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.

Acquired Hemophilia: A Rare Complication of Pediatric Idiopathic Multicentric Castleman Disease.

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.

Urologic Presentation of Unicentric Pediatric Castleman Disease in the Setting of Acute Renal Colic.

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.

Kaposi sarcoma herpesvirus/human herpesvirus 8-positive diffuse large B-cell lymphoma characterized by malignant ascites: A case report.

Herein, we report a rare case of Kaposi sarcoma herpesvirus/human herpesvirus 8 (KSHV/HHV8)-positive diffuse large B-cell lymphoma (DLBCL), which is characterized by malignant ascites and complex karyotypes. A 72-year-old male patient who tested negative for human immunodeficiency virus presented with thrombocytopenia and lymphadenopathies. He was diagnosed with KSHV/HHV8-associated multicentric Castleman disease (MCD). After three years, he developed progressive lymphadenopathies and massive ascites. The lymphoma cells in the ascitic fluid presented with characteristic immunophenotype and monoclonality, which support the diagnosis of KSHV/HHV8-positive DLBCL. Lymphadenopathies and massive splenomegaly are common manifestations of KSHV/HHV8-positive DLBCL. Nevertheless, peritoneal involvement, as observed in this case, is a rare presentation. This emphasizes the diagnostic complexities of KSHV/HHV8-associated lymphoproliferative disorders. Within the context of preexisting KSHV/HHV8-associated multicentric Castleman disease, the differential diagnosis of this disorder can be challenging.

A Multicentric Castleman Disease Associated with Mixed Warm and Cold Antibody-Mediated AHA Responsive to Siltuximab.

Castleman disease is non-clonal lymphoproliferative disorders defined by hypertrophy of lymph nodes. The multicentric form (MCD), in which multiple lymph node stations are involved, is not associated with HHV8 infection, but considered idiopathic, although IL-6 appears to play a central role in its pathogenesis. Here, we report the case of a patient who presented with mixed autoimmune hemolytic anemia (AIHA) and adenopathy that was very challenging to diagnose due to very low values of hemoglobin and refractoriness of obtaining any improvement of AIHA with standard first and second lines of therapy (steroids, rituximab, immunoglobulin, erythropoietin, and cyclosporine). When we safely proceeded to lymph node biopsy, a diagnosis of MCD was established. This permitted the treatment with siltuximab, an anti-IL-6 monoclonal antibody. After only 1 week, hemoglobin raised and he was discharged. After 1 year, he was still in remission. This case underlines the challenges in diagnosis of MCD, and the first case of response to siltuximab after the failure of rituximab to relieve mixed AIHA.

Whole-Exome Sequencing Reveals the Genomic Profile and IL6ST Variants as a Prognostic Biomarker of Paraneoplastic Pemphigus-Associated Unicentric Castleman Disease.

Unicentric Castleman disease (UCD) is a rare lymphoproliferative disorder. Paraneoplastic pemphigus (PNP) is a major complication associated with poor UCD prognosis. However, the genomic profiles and prognostic biomarkers of PNP-associated UCD remain unclear. In this study, we performed whole-exome sequencing analysis for 28 matched tumor-normal pairs and 9 tumor-only samples to define the genomic landscape of Chinese patients with PNP-associated UCD. An integrative analysis was performed to identify somatic variants, the mutational signatures, and key pathways in tumors. Besides, we analyzed the relationship among mutated genes, clinical characteristics, and prognosis. Sixty-one somatic mutant genes were identified in >1 patient with PNP-associated UCD. Specifically, IL6ST and PDGFRB were the most frequently mutated genes (32%), followed by DPP6 (18%) and MUC4 (18%). Signaling molecules and interactions, cellular processes, and signal transduction pathways were enriched. Furthermore, we found that poor overall survival was related to IL6ST variants (P = .02). Finally, we classified PNP-associated UCD into 4 genomic subgroups: IL6ST, PDGFRB, IL6ST-PDGFRB, and an unknown subgroup. In summary, we defined the molecular profile of PNP-associated UCD and identified a potential molecular biomarker for predicting prognosis, which may provide therapeutic targets for treating this severe disorder.

Outcomes in Kaposi's sarcoma-associated herpesvirus -associated primary effusion lymphoma and multicentric Castleman's disease in patients with human immunodeficiency virus (HIV) in a safety-net hospital system.

