• Haematology (drugs and medicines)
• Immunology
• Paraneoplastic Syndromes

• Humans
• Castleman Disease/complications
• Castleman Disease/drug therapy
• Castleman Disease/diagnosis
• Pemphigus/drug therapy
• Pemphigus/diagnosis
• Pemphigus/complications
• Rituximab/therapeutic use
• Rituximab/administration & dosage
• Female
• Paraneoplastic Syndromes/diagnosis
• Paraneoplastic Syndromes/etiology
• Paraneoplastic Syndromes/drug therapy
• Young Adult
• Treatment Outcome

• Bronchiolitis Obliterans
• Case Report
• Castleman disease
• Paraneoplastic Pemphigus

• Back pain
• Case report
• Dyspnea
• Mediastinal Castleman disease
• Paraspinal mass
• Shortness of breath
• Unicentric Castleman disease

• Hemophagocytic lymphohistiocytosis
• Hemophagocytic syndrome
• Human herpesvirus 8 (HHV-8)
• Hyperinflammatory syndrome
• KSHV inflammatory cytokine syndrome (KICS)
• Kaposi’s sarcoma–associated herpesvirus (KSHV)
• Multicentric Castleman’s disease
• Systemic hyperinflammation

• Castleman disease
• lymphadenopathy
• supraclavicular mass
• unicentric Castleman disease

• Castleman Disease/diagnosis
• Castleman Disease/pathology
• Humans
• Female
• Adolescent
• Diagnosis, Differential
• Lymph Nodes/pathology

• CT
• Castleman disease hyaline-vascular variant
• MRI
• pathological examination diagnosis
• presacral mass
• surgery
• unicentric Castleman disease (UCD)

• Castleman disease
• Hyaline vascular variant
• Tonsil

• Castleman disease
• Paraneoplastic syndromes
• Pemphigus
• Systemic lupus erythematosus

• Female
• Child
• Humans
• Pemphigus/diagnosis
• Pemphigus/etiology
• Castleman Disease/complications
• Castleman Disease/diagnosis
• Neoplasm Recurrence, Local/complications
• Neoplasm Recurrence, Local/pathology
• Skin/pathology
• Lupus Erythematosus, Systemic/complications
• Lupus Erythematosus, Systemic/diagnosis
• Lupus Erythematosus, Systemic/pathology

• Castleman disease
• case report
• idiopathic
• multicentric
• non‐Hodgkin lymphoma

• bulky
• castleman disease
• chemotherapy
• hodgkin lymphoma
• unicentric

• Castleman disease
• Castleman’s disease
• follicular dendritic cell
• hyaline-vascular
• unicentric

• Castleman disease
• computerized tomography
• diagnosis
• imaging
• renal tumor

• Second Military Medical University

• adrenal gland
• adrenal incidentaloma
• castleman disease
• lymphoma
• pheochromocytoma

• Humans
• Adrenal Gland Neoplasms/diagnosis
• Adrenal Gland Neoplasms/surgery
• Castleman Disease/diagnosis
• Castleman Disease/surgery
• Castleman Disease/pathology
• Lymph Nodes/surgery
• Lymph Nodes/pathology
• Pheochromocytoma/diagnosis
• Pheochromocytoma/surgery
• Prognosis

• castleman disease
• differential diagnoses
• fluorodeoxyglucose positron emission tomography
• pancreatic malignancy
• pancreatic neuroendocrine tumours

Castleman disease (CD), classified as unicentric CD (UCD) or multicentric CD (MCD), is a rare non-neoplastic lymphoproliferative disorder of unknown origin. Owing to its rarity, the clinical characteristics, therapeutic modalities, treatment outcomes, and prognostic factors related to UCD or MCD are not well defined.

We retrospectively analyzed 88 patients with CD, including those with hyaline-vascular, plasma-cell, mixed type, hypervascular, and plasmablastic subtypes, for presenting symptoms, physical, laboratory, and radiologic findings, and treatment response in the Korean population.

