Hematologic Malignancies Flashcards
Cancer and Treatment
Local=surgery
Regional=Radiation
Systemic=chemotherapy
Hematological Cancers
Cancer of the blood; no solid tumor
-TNM grading system does not apply and surgery is not an option
Divided into two major types:
- leukemia
- lymphoma + myeloma
Symptoms of Hematological cancer
Can present with multiple symptoms or none at all
-tumor compression, invasion, or destruction of surrounding tissues causes symptoms–> cancer located in GI tract
Systems:
- N/V
- constipation
- diarrhea
- bloody stools
- abdominal pain
- early satiety
unexplained weight loss=more universal
7 Signs of Cancer
C: change in bladder or bowel habits A: A sore that doesnt heal U: unusual bleeding or discharge T: thickening or lump in breast or elsewhere I: indigestion or trouble swallowing O: obvious change in wart or mole N: nagging cough or hoarseness
**seek doctor
Heme Malignancy
“tumors” are uncommon
Symptoms:
- elevated/decreased blood counts (RBC, WBC, platelets)
- coagulopathies
- swollen lymph nodes
- B-symptoms: fevers, night sweats, and weight loss
- splenomegaly
- malaise
diverse and not easily identified on symptoms alone
Blood FXN
1) Transport: oxygen, carbon dioxide
- nutrients
- waste
- hormones
- ions/electrolytes
2) Protection:
- WBC
- antibodies
- platelets
3) Regulation
- body temperature
- pH
- water balance
Hematopoiesis: Bone Marrow
richly innervated, highly vascularized spongey tissue
- flat and long bones, trabecular (cancellous) bone,
Lymph Node Biopsies
whole node, fine needle aspirate, core
Bone marrow biopsy + aspirate
commonly used to examine cells for identification of various heme disorders + malignancies
- smear: direct visual examination of cells
- fluorescence in situ hybridization (FISH): chromosomal changes
- karyotype testing: chromosome map (arrangement, size, shape, number)
- flow cytometry: identification of cells; quantitative analysis
- immunophenotyping: fluorescent antibody labeled cells - immunohistochemistry (IHC): utilizes antibodies that bind to certain antigens/cell surface markers to stain protein + make visible under microscope
- polymerase chain reaction (PCR): amplification + detection of DNA segments
Hematologic Malignancies
- Essential Thrombocythemia (ET): platelets abnormal
- Polycythemia Vera (PV): red blood cells (abnormal)
- Myelofibrosis (MF): collagen and reticulin fibers (fibrosis)
- Myelodysplastic Syndromes (MDS): immature blood cells
- Acute Myelogenous Leukemia (AML): immature white cells
Leukemia
produce poorly differentiated cells; derived from disruption in hematopoiesis
- involved cells may have features of any phase of myelocytic or lymphocytic maturation depending on hematopoiesis maturation
- can develop at any stage, any cell line
- uncontrolled production of precursor WBC that cannot mature but can proliferate
- survival advantage over normal cells “crowding out” phenomenon of normal cells in marrow
- Common Myeloid Progenitor
- Common lymphoid progenitor
Presentation
Diagnosis
- Acute myelogenous leukemia (AML), chronic myelogenous leukemia (CML)
- Acute lymphoblastic leukemia (ALL), chronic lymphoblastic leukemia (CLL)
- fatigue, weight loss, anemia, thrombocytopenia, leukopenia OR leukocytosis, splenomegaly, hepatomegaly
- CBC, bone marrow aspirate + biopsy, molecular testing for FMS-like tyrosine kinase 3 (FLT3), nucelophosmin (NPM1)
Genetic alterations in leukemias
- activation of protooncogene to signal increased proliferation
- loss of differentiation signals
- loss of tumor suppressor genes (P53)
- loss of apoptotic signals
Potential chromosomal alterations
- numerical (duplication/deletion)
- inversion (exchange of genetic info within)
- translocation (between)
Acute Leukemias
most common malignancies in children, leading cause of cancer-related death in patients <20 years
Both AML + ALL