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.

Castleman disease of plasma cell type accompanied with bronchiolitis obliterans: a case report and review of the literature.

BACKGROUND: Castleman disease, also known as giant lymph node hyperplasia or angiofollicular lymph node hyperplasia, is a highly heterogeneous clinicopathological entity that belongs to the family lymphoproliferative disorders. Castleman disease accompanied by bronchiolitis obliterans is uncommon and often poses a great diagnostic challenge, which is easily confused with respiratory diseases and impeding the correct diagnosis and treatment. The main aim in presenting such rare case studies is to raise awareness and expand the diagnostic horizon of clinicians for appropriate management. CASE PRESENTATION: Here, we present a 69-year-old Chinese male who was admitted to our hospital due to right chest pain for 6 months, accompanied by cough, expectoration, and fever. Laboratory examinations revealed elevated immunoglobulin G and C-reactive protein, and normal serum levels of tumor markers and interleukin-6. Computed tomography scan detected diffuse bronchial wall thickening and patchy area of air trapping consistent with small airway disease. Pulmonary function test showed mild small airway obstructive ventilation dysfunction and moderate decrease in diffusion capacity. The pathological result of the right axillary lymph node was consistent with the plasma cell type Castleman disease. According to the above examinations, the patient was finally diagnosed with the plasma cell type Castleman disease accompanied with bronchiolitis obliterans. He received immunosuppressive medication after surgery and has been followed up for 11 months. Now the patient is currently in stable condition without recurrence. CONCLUSION: Castleman disease is a rare lymphoproliferative disorder with a variety of symptoms. At present, the treatment of Castleman disease accompanied with bronchiolitis obliterans is mostly based on experiences or previous case reports, and there is no standard treatment. Here, we report an uncommon case of Castleman disease accompanied with bronchiolitis obliterans in which the patient received immunosuppressive medication after surgery and has been followed up for 11 months without experiencing a recurrence, which may deepen and extend our understanding of this disease.

Idiopathic multicentric castleman's disease mimicking immunoglobulin G4-related disease responding well to Bortezomib: a case report.

BACKGROUND: Castleman's disease (CD) is a rare disease that has clinical and pathological similarities to lymphoma and is characterized by a high frequency of associated immunological dysfunction. ImmunoglobulinG4-related disease (IgG4-RD) is a collection of systemic disorders that affect numerous organs and are also referred to as IgG4-associated sclerosing diseases. CD and IgG4-RD are difficult to separate because they may manifest similar commin clinical features. CASE PRESENTATION: This case describes a 53-year-old female who, during routine medical check-up, exhibited a progressive increase in serum globulin levels and a simultaneous worsening of anemia symptoms, raising concern for a clonal plasma cell disease such as myeloma. However, bone marrow punctures did not reveal any abnormal plasma cells. Also, serum and urine immunofixation electrophoresis demonstrated no abnormal monoclonal protein bands. In addition, several laboratory findings excluded chronic liver disease, chronic infections caused by bacteria or viruses. Later, we found elevated serum IgG4 levels (10,700 mg/L), and identified multiple enlarged lymph nodes throughout the patient's body. Axillary lymph node aspiration revealed no abnormal lymphocytes, ruling out the possibility of lymphoma. Pathological morphology of the axillary lymph revealed a large number of plasma cells in the lymphatic follicles. In addition, there was a reduction in lymphatic follicle size and apoptosis of the germinal centres. Immunohistochemistry revealed IgG4+/IgG + in > 40% of cells, and more than 100 IgG4 + cells per high powered field (HPF) of specimen. As of now, finding strongly suggested IgG4-RD. This patient was treated with glucocorticoids and various immunosuppressive drugs, such as prednisone, cyclosporine, methotrexate, cyclophosphamide, mycophenolate mofetil, azathioprine and hydroxychloroquine. Unfortunately, the patient did not recover. Ultimately, idiopathic multicentric Castleman disease (iMCD) was diagnosed in relation to the patient's clinical presentation and laboratory tests, and after combination chemotherapy (VCD: Bortezomib, Cyclophosphamide and Dexamethasone), durable remission was achieved without serious adverse effects. During the follow-up period of one year and ten months, the patient remained stable. CONCLUSION: The diagnosis of Castleman must be distinguished from other disorders such as IgG4-RD, malignant lymphoma, reactive hyperplasia of various lymph nodes (mostly caused by viral infections), plasmacytoma, advanced HIV and rheumatic diseases. Besides observing systemic symptoms, laboratory tests such as immunoglobulin levels, complement levels, interleukin levels, and C-reactive protein levels should also be performed in order to determine a diagnosis.

