Hematologic malignancies Flashcards
(51 cards)
Acute lymphoid leukemia pathophys
Lymphoid malignancy arising in the bone marrow
All the malignant cells are blasts
Most common malignancy in children
Mutation in hematopoietic stem cell –> immortality and blast arrest, lymphoid differentiation
Most commonly pre-B cell
ALL diagnosis
Symptoms of cytopenia
Sometimes see pancytopenia, or just 1/2 cell lines low
CBC and peripheral blood smear
Bone marrow aspirate and biopsy = diagnostic
Leukemia lymphoblasts lack specific morphological features, so dependent on immunophenotyping
Cytogenics: see Philadelphia chromosome in 25% of adult cases
Flow cytometry - show lymphoid blasts
Acute myeloid leukemia pathophys
Similar to ALL, but malignant cells are myeloid blasts
More common in adults
Primary (de novo) or Secondary (hematologic malignancies - MPD of MDS, or previous chemotherapy)
AML Diagnosis
Auer rods = pathognomonic Symptoms of pancytopenia sometimes can trigger DIC Bone marrow aspirate and biopsy with special tests, like flow cytometry Blast count >20%
Chronic lymphoid leukemia pathophys
Malignant cells are all mature lymphoid cells
Disease of older adults
Same disease as small lymphocytic lymphoma, except CLL arises in BM and SLL arises in LN
CLL diagnosis
Lymphocyte counts very high, >30% of all nucleated cells
All cells look relatively normal
Patients often asymptomatic
Symptomatic - fatigue, weight loss, anorexia
May develop cytopenia long-term
Malignant cells can spread to LN
Multiple myeloma pathophys
Malignancy of plasma cells
Massive spread leads to destruction of bone = multiple lytic lesion
Malignant cells secrete clonal immunoglobulin
MM diagnosis
Serum protein electrophoresis - single band for a single clonal antibody being overproduced
Monoclonal gammopathy (presence of M-protein), also found in urine
Bone marrow aspirate and biopsy: significantly increased plasma cells (>30%)
Plasmacytoma
Bone pain and pathologic fractures
Hypercalcemia
Renal failure - dmg from monoclonal gammopathy and hypercalcemia
Thrombocytopenia, leukopenia
Anemia - bone marrow suppression and low EPO
Recurrent infections
Lymphoma pathophys
Hematologic malignancies arising in lymphoid tissue, usually within a LN but could also be extranodal
Can spread to another LN or to BM
Hodgkin lymphoma
tumour consists mostly of reactive inflammatory cells with only rare malignant Reed-Sternberg cell lymphocytes (large multinucleated or have bilobed nucleus with prominent eosinophilic inclusion-like nucleoli)
Non-Hodgkin lymphoma
all the cells in the tumour are malignant lymphocytes
Lymphoma diagnosis
LN biopsy: excisional>needle core>fine needle aspiration
Pathology
Ann Arbor Staging:
1: single node region OR extranodal site
2: >=2 nodes OR extranodal sites on the same side of the diaphragm
3: involvement of both sides of diaphragm, including one organ or area near LN or spleen
4: disseminated involvement of >=1 extralymphatic organs, including liver, BM, lungs
Myelodysplastic syndrome pathophs
Clonal disorder affecting hematopoietic maturation
Ineffective hematopoiesis - abnormal development and many cells apoptosis
BM failure with cytopenia
Abnormal clonal cell
Can develop to AML (worse than de novo AML)
Myelodysplastic syndrome diagnosis
Anemia +/- thrombocytopenia +/- neutropenia
BM aspirate/biopsy shows hypercellular BM with dysplastic cells (e.g. abnormal nucleus)
Peripheral blood film: RBC macrocytosis with no other cause
- WBC - decreased granulocytes, abnormal morphology
Platelets: thrombocytopenia, abnormalities of size and cytoplasm
Myeloproliferative disorder pathophys
Clonal myeloid stem cell abnormalities, leading to overproduction of one or more cell lines
4 types: chronic myelogenous leukemia
Polycythemia Vera
Essential thrombocytosis
Idiopathic myelofibrosis
Chronic myeloid leukemia
myeloid malignancy arising in BM
Mutations in a hematopoietic stem cell, which must include a bcr-abl rearrangement
Most common MPD
Cells retain the capacity to mature, so see full range of myeloid maturation
Essentially every case shares the Philadelphia chromosome (t(9;22))
Chronic myeloid leukemia diagnosis
Peripheral blood smear: leukoerythroblastic - immature RBCs and granulocytes
- presence of different mid-stage progenitor cells (vs. AML)
Marrow is hypercellular
Often clustering of megakaryocytes
CML presentation
fatigue and weight loss (anemia, hypermetabolic)
massive splenomegaly (due to extramedullary hematopoiesis) with LUQ discomfort, early satiety
CBC - high neutrophil count with many immature neutrophil forms and mature neutrophils
Commonly see eosinophilia and basophilia
Polycythemia vera
Elevated RBC mass with increased white cell and platelet production
Primary: excessive RBC production from abnormal BM, without EPO stimulation (mutation of JAK2 protein binds EPO receptor, promotes signalling)
Polycythemia vera diagnosis
R/O other causes:
- Spurious polycythemia: dehydration
- true polycythemia - secondary polycythemia: marrow response to hypoxia/high EPO
- hypoxia
- high EPO
Confirm with specialized test: epo-independent stem cell colony growth assay, JAL2 mutation testing
A criteria (need at least one, + 1 more or +2 B)
- elevated red cell mass
- no hypoxia
- palpable splenomegaly
- clonal genetic abnormality other than bcr-abl
- endogenous erythroid colony formation in vitro
B
- thrombocytopenia
- leukocytosis
- BM biopsy: panmyelosis
- low serum EPO
Essential thrombocythemia
Overproduction of platelets withou stimulus
Very high platelet count: >600
Negative Philadelphia chromosome
Acquired JAK2 mutation
ET: megakaryocyte hyperplasia
Platelets can be functional/dysfunctional
Thrombotic complications or bleeding complications
Idiopathic myelofibrosis
Megakaryocytes proliferation, make platelets and platelet-derived growth factor which promotes fibrosis
Fibrosis fills marrow space
Idiopathic myelofibrosis diagnosis
Blood film: leukoerythroblastosis with tear drop RBCs, nucleated RBCs, variable polychromasia, large pltaelets and megakaryocyte fragments
BM biopsy: fibrosis, atypical megakaryocytic hyperplasia, thickening and distortion of bony trabeculae (osteosclerosis)
Initial tests for potential hematologic malignancy
"Coagulation screening panel" Liver enzymes, serum creatinine Peripheral blood smear bone marrow core biopsy Bone marrow aspirate (assess rfee cells) Flow cytometry for tumour cell characteristics Karyotype/cytogenetics/FISH/PCR for specific genetic traits CSF to assess for spread CXR for mediastinal masses/widening CT/US abdomen if concerns of lymphoma
