Case Of Castleman's Disease Research Articles

Cutaneous Manifestations of Castleman Disease: Histopathological Characteristics and Review of Literature.

Castleman disease (CD) is a poorly understood lymphoproliferative disorder characterized by enlarged lymph nodes. The spectrum of differential diagnoses is wide, and it is hard to differentiate from other diseases. Cutaneous involvement of CD is rare, and studies that describe cutaneous dermatopathology of CD are scarce. The aim of this study was to collect case reports of CD with cutaneous manifestations and identify potential relevant histopathological features. We found that cases of CD with cutaneous manifestations often exhibited dermal lymphoid follicles with follicle center infiltration of lymphocytes and plasma cells. These dermal follicles also had regressive or atrophic germinal centers and were penetrated by hyalinized vessels. Patients with CD also consistently exhibited perivascular and deep dermal inflammatory infiltrate, primarily composed of lymphocytes and plasma cells. We intend to raise awareness of this rare entity and provide more histopathological information regarding its dermatological manifestations.

A Case of Castleman Disease: A Diagnostic Dilemma

Castleman disease (CD) is a disorder characterized by lymphoid proliferation. It is not usually the first differential for pyrexia of unknown origin (PUO) because of the extremely rare incidence worldwide. We report the case of a 24-year-old man with PUO for six months. He had been previously investigated for infective, rheumatological, and immunological causes. Extrapulmonary tuberculosis was considered as the most likely diagnosis because of his clinical presentation and locality. Based on this, he was given a trial of anti-tuberculous therapy. However, he did not show any signs of improvement despite being compliant with the medications. His condition was further complicated by the development of ascites. Upon treatment failure, the patient presented to our tertiary care hospital and was investigated for a possible revision of diagnosis. Based on clinical assessment and histopathology of the lymph nodes, he was diagnosed with idiopathic multicentric CD overlapping with systemic lupus erythematosus. He was started on azathioprine and prednisone and showed a positive response, indicated by a decreasing erythrocyte sedimentation rate and C-reactive protein. The patient continues to be healthy and in remission to date.

A Review of Genetic Abnormalities in Unicentric and Multicentric Castleman Disease.

Simple SummaryCastleman disease is a rare hematopoietic disorder with a broad spectrum of clinical presentations. Different subtypes have been described based on how many lymph nodes are involved, histologic appearance, and associated viral infections. Recently, significant molecular and genetic abnormalities associated with Castleman disease have been described. However, we continue to lack a framework of the biological mechanisms driving this disease process. Thus, our aim was to review all published cases of Castleman disease to date that described molecular abnormalities and correlate cytogenetic, molecular, and genetic alterations with disease subtypes. Our comprehensive review identifies subtype-specific and novel pathways which may allow for more targeted treatment options and unique biologic therapies for Castleman disease.Castleman disease (CD) is a rare lymphoproliferative disorder known to represent at least four distinct clinicopathologic subtypes. Large advancements in our clinical and histopathologic description of these diverse diseases have been made, resulting in subtyping based on number of enlarged lymph nodes (unicentric versus multicentric), according to viral infection by human herpes virus 8 (HHV-8) and human immunodeficiency virus (HIV), and with relation to clonal plasma cells (POEMS). In recent years, significant molecular and genetic abnormalities associated with CD have been described. However, we continue to lack a foundational understanding of the biological mechanisms driving this disease process. Here, we review all cases of CD with molecular abnormalities described in the literature to date, and correlate cytogenetic, molecular, and genetic abnormalities with disease subtypes and phenotypes. Our review notes complex karyotypes in subsets of cases, specific mutations in PDGFRB N666S in 10% of unicentric CD (UCD) and NCOA4 L261F in 23% of idiopathic multicentric CD (iMCD) cases. Genes affecting chromatin organization and abnormalities in methylation are seen more commonly in iMCD while abnormalities within the mitogen-activated protein kinase (MAPK) and interleukin signaling pathways are more frequent in UCD. Interestingly, there is a paucity of genetic studies evaluating HHV-8 positive multicentric CD (HHV-8+ MCD) and POEMS-associated CD. Our comprehensive review of genetic and molecular abnormalities in CD identifies subtype-specific and novel pathways which may allow for more targeted treatment options and unique biologic therapies.

