In national PID registries, the incidence of malignancies in X-linked agammaglobulinemia (XLA) seems lower than in other primitive immune deficiencies.
We describe a teenager with XLA who developed a fulminant gastric adenocarcinoma.
A boy was diagnosed from birth with XLA (mutation of BTK exon 9) and received from early infancy adapted immunoglobulin replacement. He suffered of recurrent Campylobacter colitis, megaloblastic anemia and B12 deficiency. From the age of 8, he presented a recurrent Helicobacter pylori (Hp) gastritis finally eradicated at the age of 14 (mutation for macrolide resistance, repeated courses of high doses proton pump inhibitor, clarithromycin, amoxicillin, metronidazole, and finally bismuth). At the age of 16, he consulted with abdominal pain, weight loss and abundant ascitis. Tomodensitometry identified a voluminous gastric tumor, peritoneal carcinomatosis, liver and bone metastatic spread. Gastroduodenoscopy confirmed a muco-secretant adenocarcinoma HER2/Neu+++. Absence of CDH1 mutation. The tumor rapidly progressed and the patient died 2 months after the diagnosis. Retrospectively, the gastric biopsies showed atrophic gastritis of fundus, intestinal metaplasia and focal dysplasia for at least 5 years.
Genetic causes may be responsible of rare cancers in young patients. In humoral deficiencies, chronic Hp infection is the main factor involved in gastric carcinogenesis, and in case of symptoms, it should be early detected and eradicated. The improvement of outcome for those cancers is based on pathologic and molecular survey of any potentially precancerous lesion. Another major challenge is the multidisciplinary follow-up of those rare patients with a special attention for the transition period.