Systemic lupus erythematosus combined with Castleman disease and secondary paraneoplastic pemphigus: a case report.

BACKGROUND: The literature describes a case of systemic lupus erythematosus (SLE) complicated with Castleman's disease (CD) and secondary paraneoplastic pemphigus (PNP). CASE PRESENTATION: A 12-year-old female presented with a neck mass, rash, arthralgia, and skin and mouth ulceration for 5 years were admitted. All blood cells were low. Multiple autoantibodies associated with SLE were positive. The pathology of the neck mass revealed the classical manifestations of CD. She was treated with prednisone, hydroxychloroquine, leflunomide, thalidomide, and dressings. Pathological examination of the skin revealed PNP. The neck mass was removed and continued to take antirheumatic drugs. At subsequent follow-up, the patient's disease status was stable and the skin mucosal lesion did not recur. CONCLUSION: The case of simultaneous SLE, CD, and PNP in children was rarely reported, and the correct diagnosis of the disease will help to take timely treatment.

Higher rate of progression in HIV- than in HIV+ patients after rituximab for HHV8+ multicentric Castleman disease.

Rituximab has revolutionized the treatment of Kaposi sarcoma-associated herpesvirus/human herpesvirus 8-associated multicentric Castleman disease (HHV8+ MCD), converting a rapidly fatal illness into a relapsing disease. HHV8+ MCD mainly affects patients with HIV infection but can also be observed in patients without HIV infection. We retrospectively analyzed a cohort of 99 patients (73 who tested HIV+ and 26 who tested HIV-), with HHV8+ MCD treated with rituximab-based therapy. Baseline characteristics were similar in patients who had HIV- and HIV+ results, although those who tested HIV- were older (65 vs 42 years) and presented less frequently with Kaposi sarcoma (15% vs 40%). Ninety-five patients (70 HIV+ and 25 HIV-) achieved complete remission (CR) after rituximab-based therapy. After a median follow-up of 51 months, 36 patients (12 HIV- and 24 HIV+) experienced disease progression. The 5-year progression-free survival (PFS) was 54%. The 5-year PFS was lower in HIV- patients than in HIV+ patients : 26% and 62%, respectively (P = .02). A multivariate prognostic factors analysis including time-dependent covariates revealed that HIV- status, reoccurrence of HHV8 DNA >3 log copies per mL, and serum C-reactive protein (CRP) >20 mg/mL were independently associated with an increased risk of progression after rituximab-induced CR (P = .001; P = .01; and P = .01, respectively). The lower rate of progression observed in the population with HIV+ results despite a longer follow-up period might have resulted from the possible immune restoration upon antiretroviral therapy. HHV8 viral load and serum CRP monitoring after rituximab therapy provide information on the progression risk and may help in the decision to resume specific therapy.

A case of idiopathic multicentric Castleman disease with pulmonary hyalinizing granuloma-like multiple pulmonary nodules.

A 41-year-old man presented with chronic cough and chest pain. Laboratory tests revealed anemia, inflammation, hypoalbuminemia, polyclonal hypergammaglobulinemia, and elevated interleukin-6 levels. Computed tomography revealed diffuse bilateral pulmonary nodules and multicentric lymphadenopathy. Histopathology of the pulmonary nodule resembled pulmonary hyalinizing granuloma (PHG), whereas lymph node histopathology was consistent with idiopathic multicentric Castleman disease (iMCD). The patient was diagnosed with iMCD involving PHG-like pulmonary nodules. Little is known about the association between these two diseases, and the present case provides insights regarding the relationship between PHG and iMCD.

[Multicentric Castleman disease and tuberculosis in HIV positive patient]. / Enfermedad de Castleman multicéntrica y tuberculosis diseminada en paciente HIV positivo.

