PF311 ISOLATED PRIMARY ADRENAL LYMPHOMA (IPAL) ‐ AN EMERGING LYMPHOMA ENTITY? RESULTS OF A RETROSPECTIVE MULTICENTER STUDY
Authors: F. Majidi, S. Martino, M. Kondakci, M. Haase, V. Chortis, W. Arlt, C.L. Ronchi, M. Fassnacht, C. Laurent, J.‐M. Petit, O. Casasnovas, M.A. Habra, A. Kanji, R. Salvatori, A. Ho, A. Spyroglou, F. Beuschlein, D. Villa, W. Limvorapitak, B. Wahlin, O. Gimm, M. Rudelius, M. Schott, U. Germing, R. Haas, N. Gattermann
Journal: HemaSphere (2019)

Background: Primary adrenal lymphoma (PAL) is a rare lymphoid malignancy that primarily involves the adrenal gland(s) in patients without a previous history of lymphoma. Aims: To refine the clinical picture of primary adrenal lymphoma Methods: We retrospectively analyzed clinical and pathological features of 97 patients from 14 centers in Europe, Canada and the United States. PAL was defined as histologically proven extra‐nodal lymphoma that primarily affects the adrenal gland(s). If there was involvement of other organs and/or lymph nodes, the diagnosis of PAL was accepted only in case of unequivocal dominant involvement of the adrenal gland(s). We divided the disease into two subtypes: cases with synchronous extra‐adrenal involvement at diagnosis (PAL+), and cases with isolated involvement of the adrenal(s) (iPAL). Statistical analyses were carried out using the Fisher exact test, Kaplan‐Meier method, log‐rank test, and Cox proportional hazard models. Results: Median age at diagnosis was 66 (25–89) years, and the male/female ratio was 2.3. 19/81 (23%) patients with available imaging data had isolated adrenal involvement (iPAL), while the other 62 (77%) had additional extra‐adrenal involvement (PAL+). The most common manifestations of PAL were B symptoms (55%), fatigue (45%), and abdominal pain (35%). With a median follow‐up of 41.6 months, the 3‐year progression‐free survival (PFS) and overall survival (OS) were 35.5% and 39.4%, respectively. Immunochemotherapy according to the R‐CHOP protocol showed no significant difference in outcome compared to other treatment regimens. On multivariate analysis of variables including age, tumor size, uni‐ vs. bilateral involvement, histopathology of B cell lymphoma, elevated LDH, adrenal insufficiency, and iPAL versus PAL+, iPAL was the only factor with independent, statistically significant impact on PFS. The hazard ratios of iPAL for PFS and OS were 40.1 (95% CI: 2.63–613.7, p = 0.008) and 2.69 (95% CI: 0.61–11.89, p = 0.191), respectively. PFS was much shorter in iPAL versus PAL+ (median 4 months vs. not reached, p = 0.006), and there was a trend for shorter OS (median 16 vs. not reached, p = 0.16). Isolated PAL was more frequent in females (OR = 3.81; P = 0.01) and less frequently associated with B symptoms at diagnosis (OR = 0.159; p = 0.004). Summary/Conclusion: Comprehensive characterization of rare diseases is facilitated by multi‐institutional collaboration. Our retrospective analysis of 97 patients from fourteen centers is the largest analysis of PAL so far. We showed for the first time that PAL is a heterogeneous disease, which comprises cases with isolated involvement of adrenal tissue (iPAL) and cases with additional extra‐adrenal organ manifestations (PAL+). Unexpectedly, patients with iPAL showed an unusual male/female ratio, less B symptoms and significantly worse clinical outcome than those with involvement of additional, extra‐adrenal sites. This finding should stimulate further investigation to see whether the clinical distinction between iPAL and PAL+ is corroborated by differences in molecular biology. image