Case 6 -

Castleman's Disease, Hyaline-Vascular Type (HVCD) Judith Ferry Massachusetts General Hospital Boston, MA

Case History: 28-year-old woman with abdominal pain, found to have retroperitoneal lymphadenopathy. FNA showed a monotonous population of small lymphocytes. Laparotomy was performed and an enlarged lymph node was excised. Flow cytometry showed polytypic B cells and T cells with a normal CD4:CD8 ratio. Immunohistochemistry showed B cells confined to follicles and many interfollicular T cells. Case 6 - Slide 1 Click to view with ImageScope Click to view with a Web-Based Viewer Diagnosis: Castleman's disease, hyaline-vascular type (HVCD). Discussion HVCD can affect patients of any age, but most are young adults. Females may be slightly more often affected than males. Patients present with lymphadenopathy in a single site in nearly all cases; in the remainder, the lesion involves an extranodal site. Rarely, more than one site is involved. The mediastinum is most commonly affected, followed by nodes in the neck, abdomen and other sites. Systemic symptoms are usually absent. HVCD almost never recurs after excision. The etiology is uncertain, but is most likely related to abnormal follicular dendritic cells [1]. Pathologic features: HVCD is characterized by lymphoid follicles with small, hyalinized germinal centers and broad mantle zones. Each follicle may contain one or more than one germinal center; some contain no recognizable germinal center. The germinal centers contain an increased proportion of follicular dendritic cells (FDCs) and endothelial cells, and relatively few B cells. Mantle zone lymphocytes are arranged in concentric rings ("onion skin" pattern) around the germinal center. Large, bizarre, dystrophic cells with scant cytoplasm, thought to be abnormal FDCs, may be found in the follicles. Follicles are often radially penetrated by a blood vessel ("lollipop follicle"). The interfollicular region shows increased numbers of blood vessels with hyalinized walls and sometimes clusters of plasmacytoid monocytes. Plasma cells may be present singly or in small clusters, but sheets of plasma cells are absent. Patent sinuses are typically absent. Fibrosis is common peripherally and also in bands running through the lesion [1, 2, 3]. Rarely, HVCD is complicated by the development of a follicular dendritic cell tumor or a vascular neoplasm that appear to be outgrowths of the abnormal FDCs or of the floridly proliferating blood vessels [4, 5]. Follicles contain B cells expressing polytypic immunoglobulin and FDCs (CD21+). T cells (CD3+, CD45RO+) are present in smaller than normal numbers in follicles and interfollicular area. Many interfollicular blood vessels are Factor 8+, CD34+, HECA-452+, MECA-79+, consistent with high endothelial venules. The interfollicular area also contains CD68+ plasmacytoid monocytes and S-100+ interdigitating reticulum cells. FDCs have aberrant expression of adhesion molecules and may show cytogenetic abnormalities [1]. The second principal type of Castleman's disease is plasma cell Castleman's disease (PCCD). In contrast to HVCD, nodes involved by PCCD contain interfollicular sheets of plasma cells and may have some follicles with an appearance of typical reactive follicles. Patients with PCCD may have unifocal or multicentric disease and they often have constitutional symptoms. Some patients are HIV+; some have a plasma cell neoplasm that may be associated with POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy and skin changes} and some have HHV-8 infection [2, 3, 6, 7]. References Cokelaere K, Debiec-Rychter M, De Wolf-Peeters C, Hagemeijer A, Sciot R. Hyaline-vascular Castleman's disease with HMGIC rearrangement in follicular dendritic cells. Molecular evidence of mesenchymal tumorigenesis. Am J Surg Pathol 2002;26:662-669. Castleman B, Iverson L, Menendez VP. Localized mediastinal lymph node hyperplasia resembling thymoma. Cancer 1956;9:822-830. Keller AR, Hochholzer L, Castleman B. Hyaline-vascular and plasma-cell types of giant lymph node hyperplasia of the mediastinum and other locations. Cancer 1972;29(3):670-683. Chan J, Tsang W, Ng C. Follicular dendritic cell tumor and vascular neoplasm complicating hyaline-vascular Castleman's disease. Am J Surg Pathol 1994;18:517-525. Gerald W, Kostianovsky M, Rosai J. Development of vascular neoplasia in Castleman's disease. Report of seven cases. Am J Surg Pathol 1990;14:603-614. Casper C. The aetiology and management of Castleman disease at 50 years: translating pathophysiology to patient care. British Journal of Haematology 2005;129(1):3-17. Dispenzieri A, Kyle R, Lacy M, Rajkumar S, Therneau T, Larson D, et al. POEMS syndrome: definitions and long-term outcome. Blood 2003;101:2496-2506.