Hyaline Vascular Research Articles

Enfermedad de Castleman: un enfoque integral a propósito de un reporte de caso

The clinical case of a 30-year-old female patient with supraclavicular and ipsilateral axillary lymphadenopathy who underwent excisional biopsy with subsequent study is presented. Histopathological analysis of the resected tissue sample revealed a series of distinctive features associated with hyaline vascular variant Castleman disease. The presentation of this case not only provides detailed information about the clinical evolution of the patient, but also serves as a basis to illustrate Key aspects of histopathological is and immunohistochemical implications in Castleman disease. In addition to making a review of the topic regarding this rare pathology in which case reports are essential to increase the understanding of its clinical variability and its diagnostic approach, illustrating the challenges in differential diagnosis and how they should be addressed. Key words: CASTLEMAN, LYMPHOMA, LYMPHADENOPATHY, HYALINE VASCULAR, PLASMA CELLS

Multicentric Hyaline-Vascular Castleman Disease: The Missing Link?

Introduction: Castleman disease (CD) is a rare lymphoproliferative disorder that encompasses distinct clinicopathological entities. Unicentric form of the disease (UCD) usually involves a single lymph node station, exhibits hyaline vascular (HV) pathological changes with follicular dendritic cell expansion, and may associate with specific and life-threatening complications including paraneoplastic pemphigus (PNP) and follicular dendritic cell sarcoma (FDCS). Plasma cell interfollicular infiltration is absent in the HV subtype as opposed to the Plasma-Cell (PC) or Mixed subtypes. PC subtype has been associated with inflammatory symptoms thought to be secondary to plasma cell infiltration and represents the majority of HHV8-negative “idiopathic” multicentric forms of the disease. Interestingly, patients with PC-UCD behave as PC-MCD, suggesting a stronger role of histology rather than Unicentric vs Multicentric phenotype in disease expression. We here studied the phenotype of HV-MCD, a rare subtype of CD characterized by hyaline-vascular pathological changes involving 2 or more lymph node stations. Methods: Patients were screened through the French national reference center for CD between January 1994 and June 2023. Cases were followed from first symptoms to last follow-up visit. Comparators consisted of patients with HV-UCD and patients with PC/Mixed iMCD (P/M-iMCD). All cases and biopsies were reviewed by three expert clinicians and one expert pathologist. Results: Sixteen patients with a diagnosis of HHV8-negative HV-MCD were identified. All patients had supra- and infradiaphragmatic involvement. Four were excluded because of a subsequent diagnosis of POEMS, systemic lupus erythematosus, tuberculosis, or inborn error of immunity. The 12 remaining patients were considered as having HV-iMCD and compared to 101 patients with P/M-iMCD and 139 patients with HV-UCD. Characteristics and comparison between the 3 groups are depicted in Table 1. When compared to HV-UCD, HV-iMCD displayed frequent systemic involvement with significantly higher ECOG, higher frequency of fever and splenomegaly, and higher levels of C-reactive protein, gammaglobulins, leukocytes and ferritinemia ( Figure 1). Age at diagnosis was not different between HV-UCD and HV-iMCD. No cases of TAFRO syndrome were observed in HV-UCD whereas 4 cases were observed in HV-iMCD. All cases of PNP (n=12) and FDCS (n=3) were observed in the HV-UCD group. We observed a younger age at diagnosis in HV-iMCD compared to P/M-iMCD (median 24 [range 13-70] vs median 50 [range 11-88] years respectively, p = 0.01). We also noted a trend towards lower levels of C reactive protein and gammaglobulins as well a higher albumin level in HV-iMCD vs P/M-iMCD but these differences were not significant ( Figure 1 and Table 1). Treatments were similar between HV-iMCD and P/M-iMCD with prescription of steroids or anti-IL6R as first line therapy in 8/12 (67%) and 61/101 (60%) respectively. As expected, surgery was the first line therapy in 98/139 (72%) of HV-UCD patients. One patient with HV-iMCD and two with HV-UCD died (logrank p = 0.10), whereas 13 died in the P/M-iMCD group (logrank p = 0.8). Conclusions: These data altogether indicate that HV-iMCD appears to be a distinct entity in CD landscape, sharing pathological aspects of HV-UCD and clinical/biological features of P/M iMCD. In line with this view, there seems to be no overlap between HV-UCD and HV-iMCD-related complications. The findings also suggest that nodal PC infiltration is not sufficient to explain the inflammatory pattern of iMCD.

