MDS

Question 1

Blood film features of dysplasia:

Answer 1

Red cell anisocytosis, poikilocytosis, basophilic stippling
Myeloid nuclear hypolobulation, pseudo Pelger Huet, hypogranulation
Myeloblasts
Platelet anisocytosis

Question 2

BMAT features of dysplasia

Answer 2

Erythroid binuclearity, internuclear bridging, irreg nuclear edge, megaloblastoid changes, ring sideroblasts, cytoplasmic inclusions, cytoplasmic bridging, incomplete haemoglobinisation, fringed cytoplasm or vacuolisation.
Myeloid bizarre nuclear shapes, pseudo pelger huet, nuclear hypersegmentation, Chédiak–Higashi granules, cytoplasmic hypogranulation, anisocytosis
Megakaryocytes - large monolobular forms, small binuclear forms, micromega, degranulation
Excess myeloblasts

Diagnostic = pseudo pelger huet and micro mega

Iron: >5 siderotic granules 1/3 nuclear circumference in >15% erythroid cells.

Question 3

Recurrent chromosomal abnormalities presumptive diagnosis of MDS

Answer 3

-5 del5q
-7 del7q
i(17q) t(17p)
Del of 11q 12p 13q

Question 4

Commonly mutated genes in MDS

Answer 4

SF3B1
TET2
RUNX1
ASXL1
SRSF2
TP53
NRAS KRAS
U2AF1

Question 5

2022 WHO Classification of MDS

Answer 5

I. MDS with defining genetic abN
* Low Blasts (< 2% PB and < 5% BM)
* MDS with LB and del5q
* MDS with LB and SF3B1/RS
* MDS with biTP53

II. MDS morphologically defined
* MDS-LB
* MDS-LB-SLD
* MDS-LB-MLD
* MDS-h
* MDS-IB
* MDS-IB1 (2-4% PB and 5-9% BM)
* MDS-IB2 (5-19% PB and 10-19% BM or Auer rods)
* MDS-f (MF2-3)

Question 6

Prognosis in MDS

IPSS

Answer 6

IPSS
1. Hb, Plts and Neutros
2. Blast%
3. Cytogenetics

Question 7

Treatment approach in MDS

Answer 7

I. Low risk:
1. Supportive (EPO, T/F, GCSF, anti-fungal, TXA and ?TPO agonists)
2. Specific
* MDS-LB-del5q = Len
* MDS-LB-SF3B1 = Luspartasep
* Pancytopenia with no del5q/SF3B1 = Azacitidine
* ATG and Ciclosporin = MDSh

II. High risk:
1. Trial
2. Chemo
3. Azacitidine

±AlloHSCT

Question 8

Features of MDS-LB-del5q

Answer 8

• Erythroid hypoplasia
• Plts and Megs hyperplasia and dysplasia
• Int prognosis
• Tx = Len

Question 9

Features of MDS-LB-SF3B1

Answer 9

• Erythroid hyperplasia and dysplasia and RS
• No > Plts
• Best outcome
• Tx = Luspartasept

Question 10

Features in MDS-biTP53

Answer 10

• >er blasts
• fibrosis
• Worst prognosis (AML t/f)

Question 11

If you think MDS-IB rule out…

Answer 11

1. AML
2. biTP53

Question 12

Diagnostic criteria of MDS

Answer 12

I. Cytopenias (4+ mo)
* Hb < 13 M, < 12 F
* Neutrophilia < 1.8
* Plt < 150

AND

II. Dysplasia (10% of 1+ lineage)

Question 13

What is VEXAS syndrome?

Answer 13

• Acquired mutation
• X-chr
• UBA1 gene - E1 Ubiq Act Enz
• Regulation of proteins - Cel division, imm response, etc.

V = Vacuoles
E = E1 Ubiq Act Enz
X = X-linked
A = Auto-inflammatory
S = Somatic mutation