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.
We reviewed 143 LOF STAT3 patients seen at NIH to determine the spectrum of malignancies, treatments provided, and outcomes.
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.
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.