Flashcards in Hematologic Malignancies IV Deck (64)
What are the key findings in the marrow in PM?
An increased number of megakaryocytes (often bizarre looking) and fibrosis.
The latter can be hard to pick up until a special stain (called a reticulin stain) is used.
Prognosis of PM?
Usually shorter survival than ET; can progress to marrow failure, acute leukemia
Increased platelet counts would lead you to think of what if you knew you were dealing with a myeloproliferative neoplasm?
ET or PM. Not polycythemia vera
Increased RBCs would lead you to think of what if you knew you were dealing with a myeloproliferative neoplasm?
What else would lead you to suspect PM if you knew you were dealing with a myeloproliferative neoplasm?
hypertension (with thrombosis)
Are mast cells circulating?
What mitogen plays a big role in mast cell growth and migration?
Neoplasms of mast cells usually present as what?
benign cutaneous lesions in kids (the most common is “urticaria pigmentosa”, aka itchy pigmented skin lesions).
They usually don’t spread beyond the skin. (Except when they do)
What happens if mast cell neoplasms spread beyond the skin? Most common site affected in this case?
In that case they release lots of histamine and other mediators, causing systemic symptoms (flushing, abdominal pain, tachycardia, hypotension) that can can really confuse the clinician.
The bone marrow is the most common site of systemic involvement, but multiple organs (lymph nodes, spleen, liver) can be involved
Whats a good diagnostic tool for mastocytosis diagnosis?
serum tryptase level.
Tryptase is one of the major mediators secreted by mast cells - but hyperactive normal ones can secrete it too.
What is the root cause of most mastocytoses?
Either cKIT mutants OR PDGFRA activation (FIP1 translocation)
prognosis is variable
What is the immunophenotype of mastocytosis?
tryptase, CD117 (cKIT, the SCF receptor), CD25 usually positive
Increased activity of a tyrosine kinase, whether in the form of a fusion protein or due to a point mutation, is getting to be a common motif in MPN’s (and in some non-hematologic malignancies), and more of them are likely to be discovered. By good luck, some of them turn out to be responsive to the same kind of drugs used to treat CML!.
That means you need to get molecular testing when an eosinophilia is thought to be myeloproliferative rather than reactive (there are many causes for a reactive eosinophilia, the most common being parasites and drug reactions).
More drugs which specifically inhibit particular kinases like Jak2 (like Imatinib) are also likely to emerge.
We have a poor understanding of myelodysplasias.
We diagnose these conditions based primarily on bone marrow morphologic findings in the context of unexplained cytopenias. Cytogenetic findings are often used as additional criteria. Describe these.
The cytogenetic findings in MDS cases are usually nonspecific, and we can’t point to any particular oncogenes as critical elements in the pathogenesis (although that could change in the next few years). There is a general sense of genetic instability as a root cause of some of them, but the details of that have not been worked out.
Clinical significance: MDS usually presents in elderly patients, and for some of them the condition does not affect actuarial survival – meaning that in some cases our therapies will harm rather than help. But for others the condition carries higher risks, and for some of those there are effective therapies available.
What are the five major adult forms of myelodysplasias? Best to worst prognosis.
-Refractory cytopenia with unilineage dyplasia
-Refractory anemia with ring sideroblasts
-Myelodysplastic syndrome with isolated del(5q)
-Refractory cytopenia with multilineage dysplasia
-Refractory anemia with excess blasts
Are there any other myelodysplasias?
Myelodysplastic syndrome, unclassifiable (Garbage can category)
Childhood MDS (Rare, complex diagnostic/prognostic issues)
What is Refractory cytopenia with unilineage dyplasia?
a relatively good player, although if it presents without cytogenetic findings there is wide variation in the proclivities of pathologists for diagnosing it.
In part that’s because some of the morphologic findings (megaloblastoid features) are nonspecific - they can also be caused by nutritional deficiencies, drugs, or HIV. And in part it’s because the morphologic features can be hard to recognize.
Diagnosis of Refractory cytopenia with unilineage dyplasia depends on what?
Clinical presentation of Refractory cytopenia with unilineage dyplasia?
unexplained cytopenia, usually elderly patients (65+)
Prognosis of Refractory cytopenia with unilineage dyplasia?
not much less than normal; rarely progresses to AML
same in refractory anemia with ring sideroblasts
What is diagnosis of Refractory anemia with ring sideroblasts dependent on?
morphologic findings and iron stain results
Is cytogenetic analysis normal in Refractory anemia with ring sideroblasts?
No, trisomies/monosomies may be present
Clinical presentation of Refractory anemia with ring sideroblasts?
unexplained cytopenia, usually elderly patients (65+)
What is unique about morphology in Myelodysplastic syndrome with isolated del(5q)?
all megakaryocytic are mononuclear
Are cytogenetics normal in Myelodysplastic syndrome with isolated del(5q)?
show ONLY loss of the large arm of chromosome 5
Clinical presentation of Myelodysplastic syndrome with isolated del(5q)?
- usually women, 65+ y/o
same in refractory cytopenia with multilineage dysplasia
Prognosis of Myelodysplastic syndrome with isolated del(5q)?
good median survival; 10% progress to AML
What can Myelodysplastic syndrome with isolated del(5q) be treated with?
What is unique about the morphology of refractory cytopenia with multilineage dysplasia?
affected granulocytes don't granulate normally; nuclei don't lobulate normally