Retroperitoneal fibrosis showing immunoglobulin G4-positive monoclonal B-lymphocytes

Received 1 April 2011 ; revised 15 May 2011; accepted 19 May 2011 We report herein two cases of immunoglobulin G4 (IgG4)related retroperitoneal fi brosis (RF) showing monoclonal B-cell proliferation. A 76-year-old man (case 1) underwent right hemicolectomy because of ascending colon carcinoma. At surgery, a left peritoneal tumor was incidentally found, and a biopsy was performed. Patient laboratory examinations were within normal limits except for mild anemia (hemoglobin, 10.9 g/L). Th e serum IgG4 level was not examined. Th ere was no other evidence of disease, and the patient remained free of disease on examination 14 months later. A 70-year-old-man (case 2) had had a history of diabetes mellitus for several years. During a medical check-up, a computed tomography scan demonstrated a right peritoneal mass. With a diagnosis of right ureter carcinoma, a right ureteronephrectomy was performed. Preoperative patient laboratory examinations were within normal limits. Postoperatively, the serum IgG4 level was examined and found to be increased at 341 mg/dL (normal range 135 mg/dL). Th ere was no other evidence of disease, and the patient remained free of disease on examination 6 months later. Histologically, both lesions were characterized by numerous lymphoid follicles with active germinal centers and chronic infl ammatory processes intermixed with irregular fi brosis and/or sclerosis in the adipose tissue [Figure 1(a)]. On highpower magnification, these lesions demonstrated severe infi ltration of mature plasma cells, plasmacytoid cells, large transformed lymphocytes, and small lymphocytes [Figure 1(b)]. Scattered Russell bodies (intracytoplasmic inclusions) were present in both cases, but there were no Dutcher bodies (intranuclear inclusions) or amyloid deposition. Th ere was no remarkable eosinophilic infi ltration in either lesion [Figure 1(b)]. One lesion (case 1) contained numerous histiocytes with a few multinucleated giant cells. Elastica – van Gieson staining demonstrated that there was no obliterative phlebitis or arteritis. Immunohistochemical studies were performed using the antigen retrieval method using a Histofine Histostainer (Nichirei Bioscience, Inc., Tokyo, Japan) according to the manufacturer ’ s instructions. Staining for CD20, CD3, and CD5 showed a mixed nature of small lymphocytes. Th e majority of large transformed lymphocytes including immunoblasts expressed B-cell antigen. In situ hybridization (ISH) studies of kappa-chain and lambda-chain demonstrated polyclonality of the plasma cells and plasmacytoid cells in both cases, whereas the ISH studies demonstrated monoclonality of the transformed lymphocytes including immunoblasts (case 1, lambda; case 2, kappa) [Figures 1(c) and 1(d)]. Th ere were numerous IgG-positive plasma cells, with scattered IgAor IgM-positive plasma cells. However, IgG4-positive cells constituted more than 40% of the IgG-positive plasma cells [Figures 1(e) and 1(f )]. Th ere were no CD20 , CD10 , or bcl-2 medium-to-large lymphocytes in either lesion. Staining with a monoclonal antibody cocktail of CD21, CD35, and CD23 highlighted the meshwork of follicular dendritic cells (FDCs). Th ese FDC networks usually showed a normal/reactive pattern. Th ere was no CD68 , vimentin , desmin , muscle-specifi c actin , anaplastic lymphoma kinase (ALK) , or spindle cell proliferation in either lesion. Th ere were no human herpes virus-8 (HHV-8)or Epstein – Barr virus (EBV)-encoded small nuclear RNA (EBER)-positive cells in either case. Using polymerase chain reaction (PCR) for the immunoglobulin heavy chain (IgH) gene, a discrete band of amplifi ed IgH was found in one case (case 1) (Figure 2) [1], while in the remaining case (case 2), only germline bands were detected. Retroperitoneal fi brosis is an idiopathic sclerosing lesion involving soft tissue or organs in the retroperitoneum. RF is now considered a heterogeneous disease entity, with possible involvement of autoimmune disorders or viral infection [2]. However, using the semi-nested PCR, Oshiro et al . [3] demonstrated clonal IgH chain rearrangement in all fi ve cases examined. Th ey indicated that at least a portion of RF and its L eu k L ym ph om a D ow nl oa de d fr om in fo rm ah ea lth ca re .c om b y U ni ve rs ity o f U ls te r at J or da ns to w n on 1 2/ 04 /1 4