2 hematopathology 1: Myeloid and Lymphoid Bone Marrow Disorders (mike) Flashcards
What is a chronic myeloproliferative disorder with increased neutrophils and granulocytic precursors? Is there an increase in basophils? Is it common in children?
- CML
- Yes, this is a key characteristic
- No- and its only 15% of leukemias in adults
What are some possible symptoms of CML?
lethargy, fatigue, weight loss, splenomegaly
What do we see in the peripheral blood in CML? What about the bone marrow?
- leukocytosis, left shift with full range of myeloid progenitors, ABSOLUTE BASOPHILIA.
- hyper cellular with increased myeloid:erythroid ratio
What do the megakaryocytes look like in CML?
small hypolobate
Shotened chromosome 22 is known as the what?
philadelphia chromosome
t(9;22)
What type of enzyme is ABL? what happens when it is fused to BCR? what do we treat with?
- Tyrosine Kinase
- enzyme becomes constitutively activated–> downstream proliferation and differentiation
- Imatinib
Since new drug findings, what is the current prognosis of CML?
full life expectancy
what is a clonal lymphoproliferative disorder of mature lymphocytes?
CLL
What is expressed in CLL?B-
B-cell neoplasms which express mature B-cell antigens, monotypic kappa or lambda light chains, and ABERRANTLY EXPRESS CD5.
Is CLL indolent or aggressive? is it more common in males or females?
- Indolent
2. males
Is generalized lymphadenopathy common in CLL?
50-60% will have along with lymphocytosis, liver and spleen involvement
What cells do we see on a peripheral blood smear of CLL patient?
- monomorphous small mature lymphocytes with clumped chromatin
- smudge cells
Bone marrow biopsy in CLL will show nodular, interstitial or diffuse involvement by what cells?
small mature lymphocytes with predominantly round nuclei.
What is a clonal myeloid stem cell disorder with cytopenias, ineffective hematopoiesis, and dyspoiesis? what is the increased risk of transformation to in this case?
- myelodysplastic syndromes
2. AML
What is abnormal morphologic features in the maturing myeloid, erythroid and megakaryocytic cells?
- Dyspoiesis
How do people present with Myelodysplastic Syndromes? what do 1/3 of patients progress to?
- 50% with infections, hemorrhage and fatigue and 50% asymptomatic
- acute leukemia
Review the WHO classification of MDS-
Classification based on
–Number of blasts in peripheral blood and bone marrow
–Cytologic features•Ring sideroblasts•Dyspoiesis in one, two or all three cell lines
–Cytogenetic abnormalities
What is the morphology of MDS?
Pancytopenia with dyspoietic features of RBCs, granulocytes, platelets/megak.
you may also see increased myeloblasts
Dimorphic red cells is very prominent in MDS blood smears- what are the two distinctly different morphologies?
- normochromic normocytic
2. hypochromic microcytic
What is dysgranulopoiesis?
hypersegmented neutrophils, hypolobate, hypogranular
should be able to compare with normal neutrophils on same slide to ensure that it is not just a poor stain
Review the types of dyserythropoiesis?
nuclear budding, nuclear irregularity, megaloblastic change (nuclear to cytoplasmic dyssynchrony), multinucleation, ring sideroblasts
In dysmegakaryopoiesis , what does the megakaryocytic look like?
small hypolobate or widely spaced nuclear lobes
Are specific translocations common in MDS?
No- trisomies and deletions are common
What are clonal proliferations of multi potent myeloid stem cells resulting in an increased number of differentiated granulocytes, RBCs or platelets?
Chronic myeloproliferative neoplasms- The disorders have an acquired defect of the proliferative control of the stem cell.
What are the 4 types of chronic myeloproliferative neoplasms?
- CML
- polycythemia vera
- essential thrombocythemia
- primary myelofibrosis
what major mutation leads to increased proliferation of bone marrow cells?
JAK2 V617F
most patients with polycythemia vera and approximately half the patients with essential thrombocythemia or primary mrelofibrosis
What is chronic myeloproliferative disorder associated with thrombocytosis and increased megakaryocytes in the bone marrow.?
Essential thrombocythemia-
Platelet counts can range from slightly above normal to several million/ul.
How does essential thrombocythemia present?
thrombosis or hemorrhage, splenomegaly in 50%
How does essential thrombocythemia present?
what does a blood smear show?
what does a bone marrow aspirate show?
- thrombosis or hemorrhage, splenomegaly in 50%
- increased an large platelets
- very large and atypical megakaryocyte
what is clonal myeloproliferative neoplasm characterized by a proliferation of predominantly megakaryocytes and granulocytes in the bone marrow that in fully developed disease is associated with reactive deposition of fibrous connective tissue and with extramedullary hematopoiesis?
primary myelofibrosis
progressive splenomegaly
median survival=3 years
5-20% progress to leukemia
What is the blood morphology of primary myelofibrosis?
- anemia with teardrop red blood cells
2. leukoerythroblastic reaction- immature myeloid cells and nucleated RBC circulating
What are the two types of bone marrow morphology found in primary myelofibrosis?
- cellular stage with up neutrophils and clusters of atypical megakaryocytes
- fibrotic stage- with intrasinusoidal hematopoiesis
What type of appearance does the bone marrow have in fibrotic star of primary myelofibrosis?
has streaming appearance due to reticulin fibrosis
What is an important gross anatomical feature of primary myelofibrosis?
marked splenomegaly- extra medullary hematopoiesis is taking place
What is a clonal proliferation of terminally differentiated B cells capable of secreting immunoglobulin or portions of immunoglobulin? what is the monoclonal immunoglobulin called?
- plasma cell neoplasms
2. M-protein or monoclonal protein- seen on serum protein electrophoresis
Review the 3 types of plasma cell neoplasms
Monoclonal gammopathy of undetermined significance
plasmacytoma
plasma cell myeloma
What is characterized by a solitary bone lesion or extra osseous lesion> what are the common extra osseous sites? How do we treat?
- solitary myeloma-plasmacytoma
- lung, pharynx, nasal sinuses
- radiation
Where does plasma cell myeloma originate?
bone marrow- involvement of the skeleton at multiple sites
What are the symptoms for plasma cell myeloma?
CRAB hyper calcemia renal insufficiency Anemia/Amyloid symptoms bony lytic lesions
ALSO- RECURRENT INFECTIONS
In asymptomatic plasma cell myeloma, what are we typically looking for?
significant M-protein in serum
significant bone marrow involvement
What is a classic finding in plasma cell myeloma on blood smear?
Rouleaux formation- linear arrays of red cells
T-F-Plasma cells in myeloma may be either mature/normal or immature?
True
what are the features of mature normal plasma cell morphology?
eccentric nuclei
perinuclear hof/golgi clearing
clumped chromatin
mod. abundant cytoplasm
What are the features of abnormal/immature plasma cells?
nuclear enlargement
prominent nucleoli
Is treatment of myeloma curative?
No
What general classes of drugs have increased survival in multiple myeloma from 3 to >8 years?
- immune modulators
- proteasome inhibitors
- autologous stem cell transplant tech too.
