This study illustrates the selection bias that is introduced when a strict definition of primary extranodal NHL, that excludes cases with disseminated disease, is used. Patients with primary extranodal NHL were found to have a superior DFS, irrespective of which definition of primary extranodal NHL was used.

No abstract

Breast lymphomas are rare and consensus about their treatment is lacking. A population-based study of 38 breast lymphomas, registered in the databases of two Comprehensive Dutch Cancer Centers from 1981 to 1999, was performed. The median age of all female patients was 65 years (20-92): 25 patients had localized and 13 patients had disseminated lymphoma. The most common type was diffuse large B-cell lymphoma (DLBCL), which accounted for 17 of the localized and 4 of the disseminated cases. Burkitt's lymphoma (BL), three being disseminated, was found in four patients. There were six extranodal marginal zone lymphomas (ENMZL), three being localized. Seven DLBCL and one BL showed additional histological features of mucosa-associated lymphoid tissue (MALT) lymphoma. Localized aggressive lymphomas treated with surgery and/or radiation therapy had relapse rates of 100% and 67%, respectively. Cyclophosphamide, hydroxydaunomycin, vincristine, and prednisone (CHOP)-like chemotherapy with or without local irradiation led to 17% relapses in patients with localized aggressive lymphoma. Median follow-up time was 32 months (0.6-218); 37% of the patients relapsed and 24% had progressive disease. Response to salvage regimens, given to 91% of the patients with recurrent disease, was poor. The 2-year overall survival rate was 63%, 72% for patients with localized disease, and 46% for patients with disseminated lymphoma. The majority of breast lymphomas are localized aggressive lymphomas that should be treated initially with CHOP-like chemotherapy with or without irradiation. The initial choice of treatment is very important because response to salvage regimens is poor.

It is debated whether non-Hodgkin's lymphomas originating in Waldeyer's ring (WR NHL) behave as NHL originating in lymph nodes or share common features with extranodal lymphomas originating in mucosa associated lymphatic tissue (MALT). We analyzed data from a population based NHL registry on patterns of dissemination at diagnosis, response to treatment, patterns of failure and survival of 77 primary Waldeyer's ring Non-Hodgkin's lymphomas (WR NHL) patents. Data of completely staged patients with diffuse large cell lymphomas (DLCL) originating in WR (n=44) were compared with those of patients retrieved from the same registry with DLCL originating in lymph nodes or stomach (the latter as prototype of a lymphoma originating in MALT). Primary WR NHL had favorable risk scores according to the International Prognostic Index (IPI), and responded well to therapy: a complete response (CR) rate of 74% was observed. Disease free survival (DFS) and overall survival (OS) were poor, however (47% and 31% at 10 years, respectively). The comparison of DLCL originating in WR, lymph nodes and stomach revealed that WR and gastric NHL patients shared a restricted pattern of dissemination at diagnosis, in contrast to patients with DLCL originating in lymph nodes. Although not all patients were completely restaged at relapse, analysis of patterns of failure suggested that the gastro-intestinal tract is a preferential site for recurrences, both for WR and gastric DLCL patients. CR rates of WR, nodal and gastric DLCL patients were 77%, 55% and 55% respectively (P=0.03), OS of the three patient subgroups did not differ (33%, 27% and 37% at 10 years). DFS of WR DLCL patients was similar to nodal DLCL patients but inferior to gastric DLCL patients (47%, 48% and 73% at 10 years respectively, P=0.006). After Cox regression analysis the relative relapse risk for patients with WR DLCL when compared to patients with DLCL originating in lymph nodes was 2.01 (C.I. 0.99-4.01, P=0.05), and 3.46 (C.I. 1.32-9.00, P=0.01) when compared to patients with gastric DLCL. The clinical picture of primary WR NHL emerging from this population based study is in agreement with data form hospital based studies. In the comparison of WR DLCL, nodal DLCL and gastric DLCL, the observed patterns of dissemination suggest similarities between WR DLCL and gastric DLCL. The frequent relapses after CR observed for WR DLCL patients, however, indicate that these lymphomas clinically behave as nodal DLCL, and should be treated accordingly.

Genomic rearrangements are a common cause of human congenital abnormalities. However, their origin and consequences are poorly understood. We performed molecular analysis of two patients with congenital disease who carried de novo genomic rearrangements. We found that the rearrangements in both patients hit genes that are recurrently rearranged in cancer (ETV1, FOXP1, and microRNA cluster C19MC) and drive formation of fusion genes similar to those described in cancer. Subsequent analysis of a large set of 552 de novo germline genomic rearrangements underlying congenital disorders revealed enrichment for genes rearranged in cancer and overlap with somatic cancer breakpoints. Breakpoints of common (inherited) germline structural variations also overlap with cancer breakpoints but are depleted for cancer genes. We propose that the same genomic positions are prone to genomic rearrangements in germline and soma but that timing and context of breakage determines whether developmental defects or cancer are promoted.