Clinicopathological features and possible pathogenesis of Castleman disease / 中国肿瘤临床

Castleman disease (CD) refers to a group of uncommon lymph node proliferative disorders that have highly clinically heterogeneous and obvious pathological features. The etiology and pathogenesis of CD remain unclear. The pathogenesis of unicentric CD (UCD) is most likely driven by clonal proliferation and acquired mutations of tumor stromal cells. Idiopathic multicentric CD (iMCD) intersects with a variety of diseases in terms of its clinical manifestation and pathological features including autoimmune factors, paraneoplastic syndrome, viral infectious factors and inflammatory factor disorders. The pathogenesis of iMCD is probably the common pathway of immune dysregulation and cytokine increase caused by the combined action of multiple etiologies. Here, we aim to summarize the latest reported etiology and pathogenesis of CD, aiming to deepen the understanding of this disease.

Advance in diagnosis and treatment of idiopathic multicentric Castleman disease / 中国肿瘤临床

Castleman disease (CD) is a rare lymphoproliferative disease that is clinically classified into unicentric Castleman disease (UCD) and multicentric Castleman disease (MCD). According to the status of human herpes virus-8 (HHV-8) infection, MCD is further classified into HHV-8-positive MCD, and HHV-8-negative MCD, which is also called idiopathic multicentric Castleman disease (iMCD). There are standard treatment options for both UCD and HHV-8-positive MCD, but there has been no uniform standard of diagnosis and treatment for iMCD, which mainly relied on the experience of clinicians. In recent years, Castleman Disease Collaborative Network (CDCN) has newly defined the concept and diagnostic criteria of iMCD, and a comprehensive guidance on the treatment of iMCD was established in November 2018. In this paper, we try to review the current treatment options and advances of iMCD, which might help Chinese clinicians to diagnose and treat this rare disease.

Treatment of multicentric castleman’s disease: Research advances / 国际药学研究杂志

Castleman’s disease (CD) is a rare lymphoproliferative disorder which comprises two distinct clinical subtypes: unicentric CD (UCD) and multicentric CD (MCD). Unlike UCD, which is a curable disease with surgical resection, MCD is a disease with systemic symptoms and high mortality rate (the 5-year mortality rate could be as high as 35%). There is no standard of care for MCD. Current treatment options include observation, glucocorticoids, chemotherapy (with or without rituximab) and immunomodulatory agents. Progress have been made during the recent years, interleukin-6 (IL-6) and human herpes virus 8 (HHV-8) have been recognized as key factors involved in the pathogenesis of MCD. Accordingly, drugs targeting these factors (especially IL-6) have been developed to treat MCD. In this paper, we try to review the current treatment options and new emerging therapies for MCD which might help Chinese clinicians to learn more about this rare disease.

General anesthesia in a patient with multicentric Castleman's disease: a case report / 대한마취과학회지

Castleman's disease (CD) is a rare lymphoproliferative disorder of undetermined etiology. Unicentric Castleman's disease is confined to a single lymph node; it is usually asymptomatic though sometimes has local manifestations related to mass effects. In contrast, multicentric Castleman's disease (MCD) typically presents with lymphoid hyperplasia at multiple sites; it is associated with systemic symptoms and abnormal laboratory findings, with a less favorable prognosis. In case of anesthesia in CD, an exhaustive preanesthetic evaluation is essential to identify associated clinical manifestations which may influence the management of the anesthesia. Perioperative careful monitoring and proper anesthetic management are both important. We report a case of general anesthesia with anesthetic management in a patient with MCD that has not been documented in the literature.

