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Background: Idiopathic multicentric Castleman disease (iMCD) is a rare inflammatory disorder mediated by excessive proinflammatory cytokine signaling, most notably by interleukin 6 (IL‐6). IL‐6‐induced extramedullary hematopoiesis (EMH) has been reported in murine models of iMCD. Herein we present four cases of iMCD with EMH in humans. Case Series: The index case is a 24‐year‐old white woman who presented with pancytopenia, hepatosplenomegaly, and diffuse lymphadenopathy (LAD) with EMH in core lymph node biopsies. We then searched ACCELERATE, a Castleman disease (CD) natural history registry, and identified three additional CD cases with EMH reported in biopsies: A 23‐year‐old Asian man with fatigue, edema, LAD, and splenomegaly; a 20‐year‐old white man with fever, dyspnea, LAD, and hepatosplenomegaly; and a 50‐year‐old white man with constitutional symptoms, LAD, and myelodysplastic syndrome in bone marrow with a KRAS mutation. Results: All four patients presented with thrombocytopenia and fever and/or markedly elevated C‐reactive protein. Patient 1 had iMCD‐NOS (not otherwise specified) with severe thrombocytopenia, reticulin fibrosis in bone marrow, small volume LAD and organomegaly but no anasarca. The other three patients had iMCD‐TAFRO (thrombocytopenia, anasarca, reticulin fibrosis, renal dysfunction, organomegaly). Two had mixed CD and two had hypervascular CD in lymph nodes. All four had bone marrow hypercellularity and megakaryocyte hyperplasia and two had reticulin fibrosis. Conclusions: This case series demonstrates that EMH can be seen in CD, particularly in iMCD‐TAFRO. Given the similarity of this finding to previous murine models of IL‐6‐induced marrow and lymph node changes we hypothesize that this is an IL‐6‐mediated phenomenon. [ABSTRACT FROM AUTHOR]

Diseases in which cutaneous plasma cell infiltrates predominate are rare and usually of unknown etiology, including those that transition from benign to malignant, such as cutaneous plasmacytosis, multicentric Castleman disease, and extramedullary plasmacytoma. These diseases may present as purplish, reddish‐brown cutaneous plaques or nodules. Here, we report an exceptional case of lichen planus (LP) in which the patient had classic histopathological features, but the infiltrating inflammatory cells were plasma cells with restricted light chain expression. The patient presented with severe rashes, including purplish‐red plaques and nodules, erythema, and erosions in the palmoplantar area, verrucous hyperplasia of the oral mucosa, and anonychia of the toes. These findings suggest a possible role of plasma cells with restricted light chain expression in the LP. Clinicians should closely follow patients for changes in their rash, perform repeat biopsies if necessary, and regularly conduct multisystemic evaluations. [ABSTRACT FROM AUTHOR]

ABSTRACT Castleman Disease (CD) is a rare lymphoproliferative disorder that can be separated into two primary forms: Unicentric Castleman disease (UCD) and multicentric Castleman disease (MCD). UCD is localized, while MCD is systemic. Though UCD generally has a favorable prognosis following surgical resection, more aggressive forms of this disease have been identified, including cases associated with dendritic and spindle cell proliferation. Genetic analysis has deepened our understanding of UCD. Despite advancements in better understanding the pathophysiology of UCD, challenges persist in the diagnosis, management, and treatment due to its rarity and heterogeneity. Here, we review current knowledge on UCD, highlighting the epidemiology, clinical presentation, diagnostic criteria, and treatment options while emphasizing the need for further research and innovation in therapeutic strategies. [ABSTRACT FROM AUTHOR]

Background: Human herpes virus 8 (HHV‐8) or Kaposi sarcoma herpesvirus (KSHV) is an opportunistic oncovirus that causes multiple pathologic entities. Methods: We present a case of fatal HHV‐8‐associated multisystem illness with disseminated Kaposi sarcoma and HHV8‐associated lymphoproliferative disorder with systemic inflammation. We conducted a narrative review of the literature on HHV‐8 in transplantation with a goal of illuminating the spectrum of HHV‐8‐associated diseases in this vulnerable population, modes of disease transmission, and the potential role for donor and recipient screening. Results: HHV‐8‐associated KS, primary effusion lymphoma (PEL), multicentric Castleman disease (MCD), and KSHV inflammatory cytokine disorder (KICS) may affect transplant recipients; with the exception of KS, these conditions are rare but carry high morbidity and mortality. Conclusion: HHV‐8‐associated diseases have diverse and protean manifestations in transplant recipients, with potentially fatal outcomes. HHV‐8 seroprevalence among organ donors and the magnitude of risk for donor‐derived HHV‐8 infection or clinically significant disease remain unknown and require further study. [ABSTRACT FROM AUTHOR]

Simple Summary: Kaposi sarcoma-associated herpesvirus (KSHV) is associated with lymphoproliferative disorders, including primary effusion lymphoma and multicentric Castleman disease. KSHV expresses viral proteins that aid in the evasion of antiviral immune responses and manipulate host factors and signaling to promote cell survival. By altering the cell environment, KSHV contributes to lymphomagenesis. Approximately 15–20% of cancers are caused by viruses. Kaposi sarcoma-associated herpesvirus (KSHV), also known as human herpesvirus 8 (HHV8), is an oncogenic virus that is the etiologic agent of not only Kaposi sarcoma but also the lymphoproliferative disorders, primary effusion lymphoma (PEL) and multicentric Castleman disease (MCD). KSHV can infect a broad tropism of cells, including B lymphocytes, wherein KSHV encodes specific viral proteins that can transform the cell. KSHV infection precedes the progression of PEL and MCD. KSHV establishes lifelong infection and has two phases of its lifecycle: latent and lytic. During the latent phase, viral genomes are maintained episomally with limited gene expression. Upon sporadic reactivation, the virus enters its replicative lytic phase to produce infectious virions. KSHV relies on its viral products to modulate host factors to evade immune detection or to co-opt their function for KSHV persistence. These manipulations dysregulate normal cell pathways to ensure cell survival and inhibit antiviral immune responses, which in turn, contribute to KSHV-associated malignancies. Here, we highlight the known molecular mechanisms of KSHV that promote lymphomagenesis and how these findings identify potential therapeutic targets for KSHV-associated lymphomas. [ABSTRACT FROM AUTHOR]

Summary Idiopathic multicentric Castleman disease (iMCD) is a rare and heterogeneous lymphoproliferative disorder that lacks standardised treatment options for patients with refractory or relapsed (r/r) disease. Blocking Bruton's tyrosine kinase (BTK) has emerged as a promising therapeutic approach for iMCD without depleting B cells. This single‐centre, retrospective study enrolled 10 patients with r/r iMCD who were treated with orelabrutinib, a novel, next‐generation BTK inhibitor. The median age at orelabrutinib initiation was 48 (range: 31–58) years. The overall response rate was 70% (7/10 patients, 95% CI: 34.8–93.3), with 20% (n = 2) achieving complete response and 50% (n = 5) achieving partial response. The median time to response was 9.8 (range: 5.9–20.5) months. Patients in the non‐responder group also demonstrated a continuous improvement in haemoglobin (91–105 g/L) and albumin (32–38 g/L) levels at month 12 of treatment despite not fulfilling response criteria. No grade 3 or higher adverse events occurred during the median time to the next treatment of 29.0 (range: 15.0–36.2) months. No patient mortality was recorded during the median follow‐up duration of 32.8 (range: 15.0–36.9) months. In conclusion, orelabrutinib is a safe and effective regimen for r/r iMCD. [ABSTRACT FROM AUTHOR]