The median patient age was 44 years (range: 18–84 years) with slight predominance of women (53.4%). UCD and MCD accounted for 38.6% (n=34) and 61.4% (n=54) of cases, respectively. Histopathologically, UCD patients were classified as 88.2% (n=30) hyaline-vascular and 11.8% (n=4) plasma cell types, whereas MCD patients were classified as 27.8% (n=15) hypervascular, 61.1% (n=33) plasma cell, 7.4% (n=4) mixed, and 3.7% (n=2) plasmablastic types. Twelve (13.6%) patients exhibited a poor performance status with an Eastern Cooperative Oncology Group score of 2. The most common presenting symptom was sustained fever, followed by fatigue, anorexia, peripheral edema, and weight loss. Furthermore, splenomegaly, pleural effusion, and ascites were observed to be associated with CD. Surgical resection and siltuximab were the preferred treatment modalities for UCD and MCD, respectively, with favorable symptomatic, laboratory, and radiologic outcomes and safety profiles. The overall survival was 90.2%, with no significant difference between the UCD and MCD groups (p=0.073), but progression-free survival was significantly poorer in the MCD group (p=0.001). Age ≥60 years and splenomegaly significantly affected the overall and progression-free survival rates.

Patients with UCD had favorable outcomes with surgical resection of a solitary mass, whereas in patients with MCD, old age and splenomegaly were identified as independent prognostic factors. Further well-designed prospective studies under advancing knowledge of the pathophysiology of MCD are warranted to establish suitable guidelines for the discontinuation or prolonging infusion intervals of siltuximab and treatment modalities for HHV-8 positive MCD patients or patients with siltuximab failure.

Castleman disease is a rare disease borne of a B cell lymphoproliferative disorder of uncertain cause. Standard therapy for the unicentric type of Castleman disease localized as a single mass or single lymph‐node station is surgical extirpation. Nevertheless, in the thoracic cavity, unresectable cases or cases of incomplete extirpation of the tumor without lung scarring owing to tumor size/location have been noted. In such cases, lung resection (e.g., lobectomy, pneumonectomy) or additional therapy (immunotherapy, chemotherapy, radiotherapy) after resection is required. However, few instances of patients receiving induction immunotherapy or chemotherapy followed by surgery have been reported. Here, we describe a 21‐year‐old woman with unicentric Castleman disease originating from the left hilum. The tumor seemed to involve/be in contact with the pulmonary vein and bronchus. Tumor location indicated that initial resection was necessary to sacrifice upper and lower pulmonary lobes. To avoid these pulmonary resections, induction therapy followed by surgery was selected. Induction therapy using rituximab was very efficacious. Resection after induction therapy was completed only by tumor extirpation, and resulted in preservation of pulmonary function. Thoracic surgeons might consider induction therapy followed by resection if the tumor is resectable UCAD, but initial resection is needed and sacrifices a large amount of pulmonary function.

• Unicentric Castleman disease
• rituximab
• surgery

Castleman disease (CD) is a rare disease also known as angiofollicular lymph node hyperplasia. The two main histological subtypes are the hyaline vascular and plasma cell variants. It is further classified as unicentric CD (UCD) or multicentric CD (MCD) according to the anatomical distribution of the disease and the number of lymph nodes involved. The aim of this multicenter study was to evaluate all cases of CD identified to date in Turkey to set up a national registry to improve the early recognition, treatment, and follow-up of CD.

Both adult (n=130) and pediatric (n=10) patients with lymph node or involved field biopsy results reported as CD were included in the study. Patients’ demographic information, clinical and laboratory characteristics, imaging study results, treatment strategies, and clinical outcomes were evaluated retrospectively.

A total of 140 patients (69 male and 71 female) with a diagnosis of UCD (n=73) or MCD (n=67) were included. The mean age was 39 years in the UCD group and 47 years in the MCD group. Female patients were more common in the UCD group. The most common histological subtype was hyaline vascular for both UCD and MCD patients. Asymptomatic patients were more common in the UCD group. Anemia, elevations of acute phase reactants, and hypoalbuminemia were more common in the MCD group. The most commonly used treatment strategies for UCD were surgical excision, rituximab, and radiotherapy, respectively. All UCD patients were alive at a median of 19.5 months of follow-up. The most commonly used treatment strategies for MCD were methyl prednisolone, R-CHOP, R-CVP, and rituximab. Thirteen MCD patients had died at a median of 34 months of follow-up.

