Neutropenia related to ELANE gene mutations predisposes to infection and leukemia/ myelodysplasia, but little is known about the predisposition to cancer. Among a cohort of 149 patients, we identified four with malignant solid tumors (papillary thyroid cancer, anal squamous cell cancer, papillary renal cell carcinoma, and adrenocortical carcinoma), all after the age of 25 years. Three occurred in cyclic neutropenia while 1 occurred in severe chronic neutropenia (among 49 and 100 patients, respectively). A previous radiotherapy was identified as risk factor in one patient. Moreover, among 18 other patients that underwent hematopoietic stem-cell transplantations, none developed a cancer.
To analyze the role of Epstein-Barr virus (EBV) in the biological and clinical characteristics of patients treated for classic Hodgkin lymphoma (cHL) in France. Bio-pathological data of 301 patients treated for a cHL in or according to the protocol of the EuroNet PHL-C1 trial between November 2008 and February 2013 were centrally reviewed. Median age at diagnosis was 14 [3-18] years and the F/M ratio 0.86, 0.47 before 10 years and 0.9 from 11 to 18. CHL subtypes were nodular sclerosis for 266/301 (88%) patients, mixed cellularity for 22/301 (7%), lymphocyte rich for 2/301 (1%), and 11/301 were unclassified. EBV expression in situ (EBV cHL) was observed for 68/301 (23%) patients, significantly associated with MC subtype and male gender, and there was a trend with age <10 years, it was particularly overrepresented in boys below 10 years: 15/23 (65%) vs 28/139 among other male patients (20%). Event-free and overall survival were equivalent between EBV and non-EBV cHL patients. EBV viral load was tested for 108/301 patients and detectable in 22/108 (22%) cases. A positive viral load was overrepresented in EBV cHL versus non-EBV cHL patients: 13/28 (46%) vs 9/80 (11%). Detailed semi-quantitative histological analysis showed a high number of B-cell residual follicles in EBV cHL and no significant association with CD 20 or PAX 5 immunostaining in tumoral cells relative to EBV-negative HL. Distribution of EBV cHL in children and adolescents is associated with young age and male gender, suggesting a specific physiopathology and may require a differential therapeutic approach.