myeloproliferative disorders Flashcards
What are the basic prinicples of myeloproliferative disorders?
neoplastic disorders of mature myeloid cells, usually seen in 50s-60s. cells from all myeloid lineages are increased; the disease is characterized by the predominant cell type. causes a hypercellular bone marrow with incr. WBC count. Jak-2 mutations are common.
complications: high cell turnover may lead to hyperuricemia and gout. myeloproliferative disorders may also transform into acute leukemia, or cause marrow fibrosis.
chronic myeloid leukemia
neoplastic proliferation of myeloid cells, especially granulocytes. basophils are characteristically increased. platelets also up.
driven by a 9,22 Bcr-Abl translocation that produces an activated tyrosine kinase. first line tx is imatinib (blocks tyrosine kinase activity).
splenomegaly is a common problem and may mark transformation the accelerated phase of the disease. CML can progress to AML (2/3 of cases) or ALL (1/3 of cases)- the mutation is in a pluripotent stem cell.
How can you distinguish between CML and the leukemoid rxn?
leukemoid rxn: reactive proliferative leukocytosis.
CML has increased basophils and a t(9,22) translocation. CML does NOT have a leukocyte alkaline phosphatase (LAP) stain.
leukemoid rxn is the opposite.
polycythemia vera
proliferation of RBCs, as well as platelets and granulocytes. almost always associated with a JAK2 mutation.
symptoms are due to blood viscosity: blurry vision/headache, flushing, itching after a warm shower (d/t histamine release), increased venous thrombosis risk (hepatic vein, portal vein, dural sinus), erythromelalgia (severe burning pain and reddish/bluish coloration d/t episodic blood clots in vessels of extremities).
treatment: phlemobotomy, hydroxyurea (second line; also used in sickle cell to promote more fetal Hb. decreases the production of deoxyribonucleotides).
how do you distinguish between polycythemia vera and reactive polycythemia?
- PV: low EPO, normal SaO2.
- reactive polycythemia from high altitudes or lung disease: high EPO; low SaO2
- reactive polycythemia from renal carcinoma: high EPO, normal SaO2
essential thrombocythemia
neoplastic proliferation of mature myeloid cells, esp. platelets. RBCs and granulocytes are normal-high. often associated with a Jak-2 mutation.
symptoms are related to incr. risk of bleeding and/or thrombosis. however, this disease does not have hyperuricemia/gout and only rarely progresses to acute leukemia or marrow fibrosis.
myelofibrosis
neoplastic proliferation of mature meyloid cells, esp. megakaryocytes. often associated with a JAK2 mutation. megakaryocytes produce PDGF, causing marrow fibrosis. RBCs, down. clinical features: splenomegaly from extramedullary hematopoeisis, leukoerythroblastic smear (tear drop RBCs, nucleated RBCs, immature granulocytes). incr. risk of infection, thrombosis, bleeds.
multiple myeloma definition
malignant proliferation of plasma cells within the bone marrow. this is the most common primary malignancy of bone (though mets are the most common bone malignancy overall).
high levels of IL-6 may be present, which help to stimulate plasma cell growth and immunoglobulin production.
multiple myeloma clinical features
- bone pain and hypercalcemia. malignant plasma cells activate RANK on the osteoclasts, leading to lytic bone lesions. especially common in the skull and vertebrae. can cause fracture.
- Rouleux formation on peripheral blood smear- stacked RBCs (due to decreased charge btw RBCs)
- changes to serum protein electrophoresis- increased M spike. usually due to one type of IgG or IgA.
- infection because monoclonal antibody lacks antigenic divesity. most common cause of death.
- free light chains are excreted in the urine as Bence-Jones proteins. can cause renal damage if it deposits in tubules.
- primary AL amyloidosis: free light chains circulate in the serum and deposit in tissues.
(CRAB: calcium high, renal failure/bence jones, anemia/amyloidosis, bone lesions)
MGUS
monoclonal gammopathy of undetermined significance. increased serum protein with M spike of serum protein electrophoresis. other features of multiple myeloma, like lytic bone lesions, amyloidosis, Bence-Jones proteins, hypercalcemia, are absent.
common in elderly. 1% progress to multiple myeloma each year.
Waldenstrom macroglobulinemia
B cell lymphoma with monoclonal IgM production. causes: M spike on serum protein electrophoresis.
no lytic bone lesions. generalized LAD. serum hyperviscosity because IgM is so large causes visual disturbances and neuro deficits. finally, can cause bleeding- serum viscosity interferes with proper platelet aggregation. acute symptoms can be treated with plasmaphoresis
langerhans cell histiocytosis general principles
langerhans cells are modified dendritic cells in the skin. they are derived from bone marrow monocytes and present antigen to naive T cells. in langerhans cell histiocytosis, there is a malignant proliferation of langerhans cell histiocytes. characteristically, birbeck tenis rackets granules are seen on EM. Cells are CD1a+ and S100+. kid with lytic bone lesions and skin rash or recurrent otitis media with a mass involving the mastoid bone (cells don’t effectively stimulate T cells).
letterer-siwe disease
malignant prolif of langerhans cells that causes skin rash and skeletal defects in an infant (<2). many organs are involved. rapidly fatal
eosinophilic granuloma
benign prolif of langerhans cells in bone- skin not involved. usually seen as a fracture in an adolescent. biopsy shows langerhans cells with mixed inflammatory cells, including eosinophils
hand-schuller-christian disease
malignant prolif of langerhans cells. scalp rash, lytic skull defects, diabetes insipidis, and exopthalmos in a child
