A systemic lymphoproliferative disorder with morphologic features of Castleman's disease. Pathological findings in 15 patients.
ABSTRACT This report describes the nodal and extranodal lesions observed in 15 patients with a generalized disorder that had been histologically diagnosed as Castleman's disease. The disorder was characterized by severe constitutional symptoms, constant involvement of multiple peripheral lymph nodes, and frequent hepatosplenomegaly, in association with clinical and laboratory features reminiscent of a "collagen disease." The clinical course was chronic, with remissions and exacerbations in seven patients, and aggressive and fatal in eight. The material examined included multiple lymph node biopsies, four surgical specimens of spleen, one open lung biopsy, and material from four autopsies. The diagnostic morphological findings were observed in the nodes and were represented by the following histologic triad: diffuse marked plasmacytosis, from the medulla to the subcapsular areas; prominence of the germinal centers; and good preservation of the architecture. One variant of this basic pattern featured abundant immunoblasts and blood vessels. The process appears to be a systemic reactive proliferation of B-lymphocytes, perhaps resulting from faulty immune regulation. Morphologic similarities indicate a relationship between this multicentric disorder and Castleman's disease of plasmacellular type. However, there are distinct differences between them in clinical presentation and evolution, and, consequently, in therapeutic approach.
SourceAvailable from: Pedro L. Del Valle[Show abstract] [Hide abstract]
ABSTRACT: On April 22, 2014, the FDA granted full approval to siltuximab (SYLVANT for Injection, Janssen Biotech, Inc.), a chimeric human-mouse monoclonal antibody to interleukin-6, for the treatment of patients with multicentric Castleman disease (MCD) who are human immunodeficiency virus (HIV) negative and human herpesvirus-8 (HHV-8) negative. The approval was primarily based on the results of a randomized, double-blind trial in which 79 symptomatic patients with MCD were allocated (2:1) to siltuximab plus best supportive care (BSC) or to placebo plus BSC. The primary efficacy endpoint was the proportion of patients in each arm achieving a durable tumor and symptomatic response that persisted for a minimum of 18 weeks without treatment failure. Tumor response was based on independent review of CT scans using the revised response criteria for malignant lymphoma, and symptomatic response was defined as complete resolution or stabilization of 34 MCD-related signs and symptoms as reported by the investigator. Thirty-four percent of patients in the siltuximab arm and no patients in the placebo arm met the primary endpoint (p=0.0012). The most common adverse reactions (>10% compared to placebo) during treatment with siltuximab were pruritus, increased weight, rash, hyperuricemia, and upper respiratory tract infection. Copyright © 2015, American Association for Cancer Research.