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Lambda Immunoglobulin Light Chain Restricted B Cells in the Ascitic Available online at www.annclinlabsci.org Annals of Clinical & Laboratory Science, vol. 46, no. 1, 2016 87 Lambda Immunoglobulin Light Chain Restricted B Cells in the Ascitic Fluid in Association with Terminal Ileal Florid Follicular Hyperplasia Barina Aqil*, Wei Xie, and Reka Szigeti Department of Pathology & Immunology, Baylor College of Medicine, Houston, TX, USA Abstract. Distinguishing reactive changes from neoplastic processes during lymphoid tissue evaluation is oftentimes difficult. Ancillary studies, such as flow cytometry, may aid the diagnosis by demonstrating monotypic or polytypic light chain expression on the B cells. The detection of immunoglobulin light chain restricted B cell population is considered a surrogate marker of clonality, which can be confirmed by mo- lecular assays. In general, the presence of a monotypic B cell population in the ascitic fluid is considered lymphomatous involvement rather than a reactive condition. We describe a young, previously healthy male patient who developed ascites with a lambda light chain restricted B cell population. Further investigation revealed florid follicular hyperplasia, histologically mimicking diffuse large B cell lymphoma, in the termi- nal ileum. Follicular hyperplasia in the gastrointestinal tract with lambda light chain restricted B cells has been recently described in the pediatric population. Importantly, our case demonstrates that such entity can occur in older age groups. This recognition could prevent misdiagnosis and unnecessary treatment in similar cases. Key words: follicular hyperplasia, lymphoma-like lesion, light-chain restricted B-cells. Introduction (IgH) pattern, and the clinical course of the disease confirmed the benign nature of these lesions. We The evaluation of lymphoid tissue oftentimes re- describe a young man with histopathologic and im- quires the integration of morphological, immuno- munophenotypic findings of diffuse large B cell phenotypic and molecular methodologies. If mor- lymphoma, germinal centre B-cell-like (DLBCL- phological examination suggests a possible B-cell GCB) type. An immunoglobulin lambda light lymphoproliferative disorder, the evaluation of im- chain restricted B cell population was detected in munoglobulin light chain expression by flow cy- the ascitic fluid and in the consecutive terminal il- tometry may be considered as a surrogate test to eal (TI) biopsy by flow cytometry (FC). identify clonality [1]. Monotypic light chain ex- Retrospective PCR showed polytypic pattern of pression itself, however, does not necessarily equal IgH. The patient recovered without specific neoplasia, and has been reported with benign con- intervention. ditions in multiple organ systems [2,3]. Even clonal immunoglobulin gene rearrangements have been Case Report documented in non-neoplastic B cell proliferations [4]. Recently, Martinez-Lopez, et al. described four A 29-year-old previously healthy male was admitted to pediatric cases (4 to 6 years of age) of florid follicu- an outside hospital with diffuse abdominal pain, disten- lar hyperplasia in the gastrointestinal (GI) tract tion, bilateral pleural effusions, and ascites. Since conse- with lambda light chain restriction [5]. The PCR quent computerized tomography (CT) raised concerns for bowel involvement by a lymphomatous process or an based polyclonal immunoglobulin heavy chain omental malignancy, further work up was initiated. FC of the ascitic fluid showed a monotypic, CD10 positive *Current affiliation is Washington University School of Medicine, St. Louis, MO, USA. Address correspondence to Reka Szigeti, MD, B cell population with lambda light chain expression. A PhD., Department of Pathology & Immunology, Baylor College of consecutive colonoscopy was performed. Histological Medicine, One Baylor Plaza, Houston, TX, 77030, USA; phone: 1 713 873 3205; fax: 1 713 873 3214; e mail: [email protected] examination of TI biopsies showed predominantly large lymphoid cells with high nuclear to cytoplasmic ratio. 0091-7370/16/0100-087. © 2016 by the Association of Clinical Scientists, Inc. 88 Annals of Clinical & Laboratory Science, vol. 46, no. 1, 2016 Figure 1. Histological section of the TI biopsy shows a diffuse infiltrate of large lymphoid cells with high nuclear-to-cyto- plasmic ratio, variably irregular nuclear contour, one or more prominent nucleoli and scant cytoplasm (A). The atypical lymphoid population was positive for CD20 (B) and CD10 (C). No follicular dendritic cell meshwork was identified in the background of the large cells by anti-CD23 antibody (D). These cells had irregular nuclear contour, one or more by immunohistochemical studies (Figure 1B-C); and prominent nucleoli and scant cytoplasm (Figure 1A). negative for