Alexandra Freeman, United States of America
National Institutes of health NIAID LCIMPresenter of 2 Presentations
MERKEL CELL CARCINOMA ASSOCIATED WITH MAGT1 DEFICIENCY
Abstract
Background and Aims
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.
Methods
Clinical course, laboratory tests and imaging were reviewed.
Results
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.
Conclusions
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.
MALIGNANCY IN LOSS OF FUNCTION STAT3
Abstract
Background and Aims
Loss of Function (LOF) STAT3 (AD-HIES; Job’s Syndrome) is a rare primary immunodeficiency characterized by sinopulmonary infections, eczema, connective tissue, and vascular complications. Increased STAT3 activity is thought to drive malignancies, mostly adenocarcinomas. With the dominant negative mutations in STAT3, less malignancy may be expected. However, increased rates of lymphoma are described.
Methods
We reviewed 143 LOF STAT3 patients seen at NIH to determine the spectrum of malignancies, treatments provided, and outcomes.
Results
We identified nine patients with history of malignancy. Six (4%) were treated for non-Hodgkin lymphoma (5 DLBCL, 1 Burkitt’s). Five with DLBCL were treated with EPOCH at standard doses. 4/5 patients are alive, with one dying of heart failure 16 years after treatment. Two (1%) were treated for papillary thyroid carcinoma with thyroidectomy and radioactive iodine. They have been in remission for 7 and 20 years. One was later diagnosed with DLBCL. Two had localized skin cancers; one with squamous cell CAs treated topically with 5FU, and one with basal cell CA treated with Moh’s surgery complicated by poor wound healing.
Conclusions
Papillary thyroid carcinoma and non-Hodgkin lymphoma appear to occur at higher rates in AD-HIES and should be considered in patients with thyroid nodules or lymphadenopathy. Skin cancer should be considered, especially in patients treated with voriconazole. As survival increases, more malignancy may be seen in this population. It is possible that decreased STAT 3 signaling may prove to be protective of some cancers.