Refractory/relapsed idiopathic multicentric Castleman disease (R/R iMCD) has limited treatment options. With studies showing increased mTOR activation in iMCD patients, sirolimus becomes an attractive and promising therapy for R/R iMCD. Here we report the results of a retrospective study involving 26 R/R iMCD patients treated with sirolimus-containing regimen. The median age at sirolimus initiation was 40.5 years (23–60), with a median prior treatment line of 2 (1–5). 18 patients (69.2%) achieved symptomatic and biochemical response, with a median time to at least overall partial remission of 1.9 months (0.5–14.6). The median follow-up time from sirolimus initiation was 11.7 months (1.6–50.7) and the median time to next treatment (TTNT) was 46.2 months. No patients died at the end of follow-up. Most of the patients in the cohort are in ongoing responses and continue sirolimus therapy. Sirolimus is well tolerated with minor adverse effects. In conclusion, sirolimus is effective for R/R iMCD patients with good tolerance. [ABSTRACT FROM AUTHOR]

A submandibular mass can be attributed to a variety of potential diagnoses. We report a case of a 71-year-old man presenting with left submandibular swelling associated with multiple lymph nodes.All investigations were negative except for a suspected malignant submandibular tumour.Unicentric Castleman's disease was diagnosed based on the final histological examination. [ABSTRACT FROM AUTHOR]

Abstract Background Orbital Castleman's disease is a rare benign lymphoproliferative disorder of extranodal origin. Case presentation A 72-year-old man presented with bilateral upper eyelid swelling. Radiology revealed enlarged lacrimal glands in both eyes. Castleman's disease (plasma cell type) was confirmed by histo-immunochemical examinations after excision of the left orbital mass. No extraorbital involvement was found in systemic evaluation. Postoperatively, corticosteroid therapy was given. After 1 year of follow-up, there was no recurrence in the left orbit, and the swelling of the right eyelid was improved. Conclusions Here, we report a case of orbital Castleman's disease involving the lacrimal gland bilaterally and summarize previously reported cases. For bilateral orbital masses, the possibility of Castleman's disease should be considered. Before the diagnosis, it is necessary to fully distinguish from other diseases such as IgG4-related eye diseases.

This article presents a case study of a 45-year-old woman with kidney lesions and lytic bone disease. The patient underwent various imaging tests and reported symptoms such as fatigue and pain in the left shoulder and arm. Further evaluation and testing revealed polyclonal hypergammaglobulinemia with an elevated IgG level. The article explores potential causes for the patient's symptoms, ruling out certain diseases and suggesting a histiocytic disorder as the most likely diagnosis. Treatment options for systemic Rosai-Dorfman-Destombes disease are also discussed, with the patient in the case having a complete clinical response to cobimetinib. [Extracted from the article]

Castleman disease (CD), also known as giant lymph node hyperplasia or angiofollicular lymph node hyperplasia, is a rare and indeterminate group of chronic lymphoproliferative disorders. CD is highly heterogeneous, classified into unicentric Castleman disease (UCD) and multicentric Castleman disease (MCD) based on lesion distribution, and further categorized into three pathological types: hyaline vascular type (HV), plasma cell type (PC), and mixed type (Mix). This paper describes a rare case of solitary mediastinal Castleman disease with transparent vessels in the anterior sacrum, presenting as the HV type. Surgical excision of the mass was performed following coccygectomy for treatment. The patient recovered well postoperatively. During a 6-month follow-up period, there were no signs of recurrence, and the patient's quality of life significantly improved. [ABSTRACT FROM AUTHOR]

Here, we describe a new technology, designed to accelerate peptide discovery by quick identification and optimization of the residues critical for protein–protein interactions or ligand binding. We called it PepFusion. It is based on ligation of short DNA sequences generated from known ligand‐binding regions. We tested it by selecting peptide antagonists of interleukin‐6 (IL‐6), a key mediator of inflammatory diseases such as rheumatoid arthritis (RA), Crohn's disease, and Castleman disease (CD). The PepFusion library demonstrated superiority over a random library by yielding a peptide with low micromolar affinity for IL‐6, whereas the random library failed. The affinity of the peptide from the PepFusion library was further enhanced by additional rounds of mutagenesis leading to peptide variants with low nanomolar IL‐6 affinity. In addition to generating high‐affinity peptides, our method opens the way to solve the problem of the false positive sequences, which are common with all display technologies. [ABSTRACT FROM AUTHOR]

The article discusses the successful treatment of a relapsed case of idiopathic multicentric Castleman disease-idiopathic plasmacytic lymphadenopathy with orelabrutinib monotherapy. The patient, a 54-year-old Chinese female, experienced symptoms such as fatigue, fever, weight loss, and pruritus, leading to a diagnosis of iMCD-IPL. Treatment with orelabrutinib resulted in a long-term complete response, highlighting the potential of this BTK inhibitor as a novel therapeutic option for managing iMCD. Further clinical studies are needed to validate its efficacy and safety. [Extracted from the article]

Key Clinical Message: Castleman's Disease should be considered in the differential diagnosis of retroperitoneal masses, especially in equivocal cases. Clinician should not presume all cases of retroperitoneal masses as a malignancy. Castleman's Disease is a heterogeneous group of lymphoproliferative disorders, that can develop in lymph nodes or in extranodal sites. It has three distinct histological subtypes; hyaline vascular, plasma cell or mixed. It can be unicentric or multicentric, and sometimes oligocentric or regional. In this article, we report a case of a 30‐year‐old male who presented with a palpable left lumbar mass, clinically suspected as sarcoma vs GIST, which was surgically excised and pathologically examined revealing a rare condition of intra‐abdominal unicentric Castleman's Disease with good prognosis. Castleman's Disease should be considered in the differential diagnosis of retroperitoneal masses, especially in equivocal cases. [ABSTRACT FROM AUTHOR]