Clinical features and treatment outcomes of Castleman disease in children: a retrospective cohort in China

Castleman disease (CD) is a rare lymphoproliferative disorder of undetermined etiology. Unicentric CD (UCD) and multicentric CD (MCD) are two phenotypes of CD diagnosed by the histopathology of lymph nodes. We attempted to describe a pediatric CD cohort to optimize the management of this disease. We reviewed the medical records of pediatric patients diagnosed with CD between April, 2004, and October, 2022, at the Children’s Hospital of Fudan University. Prognosis information was collected in January, 2023, by telephone inquiry. Twenty-two patients with UCD and 2 patients with MCD were identified, all with hyaline vascular (HV) type. The median ages at diagnosis were 10.75 years (IQR 8, 12.81) for UCD and 14.42 years (IQR 13.42, 15.42) for MCD. The most common lesion location of UCD was the neck (9/22, 40.91%) and abdomen (9/22, 40.91%). Systematic symptoms occurred on 10/22 (45.45%) patients with UCD and 1/2 (50%) patients with MCD, and abnormal laboratory indexes were detected in both. Resection and biopsy were performed on all patients. One out of two patients with MCD also received rituximab for upfront therapy. After a median of 4 years (IQR 1.5, 6) of follow-up time, the overall survival was 100% and the complete remission rate in UCD was 63%. There was no relapse or progression.Conclusions: Our series demonstrated that HV-UCD was the most common type in children. Resection and biopsy were used for both deterministic diagnoses and treatments. Despite the high possibility to develop systematic inflammation, children with CD showed promising outcomes.What is Known:• Castleman disease is a rare lymphoproliferative disorder with limited cohort studies, especially in pediatrics.• The ubiquity of delayed confirmations and misdiagnoses points to a lack of knowledge about etiology and characteristics, which is a prerequisite for novel therapeutics.What is New:• We retrospectively reviewed and analyzed the clinical and pathological symptoms, laboratory and imaging features, and treatment outcomes of a Chinese pediatric cohort with Castleman disease.• Our work may improve the recognition and optimize the management of this rare disease in children.

Pediatric multicentric Castleman disease; a case report

Castleman disease (CD) is a rare B-cell lymphoproliferative disorder of unknown etiology characterized by benign lymphoid follicular hyperplasia and capillary proliferation. CD can be divided histologically into four different variants: hyaline-vascular (HV), plasma-cell (PC), mixed and plasmablastic types. The unicentric CD (UCD) is localized lymphadenopathy while multicentric CD (MCD) is a systemic disorder involving cytokine-induced polyclonal lymphoproliferation and systemic inflammation due to overexpression of interleukine-6, and can be idiopathic or associated with HIV/HHV-8 infection. Surgical removal is the gold standard for patients with unicentric CD, while multicentric CD requires systemic therapy. In our presentation we wanted to show that even multicentric type of CD can be treated surgically only and that this surgical approach can be therapeutic and not mutilating at the same time. As in every rare disease, the recording of cases in rare disease registries is essential. Accumulation of the cases enables the evaluation of treatments and may provide a solid base for guidelines update.

