Hyaline Vascular Research Articles

Atypical Hyaline Vascular-Type Castleman's Disease With Thrombocytopenia, Anasarca, Fever, and Systemic Lymphadenopathy

Recently, atypical Castleman's disease (CD) was reported in Japan. This disease is considered as TAFRO syndrome or non-idiopathic plasmacytic lymphadenopathy (IPL), a constellation of clinical symptoms, namely, thrombocytopenia, anasarca, fever, reticulin fibrosis, and organomegaly without hyper-γ-globulinemia. Histopathologically, this disease is similar to hyaline vascular (HV)-type CD. Here, we present a 43-year-old Japanese woman meeting the clinical criteria of TAFRO syndrome who was successfully treated with combined corticosteroid therapy. She showed a rapidly progressive course of thrombocytopenia, systemic lymphadenopathy, fever, anasarca, and increase in acute inflammatory proteins without hyper-γ-globulinemia. Lymph node biopsy was performed and revealed HV-type CD without human herpes virus 8 infection, which was clinicopathologically compatible with non-IPL. The association of these atypical features with well-known multicentric Castleman's disease (MCD), namely, HV-type histology with systemic lymphadenopathy, marked thrombocytopenia even with a high level of interleukin-6, and increased acute inflammatory proteins without hyper-γ-globulinemia, suggests that TAFRO syndrome as presented in our case is a novel entity, which may have been diagnosed as MCD in the past. To define this novel entity more clearly and to demonstrate its etiology, further nationwide surveys of this syndrome and MCD are needed.

Comparison of Plasma Cell Type of Castleman’s Disease and IgG4-Related Sclerosing Disease: A Histopathological and Immunohistochemical Study

Objectives: Castleman’s disease (CD) is a group of rare atypical lymphoproliferative disorders classified as hyaline vascular (HV) and plasma cell (PC) types. CD may be closely mimicked by IgG4-related sclerosing disease (IgG4-SD) involving the lymph nodes. We retrospectively analyzed findings in patients with CD to elucidate the relationship between CD and IgG4-SD. Methods: Clinicopathological and immunophenotypical characteristics, including IgG+ and IgG4 expression by plasma cells, were analyzed in 87 consecutive patients diagnosed with CD from 1999 to 2010 at two major Korean hospitals. Results: The numbers of IgG+ (p < 0.001) and IgG4+ (p < 0.001) cells and the IgG4:IgG ratio (p = 0.003) were significantly higher in the PC than in the HV group. The mean IgG4+:IgG+ plasma cell ratio in the PC group was 25.1%, with 10 patients having a ratio >40%, the threshold IgG4:IgG ratio in patients with IgG4-SD. Conclusions: Patients with the PC form of CD and IgG4-related lymphadenopathy share some features, including the pattern of plasma cell distribution and high-level infiltration of IgG4+ cells. Some patients thought to have the PC form of CD could be reclassified as showing IgG4-related lymphadenopathy.

The value of MDCT in diagnosis of hyaline-vascular Castleman's disease

PurposeCastleman's disease (CD) is an uncommon entity characterized by a massive growth of lymphoid tissue. There are two types: the hyaline-vascular (HV) type and the plasma cell (PC) type. The purpose of this study was to evaluate the clinical value of multiple detector computed tomography (MDCT) in the diagnosis and planning of treatment for hyaline-vascular CD. Materials and methodsFifty-two cases of confirmed hyaline-vascular CD were retrospectively reviewed. Unenhanced and contrast-enhanced MDCT scans had been performed in all patients, followed by surgery and pathological analysis of the lesion. Original MDCT transverse and reconstructed images were used for image interpretation. Features of the lesion and its adjacent structures were identified. ResultsThe lesion was present in the thorax of 24 patients and the abdomen in 28. Obvious features of hyaline-vascular CD (especially feeding vessels and draining veins) and its adjacent structures were demonstrated on 52 patients. ConclusionOn MDCT imaging, original MDCT transverse and reconstructed images provide an excellent tool for diagnosis of hyaline-vascular CD and have high value in the determination of a treatment plan.

Hyaline-Vascular Castleman Disease: A Rare Cause of Solitary Subcutaneous Soft Tissue Mass

Castleman disease (CD) is a rare lymphoproliferative disorder that primarily affects mediastinal, retroperitoneal, and cervical lymph nodes. Clinically, these lesions occur as a localized (unicentric) or less frequently as a systemic (multicentric) disease. Two main distinct histologic variants are recognized, the more common hyaline-vascular (HV) type and the plasma cell (PC) type. Extranodal Castleman disease, HV type (HVCD) is even less common. We describe a case of subcutaneous HVCD in a 57-year-old woman with a palpable chest mass and without systemic symptoms. Although the histologic findings are similar to those of HVCD in lymph nodes and other sites, a plethora of differential diagnosis is raised particularly with the more commonly occurring lymphoproliferative lesions in this location. This is one of the few bona fide cases of HVCD in subcutaneous location published to date. A review of the literature with an emphasis on pathogenesis of the disease subtypes is presented.

