Unique Recognizable Histopathologic Variant of Palisaded Neutrophilic and Granulomatous Dermatitis that Is Associated With SRSF2-Mutated Chronic Myelomonocytic Leukemia: Case Report and Review of the Literature

Abstract

Palisaded neutrophilic and granulomatous dermatitis (PNGD) represents a cutaneous histopathologic reaction spectrum associated with several underlying disorders. Few cases of PNGD have been associated with chronic myelomonocytic leukemia (CMML), a malignant hematopoietic disorder with features in between those of a myeloproliferative neoplasm and myelodysplastic syndrome. We present a patient with a generalized papular skin reaction involving the neck, chest, and shoulders with histomorphological features on the spectrum of PNGD. Subsequent laboratory workup demonstrated a persistent mild monocytosis, raising concern for CMML. The diagnosis was ultimately confirmed with a bone marrow biopsy and associated mutational analysis through nextgeneration sequencing which identified deleterious variants in SRSF2, IDH2, and ASXL1. The findings in this case strengthen the previously made association between PNGD and SRSF2-mutated CMML and may help better define a unique recognizable clinicalhistopathological-molecular subtype for dermatopathologists.

Plasmacytoid Dendritic Cell Dermatosis Associated to Myeloproliferative/Myelodysplastic Neoplasms

“…22 This has been shown particularly for histiocytoid Sweet's syndrome, palisaded neutrophilic and granulomatous dermatitis, and in rare instances for erythema nodosum and pyoderma gangrenosum. [22][23][24][25][26][27][28][29] Moreover, this relationship has also been established for the L-Group histiocytosis or histiocytic sarcoma. [30][31][32] The reason for MDS/MPN presenting with this broad spectrum of clinical and histologic cutaneous manifestations is not known.…”

“…Interestingly, there are more and more papers coming out based on FISH or next-generation sequencing studies suggesting that the skin infiltrate of neutrophilic dermatoses that arise in the context of myeloid malignancies carry the same molecular alterations than the malignant clone 22. This has been shown particularly for histiocytoid Sweet’s syndrome, palisaded neutrophilic and granulomatous dermatitis, and in rare instances for erythema nodosum and pyoderma gangrenosum 22–29…”

Clinical, Histopathological and Molecular Spectrum of Cutaneous Lesions in Myelodysplastic Syndrome and Myeloproliferative Neoplasms (MDS/MPN): An Integrative Review

“…In addition, in one of them, these mutations were already found 5 years before the diagnosis of the hematologic neoplasia [37]. Since then, only a few more cases have been reported [36,38,39]. All but one were patients with CMML, in all cases where molecular techniques were performed, SRSF2 mutations were found in the BM and in the cutaneous infiltrates of the patients.…”

“…All but one were patients with CMML, in all cases where molecular techniques were performed, SRSF2 mutations were found in the BM and in the cutaneous infiltrates of the patients. For that reason, Enescu et al proposed that this kind of dermatitis is specific for CMML patients with this molecular alteration [39]. The molecular technique used for the study of mutations in the BM and skin of these patients was variable, including NGS, pyrosequencing or RFLP analysis by BsaJI digestion and/or sequencing of SRSF2 polymerase chain reaction products containing the hotspot region in codon 95 (2 p.Pro95His;1 p.Pro95Leu) [36,37,39].…”

“…For that reason, Enescu et al proposed that this kind of dermatitis is specific for CMML patients with this molecular alteration [39]. The molecular technique used for the study of mutations in the BM and skin of these patients was variable, including NGS, pyrosequencing or RFLP analysis by BsaJI digestion and/or sequencing of SRSF2 polymerase chain reaction products containing the hotspot region in codon 95 (2 p.Pro95His;1 p.Pro95Leu) [36,37,39]. Before the description of the Federmann cases in 2017, this type of granulomatous reaction had been published in association with MDS, and the authors argued that it could be a manifestation of the disease, because the cutaneous lesions did not respond to conventional treatments for reactive dermatoses, but they improved with the specific chemotherapy treatment for the myeloid neoplasia [35].…”