CASTLEMAN＇S DISEASE IN THE RETROPERITONEAL AREA：REPORT OF 5 CASES AND REVIEW OF THE LITERATURE

Objective To investigate the diagnostic and treatment methods of Castleman＇s disease（CD）.Methods Five CD cases were treated in our department,we presented its clinical characteristics and had a comprehensive review of different reports from other centers.Results We presented five patients who had retroperitoneal mass and postoperative pathological results confirmed all of them had hyaline vascular（HV）type CD.We also discussed CD by reviewing different literatures on its diagnosis,treatment and outcome.Conclusion CD is an atypical lymphoproliferative disorder and a heterogeneous entity that can be either localized or systematic.The etiology and pathogenesis of this entity is still unclear.The imaging findings though are not specific,still can help make differential diagnosis.The hyaline vascular type frequently appears as a benign isolated mediastinal or rarely retroperitoneal mass,which does not recur after curative surgical excision.     

Castleman disease: an unusual diagnosis of a portal mass in an 8-year-old boy

An 8-year-old boy presented with a mass located in the portal hilum and hepatosplenomegaly, and the presumed initial diagnosis was lymphoma. The pathology result was Castleman disease of hyaline vascular type. Castleman disease is an unusual diagnosis that should be kept in mind in the differential diagnosis of portal masses. In the case of solitary lesions, total excision can be curative.     

Leucine-rich a-2 glycoprotein as a potential biomarker of idiopathic multicentric Castleman disease with pulmonary involvement: a single-center case-control study from Japan

BackgroundThere are no known biomarkers for monitoring disease activity in idiopathic multicentric Castleman disease (MCD) with pulmonary involvement. We investigated the utility of serum leucine-rich α2-glycoprotein levels, which reflects interleukin 6 independent inflammatory change, for monitoring disease activity in patients with idiopathic MCD with pulmonary involvement.MethodsWe retrospectively examined cases of idiopathic MCD diagnosed at Osaka University Hospital. The serum levels of leucine-rich α2-glycoprotein were compared between patients with idiopathic MCD and healthy controls. The difference in leucine-rich α2-glycoprotein levels before and after treatment (∆leucine-rich α2-glycoprotein) was evaluated with respect to the relationship with pulmonary function. In addition, the relationship between cytokine and chemokine profiles and the leucine-rich α2-glycoprotein concentration was investigated. The results were analyzed using pathway analysis.ResultsThe leucine-rich α2-glycoprotein concentrations were significantly higher in treatment-naïve patients (n=5) than in healthy controls (n=3) (P=0.035). Further, the ∆leucine-rich α2-glycoprotein concentration was significantly correlated with ∆ percent diffusing capacity of the lung for carbon monoxide (r=−0.88, P=0.049) and tended to correlate with ∆ percent vital capacity (r=−0.68, P=0.21) although the difference was not significant for the latter association. The concentrations of chemokines and cytokines, such as CXCL9, CXCL11, CXCL1, and a proliferation-inducing ligand, were higher in the patient group than in the healthy control group. Enrichment analysis indicated that leucine-rich α2-glycoprotein could be elevated via the upregulation of chemokines in patients with idiopathic MCD using these parameters.ConclusionsLeucine-rich a2-glycoprotein may be useful for monitoring disease activity in patients with idiopathic MCD with pulmonary involvement.     

Idiopathic multicentric Castleman disease with positive antiphospholipid antibody: atypical and undiagnosed autoimmune disease?

Idiopathic multicentric Castleman disease (iMCD) is a systemic disorder characterized by systemic inflammation and organ dysfunction associated with an increase in pro-inflammatory cytokines. Some patients with iMCD are positive for autoantibodies, although their significance and relationship with specific associated autoimmune diseases are unclear. This study retrospectively analyzed the clinicopathological features of iMCD patients focusing on autoantibodies. Among 63 iMCD patients in our database, 19 were positive for at least one autoantibody. Among the 19, we identified five with plasma cell type (PC)-iMCD lymph node histopathology and positive anti-phospholipid antibodies. These patients were likely to have thrombocytopenia, anasarca, fever, reticulin fibrosis or renal insufficiency, organomegaly (TAFRO) symptoms, and thrombotic events. The present study suggests that patients with undiagnosed or atypical autoimmune diseases, including anti-phospholipid syndrome (APS), were treated for iMCD. APS may present with thrombocytopenia or even multi-organ failure, which overlap with clinical presentations of iMCD. Due to differences in the treatment regimen and follow-up, recognition of the undiagnosed autoimmune disease process in those suspected of iMCD is essential. Our study highlights the importance of complete exclusion of differential diagnoses in patients with iMCD in their diagnostic workup.     