A case of Castleman disease and literature review

A case of Castleman disease and literature review

Castleman’s disease: A case report

Castleman’s disease (CD) is a rare non-malignant lymphoproliferative disorder of uncertain etiology. Its localized variety presents with incidentally found mass or symptomatic mass, whereas other type presents with generalized lymphadenopathy with systemic manifestations. Here, we report the case of localized CD in a 46-year-old female who presented with a complaint of vague upper abdominal pain for the past 6 months. The patient was managed with surgical resection only. Microscopic examination confirmed the entity to be CD of hyaline vascular type. The patient was asymptomatic at 15 months follow-up.

Classic Hodgkin lymphoma and Castleman disease: an entity appears to be emerging.

Hodgkin lymphoma is a B cell neoplasm characterized by Hodgkin and Reed-Sternberg (HRS) cells in an inflammatory background. Classic Hodgkin lymphoma (CHL) accounts for approximately 90% of all cases of HL and four types are recognized in the World Health Organization (WHO) classification: lymphocyte-rich, nodular sclerosis, mixed cellularity, and lymphocyte depleted. Castleman disease (CD) is a designation used for a heterogeneous group of diseases that involve lymph nodes. Histologically, there are hyaline vascular and plasma cell variants, the latter including human herpes virus 8 (HHV8)-positive and HHV8-negative subsets. In this study, we describe three men, 45-57years of age, one HIV-positive, who had coexistent CHL and CD. All patients had the interfollicular variant of CHL and HHV8-negative plasma cell variant CD. Immunohistochemical analysis supported the diagnosis of CHL; the HRS cells were positive for CD15, CD30, and PAX-5 (dim). In two cases, the HRS cells and the plasma cells of CD expressed interleukin-6 (IL-6). Our review of the literature identified 34 cases of coexistent CHL and CD reported previously. In aggregate, about two-thirds of all cases of CHL have been the interfollicular variant and around 90% of CD cases were plasma cell variant, HHV8-negative in the subset of cases tested. We suggest that interfollicular variant CHL and plasma cell variant CD may be a distinct entity with a common pathogenesis, possibly related to IL-6 dysregulation. The few cases in the literature describing other forms of CHL and hyaline vascular variant CD are different from the entity reported here, with a different pathogenesis, likely similar to focal Castleman-like changes that have been described in association with various types of non-Hodgkin lymphoma.

Fiebre de origen desconocido y linfadenopatia en contexto de lupus: presentación de un caso clínico de enfermedad de Castleman

La linfadenopatía ocurre en aproximadamente el 60% de los pacientes con lupus eritematoso sistémico (LES) durante la evolución de la enfermedad. Estas lesiones de ganglios linfáticos son caracterizadas por hiperplasia folicular, necrosis coagulativa, cuerpos de hematoxilina y deposición de ADN dentro de los vasos. Como consecuencia, se subestima al examen histopatológico de los ganglios linfáticos en LES1. Se han notificado casos de linfadenopatía de LES conmorfología de enfermedad de Castleman (EC), que se descubre con el fin de excluir el linfoma maligno. La EC es un trastorno de linfoproliferación atípica que puede presentarse con o sin síntomas sistémicos2-3. Histológicamente, la EC se clasifica como variante hialino-vascular, de células plasmáticas o mixtas. La histología hialino-vascular representa la mayoría de casos de EC unicéntrico (ECU) y el tipo de célula plasmática caracteriza más a la EC multricéntrico (ECM). Se ha demostrado que la ECM tiene asociación con varias enfermedades autoinmunes4-5. En este informe, presentamos una paciente con LES y enfermedad de Crohn con fiebre de origen desconocido (FOD) y linfadenopatías con EMC asociado a infección por virus herpes 8 (HHV-8).

