Clinico-pathologic, genetic, and therapeutic features of 14 patients with MN and with pDC dermatosis
| Patient,Sex,age . | Clinical presentation . | Pruritus . | Myeloid neoplasm (ICC 2022) and time of diagnosis related to pDC dermatosis . | Pronostic scoring (IPSS-M or CPSS-mol) . | Skin histology (% of cell type in the sample∗); total percentage of pDC+iDC in the sample∗ . | Percentage of CD163+ myeloid cells in the skin sample . | Targeted sequencing of skin biopsy (gene, VAF %) . | Targeted sequencing of bone marrow or blood (gene, VAF%) / cytogenetic . | Hematological Treatment and response . | Skin-directed treatment and response . | Death, follow-up time after cutaneous sign, after diagnosis of myeloid neoplasm and cause of death . |
|---|---|---|---|---|---|---|---|---|---|---|---|
| #1, F, 46 | Papules, face, trunk | No | AML with myelodysplasia-related gene mutations concurrent | — | Dermal infiltrate of pDC (30), iDC (1); 31% | 5 | RUNX1 x 2 (26,23) BCORL1 (23) FLT3-ITD (duplication) | RUNX1 x2 (45,43) BCORL1 (41) FLT3-ITD (duplication) /normal | Allo-HCT (CR) | Allo-HCT (CR) | No, 3 y and 3 y |
| #2, M, 74 | Papules, legs | yes | MDS, NOS with multilineage dysplasia 4 y later | Low –0.81 | Dermal infiltrate of pDC (10), iDC (15); 25% | 10 | BRCC3 (16) TET2 (10) SRSF2 (9) RUNX1 (9) | TET2 (38) SRSF2 (43) RUNX1 (44) BRCC3 (NA) /normal | NA | NA | No, 4 y and 4.4 y |
| #3, M, 65 | Papules, head, trunk, arms, legs | yes | CMML 1 y before | Intermediate 1 | Dermal infiltrate of pDC (20), iDC (10); 30% | 15 | IDH2 (19) BRCC3 (18) SRSF2 (10) NF1 (8) CBL (6) | CBL (73) IDH2 (43) SRSF2 (35) NF1 (4) CBL (73) /normal | Azacitidine and Allo-HCT (CR) | Azacitidine and Allo-HCT (CR) | No, 6 y and 7 y |
| #4, M, 63 | Papules, trunk | yes | CMML 3 mo later | Intermediate 2 | Dermal infiltrate of pDC (25),iDC (10); 35% | 10 | TET2 x2 (23, 19) 20CTCF (1930) NRAS (1019) ASXL101 (17)20 | TET2 x2 (53, 22) NRAS (53) SRSF2 (40) ASXL1 (35) /normal | Allo-HCT (CR) | Allo-HCT (CR) | No, 2.25 y 2 y |
| #5, M, 84 | papules, trunk, arms, legs | yes | CMML Concurrent | Intermediate 1 | Dermal infiltrate of pDC (35); 35% | 20 | JAK2 (3106) TET2 5 (27) SRSF2 10(22) | JAK2 (70) TET2 (44) SRSF2 (43) /normal | NA | NA | NA |
| #6, M, 84 | Papules, nodules, Head | yes | CMML 1 y later | Intermediate 2 | Dermal infiltrate of pDC (45), iDC (2); 47% | 30 | TET2 x3 (55,20,17) ASXL1 (31) NRAS (23) SRSF2 (21) | TET2 x3 (88,4,4) SRSF2 (44) ASXL1 (42) NRAS (24) /46,XY,add(11)(p11)/46,XY | No treatment, surveillance | High potent topical corticosteroids and tacrolimus (PR) Prednisone 1 mg/kg per day (CR) | Yes, 4 y, 3 y, sepsis from lung infection |
