Granulomatous Dermatitis Heralding Myelodisplastic/Myeloproliferative Neoplasms. Neoplastic or Reactive Cells? A Study of 2 Cases

Abstract

:Skin manifestations in the context of underlying hematological malignancies are well known and not an infrequent clinical finding. They can represent specific neoplastic infiltrates or be considered as reactive. In the latter group, where granulomatous dermatitis is included, controversy has emerged recently. According to newly reported data, the histiocytes comprising these granulomata can carry the same molecular alterations found in the primary process. Moreover, the skin manifestations in these patients are sometimes the initial clue for the diagnosis of the underlying malignancy. We present here 2 cases with granulomatous skin infiltrates preceding the diagnosis of myelodysplastic/myeloproliferative neoplasms. In one of them, the same IDH2 mutation was detected in granulomatous lesions on the skin and in the bone marrow. This was performed by pyrosequencing instead of next-generation sequencing, with improved cost-effectiveness.

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.…”

“…These cutaneous lesions have been mainly related to rheumatologic diseases and drug reactions. However, the association of PNGD or IGD with hematological malignancies, including CMML and MDS, has been reported firstly as a reactive dermatitis in the setting of the hematological condition and lately as a possible skin manifestation of the disease [35,36].…”

“…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].…”

Granulomatous dermatitis in the context of chronic myelomonocytic leukemia: More than just reactive infiltrates. An illustrative case report with literature review

“…More recently, the true nature of the myeloid cells present in the cutaneous infiltrates of this theoretically reactive dermatitis has generated considerable controversy in some publications from our group and others by showing the same molecular pathologic alterations in the patient's skin and bone marrow (BM) samples. [2][3][4] Here, we report another original case in which the patient initially presented with cutaneous lesions with clinical and histopathological features of superficial granulomatous dermatitis, in whom, later on, the diagnosis of CMML was made. In this patient, the same molecular alterations were detected in BM and skin by next-generation sequencing (NGS) methods with high variant allele frequency (VAF).…”