Castleman disease (CD) is a rare lymphoproliferative disorder, with non‐specific clinical manifestations, often delayed diagnosis and treatment, which pose a significant challenge in the present times. Patients diagnosed with this disease have poor prognosis due to the limited treatment options. Multicentric CD occurs at multiple lymph node stations and is associated with a proinflammatory response that leads to the development of the so‐called 'B symptoms'. IL‐6 seems to be a key cytokine involved in various manifestations such as lymphadenopathies, hepatosplenomegaly, and polyclonal hypergammaglobulinemia. Its levels correlate with the activity of the disease. Other consequences of MCD include increased fibrinogen levels leading to deep vein thrombosis and thromboembolic disorders, high hepcidin levels causing anaemia, elevated VEGF levels promoting angiogenesis and vascular permeability, which, along with hypoalbuminemia, induce oedema, ascites, pleural and pericardial effusions, and in severe cases, generalized anasarca. In extreme cases multiple organ failure can occur, often resulting in death. We propose the use of continuous renal replacement therapy (CRRT) in managing severe multicentric CD. Our arguments are based on the principles that CRRT is able to remove IL‐6 from circulation thus attenuating the cytokine storm, can influence hepcidin levels, and reduction in oedema, and is often used in multiple organ failure to regain homeostasis control. Therefore, it could be used as a therapy or bridge therapy in severe cases. To sustain our hypothesis with evidence, we have gathered several studies from the literature confirming the successful removal of cytokines, especially IL‐6 from circulation, which can be used as a starting point. [ABSTRACT FROM AUTHOR]

Castleman disease (CD) is a benign lymphoproliferative disease causing severe systemic inflammation. Interleukin-6 (IL-6) is a major pathogenesis of multicentric CD (MCD), but only 30–60% of patients respond to IL-6 inhibitors. Novel agents for IL-6 inhibitor-refractory cases are needed. Clinical data and samples are being collected on a large scale and the clinical, pathological, and pathogenetic aspects are being elucidated. The pathological and clinical classification of CD is outlined. Focusing on idiopathic MCD (iMCD), this review identifies therapeutic targets and summarizes currently recommended drugs and promising therapeutic candidates. The pathogenesis of MCD has been implicated in the activation of the Janus kinase (JAK)-transcriptional signaling activator (STAT) 3 pathway and the phosphatidylinositol 3-kinase (PI3K)/Akt/mechanical target of rapamycin (mTOR) signaling pathway. iMCD-TAFRO (thrombocytopenia, anasarca, fever/elevated CRP, reticulin myelofibrosis/renal dysfunction, organ enlargement) is resistant to IL-6 inhibitors, and cyclosporine and mTOR inhibitors are sometimes effective. JAK inhibitors and mTOR inhibitors may be therapeutic agents for iMCD. Recently, we have shown that peripheral helper T (Tph) cell abnormalities are at the core of iMCD pathogenesis. Therapies targeting chemokine (C-X-C motif) ligand 13 (CXCL13) produced by Tph cells and blocking the Tph-CXCL13-B cell pathway may satisfy unmet need in refractory cases. [ABSTRACT FROM AUTHOR]

Introduction: Idiopathic multicentric Castleman disease (iMCD) is a rare, chronic, debilitating lymphoproliferative disorder where the mainstay of treatment is symptom management. Our recent international patient survey showed that patients with iMCD have a high symptom burden that has a significant negative patient-reported impact on several aspects of daily life. As part of our ongoing work towards the development of an iMCD symptom burden scale, assessing the survey's psychometric properties is a critical step in understanding its adequacy, relevance, and usefulness. As iMCD is a rare disease, there are challenges to conducting such psychometric analyses which we describe. Methods: As part of the exploratory psychometric analysis, three a priori hypothesis sets (HS) were generated by interviewing an iMCD-experienced clinician, a patient, and a caregiver to explore the iMCD patient survey's internal construct validity, given no gold standard iMCD measure exists for external construct validation. HS-1 hypothesized that a convergent or discriminant relationship exists with the patients' self-assessment of symptom effect on daily life between two potentially related or unrelated symptoms, respectively. HS-2 hypothesized that having a greater number of symptoms has a positive convergent relationship with the patients' assessment of symptoms' effect on daily life. Finally, HS-3 hypothesized that patients receiving treatment versus no treatment was associated with patients reporting less effect of symptom burden on their daily life. Spearman's rank absolute correlation strength (ACS) was used for HS-1 and HS-2 (convergent relationship, ACS ≥ 0.3 and p value < 0.05; divergent relationship, ACS < 0.3), and Cohen's d to quantify standardized absolute effect sizes (AES) for HS-3 (AES ≥ 0.5 and p value < 0.05). Results: Our analyses partially supported HS-1. None of the three positive convergent relationships were supported. Of the six discriminant relationships, only dizziness with impaired cognitive function and tiredness with dizziness were supported. HS-2 analyses showed there was convergent validity between the number of symptoms and their effect on aspects of daily life. HS-3 analyses did not provide evidence to support the hypothesis. Conclusion: These internal psychometric construct analyses provide initial support for the bespoke iMCD patient survey and will guide additional work towards the development of the first iMCD-specific symptom burden scale. [ABSTRACT FROM AUTHOR]

The optimal treatment endpoints and duration of continuous therapy for multicentric Castleman disease (MCD) remain controversial. We retrospectively analyzed data from 123 patients with Human Herpesvirus (HHV)-8 negative MCD. We demonstrated that continuous therapy significantly enhanced progression-free survival (PFS) in patients who achieved an optimal response after initial treatment. These findings underscore the critical role of continuous therapy in HHV-8 negative MCD. Further studies with larger cohorts are required to validate these findings. [ABSTRACT FROM AUTHOR]

In this report, we present an Asian male patient who was 30 years old and admitted to the hospital due to pancreatitis. While undergoing a CT scan, an isolated mass was unexpectedly discovered in the patient's abdomen. The patient's abdominal pain, which was caused by pancreatitis, had resolved before he underwent surgical resection to remove the mass. Subsequently, the patient was diagnosed with Castleman disease based on pathology. Castleman disease occurring in the mesentery is exceptionally rare. Therefore, we have reviewed the essential information regarding Castleman disease and have found that the crucial part lies in the diagnosis and the consideration of distinct treatment strategies based on different types. [ABSTRACT FROM AUTHOR]

Objective: Characterize the CT findings of abdominopelvic Castleman disease, including a new observation involving the perinodal fat. Methods: Multi-centre search at 5 institutions yielded 76 adults (mean age, 42.1 ± 14.3 years; 38 women/38 men) meeting inclusion criteria of histopathologically proven Castleman disease with nodal involvement at abdominopelvic CT. Retrospective review of the dominant nodal mass was assessed for size, attenuation, and presence of calcification, and for prominence and soft-tissue infiltration of the perinodal fat. Hypervascular nodal enhancement was based on both subjective and objective comparison with aortic blood pool attenuation. Results: Abdominal involvement was unicentric in 48.7% (37/76) and multicentric in 51.3% (39/76), including 31 cases with extra-abdominal involvement. Histopathologic subtypes included hyaline vascular variant (HVV), plasma cell variant (PCV), mixed HVV/PCV, and HHV-8 variant in 39, 25, 3 and 9 cases, respectively. The dominant nodal mass measured 4.4 ± 1.9 cm and 3.2 ± 1.7 cm in mean long- and short-axis, respectively, and appeared hypervascular in 58.6% (41/70 with IV contrast). Internal calcification was seen in 22.4% (17/76). Infiltration of the perinodal fat, with or without hypertrophy, was present in 56.6% (43/76), more frequent with hypervascular vs non-hypervascular nodal masses (80.5% vs 20.7%; P < .001). Among HVV cases, 76.9% were unicentric, 71.1% appeared hypervascular, and 69.2% demonstrated perinodal fat infiltration. Conclusion: Hypervascular nodal masses demonstrating prominence and infiltration of perinodal fat at CT can suggest the specific diagnosis of Castleman disease, especially the HVV. Advances in knowledge: Abdominopelvic nodal masses that demonstrate hypervascular enhancement and prominent infiltration of the perinodal fat at CT can suggest the diagnosis of Castleman disease, but nonetheless requires tissue sampling. [ABSTRACT FROM AUTHOR]

