Analysis for CSF3R Mutation Confirms Cutaneous Involvement by Neoplastic Neutrophils in a Patient With Chronic Neutrophilic Leukemia

Abstract

Chronic neutrophilic leukemia (CNL) is a rare myeloproliferative neoplasm (MPN) characterized by unexplained sustained neutrophilia with few immature forms and no dysplastic changes. Interestingly, patients with CNL can develop neutrophilic dermatosis. It is not known whether the neutrophils in these cases are neoplastic or not since both can have identical morphology. Mutations of the CSF3R gene have been recently found to be prevalent in CNL. We investigated whether CSF3R mutation can be detected in a lesional skin biopsy from a patient with underlying CNL. The patient is a 79-year-old woman who presented with a few weeks' history of skin rash. Physical examination revealed disseminated maculopapular rash with focal bullae formation. Complete blood count revealed: WBC 31.7 K/μL; Hgb 12 g/dL; platelets 423K/μL. Review of the peripheral smear revealed a marked neutrophilic leukocytosis with significant toxic granulation, minimal left shift up to the promyelocyte stage and no dysplastic features. Skin punch biopsies of two lesional sites revealed a diffuse superficial dermal infiltrate composed of mature neutrophils, epidermal ulceration and dermal hemorrhage. A diagnosis of Sweet syndrome was favored. Upon follow up 1 month later, the patient was found to have persistent skin rash and neutrophilia. Complete blood count revealed: WBC 59.0 K/μL; Hgb 10.8 g/dL; platelets 295K/μL. Extensive workup failed to reveal a specific etiology. Bone marrow biopsy showed a hypercellular bone marrow (>95%) with predominance of mature myeloid elements. A diagnosis of CNL was made and after 2 months of hydroxyurea and prednisone therapy, the skin rash resolved. High resolution melting followed by Sanger sequencing was separately performed on DNA isolated from paraffin blocks of bone marrow clot and skin biopsy and revealed the presence of CSF3R T618I mutation in each specimen. These results confirm that skin can be involved by neoplastic neutrophils in patients with CNL.