Pearls and Pitfalls in Lymph Node Diagnosis
Case 6 -
Castleman's Disease, Hyaline-Vascular Type (HVCD)
Massachusetts General Hospital
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
Castleman's disease, hyaline-vascular type (HVCD).
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 .
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
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
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
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
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- 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.