Monoclonality and cytogenetic abnormalities in hyaline vascular Castleman disease

Abstract

Hyaline vascular Castleman disease is traditionally regarded as a reactive hyperplastic process. Occasional cases, however, have been reported with cytogenetic anomalies bringing this concept into question. In this study, we used conventional and methylation-specific polymerase chain reaction methods to assess the human androgen receptor a (HUMARA) gene in 29 female patients with hyaline vascular Castleman disease and compared the results with three cases of plasma cell Castleman disease and 20 cases of age-matched lymphoid hyperplasia. We also assessed for immunoglobulin gene and T-cell receptor gene rearrangements, and conventional cytogenetic analysis was performed in three cases of hyaline vascular Castleman disease. In cases with informative results, conventional and methylation-specific human androgen receptor a gene analyses yielded a monoclonal pattern in 10 of 19 (53%) and 17 of 23 (74%) cases of hyaline vascular Castleman disease, respectively. A monoclonal pattern was also detected in three cases of plasma cell Castleman disease but not in cases of lymphoid hyperplasia. The frequency of monoclonality was higher for lesions 45 cm in size (100%) and for the stromal-rich variant (91%). Cytogenetic abnormalities in stromal cells were revealed in two cases of hyaline vascular Castleman disease and no cases showed monoclonal immunoglobulin or T-cell receptor gene rearrangements. Follow-up data showed persistent disease in 4 of 23 (17%) patients. We conclude that hyaline vascular Castleman disease is often a monoclonal proliferation, most likely of lymph node stromal cells.

HHV-8-negative, idiopathic multicentric Castleman disease: novel insights into biology, pathogenesis, and therapy

“…A small population of monoclonal stromal cells in multiple lymph nodes or in a sentinel node could be the hypercytokine-secreting cells that trigger an enormous reactive response, such as has been observed in Hodgkin lymphoma and recently in 4 cases of iMCD. 28 The following 4 lines of evidence support the paraneoplastic syndrome hypothesis:…”

“…The authors concluded that most cases of HV-UCD and HV-MCD are monoclonal proliferations, most likely of stromal actin-positive myoid cells and FDCs. 28 Further investigations of stromal cell monoclonality in iMCD are needed. For personal use only.…”

“…76 Chang et al's recent finding of monoclonality in all 4 iMCD cases (3 HV and 1 PC) suggests that stromal cells, such as myoid cells and follicular dendritic cells, may be the pathologic cell in iMCD. 28 Activated T cells may play an important role as well, as soluble IL-2 receptor levels are often elevated and cyclosporine A is an effective monotherapy in a small number of cases. 2,77 Further studies involving in situ hybridization for IL-6 mRNA and investigations of stromal cell monoclonality in iMCD are needed.…”

Current Concepts and Evaluation of Uro-Rectal Diseases by Transrectal Ultrasound: A Review

“…Prostate Cancer [107] Perianal Paget's Disease [108] Myxoid Liposarcoma [109] Malignant Fibrous Histiocytoma [110] Hemangiopericytoma [111] Cauda Equina Syndrome [112] Carcinoma of the Cervix [113] Carcinoma of the Vagina [114] Epidermoid Cysts [115] Prader-Willi Syndrome [116] Colorectal Carcinoma [117] Benign Prostate Hyperplasia [118] Microglandular Hyperplasia [119] Adenocarcinoma of Cervix [120] Adenoma Malignum [121] Adenosquamous Carcinoma of Cervix [122] Glassy Cell Carcinoma of Cervix [123] Adenoid Basal Carcinoma of Cervix [124] Adenomyosis [125] Uterine Fibroids [126] Endometrial Polyps [127] Hematoma [128] Fournier's Gangrene [129] Malakoplakia [130] Aneurysmal bone cyst [131] Ewing Sarcoma [132] Osteosarcoma [133] Chondrosarcoma [134] Neurofibroma [135] Neuroblastoma [136] Schwannoma [137] Chordoma [138] Malignant Schwannoma [139] Hemangioma [140] Myelolipoma [141] Leiomyoma [142] Villous Adenoma [143] Solitary Fibrous tumor [144] Castleman disease [145] Lymphoma [146] Gastrointestinal Stromal Tumor [147] Epithielial Malignancies …”

Enfermedad de Castleman. Análisis histopatológico e inmunohistoquímico de treinta y nueve casos

“…Las CDF de los centros germinales pueden presentar datos variables de displasia, y han sido descritos sarcomas de CDF asociados a la EC 2,8,9,26 . De hecho, estudios moleculares recientes han demostrado clonalidad en las CDF de la variante HV y sugieren que la alteración genética en estas células pueden ser la causa de la enfermedad [26][27][28] . Es de interés que las CDF en los casos de EC, tanto HV como CP, presentan expresión difusa e intensa de EGFR, que no se observa en las CDF de otras enfermedades, como diversos linfomas y ganglios reactivos, dato que puede ser de utilidad en el diagnóstico diferencial con otros procesos reactivos 8,9,[26][27][28] .…”