Residency Program - Case of the Month
October 2013 - Presented by Adam Stelling, M.D.
Castleman Disease, Unifocal, Hyaline-vascular type
Castleman disease is an uncommon benign lymphoproliferative disorder. It is currently classified into two distinct subtypes, unifocal and multifocal, which have important prognostic differences. In addition, two histopathologic variants are seen, hyaline-vascular and plasma cell types, which correlate well with clinical presentation.
The most common pattern encountered is the hyaline-vascular variant which comprises 80% of the unifocal form of Castleman disease. Often presenting as a solitary mediastinal mass, it can initially mimic Hodgkin lymphoma or thymoma although cases in locations throughout the body have also been reported. Aside from local mass effect, these masses are generally asymptomatic and surgical excision is curative. Microscopically, many dense regressed follicular germinal centers are seen surrounded by an expanded mantle zone with a layered appearance often referred to as “onion skinning” that may raise suspicion for mantle cell lymphoma. Hyalinized arterioles are seen penetrating the germinal centers to form a pattern known as a “lollipop” follicle. The peculiar appearance to these follicles is partly due to a marked hyperplasia of follicular dendritic cells which can be highlighted with CD21.
In contrast, lesions of the plasma cell type usually presents with more severe clinical features and most of the cases of multifocal disease are of this variant. Patients show features of systemic disease with fever, weight loss, fatigue, elevated ESR, polyclonal hypergammaglobulinemia, bone marrow plasmacytosis, hepatosplenomegaly, peripheral neuropathy, iron deficiency anemia, or autoimmune hemolytic anemia. Microscopically, the follicles contain large hyperplastic germinal centers with an attenuated mantle zone with concentric “onion skinning”. The perifollicular region is comprised of sheets of plasma cells which can contain scattered hyalinized collagen ensheathed blood vessels. The plasma cell subtype has associations with HIV and HHV-8 with virtually 100% of multifocal cases testing positive for HHV-8 in patients who are HIV positive. Kaposi sarcoma is seen concurrently in many cases. Other significant complications include progression into lymphoma, especially plasmablastic lymphoma, and POEMS syndrome which is thought to be linked with high levels of interleukin 6: the key cytokine responsible for plasma cell differentiation.
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