Castleman's Disease of the Retroperitoneum : With Special Reference to IgG4-Related Disorder

Localized Castleman's disease (CD) has been divided two types, the classical hyaline vascular (HV) type and the rare plasma cell (PC) type. Recently, we have reported two cases of IgG4-related disorder of the retroperitoneum showing PC type of CD. To further clarify the clinicopathological findings of CD of the retroperitoneum, eight such cases have been studied. A single lesion was located in the retroperitoneum (n=3), ureter (n=2) and renal hilum (n=2). One case had bilateral ureter lesions. The HV type of CD accounts for approximately 90% of cases. However, 50% (n=4) of our cases were the PC type of CD. Three of the four lesions of HV type had lymph node lesions, whereas all four PC type of CD were soft tissue masses. These clinicopathologic findings appear quite different from previous descriptions. Immunohistochemical study demonstrated numerous IgG4(+) plasma cells accounting for more that 50% of IgG4(+) cells in three cases of the four PC type of CD. Moreover, serum IgG4 concentration was increased in two of the four cases of PC type of CD that were examined. The serum interleukin-6 levels were within the normal range in two cases of PC type that were examined. The present study suggests that a majority of the PC type of CD arising in the retroperitoneum appears to be an IgG4-related disorder.

Castleman′s disease - hyaline vascular type - clinical, cytological and histological features with review of literature

Castleman's disease (CD) is a rare disease of lymph node with two identified forms - the hyaline vascular (HV) type or angiofollicular type and plasma cell (PC) type. It usually presents as localized or systemic lymphadenopathy or even as extra nodal mass and may give rise to several differential diagnoses. Fine needle aspiration cytology (FNAC), as the initial investigation, may be misleading. Excision biopsy usually gives the diagnosis. This study analyzes the clinical, cytological and histological features of CD of HV type. All the cases of CD reported between 2001 and March 2008 have been reviewed. Cytology and histopathology slides of all cases were reviewed by two reporting pathologists independently and the clinical records were analyzed. We had five cases of CD all of which presented as cervical lymphadenopathy of 1 to 5 cms in young patients. Patients were mostly asymptomatic with all relevant investigations within normal limits. The cytology findings mostly showed a predominance of small lymphocytes with capillary fragments. On excision biopsy, all cases were diagnosed as CD of HV type. CD should be kept as a differential of lymphadenopathy, especially in asymptomatic and young patients.

Progressive transformation of germinal center presenting with histological features of hyaline‐vascular type of Castleman's disease

We report three cases showing progressive transformation of the germinal center (PTGC) with histological features reminiscent of the hyaline-vascular (HV) variant of Castleman's disease (CD). Each case contained a few small HV germinal centers as well as PTGC and hyperplastic germinal centers with or without follicular lysis. Moreover, some of the PTGC were penetrated by hyalinized small vessels. Our three cases also showed some of the characteristic histological findings of HV type of CD: (i) reactive lymphoid follicles with small hyaline-vascular germinal centers surrounded by small lymphocytes in a concentrated fashion; (ii) a few small foci of plasmacytoid monocytes; (iii) perivascular fibrosis; (iv) interfollicular vascularity; (v) tight/concentric pattern of the follicular dendritic cell network; and (vi) absence of CD57+ T-cells in the HV follicles. The PTGC with coexistent HV type of CD may represent a certain form of reactive follicular hyperplasia. The possibility of PTGC should be considered and excluded before diagnosing CD.

Diagnosis of Castleman's disease by identification of an immunophenotypically aberrant population of mantle zone B lymphocytes in paraffin-embedded lymph node biopsies.

