Castleman Disease: A Clinicopathological And Immunophenotypic Study Of 52 Chinese Cases And Its Relationship With Human Herper Virus 8 Infection

[Backglound and Objective] Castleman's disease (CD) is a rare lymphoproliferative disorder which is also called angiofollicular lymph node hyperplasia or giant lymph node hyperplasia. CD is difficult to be diagnosed due to its unknown etiology, complicated clinical symptoms and various pathological features. Therefore, CD is attended by more and more researches with an increasing number of reports of CD cases recently. In China, there were few clinicopathological and immunohistochemical studies of CD, and no information about its relationship with human herpes virus 8 (HHV-8). So the aim of this study is to investigate the clinicopathological features, immunophenotypes of 52 cases of CD in west China and its relationship with HHV-8 infection.[Matelials and Methods] 52 cases of CD from 1975 to 2005 in the surgical pathologic files of West China Hospital were collected and all their histological features, clinical data and follow-up information were analyzed. From them, 37 cases with enough paraffin embedded tissues were selected for immunohistochemical staining using a panel of antibodies (CD21, CD3, CD79a, κ, λ and a mouse monoclonal antibody directed against the C-terminus of the latent nuclear antigen-1 molecule of HHV-8 (clone 13B10; Novocastra).[Results] Histopathologically, there were 37 cases of hyaline vascular type (HV), 13 cases of plasma cell type (PC) and 2 cases of mixed type. The histopathological features of HV included prominent proliferation of follicles, onionskin-like germinal centers surrounded by circumferentially arranged layers of small lymphocytes in mantle zone with capillaries penetrating, striking proliferation of capillaries in interfollicular zone and disappearance of lymph sinus. The morphological features of 13 cases of PC were proliferation of follicles, expanded interfollicular zone with prominent accumulation of mature plasma cells and less proliferation of capillaries. Immunohistochemically, all 37 stained cases showed polyclonal patterns of light chain expression in interfollicular lymphocytes and plasma cells by k and X staining, hi 12 cases of PC type, polyclonal lymphocytes and plasma cells predominated in interfollicular zone and formed broad sheets while the polyclonal plasma cells sprinkled in interfollicular zone in 23 HV type, hi all 37 stained cases, CD79a positive cells were observed in mantle zone, CD3 positive cells were mainly distributed in interfollicular zone, and germinal centers turned to be "burned out" patterns containing proliferated CD21 positive follicular dentritic cells with vesicle-like nuclei and occasional germinal center cells. No positive expression of HHV-8 was observed in all 37 stained cases. Clinically, there were 36 cases of local type (LCD) and 16 cases of multicentric (MCD) type. The age of the 36 patients with LCD ranged from 1 to 73 and averaged 32.8 years. The ratio of men to women was 0.7:1. The enlarged lymph nodes were usually found in neck and mediastinum. 33 patients of LCD type were asymptomatic and all of them cured by surgical resections. 1 patient with cough due to the press of mediastinum mass was cured after surgical resection. And systemic symptoms disappeared after resection in 2 other cases. The age of thel6 patients with MCD ranged from 13 to 74 and averaged 41.2 years. The ratioof men to women was 1.3:1. The masses usually involved both deep and peripheral lymph nodes. ALL 16 patients with MCD were symptomatic with abnormal examining results. 14 MCD patients accepted systemic therapy (12 showed partial remission and 2 were not improved). Another 2 patients accepted surgical operation (1 showed partial remission and 1 was no improved. Patients with MCD showed 72.9% 1-year survival rate, 50.75 months median survival time and poorer prognosis than those with LCD. The survival curves of patients with MCD or LCD showed significant difference (p=0.0174). Impairment of terminal nerves in the patients with MCD might have bad effect on prognosis.[Conclusion] The histopathological changes of CD must distinguish from other malignant and benign lymphoid disorders, such as mantle cell lymphoma, plasmacytoma, follicular lymphoma, Hodgkin's lymphoma and various reactive lymphoid hyperplasia. Immunohistochemical technique, especially iromunoglobulin light chain staining is a useful method to distinguish CD from other diseases and two pathological subtypes from each other. The clinical symptoms of CD are complicated and unspecific so the swelling lymph node biopsy is needed. Two clinical subtypes have different clinical symptoms, treatments and prognosis. LCD is a benign disease and surgical therapy can cure it, while MCD appears to be more aggressive and systemic therapy can help to alleviate symptoms. Therefore, distinguishing from two clinical subtypes of CD are important and helpful. HHV-8 infection does not associate with CD in west China and further study is needed.