Warts, hypogammaglobulinemia, infections, and myelokathexis syndrome (WHIMS) is a rare combined primary immunodeficiency caused by gain-of-function mutations in the chemokine receptor CXCR4 gene. While the susceptibility to human papillomavirus (HPV) induced malignancy is established, the overall malignancy risk is less well characterized. We present here an update on the global incidence of malignancy in WHIMS based on a literature review and data from the French Severe Chronic Neutropenia Registry.
We analyzed retrospective cohort data from 14 patients diagnosed with WHIMS from the French Severe Chronic Neutropenia Registry and conducted a literature review in PubMed to identify all cases of WHIMS associated with malignancy.
Five Registry patients developed malignancy at median age of 37 years. The 40-years rate of malignancy was 46% (95% CI 17-88%). We observed two HPV-induced vulvar cancers (one lethal), 2 lymphomas (one bone, one skin lymphoma) and one basal cell carcinoma. In the literature, malignancy was reported in 12 reports (excluding our data) mainly in the 3 rd and 4 th decades. Malignancies included Epstein–Barr Virus (EBV) associated lymphoproliferative disorders, cutaneous B-cell lymphoma, melanoma, HPV oral squamous cell carcinoma, and multiple cases of HPV-related genital and anal cancers. In total, 8 cases of malignancy were linked to HPV and 3 to EBV. The CXCR4 variant Ser338* (c.1013C>G) was present in 6 WHIMS patients with malignancy reported in the literature.
Immunocompromised WHIMS patients are at high risk of malignancy, mainly HPV induced followed by lymphoma which is frequently EBV related.