Merkel cell carcinoma (MCC) is a rare, aggressive skin cancer. MCC risk is elevated in older patients (mean age 70s) and those with secondary immunodeficiency, including HIV, Chronic Lymphoblastic leukemia (CLL), and solid organ transplants. Diagnosis of MCC before age 40 is vanishingly rare. We describe two patients with MCC presenting at young age who were diagnosed with MAGT1 deficiency, a rare immunodeficiency associated with T cell lymphopenia, chronic EBV viremia, and lymphoma susceptibility.
Clinical course, laboratory tests and imaging were reviewed.
Patient 1 presented at 14 years with metastatic MCC, which was successfully treated with chemotherapy, radiation therapy and an autologous stem cell transplant. His history included recurrent ear and lung infections, zoster, and splenomegaly. He had CD4 lymphopenia, B cell lymphocytosis, and post- chemotherapy had hypogammaglobulinemia requiring immune globulin replacement therapy. Ten years later he reports good health without recurrence of the MCC. Whole Exome sequencing (WES) analysis detected a hemizygous MAGT1 c.486+1G>T splice site mutation . Patient 2 presented at 22 years of age with Stage III MCC treated with surgical resection and radiation therapy. His history included recurrent ear and lung infections, prolonged Coxsackie and influenza infections, extensive molluscum, chronic EBV viremia, chronic elevated liver enzymes and mucocutaneous candidiasis. CD4 lymphopenia and B cell lymphocytosis were present with preserved IgG and specific antibodies. WES analysis showed a hemizygous c.991C>T (p.Arg331Ter) pathogenic variant in MAGT1.
MAGT1 deficiency is associated with young-onset MCC, expanding the malignancy association beyond lymphomas. MCC has been reported in GATA2 deficiency, also characterized by viral susceptibility and malignancy.