Castleman disease: an update on classification and the spectrum of associated lesions.

Department of Pathology, Stanford University School of Medicine, 300 Pasteur Drive, Stanford, CA 94304, USA.
Advances in anatomic pathology (Impact Factor: 3.1). 08/2009; 16(4):236-46. DOI: 10.1097/PAP.0b013e3181a9d4d3
Source: PubMed

ABSTRACT Since its initial description, researchers have expanded the spectrum of Castleman disease to include not only the classic and well-recognized hyaline-vascular type, but also the plasma cell type and multicentric types of broader histologic range, including human herpes virus-8-associated Castleman disease. These less common subtypes of Castleman disease are less familiar, and may be under-recognized. Also of practical importance, current authors are restructuring the classification of multicentric Castleman disease to accommodate the emerging pathogenic role of human herpes virus-8 and its association with the recently described plasmablastic variant. In addition to an increased risk of lymphoma, patients with Castleman disease also are at increased risk for other related neoplasms, including Kaposi sarcoma and follicular dendritic cell tumors, which are of prognostic and therapeutic relevance. This review focuses on the histologic diagnosis of Castleman disease, current and emerging concepts in its pathogenesis and classification, and associated histopathologic entities.

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    ABSTRACT: Castleman disease (CD) is a rare benign lymphoproliferative disorder, the etiology of which is unclear. Clinically it may manifest as localized disease (unicentric) or disseminated disease (multicentric). CD occurs in the thorax in 70% of cases, abdomen and pelvis in 15%, and in the neck in 10-15% of cases. We present a case of a pleural mass located posteriorly in a paraspinal location, which was discovered incidentally in a 50-year-old man and was subsequently resected followed by an unexpected diagnosis of Castleman disease on histological examination. In this report, we review the clinical and histological findings in a rare presentation of Castleman disease and discuss the findings in this case as part of an overall review of the typical radiological findings seen in Castleman disease.
    09/2013; 2013:130515. DOI:10.1155/2013/130515
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    ABSTRACT: Soon after the discovery of Kaposi sarcoma (KS)-associated herpesvirus (KSHV), it was appreciated that this virus was associated with most cases of multicentric Castleman disease (MCD) arising in patients infected with human immunodeficiency virus. It has subsequently been recognized that KSHV-MCD is a distinct entity from other forms of MCD. Like MCD that is unrelated to KSHV, the clinical presentation of KSHV-MCD is dominated by systemic inflammatory symptoms including fevers, cachexia, and laboratory abnormalities including cytopenias, hypoalbuminemia, hyponatremia, and elevated C-reactive protein. Pathologically KSHV-MCD is characterized by polyclonal, IgM-lambda restricted plasmacytoid cells in the intrafollicular areas of affected lymph nodes. A portion of these cells are infected with KSHV and a sizable subset of these cells express KSHV lytic genes including a viral homolog of interleukin-6 (vIL-6). Patients with KSHV-MCD generally have elevated KSHV viral loads in their peripheral blood. Production of vIL-6 and induction of human (h) IL-6 both contribute to symptoms, perhaps in combination with overproduction of IL-10 and other cytokines. Until recently, the prognosis of patients with KSHV-MCD was poor. Recent therapeutic advances targeting KSHV-infected B cells with the anti-CD20 monoclonal antibody rituximab and utilizing KSHV enzymes to target KSHV-infected cells have substantially improved patient outcomes. Recently another KSHV-associated condition, the KSHV inflammatory cytokine syndrome (KICS) has been described. Its clinical manifestations resemble those of KSHV-MCD but lymphadenopathy is not prominent and the pathologic nodal changes of KSHV-MCD are absent. Patients with KICS exhibit elevated KSHV viral loads and elevation of vIL-6, homolog of human interleukin-6 and IL-10 comparable to those seen in KSHV-MCD; the cellular origin of these is a matter of investigation. KICS may contribute to the inflammatory symptoms seen in some patients with severe KS or primary effusion lymphoma. Additional research is needed to better define the clinical spectrum of KICS and its relationship to KSHV-MCD. In additional, research is needed to better understand the pathogenesis and epidemiology of both KICS and KSHV-MCD, as well as the optimal therapy for both of these disorders.
    Frontiers in Microbiology 01/2012; 3:73. DOI:10.3389/fmicb.2012.00073 · 3.94 Impact Factor
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    ABSTRACT: We report three cases of follicular dendritic cell sarcoma (FDCS) showing a hitherto undescribed histological pattern consisting of nodular tumor growth associated with small B lymphocytes. FDCS tumor cells consistently showed large epithelioid features and were intermingled with small lymphocytes in the nodules in two cases, whereas they formed cohesive aggregates surrounded by lymphocyte mantle in the other. These features were easily confused with lymphomatous proliferations and, in particular, subtypes of Hodgkin lymphoma, high-grade follicular lymphoma, and germinotropic large B-cell lymphomas. The diagnosis was established by the use of a broad panel of antibodies that showed a variable expression of the FDC markers CD21, CD23, CD35, clusterin, podoplanin, claudin 4, epidermal growth factor receptor, and CXCL13. The associated B lymphocytes revealed a mantle zone B phenotype, with expression of CD20 and PAX5, together with TCL1 and IgD. Of notice, in all cases, morphological features suggesting hyaline-vascular Castleman disease were recognized in the interfollicular areas, containing scattered epithelioid cells similar to those found in the nodules, thus providing a useful clue for FDCS diagnosis. Of the 3 cases, 1 presented multiple recurrences unresponsive to chemotherapy and radiotherapy and finally died of disease 14 years after diagnosis. This study further emphasizes the extreme variability of morphological presentation of FDCS and expands the spectrum of lesions showing a nodular growth pattern occurring in human lymph nodes.
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