A National, Multicenter, Retrospective Study of Castleman Disease Implementing Cdcn Criteria: 'severe Imcd' Is Indeed Severe

Objective: To delineate the distribution, clinical characteristics and prognostic features of different subtypes of Castleman disease based on the CDCN criteria. To describe the first-line treatment choice for iMCD in China before the era of IL-6-directed therapy. Methods: This was a national, observational, retrospective study which enrolled consecutive patients with CD diagnosed at 40 large Chinese institutions from 2000 to 2021. Patients were classified into different CD subtypes according to the CDCN criteria. The primary outcomes were the distribution of different CD subtypes, descriptions of demographic and clinical characteristics, treatment options and overall survival. Results: A total of 1634 CD patients (unicentric CD(UCD), n=903; multicentric CD(MCD), n=731) were enrolled. Among UCDs, hyaline-vascular (HV) was the major pathological subtype, and there were 162(17.9%) patients with an MCD-like inflammatory state (UCD-MIS). Among the MCD patients, there were 12 HHV-8-related MCD patients and 719 HHV-8-negative MCD patients (asymptomatic MCD (aMCD), n=139; iMCD, n=580). Of the 580 iMCD patients, 41(7.1%) were classified as having iMCD-TAFRO, while the others were classified as having iMCD-NOS. Among the iMCD patients with first-line treatment information, a trend from pulse combination chemotherapy toward a continuous approach was noticed (Fig 1A). Survival analysis revealed significant differences between different subtypes, and the estimated 3-year overall survival rates for UCD, iMCD-NOS and iMCD-TAFRO patients were 98.0%, 89.6% and 65.7%, respectively. Among the iMCD-NOS patients, the multivariate Cox regression model identified 'severe iMCD' (HR=4.540; 95% CI 1.888-10.915, p=0.001) as the only independent risk factor for death (Fig 1B). The estimated 3-year overall survival rates for severe and nonsevere iMCD-NOS patients were 93.8% and 75.6%, respectively. Conclusion: This study depicts a whole picture of CD subtype distribution, treatment options and survival information in China and validates the rationality of the concept of severe iMCD proposed by the CDCN. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

A Cytological Review of Follicular Dendritic Cell-Derived Tumors with Emphasis on Follicular Dendritic Cell Sarcoma and Unicentric Castleman Disease.

Follicular dendritic cells (FDCs) are antigen-presenting cells located in the germinal centers of the lymph nodes. Among the few tumors showing FDC differentiation are follicular dendritic cell sarcoma (FDCS) and Castleman disease (CD), more precisely the unicentric hyaline vascular (HV) variant. Both are relatively rare tumors, and the diagnostic cytological experience is limited to descriptions of isolated cases or small series. The purpose of this review is to bring together all the available cytological published information, and our personal experience, in order to obtain a global idea of the cytological features of these peculiar FDC-derived tumors. The different descriptions of FDCS are very similar, reflecting a tumor that shows repetitive and characteristic cytological features. It shows a dimorphic population of mature lymphocytes and large tumoral cells with partial spindle morphology. Most cases of HV variant of CD can be recognized as benign upon cytology, however a precise diagnosis seems more difficult. It is characterized by reactive lymphocytes mixed with vessels and FDCs, either single or forming syncytial aggregates. Both, FDCS and CD are challenging for cytological diagnosis in which a high index of suspicion is necessary for a correct preoperative assessment. Cytology is very useful for follow-up of recurrences and metastases.

Abstract #994509: Adrenal Insufficiency: A Unique Presentation of Multicentric Castleman Disease with Human Herpes Virus 8 Positivity and Concomitant Kaposi Sarcoma

Multicentric Castleman Disease (MCD) is a lymphoproliferative disorder involving multiple lymph nodes and can be associated with human herpes 8 virus (HHV-8). Hyaline vascular (HV) MCD is rare, occurring in < 10% of cases. MCD with concomitant HIV negative Kaposi Sarcoma (KS) is also uncommon and can peculiarly present with adrenal insufficiency.