Clinical features and outcomes in patients with human immunodeficiency virus-negative, multicentric Castleman's disease: a single medical center experience

BACKGROUND: Multicentric Castleman's disease (CD) is commonly associated with poor prognosis, and well-known prognostic factors are scarce. We performed a retrospective analysis to define the clinical features and prognostic factors for patients with multicentric CD. METHODS: Between 1990 and 2013, 32 patients with multicentric CD were identified from the database of the Asan Medical Center, Seoul, Korea. Clinicopathologic data were collected by reviewing the medical records. With the exclusion of 4 patients because of unknown human immunodeficiency virus infection status, 28 human immunodeficiency virus-negative patients with multicentric CD were included in this analysis. RESULTS: Most of the patients were male (76%) and had a median age of 54 years. Hyaline vascular variant was the most common subtype (N=11, 39%). Hepatosplenomegaly (61%), fever (39%), edema (29%), and ascites (18%) were the most frequently reported symptoms and signs at diagnosis. With a median follow-up of 67 months, the 5-year overall survival (OS) was 77%. Patients with extravascular fluid accumulation (i.e., peripheral edema, ascites, and/or pleural effusions) were significantly associated with a poor survival rate (5-year OS, 94% vs. 56%; P=0.04). The extent of disease involvement was also a significant prognostic factor (5-year OS, 91% for involvement on a single side vs. 73% on both sides of the diaphragm; P=0.03). Other clinicopathologic factors were not significantly associated with patient survival. CONCLUSION: Our findings suggest that the hyaline vascular variant is not a rare subtype of multicentric CD. Extravascular fluid accumulation and disseminated disease involvement seem to be significant prognostic factors.

Castleman disease

Castleman and Towne described a disease presenting as a mediastinal mass resembling thymoma. It is also known as "giant lymph node hyperplasia", "lymph node hamartoma", "angiofollicular mediastinal lymph node hyperplasia", and "angiomatous lymphoid hyperplasia". The pathogenesis is unknown, but the bulk of evidence points toward faulty immune regulation, resulting in excessive B-lymphocyte and plasma-cell proliferation in lymphatic tissue. In addition to the mediastinal presentation, extrathoracic involvement in the neck, axilla, mesentery, pelvis, pancreas, adrenal gland, and retroperitoneum also have been described. There are 2 major pathologic variations of Castleman disease: (1) hyaline-vascular variant, the most frequent, characterized by small hyaline-vascular follicles and capillary proliferation; and (2) the plasma-cell variant, in which large lymphoid follicles are separated by sheets of plasma cells. The hyaline-vascular cases usually are largely asymptomatic, whereas the less common plasma-cell variant may present with fever, anemia, weight loss, and night sweats, along with polyclonal hypergamma-globulinemia. Castleman disease is a rare lymphoproliferative disorders. Few cases have been described world widely. In this article we reviewed the classification, pathogenesis, pathology, radiological features and up to date treatment with special emphasis on the role of viral stimulation, recent therapeutic modalities and the HIV-associated disease.

Case report of six multicentric Castleman's disease and related literature review / 中国综合临床

Objective To retrospectively analyze the diagnosis and treatment of multicentric Castleman's disease (MCD) ,and review related literatures. Methods A total of six patients were first-ever diagnosed as MCD and treated with combination chemotherapy and/or interferon α. The clinical manifestation, laboratory findings and therapeutic strategies were recorded in detail. Results In the six HIV-negative patients, histologically, four of them were diagnosed with plasma cell type of Castleman's disease, two with mixed type. All the six patients showed multiple lymphadenopathy, polyclonal hypergammaglobulinemia and hypoalbuminemia. One of the two patients treated with interferon α achieved complete remission, and the other,who showed no effects with hormone and combination chemotherapy ,achieved sustained partial remission after treatment with interferon α for 3 months. Of the four patients treated with combination chemotherapy, three achieved partial remission, and one died of no effects. Conclusions Interferon α and combination chemotherapy might be the most effective and convenient therapeutic methods for MCD. Serum albumin level may be used as a diagnostic and monitoring index for MCD.

