Clinical and Morphological Features of Different Variants Castleman's Disease
Authors: Melikyan Anait L. , Egorova Elena K. , Kovrigina Alla M. , Subortseva Irina N. , Gilyazitdinova Elena A. , Gemdzhian Eduard G. , Savchenko Valeri 
Published: October 2019

Abstract
Background: Castleman' s disease (CD) is rare lymphoproliferative disorder with long asymptomatic current and high risk of transformation in malignant lymphoma. For last years, diagnostics of CD improved and uniform classification of an illness was accepted. Depending on morphological features allocate 3 variant of CD: hyaline-vascular (HVV), plasma cell (PCV) and mixed cell. Most cases of the ÑD involve a single or localized group of lymph nodes and can be asymptomatic. In these cases the histologic picture can be characterized as a HVV or mixed cell and PCV morphology. Less often the disease proceeds with multiple lymphoid regions (multicentric CD, MCD) and is usually accompanied by various systemic inflammatory symptoms (fever, weight loss and night sweats). In these cases histologic picture in the involved lymph nodes meet mix cell or PCV of CD. The role of a human herpes virus-8 (HHV-8) in pathogenesis of MCD is studied. It is known that HHV-8 codes in a genome of a cell of the person some regulatory proteins and cytokines, first of all a virus homolog interleukin-6 which stimulates development of human IL-6 and endothelial factor of growth that conducts to a neoangiogenesis in not tumoral lymph nodes. HHV-8-positive MCD allocate separately in due to its extremely aggressive course and a high risk of transformation into HHV-8-positive plasmablastic lymphoma.
Aim: Explore the features of a clinical current and of therapeutic approaches at different variants CD.
Patients and Methods: In Center for Hematology since 1996 to the present time observed clinical and morphological features of 76 pts with CD. Clinical data were obtained during the retrospective analysis of 17 outpatient clinical records and prospective supervision over 59 pts. The diagnosis was established from results of histological and immunohistochemical examinations of removed lymph nodes in all cases. Frequency analyses were performed using z-tests with SAS 9.1 software.
Results: HVV with local lymph nodes involvement was diagnosed in 38 (50%) pts. The average age of pts was 40 years The PCV was also observed in 38 (50%) cases, among them in 17 (22%) pts were found to have local involvement and 21 (28%) had multicentric involvement. Five (24%) pts with MCD were established to be infected with human herpesvirus type 8. Male (37 pts) and female (39 pts) are suffering with an identical frequency. However, HVV is more often diagnosed for female, than at male (71% to 29% respectively), PCV equally often meets both at male, and at female (47% of male, 53% of female) and, at last, at MCD the share of male statistically significantly is more than share of female (86% against 14%, p=0,05) (Figure 1). The basic involvement areas in local HVV and PCV were peripheral (38%), mediastinal (29%), retroperitoneal (18%) abdominal (9%) and small pelvic (6%) lymph nodes (95% CI). Local HVV and PCV proceed benign and in 94.5% of cases are cured by surgical removal of lymph nodes involved in the pathological process, in 5.5% of cases with inoperable cases require followed by radiation therapy. MCD was significantly more common in male, occurs aggressively with severe constitutional symptoms, generalized lymphadenopathy, hepatosplenomegaly, hypergammaglobulinemia, autoimmune hemolysis, thrombocytopenia, and involvement of extranodal foci in the pathological process. MCD transformation to plasmoblastic lymphoma was observed in 4 of 5 HHV8-positive pts and followed by a poor outcome. The prognosis of untreated MCD was unfavorable. In a number of cases prednisolone monotherapy worsened and the MCD pts receiving timely R-CHOP or R-VD chemotherapy could achieve sustained remission (the 5-year OS was 55%).
Conclusion: The prognosis of HVV and local PCV is favorable: the disease is surgically cured in 95% of cases. Chemotherapy according to the program of Non-Hodgkins Lymphomas indicated for the treatment of MCD: sustained remission can be achieved by the use of R-CHOP or R-VD programs. HHV8-positive MCD characterized by high risk disease transformation to incurable plasmablastic lymphoma. Overall, prognosis and therapy choice in HIV-negative pts with CD depend on the histological type of the disease, the extent of a tumor and HHV-8 infection.
Figure 1. Gender distribution for three variants of CD; there is male-female imbalance in HVV and MCD groups (z-test, ð<0.05); analysis based on initial diagnosis data. Figure 1. Gender distribution for three variants of CD; there is male-female imbalance in HVV and MCD groups (z-test, ð<0.05); analysis based on initial diagnosis data.

Disclosures
No relevant conflicts of interest to declare.