Cytological diagnosis of hyaline-vascular type of Castleman disease.

Castleman disease (CD) is a rare, benign lymphoproliferative disorder, mostly involving the mediastinal lymph nodes, but can occur wherever lymphoid tissue is found. With only a few published case reports, there needs to be more literature on its cytological findings. We report the case of a 63-year-old female presenting with left upper cervical swelling. Fine needle aspiration cytology smears showed variably sized lymphoid follicles with diminished germinal centers, prominence of follicular dendritic cells, and capillaries traversing some of the follicles. The possibility of a hyaline-vascular type of Castleman disease was suggested. Histopathology confirmed the cytological diagnosis. The index case is being presented to discuss the cytological features of the CD along with its histological and immunohistochemical correlation.

Coexistence of HHV-8-Associated Plasmacytic Multicentric Castleman Disease, Kaposi's Sarcoma, and Multiple Myeloma in a HIV-Negative Patient.

Background: Multicentric Castleman disease (MCD) is a rare, aggressive lymphoproliferative disorder. Human herpesvirus-8 (HHV-8) has an important role in the pathogenesis of the disease and its association with Kaposi's sarcoma has been reported, especially in people living with human immunodeficiency virus (HIV). In this report, we present the case of HHV-8 positive MCD accompanied by Kaposi's sarcoma and multiple myeloma in an HIV-negative patient. Case Report: A 78-year-old man with Kaposi's sarcoma presented with B symptoms, pancytopenia, lymphadenopathy, and splenomegaly. The bone marrow biopsy demonstrated 70% lambda-restricted monotypic plasma cell infiltration consistent with plasma dyscrasia. Also, the patient was diagnosed with HHV-8 positive MCD as a result of inguinal lymph node excisional biopsy. Treatment was initiated including ganciclovir and methylprednisolone and followed by rituximab. The patient passed away at the 24th hour of rituximab infusion due to shock. Conclusions: MCD and associated malignancies are difficult to treat and have a poor prognosis. More studies and data are needed to manage these patients. LEARNING POINTS: Multicentric Castleman disease (MCD), often linked with human herpesvirus-8 (HHV-8) and Kaposi's sarcoma, is rare and aggressive condition, particularly in human immunodeficiency virus (HIV)-positive patients.The coexistence of MCD, Kaposi's sarcoma, and multiple myeloma is exceptionally rare in HIV-negative, immunocompetent patient.This case highlights the challenges in diagnosing and managing complex presentations of MCD and related malignancies, with poor outcomes despite treatment.

Diaphragmatic Castleman's disease: A rare lymphoproliferative disorder: Clinical and radiological perspectives.

Castleman's disease (CD) is a rare, benign nonclonal lymphoproliferative disorder with an unclear etiology, presenting significant diagnostic challenges due to its nonspecific features. CD is categorized into unicentric (UCD) and multicentric (MCD) types, with MCD further divided into HHV-8-associated and idiopathic (iMCD) forms. Clinical manifestations include fever, weight loss, night sweats, and organomegaly, with specific symptoms depending on the subtype. Diagnostic criteria for CD involve a combination of major criteria-histopathologic examination and minor criteria. Imaging techniques, including CT, MRI, and PET-CT, play a crucial role in diagnosis, staging, and differentiation from other diseases. This paper discusses the pathophysiology, clinical features, diagnostic criteria, and imaging findings of CD, illustrated by a case of a patient with renal disease with incidentally detected a right cardiophrenic mass. The case highlights the importance of comprehensive imaging and clinical evaluation in managing CD.

Clinicopathological characteristics of unicentric Castleman disease: A single-center experience of 12 patients.

BACKGROUND: Castleman disease (CD) is an uncommon lymphoproliferative disorder with distinct pathological characteristics. Unicentric Castleman disease (UCD) presents as a single lymph node enlargement, often without significant symptoms. Complete surgical resection is the standard treatment for UCD. This study aimed to explore the clinicopathological features of UCD in a Taiwanese population. METHODS: We retrospectively identified 12 patients with UCD who had undergone surgical treatment between January 1, 2006 and June 30, 2022 at the National Taiwan University Hospital. Clinical and radiological findings were retrieved from medical records. All available pathological slides were reviewed. RESULTS: The patients' mean age was 38.1 years (range, 17 to 69); five (41.7%) were male, and seven (58.3%) were female. Nearly all cases of UCD were in the mediastinum, except for one case in the neck. Most patients were asymptomatic and without abnormal laboratory test results. Computed tomography revealed well-defined tumor borders, contrast enhancement, and occasional calcification. Ten patients underwent en bloc tumor resection, while the remaining two underwent partial resection. Among them, seven (58.3%) underwent video-assisted thoracoscopic surgery (VATS), and four (33.3%) underwent thoracotomy. The mean follow-up duration was 92 months. The patients who underwent total resection had no recurrence. CONCLUSION: Detailed clinicopathological information on UCD in the Taiwanese population is present in our article. Both complete and partial surgery are effective for treatment. VATS may be preferred over thoracotomy due to less operative time and bleeding.