Clinicopathological comparison and therapeutic approach to Castleman disease-a case-based review.

Castleman disease (CD) is a rare, B-cell lymphoproliferative disorder affecting lymph nodes and extranodal anatomical locations. Four types of clinical presentations can be distinguished after exclusion of mimics. The first division is into unicentric CD (UCD) and multicentric CD (MCD). MCD is classified further as HHV-8-negative (idiopathic), MCD associated with HHV-8 infection, and POEMS associated MCD. From the histological standpoint, UCD and MCD can be classified as hyaline-vascular (HV), plasma cell (PC), or mixed cellularity (MC) type, with a spectrum of histopathological manifestations. We present clinical and histopathological features and grading of 25 cases of CD classified according to CDCN histological criteria and according to this clinical algorithm, along with outcomes. Here we provide a fine-resolution description of the histological features of CD. We review and discuss the current diagnostic algorithm, grading system, and recently recommended treatment options. In the presented group of 25 patients with CD there were 14 women and 11 men in the age range 15-79 years. UCD was identified in 15 patients and it was most often located in mediastinum. MCD most frequently occurred as generalized lymphadenopathy. The most common type of CD was HV. All patients with UCD underwent complete surgical resection with a positive outcome. Patients with MCD had diagnostic partial surgical excision of the lesions, later followed by different types of treatment (corticosteroids, chemotherapy, radiotherapy, immunomodulatory agents) or 'watch and wait'. In four cases CD was associated with other malignancies (laryngeal cancer, small lymphocytic lymphoma, gallbladder cancer with hepatic metastases, primary squamous cell lung cancer). The accuracy of histopathological examination is essential and re-evaluation has to be performed in case of relapse or unexpected course of CD. Treatment tailored to fit the disease type and severity should follow the novel recommendations, including anti-IL-6 treatment in the case of MCD.

Clinicopathological Profile of Castleman's Disease in Indian Population: Experience From a Tertiary Care Center.

Castleman's disease (CD), also known as angiofollicular lymph node hyperplasia, a rare, non-malignant chronic lymphoproliferative disease characterized by, uni or multicentric lymphadenopathy. There is limited information about the clinicopathological variations and associations of this entity. A total of 50 cases of CD were retrieved from the archives, between the years 2005-2017. The cases were divided into pediatric (0-18years), young adult (age ≤ 40years) and older adult groups (age > 40years respectively). Detailed clinicopathological correlation was done. The age range was 6-74years. There was a male predominance (M: F-1.6:1). The majority (72%; 36/50) of the patients were adults; 46% young adult and 28% older adult, while only 28% (14/50) were of pediatric. Majority (78%) showed features of unicentric Castleman disease (UCD) while rest 22% presented with multi centric Castleman disease (MCD). Systemic symptoms were more frequent in MCD as compared to UCD cases (p = 0.06). The majority of the cases (40/50; 80%) were of the hyaline vascular type. Two of the cases showed mixed histological feature. Out of 50 patients 29 patient's treatment details are available. Majority unicentric cases were cases surgically excised 14/17 (82.3%). Three patients 3/17 (17.6%) were treated with chemotherapy. In multicentric Castleman's disease group, six of the 12 cases with MCD were managed by chemotherapy. One patient died of progressive disease. Castleman disease has varied clinical presentation and is often associated with other diseases. A high degree of suspicion and careful histological examination is required in order not to miss this entity.