Castleman disease (CD) is a rare lymphoproliferative disorder characterized by benign lymph node enlargement. We present the case of a 43‐year‐old male with a complex medical history, including Crohn's disease treated with Adalimumab and later complicated with tuberculosis (TB) infection. Subsequently, in May 2021, he was diagnosed with human immunodeficiency virus (HIV) and started on antiretroviral therapy (efavirez, emricitabine, and tenofovir). Despite stropping adalimumab, anti‐Tb, and antiviral therapy, he experienced persistent fever, neurological symptoms, and lymphadenopathy. Toxoplasmosis, Cytomegalovirus (CMV), and Human Herpesvirus‐8 (HHV‐8) were diagnosed and then treated. Furthermore, the patient displayed intermittent febrile episodes, pancytopenia, altered coagulation parameters, hypoalbuminemia, edema, and generalized abdominal pain, as well as radiological evidence of hepatosplenomegaly and pulmonary infiltrates. Left axillary lymph node biopsy (ALNB) was done and confirmed multicentric castleman disease (MCD). Moreover, the bone marrow aspirate showed plasmocytes. His treatment included chemotherapy with doxorubicin and rituximab while continuing his anti‐Tb and antiretroviral therapy. This complex case highlights the diagnostic challenges of managing CD in the presence of multiple coexisting conditions, emphasizing the need for comprehensive evaluation in complex clinical presentations. [ABSTRACT FROM AUTHOR]

POEMS syndrome is a rare multisystemic disease, characterized by polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes. The presence of polyneuropathy and monoclonal plasma cell proliferation is mandatory for the diagnosis of typical POEMS syndrome. However, some patients lack one of the mandatory features and are classified as the variants of POEMS syndrome. A 61-year-old male presented with the clinical picture of progressive numbness in both lower extremities and weakness in all four extremities for a 6-month duration associated with bilateral axillary lymphadenopathies, pedal edema, clubbing, and unintentional weight loss of 15 kg in 6 months. A nerve conduction study showed severe sensorimotor polyneuropathy of demyelinating type in all four extremities. A lymph node biopsy showed Castleman disease, and the computed tomography scan was suggestive of multiple osteosclerotic lesions. A diagnosis of the Castleman variant of POEMS syndrome was made, and the patient was treated with Bortezomib-based therapy with improvement in his symptoms on follow-up at 1 year. Due to the lack of definite treatment guidelines for this disease, the information provided through case reports and case series becomes very important for the treatment of such patients leading to the resolution of polyneuropathy and the maintenance of functionality in patients. [ABSTRACT FROM AUTHOR]

Castleman disease (CD) is a heterogeneous hematological condition characterized by distinctive histopathological features. The etiology remains unclear, and clinical symptoms are generally nonspecific. CD can occur in any location containing lymphatic tissue, with the mediastinum being the most common site, while adrenal involvement is rare. Adrenal CD is typically incidentally discovered during physical examination, commonly affecting one side. Imaging studies often make it challenging to differentiate from common adrenal tumors, necessitating pathological confirmation. Surgical intervention is the preferred treatment, and the prognosis is generally favorable.This paper presents a rare case of a left adrenal mass, which was diagnosed as Castleman disease following surgical resection.

This letter to the editor published in Leukemia & Lymphoma discusses a rare case of HHV8-related Castleman disease presenting with nephrotic syndrome and pauci-immune glomerulonephritis in an immunocompetent patient. The patient's condition improved with treatment, including steroids and Rituximab, leading to complete resolution of symptoms. The article highlights the challenges in diagnosing and treating this condition, emphasizing the importance of considering Castleman disease in cases of ANCA-negative pauci-immune glomerulonephritis, especially in the presence of specific symptoms. [Extracted from the article]

Introduction: Multicentric Castleman’s disease (MCD) with cutaneous involvement has rarely been discussed in dermatologic literature, with few reports. Cutaneous lesions in MCD may induce deep scars, causing a significant impact in the daily life of the patients. The treatment of Castleman’s disease (CD) is usually a challenge, especially in case of cutaneous involvement. Case Presentation: We report the case of a 35-year-old Caucasian man with a 3-year-old history of MCD with cutaneous involvement that we treated with a combined therapy characterized by siltuximab and 1,927 nm fractional laser. The patient showed a therapeutic response, characterized by a reduction of systemic symptoms and cutaneous manifestations. Conclusion: We believe that the combination of siltuximab and 1,927 nm fractional laser might have a synergistic beneficial role in patients with cutaneous iMCD and maximize esthetic outcomes. Anyway, additional evidence is needed to validate our findings.

Abstract Background Castleman’s disease is a rare lymphoproliferative disorder that is often misdiagnosed because of its untypical clinical or imaging features except for a painless mass. Besides, it is also difficult to cure Castleman’s disease due to its unclear pathogenesis. Case presentation We present a Castleman’s disease case with diagnostic significance regarding a 54-year-old Chinese male who has a painless mass in his left parotid gland for 18 months with a 30-years history of autoimmune disease psoriasis. Computed tomography scan showed a high-density nodule with clear boundaries in the left parotid and multiple enlarged lymph nodes in the left submandibular and neck region. General checkup, the extremely elevated serum interleukin-6 and lymph node biopsy in the left submandibular region gave us an initial suspicion of Castleman’s disease. Then the patient underwent a left superficial parotidectomy. Based on histopathologic analysis, we made a certain diagnosis of Castleman’s disease and gave corresponding treatments. In 18 months of follow-up, the patient showed no evidence of recurrence, with the level of serum interleukin-6 decreased. Conclusions Clinicians should be aware of the possibility of Castleman’s disease when faced with masses or enlarged lymph nodes in the parotid gland to avoid misdiagnosis, especially in patients with autoimmune diseases and elevated serum interleukin-6.

