Sweet’s Syndrome (SS) is characterized by an accumulation of mature polymorphonuclear cells (PMN) in the skin. Ten percent of SS patients have an associated myeloid neoplasm (MN) but the pathophysiological link between these two diseases is unclear. 
To determine the clonal origin of skin-infiltrating PMN in MN-associated SS, we conducted a retrospective study and reviewed patients with concomitant SS and MN diagnosed at Saint-Louis or Saint-Antoine hospital, Paris, France, between 2010 and 2018. Targeted next-generation sequencing (NGS) of 80 myeloid target genes was performed on DNA extracted from bone marrow or blood (hematopoietic samples) and from formalin-fixed paraffin-embedded (FFPE) tissue sections of skin-lesion biopsy. 
Ten patients were analyzed, including 6 with acute myeloid leukemia, 2 with myelodysplastic syndromes (MDS), 1 with myeloproliferative neoplasm (MPN) and 1 with MDS/MPN. NGS analysis of hematopoietic samples found oncogenic mutations in 9 out of 10 patients (range 1-10 mutations, median 3 per patient). Major recurrent mutations affected genes encoding factors involved in splicing (SRSF2, PRPF8), epigenetic modification (TET2, DNMT3A), transcription (TP53, RUNX1) and cohesin complex (STAG2). Strinkingly, in all cases, the major clone of the MN in hematopoietic samples was also found in skin biopsies, demonstrating a clonal link between both diseases.
This is the first study investigating the mutational profile of skin-infiltrating PMN and malignant myeloid cells within a cohort of patients with MN. Their clonal relation, previously suggested by FISH analyses and definitely confirmed by the present study, demonstrates that the mature PMN infiltration have differentiated from the malignant myeloid progenitor cells.

Next generation sequencing of myeloid neoplasm-associated Sweet syndrome shows similar mutational profile of skin and myeloid disorder