title: Clinical and pathological characteristics of HIV- and HHV-8-negative Castleman disease.
abstract: 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 (HHV-8-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 response of 96 patients (43 with UCD and 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, 5.88 ± 6.52) 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 progression-free 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.
authors.affiliation: Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX.|Department of Hematology, The Second Affiliate Hospital of Nanchang University, Nanchang, China.
authors.forename: Li
authors.initials: L
authors.lastname: Yu
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Lymphoma, Peking University Cancer Hospital and Institute, Peking, China.
authors.forename: Meifeng
authors.initials: M
authors.lastname: Tu
authors.affiliation: Department of Leukemia and.
authors.forename: Jorge
authors.initials: J
authors.lastname: Cortes
authors.affiliation: Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX.
authors.forename: Zijun Y
authors.initials: ZY
authors.lastname: Xu-Monette
authors.affiliation: Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX.
authors.forename: Roberto N
authors.initials: RN
authors.lastname: Miranda
authors.affiliation: Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Lymphoma/Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX.
authors.forename: Robert Z
authors.initials: RZ
authors.lastname: Orlowski
authors.affiliation: Department of Lymphoma/Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX.
authors.forename: Sattva
authors.initials: S
authors.lastname: Neelapu
authors.affiliation: Department of Leukemia and.
authors.forename: Prajwal C
authors.initials: PC
authors.lastname: Boddu
authors.affiliation: Department of Leukemia and.
authors.forename: Mary A
authors.initials: MA
authors.lastname: Akosile
authors.affiliation: HIV and AIDS Malignancy Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD.
authors.forename: Thomas S
authors.initials: TS
authors.lastname: Uldrick
authors.affiliation: HIV and AIDS Malignancy Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD.
authors.forename: Robert
authors.initials: R
authors.lastname: Yarchoan
authors.affiliation: Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX.
authors.forename: L Jeffrey
authors.initials: LJ
authors.lastname: Medeiros
authors.affiliation: Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH.
authors.forename: Yong
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA; and.
authors.forename: David C
authors.initials: DC
authors.lastname: Fajgenbaum
authors.affiliation: Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX.|Graduate School of Biomedical Sciences, The University of Texas Health Science Center, Houston, TX.
authors.forename: Ken H
authors.initials: KH
authors.lastname: Young
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D005871:Castleman Disease / Q000473:pathology / Q000628:therapy* / Q000821:virology; D018572:Disease-Free Survival; D005260:Female; D015497:HIV-1; D019288:Herpesvirus 8, Human; D006801:Humans; D016130:Immunophenotyping; D007249:Inflammation; D008297:Male; D008875:Middle Aged; D055815:Young Adult
chemical_list: D000911:Antibodies, Monoclonal; C504234:siltuximab