conducted by clinic visits and telephone interviews. In this article, we describe these 3 cases, and we review the entire course of Castleman's disease, including its clinical features at presentation, its histopathologic characteristics, and the diagnostic and treatment challenges it poses.

Case reports

Patient 1. A 58-year-old woman presented with a 5-year history of a persistent, enlarging left lateral neck mass. Because she had previously undergone multiple excisions of benign neuromas in her neck, we suspected that this mass represented another recurrence. The patient also complained of right-sided neck numbness and tingling. The remainder of her medical history was unremarkable.