Castleman's Disease Mimicking Malignant Submandibular Tumor: A Case Report.

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.

Peculiar hyper vascular manifestations in idiopathic multicentric castleman disease without tafro syndrome: a case report.

BACKGROUND: Castleman disease affects lymph nodes with abnormal cell growth. It has unicentric (single node) Castleman disease (UCD) and multicentric (multiple nodes) Castleman disease (MCD) forms. MCD is systemic, with diverse symptoms, necessitating systemic treatment. Idiopathic MCD (iMCD) clinical subtypes are divided into iMCD- not otherwise specified (NOS) and iMCD-TAFRO (thrombocytopenia, anasarca, fever, reticular fibrosis, organomegaly). UCD, iMCD-NOS, and iMCD-TAFRO mainly exhibit histopathology of hyaline vascular type, plasma cell type, and hyper vascular type, respectively. CASE PRESENTATION: A 21-year-old female with no comorbidities presented to the outpatient department (OPD) with left inguinal swelling, gradually growing over four years, accompanied by fever and weight loss. Her past medical history included pulmonary TB 5 years prior and miscarriages. Vitals are within normal limits. Examination revealed a tender, nonreducible inguinal lump and a smaller neck swelling. Serological tests for infections were negative. Imaging revealed enlarged lymph nodes. Biopsy confirmed Castleman disease of the hyper vascular type. We performed surgical removal of the enlarged lymph nodes followed by close regular follow-up along with potential chemotherapy for relapse. CONCLUSION: Hyper vascular type of the lymph node histology in Idiopathic multicentric Castleman disease without TAFRO syndrome must be considered a differential diagnosis in lymphoproliferative disease.

Unicentric Castleman disease masquerading as a gluteal mass: A diagnostic challenge.

Castleman disease, a rare lymphoproliferative disorder characterized by non-neoplastic lymph node enlargement, typically presents as nodal involvement, while extranodal manifestations are uncommon. We present a unique case of unicentric Castleman disease localized to the gluteal region in a 27-year-old female. Initially mistaken for a neurogenic or vascular tumour, fine needle aspiration cytology (FNAC) revealed a polymorphous population of lymphoid cells with numerous traversing capillaries suggestive of reactive hyperplasia, possibly Castleman disease, which was later confirmed by histopathology. This case highlights the diagnostic challenges posed by rare extranodal presentations of Castleman disease and underscores the importance of interdisciplinary collaboration in accurate diagnosis and management.

Efficacy and safety of orelabrutinib in relapsed/refractory idiopathic multicentric Castleman disease: A single-centre, retrospective study.

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.

Castleman Disease: A Rare Lymphoproliferative Disorder With Diverse Clinical Presentation, Diagnosis, and Treatment Approach.

Castleman disease (CD) includes rare and intricate lymphoproliferative disorders characterized by the abnormal growth of lymph nodes and immune system disturbances. It primarily presents in two forms: unicentric Castleman disease (UCD), which affects a single lymph node area, and multicentric Castleman disease (MCD), which involves multiple lymph nodes and systemic manifestations. The disease's underlying mechanisms are often linked to immune system irregularities, especially involving interleukin-6 (IL-6). The condition was first documented by Dr. Benjamin Castleman in 1954, laying the groundwork for understanding this complex disorder. MCD can be further divided into idiopathic MCD (iMCD), which includes thrombocytopenia, ascites, fibrosis, renal impairment, and organ enlargement (TAFRO) syndrome, and human herpesvirus-8 (HHV-8)-associated MCD, which can occur in individuals with or without HIV. The prevalence of CD shows a higher occurrence of UCD, with the disease typically presenting in individuals in their fifth to seventh decades of life and being more common in areas with high HIV prevalence. The clinical presentation of CD can include symptoms such as swollen lymph nodes, fever, anemia, and systemic inflammation. Diagnostic challenges arise due to the disease's rarity, and its symptoms overlap with other conditions. Treatment approaches differ based on the subtype. UCD generally responds favorably to the surgical removal of the affected lymph nodes, while MCD often requires antiviral treatments, interleukin-6 (IL-6) inhibitors, and new biologic therapies. Recent advances in treatment, including innovative biologic agents and combination therapies, offer promising prospects for improving patient outcomes. Accurate diagnosis and customized treatment strategies are essential for the effective management of this complex disease.

Diagnostic challenges in patients with Castleman disease, a single center experience from Hungary.