| #7, F, 86 | Papules | no | CMML, 8 mo before | Intermediate 2 | Dermal infiltrate of pDC (30), iDC (1); 31% | 10 | KRAS(22), SF3B1 (21) SMC3 (17) RUNX1 (17) FLT3-ITD | KRAS (43) SF3B1 (42) SMC3 (42) RUNX1 (13) FLT3-ITD /normal | Sorafenib 200 mg twice a day and decitabine (NR) | High potent topical corticosteroids (NR) Prednisone 1m/kg per day (CR) | Yes, 1.1 y, 6 mo, AML |
| #8, M, 89 | Papules | Yes | CMML, concurrent | Intermediate 1 | Dermal infiltrate of pDC (10), iDC (30); 40% | 10 | ASXL1 (17) ETV6 (19) BRAF(17) CUX1 (15) SRSF2 (11) TET2 (11) | ASXL1 (41), ETV6 (38), BRAF (37) CUX1 (35) SRSF2 (32) TET2 (16) /normal (BLOOD) | Hydroxycarbamide (NR) | high potent topical corticosteroids (NR) | Yes, 3 y, 3 y AML |
| #9, M, 80 | Papules | yes | MDS, NOS with multilineage dysplasia, concurrent | Low –1.41 | Dermal infiltrate of pDC (10), iDC (10); 20% | 20 | ASXL2 (11) CBL (9) CHEK2 (9) TET2 (15) BRCC3 (15) TP53 (2) | TET2 (40) BRCC3 (40) ASXL2 (25) CBL (16) CHEK2 (15) /normal | No treatment | High potent topical corticosteroids (PR) Prednisone 0.1mg/kg per day (CR) | No, 7 y, 7 y |
| #10, M, 64 | Papules | yes | CMML concurrent | Intermediate 2 | Dermal infiltrate of pDC (20), iDC (5); 25% | 10 | ZRSR2 (56) TET2 (9) ASLX1 (4) | TET2x2 (35, 42) ASXL1 (32) ZRSR2 (3) PTPN11 (2) /normal | NA | High potent topical corticosteroids (PR) | No, 2.5 y 2.5 y |
| #11, M, 87 | Papules, face | yes | CMML concurrent | NA | Dermal infiltrate of pDC (5), iDC (80); 85% | 5 | TET2 (73) ZRSR2 (19) KRAS (17) ASXL1 (7) | TET2 (86) ZRSR2 (19) ASXL1 (9) /normal (BLOOD) | Transfusion, no treatment | No treatment | No, 3 mo, 3 mo |
| #12, F, 80 | Papules,and nodules Trunk | yes | CCUS 6 mo later | NA | Dermal infiltrate of pDC (40); 40% | 10 | RUNX1 (25) SF3B1 (22) WT1 (16) KRAS (9) | NA | no | Anti-H1 (NR) | Yes, 1.1 y, 6 mo AML |
| #13, M, 76 | Papules, Nodules, Trunk, legs, arms | yes | CMML concurrent | Intermediate 2 | Dermal infiltrate of pDC (15), iDC (10); 25% | 10 | ARID2 (24) RIT1 (24) ASXL1 (24) SRSF2 (19) SMC3 (8) | ARID2 (NA) RIT1 (NA) ASXL1 (NA) /normal | EPO for anemia (no progression) | Anti H1 (NR) High potent topical corticosteroids (NR) Prednisone 0.5mg/kg per day (CR) | No, 2 y, 2 y |
| # 14, M, 60 | Papules, head and neck | no | CMML 3 y before | Intermediate 2 | Dermal infiltrate of pDC (20), iDC (15); 35% | 15 | SH2B3 (22) NF1 (21) SRSF2 (16) IDH2 (11) | SH2B3 (36) NF1x3 (50, 33 & 2), SRSF2 (42) IDH2 (46) KRAS (7) MPL (5) /normal | Hydroxycarbamide (NR) | — | No, 4 y, 3 y |
