Clinical, cytogenetic, phenotypic, and molecular findings on 6 patients with isolated MS without AML at or before MS presentation
| Case . | Sex/age, y . | Medical history . | MS site and size . | MS . | BM at MS diagnosis . | Therapy . | Subsequent clinical history . | |||
|---|---|---|---|---|---|---|---|---|---|---|
| Cytogenetics and phenotype . | Variants detected by WES . | Cytogenetics and hematology . | Variants detected by WES . | |||||||
| 1 | F/59 | BMI 31 Concomitant serous adenocarcinoma of the ovary. | Vagina, cervix 5 × 4 cm | Karyotype: 46,XX IHC: CD34−, CD117+, CD56−, muramidase-, MPO−, CD61−, glycoA− | Variants detected in AML-associated genes: DNMT3A (p.V704fs) FLT3 (p.Y572C) NPM1 (p.W288fs) | Karyotype: 46,XX BM morphology: normal FCM: normal Normal CBC | Variants detected in AML-associated genes: DNMT3A (p.V704fs) | Daunorubicin + cytarabin. Surgery. Carboplatin + paclitaxel for ovarian cancer | Development of overt AML in the BM 28 mo after diagnosis. Dead | |
| Novel variants detected in: APOB CDH23 CMYA5 ETFDH FAM227B GIGYF2 LOC100128326 | MGA NFE2 (p.R272Q) PCDHGA1 PNPT1 PTEN RPL5 SETD2 STARD8 TTN | |||||||||
| 2 | F/59 | BMI 46. Subtotal hystero-oophorectomy with myoma and ovarian cysts. Ulcerative colitis | Cervix, uteri 9 × 7 cm | Karyotype: 46, XX IHC: CD34−, CD117+, muramidase−, MPO−, CD61−, glycoA− | Variants detected in AML-associated genes: DNMT3A (p.R320) IDH2 (p.R140Q) NPM1 (p.W288fs) | Karyotype: 46,XX BM morphology: normal FCM: normal Normal CBC | Variants detected in AML-associated genes: DNMT3A (p.R320*) Novel variants detected in: NFE2 (p.Y99fs) ODF1 TRAFD1 | Daunorubicin + cytarabin. | Development of overtAML in the BM 8 mo after diagnosis. Dead | |
| Novel variants detected in: BPIFB3 CKMT1 CLASP1 DLEC1 KCNB1 LPCAT2 MAMSTR | MASP2 NFE2 (p.Y99fs) ODF1 PCLO PRAMEF1 SEMA5A SOS1 TMEM44 TRAFD1 | |||||||||
| 4 | F/80 | MDS with 5q− since 2 y | Terminal ileum, 3 cm | Karyotype: NA IHC: CD34+, CD117+, muramidase+, MPO+ | Novel variants detected* in: NFE2 (p.D332N) | Karyotype: NA BM morphology: MDS, 4% blasts. Hb 111, WBC 2.3, ANC 0.4, Plt 129 | NA | Surgery due to ileus No further treatment | Died after 4 mo | |
| 5 | M/36 | Diabetes | Sub-mandibular tumor, 3 cm. | Karyotype: NA IHC: CD34−, CD117−, CD56+, muramidase−, MPO− | Novel variants detected* in: No variant detected in NFE2 | Karyotype: NA BM morphology: MDS EB1. Hb 137, WBC 10, ANC 9.4, Plt 344. | NA | AML-type chemotherapy | Allogeneic SCT. Alive | |
| 16 | F/69 | None | Vagina, cervix, 4 cm, with hydronephrosis | Karyotype: NA IHC: CD34−, CD117+, muramidase+, MPO− | Novel variants detected* in: No variant detected in NFE2 | Karyotype: NA BM morphology: MDS EB2. 11% blasts, abnormal monocytes. Hb 100, WBC 4.9, ANC 3.0, Plt 248 | NA | Nephrostomy. AML-type chemotherapy. CR | Local relapse at 10 mo. BM normal. Chemorefractory. Dead | |
| 17 | F/70 | PV since 12 y, P32 thrice, MF 1 y | Tonsil 3 × 2 cm + neck nodes | Karyotype: NA IHC: CD117+, MPO+ | Novel variants detected* in: NFE2 (p.A133V) | Karyotype: NA BM morphology: post PV-MF, cellularity 80%, no blast increase. Hb 120, WBC 3.2, ANC 2.0, Plt 81 | NA | Surgery | Two months later: WBC 29, ANC 9.1, monocytes 12.3, Plt 30. Dead | |
| Case . | Sex/age, y . | Medical history . | MS site and size . | MS . | BM at MS diagnosis . | Therapy . | Subsequent clinical history . | |||
|---|---|---|---|---|---|---|---|---|---|---|
| Cytogenetics and phenotype . | Variants detected by WES . | Cytogenetics and hematology . | Variants detected by WES . | |||||||