Epidemiology of Castleman disease associated with AA amyloidosis: description of 2 new cases and literature review

Introduction: HHV8-negative Castleman disease (CD) is classified as hyaline vascular (HV) type, or mixed or plasma cell (PC) types. It may present as multicentric CD (MCD) or unicentric CD (UCD). CD is a rare cause of AA amyloidosis (AAA). We aimed to report the main features of CD with secondary AAA through a description of new cases and a systematic literature review.Patients and methods: New cases were identified from the French National Reference Center for AAA. A systematic literature review was performed to identify HHV8-negative CD cases associated with AAA.Results: Thirty-seven patients were analysed, consisting of two new cases and 35 from literature. Twenty-three had UCD and 14 had MCD. PC was the main histologic subtype (n = 25; 68%) in both UCD and MCD patients. Surgical excision of UCD was performed in 21 patients (91%) with a favourable outcome, except for four patients (19%). Clinical and biologic remission was achieved in six patients with MCD (43%), all of whom were treated with anti-interleukin-6 (IL-6) therapy.Conclusions: AAA is a rare complication of CD, namely idiopathic MCD and UCD presenting with the PC histologic subtype. Surgical excision of UCD should be the first-line treatment whenever possible, while anti-IL-6 therapies seem effective for MCD.

Virome capture sequencing does not identify active viral infection in unicentric and idiopathic multicentric Castleman disease.

Castleman disease (CD) describes a spectrum of heterogeneous disorders defined by characteristic lymph node histopathology. Enlarged lymph nodes demonstrating CD histopathology can occur in isolation (unicentric CD; UCD) sometimes accompanied by mild symptoms, or at multiple sites (multicentric CD, MCD) with systemic inflammation and cytokine-driven multi-organ dysfunction. The discovery that Kaposi sarcoma herpesvirus/human herpesvirus (HHV)-8 drives MCD in a subset of patients has led to the hypotheses that UCD and MCD patients with negative HHV-8 testing by conventional methods may represent false negatives, or that these cases are driven by another virus, known or unknown. To investigate these hypotheses, the virome capture sequencing for vertebrate viruses (VirCapSeq-VERT) platform was employed to detect RNA transcripts from known and novel viruses in fresh frozen lymph node tissue from CD patients (12 UCD, 11 HHV-8-negative MCD [idiopathic MCD; iMCD], and two HHV-8-positive MCD) and related diseases (three T cell lymphoma and three Hodgkin lymphoma). This assay detected HHV-8 in both HHV-8-positive cases; however, HHV-8 was not found in clinically HHV-8-negative iMCD or UCD cases. Additionally, no novel viruses were discovered, and no single known virus was detected with apparent association to HHV-8-negative CD cases. Herpesviridae family members, notably including Epstein-Barr virus (EBV), were detected in 7 out of 12 UCD and 5 of 11 iMCD cases with apparent correlations with markers of disease severity in iMCD. Analysis of a separate cohort of archival formalin-fixed, paraffin-embedded lymph node tissue by In situ hybridization revealed significantly fewer EBV-positive cells in UCD and iMCD compared to tissue from HHV-8-positive MCD and EBV-associated lymphoproliferative disorder. In an additional cohort, quantitative testing for EBV by PCR in peripheral blood during disease flare did not detect systemic EBV viremia, suggesting detection lymph node tissue is due to occult, local reactivation in UCD and iMCD. This study confirms that HHV-8 is not present in UCD and iMCD patients. Further, it fails to establish a clear association between any single virus, novel or known, and CD in HHV-8-negative cases. Given that distinct forms of CD exist with viral and non-viral etiological drivers, CD should be considered a group of distinct and separate diseases with heterogeneous causes worthy of further study.

A Case Report of Adrenal Castleman’s Disease

Castleman’s disease(CD) is a rare angiofollicular lymph node hyperplasia. It is difficult to diagnose CD preoperatively due to its occurrence in multiple regions. It is reported that CD generally occurred in the mediastinum and there were very few reports which mentioned adrenal area. We report a case of Castleman’s disease in the adrenal area. We reviewed the patient’s hospitalization records, including clinical manifestations, diagnostic tools, management, and outcomes. Histopathological examination was the method for diagnosis. In this case report, we present a case of CD that occurred in the adrenal area. The patient was initially diagnosed with adrenal tumor by CT. After operation, histopathological examination showed unicentric CD of the hyaline vascular type. Castleman’s disease rarely occurs in adrenal, which is easily neglected and misdiagnosed. Histopathological examination is the gold standard in the diagnosis of CD, and surgical excision is effective in the treatment of unicentric CD.