Complete Remission in a Patient with Human Herpes Virus-8 Negative Multicentric Castleman Disease Using CHOP Chemotherapy / Journal of the Korean Cancer Association, 대한암학회지

Multicentric Castleman disease (MCD) is a rare lymphoproliferative disorder. Although MCD pathogenesis is unclear, studies have suggested that human herpesvirus 8 (HHV-8) may be associated with the disorder. Recent reports have identified MCD cases without viral infection. A 43-year-old woman presented to our hospital for fever and myalgia of 6 months' duration. The complete blood count revealed an elevated leukocyte count (15.1x10(3)/microliter) and a decreased hemoglobin level of 10.0 g/dL. The C-reactive protein level was elevated at 276.5 mg/L. Thoracic computed tomography (CT) scans revealed bilateral axillary lymphadenopathy. There was no evidence of HHV-8, human immunodeficiency virus (HIV), or Mycobacterium infection. Histologic evaluation of a lymph node biopsy from the left axilla yielded a diagnosis of MCD. Cyclophosphamide, adriamycin, vincristine, and prednisone (CHOP) were administered for a total of 4 cycles. The patient's fever and lymphadenopathy resolved after the course of chemotherapy. She has been in complete remission for 24 months at this writing. As previously reported, this case report suggests that MCD can develop without viral infection. CHOP chemotherapy may be an effective treatment option for newly diagnosed MCD patients.

A Case of Multicentric Castleman's Disease Diagnosed with Lymph Node Biopsy and Bone Marrow Examination

Castleman's disease (CD) is an uncommon lymphoproliferative disorder presenting with a variable spectrum of clinical manifestations. CD is classified into two subtypes, Localized CD and Multicentric CD, by clinical manifestation, and is divided into 2 histopathologic types: a hyaline-vascular type (HV) or a plasma-cell type (PC). Multicentric CD show PC type predominantly and show systemic symptoms, such as fever, night sweat, malaise, ascites, edema, and more than half show multiple lymphadenopathy and hepatosplenomegaly. We report a case of 67 year old man with multicentric CD presented with fever of unknown origin and diagnosed with lymph node biopsy and bone marrow examination with a brief review of the literature.

Prevention and Treatment of KSHV-associated Diseases with Antiviral Drugs / 中国病毒学·英文版

s Kaposi's sarcoma-associated herpesvirus (KSHV) was first identified as the etiologic agent of Kaposi's sarcoma (KS) in 1994.KSHV infection is necessary,but not sufficient for the development of Kaposi sarcoma (KS),primary effusion lymphoma (PEL),and multicentric Castleman disease (MCD).Advances in the prevention and treatment of KSHV-associated Diseases have been achieved,even though current treatment options are ineffective,or toxic to many affected persons.The identification of new targets for potential future therapies and the randomized trial to evaluate the efficacy of new antivirals are required.

Pathogenesis and Associated Diseases of Kaposi's Sarcoma-associated Herpesvirus / 中国病毒学

Kaposi's sarcoma-associated herpesvirus (KSHV) is the primary etiological agent of Kaposi's sarcoma, primary effusion lymphoma and muticentric Castleman's disease. In common with the other herpesviruses, KSHV exhibits both latent and lytic life cycles, both of which are characterized by distinct gene expression profiles and programs. KSHV encodes proteins which play essential roles in the inhibition of host adaptive and innate immunity, the inhibition of apoptosis, and the regulation of the cell cycle. KSHV also encodes several proteins which have transforming and intrcellular signalling activity.

Multicentric Castleman Disease:CT Findings(A Report of one Case and a Review of the Literature) / 实用放射学杂志

Objective To evaluate the CT findings of multicentric Castleman disease(CD).Methods The CT findings of thorax and abdomen in a patient with multicentric CD biopsy-proved were retrospectively analyzed, and a literature review was conducted.Results The patient had systemic symptoms, polyclonal hypergammaglobulinemia, extensive lymph node enlargement and mild enhancement, and specific pulmonary infiltration. The lung lesions on thin-section CT were showed poorly-defined centrilobular nodules, ground-glass attenuation, thin-walled cysts, thickening of the bronchovascular bundles, and interlobular septal thickening. The above were highly coincident with that in the literatures.Conclusion Multicentric CD is characterized by the presence of systemic symptoms, extensive lymph node enlargement and mild enhancement, and specific pulmonary lesions when infiltrated. Typical manifestation might suggest multicentric CD.