| 1 | F/59 | BMI 31 Concomitant serous adenocarcinoma of the ovary. | Vagina, cervix 5 × 4 cm | Karyotype: 46,XX IHC: CD34−, CD117+, CD56−, muramidase-, MPO−, CD61−, glycoA− | Variants detected in AML-associated genes: DNMT3A (p.V704fs) FLT3 (p.Y572C) NPM1 (p.W288fs) | Karyotype: 46,XX BM morphology: normal FCM: normal Normal CBC | Variants detected in AML-associated genes: DNMT3A (p.V704fs) | Daunorubicin + cytarabin. Surgery. Carboplatin + paclitaxel for ovarian cancer | Development of overt AML in the BM 28 mo after diagnosis. Dead | |
| Novel variants detected in: APOB CDH23 CMYA5 ETFDH FAM227B GIGYF2 LOC100128326 | MGA NFE2 (p.R272Q) PCDHGA1 PNPT1 PTEN RPL5 SETD2 STARD8 TTN | |||||||||
| 2 | F/59 | BMI 46. Subtotal hystero-oophorectomy with myoma and ovarian cysts. Ulcerative colitis | Cervix, uteri 9 × 7 cm | Karyotype: 46, XX IHC: CD34−, CD117+, muramidase−, MPO−, CD61−, glycoA− | Variants detected in AML-associated genes: DNMT3A (p.R320) IDH2 (p.R140Q) NPM1 (p.W288fs) | Karyotype: 46,XX BM morphology: normal FCM: normal Normal CBC | Variants detected in AML-associated genes: DNMT3A (p.R320*) Novel variants detected in: NFE2 (p.Y99fs) ODF1 TRAFD1 | Daunorubicin + cytarabin. | Development of overtAML in the BM 8 mo after diagnosis. Dead | |
| Novel variants detected in: BPIFB3 CKMT1 CLASP1 DLEC1 KCNB1 LPCAT2 MAMSTR | MASP2 NFE2 (p.Y99fs) ODF1 PCLO PRAMEF1 SEMA5A SOS1 TMEM44 TRAFD1 | |||||||||
| 4 | F/80 | MDS with 5q− since 2 y | Terminal ileum, 3 cm | Karyotype: NA IHC: CD34+, CD117+, muramidase+, MPO+ | Novel variants detected* in: NFE2 (p.D332N) | Karyotype: NA BM morphology: MDS, 4% blasts. Hb 111, WBC 2.3, ANC 0.4, Plt 129 | NA | Surgery due to ileus No further treatment | Died after 4 mo | |
| 5 | M/36 | Diabetes | Sub-mandibular tumor, 3 cm. | Karyotype: NA IHC: CD34−, CD117−, CD56+, muramidase−, MPO− | Novel variants detected* in: No variant detected in NFE2 | Karyotype: NA BM morphology: MDS EB1. Hb 137, WBC 10, ANC 9.4, Plt 344. | NA | AML-type chemotherapy | Allogeneic SCT. Alive | |
| 16 | F/69 | None | Vagina, cervix, 4 cm, with hydronephrosis | Karyotype: NA IHC: CD34−, CD117+, muramidase+, MPO− | Novel variants detected* in: No variant detected in NFE2 | Karyotype: NA BM morphology: MDS EB2. 11% blasts, abnormal monocytes. Hb 100, WBC 4.9, ANC 3.0, Plt 248 | NA | Nephrostomy. AML-type chemotherapy. CR | Local relapse at 10 mo. BM normal. Chemorefractory. Dead | |
| 17 | F/70 | PV since 12 y, P32 thrice, MF 1 y | Tonsil 3 × 2 cm + neck nodes | Karyotype: NA IHC: CD117+, MPO+ | Novel variants detected* in: NFE2 (p.A133V) | Karyotype: NA BM morphology: post PV-MF, cellularity 80%, no blast increase. Hb 120, WBC 3.2, ANC 2.0, Plt 81 | NA | Surgery | Two months later: WBC 29, ANC 9.1, monocytes 12.3, Plt 30. Dead | |
Variants with a variant allele frequency (VAF) >10% were first identified in the myelosarcoma, and subsequently their VAFs were determined in the corresponding bone marrow (BM); only variants with a VAF >5% are shown.
ANC, absolute neutrophil count 109/L; BM, bone marrow; BMI, body mass index; CBC, complete blood count; CD, cluster of differentiation; CR, complete remission; EB, excess blasts; F, female; FCM, flow cytometry; GlycoA, glycophorin A; Hb, hemoglobin, g/L; IHC, immunohistochemistry; M, male; MDS, myelodysplastic syndrome; MF, myelofibrosis; MPO, myeloperoxidase; NA, not available; Plt, platelet count 109/L; PV, polycythemia vera; P32, phosphorus-32; SCT, stem cell transplant; WBC, white blood cell count, 109/L.
No whole exome sequencing was performed, only targeted analysis of NFE2.