Kidney biopsy findings in two patients with TAFRO syndrome: case presentations and review of the literature

BackgroundTAFRO syndrome is a clinical subtype of idiopathic multicentric Castleman disease (iMCD) that is characterized by thrombocytopenia, anasarca, fever, reticulin myelofibrosis (or renal dysfunction), and organomegaly. TAFRO syndrome has only recently been described, and many clinicians are unaware of this disease, leading to delays in diagnosis and treatment. We present two patients with TAFRO syndrome in whom renal biopsies were performed.Case presentationBoth patients had subacute onset and exhibited renal insufficiency, edema, anemia, thrombocytopenia, polyserositis and lymphadenopathy over the disease course. However, there were many differences in their clinical manifestations. Case 1 was a 30-year-old woman admitted due to intermittent vaginal bleeding for 3 weeks. Laboratory tests on admission showed severe renal insufficiency (creatinine: 624 μmol/L), severe anemia (Hb: 41 g/L), and moderate thrombocytopenia (61 × 109/L). Case 2 was a 42-year-old man. Acute epigastric pain was his initial complaint, and computed tomography (CT) revealed retroperitoneal exudation around the pancreas. He was diagnosed with acute pancreatitis, and after treatment with a proton pump inhibitor (PPI) and somatostatin, his abdominal pain still recurred. During treatment, renal failure gradually increased, with oliguria, fever, anemia, thrombocytopenia, edema and massive ascites. Lymph node histologies were consistent with the hyaline-vascular (HV) type and mixed type, respectively, and renal histopathologies were consistent with thrombotic microangiopathy (TMA)-like renal lesions and membranoproliferative glomerulonephritis (MPGN), respectively. Their general conditions improved after glucocorticoid therapy, but their renal functions did not recover completely. On the basis of glucocorticoids, second-line treatments with tocilizumab and rituximab, respectively, were applied.ConclusionsThe diagnosis of TAFRO syndrome is based mainly on clinical manifestations and lymph node biopsies. A reliable early diagnosis and appropriate rapid treatment are essential to improve patient outcomes. Clinicians should deepen their understanding of this disease and similar conditions. Once the disease is suspected, lymph node biopsies should be performed as soon as possible. In addition, renal biopsies should be actively performed in patients with renal involvement.

Predominant Stroma-Rich Feature in Hyaline Vascular Variant of Castleman Disease Is Associated With Paraneoplastic Pemphigus

We aimed to describe the clinical and histopathologic features of Castleman disease (CD), particularly emphasizing its associations with paraneoplastic pemphigus (PNP) and prognosis. We retrospectively enrolled 123 CD patients at our center. Clinical, pathologic, and laboratory data were reviewed. Fifty percent of the patients had PNP. Compared with those without PNP, patients with PNP-associated CD had more hyaline vascular (HV) variants (83.9% vs 57.4%), fewer mixed cellular variants (16.1% vs 24.6%), and no plasmacytic variants (0% vs 18.0%). Thirty-eight of 87 patients with the HV variant of CD (HV-CD) had stroma-rich (SR) features, and the incidence rate was higher in those with PNP-associated CD than in those without PNP (48.4% vs 13.1%, P < .001). The SR variant was associated with higher PNP-associated IgG titers than SR absence before surgery (median 1:160 vs 1:80, P = .019) or after surgery (median 1:160 vs 1:40, P = .013). The SR variant was also an unfavorable prognostic factor for CD survival in univariate analysis. The 3-year survival rates were 47.5% among those with PNP and 87.7% among those without PNP (P < .001). PNP is associated with specific subtypes of CD and affects survival. The SR variant of HV-CD positively correlates with the incidence of PNP.

Castleman disease spectrum.