Lymphadenopathy is a common clinical finding and diagnostic challenge within general medicine and rheumatology practice. It may represent a primary manifestation of an underlying immune-mediated disease or indicate an infectious or neoplastic complication requiring differing management. Evaluating lymphadenopathy is of particular relevance in rheumatology, given that lymph node enlargement is a common finding within the clinical spectrum of several well-known rheumatologic disorders including RA, SLE and SS. In addition, lymphadenopathy represents a hallmark manifestation of rare immunological diseases such as Castleman disease and IgG4-related disease that must be considered in the differential diagnosis because effective targeted treatments can now impact the prognosis of these conditions. In this review we present an overview of the clinical significance of lymphadenopathy in common and rare rheumatologic diseases and propose a practical approach to lymphadenopathy in the rheumatology practice. Differential diagnosis of Castleman disease and therapeutic options for this condition of increasing rheumatologic interest will be discussed in detail. [ABSTRACT FROM AUTHOR]

Human herpesvirus 8 (HHV-8), associated with Kaposi sarcoma, primary effusion lymphoma (PEL), and multicentric Castleman disease, encodes four interferon regulatory factor homologs, vIRFs 1–4, that interact with and inhibit various mediators of host-cell defense against virus infection. A cellular protein targeted by all the vIRFs is ubiquitin-specific protease 7 (USP7); while replication-modulatory and latently infected PEL-cell pro-viability phenotypes of USP7 targeting have been identified for vIRFs 1–3, the significance of the interaction of vIRF-4 with USP7 has remained undetermined. Here we show, through genetic ablation of the vIRF-4-USP7 interaction in infected cells, that vIRF-4 association with USP7 is necessary for optimal expression of vIRF-4 and normal HHV-8 replication. Findings from experiments on transfected and infected cells identified ubiquitination of vIRF-4 via K48-linkage and USP7-binding-associated suppression of vIRF-4 ubiquitination and, in infected cells, increased vIRF-4 expression. Analysis of IFN-I induction and associated signaling as a function of vIRF-4 and its interaction with USP7 identified a role of each in innate-immune suppression. Finally, activation via K63-polyubiquitination of the innate-immune signaling mediator TRAF3 was found to be suppressed by vIRF-4 in a USP7-binding-associated manner in infected cells, but not in transfected cells, likely via binding-regulated expression of vIRF-4. Together, our data identify the first examples of vIRF ubiquitination and a vIRF substrate of USP7, enhanced expression of vIRF-4 via its interaction with USP7, and TRAF3-inhibitory activity of vIRF-4. The findings address, for the first time, the biological significance of the interaction of vIRF-4 with USP7 and reveal a mechanism of vIRF-4-mediated innate-immune evasion and pro-replication activity via TRAF3 regulation. IMPORTANCE HHV-8 homologs of cellular interferon regulatory factors (IRFs), involved in host-cell defense against virus infection, interact in an inhibitory fashion with IRFs and other mediators of antiviral innate immunity. These interactions are of demonstrated or hypothesized importance for successful primary, productive (lytic), and latent (persistent) infection by HHV-8. While HHV-8 vIRF-4 is known to interact physically with USP7 deubiquitinase, a key regulator of various cellular proteins, the functional and biological significance of the interaction has not been addressed. The present study identifies the interaction as important for HHV-8 productive replication and, indeed, for vIRF-4 expression and reveals a new function of vIRF-4 via inhibition of the activity of TRAF3, a pivotal mediator of host-cell antiviral activity through activation of cellular IRFs and induction of type-I interferons. These findings identify potential targets for the development of novel anti-HHV-8 agents, such as those able to disrupt vIRF-4–USP7 interaction or vIRF-4-stabilizing USP7 activity. [ABSTRACT FROM AUTHOR]

Kaposi sarcoma-associated herpesvirus (KSHV), also known as human herpesvirus-8, is the causal agent of Kaposi sarcoma, a cancer that appears as tumors on the skin or mucosal surfaces, as well as primary effusion lymphoma and KSHV-associated multicentric Castleman disease, which are B-cell lymphoproliferative disorders. Effective prophylactic and therapeutic strategies against KSHV infection and its associated diseases are needed. To develop these strategies, it is crucial to identify and target viral glycoproteins involved in KSHV infection of host cells. Multiple KSHV glycoproteins expressed on the viral envelope are thought to play a pivotal role in viral infection, but the infection mechanisms involving these glycoproteins remain largely unknown. We investigated the role of two KSHV envelope glycoproteins, KSHV complement control protein (KCP) and K8.1, in viral infection in various cell types in vitro and in vivo. Using our newly generated anti-KCP antibodies, previously characterized anti-K8.1 antibodies, and recombinant mutant KSHV viruses lacking KCP, K8.1, or both, we demonstrated the presence of KCP and K8.1 on the surface of both virions and KSHV-infected cells. We showed that KSHV lacking KCP and/or K8.1 remained infectious in KSHV-susceptible cell lines, including epithelial, endothelial, and fibroblast, when compared to wild-type recombinant KSHV. We also provide the first evidence that KSHV lacking K8.1 or both KCP and K8.1 can infect human B cells in vivo in a humanized mouse model. Thus, these results suggest that neither KCP nor K8.1 is required for KSHV infection of various host cell types and that these glycoproteins do not determine KSHV cell tropism. IMPORTANCE Kaposi sarcoma-associated herpesvirus (KSHV) is an oncogenic human gamma-herpesvirus associated with the endothelial malignancy Kaposi sarcoma and the lymphoproliferative disorders primary effusion lymphoma and multicentric Castleman disease. Determining how KSHV glycoproteins such as complement control protein (KCP) and K8.1 contribute to the establishment, persistence, and transmission of viral infection will be key for developing effective anti-viral vaccines and therapies to prevent and treat KSHV infection and KSHV-associated diseases. Using newly generated anti-KCP antibodies, previously characterized anti-K8.1 antibodies, and recombinant mutant KSHV viruses lacking KCP and/or K8.1, we show that KCP and K8.1 can be found on the surface of both virions and KSHV-infected cells. Furthermore, we show that KSHV lacking KCP and/or K8.1 remains infectious to diverse cell types susceptible to KSHV in vitro and to human B cells in vivo in a humanized mouse model, thus providing evidence that these viral glycoproteins are not required for KSHV infection. [ABSTRACT FROM AUTHOR]

TAFRO (thrombocytopenia (T), anasarca (A), fever (F), reticulin fibrosis (F/R), renal failure (R), and organomegaly (O)) is a heterogeneous clinical subtype of idiopathic multicentric Castleman disease (iMCD) associated with a significantly poorer prognosis than other subtypes of iMCD. TAFRO symptomatology can also be seen in pathological contexts outside of iMCD, but it is unclear if those cases should be considered representative of a different disease entity or simply a severe presentation of other infectious, malignant, and rheumatological diseases. While interleukin-6 (IL-6) is an established driver of iMCD-TAFRO pathogenesis in a subset of patients, the etiology is unknown. Recent case reports and literature reviews on TAFRO patients suggest that vascular endothelial growth factor (VEGF), and the interplay of VEGF and IL-6 in concert, rather than IL-6 as a single cytokine, may be drivers for iMCD-TAFRO pathophysiology, especially renal injury. In this review, we discuss the possible role of VEGF in the pathophysiology and clinical manifestations of iMCD-TAFRO. In particular, VEGF may be involved in iMCD-TAFRO pathology through its ability to activate RAS/RAF/MEK/ERK and PI3K/AKT/mTOR signaling pathways. Further elucidating a role for the VEGF-IL-6 axis and additional disease drivers may shed light on therapeutic options for the treatment of TAFRO patients who do not respond to, or otherwise relapse following, treatment with IL-6 targeting drugs. This review investigates the potential role of VEGF in the pathophysiology of iMCD-TAFRO and the potential for targeting related signaling pathways in the future. [ABSTRACT FROM AUTHOR]

