Mesenteric Castleman Disease Mimicking Neuroendocrine Tumor.

Castleman disease (CD) is a benign lymphoproliferative disorder of unknown etiology, which can involve any part of the body. CD can involve a single lymph node (unicentric) or multiple lymph nodes (multicentric) of which unicentric CD is the most common type. The unicentric CD is usually localized, asymptomatic, and often appears as an incidental mass on radiographs, whereas multicentric CD is characterized by systemic involvement. Mesenteric involvement of CD is very rare. In this article, we present a case of the unicentric CD of small bowel mesentery, which mimicked a neuroendocrine tumor preoperatively.

Mesenteric Mixed Type of Castleman Disease: A Report of a Rare Case.

Castleman disease is a rare type of lymph node hyperplasia primarily affecting the mediastinum, with mesenteric localization being extremely uncommon. It is classified into solitary and multicentric forms. In this case report, we present the case of a 46-year-old female patient in whom an incidental mesenteric mass was discovered during the workup for a ventral hernia. The mass was completely excised, and the histopathological examination confirmed the diagnosis of mixed-type Castleman disease. Surgery is the treatment of choice for localized forms of this condition, and histological examination is crucial in confirming the diagnosis.

A rare presentation of unicentric Castleman's disease in the thigh: A case report and review of literature.

BACKGROUND: Castleman's disease (CD) is a rare lymphoproliferative, emulating both benign and malignant diseases. The diagnosis of CD is formulated upon the combination of clinical and laboratory criteria and ultimately confirmed by histopathological assessment. Due to its rarity, CD presents a challenge in treatment selection, with available options encompassing surgery, chemotherapy, and autologous stem cell transplantation. However, studies suggest that surgical resection of the lesion is the most effective treatment modality, especially for unicentric CD (UCD). CASE SUMMARY: Here, we describe the case of a 25-year-old woman who presented with painless left thigh swelling for 10 wk. She had been following a low-fat diet to lose weight and had normal laboratory results. Magnetic resonance imaging revealed a well-circumscribed, demarcated cystic lesion located in the left inguinal region with eccentrically positioned signal void vascular structures, measuring 4.3 cm × 3 cm × 3.2 cm, likely of lymphoid origin. The patient underwent surgical resection, and the final histopathology showed a vascular proliferation and hyalinization of the vessel walls, along with atretic germinal centers traversed by penetrating vessels, consistent with CD. The patient was discharged home one day after the procedure in good condition, with a follow-up appointment scheduled in our outpatient clinic. CONCLUSION: Although surgical resection is the mainstay for UCD, a multidisciplinary approach is needed due the lack of specific diagnostic features and treatments.

Ten-year anemia as initial manifestation of Castleman disease in the abdominal cavity: A case report.

Castleman disease (CD) is a relatively rare lymphoproliferative disorder. Lesions predominantly originate on the chest and neck and rarely occur on the abdomen. A 34-year-old female presented to our hospital with an unexplained 10-year history of anemia. A pathological diagnosis of plasma cell-type CD was established. One cycle of chemotherapy (thalidomide, cyclophosphamide, and prednisolone) improved her anemia significantly. Prompt etiological diagnosis and early intervention are essential to address systemic manifestations in patients with CD, and it is crucial to consider CD as a differential diagnosis when intra-abdominal masses are detected.

The Transformation of Neck Unicentric Castleman's Disease to Follicular Dendritic Cell Sarcoma.

A patient with a large neck mass underwent appropriate imaging, routine blood tests, and serological evaluations. The medical history revealed the patient had undergone a lymphadenectomy in the same region 8 years ago, and the pathological diagnosis was the hyaline-vascular subtype of unicentric Castleman's disease (UCD). The incisional biopsy and subsequent histopathological and immunohistochemical examination revealed the diagnosis of follicular dendritic cell sarcoma, consistent with the malignant transformation of UCD. UCD is uncommon and the malignant transformation of UCD is extremely rare in the head and neck region. Regional lymph node resection of one or more adjacent regions is the preferred treatment choice. Appropriate treatment procedures for UCD and regular follow-up are essential for a good prognosis. Laryngoscope, 2024.