This study is important in presenting the patient characteristics and treatment strategies for CD from Turkey, with the potential of increasing awareness about CD. Treatment data may help in making decisions, particularly in countries that do not have access to siltuximab. However, larger prospective studies are needed to make definitive conclusions.

• Castleman disease
• multicentric
• treatment
• unicentric

• Castleman Disease/diagnostic imaging
• Castleman Disease/pathology
• Diagnosis, Differential
• Humans
• Lymphadenopathy/diagnostic imaging
• Radiography
• Radiology
• Tomography, X-Ray Computed

A cytokine storm is a hyperinflammatory state secondary to the excessive production of cytokines by a deregulated immune system. It manifests clinically as an influenza-like syndrome, which can be complicated by multi-organ failure and coagulopathy, leading, in the most severe cases, even to death. The term cytokine storm was first used in 1993 to describe the graft-versus-host disease following allogeneic hematopoietic stem cell transplantation. It was then reused to define the adverse syndromes secondary to the administration of immunostimulating agents, such as anti-CD28 antibodies or bioengineered immune cells, i.e., CAR T-cell therapy. Currently, the concept of cytokine storm has been better elucidated and extended to the pathogenesis of many other conditions, such as sepsis, autoinflammatory disease, primary and secondary hemophagocytic lymphohistiocytosis, and multicentric Castleman disease. Moreover, cytokine storm has recently emerged as a key aspect in the novel Coronavirus disease 2019, as affected patients show high levels of several key pro-inflammatory cytokines, such as IL-1, IL-2, IL-6, TNF-α, IFN-γ, IP-10, GM-CSF, MCP-1, and IL-10, some of which also correlate with disease severity. Therefore, since the onset of the pandemic, numerous agents have been tested in the effort to mitigate the cytokine storm in COVID-19 patients, some of which are effective in reducing mortality, especially in critically ill patients, and are now becoming standards of care, such as glucocorticoids or some cytokine inhibitors. However, the challenge is still far from being met, and other therapeutic strategies are being tested in the hope that we can eventually overcome the disease.

• Multicentric Castleman
• nephrotic syndrome
• polyneuropathy

To investigate the long-term clinical efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for patients with human herpes virus 8 (HHV8)-positive multicentric Castleman’s disease (MCD).

A 17-year-old female patient was admitted to Henan Provincial People’s Hospital with the complaint of febrile for half a month, headache, and enlarged superficial lymph nodes on October 5, 2010. HHV8-positive mixed cellular Castleman’s disease was found by pathological diagnosis of lymph nodes biopsy. After the administration of CHOP and Hyper-CVAD-B, the patient was still febrile, we administrated the followed COAP, two courses of VAD(Vincristine, Adriamycin, Dexamethasone), the patient received CR. Six months after CR, the patient relapsed, we administrated VAD and two courses of bortezomide+dexamethasone chemotherapy, and then the patient received PR. After that, the patient underwent allo-HSCT from his human leukocyte antigen (HLA)-matched unrelated donor after conditioning with Bu/Cy+Etoposide+Smoustin.graft-vs-host disease (GVHD) prophylaxis, which consisted of ATG (7.5 mg/kg, qd, ivdrip) from d-5 to d-2, cyclosporine (3 mg/kg/d, qd, ivdrip, for 24 h) started from day-1, MMF(0.5 g, tid, po.) started from day+1 to +28, and MTX (15 mg per time, ivdrip, d+1,+4,+7,+11). She received 3.5×10⁶/L CD34⁺cells and 8.1×10⁸/LMNC.

Granulocyte engraftment occurred on day+12, platelet engrafted on day+14. Bone marrow biopsy showed normalization of trilineage hematopoiesis on day+33, chimerism: 97.6%. The transplantation was successful and followed up for 7 years with CR.

Allo-HSCT might cure patients with refractory/relapsed HHV8+ MCD.

