Castleman disease (CD) is a rare lymphoproliferative disorder of unknown etiology with different clinical manifestations. A previous healthy 50 year-old man was hospitalized for right upper quadrant (RUQ) abdominal pain. He had jaundice and a 1 cm-sized lymph node in the right supraclavicular area. Pancreas and biliary computed tomography (CT) showed masses at the right renal hilum and peripancreatic areas. Positron emission tomography (PET) showed widespread systemic lymphadenopathy. Excisional biopsy of the right supraclavicular node revealed a hyaline vascular variant of CD. Corticosteroid therapy was started and the extent of disease decreased. We here report a case of multicentric CD, the hyaline vascular variant, presenting with jaundice, diagnosed by excisional biopsy and successfully treated with corticosteroids.
Abdominal Pain/etiology ; Adrenal Cortex Hormones/therapeutic use ; Biopsy ; Giant Lymph Node Hyperplasia/*diagnosis/drug therapy/pathology ; Humans ; Jaundice/*complications ; Male ; Middle Aged ; Positron-Emission Tomography ; Tomography, X-Ray Computed ; Vascular Diseases/*diagnosis/pathology

BACKGROUND: Kaposi's sarcoma-associated herpesvirus (KSHV) been shown to be associated with human diseases including Kaposi's sarcoma, pleural effusion lymphoma, multicentric Castleman's disease. The IL-6 may both stimulate myeloma growth and prevent apoptosis of malignant plasma cells. Interestingly, viral IL-6(vIL-6), homolog to human interleukin-6(IL-6) in KSHV genome retains biologic activity. Thus, oncogenic role of the KSHV has been proposed as a pathogenesis of the multiple myeloma. We used ISH to determine the frequency of patients with multiple myeloma and plasmacytosis associated with KSHV-infected BM cells in fresh core biopsies and to determine the correlation between KSHV infection and clinical characteristics. METHODS: Bone marrow(BM) biopsy samples from 16 cases of multiple myeloma, 2 cases of monoclonal gammopathy of undetermined significance(MGUS) were obtained from the pathology division of Soon Chun Hyang University Hospital, Seoul, Korea. Biopsy sample of Kaposi's sarcoma for positive control and BM biopsy samples of myelodysplastic syndrome(MDS) and malignant lymphoma for negative control were obtained. Bitinylated probe to KSHV were prepared with the following sequences: 5' to 3' TGCAGCAGCTGTTGGTGTACCACATATCT. and in situ hybridization (ISH) was performed. RESULTS: Among the 18 patients. Two patients were MGUS and among 16 patients with multiple myeloma, 1 in stage IB disease, 1 stage IIB disease, 8 stage IIIA disease, 4 stage IIIB diseases and 2 in variant of multiple myeloma, extramedullary plasmacytoma. Strong positive signal was detected in nuclei and cytoplasm of the malignant cells of biopsy sample from 1 cases of Kaposi's sarcoma by ISH(positive control). Signal was not detected in BM biopsy samples of 7 cases from MDS and malignant lymphoma(negative control). Among 16 patients with multiple myeloma, 15 demonstrated viral positive cells and 2 cases with MGUS also showed viral positive cells by ISH. Signal was detected in nuclei and cytoplasm of stromal cells. Signal was strongly detected in MGUS than multiple myeloma. Positivity of the KSHV was not related with stage of the patients with multiple myeloma. One patients with multiple myeloma was studied at diagnosis and after chemotherapy. After chemotherapy KSHV was not detected. CONCLUSION: In MGUS and multiple myeloma, KSHV infects the stromal cells of BM rather than malignant plasma cells. On the basis of these data, we have supposed KSHV to play a role in transformation from MGUS to multiple myeloma. Particularly, due to the fact that signal of ISH was strongly detected in MGUS and was not detected in one case with multiple myeloma, it was presumed that KSHV was not major role in already advanced multiple myeloma but statistic significance was not demonstrated because of small numbers of cases. Further studies to reveal the correlation of KSHV and pathogenesis of multiple myeloma are needed.
Apoptosis ; Biopsy ; Cytoplasm ; Diagnosis ; Drug Therapy ; Genome ; Giant Lymph Node Hyperplasia ; Herpesvirus 8, Human ; Humans ; In Situ Hybridization ; Interleukin-6 ; Korea ; Lymphoma ; Multiple Myeloma* ; Paraproteinemias ; Pathology ; Plasma Cells ; Plasmacytoma ; Pleural Effusion ; Sarcoma, Kaposi ; Seoul ; Stromal Cells

This report presents the case of a patient demonstrating multicentric Castleman's disease (MCD) with a lung lesion that was successfully treated with an anti-interleukin-6 receptor antibody, tocilizumab in combination with corticosteroid and tacrolimus. A 43-yr-old female with abnormal shadows on a chest X-ray was referred to the hospital for further examination. She was diagnosed as having MCD based on the characteristic pathology of inguinal lymph node, lung lesions, laboratory data, and undifferentiated arthritis. Corticosteroid and rituximab therapy did not fully ameliorate the symptoms; thus, the therapeutic regimen was changed to include tocilizumab, oral corticosteroid and tacrolimus. This regimen resulted in clinical remission and the dose of tocilizumab and corticosteroid could be tapered. Tocilizumab in combination with corticosteroid and tacrolimus may therefore be a beneficial treatment regimen for lung lesions associated with MCD.
Adrenal Cortex Hormones/therapeutic use ; Adult ; Antibodies, Monoclonal/*therapeutic use ; Drug Therapy, Combination ; Female ; Giant Lymph Node Hyperplasia/*diagnosis/drug therapy/radiography ; Humans ; Immunosuppressive Agents/therapeutic use ; Lung Diseases, Interstitial/*drug therapy/pathology ; Lymph Nodes/pathology ; Receptors, Interleukin-6/antagonists & inhibitors ; Tacrolimus/therapeutic use ; Tomography, X-Ray Computed