Idiopathic multicentric Castleman disease and connective tissue disorder successfully treated by siltuximab: a pediatric case report.

Background: Castleman disease (CD) is a rare lymphoproliferative disease. Idiopathic multicentric CD (iMCD), representing a distinct entity in CD, is partly attributed to autoimmune abnormalities and the hyperplastic process in iMCD involving the immune system. Consequently, iMCD presents a range of overlapping manifestations with connective tissue disorder (CTD), resulting in an inability to tell whether they coexist or imitate each other. Reports of CD combined with CTD are rare, more cases are needed to be summarized and analyzed to improve the efficiency of diagnosis and accelerate the development of novel treatments. Case Description: A male pediatric patient was diagnosed with CTD in October 2019 and had been receiving regular treatment with tocilizumab and glucocorticoid or methotrexate since April 2020. He was further diagnosed with iMCD of the hyaline vascular subtype according to biopsy-proven histopathological features and imaging-proven multiple involvement in August 2021. He received 4 doses of rituximab and then a combination of thalidomide and dexamethasone for about 1 year. His clinical symptoms were well controlled throughout the disease for a long period, but inflammatory markers were repeatedly elevated, which eventually turned normal after switching to siltuximab from July 2023, although a significant elevation of interleukin-6 occurred. Conclusions: We reported a pediatric case diagnosed as CTD and iMCD, whose inflammation finally be well controlled by siltuximab. Hopefully, our work will add insight into such rare situations and it is undoubtedly that the pathophysiological mechanism of CD and CTD coexistence and prediction models of treatment response remains to be explored to facilitate the clinical management and optimal treatment.

TAFRO Syndrome: Guidance for Managing Patients Presenting Thrombocytopenia, Anasarca, Fever, Reticulin Fibrosis, Renal Insufficiency, and Organomegaly.

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.

Abdominal CT findings characteristic of castleman disease: multi-center review of 76 adult cases with abdominopelvic nodal involvement.

OBJECTIVE: Characterize the CT findings of abdominopelvic Castleman disease, including a new observation involving the perinodal fat. METHODS: Multi-center 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 < 0.001). 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 hyaline vascular variant. 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.

HHV-8 Linked to Kaposi's Sarcoma and Castleman's Disease in HIV-1-infected patient: Case Report and Review of the Literature.

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.

Immunology and targeted therapy in Castleman disease.

INTRODUCTION: 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. AREAS COVERED: 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. EXPERT OPINION: 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.

Rituximab as a First-line Treatment for Autoimmune Hemolytic Anemia in Multicentric Castleman's Disease.

Castleman´s disease (CD) is a rare lymphoproliferative disorder. Concurrent autoimmune disease and CD are uncommon, but even more so, comorbid CD and autoimmune hemolytic anemia (AIHA). To the best of our knowledge, this case represents the first successful AIHA and multicentric CD (MCD) treatment using rituximab as first-line treatment. We present the case of a 53-year-old woman with a 10-year history of plasma cell variant CD who arrived at the emergency department with signs and symptoms of anemia. On admission, we made a preliminary diagnosis of hemolytic anemia and initiated immunosuppressive therapy with rituximab and steroids. After seven days, the patient recovered according to clinical and laboratory parameters, and we discharged her early. We portray a rare occurrence of CD and AIHA successfully treated with rituximab and steroid therapy, which makes our case unique.

Tacrolimus Treatment for TAFRO Syndrome.

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.

Stroma-Rich Hyaline Vascular Type of Castleman Disease: A Case Report and Literature Review.