• Castleman’s disease
• allogeneic
• hematopoietic stem cell
• multicentric type
• transplantation

• Adolescent
• Castleman Disease/pathology
• Castleman Disease/therapy
• Castleman Disease/virology
• Female
• Hematopoietic Stem Cell Transplantation/methods
• Herpesvirus 8, Human/isolation & purification
• Humans
• Sarcoma, Kaposi/pathology
• Sarcoma, Kaposi/therapy
• Sarcoma, Kaposi/virology
• Transplantation Conditioning/methods
• Transplantation, Homologous/methods

• grants from the National Natural Science Foundation of China

• human herpesvirus 8
• human immunodeficiency virus

• diagnosis
• long-term follow up
• resection
• retroperitoneal
• unicentric castleman disease

• Adrenal Gland Neoplasms/diagnosis
• Adult
• Castleman Disease/blood
• Castleman Disease/diagnostic imaging
• Castleman Disease/pathology
• Castleman Disease/surgery
• Diagnosis, Differential
• Female
• Fluorodeoxyglucose F18/administration & dosage
• Follow-Up Studies
• Humans
• Interleukin-6/blood
• Lymph Node Excision
• Lymph Nodes/diagnostic imaging
• Lymph Nodes/pathology
• Lymph Nodes/surgery
• Male
• Middle Aged
• Paraganglioma/diagnosis
• Pheochromocytoma/diagnosis
• Positron Emission Tomography Computed Tomography
• Retroperitoneal Space/diagnostic imaging
• Retroperitoneal Space/pathology
• Retroperitoneal Space/surgery
• Retrospective Studies
• Treatment Outcome
• Ultrasonography

•

Castleman disease is an overgrowth of lymphatic cells, usually in the chest or abdomen.

Castleman disease (CD) is a rare lymphocytic disorder. Unicentric CD (UCD) has an excellent long-term prognosis after surgical excision; however, multicentric CD (MCD) has a severe clinical course with poor outcomes.

We analyzed the clinical presentation of 28 patients treated at a single institution from 1995 to 2017. Demographics, clinical variables, anatomical site, centricity, histopathology, immunochemistry, and surgical approach were reviewed. We evaluated the 5-year recurrence and survival for patients with UCD and MCD.

Of the 28 patients, 57 % (n = 16) were female, with a mean age of 41.6 ± 15.6 years. CD was asymptomatic in 57 % (n = 16) of patients, 21 % (n = 6) presented with local symptoms such as pain, and 21 % (n = 6) of patients also had systemic symptoms, including weight loss and fever. CD was unicentric in 64 % (n = 18) and multicentric in 36 % (n = 10). The hyaline vascular variant was noted in 57 % (n = 16) of the tumors, plasmacytoid variant in 36 % (n = 10), and mixed variants in 7% (n = 2) of tumors. Anatomical distributions included: head and neck (20 %), thorax and axilla (24 %), retroperitoneal (13 %), abdominopelvic (30 %) regions, and other (13 %). Complete surgical resection was performed in 95 % of patients with UCD. Surgical biopsy and medical therapy were provided to all patients with MCD. The recurrence rate for UCD and MCD was 6 % (n = 1) and 14 % (n = 1), respectively. The five-year disease-free survival rate for UCD was 95 % (n = 19) and MCD was 33 % (n = 2). We found 100 % survival in patients with UCD and histology demonstrating the HV variant.

CD is rare and often misdiagnosed due to the absence of specific clinical symptoms. Surgeons should include CD in their differential diagnoses when evaluating patients with lymph node hyperplasia. Surgery can be curative in nearly all patients with UCD. Patients with MCD require a combination of surgical therapy, chemotherapy, and immunotherapy; however, cytoreductive surgery benefits for patients with MCD have not been established.

• Hyaline vascular
• Multicentric Castleman disease
• Plasmacytoid
• Unicentric Castleman disease

• KSHV
• Kaposi sarcoma
• Kaposi sarcoma-associated herpesvirus
• multicentric Castleman disease
• primary effusion lymphoma

Multicentric Castleman disease (MCD) is an uncommon systemic lymphoproliferative disease. The diagnosis of this disease is typically challenging and requires collaboration between clinicians and pathologists. Moreover, it is important to exclude other diseases (such as malignancies, autoimmune diseases, and infectious diseases) that have similar clinical manifestations and pathological findings. Patients with untreated severe MCD have high mortality due to devastating cytokine storms. Thus, early diagnosis and prompt treatment is a key imperative. The diagnosis of MCD is based on the clinical signs of systemic inflammation, serological tests, and typical pathological features. In this review article, we provide an overview of MCD with a focus on the emerging evidence pertaining to its diagnosis and treatment.

