Answer: Castleman’s disease

Histology: Architectural distortion of lymph node parenchyma is highlighted by a paracortical expansion that surrounds scattered lymphoid follicles. The paracortex is notable for a marked proliferation of capillaries and post-capillary venules as well as numerous mature plasma cells. Fewer lymphocytes are admixed with the plasma cells. The vascular endothelial cells are plump but bland in appearance; mitoses and nuclear atypia are not identified. The lymphoid follicles have small, atretic germinal centers surrounded by concentric layers of small, mature lymphocytes. Moreover, many of the germinal centers are penetrated by hyalinized vessels.

Discussion: Castleman’s disease was first described in 1954 and has since gained significant attention due to its association with HIV. Castleman’s disease can be separated into localized disease and multicentric disease. Localized disease typically presents in young adults with lymphoid masses in the mediastinum or localized lymphadenopathy, and an absence of systemic symptoms. In contrast, multicentric Castlemans’s disease presents with polylymphadenopathy
and multiorgan involvement and is associated with systemic features. Organ systems commonly involved include the bone marrow, liver, kidney, skin and peripheral nervous system. A small proportion of patients exhibit the clinical manifestations of POEMS syndrome, which includes Polyneuropathy, Organomegaly, Endocrinopathy, M protein and Skin changes. Multicentric disease usually presents in the 5th to 6th decade, and is clinically more aggressive. While it is less common than localized disease, multicentric disease has increased incidence in the HIV+ population.

The histology of Castleman’s disease is also divided into two groups. The hyaline-vascular type is characterized by numerous small lymphoid follicles with concentrically arranged mantle zones and
lymphocyte-depleted germinal centers that are penetrated by hyalinized vessels. Furthermore, the interfollicular regions may or may not show a benign proliferation of high-endothelial vessels. The histology of the plasma cell variant is similarly remarkable for a benign vascular proliferation as well as a florid plasmacytosis that expands the paracortex. The plasma cells may be monoclonal or polyclonal. The plasma cell variant can be observed in localized Castleman’s disease or more commonly in multicentric Castleman’s disease. In addition, many cases of multicentric disease, such as the current case, demonstrate hybrid histology that includes features of both the plasma cell and hyaline-vascular variants. In contrast, a pure hyaline-vascular type of Castleman’s disease almost always characterizes the localized form of disease.

Multicentric Castleman’s disease is associated with a human herpesvirus 8 (HHV8) infection. HHV8, which is otherwise known as Kaposi sarcoma virus, encodes a homologue of interleukin 6 (vIL6) that likely mediates systemic manifestations. The diagnosis of Castleman’s disease is established by
biopsy, and treatment ranges from surgical debulking of localized disease to anti-viral therapy and chemotherapy for systemic disease. More recently, monoclonal antibodies specific for IL6 and CD20 have been employed to ameliorate symptoms and reduce disease burden.