Oral follicular lymphomas. A short report of 8 cases with assessment of the IGH/BCL2 gene fusion with fluorescence in situ hybridization Prokopios P. Argyris, DDS, a,b Michelle Dolan, MD, c Evangelia Piperi, DDS, MSc, PhD, a Konstantinos I. Tosios, DDS, PhD, a Stefan E. Pambuccian, MD, c and Ioannis G. Koutlas, DDS, MS b National and Kapodistrian University of Athens, Greece and University of Minnesota, Minneapolis, MN, USA Objective. To present the clinicopathologic features and confirm the presence of the IGH/BCL2 gene fusion in an oral follicular lymphoma (OFL) series. Study design. Cases of OFLs were retrieved from a data base of non-Hodgkin lymphomas (NHL). Fluorescence in situ hybridization (FISH) was performed to confirm the IGH/BCL2 fusion. Results. Eight (8.7%) of 92 NHL were OFLs. Six (75%) patients were male and two female (mean age: 73.4  14.8). The most frequent site was the palate. Five of the 8 patients are alive and without disease. Five (three grade 1 and two grade 2) of six successfully hybridized cases revealed the IGH/BCL2 gene fusion. The sixth case, a grade 3 follicular lymphoma (FL), demonstrated multiple BCL2 signals without IGH/BCL2 fusion. Conclusions. OFLs exhibit an indolent clinical behavior. In the present study, 5/6 cases in which FISH was successful had an IGH/BCL2 fusion as would result from the t(14; 18)(q32; q21) translocation commonly seen in FL of extraoral sites. (Oral Surg Oral Med Oral Pathol Oral Radiol 2013;116:343-347) Follicular lymphomas (FL) are neoplastic proliferations of germinal center B-cells exhibiting at least a partially follicular architectural pattern. 1 According to recent epidemiological data, FLs account for 15%-20% of all lymphomas, affecting predominantly adults (median age > 50 years) with a slight female preponderance (male:female, 1:1.7). 1-3 FL is the most common subtype of indolent (low grade) lymphoma; however, trans- formation to a high-grade, aggressive histologic subtype, usually diffuse large B-cell lymphoma (DLBCL), occurs in 20%-30% of cases. 4 The molecular mechanism underlying the pathogen- esis of FL has been well characterized. 5,6 A t(14; 18)(q32; q21) translocation is detected in up to 90% of stage I and II FLs. 5,7 The t(14; 18) translocation results in IGH/BCL2 gene fusion, leading to constitutive overexpression of the anti-apoptotic intracellular protein Bcl-2. This over- expression allows neoplastic B-cells to abrogate the programmed apoptotic process, thus resulting in pro- longed survival. 5 OFLs constitute uncommon extranodal manifesta- tions of FL and limited data exist about the role of IGH/BCL2 gene fusion in this category of tumors. We present the clinicopathologic and molecular cytoge- netic findings of OFLs accessioned in the University of Minnesota Oral Pathology Laboratories. 8 These cases were evaluated for the presence of the IGH/ BCL2 gene fusion using fluorescence in situ hybrid- ization (FISH). MATERIALS AND METHODS All cases of non-Hodgkin lymphoma (NHL) acces- sioned in the Division of Oral and Maxillofacial Pathology, School of Dentistry, University of Minne- sota during the period 1992-2006 were retrieved and for those cases diagnosed as FL, clinical information was obtained from the patients’ medical records. For purposes of meaningful follow-up we excluded cases diagnosed after 2006. According to our records, infor- mation reported in the biopsy request form during submission of the specimens did not reveal any history of nodal or extranodal disease prior to biopsy of the lesions. FISH was performed on formalin-fixed, paraffin-embedded tissue sections using a dual-color This paper presented at the XXVIIth International Congress of the Inter- national Academy of Pathology, October 12-17, 2008, Athens, Greece. Dr. Argyris was a Fellow in the Division of Oral and Maxillofacial Pathology, University of Minnesota, Minneapolis, MN, USA. a Department of Oral Pathology and Medicine, School of Dentistry, National and Kapodistrian University of Athens. b Division of Oral and Maxillofacial Pathology, School of Dentistry, University of Minnesota. c Department of Laboratory Medicine and Pathology, University of Minnesota Medical Center, University of Minnesota. Received for publication Jan 21, 2013; returned for revision Jun 11, 2013; accepted for publication Jun 14, 2013. Ó 2013 Elsevier Inc. All rights reserved. 2212-4403/$ - see front matter http://dx.doi.org/10.1016/j.oooo.2013.06.014 Statement of Clinical Relevance This paper presents the intraoral manifestation of a series of follicular lymphomas. Immunohistochem- ical and molecular techniques are useful in rendering an accurate final diagnosis. 343 Vol. 116 No. 3 September 2013