We present the case of a 40-year-old man, HIV positive with regular adherence to treatment, who consulted for intermittent febrile episodes during a two-years period, progressive diffuse abdominal pain and painless generalized lymphadenopathy in the last two months. Laboratory analysis showed pancytopenia, altered coagulation tests, hypoalbuminemia, and increased acute phase reactants. Computed tomography (CT) of the chest, abdomen and pelvis revealed hepato-splenomegaly and generalized lymphadenopathy. Multiple microbiological tests were performed, including cultures for Mycobacterium sp. from different samples, with negative results, except for the RT-PCR for HHV-8. An excisional biopsy of the left iliac lymph node was taken with findings compatible with Castleman's disease. Despite restarting antiretroviral therapy, the symptoms progressed, starting treatment with steroids and ganciclovir. After a week, he developed multiple organ failure and anasarca, which contraindicated the drugs previously started. A new CT of the chest showed infiltrates with a tree-in-bud pattern in the right upper lobe with bilateral pleural effusion, and at the abdominal level, progression of hepatosplenomegaly and ascites. He was transferred to the intensive care unit 48 hours later due to fulminant hepatic failure. The patient died within a few hours. Postmortem recieved culture results of the tracheal aspirate were positive for tuberculosis (TB) and the histopathology of the liver biopsy showed non-necrotizing granulomas. Our objective is to highlight the importance of screening for active TB, in our country, when Castleman's disease is suspected, before starting treatment, and to stand out that TB can also present as an infectious complication, increasing morbidity and mortality.

Presentamos el caso de un hombre de 40 años, HIV positivo con regular adherencia al tratamiento, que consultó por episodios febriles intermitentes de dos años de evolución, agregando en los últimos dos meses dolor abdominal difuso progresivo y adenomegalias generalizadas indoloras. En el laboratorio presentó pancitopenia, coagulopatía, hipoalbuminemia y reactantes de fase aguda aumentados. La tomografía computarizada (TC) de tórax, abdomen y pelvis únicamente evidenció hepato-esplenomegalia y adenomegalias generalizadas. Se realizaron múltiples exámenes microbiológicos, incluyendo cultivos para Mycobacterium sp. de distintas muestras, todos con resultados negativos, a excepción de la RT-PCR para VHH-8. Se tomó biopsia escisional de ganglio iliaco izquierdo con hallazgos compatibles con enfermedad de Castleman. A pesar de reiniciar terapia antirretroviral, la sintomatología progresó, iniciando tratamiento con corticoides y ganciclovir. Luego de una semana, desarrolló falla mulitorgánica y anasarca, que contraindicaron los fármacos iniciados. Se realizó nueva TC de tórax que mostró infiltrados con patrón en árbol en brote en lóbulo superior derecho asociado a derrame pleural bilateral, y a nivel abdominal, progresión de hepato-esplenomegalia y ascitis. Pasó a unidad de cuidados intensivos 48 horas después por falla hepática fulminante. El paciente falleció en pocas horas. Se recibió postmortem el cultivo del aspirado traqueal positivo para Mycobacterium tuberculosis y la punción-biopsia hepática con granulomas no necrotizantes. Nuestro objetivo es remarcar la importancia de pesquisar tuberculosis activa en nuestro país frente a la sospecha de enfermedad de Castleman antes de iniciar tratamiento, y resaltar que la TBC también puede presentarse como complicación infecciosa elevando la morbimortalidad.

Multicentric Castleman Disease and Concurrent Hematological Disorders: The Occurrence of Plasmacytoma and the Hypotheses Arising from Literature Review.

The concomitant presence of Castleman disease (CD) with other hematological pathology is an event described in the literature with increasing frequency, able to modify the diagnostic and curative approach in such patients. Very few studies in the literature describe the association of CD with concomitant neoplastic diseases; the most frequent are Kaposi's sarcomas (especially in HIV and human herpes virus-8-positive patients) and lymphoproliferative disorders, such as lymphomas. Instead, since the association with plasma cell diseases such as multiple myeloma and plasmacytoma is infrequent, there is a lack of literature. This manuscript aimed to revise the literature by describing a rare case of CD and plasmacytoma and attempting to explain the underlying triggering mechanisms.

Paraneoplastic pemphigus and Castleman's disease: a case report and a revision of the literature.

