Idiopathic multicentric Castleman disease with novel heterozygous Ile729Met mutation in exon 10 of familial Mediterranean fever gene

Abstract Objective While the aetiology of idiopathic multicentric Castleman disease (iMCD) remains unclear, the involvement of autoinflammatory mechanisms has been suggested. Herein we report a Japanese patient with iMCD with a novel heterozygous Ile729Met mutation in exon 10 of the Mediterranean fever (MEFV) gene. Methods We performed genetic analysis via targeted next-generation sequencing analysis and Sanger sequencing and conducted molecular dynamics simulations to investigate the hydrophobic interactions around the 729th amino acid in human pyrin. Results In February 2011, a 59-year-old man was diagnosed with IgG4-related disease at our department based on the findings of cervical and hilar lymphadenopathies, typical lung lesions and cervical lymph node biopsy. The patient was followed up without treatment, as he was asymptomatic. However, he had been experiencing prolonged fatigue and fever with high levels of CRP since June 2017. Axillary lymph node biopsy findings led to the diagnosis of iMCD. He was successfully treated with an IL-6 inhibitor and has been in remission for 12 months. Genetic analyses for hereditary autoinflammatory disease–related genes were performed, revealing a novel heterozygous Ile729Met mutation in exon 10 of the MEFV gene. We identified that this novel mutation significantly altered the local interaction of the human pyrin B30.2 domain by molecular dynamics simulation analysis and experimentally had the potential for inflammasome activation with increased inflammatory cytokines. Conclusion The abnormal function of pyrin due to a mutation in the MEFV gene in this patient may have contributed to the development of MCD by inducing IL-6 production via inflammasome signalling.

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Five biopsies, one diagnosis: challenges in idiopathic multicentric Castleman disease

BMJ Case Reports ◽

10.1136/bcr-2020-236654 ◽

2020 ◽

Vol 13 (11) ◽

pp. e236654

Author(s):

Julie Semenchuk ◽

Asad Merchant ◽

Ali Sakhdari ◽

Vishal Kukreti

Keyword(s):

Lymph Node ◽

Kidney Injury ◽

Lymph Node Biopsy ◽

Castleman Disease ◽

Pleuritic Chest Pain ◽

Multicentric Castleman Disease ◽

Node Biopsy ◽

Significant Clinical Improvement ◽

Night Sweats ◽

Inflammatory Changes

A previously healthy 29-year-old man initially presented to the hospital with pleuritic chest pain and shortness of breath. Over the next 2 months he developed ongoing fevers and night sweats with recurrent exudative pleural effusions and ascites. He had an extensive infectious and autoimmune workup that was unremarkable. He had an initial lymph node biopsy that showed reactive changes only. He had an acute kidney injury and his renal biopsy revealed thrombotic microangiopathy. His liver biopsy showed non-specific inflammatory changes. His bone marrow biopsy showed megakaryocyte hyperplasia and fibrosis, which raised suspicion for the thrombocytopenia, ascites, reticulin fibrosis, renal dysfunction and organomegaly syndrome subtype of multicentric Castleman disease. This prompted a repeat lymph node biopsy, showing changes consistent with mixed type Castleman disease that fit with his clinical picture. He was initiated on steroids and siltuximab with significant clinical improvement.

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Multicentric Castleman Disease with Complete Duodenal Obstruction in an HIV Patient

Blood ◽

10.1182/blood.v120.21.4834.4834 ◽

2012 ◽

Vol 120 (21) ◽

pp. 4834-4834

Author(s):

Tarsheen K Sethi ◽

Abdolmohammadi Alireza ◽

Goetz H Kloecker ◽

Stephen P Slone

Keyword(s):