• Anasarca
• Anti-CD20 monoclonal antibody
• Fever
• Human herpesvirus-8
• Interleukin-6 targeted therapy
• Multicentric Castleman disease
• Reticulin fibrosis
• Thrombocytopenia
• and Organomegaly syndrome

• Angiofollicular lymph node hyperplasia
• Giant lymph node hyperplasia
• Local therapy
• Lymphoproliferative disorder
• Rare diseases

• Multicentric
• Paediatric Castleman disease
• Tocilizumab
• Unicentric

• acquired immunodeficiency syndrome
• angiofollicular lymph node hyperplasia
• anti-interleukin 6
• case report
• hhv-8
• kaposi sarcoma
• literature review
• multicentric castleman disease
• tocilizumab

• Autoimmune Diseases/diagnosis
• Castleman Disease/diagnosis
• Castleman Disease/pathology
• Child
• Diagnosis, Differential
• Female
• Fever/etiology
• Humans

Castleman's disease (CD) is an uncommon group of atypical lymphoproliferative disorders. Extranodal involvement such as the orbit is extremely rare. We aim to report a case of a 62-year-old male who presented with left painless proptosis for the past three years. Examination revealed a firm, lobulated mass in the left superotemporal orbit, displacing the globe inferomedially. A well-defined extraconal orbital lesion encasing the left lateral rectus muscle with intraconal extension was seen on Magnetic Resonance Imaging (MRI) that led to the provisional diagnosis of left solitary encapsulated venous malformation. Excision of the mass via lateral orbitotomy was performed. However, on histopathology, the features were consistent with a mixed-cell variant of Castleman's disease. A detailed systemic workup was unremarkable. Proptosis resolved after surgery and no recurrence was noted in the three-year follow-up. To the best of our knowledge, this is the first case report of a mixed-cell variant of unicentric orbital CD without any systemic features. This case highlights the importance of including CD in the differential diagnosis of well-defined orbital lesions so as to enable its early detection and timely management.

Polyneuropathy is a key feature of polyneuropathy, organomegaly, endocrinopathy, monoclonal band, and skin changes syndrome, which is a paraneoplastic manifestation of an underlying lymphoproliferative neoplasm. We report the first case of polyneuropathy, organomegaly, endocrinopathy, monoclonal band, and skin changes syndrome presenting with a pseudosensory level.

A 59-year-old Tamil woman with long-standing diabetes mellitus and hypertension developed painless, progressive inguinal lymphadenopathy. A contrast-enhanced computed tomography scan showed mild hepatomegaly and intra-abdominal lymphadenopathy. A histological examination of an enlarged inguinal lymph node showed features of a plasma cell-type Castleman disease. She was treated with rituximab. Six months later, she developed gradually ascending numbness and weakness of both lower limbs. On examination, she had flaccid paraparesis (power 3/5) with a sensory level to pinprick at thoracic level 9. Joint position sense was preserved. Her cranial nerves and upper limbs were neurologically normal. Nerve conduction studies confirmed peripheral neuropathy with conduction slowing and a magnetic resonance imaging of her spine did not show cord or root compression. Serum protein electrophoresis showed a monoclonal band. A bone marrow biopsy showed a hypercellular marrow with 30% plasma cells. A repeat contrast-enhanced computed tomography scan showed sclerotic bony lesions involving multiple vertebrae in addition to mild hepatomegaly and intra-abdominal lymphadenopathy. Polyneuropathy, organomegaly, endocrinopathy, monoclonal band, and skin changes syndrome was diagnosed and she was treated with intravenously administered pulse therapy of dexamethasone and cyclophosphamide. After three cycles of treatment, she regained normal muscle power and sensation.

Polyneuropathy in polyneuropathy, organomegaly, endocrinopathy, monoclonal band, and skin changes syndrome can present as a pseudosensory level.

