Atypical reactive/pseudohistiocytosis associated with myeloid neoplasms

Introduction: Clonal or atypical myelo-monocytic proliferations in the skin may represent the first sign of underlying myeloid neoplasms, the prototype being histiocytosis and the histiocytoid variant of Sweet syndrome. Methods: Three cases of cutaneous manifestations of myeloid neoplasm, mimicking histiocytosis, but lacking clonality are discussed; published literature is critically appraised. Results: Case 1. 67 y.o. woman with a diagnosis of ETV6::SYK rearranged myeloid neoplasm with eosinophilia (MLN-E). Cutaneous manifestation comprised a dense, interstitial accumulation of histiocytoid histiocytes with a nondescript phenotype, in a clinic-pathologic pattern reminiscent of interstitial granuloma annulare (GA), found to be consistent along all 5 published cases, and restricted to MLN-E carrying ETV6::SYK. Molecular characterization of cutaneous infiltrate proved non-clonal (i.e., lacking both ETV6::SYK and an additional ASXL1 mutation, present in the peripheral blood), despite almost complete response to imatinib. Cases 2-3. Two 81- and 86-year-old males, both affected by chronic myelomonocytic leukemia (CMML) and carrying, respectively, del(16) and KRAS mutation. Skin lesions, initially interpreted as tuberculid in both cases, consisted of papules and plaques, comprising a pseudolymphomatous infiltrate, intermixed with necrotizing granuloma-like accumulation of atypical, indeterminate cells (CD1a+, langerin-, CD68R-, CD33+). Notably, both patients shared Quantiferon Test+, but lacking Mycobacteria at PCR, as well as clonal marker in the first patient. Published experience summarized in the Table.