- arise from single leukemia cell: acquires from additional mutations
- fail to maintain balance of proliferation + differentiation –> myeloblasts/ lymphoblasts proliferate uncontrollably)
Acute Leukemia Causes
infection, genetic factors: strongest association to development of acute leukemias
- drugs: alkylating agents, anthracyclines
- genetic conditions
- chemical exposure: benzene, pesticides
- ionizing radiation
- viruses: Epstein-Barr, human T-lymphoctye virus
= social habits: cigarette smoking, maternal ethanol/marijuana use
MOST cases diagnosed do not have a cause identified
Acute Myeloid Leukemia
Rapidly progressing leukemia; can be fatal if not treated rapidly
Improper maturation; not differentiated
- arise from pluripotent stem cell
- older patients: arises from stem/early progenitor cell
- younger patients: differentiated cell becomes malignant (different forms of resistance)
Secondary leukemias: prolonged “preleukemic phase” of hypoproduction/abnormal maturation
Chronic Myeloid Leukemia
indolent leukemia from immature granulocytes in marrow and circulation
50% are asymptomatic at time of diagnosis (chronic phase-CP)
-accelerated phase: progressive myeloid maturation arrest (increased blasts), exacerbation of symptoms
HALLMARK SIGN: Philadelphia chromosome-translocation of chromosomes 9 + 22
Targeted therapy: inhibit BCR-ABL by competitively interfering with ATP-binding site
Lymphocytic Leukemias: Acute Lymphocytic (ALL)
Rapidly progressive, derived from lymphoblasts; more common in adults
Classified according to B-cell or T-cell lineage, includes cytogenetic abnormalities (immunophenotyping)
Philadelphia chromosome: different role than CML; targeted therapies not effective
Lymphocytic Leukemia: Chronic Lymphocytic (CLL)
Most common leukemia in US
Neoplasm of more mature, but nonfunctioning B-cells, lymphocytes may not be morphologically different
- Same underlying disease as lymphocytic non-bodkin lymphoma
- Chromosome 17 short arm deletion: p53 silencing –> more proliferation + maturation of cells
Signs+Symptoms: anemia, thrombocytopenia, lymphadenopathy, splenomegaly, hepatomegaly, fatigue, weight loss
Lymphoma
Diverse group of neoplasms characterized by proliferation of malignant lymphocytes in the lymphoid system; most common heme malignancy in US
- Germinal center = site of differentiation for B-cells in the lymph nodes
Non-Hodgin lymphoma: ~85%
-B or T cell; indolent or aggressive
Hodgkin Lymphoma
Most curable form; affects patients in 20-30s + after age 50
Signs + Symptoms:
-fatigue, pruritis, lymphadenopathy, B symptoms (fever, night sweats, weight. loss)
Clonal malignant lymphoid disease of transformed B-lymphocytes: Reed-Sternberg cells
-found in an inflammatory microenvironment
Infectious Associations: immunosuppression (congenital, organ transplant, HIV infection)
Non Hodgkin Lymphoma
Heterogenous group of lymphoproliferative disorders
Causes: genetic disease, environmental exposure, infection
Smoking does NOT have strong association
NHL
- Indolent
- Aggressive
- Very Aggressive
Indolent: small cell lymphocytic, follicular, marginal zone
- untreated survival: years
- curable: no
- treat? defer (asymptomatic)
Aggressive: diffuse large B-cell, mantle cell
- untreated survival: months
- curable: possible
- treat? yes
Very Aggressive: Burkett’s
- untreated: weeks
- curable: possible
- treat? yes
Multiple Myeloma
Malignant plasma cells (differentiated B cells)
- overproduction of monoclonal paraprotein
- plasmacytosis
- M protein: abnormal, ineffective antibodies
Microenvironment promotes further expansion of myeloma clones, disease progression, resistance to therapy
Signs + Symptoms: CRAB
- Calcium elevation
- Renal insufficiency
- Anemia
- Bone lesions/pain
Diagnosis: bone marrow biopsy with >10% plasma cells, M-protein spike (urine or plasma); Swiss cheese type lesions