8548 Background: Castleman disease (CD) describes a group of lymphoproliferative disorders that share characteristic histopathology. Unicentric CD (UCD) and idiopathic multicentric CD (iMCD) are differentiated by the number of enlarged lymph node (LN) regions: UCD involves 1 region and iMCD involves &gt; 1 region. UCD typically has mild or no symptoms whereas iMCD requires abnormal labs and symptoms for diagnosis and can progress to life-threatening multi-organ failure. Review of an international natural history registry of CD revealed patients across a broad spectrum with regards to number of enlarged LN regions and disease severity. We hypothesize that there is a positive correlation between disease activity and the number of enlarged LNs and that the spectrum of CD is more complex than a binary UCD-iMCD dichotomy. Methods: Herein, enrolled UCD and iMCD patients whose diagnosis was confirmed by an expert-panel were selected for analysis (N = 81). A standardized disease activity score (scale 0-1) was computed for each patient using available diagnostic values of C-reactive protein, hemoglobin, and albumin (CHA score). Results: We looked at the association between number of enlarged LNs and CHA and found a significant positive correlation (R = 0.65, p &lt; 0.0001). Given this, we divided the cohort into groups of mild, moderate, and extensive lymphadenopathy according to the number of regions of enlarged LNs at the time of diagnosis: group 1 (1 enlarged LN region); group 2 (2-4 enlarged LN regions); and group 3 (≥5 enlarged LN regions). We identified 20 patients in group 1, 19 in group 2, and 42 in group 3 with no statistical differences in sex, race, or age at diagnosis. Histopathological subtype differed significantly among groups. Group 1 was 89% hyaline vascular (HV)/ hypervascular (HpV) and 11% mixed (Mx); group 2 was 74% HV/HpV, 21% Mx, and 5% plasmacytic (Pl); and group 3 was 64% HV/HpV, 32% Mx, and 5% Pl. We then looked at CHA score in these groups and found that group 3 patients have a significantly greater CHA score (median [IQR]: 0.46 [0.49]) than both group 2 (0.08 [0.14]) and group 1 (0.0 [0.10]) (adjusted p &lt; 0.001 for both) while there was no difference between groups 1 and 2. Conclusions: These results suggest that disease severity is positively associated with the number of enlarged LNs. The different proportions of histopathological subtypes between the three groups could indicate different pathologic mechanisms are involved. Further work is needed to determine if patients with a few enlarged LNs exhibit disease more closely to UCD or iMCD and to understand long-term outcomes for these patients.

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.

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.

Hyaline vascular variant of unicentric Castleman disease of the tonsil: a case report

BackgroundCastleman 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.Case presentationThe 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.ConclusionWe 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’s Disease: A Unicentric Case of Abdominal Origin and Literature Review

Castleman’s disease (CD) is a rare lymphoproliferative disorder, which may be unicentric or multicentric. We present the case of a young man with the hyaline vascular (HV) variant of unicentric CD, with a review of cases of CD in the abdominal cavity. A 38-year-old man presented with post-meal epigastric pain and lactose intolerance that had started two months earlier. A solitary 7 cm retroperitoneal mass was detected using computed tomography (CT) scan. The mass was surgically resected and histological examination revealed CD of the HV variant. The symptoms resolved following the operation and the patient was free of disease at 1-year follow-up. A comprehensive literature review yielded reports of a further 214 patients with CD in the abdominal cavity. The female: male ratio was 1.64:1 (133 females, 81 males). The multicentric type of the disease was reported in 9/194 (4.6%) and the unicentric type in 185/194 (95.4%). The HV variant of the disease was reported in 168/191 patients (87.9%), the plasma cell variant in 13/191 (6.8%), the mixed variant in 9/191 (4.7%) and the stroma rich variant in 1/191 (0.5%). Regarding the location, 106/187 (56.6%) of the lesions were found in the retroperitoneal space, 34/187 (18.2%) in the mesentery, 8/187 (4.1%) in the liver and biliary tract, 12/187 (6.3%) adjacent to the pancreas and 17/187 (9%) in an unspecified region of the abdomen. Although further research is required to identify the exact etiology of the disease, the HV variant of CD, which is the most common, can be effectively treated with surgical resection. The plasma cell type of CD is a more serious condition and the high risk associated with misdiagnosis and delay in its treatment renders high clinical suspicion and early identification of this variant of the utmost importance.

Castleman disease. Histopathological and immunohistochemical analysis of 39 cases.

