Reliable information regarding the current prevalence of peripheral T-cell lymphoma (PTCL) entities is missing. Herein we report on the frequency of PTCL entities in France between 2010 and 2013. Using Lymphopath, a national lymphoma network established by the French National Cancer Agency, which covers about 70 % of all lymphomas currently diagnosed in France, we found that PTCL comprised 6.5 % of non-cutaneous lymphomas with angioimmunoblastic T-cell lymphoma (AITL) being the most frequent (739 cases; 36 %), followed by peripheral Tcell lymphoma not otherwise specified (PTCL-NOS) (550 cases, 27%). These data were verified in an independent data set from a transnational research consortium active in three European countries. In comparison to epidemiologic data reported previously, we show that AITL is by far the most common PTCL subtype. In light of the results of recent molecular findings highlighting the heterogeneity of T-cell lymphomas and the advent of targeted therapies, these data have important implications for both basic and clinical research.Peripheral T-cell lymphomas (PTCLs) represent diverse and complex diseases, estimated to represent an overall 10-15% of all lymphomas worldwide, with the highest incidence rates occurring in Asia.1,2 The relative prevalence of PTCL entities delineated according to the criteria of the REAL (1994) /WHO (2001) classification systems, was evaluated in multiple institutions in the late 1990s and early 2000s, based on retrospective cohorts of patients. In those series, PTCL-NOS (a "by default" diagnosis for cases not fulfilling the criteria for other more specific entities) was the most frequent entity, followed by anaplastic large cell lymphoma (ALCL) and AITL, while extranodal entities, in general, accounted for a small proportion of the cases. 1,3,4 This worldwide epidemiology was most recently addressed by the International PTCL study, which reviewed more than 1,300 patients diagnosed with PTCL between 1990 and 2002 in North America, Europe and Asia.5 In this cohort, PTCL-NOS was the most common diagnosis (25,9%), followed by AITL (18,5%), representing 30.4% and 21.7% of non-cutaneous PTCL, respectively (Figure 1). 5This study also confirmed geographic variations in the distribution of PTCL entities, notably demonstrating that the highest frequencies of AITL and enteropathy-associated Tcell lymphoma (EATL) are in Europe.Here, we provide recent data obtained from a large prospective survey in France. The prevalent analysis of PTCL was derived from data collected through Lymphopath, a national network of 33 expert reference centers for hematopathology which was established by the French National Cancer Agency in 2010. Non-expert pathologists are encouraged to refer every newly diagnosed lymphoma for review to a Lymphopath center. Diagnoses provided by experts, following slide review and additional ancillary techniques performed in the reference center, are entered into a central database. Of the 31,401 non-cutaneous lymphomas reviewed in Lymphopath over four years (20...

Monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL) is a rare aggressive T-cell lymphoma most reported in Asia. We performed a comprehensive clinical, pathological and genomic study of 71 European MEITL patients (36 males; 35 females, median age 67 years). The majority presented with gastrointestinal involvement and had emergency surgery, and 40% had stage IV disease. The tumors were morphologically classified into two groups: typical (58%) and atypical (i.e. nonmonomorphic or with necrosis, angiotropism or starry-sky pattern) (42%), sharing a homogeneous immunophenotypic profile (CD3+ (98%) CD4- (94%) CD5- (97%) CD7+ (97%) CD8+ (90%) CD56+ (86%) CD103+ (80%) cytotoxic marker+ (98%)) with more frequent expression of TCRgd (50%) than TCRab (32%). MYC expression (30% of cases) partly reflecting MYC gene locus alterations, correlated with nonmonomorphic cytology. Almost all cases (97%) harbored deleterious mutation(s) and/or deletion of the SETD2 gene and 90% had defective H3K36 trimethylation. Other frequently mutated genes were STAT5B (57%), JAK3 (50%), TP53 (35%) JAK1 (12.5%), BCOR and ATM (11%). Both TP53 mutations and MYC expression correlated with atypical morphology. The median overall survival (OS) of 63 patients (43/63 only received chemotherapy after initial surgery) was 7.8 months. Multivariate analysis found a strong negative impact on outcome of MYC expression, TP53 mutation, STAT5B mutation and poor performance status while aberrant B-cell marker expression (20% of cases) correlated with better survival. In conclusion, MEITL is an aggressive disease with resistance to conventional therapy, predominantly characterized by driver gene alterations deregulating histone methylation and JAK/STAT signalling and encompasses genetic and morphologic variants associated with very high clinical risk.

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Composite and sequential lymphomas involving both classical Hodgkin lymphoma (CHL) and primary mediastinal B-cell lymphoma (PMBCL) are rare phenomena. Beyond the relevant biological interest raised by these cases, treatments and outcome data are poorly covered in the recent literature. This retrospective analysis describes the pathological and clinical characteristics of 10 composite and 15 sequential cases included after a central pathological review. At diagnosis, 70% of the composite lymphomas presented a disseminated and extranodal disease. Among the 15 sequential lymphomas, 12 were CHL at first occurrence and three were PMBCL. Based on their clinical evolution, these sequential lymphomas could be divided into early (i.e., diagnosis of second lymphoma within a year) and late [(i.e., a second lymphoma occurrence occurring after a long period of complete remission]). All composite cases were alive in complete remission after a median follow-up of 34 months. If the early sequential lymphoma presented a particularly poor outcome with a median overall survival shorter than one year, the late cases were efficiently salvaged. Further molecular studies are needed to describe the underlying biology of these rare diseases, possibly representing the extreme of tumour cell plasticity found in grey-zone lymphoma.

We report 2 new cases of invasive infections caused by Nannizziopsis spp. molds in France. Both patients had cerebral abscesses and were immunocompromised. Both patients had recently spent time in Africa.