| Patient,Sex,age . | Clinical presentation . | Pruritus . | Myeloid neoplasm (ICC 2022) and time of diagnosis related to pDC dermatosis . | Pronostic scoring (IPSS-M or CPSS-mol) . | Skin histology (% of cell type in the sample∗); total percentage of pDC+iDC in the sample∗ . | Percentage of CD163+ myeloid cells in the skin sample . | Targeted sequencing of skin biopsy (gene, VAF %) . | Targeted sequencing of bone marrow or blood (gene, VAF%) / cytogenetic . | Hematological Treatment and response . | Skin-directed treatment and response . | Death, follow-up time after cutaneous sign, after diagnosis of myeloid neoplasm and cause of death . |
|---|---|---|---|---|---|---|---|---|---|---|---|
| #1, F, 46 | Papules, face, trunk | No | AML with myelodysplasia-related gene mutations concurrent | — | Dermal infiltrate of pDC (30), iDC (1); 31% | 5 | RUNX1 x 2 (26,23) BCORL1 (23) FLT3-ITD (duplication) | RUNX1 x2 (45,43) BCORL1 (41) FLT3-ITD (duplication) /normal | Allo-HCT (CR) | Allo-HCT (CR) | No, 3 y and 3 y |
| #2, M, 74 | Papules, legs | yes | MDS, NOS with multilineage dysplasia 4 y later | Low –0.81 | Dermal infiltrate of pDC (10), iDC (15); 25% | 10 | BRCC3 (16) TET2 (10) SRSF2 (9) RUNX1 (9) | TET2 (38) SRSF2 (43) RUNX1 (44) BRCC3 (NA) /normal | NA | NA | No, 4 y and 4.4 y |
| #3, M, 65 | Papules, head, trunk, arms, legs | yes | CMML 1 y before | Intermediate 1 | Dermal infiltrate of pDC (20), iDC (10); 30% | 15 | IDH2 (19) BRCC3 (18) SRSF2 (10) NF1 (8) CBL (6) | CBL (73) IDH2 (43) SRSF2 (35) NF1 (4) CBL (73) /normal | Azacitidine and Allo-HCT (CR) | Azacitidine and Allo-HCT (CR) | No, 6 y and 7 y |
| #4, M, 63 | Papules, trunk | yes | CMML 3 mo later | Intermediate 2 | Dermal infiltrate of pDC (25),iDC (10); 35% | 10 | TET2 x2 (23, 19) 20CTCF (1930) NRAS (1019) ASXL101 (17)20 | TET2 x2 (53, 22) NRAS (53) SRSF2 (40) ASXL1 (35) /normal | Allo-HCT (CR) | Allo-HCT (CR) | No, 2.25 y 2 y |
| #5, M, 84 | papules, trunk, arms, legs | yes | CMML Concurrent | Intermediate 1 | Dermal infiltrate of pDC (35); 35% | 20 | JAK2 (3106) TET2 5 (27) SRSF2 10(22) | JAK2 (70) TET2 (44) SRSF2 (43) /normal | NA | NA | NA |
| #6, M, 84 | Papules, nodules, Head | yes | CMML 1 y later | Intermediate 2 | Dermal infiltrate of pDC (45), iDC (2); 47% | 30 | TET2 x3 (55,20,17) ASXL1 (31) NRAS (23) SRSF2 (21) | TET2 x3 (88,4,4) SRSF2 (44) ASXL1 (42) NRAS (24) /46,XY,add(11)(p11)/46,XY | No treatment, surveillance | High potent topical corticosteroids and tacrolimus (PR) Prednisone 1 mg/kg per day (CR) | Yes, 4 y, 3 y, sepsis from lung infection |
| #7, F, 86 | Papules | no | CMML, 8 mo before | Intermediate 2 | Dermal infiltrate of pDC (30), iDC (1); 31% | 10 | KRAS(22), SF3B1 (21) SMC3 (17) RUNX1 (17) FLT3-ITD | KRAS (43) SF3B1 (42) SMC3 (42) RUNX1 (13) FLT3-ITD /normal | Sorafenib 200 mg twice a day and decitabine (NR) | High potent topical corticosteroids (NR) Prednisone 1m/kg per day (CR) | Yes, 1.1 y, 6 mo, AML |
