Ruben Duarte Ferreira, Portugal
CAML Centro de Imunodeficiências PrimáriasPresenter of 1 Presentation
SYNCHRONOUS GASTRIC AND HEPATOCELLULAR CARCINOMAS IN A PATIENT WITH PRIMARY ANTIBODY DEFICIENCY
Abstract
Background and Aims
Neoplasia, particularly gastric adenocarcinoma, has been increasingly recognized as an important cause of death in CVID, but the mechanisms underlying this increased oncogenic risk remain largely unknown. We report here a patient with primary hypogammaglobulinemia that presented synchronous and rapidly progressing gastric adenocarcinoma and hepatocellular carcinoma.
Methods
Clinical report with immune profile and WGS.
Results
Poorly differentiated antral adenocarcinoma and high-grade pyloric dysplasia were diagnosed at 45y during a screening protocol with gastroscopy every 1-3y. The tumor staging evaluation revealed multiple lesions of hepatocellular carcinoma that led to the patient death within one month. There was no evidence of previous liver disease, including viral hepatitis or increased alcohol consumption. The patient reported intermittent treatment with omeprazole since 21y due to gastritis, and diffuse gastric atrophy and intestinal metaplasia were diagnosed at the age of 39 prompting H. pylori eradication that was achieved after 2 treatment courses. Primary antibody deficiency was diagnosed at 15y due to recurrent sino-pulmonary infections (since 6y), meningitis, giardiasis and severe autoimmune cytopenias. Subsequently, he featured lymphadenopathy, lung and gut granulomatous-lymphocytic infiltration, and Pseudomonas and BK infections, in agreement with concomitant T cell deficiency, as attested by the marked loss of naïve CD4+ T cells. WGS did not reveal mutations in genes typically associated with familial gastric cancer or CVID, but there were multiple potentially pathogenic variants in genes of interest favoring a polygenic basis.
Conclusions
This case points to a reappraisal of cancer surveillance in primary antibody deficiencies and reinforces the need of WGS validation algorithms for multigenic diseases.