Storming the castle: A case report of multi‐system dysregulation in a child with Castleman disease

Castleman disease is a non‐clonal, lymphoproliferative disorder rarely seen in children. Presented is a 12‐year‐old male with progressive abdominal pain, vomiting, and fever. Diagnostic testing revealed multi‐organ system involvement and the diagnosis was ultimately made with tissue biopsy. Marked disease regression occurred after high‐dose steroids and continued interleukin‐6 inhibition.     

Paraneoplastic pemphigus uncovers distinct clinical and biological phenotypes of western unicentric Castleman disease

Unicentric Castleman disease (UCD) is a lymphoproliferative disease of unknown cause. Paraneoplastic pemphigus (PNP) is a major complication shown to be associated with a poor prognosis, with particular severity in patients with bronchiolitis obliterans (BO). This study describes the clinical and biological characteristics of UCD-PNP patients in a large Western cohort. A total of 148 patients diagnosed with UCD were identified, including 14 patients with a defined PNP. PNP was significantly associated with myasthenia gravis (MG) and FDC sarcoma during follow-up (FDCS). PNP was also significantly associated with reduced survival. These data, together with a multivariate analysis by principal components, led to the identification of UCD-PNP as a group at risk of MG, FDCS and death. PDGFRB sequencing performed on UCD lesions from six patients found the gain-of-function p.N666S variant in two. Interestingly, both patients had hyaline-vascular UCD subtype, were in the UCD-PNP subgroup and had FDCS. Sera from 25 UCD-PNP patients and 6 PNP patients without UCD were tested for PNP-associated autoantibodies. Sera from UCD-PNP patients had a strong reactivity against the N-terminal domain of recombinant periplakin (rPPL, 82%) and showed reactivity against at least two domains of rPPL. These features were not found in patients with UCD alone or in the PNP group without UCD. These data indicate that UCD-PNP patients belong to a subgroup sharing strong clinical and biological identity that might help to decipher the different dynamics of UCD natural history.     

Rituximab–bortezomib–dexamethasone induce high response rates in iMCD in clinical practice

Treatment options for idiopathic multicentric Castleman disease (iMCD) are currently limited, especially for patients who do not respond or are resistant to interleukin-6 inhibitors. For the first time, we innovatively designed a protocol using rituximab–bortezomib–dexamethasone (RVD) as first-line consolidation therapy in patients newly diagnosed with iMCD. Furthermore, we adopted a no-maintenance treatment strategy to simplify post-remission care. Five patients with iMCD were enrolled (including one with TAFRO syndrome) and underwent the RVD regimen, all of whom achieved partial response (PR) or better. After four cycles of RVD, three (60%) patients achieved PR, while one (20%) achieved a complete response. These five patients, who achieved PR or better, discontinued treatment but remained stable for a median follow-up of 11 months, with a duration of response of 7, 7, 10, 12 and 13 months, respectively. None of the patients experienced grade ≥3 adverse events during the observation period. Collectively, these findings demonstrated that the RVD regimen may be a promising treatment option for patients with iMCD. It was a safe and effective approach that resulted in lasting responses without the need for ongoing maintenance therapy.     

颈部Castleman病5例临床分析

目的探讨颈部Castleman病的临床及病理学特点，并总结其临床症状、分型、诊疗经验及预后情况。方法回顾性分析2011年1月~2017年11月收治的5例颈部Castleman病的临床资料，并复习相关文献。结果5例颈部Castleman病均以颈部单发或多发无痛性肿物起病，临床症状较轻，临床分型分别为局灶型（unicentric CD, UCD）和透明血管型（hyaline vascular type, HV)，治疗上均手术切除肿物，随访9~87个月,1例复发。结论头颈部Castleman病需通过病理学检查及免疫组化分析确诊。临床分型以局灶型（UCD）为主，以手术方式切除肿物可有效治疗，若出现复发可辅以药物治疗。预后方面UCD型患者治愈率高。