A case of Castleman disease that improved after kidney transplantation

This is a case of a 56-year-old man with Castleman disease (CD) who improved after kidney transplantation (KTP). CD is an uncommon lymphoproliferative disorder that was found incidentally on biopsy during dialysis in the current patient and was followed up without further treatment. However, the lesion showed improvement after KTP. Therefore, active KTP can be considered even if CD is one of the lymphoproliferative disorders that can occur as a complication after KTP.

Radiologic and Histopathologic Features in an Intracranial Localized Castleman Disease

Castleman disease (CD) is a rare pathologic process of unknown etiology, characterized by non-neoplastic lymph node enlargement. Two distinct histologic patterns are recognized; the hyaline-vascular type and the less common plasma cells type. Another intermediate type has been described. The clinical features are classified into 2 categories, localized (unicentric) and generalized (multicentric), the later associated with systemic manifestations and poor prognosis. CD affecting the central nervous system is extremely rare. We report a new case of localized intracranial CD and we accomplish a review of the literature. A 30-year-old man presented with a generalized tonic-clonic seizure. Computerized tomography and magnetic resonance imaging showed a small mass in the right temporoparietal convexity with homogenous enhancement after contrast administration. Extensive vasogenic edema in comparison with the size of the mass was also identified and based on the neuroradiologic finding, a suspected diagnosis of meningoangiomatosis was formulated. The mass was completely resected and his histologic examination identified the hyaline-vascular type of CD. One year after surgery, the patient remains seizure free, without evidence of systemic involvement or recurrence of the mass. Our case and review of the literature show the value of the extensive brain edema on neuroimaging finding to the differential diagnosis for a solitary mass arising from the meninges. We emphasize on the need for histologic examination when the diagnosis of meningioma is not entirely clear.

Castleman disease versus lymphoma in neck lymph nodes: a comparative study using contrast-enhanced CT

BackgroundThe purpose of this study was to determine the contrast-enhanced CT characteristics for differentiating between Castleman disease (CD) and lymphoma in neck lymph nodes.MethodsThis retrospective study evaluated the number (solitary or multiple), strength of contrast-enhancement, type of contrast-enhancement, surrounding vessels, contrast-enhanced Hounsfield unit (HU) values, and anatomical distributions of lymph nodes in 34 patients with confirmed CD and 55 patients with newly diagnosed untreated lymphoma. Independent t-tests, receiver operating characteristic (ROC) curve analysis, and chi-square tests were used to evaluate the variables and CT features.ResultsSeveral significant differences were found between CD and lymphoma. The interval between first contrast-enhanced CT and biopsy/surgery was significantly longer in the CD group (mean 72 ± 105 days, median 60 days) than in the lymphoma patients (mean 30 ± 2 days, median 12 days; p = 0.015). The lymphoma patients presented significantly more often with fatigue and fever (p = 0.023 and p = 0.016 respectively) than did the CD subjects. HU values of nodules after enhancement were significantly higher in the CD patients than in the lymphoma patients. In cases involving multiple lymph nodes, in all the CD cases, all affected nodes were located in only the left or right side of the neck, not bilaterally. ROC analysis showed a significant difference in contrast-enhanced CT attenuation values between lymphoma and CD (p < 0.001, area under the curve = 0.954), with a cut-off value of 92.5 HU. We constructed a decision tree according to these imaging characteristics.ConclusionsContrast-enhanced CT can be useful for differentiating between CD and lymphoma.

Clinical and molecular characteristics of unicentric mediastinal Castleman disease.

