Myelodysplastic Syndrome

Today, we discussed a case of a 29 year-old man who presented with mild hemoptysis, bleeding gums, and orthostatic symptoms, found to have platelets 25, Hgb of 6.9, WBC 11.7 with 2% circulating blasts and pseudo Pelger-Huet cells (see below) on peripheral smear--and bone marrow biopsy demonstrating hypercellularity (95%) with multilineage dysplasic morphology and FLT3 positivity on cytogenetics--overall consistent with a new diagnosis of high risk myelodysplastic syndrome.

A few of learning points from this case:

1) Myelodysplastic syndrome is on a spectrum with acute myeloid leukemia. A diagnosis of AML rather than MDS is made in patients with AML-consistent cytogenetics and a peripheral blast count of <20% (which is arbitrary).

2) The combination of thrombocytopenia and anemia should trigger an initial differential including :

  • Sepsis with disseminated intravascular coagulation (DIC)
  • TTP, HUS, or DITMA
  • Autoimmune disorders (eg, Felty's syndrome)
  • Nutrient deficiencies (eg, folate, vitamin B12, copper)
  • Infections
  • Bone marrow disorders (eg, myelodysplastic syndromes, leukemia, bone marrow infiltration by malignancy

3) Standard of care for high risk MDS is bone marrow transplant.

A neutrophil with pseudo-Pelger-Huet nucleus (aka "Aviator nucleus" per Dr. Lachowiez given it's sunglasses appearance) with decreased lobes that are connected by a thin strand giving a "pince-nez" appearance. This neutrophil also has markedly reduced granulation, a finding commonly seen in MDS.

A neutrophil with pseudo-Pelger-Huet nucleus (aka "Aviator nucleus" per Dr. Lachowiez given it's sunglasses appearance) with decreased lobes that are connected by a thin strand giving a "pince-nez" appearance. This neutrophil also has markedly reduced granulation, a finding commonly seen in MDS.

Illness script for Myelodysplastic Syndrome:

  • Epidemiology/predisposing conditions: In older adults with a median age at diagnosis of ≥65 years and a male predominance often with an exposure to environmental factors (eg, chemicals, particularly benzene, radiation, tobacco, or chemotherapy drugs)--or--with inherited genetic abnormalities (eg, trisomy 21, Fanconi anemia) or other benign hematologic diseases (eg, PNH)
  • Pathogenesis: The stepwise acquisition of oncogenic driver mutations thought to develop from a single transformed hematopoietic progenitor cell that has acquired multiple mutations resulting in clonal dysplasia and ineffective hematopoieses
  • Clinical Manifestations: Typically presenting as asymptomatic or with nonspecific signs and symptoms of cytopenias (most commonly from anemia with fatigue, weakness, dizziness, angina, etc--but also infections due to neutropenia and granulocyte dysfunction) 

Check out this great review article on MDS in NEJM from 2009.