Clinicopathologic Features of Lymphomatoid Granulomatosis, a Single Institute Experience.
Joo Y Song, Kieron Dunleavy, Nicole Grant, Theresa Davies-Hill, Mark Raffeld, Wyndham H Wilson, Elaine S Jaffe, Stefania Pittaluga. NCI, Bethesda, MD
Background: Lymphomatoid granulomatosis (LYG) is a rare angiocentric and angiodestructive EBV-associated B-cell lymphoproliferative disorder. It is hypothesized that these patients have defective immune surveillance of EBV+ B-cells. Historical outcomes of patients treated with steroids and/or chemotherapy have been poor (median survivals of 14 months). In our institution LYG grade I/II is now treated with IFα, while grade III is treated with immunochemotherapy (EPOCH-R). LYG is both challenging diagnostically and therapeutically. We report our institution's experience with this rare disease.
Design: We reviewed biopsies of LYG collected at our institution from 1993-2010. Grading of these lesions was based on morphologic features and the number of EBV+ B-cells (grade I 0-5, grade II <50, grade III >50) evaluated by in situ hybridization (2008 WHO classification).
Results: 64 patients (M:F 2.1:1, median age 43 years) with 131 biopsies were diagnosed with LYG. 92/131 biopsies were further graded based on the WHO classification with 32/92 grade I (34.8%), 20/92 grade II (21.7%), and 40/92 grade III (43.5%). The most frequently biopsied site was the lung (75/92, 81.5%). Other involved biopsy sites included kidney (2/92), brain (1/92), adrenal (1/92), pleura (1/92), liver (1/92), eye (1/92), and nasal cavity (2/92). However, lesions involving skin (15) and subcutaneous tissue (5) had distinctive features, showing prominent granulomatous inflammation and lacking EBV+ cells. IGH PCR on 34 biopsies was positive for a clonal process in 1/10 grade I (10%), 3/8 grade II (37.5%), and 7/16 grade III (43.8%), reflecting the greater number of large atypical cells in high grade lesions. Interestingly, 2/20 biopsies also showed clonal rearrangement for TRG PCR (1 grade I and 1 grade III), which is attributed to T-cell response to EBV infected cells. 18 patients had more than one biopsy (range 2-5 biopsies) performed within a 6 month interval to evaluate response to therapy. 6/18 had the same grade (3 grade I, 3 grade III) and 12/18 had different grades (1 grade I/II; 4 grade I/III; 6 grade II/III; 1 grade III/DLBCL). Of these 18 patients, 10 had extrapulmonary lesions which had a higher grade when compared to the pulmonary lesion in all except one. Histologic progression requires a change in treatment.
Conclusions: LYG is a rare EBV-associated lymphoproliferative disorder for which grading is important for choice of therapy. However, cutaneous lesions have distinctive features. Rebiopsy is advised to determine evidence of histological progression.
Wednesday, March 2, 2011 9:30 AM
Poster Session V # 176, Wednesday Morning