Castleman's disease (CD) is characterized by lymph node enlargement due to hyperplasia of abnormal lymphoid follicles and paracortical lymphocytic hyaline vascular (HV) stroma or plasmacytosis (PC). The lymphoid follicles in CD show involuted germinal centers and prominent mantle zone lymphocytes. Ninety-seven cases clinically suspected to be CD were analyzed according to conventional histologic criteria established by Castleman and Keller for diagnosis. Twenty-two cases were excluded as nonspecific hyperplasia (12); Hodgkin's and non-Hodgkin's lymphoma (9); and multiple myeloma involving lymph node paracortex (1). The 75 remaining cases, consisting of 51 cases of CD and 24 with altered follicles or paracortex suggestive of CD, were further analyzed immunohistologically for changes in follicular dendritic reticulum cells (FDRC) using the monoclonal antibody Ki-M4p, for germinal center proliferation with Ki-S5, for mantle zone immunophenotype with Ki-B3 and Ki-B5, for paracortical plasmacytoid monocytes with Ki-M1p, and for plasma cell clonality by applying antibodies to kappa and lambda immunoglobulin light chains. Lymph nodes showing nonspecific follicular and paracortical hyperplasia were included as controls. Hyaline vascular CD and plasma cell CD showed enlarged, polyploid FDRC with prominent nucleoli, decreased germinal center proliferation, and mantle zone populations of immunophenotypically aberrant, Ki-B3-negative B lymphocytes. Thirty-seven percent of hyaline vascular CD and plasma cell CD contained plasmacytoid monocytes, and 15% showed interstitial areas of lambda predominant plasma cells. Plasmacytoid monocytes were common in hyaline vascular CD but rare in plasma cell CD. Cases suspected to be CD that demonstrated a mantle zone population of Ki-B3-negative B lymphocytes had clinical finding of POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal paraprotein, and skin changes or sclerotic bone lesions) syndrome and were reclassified as hyaline vascular CD, plasma cell CD, and mantle zone CD with an aberrant mantle zone immunophenotype only (lacking follicular center and paracortical histologic or immunohistologic abnormalities). Immunohistochemistry was valuable for identification of dysplastic FDRC, decreased germinal center proliferation, and plasmacytoid monocytes. In addition, immunohistochemistry was essential for detection of plasma cell clonality, an aberrant mantle zone immunophenotype, and mantle-zone-restricted CD that was devoid of diagnostic alterations of germinal center or paracortex.

Expression of EGFR and follicular dendritic markers in lymphoid follicles from patients with Castleman's disease

This study investigated the useful morphologic and immunophenotypic findings for the diagnosis of Castleman's disease (CD). We focused on the distribution and expression of follicular dendritic cells (FDC) in lymphoid follicles from patients with CD. Eleven CD cases of the hyaline vascular (HV) variant and six cases of the plasma cell (PC) variant were studied using tissue microarray and paraffin resistant monoclonal antibodies CD21, CD35, and EGFR, a new novel marker of FDC, as well as an antibody against human herpes virus 8 (HHV8). Epstein-Barr virus (EBV) was detected by means of in situ hybridization with a fluorescein isothiocyanate-labeled EBV-encoded RNA (EBER) specific oligonucleotide. The FDC network of the PC variant (n=4) was similar to that seen in normal or reactive germinal centers. In contrast, all HV variants and 2 cases of the PC variant were either expanded, disrupted, or exhibited multiple tight collections of FDC both in germinal centers and in mantle zone lymphocytes. The expanded mantle zone lymphocytes were CD20+, Bcl2+, PAX5+, and MUM1- with less number of CD3+ T cells admixed. Other features of the HV variant included follicular regression and vascular ingrowth of the germinal centers, whereas features of the PC variant were follicular hyperplasia and interfollicular plasmacytosis. In addition, EBV infection was positive in three CD cases, and one case had co-expression of HHV8 and EBV infection. Taken together, we found immunophenotypic differences of mantle zone lymphocytes and FDC network patterns of lymphoid follicles in CD. Thus, we conclude that these differences are relevant for the differential diagnosis of the two histopathologic variants of CD.

Multicentric angiofollicular lymph node hyperplasia: A clinicopathologic study of 16 cases

A clinicopathologic analysis of 16 cases of multicentric angiofollicular lymph node hyperplasia (MAFH) was performed. Histologically, the disease was characterized by recognizable lymph node architecture that was at least partially intact, by paracortical hyperplasia with prominent vascular proliferation, and by numerous evenly distributed, apparently benign germinal centers of various types, usually including some typical hyaline-vascular centers. At the onset of the disease, 12 patients had the plasma cell (PC) type of MAFH, three patients had the hyaline-vascular (HV) type, and one patient presented with PC and HV types at separate sites. Transitions between the PC and HV types were observed in two cases. Immunologic studies demonstrated polyclonal populations of plasma cells in the lymph nodes of all patients and the absence of suppressor T lymphocytes in the one patient tested. Clinically, the patients had constitutional symptoms, multicentric lymphadenopathy, hepatosplenomegaly in many cases, and abnormal laboratory findings, including anemia, polyclonal hypergammaglobulinemia, and bone marrow plasmacytosis. The 16 patients were placed in four different clinical groups based on presentation and course: stable disease, chronic relapsing disease, aggressive disease, and development of malignant lymphoma. Ten of the 16 patients died (median survival, 26 months; range, eight to 170 months). Multicentric angiofollicular lymph node hyperplasia appears to be a variant of classic angiofollicular lymph node hyperplasia (Castleman's disease) and is associated with significant morbidity and mortality.