Clinical and pathological characteristics of HIV- and HHV-8-negative Castleman disease

Castleman disease (CD) comprises 3 poorly understood lymphoproliferative variants sharing several common histopathological features. Unicentric CD (UCD) is localized to a single region of lymph nodes. Multicentric CD (MCD) manifests with systemic inflammatory symptoms and organ dysfunction due to cytokine dysregulation and involves multiple lymph node regions. Human herpesvirus 8 (HHV-8) causes MCD (HHV8-associated MCD) in immunocompromised individuals, such as HIV-infected patients. However, > 50% of MCD cases are HIV and HHV-8 negative (defined as idiopathic [iMCD]). The clinical and biological behavior of CD remains poorly elucidated. Here, we analyzed the clinicopathologic features of 74 patients (43 with UCD and 31 with iMCD) and therapeutic responseof 96 patients (43 with UC Dand 53 with iMCD) with HIV-/HHV-8-negative CD compared with 51 HIV-/HHV-8-positive patients. Systemic inflammatory symptoms and elevated inflammatory factors were more common in iMCD patients than UCD patients. Abnormal bone marrow features were more frequent in iMCD (77.0%) than UCD (45%); the most frequent was plasmacytosis, which was seen in 3% to 30.4% of marrow cells. In the lymph nodes, higher numbers of CD3(+) lymphocytes (median, 58.88 +/- 20.57) and lower frequency of CD19(+)/CD5(+) (median, 5.8866.52) were observed in iMCD patients compared with UCD patients (median CD3(+) cells, 43.19 +/- 17.37; median CD19(+)/CD5(+) cells, 17.37 +/- 15.80). Complete surgical resection is a better option for patients with UCD. Siltuximab had a greater proportion of complete responses and longer progressionfree survival (PFS) for iMCD than rituximab. Centricity, histopathological type, and anemia significantly impacted PFS. This study reveals that CD represents a heterogeneous group of diseases with differential immunophenotypic profiling and treatment response.National Institutes of Health National Cancer Institute [R01CA138688, R01CA187415, 1RC1CA146299]; Intramural Research Program of the National Institutes of Health National Cancer Institute; Hematology/Oncology Scholarship Award; University of Texas MD Anderson Cancer Center Institutional Research Grant Award; Anderson Lymphoma Specialized Programs of Research Excellence (SPORE) Research Development Program Award; Anderson Myeloma SPORE Research Developmental Program Award; University Cancer Foundation via the Sister Institution Network Fund at The University of Texas MD Anderson Cancer Center; National Institutes of Health, National Cancer Institute [P50CA136411, P50CA142509]; National Institutes of Health, Anderson Cancer Center [CA016672]SCI(E)ARTICLE121658-166812