Castleman disease (CD) is a rare lymphoproliferative disorder characterized by abnormal lymph node enlargement. We present the first documented case of a stroma-rich variant of hyaline vascular Castleman disease in Saudi Arabia. A 24-year-old Saudi female known to have acetylcholine receptor antibody-positive myasthenia gravis (MG) presented with shortness of breath, oral thrush, and an acute myasthenia gravis exacerbation, necessitating intensive care unit (ICU) admission. During her hospitalization, she was found to have a large pelvic mass. The mass was surgically excised. The diagnosis of stroma-rich hyaline vascular Castleman disease was rendered after histopathological examination. The patient's symptoms improved after the surgery. This case underscores the importance of considering Castleman disease in complex clinical presentations, especially in the context of autoimmune and paraneoplastic diseases. Recognition and timely intervention are crucial for patient management. Additionally, the report adds to the global literature on Castleman disease, emphasizing the need for further research into its clinical manifestations and associations.

TAFRO Syndrome on 18F-FDG-PET/CT: An Appealing Diagnostic Tool.

TAFRO syndrome (TS) is a recently recognized and heterogenous systemic disease characterized by a confluence of symptoms: thrombocytopenia (T), anasarca (A), fever (F), reticulin myelofibrosis (R), and organomegaly (O). First described in Japan in 2010, the pathogenesis remains unclear and includes various clinical conditions such as malignancies, rheumatologic disorders, infections, and "Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal plasma cell disorder, and Skin changes" (POEMS) syndrome. Due to its heterogeneous presentation and potential life-threatening delays in diagnosis, accurate diagnosis is crucial. According to the literature, no specific imaging modality has been recommended for the work-up of patients with suspected TS. Here, we report a case of TS and its management using 18F-FDG-PET/CT imaging as an attractive complementary diagnostic tool.

Castleman disease of the renal hilum: A rare case report.

Castleman's disease is a rare benign lymphangioproliferative disorder. The hyaline vascular subtype has a better outcome and is curable after surgical resection. Typically, Castleman disease manifests in the thorax, with rare reports of a renal hilum location. We present a 42-year-old male patient who had an incidentally detected right hilar hyaline vascular type of Castleman's disease, which we managed with surgical excision. Cross-sectional imaging modalities help in suggesting the diagnosis based on enhancement patterns and, more importantly, define the extent of the tumor pre-operatively. Although the renal hilum is a rare location for Castleman disease, it needs to be considered when imaging features suggest it.

Sirolimus is effective for refractory/relapsed idiopathic multicentric Castleman disease: A single-center, retrospective study.

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.

Successful outcome in a case of idiopathic multicentric Castleman disease with atypical lymphadenopathy and kidney injury: Diagnostic challenges and treatment approach-Case report.

Idiopathic multicentric Castleman disease is a rare and complex disease characterized by systemic inflammation, lymphadenopathy, and multiorgan involvement. This case report presents a 66-year-old Chinese man with idiopathic multicenter Castleman disease without significant lymphadenopathy and challenging diagnosis. Patients present with fever, fatigue, loss of appetite, weight loss, and acute kidney injury. Initially, a urinary tract infection was suspected, but despite anti-infective treatment, the patient's symptoms persisted. Lymph node biopsy, although there is no significant lymphadenopathy, confirms idiopathic multicenter Castleman disease. Treatment includes thalidomide, cyclophosphamide, and dexamethasone, as well as supportive measures and infection control. After 8 months of follow-up, the patient's clinical symptoms, inflammatory markers and renal function were significantly improved, and there was no symptomatic recurrence. This case underscores the importance of considering idiopathic multicenter Castleman's disease in patients with persistent fever and systemic inflammation, even in the absence of significant lymphadenopathy. Early identification and accurate diagnosis of idiopathic multicenter Castleman's disease can lead to the initiation of targeted therapy strategies that ultimately yield favorable outcomes.

Unicentric Castleman's disease in the parotid gland associated with psoriasis: a case report.

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.