Final Diagnosis -- Angiofollicular hyperplasia (Castleman's disease)



Angiofollicular lymph node hyperplasia, also known as giant lymph node hyperplasia, lymph nodal hamartoma or Castleman's disease (CD), represents a benign lymph node hyperplasia with two major histological variants.

The hyaline vascular type (angiofollicular type) presents most frequently as a solitary mass within the chest and no general symptoms. Involvement of the cervical lymph nodes, nasopharynx, lung, axilla, and retroperitoneum has also been described.

Microscopically, the lymph node shows regressively transformed follicles scattered in a mass of lymphoid tissue. There usually is nodal architectural obliteration with scattered depleted small follicular centers surrounded by wide onion-skin-like zones of small lymphocytes, resembling Hassall's corpuscles. Concentric rings of reticulin fibers divide these tight layers of lymphocytes located at the periphery of the follicles (corresponding to the mantle zone). Penetrating hyalinized small vessels frequently give some of the abnormal follicles a lollipop-like appearance. Large cells with vesicular nuclei can be present in the hyaline center and represent follicular dendritic cells, as evidenced by their strong reactivity with CD21. The interfollicular areas demonstrate numerous hyalinized small vessels and an admixture of predominantly small lymphocytes, scattered plasma cells, and variable number eosinophils and transformed cells. The sinuses are characteristically absent.

The prognosis is excellent. Surgical excision is usually curative.

The second major morphologic category of Castleman's disease is known as the plasma cell variant. It usually presents as a solitary mass composed of multiple discrete lymph nodes. It also can present as multicentric or systemic variant, with generalized adenopathy, involvement of spleen, systemic symptoms (fever, anemia) and laboratory abnormalities (elevated erythrocyte sedimentation rate, hypergammaglobulinemia or hypoalbuminemia). The systemic form is seen in older individuals and is frequently aggressive. Sometimes, it can be associated with the POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, M protein and skin changes), amyloid deposits, HIV and HHV-8 infection (1).

Microscopically, the lymph nodes demonstrate extensive architectural obliteration by sheets of plasma cells between hyperplastic follicular centers with accompanying interfollicular vascular proliferation; however, the sinuses are usually preserved. The hyaline-vascular changes in the follicles are inconspicuous or absent. The abundant expression of interleukin-6 detected in this condition is thought to be responsible for the plasma cell infiltration.

Most cases of CD are polyclonal, but the plasma cell variant is one of the reactive disorders in which monoclonal plasma cells may be documented (2). Evidence of clonal immunoglobulin and T-cell receptor rearrangement, together with copies of EBV genome in some cases has been detected (3).

The long-term prognosis of systemic Castleman's disease is poor. The disease tends to persist for years and in some cases, may be associated with simultaneous or subsequent lymphomas, plasmacytomas and vascular neoplasms including Kaposi's sarcoma (4). Also, Hodgkin's disease may be accompanied or preceded by lymph node changes that greatly resemble those of Castleman's disease of either type (5, 6).

In summary, we have presented the case of a 17 year-old female with a 2cm. left upper neck mass, which microscopically demonstrated to be composed of numerous regressively transformed follicles separated by an admixture of predominantly small lymphocytes, few scattered plasma cells, eosinophiles and multiple proliferating blood vessels with hyalinized walls. These features indicated the hyaline-vascular variant of angiofollicular hyperplasia. Further, whole body PET CT scans, performed in our case, confirmed the localized aspect of this proliferation.


  1. Cathomas G. Human herpes virus 8: a new virus discloses its face, Virchows Arch. 2000 Mar; 436(3): 195-206.
  2. Hall PA et. all An immunohistological and genotypic study of the plasma cell form of Castleman's disease. Histopathology 1989 Apr; 14 (4): 333-46.
  3. Hanson CA et. all. Clonal rearrangement for immunoglobulin and T-cell receptor genes in systemic Castleman's disease. Association with Epstein-Barr virus. Am J Pathol. 1988 Apr;131(1): 84-91.
  4. Oksenhendler E, et all: High incidence of Kaposi sarcoma-associated herpesvirus-related non-Hodgkin lymphoma in patients with HIV infection and multicentric Castleman disease. Blood. 2002 Apr 1; 99(7): 2331-6.
  5. Caussinus E. et all: Simultaneous occurrence of Epstein-Barr virus associated Hodgkin's disease and HHV-8 related multicentric Castleman's disease: a fortuitous event? J Clin Pathol. 2001 Oct; 54 (10): 790-1.
  6. Molinie V et all: Association of Castleman's disease and Hodgkin's disease. Eight cases and review of the literature. Ann Pathol. 1994; 14(6): 384-91. Review.

Contributed by Laurentia Nodit, MD and Fiona Craig, MD

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