Unicentric mediastinal Castleman disease (CD) is a rare condition, poorly characterized due to the small number of cases and the absence of genomic study. We analyzed clinical, radiological, histological and genomic patterns associated with mediastinal CD in a substantial case series.Methods: We retrospectively reviewed cases of unicentric mediastinal CD managed in 2 French thoracic surgery departments between 1988 and 2012. Clinical, radiological, surgical and pathological data were recorded. On available FFPE blocks we performed mutation screening by next-generation-sequencing, using AmpliSeq™ Cancer Hotspot v2 (Life Technologies) and immunohistochemistry (IHC) (AKT-mTOR pathway). Eleven patients were identified (mean age 41±15 years, sex-ratio 0.8, median follow-up 78 months). Surgical approach was thoracotomy (n=6), sternotomy (n=4), and VATS (n=1). Additional procedures included thymectomy in three cases, mediastinal lymphadenectomy in two cases, and bilobectomy in one case. One patient presented local relapse as a follicular dendritic cell sarcoma, leading to death 48 months after the first resection. Within 9 patients whose FFPE blocks were available, 2 mutations were found: VHL (p.F119L, 35%, n=1) and JAK3 (p.V718L, 53%, n=1). Phospho-AKT and phospho-mTOR stainings were negative in all cases, whereas phospho-S6RP staining was positive in eight cases, mainly in interfollicular cell cytoplasm. From this series of patients with unicentric mediastinal CD, we observed 2 cases of potential driver mutations and 8 cases of phospho-S6RP activation not related to AKT-mTOR. Larger studies are required to decipher more precisely the molecular abnormalities and potential therapeutic targets underlying this uncommon condition.

Primary Castleman's disease in the liver: A case report and literature review

Castleman's disease (CD) is a lymphoproliferative abnormality, also referred to as giant lymph node hyperplasia or follicular lymphoid hyperplasia. The occurrence of CD in the liver is rare. Radiological diagnosis of hepatic CD by computed tomography (CT) and magnetic resonance imaging (MRI) remains difficult. On imaging, hepatic CD is often expressed as a single, well-defined soft tissue lesion, with rare cystic degeneration and focal necrosis. The CD lesions appear as hypervascular with abundant cell proliferation on CT and MRI. Polymorphic calcification is commonly identified in the lesion. However, these findings are non-specific for a definitive radiological diagnosis. We herein present a case of hepatic CD and review its pathological and imaging characteristics. In particular, a strip-like area was observed extending from the nodule, which may be helpful for the diagnosis of CD in the liver.

Castleman Disease- An Uncommon And Intriguing Condition Revisited: A Report Of Two Cases

Castleman disease (CD) also called as angiofollicular hyperplasia or giant lymph node hyperplasia of unknown cause is a benign lymphoproliferative disorder. It is a localised (unicentric) or disseminated (multicentric) disease. This disease is uncommon with an incidence of 25 cases per million person per year. Castleman disease is a heterogeneous group of disorders with four characteristic histological variants. The etiology of this disease is poorly understood. We report two cases of CD, one presenting with a neck mass and the other presenting with para-aortic and mesenteric lymphadenopathy which were classified as hyaline vascular type and mixed type of CD respectively. DOI: 10.21276/APALM.1559

Unicentric hyaline vascular type of castleman disease of the renal hilum with diagnostic dilemma: A case report and review of literature

Castleman disease (CD) represents a morphologically distinct variety of benign proliferation of lymphoid tissue. Renal hilum involvement is rare and may be confused with renal malignancy or granulomatous diseases. Here, we report a rare case of unicentric CD of renal hilum. A 56-year-old male patient presented with flank pain and voiding symptoms. Contrast-enhanced computed tomography scan showed a left renal hilar tumor mimicking a renal malignancy which led to nephrectomy. Our case is the first report of the unicentric hyaline vascular type of CD of the renal hilum reported from India. Awareness of such cases is important for radiologists and surgeons to prevent the misdiagnosis of a renal malignant tumor and to avoid nephrectomy.

Axillary Castleman's Disease: A Rare Case Report

Castlemans Disease (CD) is a rare benign lymphoproliferative disorder of uncertain origin which most commonly involves the mediastinum but rarely affects the axilla. We report a case of voluminous axillary unicentral CD, detected due to palpation of a painless mass in the left axilla in a healthy 32-year-old woman.