A controversial conclusion regarding primary extranodal diffuse large B-cell lymphoma

which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. A controversial conclusion regarding primary extranodal diffuse large B-cell lymphoma TO THE EDITOR: Recently, primary extranodal non-Hodgkin's lymphoma (NHL) has gained considerable attention. Many controversies are associated with primary extra-nodal NHL, mainly due to inadequate and contradictory literatures, and lack of uniformity in definition, clin-icopathological characteristics, and clinical outcomes according to the involved sites. Jang et al. put forth prospects for further research to evaluate primary extranodal DLBCL [1]. Although they concluded that rituximab had no role in the treatment of primary extranodal DLBCL, their report included several limitations that were obstacles to achieve conclusive results. The diversity in clinical presentation, morphology, im-munophenotype, and genetic alterations strongly suggest that DLBCL belongs to a heterogeneous group of aggressive B-cell lymphomas. Extranodal disease is the predominant disease manifestation (incidence, about 40%) among DLBCL patients. Even in patients with stage I disease, 56% had extranodal DLBCL [2]. On the basis of the results of routine staging, the authors defined PENL (primary extranodal lym-phoma) as a lymphoma with no or minor nodal involvement, along with a clinically dominant extranodal component. The definition of extranodal disease has been controversial, particularly in the presence of both nodal and extranodal manifestations. The designation of stage III and IV lympho-mas as PENLs is debatable, since many clinicians consider only stage I and II presentations as primary extranodal disease [3]. For patients in the advanced stage of disease, this diagnostic approach may be inappropriate, because many extranodal lymphomas can disseminate and vice versa. In the above study, patients with stage III or IV disease constituted more than 50% of all subjects. Therefore, this definition for PENL inevitably introduces a selection bias. The second controversial issue is the different prognosis according to the involved site. López-Guillermo et al. [4] reported that the clinical characteristics of nodal and extra-nodal DLBCLs were heterogeneous. Lymphomas arising from two specific sites [Waldeyer's ring (nodal) and gastro-intestinal region (extranodal)] showed very favorable characteristics at diagnosis (e.g., early stage, absence of bone marrow involvement, normal serum LDH level, and low-risk IPI), whereas DLBCLs arising in the remaining areas (lymph nodes or other extranodal sites) presented with poorer diagnostic characteristics. In terms of response to therapy, risk of relapse and overall survival, both Waldeyer's ring and gastrointestinal lymphomas showed notably better outcomes than those shown by the other groups …