BACKGROUND: In literature, a few reports described an association between paraneoplastic pemphigus (PNP) and Castelman's disease (CD), but no consensus have been proposed for the diagnostic-therapeutical approach. Aim of this study is to present a case report and explore the relationship between PNP and CD in pediatric patients, focusing on clinical manifestations, histopathological findings, treatment and outcome to find elements for an early diagnosis. CASE PRESENTATION: We present the clinical case of a 13 years old girl with a challenging diagnosis of PNP and CD who underwent therapy at first with Rituximab and then with Siltuximab, for the control of symptoms. CONCLUSIONS: Reviewing literature, 20 clinical cases have been described in the pediatric age. Diagnosis may be challenging, requiring an average of 3 months (range from 3 weeks to 2 years). In all cases, the initial manifestations were mucocutaneous lesions, especially oral lesions with poor response to conventional treatment. Systemic symptoms may be present as well. Therapeutical approach is still discussed with no consensus. Almost all patients received corticosteroids with poor response. Other drugs including azathioprine, methotrexate, cyclosporine and monoclonal antibodies have been evaluated for the control of the disease. Further studies and experimental trials urge to define the diagnostic criteria and therapy protocol.

Diffuse cryptococcal pneumonia in multicentric Castleman's disease with elevated serum IgG4.

A woman in her 60s with suspected multicentric Castleman's disease, who was receiving treatment with oral prednisolone, presented to our hospital with mild cough and malaise. Chest CT showed diffuse infiltrative and granular shadows, indicating exacerbation of lung lesions caused by steroid-resistant multicentric Castleman's disease. A video-assisted thoracoscopic lung and mediastinal lymph node biopsy was performed. The biopsy revealed mediastinal lymph node tissue consistent with multicentric Castleman's disease, as well as presence of Cryptococcus neoformans in the alveolar space. C. neoformans infection in immunocompromised individuals may present with diffuse lung lesions and should be noted as a mimicker of acute exacerbation of Castleman's disease.

Evolution of Pulmonary Involvement in Idiopathic Multicentric Castleman Disease-Not Otherwise Specified: From Nodules to Cysts or Consolidation.

BACKGROUND: Previous studies about multicentric Castleman disease-associated pulmonary manifestations have been limited by small cohorts and not following the Castleman Disease Collaborative Network classification criteria of multicentric Castleman disease. The pulmonary manifestations in idiopathic multicentric Castleman disease-not otherwise specified (iMCD-NOS), a distinct clinical phenotype in the classification criteria, have not been reported. RESEARCH QUESTION: Which pulmonary abnormalities in iMCD-NOS are advanced manifestations and which are reversible after effective treatment? STUDY DESIGN AND METHODS: Patients diagnosed with iMCD-NOS with pulmonary involvement were enrolled. The baseline CT scan was evaluated for the presence and anatomic locations of pulmonary abnormalities. Patients were further divided into different subgroups according to baseline CT scan manifestations. Follow-up CT scan was reviewed to assess the changes in pulmonary lesions among patients without and with treatment. RESULTS: Of 162 patients with iMCD-NOS, 58 individuals (35.8%) with pulmonary involvement were identified. Pulmonary manifestations included nodules (96.6%), cysts (65.5%), consolidation (22.4%), interstitial thickening (50.0%-87.9%), and ground-glass opacities (55.2%). Patients (n = 58) were further classified into nodule (n = 15), cyst (n = 33), and consolidation (n = 10) subgroups. Patients in the consolidation (median, 67 months) and cyst (median, 23 months) subgroups had a longer duration of symptoms before the baseline CT examination than those in the nodule subgroup (median, 12 months) (P = .016). During follow-up, the evolution of pulmonary lesions from nodules to cysts was observed in two patients without treatment. After treatment, pulmonary lesions, except for cysts, improved in most patients. Moreover, nodules or cysts progressed into consolidation in two patients. INTERPRETATION: Pulmonary involvement is not rare in iMCD-NOS. Chest CT scan examination is very essential in finding potential pulmonary abnormalities. Pulmonary manifestations follow a unique pattern with evolution from nodules to cysts or consolidation, the latter of which can also form in cystic areas. Timely diagnosis of pulmonary involvement is crucial because of possible reversibility after treatment.