Castleman disease is a rare and atypical lymphoproliferative disorder characterized by diverse clinical manifestations. It has both unicentric and multicentric forms, the latter with further subdivisions, i.e., human herpesvirus 8-associated and idiopathic forms. The diagnosis of Castleman disease is often delayed, as it is rare, and because it shares clinical features with different autoimmune, inflammatory, and malignant lymphoproliferative disorders. The first-line treatment in unicentric form is mainly surgical, while in idiopathic Castleman disease, anti-interleukin-6 treatment is the therapy of choice. In virus-associated diseases, antiretroviral therapy and rituximab are recommended. In Hungary, only a few cases of Castleman disease have been published. This report presents our two decades of experience in the challenging diagnosis and management of this rare disorder, most properly underdiagnosed in Hungary. We provide insights into seven unicentric and five idiopathic multicentric Castleman disease cases, the latter ones especially highlighting the diagnostic and therapeutic challenges due to the variable and unique clinical features both of patients and diseases, e.g., bronchiolitis obliterans, stage IV diabetic renal failure, anti-HBc positivity, siltuximab treatment period, respectively.

A rare case report of hyaline-vascular type Castleman disease in the presacral region.

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.

Localized retroperitoneal mass suspected malignancy: A rare case of unicentric Castleman's disease.

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.

Clinical features and outcomes of retroperitoneal unicentric Castleman disease resected as sarcomas: insights from a high-volume sarcoma center.

Background: Castleman disease (CD) is a rare lymphoproliferative disorder that can occur anywhere along the lymphatic pathway. Retroperitoneal unicentric Castleman disease (UCD) is an extremely rare manifestation. This study aims to explore the clinical features and surgical treatment of retroperitoneal UCD. Methods: We retrospectively reviewed patients who underwent retroperitoneal tumor surgery and were diagnosed with CD based on postoperative pathology before December 31, 2022. Data from these patients were collected and analyzed. Results: A total of 15 patients were included in the final analysis. All patients underwent radical resection under general anesthesia. Two out of 15 patients (13.3%) experienced serious complications but recovered well. There were no perioperative deaths. The median follow-up time was 78.5 months (range: 18-107.5 months), and no deaths or recurrences occurred during this period. Conclusions: Surgical treatment for retroperitoneal UCD is safe. Patients with retroperitoneal UCD can achieve long-time survival through complete resection.

A hypothesis on treatment strategy of severe multicentric Castleman disease with continuous renal replacement therapy.

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.

Unilateral adrenal Castleman's disease: A case report.

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.

TAFRO syndrome with abdominal pain as the first symptom accompanied by liver damage with hyperbilirubinemia: A case report.

Thrombocytopenia, anasarca, fever, reticulin fibrosis on bone marrow biopsy/renal dysfunction, and organomegaly (TAFRO) syndrome are infrequent conditions with diverse clinical and pathological characteristics related to multi-organ damage. There are few reports of TAFRO syndrome accompanied by liver damage with hyperbilirubinemia. We describe the case of a 61-year-old male who presented with sudden onset abdominal pain accompanied by liver damage with hyperbilirubinemia. His symptoms worsened, leading to fever, hepatic insufficiency, serous cavity effusions, thrombocytopenia, and acute renal failure. Fever and anasarca relapsed after steroid discontinuation. The patient was ultimately diagnosed with TAFRO syndrome by biopsies taken from the axillary lymph nodes. He was then administered steroids, which resolved his symptoms almost completely. Our case was notable for its atypical signs and total remission of TAFRO syndrome.

An Unusual Case of HHV-8 Negative, Idiopathic, Multicentric Castleman Disease Following Chronic Lymphocytic Leukaemia.

Background: Castleman disease is a rare condition characterised by polytypic lymphocytes proliferation and lymphadenopathy generally with a benign course. Whereas high grade lymphoma (Richter syndrome) is a classical complication seen in chronic lymphocytic leukaemia with a poor outcome, benign conditions mimicking this entity are infrequent. Case description: We describe the case of an 81-year-old Caucasian male who developed a human herpesvirus-8 (HHV-8)-negative, idiopathic multicentric Castleman disease (iMCD) following a treated Binet C chronic lymphocytic leukaemia (CLL). The clinical and radiological pattern raised initially the suspicion of a classical Richter transformation. Blood analysis showed auto-immune haemolytic anaemia and thrombocytopenia. He had normal immunoglobulin levels. The anatomopathological analysis of a cervical adenomegaly showed hypervascularisation and a polytypic plasmocytic proliferation compatible with a plasmocytic iMCD type. Interestingly, bone marrow examination showed reticuline fibrosis but, in the absence of anasarca or generalised oedema, we were not allowed to conclude to the diagnosis of a TAFRO syndrome. We excluded all other mimicking conditions, comprising haematological malignancies, infections, and auto-immune diseases He was first treated with corticosteroids with poor results but dramatically responded to tocilizumab (anti-Il6). Conclusion: To our knowledge, this the first case described of a Castleman disease following CLL and surprisingly mimicking Richter syndrome. Clinicians should be aware of this rare misleading condition. LEARNING POINTS: Castleman disease can mimic a Richter transformation in a CLL patient.

Idiopathic multicentric Castleman disease with marrow fibrosis and extramedullary hematopoiesis.

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.

Continuous therapy in HHV-8 negative Multicentric Castleman Disease and prolonged progression-free survival.

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.