Castleman disease (CD) is a rare lymphoproliferative that comprises two distinct clinical subtypes (unicentric and multicentric) and has two basic histopathology patterns that are hyaline-vascular (HV) and plasma-cell (PC) type. Some cases of multicentric PC disease are associated with HHV-8 infection. To present the histopathologic and immunohistochemical characteristics of 39 cases of CD. A review of cases with the diagnosis CD from the files of the Department of Pathology of the ABC Medical Centre in Mexico City was performed. Thirty-nine cases of CD were identified, and a detailed paraffin immunophenotypic study of 9 of them was completed using desmin, cytokeratin OSCAR (CO) and Epidermal growth factor receptor (EGFR), to evaluate the dendritic cell population. Of the 39 cases of CD, 24 were HV and 15 CP. All HV cases were unicentric and only one case of CP was multicentric. The most frequent localization in both subtypes was in lymph nodes; 21/24 cases in HV and 15 cases of CP. All cases were immunostained with CD20 that was expressed in the germinal centers (CGs), CD3 in the paracortical zone, and CD21 in follicular dendritic cells (CDF) within CGs, with expansion towards the area of the hyperplastic mantle zone (only in the HV variant). One case of CD CP was positive for HHV-8. Of the nine cases (6 HV and 3 PC cases) that were detailed with IHC, we found EGFR expression in FDC in all but one of the 9 cases studied and desmin was positive in fibroblastic reticulum cells (FRC) in all, but one of the cases of CD. CO was positive FRC in 3 of 6 cases of HV type and all (3) of the PC type. Clinical, histopathological and HIV and HHV-8 status markers, allow for the classification of CD into groups with markedly different outcomes and disease associations.

Clinicopathological characteristics of unicentric retroperitoneal Castleman's disease: a study of 14 cases.

BackgroundThe objectives of this study are to investigate the clinicopathological characteristics and prognosis analysis of unicentric retroperitoneal Castleman’s disease (CD), and to improve the level of diagnosis and treatment of unicentric retroperitoneal CD.MethodsThe clinical data of 14 patients with unicentric retroperitoneal CD undergoing surgery from September 2007 to March 2014 were retrospectively reviewed.ResultsThere were six males and eight females with a median age of 39 years old (range 15–58). Only three patients had a clinical manifestation of abdominal pain, and one patient associated with myasthenia gravis. All patients underwent surgical resection. The mean operation time was 137 min with a range of 72–472 min. The mean blood loss was 143 ml (range 50–500 ml). The CD was confirmed by histopathology. There were hyaline vascular (HV) type of CD in 13 cases, and mixed type of CD in one case. The mean hospital stay was 17.9 days with a mean postoperation hospital stay of 9.2 days. The duration of follow-up ranged from 21 to 99 months for 14 cases. All the 14 patients were alive without recurrence.ConclusionsUnicentric retroperitoneal CD is a rare disease that is often misdiagnosed due to the absence of specific clinical manifestations. The final diagnosis depends on pathologic examination. Complete surgical resection of the tumor is the best therapeutic alternative for unicentric CD.

Clinical spectrum of intrathoracic Castleman disease: a retrospective analysis of 48 cases in a single Chinese hospital