• Castleman
• Lymphoproliferative
• POEMS
• Polyneuropathy
• Pseudosensory

• Castleman disease (CD)
• benign lung lesion
• lymphadenopathy
• mediastinal tumor

Multicentric Castleman disease (MCD) is a rare lymphoproliferative disorder with a high mortality rate in undiagnosed patients. Traditionally, human immunodeficiency virus (HIV) positive MCD occurs due to infection with human herpes virus-8 (HHV), which is thought to play a role in the pathogenesis of MCD. We present the case of a 49-year-old woman who was referred to our oncology clinic for generalized lymphadenopathy in a waxing and waning pattern for the last four years. She was found to be HIV positive. Here we report a rare case of HIV-positive, HHV-negative MCD that responded to prompt treatment with highly active antiretroviral therapy (HAART) followed by chemotherapy as evidenced by improved CD4+ T cell numbers and reduction in lymphadenopathy. The findings in this HHV seronegative patient may indicate an alteration in the virulence and tropism between HHV and HIV, and further demonstrate the need for continued investigation into the pathogenesis of Castleman disease.

• hhv-8
• highly active antiretroviral therapy (haart)
• hiv/aids
• multicentric castleman's disease

Castleman disease (CD) is a lymphoproliferative disorder with an unknown etiology. The disease may be unicentric (UCD) or multicentric (MCD), and three histopathologic variants have been described: hyaline vascular (HV), plasma cell (PC), and mixed type. Extranodal CD is rare. Herein, we report a case of CD presenting as a tonsillar mass, which has not been documented in the literature.

The patient was a 32-year-old man. Laryngoscopy revealed tonsillar hypertrophy, and the patient underwent a low-temperature plasma tonsillectomy. Microscopic examination of permanent sections showed lymphoid follicular hyperplasia, a portion of which appeared to be a fusion of nodular hyperplasia (composed of lymphoid follicles of variable size and shape). These distinctive follicles with atrophic hyalinized germinal centers and a broad mantle zone of small lymphocytes formed concentric rings (so-called onion-skin arrangement). Medium-sized vessels and a plethora of capillaries were present in the center of the lymphatic follicles, mantle zones, and interfollicular areas. A characteristic lollipop appearance was also observed due to the onion-skin arrangement of the expanded mantle zone lymphocytes with a vessel penetrating the germinal center. No aberrant lymphoid population was present based on CD3, CD5, CD20, CD79α, CD21, CD23, bcl-2, cyclin D1, and ki-67 immunostaining. Tests for human herpesvirus (HHV)-8 and Epstein Barr virus (EBV)-encoded small RNA (EBER) were negative. Therefore, a diagnosis of an HV variant UCD was rendered. The patient was treated by local excision without any other therapy based on the diagnosis. At the 7-month follow up, the patient had no recurrent symptoms or masses.

We present an unusual case of a tonsil presenting hyaline vascular Castleman disease (HVCD). This study aims to highlight CD as a differential diagnosis that should be considered by otolaryngologists and pathologists for lymphoproliferative disorders of the tonsil.

• Castleman disease (CD)
• Hyaline vascular variant
• Lymphoproliferative disorder
• Tonsil
• Unicentric Castleman disease (UCD)

Masses in the parapharyngeal space often pose a diagnostic and therapeutic challenge due to an inaccessible location for biopsy and proximity to critical neurovascular structures of the neck. The aims of this study are to describe a rare case of Castleman disease (CD) presenting in the parapharyngeal space.

Case report of a 38-year-old male presenting to a tertiary care center and literature review.

The parapharyngeal space is an unusual location for CD. Surgeons, radiologists, and pathologists must be aware of this disease entity within the differential diagnosis to provide appropriate perioperative counseling for patients.

• Castleman disease
• lymphadenopathy
• neck mass
• parapharyngeal space masses

• Castleman's disease
• lymphadenopathy
• peribronchovascular interstitial thickening

• HHV-8 positive
• HIV negative
• Multicentric castleman disease
• cytokine
• lymphoproliferative
• rituximab.

