FINAL DIAGNOSIS: ANGIOFOLLICULAR LYMPH NODE HYPERPLASIA, HYALINE VASCULAR TYPE (CASTLEMAN'S DISEASE).
Angiofollicular lymph node hyperplasia, or Castleman's disease, is a nonneoplastic lymphoid and vascular proliferation first described by Castleman and associates(1). It is generally seen in adults, usually prior to age 30. The proliferation commonly is diagnosed as a widened mediastinum in the chest radiographs of asymptomatic individuals, although other sites including the retroperitoneum, cervical lymph nodes, pulmonary parenchyma, axillary lymph nodes, and skeletal muscle may be involved (2).
The most common subtype of Castleman's disease, the hyaline vascular type, is typified by a collection of numerous follicular proliferations of lymphoid cells of varying maturity, which often form a layered, or "onion-skin" pattern surrounding a small vessel in the center of the follicle. This vessel usually displays hyalinization of its wall. The endothelial cells lining these central vessels are often prominent and reactive in appearance. The areas between follicular structures contain variable numbers of plasma cells and prominent vascularity. Overall, this histological pattern can bear a significant superficial resemblance to a thymoma, which is an important entity to consider in the differential diagnosis of any mediastinal lesion (2).
The second subtype of Castleman's disease, the plasma cell variant, contains sheets of interfollicular plasma cells, and tends to involve multiple lymph node involvement at presentation, as opposed to the hyaline-vascular subtype which is most commonly a solitary mediastinal nodule. In contrast to the smaller follicles seen in the hyaline vascular type of CD, the follicles in the plasma cell variant are hyperplastic, with many mitoses and tingible body macrophages. This variant is much more likely to present with symptoms such as fever and findings such as anemia and hypergammaglobulinemia.(2) Laboratory abnormalities mimicking autoimmune disease, such as elevated erythrocyte sedimentation rate, positive antinuclear and anti smooth muscle antibodies, thrombocytopenia, cryoglobulinaemia, serum immune complexes and peripheral polyneuropathies may be noted. The plasma-cell type has also been associated with an increased risk for later development of lymphoma (3).
A third type of Castleman's disease, first described in 1978 (4), is termed multicentric Castleman's disease (MCD). Multiple lymph node areas can be involved by this process, and hepatosplenomegaly is noted in many patients. Abnormal laboratory findings similar to those seen in the plasma cell variant (as mentioned above) are noted in MCD. Histologically, MCD may manifest as both hyaline vascular and plasma cell variant morphology, and commonly is a transitional or combined variant of the other types of CD. Recently, the association of MCD and Kaposi's sarcoma (KS) in AIDS patients prompted investigation of Herpesvirus- 8 (HHV-8, which is commonly associated with KS); MCD in these individuals contained viral DNA sequences. Other studies have found a number of MCD cases in the non-AIDS population also harbor the virus. The pathogenetic role of the virus in MCD is not yet entirely clear (5,6).
Other less commonly reported associations with Castleman's disease have included membranoproliferative glomerulonephritis type I (7), crescentic glomerulonephritis with interstitial tubulitis and kidney failure (8), and membranous nephropathy with nephrotic syndrome (9); in addition, various skin lesions such as pemphigus vulgaris (10), generalized plane xanthomas, and cutaneous vasculitis (11). It has been postulated that the various autoimmune dysfunctions noted in conjunction with Castleman's disease promote many of these renal and cutaneous findings. Steroid therapy, in conjunction with surgical excision of the lesion, has been helpful in resolving these secondary phenomena (3).
The finding of increased serum IL-6 originating from affected lymph nodes has been noted in the plasmacellular variant; the levels of IL-6 correlate with symptoms and decrease with successful therapy (12).
Angiofollicular lymph node hyperplasia commonly has an indolent course; however, it is uncommon enough that the long term morbidity of this entity is still a matter of dispute. Surgical excision is considered to be curative on the basis of current studies, however (13).
Contributed by Kevin D. Horn, MD and David Sholehvar, MD