BackgroundThorax is the common place to develop Castleman disease (CD), but there is no systemic clinical analysis for intrathoracic CD.MethodsWe conducted a retrospective analysis of 48 intrathoracic CD patients with definite pathological diagnosis who were hospitalized between 1992 and 2012 in a Chinese tertiary referral hospital.ResultsThe study included 16 cases with unicentric CD (UCD) and 32 cases with multicentric CD (MCD). UCD were younger than MCD (30.5y vs 41.6ys, P < 0.05). MCD were more symptomatic (50% vs 96.9%, P < 0.001) and sicker than UCD, including more fever, hepatomegaly and/or splenomegaly and hypoalbuminemia. All of UCD showed solitary mass in various sites and two of them were complicated by small pleural effusion. In the MCD group, their chest CT showed obvious lymphadenopathy in the hilum and/or mediastinum (100%), diffuse parenchymal lung shadows (43.75%), pleural effusion (40.6%), mass in the mediastinum (6.25%) or hilum (3.12%) and bronchiolitis obliterans (BO) (3.12%). Besides LIP-like images, multiple nodules of different size and sites, patchy, ground-glass opacities and consolidation were showed in their chest CT. Surgery were arranged for all UCD for diagnosis and treatment and all were alive. In MCD group, superficial lymph nodes biopsies (21 cases), surgery biopsy (9 cases) and CT-guided percutaneous lung biopsy (2 cases) were performed. Hyaline vascular (HV) variant were more common in the UCD group (75% vs 37.5%, P < 0.05). In MCD group, 28 cases were prescribed with chemotherapy, one refused to receive therapy and the rest three were arranged for regular follow-up. Among MCD, 18 cases was improved, 7 cases was stable, 4 cases lost follow-up and 3 cases died.ConclusionsIntrathoracic MCD was more common than UCD in our hospital. MCD was older, more symptomic and sicker than UCD. HV variant were more common in UCD. All of UCD showed mass in various intrathoracic locations and surgery resection was performed for all and all were alive. Mass, pleural effusion, BO and diffuse pulmonary shadows, including LIP-like images, multiple nodules of different size and sites, patchy, GGO and consolidations were showed in our MCD. Most of MCD cases were arranged with chemotherapy and their prognosis were worse than UCD’s.

Hyaline vascular type of unicentric Castleman’s disease with proliferation of glomerular endothelial cells

Castleman’s disease (CD) is a lymphoproliferative disorder of uncertain etiology. It can be classified histopathologically as hyaline vascular (HV) or plasma cell (PC) type; and clinically as unicentric or multicentric. Multicentric CD mostly manifests as the PC type and is often associated with a variety of systemic complications, although renal complications are uncommon. We present here a case of HV type, unicentric CD with a variety of systemic and renal complications, including the proliferation of glomerular endothelial cells. Various cytokines are thought to be involved in the etiology of this disease, especially interleukin-6 (IL-6) and vascular endothelial growth factor (VEGF), which are the main cytokines inducing systemic complications. It has been reported that most PC types and/or multicentric types of CD show increasing levels of serum IL-6 and VEGF, as well as systemic symptoms. Although the current case showed high serum IL-6 and VEGF levels as well as systemic symptoms, the pathological and clinical type were of the HV type and unicentric type, respectively. After immunosuppressive therapy, the serum levels of IL-6 and VEGF returned to the normal range, and systemic complications, including renal involvement, also improved. We report the possibility of pathogenesis via the serum and the pathology of this rare case.

Siltuximab Reverses Muscle Wasting In Patients With Multicentric Castleman's Disease