Lymph Node ◽

Duodenal Obstruction ◽

Castleman’S Disease ◽

High Plasma ◽

Body Cavity ◽

Lymph Node Biopsy ◽

Castleman Disease ◽

Castleman's Disease ◽

Node Biopsy ◽

Pet Ct

Abstract Abstract 4834 Multicentric Castleman's Disease(MCD) can have an aggressive course making early diagnosis and treatment important. Although rare, peripancreatic involvement is known in Castleman's disease and an unusual presentation should be considered especially in the setting of HIV. An excisional lymph node biopsy is required for diagnosis. High plasma titers of Human Herpes Virus 8 DNA should also raise this possibility. Coexistence of Castleman disease and body cavity lymphoma has been reported but is rare. Case Presentation: A 42 year old African American gentleman with a history of HIV and CD4 count 271 presented with intractable nausea and vomiting of 1 month duration; associated with epigastric pain and weight loss. Past history was significant for presentation with jaundice 6 months earlier when he was found to have a pancreatic head mass with portocaval and retroperitoneal lymphadenopathy raising the suspicion of pancreatic adenocarcinoma. Endoscopic ultrasound guided fine needle aspiration of the mass had revealed a poorly differentiated malignant neoplasm that could not be further characterized by immunohistochemistry. Considering the HIV status of the patient, there was a strong suspicion of lymphoma. A PET-CT was planned to identify an appropriate site for tissue diagnosis but the patient was lost to follow up. Repeat imaging during the current admission revealed increasing size of the pancreatic mass causing complete obstruction of second part of duodenum. The patient subsequently underwent gastro-jejunostomy to bypass the duodenal obstruction and an excisional biopsy of two mesenteric lymph nodes was performed during the procedure. Pathology revealed HHV-8 positive plasma cell variant of Castleman's disease. Patient also had high plasma titers of HHV-8. Furthermore, the patient was also found to have bilateral pleural effusions and a thoracentesis was performed. Pleural cytology revealed large plasmablastic lymphoid cells that were positive for HHV-8, CD30, CD45, CD138, Ebstein-Barr virus (EBV), epithelial membrane antigen, and multiple myeloma oncogene-1. These findings suggested a diagnosis of body cavity lymphoma. Discussion: Although rare, the association of Multicentric Castleman's disease (MCD) with HIV is well recognized. The incidence is independent of CD4 count and the use of HAART. There are isolated case reports of pancreatic involvement with Castleman's disease and only one involving the duodenum. While most patients with peripancreatic involvement presented with abdominal discomfort, nausea or systemic symptoms, our patient was severely symptomatic from complete duodenal obstruction. Our case also highlights that the diagnosis can be elusive and requires excisional lymph node biopsy. Moreover, HIV MCD is fluorodeoxyglucose avid, and a PET-CT may help identify the gland to biopsy next in difficult to diagnose cases. Body cavity lymphoma is also HHV-8 related and this diagnosis should be considered in any HIV patient with effusions. Pleural fluid cytology and immunohistochemistry usually clinch the diagnosis. Disclosures: No relevant conflicts of interest to declare.

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Idiopathic Multicentric Castleman Disease

10.47363/jonrr/2021(2)138 ◽

2021 ◽

pp. 1-4

Author(s):

Aravind Reddy Kuchkuntla ◽

Keyword(s):

Lymph Node Biopsy ◽

Castleman Disease ◽

Multicentric Castleman Disease ◽

Non Hodgkin Lymphoma ◽

Node Biopsy ◽

Lytic Lesions ◽

Initial Work ◽

History Of ◽

M Spike ◽

Work Up

Castleman Disease (CD) is a spectrum of heterogenous hematological diseases that share characteristic clinical, histopathological, and immunological features. We present a case of a 61-y female with history of non-Hodgkin Lymphoma and hypothyroidism presenting with fatigue, generalized weakness, nausea, and poor appetite. On admission, physical examination was unremarkable, and labs were notable for hyperkalemia, hyperuricemia and worsening renal function. Imaging showed lymphadenopathy in neck, mediastinum, and left axilla along with mediastinal and retroperitoneal lymphadenopathy. Initial work up of serum electrophoresis was suggestive of multiple myeloma however bone scan did not reveal any lytic lesions. As biopsy results were pending, patient developed worsening cytopenia’s and a repeat serum electrophoresis showed a M spike with IgG lambda against a polyclonal background. Bone marrow biopsy showed polytypic plasmacytosis that was negative for HHV 8 and lymph node biopsy also showed polytypic plasmacytosis. Further work confirmed the diagnosis of idiopathic multicentric Castleman disease and patient was treated with silutuximab and responded well.

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