WHIM syndrome is a condition in which affected persons have chronic peripheral 
neutropenia, lymphopenia, abnormal susceptibility to human papilloma virus 
infection, and myelokathexis. Myelokathexis refers to the retention of mature 
neutrophils in the bone marrow (BM), which accounts for degenerative changes and 
hypersegmentation. Most patients present heterozygous autosomal dominant 
mutations of the gene encoding CXCR4. Consequently, aberrant CXCL12/CXCR4 
signaling impairs the receptor downregulation causing hyperactivation 
(gain-of-function) that affects BM homing for myelopoiesis and lymphopoiesis and 
the release of neutrophils in the bloodstream. We report the case of a 
26-year-old female with severe foot and hand cutaneous warts since childhood, 
recalcitrant genital condylomatas, bacterial infections, and intraepithelial 
cervical neoplasia. Laboratory tests revealed severe B lymphopenia and HPV high 
and low risk types. HIV testing was negative. Not only CXCR4 but also GATA2, 
NEMO, and CD40L gene mutations were excluded. BM smears revealed, in the 
presence of a normal cellularity, hyperplasia of myeloid cells (MPO positive) 
and karyorrhexis, especially in neutrophils and eosinophils. Of note, 
neutrophils with altered lobation of nuclei connected by long thin chromatin 
filaments were observed. Our patient presented a clinical and histological 
picture reminiscent of WHIM in the presence of normal peripheral neutrophil 
counts and wild-type CXCR4 gene. Although the BM did not reveal a classical 
pattern of myelokathexis, the observation of consistent signs of neutrophil 
dysplasia has fuelled the hypothesis of a novel WHIM variant or a novel 
immunodeficiency. We speculate that abnormalities that affect CXCR4/CXCL12 pair, 
including GRK levels or activity, might be responsible for this WHIM-like 
disorder.