TAFRO syndrome is an inflammatory disorder of unknown etiology characterized by thrombocytopenia, anasarca, fever, reticulin fibrosis, renal insufficiency, and organomegaly. Despite great advancements in research on the TAFRO syndrome in the last decade, its diagnosis and treatment are still challenging for most clinicians because of its rarity and severity. Since the initial proposal of the TAFRO syndrome as a distinct disease entity in 2010, two independent diagnostic criteria have been developed. Although these are different in the concept of whether TAFRO syndrome is a subtype of idiopathic multicentric Castleman disease or not, they are similar except for the magnitude of lymph node histopathology. Because there have been no specific biomarkers, numerous diseases must be ruled out before the diagnosis of TAFRO syndrome is made. The standard of care has not been fully established, but interleukin-6 blockade therapy with siltuximab or tocilizumab and anti-inflammatory therapy with high-dose corticosteroids are the most commonly applied for the treatment of TAFRO syndrome. The other immune suppressive agents or combination cytotoxic chemotherapies are considered for patients who do not respond to the initial treatment. Whereas glowing awareness of this disease improves the clinical outcomes of patients with TAFRO syndrome, further worldwide collaborations are warranted. [ABSTRACT FROM AUTHOR]

Idiopathic multicentric Castleman disease (iMCD) and TAFRO syndrome present a variety of symptoms thought to be caused by excessive inflammatory cytokines and chemokines, but the underlying mechanisms are unknown. iMCD is broadly classified into two types: iMCD-NOS and iMCD-TAFRO, which have distinct laboratory findings, pathological features, and responses to treatments. It is thought that iMCD-NOS, particularly the IPL type, responds favorably to IL-6 inhibitors due to its IL-6-centric profile. iMCD-TAFRO frequently progresses acutely and seriously, similar to TAFRO syndrome. Elevated levels of cytokines, including IL-1β, TNF-α, IL-10, and IL-23, as well as chemokines like CXCL13 and CXCL-10 (especially in iMCD-TAFRO), SAA, and VEGF, have been linked to the disease's pathology. Recent research has identified key signaling pathways including PI3K/Akt/mTOR and JAK-STAT3, as well as those regulated by type I IFN, as crucial in iMCD-TAFRO. These results suggest that dominant pathways may vary between subtypes. Further research into the peripheral blood and lymph nodes is required to determine the disease spectrum of iMCD-NOS/iMCD-TAFRO/TAFRO syndrome. [ABSTRACT FROM AUTHOR]

Summary: Idiopathic multicentric Castleman disease (iMCD) is subclassified into iMCD‐thrombocytopenia, anasarca, reticulin fibrosis, renal dysfunction, organomegaly (TAFRO) and iMCD‐not otherwise specified (NOS) according to the Castleman Disease Collaborative Network (CDCN) consensus criteria. With a deeper understanding of iMCD, a group of patients with iMCD‐NOS characterised by polyclonal hypergammaglobulinaemia, plasmacytic/mixed‐type lymph node histopathology and thrombocytosis has attracted attention. This group of patients has been previously described as having idiopathic plasmacytic lymphadenopathy (IPL). Whether these patients should be excluded from the current classification system lacks sufficient evidence. This retrospective analysis of 228 patients with iMCD‐NOS identified 103 (45.2%) patients with iMCD‐IPL. The clinical features and outcomes of patients with iMCD‐IPL and iMCD‐NOS without IPL were compared. Patients with iMCD‐IPL showed a significantly higher inflammatory state but longer overall survival. No significant difference in overall survival was observed between severe and non‐severe patients in the iMCD‐IPL group according to the CDCN severity classification. Compared with lymphoma‐like treatments, multiple myeloma‐like and IL‐6‐blocking treatment approaches in the iMCD‐IPL group resulted in significantly higher response rates and longer time to the next treatment. These findings highlight the particularities of iMCD‐IPL and suggest that it should be considered a new subtype of iMCD‐NOS. [ABSTRACT FROM AUTHOR]

Lymphoproliferation is defined by lymphadenopathy, splenomegaly, hepatomegaly, or lymphocytic organ and tissue infiltration. The most common etiologies of lymphoproliferation are represented by infectious diseases and lymphoid malignancies. However, it is increasingly recognized that lymphoproliferative features can be the presenting sign of rare conditions, including inborn errors of immunity (IEI) and inborn errors of metabolism (IEM). Among IEI, lymphoproliferation is frequently observed in autoimmune lymphoproliferative syndrome (ALPS) and related disorders, common variable immunodeficiency (CVID), activated phosphoinositide 3-kinase δ syndrome, and Epstein-Barr virus (EBV)-related disorders. Gaucher disease and Niemann-Pick disease are the most common IEMs that can present with isolated lymphoproliferative features. Notably, other rare conditions, such as sarcoidosis, Castleman disease, systemic autoimmune diseases, and autoinflammatory disorders, should be considered in the differential diagnosis of patients with persistent lymphoproliferation when infectious and malignant diseases have been reasonably ruled out. The clinical features of lymphoproliferative diseases, as well as the associated clinical findings and data deriving from imaging and first-level laboratory investigations, could significantly help in providing the correct diagnostic suspicion for the underlying etiology. This paper reviews the most relevant diseases associated with lymphoproliferation, including infectious diseases, hematological malignancies, IEI, and IEM. Moreover, some practical indications to orient the initial diagnostic process are provided, and two diagnostic algorithms are proposed for the first-level assessment and the approach to persistent lymphoproliferation, respectively. [ABSTRACT FROM AUTHOR]

Objective: To describe cases of Kaposi's sarcoma‐associated herpesvirus (KSHV)‐associated multicentric Castleman's disease (MCD) and primary effusion lymphoma (PEL) in patients with HIV from a large, safety‐net hospital system in Dallas, Texas, USA. Methods: We conducted a retrospective review of patients with HIV‐associated PEL and/or MCD. Results: Twelve patients with PEL and 10 patients with MCD were identified. All patients were male and 17 of 20 were men who have sex with men; 66.7% of PEL patients and 50% of MCD patients had concurrent KS at the time of diagnosis; 42% of patients with PEL and 20% of patients with MCD died during the follow‐up period. We noted improved survival in our cohort compared to previous studies, particularly in our PEL patients with a median survival of 11.4 months compared to 3–6‐month median survival historically. Median follow‐up time for MCD patients was 17.5 months. This improved survival is despite suboptimal antiretroviral therapy (ART) adherence at diagnosis, with only 50% of patients on ART at the time of MCD/PEL diagnosis. Conclusion: These data highlight the importance of early recognition of PEL and MCD, and the larger‐scale efforts needed to better understand the pathogenetic drivers of clinical outcomes in patients affected by KSHV‐related diseases. [ABSTRACT FROM AUTHOR]