bcl-2. Proliferation index (Ki-67) was high Tissue fragments not involved by the atypical infiltrate (>90%). No follicular dendritic cell meshwork was iden- showed increased eosinophils along with plasma cells in tified by CD21 and CD23 in the background of the the lamina propria. Occasional neutrophils in the glan- large cell proliferation (Figure 1D). Residual dendritic dular epithelium, and rare giant cells were also seen. The cell meshworks were presen in the surrounding reactive lymphoid population was positive for CD20 and CD10 lymphoid tissue. The corresponding FC detected the Follicular hyperplasia mimicking lymphoma 89 lambda restricted B cell population, which was identified Martinez-Lopez, et al. reviewed 4 pediatric cases in the prior study of his ascitic fluid. Based on the com- where the presence of the restricted B cell popula- bined histologic and immunophenotypic findings the tion in the gastrointestinal tract (appendix and rec- diagnosis of DLBCL-GCB type was made. tum) in combination with morphological findings raised the differential diagnostic consideration of The patient presented in our institution three weeks after the original diagnosis without any specific intervention pediatric follicular lymphoma vs florid follicular initiated. At that time, he had no complaints. Staging hyperplasia [5]. In those cases, polytypic IgH rear- workup was performed. CT of chest, abdomen, and pel- rangement along with the clinical course confirmed vis, and positron emission tomography scan revealed no the benign nature of the lesions. Three of the pa- mass or significant lymphadenopathy. There were sub- tients (75%) were male. Our case represents a simi- centimeter mesenteric lymph nodes, which in compari- lar scenario, but in a young adult male patient. The son with the outside CTs were found to be significantly histomorphology and immunoarchitecture, how- smaller and considered to be reactive. Bone marrow bi- ever, was most consistent with DLBCL-GCB. opsy was negative. Repeat colonoscopy showed no gross Similarly to the reported pediatric cases, lambda abnormalities. Histology did not reveal lymphoma on restricted B cell population was detected in both random TI biopsies. Retrospective PCR for IgH rear- rangement showed a polytypic pattern on the original the biopsy and the ascitic fluid, suggesting the clon- biopsy. The patient was clinically followed for 11 months al nature of the lesion. Reassuringly, IgH rearrange- with no sign of lymphoma developing. ment showed a polytypic pattern and the patient remained asymptomatic during the 11 months fol- Discussion low-up period. Importantly, our patient being a young adult male expands the age spectrum of these Our clinical-pathological case highlights numerous lymphoma-like lesions. Our case also supports the important considerations when approaching mono- previously reported observation that male predomi- typic B cell proliferations in the background of nance may be characteristic of these ultimately be- acute gastrointestinal symptoms. The pathologic nign, but challenging clinico-pathologic entities. evaluation commonly has to be performed on small References fragmented tissue samples. The interpretation of histological findings on such small tissue specimens 1. Kroft SH. Monoclones, monotypes and neoplasia, pitfalls in requires a comprehensive approach with clinical- lymphoma diagnosis. Am J Clin Path 2004;121:457-459. 2. Chen HI, Akpolat I, Mody DR, Lopez-Terraga D, Ponce De radiological-pathological correlation, including Leon A, Luo Y, Jorgensen J, Schwartz MR, Chang, C. molecular data, to prevent misdiagnosis and unnec- Restricted kappa/lambda light chain ratio by flow cytometry in germinal center B cells in Hashimoto thyroiditis. Am J Clin essary treatment. Histologic features, which may Path 2006;125:42-48. suggest a reactive or underlying process (IBD, in- 3. Nam-Cha SH, San-Millan B, Mollejo M, Garcia-Cosio M, fection, etc.) along with the germinal center B-cell Garijo G, Gomez M, Warnke RA, Jaffe ES, Piris MA. Light- chain-restricted germinal center in reactive lymphadenitis: re- immunophenotype should raise the suspicion of a port of eight cases. Histopathology 2008;52:436-444. non-neoplastic etiology, even if an immunoglobu- 4. Turbiner Geyer J, Ferry JA, Harris NL, Young RH, Longtine lin light chain restricted population is identified. JA, Zukerberg LR. Florid reactive lymphoid hyperplasia of the lower female genital tract (lymphoma-like lesion): A benign Careful consideration must be made especially for condition that frequently harbors clonal immunoglobulin lesions originating from the TI, appendix, or rec- heavy chain gene rearrangements. Am J Surg Pathol 2010;34:161-168. tum, which intestinal regions are prone to follicular 5. Martinez-Lopez A, Montes-Moreno S, Ramos R, Afonso-
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