• Benign
• Calcifications
• Malignant
• Ossification
• Soft tissue lesion

• Calcinosis/diagnostic imaging
• Castleman Disease/diagnostic imaging
• Chondroma/diagnostic imaging
• Diagnosis, Differential
• Fibroma, Ossifying/diagnostic imaging
• Gout/diagnostic imaging
• Humans
• Joint Diseases/diagnostic imaging
• Lipoma/diagnostic imaging
• Muscular Diseases/diagnostic imaging
• Myositis Ossificans/diagnostic imaging
• Neoplasms, Connective and Soft Tissue/diagnostic imaging
• Neurilemmoma/diagnostic imaging
• Soft Tissue Neoplasms/diagnostic imaging
• Vascular Diseases/diagnostic imaging

• University Medical Center Groningen (UMCG)

The spectrum of lymphoproliferative disorders linked to human herpesvirus 8 (HHV-8) infection has constantly been increasing since the discovery of its first etiologic association with primary effusion lymphoma (PEL). PEL is a rapidly progressing non-Hodgkin’s B-cell lymphoma that develops in body cavities in an effusional form. With the increase in the overall survival of PEL patients, as well as the introduction of HHV-8 surveillance in immunocompromised patients, the extracavitary, solid counterpart of PEL was later identified. Moreover, virtually all plasmablastic variants of multicentric Castleman’s disease (MCD) developing in HIV-1-infected individuals harbor HHV-8, providing a strong etiologic link between MCD and this oncogenic herpesvirus. Two other pathologic conditions develop in HIV-1-infected persons concomitantly with MCD: MCD with plasmablastic clusters and HHV-8-positive diffuse large B-cell lymphoma not otherwise specified (HHV-8+ DLBCL NOS), the first likely representing an intermediate stage preceding the full neoplastic form. MCD in leukemic phase has also been described, albeit much less commonly. The germinotropic lymphoproliferative disorder (GLPD) may resemble extracavitary PEL, but develops in immune competent HHV8-infected individuals, and, unlike the other disorders, it responds well to conventional therapies. Almost all HHV-8-mediated lymphoproliferative disorders are the result of an interaction between HHV-8 infection and a dysregulated immunological system, leading to the formation of inflammatory niches in which B cells, at different developmental stages, are infected, proliferate and may eventually shift from a polyclonal state to a monoclonal/neoplastic disorder. Herein, we describe the association between HHV-8 and lymphoproliferative disorders and highlight the predominant distinctive features of each disease.

• Germinotropic lymphoproliferative disorder
• HHV-8
• Human herpesvirus
• KSHV
• Kaposi’s sarcoma-associated herpesvirus
• Lymphoproliferative disease
• Multicentric Castleman’s disease
• Primary effusion lymphoma

Multicentric Castleman disease (MCD) is an uncommon lymphoproliferative disease characterized by systemic inflammatory reactions associated with the dysregulated production of interleukin-6 (IL-6). In patients with MCD, renal involvement is uncommon, with only one report published regarding kidney transplantation (KTx) to treat end-stage renal disease (ESRD) secondary to MCD. Recent clinical observations have shown that IL-6 production is implicated in allograft rejection, while IL-6 receptor blockade (with tocilizumab [TCZ]) reduces alloantibody generation and thereby improves graft survival; however, the efficacy and safety of TCZ in MCD patients undergoing KTx is still unknown.

Herein, we describe the case of a 50-year-old man with MCD who received living-donor KTx for ESRD. Post-operative immunosuppression consisted of a triple-drug regimen (tacrolimus, mycophenolate mofetil and methylprednisolone) with TCZ that was administered intravenously every 2 weeks. At 17 months post-transplantation, the patient remains asymptomatic, and the allograft pathology has shown no evidence of rejection and no development of de novo donor-specific antibody (DSA).

To our knowledge, this is the second reported case of an MCD patient with ESRD who underwent successful KTx. TCZ safely supported the patient during the perioperative period, and this drug may be useful for blocking the generation of donor-specific antibodies and reducing the risk of rejection episodes. KTx in combination with TCZ is thus considered a viable treatment option for ESRD due to MCD.

• Castleman disease
• IL-6
• IgA nephropathy
• Kidney transplantation
• Tocilizumab