| #8, M, 89 | Papules | Yes | CMML, concurrent | Intermediate 1 | Dermal infiltrate of pDC (10), iDC (30); 40% | 10 | ASXL1 (17) ETV6 (19) BRAF(17) CUX1 (15) SRSF2 (11) TET2 (11) | ASXL1 (41), ETV6 (38), BRAF (37) CUX1 (35) SRSF2 (32) TET2 (16) /normal (BLOOD) | Hydroxycarbamide (NR) | high potent topical corticosteroids (NR) | Yes, 3 y, 3 y AML |
| #9, M, 80 | Papules | yes | MDS, NOS with multilineage dysplasia, concurrent | Low –1.41 | Dermal infiltrate of pDC (10), iDC (10); 20% | 20 | ASXL2 (11) CBL (9) CHEK2 (9) TET2 (15) BRCC3 (15) TP53 (2) | TET2 (40) BRCC3 (40) ASXL2 (25) CBL (16) CHEK2 (15) /normal | No treatment | High potent topical corticosteroids (PR) Prednisone 0.1mg/kg per day (CR) | No, 7 y, 7 y |
| #10, M, 64 | Papules | yes | CMML concurrent | Intermediate 2 | Dermal infiltrate of pDC (20), iDC (5); 25% | 10 | ZRSR2 (56) TET2 (9) ASLX1 (4) | TET2x2 (35, 42) ASXL1 (32) ZRSR2 (3) PTPN11 (2) /normal | NA | High potent topical corticosteroids (PR) | No, 2.5 y 2.5 y |
| #11, M, 87 | Papules, face | yes | CMML concurrent | NA | Dermal infiltrate of pDC (5), iDC (80); 85% | 5 | TET2 (73) ZRSR2 (19) KRAS (17) ASXL1 (7) | TET2 (86) ZRSR2 (19) ASXL1 (9) /normal (BLOOD) | Transfusion, no treatment | No treatment | No, 3 mo, 3 mo |
| #12, F, 80 | Papules,and nodules Trunk | yes | CCUS 6 mo later | NA | Dermal infiltrate of pDC (40); 40% | 10 | RUNX1 (25) SF3B1 (22) WT1 (16) KRAS (9) | NA | no | Anti-H1 (NR) | Yes, 1.1 y, 6 mo AML |
| #13, M, 76 | Papules, Nodules, Trunk, legs, arms | yes | CMML concurrent | Intermediate 2 | Dermal infiltrate of pDC (15), iDC (10); 25% | 10 | ARID2 (24) RIT1 (24) ASXL1 (24) SRSF2 (19) SMC3 (8) | ARID2 (NA) RIT1 (NA) ASXL1 (NA) /normal | EPO for anemia (no progression) | Anti H1 (NR) High potent topical corticosteroids (NR) Prednisone 0.5mg/kg per day (CR) | No, 2 y, 2 y |
| # 14, M, 60 | Papules, head and neck | no | CMML 3 y before | Intermediate 2 | Dermal infiltrate of pDC (20), iDC (15); 35% | 15 | SH2B3 (22) NF1 (21) SRSF2 (16) IDH2 (11) | SH2B3 (36) NF1x3 (50, 33 & 2), SRSF2 (42) IDH2 (46) KRAS (7) MPL (5) /normal | Hydroxycarbamide (NR) | — | No, 4 y, 3 y |
CCUS, clonal cytopenia of undetermined significance; CPSS-mol, molecular CMML-specific prognostic scoring system; CR, complete response; ICC, International Consensus Classification; IPSS-M, International Prognostic Scoring System; MDN, myelodysplastic neoplasm; NA, not available; NR, no response; PR, partial response; VAF, variant allele frequency.
Percentages of cells in the skin sample correspond to the following: the number of CD123+ TCF4+ CD2AP+ cells on immunohistochemistry out of total nucleated cells of the sample for pDCs; the number of CD1a+ S100+/− CD207− cells on immunohistochemistry out of total nucleated cells of the sample for iDCs; the sum of pDC percentage and iDC percentage for total percentage of pDC+iDC in the sample.