Association Between High-grade Myelodysplastic Syndrome and Cutaneous Langerhans Cell Histiocytosis Suggested by Next-Generation Sequencing

Abstract

treatment (4 patients) but was followed by minimal improvement in 2 cases, stabilization in 1 patient, and progression in 1 patient.Discussion | The pathogenesis of cutaneous calcinosis in autoimmune disease is unclear. Sclerotic-type chronic skin graftversus-host disease shares many clinical features with SS, suggesting a common pathway leading to calcinosis. The 7 cases described herein are similar to 2 previously reported cases in the literature, including a long latency period (12 and 14 years) and antecedent ScGVHD. 3,4 The lower extremities are a common site of skin sclerosis in ScGVHD and were the most common location for calcinosis in these patients. Joint range-ofmotion restriction was frequently observed and calcinosis likely worsened existing functional limitations caused by ScGVHD.Elevated antinuclear antibody (ANA) was detected in 4 of the 5 patients who underwent testing, which appears to be higher than in other reports in cGVHD populations. Although ANA titers do not correlate with specific cutaneous features, 5,6 elevated ANA in the setting of ScGVHD may be a risk factor for GVHD-CC. One patient had strongly positive anticentromere antibodies, which are seen in limited SS, a condition associated with calcinosis cutis. Further exploration of autoantibodies associated with calcinosis in cGVHD, particularly anticentromere antibodies, is warranted.In addition to systemic therapy for cGVHD, treatment with STS for calcinosis yielded mixed results. Success with diltiazem has been reported, 3 but failed to benefit 2 patients in this series. The rarity of GVHD-CC makes drawing conclusions difficult. We hope to increase awareness of GVHD-CC because subtle calcinosis may be overlooked, particularly in patients with long-standing skin sclerosis.

Spectrum of histiocytic neoplasms associated with diverse haematological malignancies bearing the same oncogenic mutation

“…For example, in Case 1, the MAP2K1 and RAF1 mutations were (presumably) only present in the HS and not in the CMML, suggesting that these mutations may have contributed to the development of the HS from a common KRAS mutated HSPC or primary CMML clone. Similar situations of one or more shared genetic alterations and additional unique mutations in the histiocytic neoplasm and/or associated haematological malignancy have been reported in other cases [15,18,23,25–27,29,31,32,39,41,44,45,47,52–57,59,60,63–67,87–95]. The histiocytic neoplasms often harboured unique mutations in genes encoding proteins of the MAPK signalling pathway, including NRAS [52,55], KRAS [39,53,56], BRAF [15,23,44,45,54,92,94] and RAF1 [32], again demonstrating the importance of constitutive MAPK pathway activation in the pathogenesis of the histiocytic neoplasms [3,96].…”

Atypical cutaneous histiocytic eruption in a patient with chronic myelomonocytic leukemia: A case report

“…For example, a case with concomitant AML and BRAF ‐mutated cutaneous LCH had common IDH2 , ASXL1 , and STAG2 mutations in the LCH and the bone marrow affected by AML, demonstrated by NGS. The LCH was thus postulated to be derived from the myeloblast via transdifferatiation and acquisition of BRAF V600E mutation 20 . Our case, however, lacked the characteristic accompanying eosinophils and the positive staining for S100, CD1a, and langerin that should be seen in LCH.…”

“…Langerhans cell histiocytosis (LCH) can be associated with myeloid and lymphoid neoplasms, including CMML, with some of the cases demonstrating a clonal relationship between the LCH and the hematological neoplasms 13‐20 . For example, a case with concomitant AML and BRAF ‐mutated cutaneous LCH had common IDH2 , ASXL1 , and STAG2 mutations in the LCH and the bone marrow affected by AML, demonstrated by NGS.…”

Case report: Common clonal origin of concurrent langerhans cell histiocytosis and acute myeloid leukemia

“…In the other two reports of shared mutation between LCH and AML, both adult males were diagnosed with LCH on skin biopsy and AML from bone marrow biopsy. One patient shared ASXL1, IDH2, and STAG2 mutations (36), and the other shared KRAS mutation and trisomy 8 (37). Of note, in both cases, BRAF-V600E mutation was detected only in LCH cells.…”