IntroductionMulticentric Castleman's disease (MCD) is a rare lymphoproliferative disease characterized by fevers, night sweats, fatigue, anorexia, and wasting. Interleukin-6 (IL-6) plays a pivotal role in MCD and is involved in muscle wasting. Siltuximab (CNTO328) is a chimeric IgG1κ mab that binds IL-6 and prevents its interaction with IL-6 receptors. We analyzed prospectively collected computed tomography (CT) scans to determine siltuximab's effects on muscle mass. MethodsCT scans of MCD patients (pts) from a phase 1 siltuximab study were studied for changes in body composition from siltuximab treatment. Pts (n=37) were treated with CNTO328 q weekly, 2 wks or 3 wks at doses ranging from 2.8 to 11 mg/kg, and 34/37 pts had CT scans that were suitable for evaluating body composition. The median age was 49 (range 18-76) with 18 M/16 F. Median body weight was 78 kg (mean 87 kg, range 40 to 170 kg). Eleven pts had not received prior treatment; the other 23 pts had a median of 2 prior therapies, range 1 to 5. Pts' histology was hyaline vascularity (n=17), plasmacytic (n=15), and mixed cellularity (n=2). CT scans for each pt at each time point in their treatment were landmarked at the axial 3rd lumbar vertebra (L3). L3 images were then tissue cross sectional area analyzed using Slice-O-Matic® (Tomovision, Montreal, Canada) with Hounsfield units (HU) set at different levels for each tissue: skeletal muscle within the range of -29 HU to 150 HU, visceral adipose tissue within -150 HU to -50 HU, intramuscular adipose tissue within -190 HU to -30 HU, and subcutaneous adipose tissue within -190 HU to -30 HU. Tissue areas were used to estimate tissue mass Shen et al. 2004 J Appl Physiol 97:2333-2338). ResultsThe median duration of treatment in this phase I study was 703 days (range 21 to 1843 days). During siltuximab treatment 38% of pts gained > 1 kg of muscle, mean 2.3 kg ± 1.1 kg (all mean values reported as mean±SD), 47% of pts had a stable muscle mass, muscle gain or loss less than 1 kg, mean 0.2 kg ± 0.5 kg and 15% of pts lost more than 1 kg, mean loss 3.1 ± 1.7 kg. Over the entire patient population (n=34) the mean gain in muscle was 0.5 kg (median 0.6 kg, range -5.5 to 4.4 kg); and the mean gain in adipose tissue was 3.1 kg (median 3.05, range -13.8 to 35.8 kg). By MCD histology the gain in muscle was 0.25 kg for hyaline vascular, 0.33 kg for mixed cellularity, and 0.85 kg for plasmacytic. Changes in fat mass by MCD histology was 5.1 kg for hyaline vascular, 5.8 for mixed cellularity, and 3.8 kg for plasmacytic. By Cheson radiologic disease response criteria the change in muscle mass was 0.9 kg for pts with partial response (PR, n=11), 0.5 kg for patients with stable disease (SD, n=22), and -3.7 kg for the one patient with progressive disease (PD). The change in fat mass was 8.5 kg for patients with PR (n=11), 2.85 kg for patients with SD (n=22) and -0.6 kg for the one patient with PD. At the recommended phase II dose of 11mg/kg q 3 wks (n=17), the mean gain in muscle mass was 0.6 kg (median 0.9 kg, range -5.5 kg to 4.4 kg). The pattern of muscle and fat mass gain was interesting in that the fat mass increased first followed by a delay and then muscle gains occurred. Pts who continued to respond to siltuximab continued to gain muscle mass up to the time that they were censored. ConclusionsIn addition to objective responses that were durable in MCD (median duration of response was not reached at follow-up of 29.4 months), siltuximab caused reversal of muscle wasting in 38% of patients, stabilization of muscle wasting in another 47% and in only 15% of patients did muscle wasting worsen. This stabilization and improvement in muscle wasting could lead to functional status improvements in MCD patients. Disclosures:Kurzrock:Janssen Research & Development: Research Funding. van Rhee:Janssen Research & Development: Research Funding. Ming:Janssen Research & Development: Employment. Vermeulen:Janssen Research & Development: Employment; Johnson & Johnson: Equity Ownership.

Incidental diagnosis of Castleman's disease in a large recurrent ameloblastoma of the mandible

Castleman's disease (CD) is an uncommon lymphoproliferative disorder that was first described by Benjamin Castleman. In 1969 Flendrig published the first retrospective study of CD, in 1972 Keller identified histological features of the two subtypes of CD and classified them into into hyaline vascular (HV) and plasma cell (PC). In this abstract we pressent a case of large recurrent ameloblastoma that was treated with segmental mandibulectomy and immediately reconstruction with a free vascularized fibula flap, a super selective neck dissection performed to expose vessels for microvascular anastomosis for free fibula flap at the same time excision of the lymphnodes in the right level Ib and left Ia and IIa was performed due to their enlarged size on the preoperative CT-scan and were sent as frozen section for histopathologial analysis to role out the ameloblastic carcinoma. The final pathology confirmed the diagnosis of amleoblastoma and revealed that the involved lymphnodes were constant with CD.