Copyright of Colombian Journal of Nephrology / Revista Colombiana de Nefrología is the property of Colombian Association of Nephrology & Hypertension and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

TAFRO syndrome is a rare and aggressive inflammatory entity characterized by thrombocytopenia, anasarca, fever, renal failure, reticulin fibrosis, and organomegaly. This entity supposes a diagnostic and therapeutic challenge due to its significant overlap with Castleman's disease. However, distinct clinical and histological features warrant its classification as a separate subtype of idiopathic multicentric Castleman's disease (iMCD). While recent modifications have been made to the diagnostic criteria for iMCD, these criteria lack specificity for this particular condition, further complicating diagnosis. Due to its inflammatory nature, several complex molecular signaling pathways are involved, including the JAK-STAT pathway, NF-kB, and signal amplifiers such as IL-6 and VEGF. Understanding the involvement of immune dysfunction, some infectious agents, genetic mutations, and specific molecular and signaling pathways could improve the knowledge and management of the condition, leading to effective treatment strategies. The current therapeutic approaches include corticosteroids, anti-IL6 drugs, rituximab, and chemotherapy, among others, but response rates vary, highlighting the need for personalized strategies. The prognosis is uncertain due to diagnostic difficulties, emphasizing the importance of early intervention and appropriate targeted treatment. This comprehensive review examines the evolving landscape of TAFRO syndrome, including the pathophysiology, diagnostic criteria, treatment strategies, prognosis, and future perspectives. [ABSTRACT FROM AUTHOR]

TAFRO syndrome is an acute systemic inflammatory disorder characterized by thrombocytopenia, anasarca, fever, reticulin myelofibrosis, renal dysfunction, and organomegaly. While its lymph node pathology is similar to that of idiopathic multicentric Castleman disease (iMCD), the clinical features of TAFRO syndrome differ from those of typical iMCD, as they include a more aggressive clinical course and high mortality. However, an optimal treatment strategy for TAFRO syndrome has not yet been established, owing to a poor understanding of its pathogenesis. The limited cases we encountered suggest that tacrolimus treatment in combination with glucocorticoids may potentially be effective and well tolerated as an initial treatment, and hold promise as a glucocorticoid-sparing agent. Herein, we report an additional case and review the sparse literature available regarding TAFRO syndrome treated via tacrolimus. [ABSTRACT FROM AUTHOR]

Copyright of Zeitschrift für Rheumatologie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Objective: Rare disease Background: Castleman's disease (CD) is a reactive lymph node hyperplasia initially identified by Castleman in 1956. CD predominantly affects individuals 20-50 years of age, with low incidence in children. This case report describes 3 cases of CD treated in our hospital and reviews the relevant literature. The purpose of this case report was to enhance clinical understanding and treatment of CD in the head and neck in children. Case Reports: To enhance clinical understanding and improve treatment of CD in the head and neck region in children, we present the cases of 3 patients who were admitted to the hospital, primarily presenting with a neck mass. Preoperatively, the patients collectively exhibited non-specific findings. Surgical interventions were performed with Cases 1 and 3 undergoing left functional (radical) neck lymph node dissection, in contrast to Case 2, in which bilateral functional (radical) neck lymph node dissection was executed. Pathological examination confirmed the diagnosis of CD in each of the 3 patients. Following surgery, a follow-up period ranging from 3 months to 1 year revealed that all patients had successfully recovered, with no recurrence. Conclusions: Castleman disease is a rare disease in children and difficult clinical diagnosis. Some patients with unicentric Castleman disease (UCD) can be treated with surgery, and those with multicentric Castleman disease (MCD) need chemotherapy, but at present there is no widely accepted treatment plan. [ABSTRACT FROM AUTHOR]

An 11-year-old otherwise healthy female presented with renal colic and during computed tomography imaging evaluation, she was found to have a right distal ureteral stone with associated hydroureteronephrosis, medially deviated ureter, and 4-cm solid retroperitoneal mass. The mass was palpable on physical exam and was further categorized with magnetic resonance imaging, ultrasound, and laboratory testing. A multidisciplinary team approach, including pediatric surgery, radiology, oncology, and urology, led to the patient undergoing a right retrograde pyelogram, ureteroscopy with stent placement, and laparoscopic excision of retroperitoneal mass. Her pathology revealed lymphoid hyperplasia with histologic features of Castleman disease. [ABSTRACT FROM AUTHOR]

Acquired hemophilia is caused by acquired autoantibodies to 1 of the factors of the coagulation cascade, usually factor VIII or IX, and is an exceedingly rare phenomenon in children. The finding of an acquired factor VIII inhibitor in a pediatric patient with idiopathic multicentric Castleman disease has never been reported. Patients with acquired hemophilia can have life-threatening bleeds that are refractory to blood product support, requiring bypassing agents to manage bleeding symptoms. We present the novel finding of acquired hemophilia resulting from an autoantibody to factor VIII in a pediatric patient with idiopathic multicentric Castleman disease and discuss the optimal management of bleeding in a patient with acquired hemophilia. [ABSTRACT FROM AUTHOR]

Background: Castleman's disease is a rare lymphoproliferative disorder that is often misdiagnosed because of its untypical clinical or imaging features except for a painless mass. Besides, it is also difficult to cure Castleman's disease due to its unclear pathogenesis. Case presentation: We present a Castleman's disease case with diagnostic significance regarding a 54-year-old Chinese male who has a painless mass in his left parotid gland for 18 months with a 30-years history of autoimmune disease psoriasis. Computed tomography scan showed a high-density nodule with clear boundaries in the left parotid and multiple enlarged lymph nodes in the left submandibular and neck region. General checkup, the extremely elevated serum interleukin-6 and lymph node biopsy in the left submandibular region gave us an initial suspicion of Castleman's disease. Then the patient underwent a left superficial parotidectomy. Based on histopathologic analysis, we made a certain diagnosis of Castleman's disease and gave corresponding treatments. In 18 months of follow-up, the patient showed no evidence of recurrence, with the level of serum interleukin-6 decreased. Conclusions: Clinicians should be aware of the possibility of Castleman's disease when faced with masses or enlarged lymph nodes in the parotid gland to avoid misdiagnosis, especially in patients with autoimmune diseases and elevated serum interleukin-6. [ABSTRACT FROM AUTHOR]

Kaposi's sarcoma (KS) and multicentric Castleman's disease (MCD) are both linked to human herpesvirus-8 (HHV-8) infection which most commonly affects people living with human immunodeficiency virus (HIV). Herein, we describe the case of a 57-year-old patient who has been admitted for fever, night sweats, weight loss, and diffuse lymphadenopathy with abdominal pain. HIV status was confirmed by a positive Western blot test. His initial CD4 cell count was equal to 270 cells/µL. A histological study of a peripheral lymph node concluded that KS is associated with MCD. These two conditions found in the same patient highlight the malignant potential of HHV-8, particularly in the case of HIV-induced immunodeficiency. [ABSTRACT FROM AUTHOR]

