Final Diagnosis -- Retroperitoneal Angiofollicular Lymph Node Hyperplasia (Castleman's disease), Hyaline Vascular Type


Contributor's Note:

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).


  1. Castleman B, Iverson I, Menendez VP. Localized mediastinal lymph node hyperplasia resembling thymoma. Cancer 1956; 9: 822-830.
  2. Keller AR, Hochhholzer L, Castleman B. Hyaline-vascular and plasma-cell types of giant lymph node hyperplasia of mediastinum and other locations. Cancer 1972; 29: 670-683.
  3. Gohlke F, Marker-Hermann E, Kanzler S, Mitze M, Meyer zum Buschenfelde KH. Autoimmune findings resembling connective tissue disease in a patient with Castleman's disease. Clin Rheum 1997; 16(1):87-92.
  4. Gaba AR, Stein RS, Sweet DL, Variakojis D. Multicentric giant lymph node hyperplasia. Am J Clin Pathol 1978; 69: 86-90.
  5. Cesarman E, Knowles DM. Kaposi's sarcoma-associated herpesvirus: a lymphotropic human herpesvirus associated with Kaposi's sarcoma, primary effusion lymphoma, and multicentric Castleman's disease. Semn Diag Pathol 1997; 14(1):54-66.
  6. Gaidano G, Pastore C, Gloghini A, Volpe G, Capello D, Polito P, Vaccher E, Tirelli U, Saglio G, Carbone A. Human herpesvirus type-8 (HHV-8) in haematopoietic neoplasia. Leuk and Lymph 1997; 24(3-4):257-66.
  7. Said R, Tarawneh M. Membranoproliferative glomerulonephritis associated with multicentric angiofollicular lymph node hyperplasia. Case report and review of the literature. Am J Nephrol 1992; 12(6):466-70.
  8. Tsukamoto Y, Hanada N, Nomura Y, Hiki Y, Kasai K, Shigematsu H, Kobayashi Y. Rapidly progressive renal failure associated with angiofollicular lymph node hyperplasia. Am J Nephrol 1991; 11(5):430-6.
  9. Ruggieri G, Barsotti P, Coppola G, Spinelli C, Balducci A, Ventola FR, d'Adamo G, Tata MV, Marinozzi V. Membranous nephropathy associated with giant lymph node hyperplasia. A case report with histological and ultrastructural studies. Am J Nephrol 1990; 10(4):323-8.
  10. Gili A, Ngan BY, Lester R. Castleman's disease associated with pemphigus vulgaris. J of the Am Acad Derm 1991; 25(5 Pt 2):955-9.
  11. Sherman D, Ramsay B, Theodorou NA, Woodrow D, Paradinas FP, Cream JJ, Murray-Lyon IM. Reversible plane xanthoma, vasculitis, and peliosis hepatis in giant lymph node hyperplasia (Castleman's disease): a case report and review of the cutaneous manifestations of giant lymph node hyperplasia. J of Am Acad Derm 1992; 26(1):105-9.
  12. Akira S, Kishimoto T. The evidence for interleukin-6 as an autocrine growth factor in malignancy. Semn in Cancer Biol 1992; 3(1):17-26.
  13. Seco JL, Velasco F, Manuel JS, Serrano SR, Tomas L, Velasco A. Retroperitoneal Castleman's disease. Surgery 1992; 112(5):850-5.

Contributed by Kevin D. Horn, MD and David Sholehvar, MD


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