CASE 106. Pancytopenia in the setting of marrow hypoplasia, a PNH clone, and a DNMT3A mutation
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1 CASE 106 Pancytopenia in the setting of marrow hypoplasia, a PNH clone, and a DNMT3A mutation Gabriel C. Caponetti, MD University of Pennsylvania, US
2 Clinical history 69, F peripheral neuropathy, refractory dermatitis osteopenia (1 year) Medications: Vit. D, Calcium carbonate-vit. D, Gabapentin Recently: bruising and petechiae on her arms chest tightness improved after a red blood cell transfusion pancytopenia
3 Laboratory values (8 12/2016) Hb 11,4 (6,8) g/l retikulocytes 3% Platelets K/uL WBC 3-2 K/uL Abs. neutrophil count 1,8-0,23 K/uL Serum Ferritin: 240 ng/ml (Ref. range: 12 to 150 ng/ml) Haptoglobin: <30 mg/dl (low) (Ref. range: mg/dl) LDH: 276 U/L (Ref. range: U/L) Coombs Test: IgG and C3 negative; G6PD Screen: Normal
4
5 Myeloid and erythroid elements full maturation and no dysplasia Megakaryocytes not identified The myeloid to erythroid ratio 2:1 No ring sideroblasts
6 Granulocytes Red cells Red blood cells Partial CD59 deficiency (Type II) 0.8% Complete CD59 deficiency (Type III) 1.7% Total RBC PNH clone 2.4% Granulocytes FLAER/CD24 deficient clone 11.1%
7 Conventional cytogenetics:46,xx[20] DNA Sequencing(Bone Marrow) GENE PROTEIN cdna CHANGE CHANGE DNMT3A p.l595p c.1784t>c Allele frequency: 22%.
8 CASE DR. CAPONETTI PANEL DIAGNOSIS Hypocellular bone marrow with paroxysmal nocturnal hematuria clone, and clonal cytopenia of undetermined significance (CCUS), suggestive of evolving aplastic anemia
9 CASE 201 Isolated vertebral pain and 12% JAK2 V617F allelic burden: myeloproliferation of undetermined significance? Alexandar Tzankov Basel, Switzerland
10 Clinical history M, 47 isolated pain in the 1 lumbar vertebra PET-CT: FDG-avid lesion in the L1 vertebrum no osteolysis, no osteosclerosis normal peripheral blood values slightly decreased erythropoietin 3.6 IU/L
11 Biopsy from the painful vertebral lesion Focal bone pain-causing myeloproliferation of undetermined significance
12 PAS, «staging biopsy» the iliac crest - normal
13 Genetic studies 46, XY JAK2 V617F mutation allelic burden: 12% peripheral blood 2% BM (iliac crest) vertebral lesion not examined Focal bone pain-causing JAK2+ myeloproliferation of undetermined significance
14 pstat5 Vertebra Iliac crest
15 Follow-up aspirin 100mg/day watch-wait strategy - check-up 1/6 months a recent case, no follow-up data
16 CASE 201 DR. TZANKOV PANEL DIAGNOSIS myeloproliferative neoplasm, unclassifiable
17 CASE 311 Myeloid Neoplasm Associated with Trisomy 8 and SRSF2 and IDH2 mutations Enrique Ballesteros University of Connecticut, US
18 67, M Clinical history anemia and thrombocytopenia rheumatoid arthritis on methotrexate and steroids (since 2011) marginal zone lymphoma of the conjunctiva treated with low-dose radiation (2005; no chemo) no lymphadenopathy or splenomegaly
19 Laboratory values HGB 10.2 g/dl; MCV 84 fl PLT 113 K/uL WBC 14.1 K/uL abs. neutrophil count 11.8 K/uL; abs. monocyte count 0.8 K/uL
20
21 Reticulin slightly increased No increase of CD34+ blasts
22 Cytogenetics: 47, XY, +8 [14/20] Trisomy 8 - common in MDS (10%), but not definitive evidence for MDS in the absence of morphological criteria
23 Molecular studies - peripheral blood Next Generation Sequencing - mutation analysis SRSF2 c.284c>a, p.pro95his; VAF: 47.2% IDH2 c.419g>a, p.arg140gln; VAF: 46.0% known significance in myeloid malignancies Negative: JAK2, MPL, and calreticulin mutations, BCR/ABL rearrangement
24 Interesting features - borderline case persistent cytopenias, hypercellular BM, dysplasia in <10% of cells, and clonal cytogenetic and molecular findings (trisomy 8 in BM and SRSF2 and IDH2 mutations in PB) open the question of MDS, unclassifiable? therapy-related myeloid neoplasm radiation? low-dose radiation to the anterior orbit 3 weeks x risk of 2 nd cancers with low-dose radiation to orbit - small sustained neutrophilia? chronic steroid therapy effect? megaloblastoid changes? related to methotrexate?
25 Follow-up active surveillance blood counts stable not required transfusions or growth factors chief complaint: rheumatoid arthritis cont. prednisone + methotrexate
26 CASE 311 DR. BALLESTEROS PANEL DIAGNOSIS Hypercellular bone marrow on active therapy, not diagnostic of MDS or MDS/MPN, reccomend repeat bone marrow biopsy after stopping methotrexate
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