Blood and BM Path Chapters 20-21 - MDS and MDS/MPN Flashcards
Diagnostic flow diagram in suspected MPN
The bone marrow in MDS is usually ____
The bone marrow in MDS is usually hypercellular
It is characterized by ineffective hematopoiesis, not asplasia
Defining features of MDS with refractory anemia/thrombocytopenia/neutropenia
Dyshematopoiesis in one, two, or all three lineages. (If 2 or more linages, diagnosed as “with multilineage dysplasia”)
<5% bone marrow blasts.
<1% peripheral blasts.
Not meeting criteria for another category.
Defining features of MDS with refractory anemia and ringed sideroblasts
Dyshematopoiesis in erythrocytes.
<5% bone marrow blasts.
<1% peripheral blasts.
Ringed sideroblasts comprising >15% of bone marrow erythroblasts
Defining features of MDS with excess blasts
Dyshematopoiesis in one, two, or all three lineages.
EB stage I: 5-9% blasts in the bone marrow and <5% circulating blasts
EB stage II: 10-19% blasts in the bone marrow or >5% circulating blasts or Auer rods in a blast
If dysplasia is present, >20% BM blasts automatically puts you in AML with myelodysplastic features
Defining features of CMML
Meeting criteria for any diagnosis of myelodysplastic syndrome
plus
> 1 × 109/L absolute monocytes/promonocytes in peripheral blood
“Minimum” diagnostic criteria for MDS
Evidence of dysplasia in >10% of cells of a given lineage in the bone marrow, in the appropriate clinical context
Translocations and diagnosis of MDS vs AML with myelodysplastic features
The holy trinity of hematology, t(15:17), inv(16)/t(16;16), and t(8;21) automatically get a diagnosis of AML irrespective of their blast count.
Any other translocation, including t(9;11), t(6;9), inv(3)/t(3;3), and t(1;22), still need to meet the >20% bone marrow or circulating blasts criterion to qualify as AML. Otherwise, these are diagnosed as MDS with recurrent genetic anomalies. However, they may become a diagnosis of AML on 2 month follow-up biopsies.
MDS with del(5q)
Form of MDS with recurrent genetic anomalies
Usually associated with anemia, but normal or even increased platelet count. No or rare blasts in BM.
BM will have normal to increased number of megakaryocytes, but significant megakaryocyte dysplasia with monolobed nuclei is typically present.
This phenotype is due to loss of RPS14, ribosomal protein S14, a component of the 40S ribosome. Selective loss of this gene also produces this phenotype.
Autoimmunity in patients with MDS
~10% of patients with MDS have or develop comorbid autoimmune conditions
The TSG interferon regulatory factor-1 (IRF-1) has been linked to this phenomenon. It is frequently overexpressed in MDS, and high expression predisposes to autoimmunity.
Elevated serum __ is a poor prognostic factor for MDS
Elevated serum LDH is a poor prognostic factor for MDS
DDx for dysgranulopoiesis
- GCSF / GMCSF therapy
- Viral infections (HIV, EBV)
- Paraneoplastic condition
- Immediately post-chemotherapy
-
Drug-induced
- Bactrim
- Mofetil
- Clozapine
- Methimazole
- Prophythiouracil
- Dapsone
- Beta lactams
- NSAIDs
- Anticonvulsants
DDx for dysmegakaryocytosis
Infections (HIV)
Myelofibrosis (paraneoplastic or autoimmune)
Post-transplant
Post-chemotherapy
Best staining method to evaluate for MDS
Giemsa-Wright
This allows you to see both granulation in neutophils and basophilic stippling in red cells.
Sideroblastic anemia as a “microcytic anemia”
Many textbooks list it this way, but this only applies for hereditary or lead-induced sideroblatic anemia – NOT MDS
Acquired Hgb H disease
Can rarely occur in the setting of myelodysplasia
This will appear as a perponderance of small, hypochromic red cells in the presence of normal iron studies. These cells will be even more hypochromic than IDA – they will have only a thin lining of red around the periphery, with a ratio of ~1:4 or ~1:5.
Brilliant cresyl blue stain will reveal the characteristic “golf ball” inclusions
Associated eosinophilia or basophilia in MDS
Portends a poor prognosis
MDS with fibrosis
Arbitrarily defined as a “moderate to severe” increase in reticulin fiber in the setting of MDS
Diagnosed via reticulin silver stain on trephine biopsy
What’s wrong with this picture?
This is clearly an erythyroid nest, but none of the cells are immature! What you want to see is nests with cells in various stages of maturation.
This is evidence of dyserythropoiesis.
Paratrabecular megakaryocytes
Pretty atypical
Suggestive of myelodysplasia
Clues to secondary myelodysplasia
In secondary cases, stroma is usually affected too:
- Reticulin deposition
- Stromal edema
- Interstitial leakage of red cells
- In severe cases, gelatinous change (alcian blue positive)
Evidence of prior tissue necrosis also helps:
- Collagen fibrosis
- Dead bone trabeculae
- Dystrophic calcification
A repair-type inflammatory infiltrate is also suggestive:
- Activated efferocytosing macrophages (gobbling up debris)
- Perivascular plasma cell infiltrate
- Reactive lymphoid follicles or granulomas
MDS with del(17p)
Characterized by myelodysplasia with small, vacuolated neutrophils with monolobed nucleus (Pseudo Pelger-Huet anomaly)
MDS with del(20q)
Characterized by relatively minimal dysplasia that tends to have more pronounced thrombocytopenia, mimicking ITP
Morphologically, associated with small vacuolated, hypogranular myeloid cells/PMNs that demonstrate erythrophagocytosis
MDS with mutated Tet2
Positive prognostic factor for MDS
Present in ~20% of cases
MDS with mutated nRAS
Poor prognosis
10-15% of cases
MDS with mutated PIG-A
Yes, the same PIG-A as PNH
This group of patients is thought to have an immunologic component to their disease – they have low rates of progression to AML and tend to respond well to immunosuppression.
Therapy of choice for MDS with del(5q)
These patients respond quite well to lenalidomide, an immunomodulator with pleiotropic effects
It is thought that its efficacy in del5q is explained by its upregulation of SPARC (a tumor suppressor lost with del5q) and its anticytokine signaling activity.
Therapy of choice for most MDS
5-azacytodine has become accepted as the superior chemotherapeutic for treating MDS, however this only extends the median prognosis from 15 months to 25 months. Decitabine has similar results. They have largely replaced cytarabine for this purpose.
Immunosuppression is effective in young patients with cytogenetically normal MDS without longstanding transfusion requirement.
HSC transplant is the only definitive cure for MDS.
Dr. Hasserjian’s “holt trinity” of MDS stains
p53, CD34, CD61
Dysmyelopoiesis in the setting of marrow lymphoma involvement
When lymphomas involve the bone marrow, you can sometimes see morphologic changes associated with dysmyelopoiesis even without cytopenias.
These changes should not necessarily be interpreted as myelodysplastic syndrome, and may simply be reactive changes in the setting of the lymphoma – paricularly a T cell lymphoma.
MDS with acquired alpha thalassemia
Alpha thalassemia myelodysplastic syndrome (ATMDS)
Associated with mutations in the epigenetic regulator ATRX.
Congenital heterozygous loss is also found and is a rare cause of alpha thalassemia, however is not known to be cancer-associated. Homozygous loss is incompatible with life. As the name suggests, the gene is X-linked.
Loss of ATRX results in activation of alternative telomere lengthening pathways and a variety of other complex epigenetic phenomena.