Background: Castleman disease (CD) is an uncommon benign lymphoproliferative disease characterized by hypervascular lymphoid hyperplasia. We present a unique case of unicentric CD of the parotid gland treated by preoperative direct puncture embolization. Case presentation: A 27-year-old female patient was admitted for a right neck mass. Ultrasound examination and MRI scan documented a hypervascular mass within the right parotid gland. Preoperative embolization was performed by direct puncture technique: a needle was inserted into the core of the mass under both ultrasound and fluoroscopic guidance and SQUID 12 was injected into the mass under fluoroscopic control, achieving a total devascularization. Conclusion: Preoperative direct puncture embolization was safe and effective and provides excellent hemostatic control during the surgical operation, limiting the amount of intraoperative bleeding. [ABSTRACT FROM AUTHOR]

Human herpesvirus 8 (HHV8)-associated diseases include Kaposi sarcoma (KS), multicentric Castleman disease (MCD), germinotropic lymphoproliferative disorder (GLPD), Kaposi sarcoma inflammatory cytokine syndrome (KICS), HHV8-positive diffuse large B-cell lymphoma (HHV8+ DLBCL), primary effusion lymphoma (PEL), and extra-cavitary PEL (ECPEL). We report the case of a human immunodeficiency virus (HIV)-negative male treated for cutaneous KS, who developed generalized lymphadenopathy, hepatosplenomegaly, pleural and abdominal effusions, renal insufficiency, and pancytopenia. The excised lymph node showed features of concomitant involvement by micro-KS and MCD, with aggregates of HHV8+, Epstein Barr virus (EBV)-negative, IgM+, and lambda+ plasmablasts reminiscent of microlymphoma. Molecular investigations revealed a somatically hypermutated (SHM) monoclonal rearrangement of the immunoglobulin heavy chain (IGH), accounting for 4% of the B-cell population of the lymph node. Mutational analyses identified a pathogenic variant of KMT2D and variants of unknown significance in KMT2D, FOXO1, ARID1A, and KMT2A. The patient died shortly after surgery. The histological features (HHV8+, EBV−, IgM+, Lambda+, MCD+), integrated with the molecular findings (monoclonal IGH, SHM+, KMT2D mutated), supported the diagnosis of a monoclonal HHV8+ microlymphoma, with features intermediate between an incipient HHV8+ DLBCL and an EBV-negative ECPEL highlighting the challenges in the accurate classification of HHV8-driven lymphoid proliferations. [ABSTRACT FROM AUTHOR]

Background: Castleman disease (CD), also known as angiofollicular lymph node hyperplasia or large lymph node hyperplasia, is a rare medical condition. Despite its rarity, it exhibits diverse clinical presentations and outcomes, which pose challenges for comprehensive understanding and management. This study aims to shed light on the demographics, associations, and outcomes of CD by conducting a retrospective analysis. Methods: The National Inpatient Sample (US) was used to identify patients with the diagnosis of Castleman disease using ICD-10 diagnosis code D47.Z2, during the years 2016–2019. Data was collected on demographics, associated diagnoses, treatments and outcomes. Data analysis was performed using STATA Version 17, College Station, TX: Stata Corp LLC. Results: Our study identified 791 hospitalizations involving adult CD patients. The mean age of these patients was 52.4 years, with a male predominance (56.1%). Whites comprised the largest racial group affected (50.1%). Most patients were covered by Medicare (39.6%). The majority received treatment in urban teaching hospitals (84.0%) and large-bed size facilities (62.5%). In-hospital mortality was low at 2.8%, with an average length of stay of 7.5 days and average total charges of $109,308. Common associations included acute kidney injury (27.0%), congestive heart failure (17.1%), sepsis (16.4%), and acute respiratory failure (12.6%). Hematological and lymphatic associations featured anemia (47.5%), thrombocytopenia (12.2%), and other conditions. Red blood cell transfusions were administered to 11.1% of patients. Conclusion: This study contributes valuable insights into CD, a rare and clinically heterogeneous disease. It underscores the importance of recognizing its associations and complications. Additionally, it highlights the need for further research and improved diagnostic and treatment guidelines to address the complexity of this condition. [ABSTRACT FROM AUTHOR]

This systematic review article aims to investigate the clinical and radiological imaging characteristics of adrenal abnormalities in patients with thrombocytopenia, anasarca, fever, reticulin fibrosis, renal dysfunction, and organomegaly (TAFRO) syndrome. We searched the literature in PubMed, the Cochrane Library, and the Web of Science Core Collection. Ultimately, we analyzed 11 studies with 22 patients plus our 1 patient, totaling 23 patients. The mean age was 47.0 ± 12.6 years. There were 20 male and 3 female patients, respectively. The histopathological analysis of lymph nodes was conducted in 15 patients (65.2%), and the diagnosis was consistent with TAFRO syndrome in all 15 patients. Among the 23 patients, 11 patients (18 adrenal glands) showed adrenal ischemia/infarction, 9 patients (13 adrenal glands) showed adrenal hemorrhage, and 4 patients (7 adrenal glands) showed adrenomegaly without evidence of concurrent ischemia/infarction or hemorrhage. One patient demonstrated unilateral adrenal hemorrhage and contralateral adrenomegaly. In patients with adrenal ischemia/infarction, the adrenal glands displayed poor enhancement through contrast-enhanced computed tomography (CT). In patients with adrenal hemorrhage, the adrenal glands revealed high attenuation through non-enhanced CT and hematoma through magnetic resonance imaging. Adrenomegaly, with or without adrenal ischemia/infarction or hemorrhage, was observed in all patients (23/23, 100%). The subsequent calcification of the affected adrenal glands was frequently observed (9/14, 64.3%) when a follow-up CT was performed. Abdominal pain was frequent (15/23, 65.2%), all of which occurred after the disease's onset, suggesting the importance of considering TAFRO syndrome as a cause of acute abdomen. Given the absence of evidence of adrenal abnormalities in non-TAFRO-idiopathic multicentric Castleman disease (iMCD), they may serve as diagnostic clues for differentiating TAFRO syndrome from non-TAFRO-iMCD. [ABSTRACT FROM AUTHOR]

Key Clinical Message Castleman's Disease should be considered in the differential diagnosis of retroperitoneal masses, especially in equivocal cases. Clinician should not presume all cases of retroperitoneal masses as a malignancy. Abstract Castleman's Disease is a heterogeneous group of lymphoproliferative disorders, that can develop in lymph nodes or in extranodal sites. It has three distinct histological subtypes; hyaline vascular, plasma cell or mixed. It can be unicentric or multicentric, and sometimes oligocentric or regional. In this article, we report a case of a 30‐year‐old male who presented with a palpable left lumbar mass, clinically suspected as sarcoma vs GIST, which was surgically excised and pathologically examined revealing a rare condition of intra‐abdominal unicentric Castleman's Disease with good prognosis. Castleman's Disease should be considered in the differential diagnosis of retroperitoneal masses, especially in equivocal cases.