Intro to Oncology Flashcards
Top 3 new cases of CA for men and women?
- Prostate/Breast
- Lung and bronchus
- Colon and rectum
Top 3 CA deaths for men and women?
- Lung and bronchus
- Prostate/Breast
- Colon and rectum
What accounts for at least 30% of cancer deaths?
30%
What are some CA prevention strategies?
- Smoking cessation
- Smoking prevention
- Sun avoidance
- Dietary modifications
What % of American smokers began before age 18?
Over 80%
What % of high school students have tried smoking?
58%
Do people who quit smoking regardless of age live longer than those who continue to smoke?
YES
Qutting before age 50 cuts the risk of dying in the next 15 years by what?
50%
What cancers are 85-90% preventable with appropriate screening?
- Colorectal: Fecal occult blood testing and colonoscopy
- Cervical: Pap and pelvis
- Breast: Self-exams and mammography
- Prostate: DRE and PSA
- Oral Cavity: Visits
- Skin: Physical exam
What 4 things are part of the approach to CA dx?
- Careful history
- Careful physical exam
- Radiological imaging
- Tissue biopsy
What 4 things should be assessed when taking history?
- Underlying diseases
- Smoking and alcohol
- Occupational exposures
- Family history
How much tissue should be taken for biopsy?
As much as is safely possible
What 4 things are determined from a tissue biopsy?
- Histology
- Grade
- Degree of invasiveness
- Molecular diagnostic and prognostic information
What is it called when the entire tumor mass is removed with a margin of normal tissue surrounding the mass?
Excisional biopsy
What is it called when a wedge of tissue is removed trying to include the majority of the cross-sectional diameter of the tumor?
Incisional biopsy
How is a core needle biopsy usually done?
With endoscope or CT… smaller tissue sample
What gets a cell suspension from within the mass and is very limited sample… usually CT guided or direct palpation of mass?
Fine needle aspiration
What 3 things are used for clinical staging?
- Physical examination
- Imaging procedures like XR, CT, Isotope scans
- BM examination for some tumors
What is done to determine pathologic staging?
Histologic examination of all tissues removed at surgery
What does higher clinical stage correlate with?
Higher tumor burden and less curability
What does the stage usually dictate or mandate?
Specific treatments
What 2 things must be taken into account with prognosis and planning treatment?
Physiological reserve of the patient (age and karnofsky and ECOG performance scores) and molecular markers
Where is hematopoiesis week 2 to 12 of gestation?
Yolk sac
What is produced from the yolk sac?
Only RBC for oxygenation
Where is hematopoisis from week 6 of gestation until postnatal week 1?
Fetal liver and spleen
When does hematopoiesis peak in the fetal liver and spleen?
Months 3-6
-Declines after month 6 and ends shortly after birth
When does hematopoesis begin in the BM?
2-4 months gestation
What is the major site of hematopoiesis after month 6 gestation?>
BM
In infancy, where is hematopoeisis?
All bones
What happens to hematopoeisis in childhood and adolescence?
Progressive decrease of hematopoetic marrow in the long bones
At age 25 where is the extent of hematopoesis in long bones?
Only in the proximal quarter of femoral and humeral shafts
In adults, where is hematopoesis?
Central skeleton and proximal ends of the long bones
Why do we have hematopoeisis?
To replace normal losses and maintain hemostasis
What does the diversity of blood cells reflect?
Need for cells with highly specialized functions
What is the process that involves the development of unique biochemical, structural, and functional characteristics known as?
Differentiation
True or False: Differentiation is a one-way process
TRUE
What is for the replacement of normal loss of blood cells and amplification of the number of mature blood cells during times of stress?
Proliferation
What 4 things does differentiation result in?
- Oxygen carrying capacity: red blood cells/hemoglobin
- Hemostasis: platelets
- Innate Immunity: neutrophilic granulocytes and NK cells
- Adaptive Immunity: T- and B- lymphocytes
What is it called when there is inadequate production and too few blood cells develop?
Cytopenias
What is it called when there is excessive production or if there is replacement of marrow by tumor or fibrosis to too many blood cells develop?
Cytosis
What are 2 ways cytosis can happen?
- Expansion of hematopoiesis down the shaft of the long bones
- Extramedullary hematopoiesis in liver, spleen, lymph nodes
What cell initiates hematopoiesis?
Hematopoietic stem cell
What 2 things is a hematopoietic stem cell?
- Multipotent
2. Self-Renewing
Define multipotent
Can give rise to all other hematopoietic cells by differentiating into committed progenitor cells
Define self-renewing
Can replace itself. When a HSC divides at least one of the progeny cells remains a HSC.
What differentiates a stem cell from any other cell?
Self-renewal capacity
What is the ability to self-renew dependent on?
Intrinsic characteristics of the stem cell and on its interaction with the bone marrow microenvironment: the bone marrow niche.
What is essential to confer self-renewal capacity to stem cells?
Both direct cell-cell contact between bone marrow microenvironment and the stem cell, as well as stimulation of stem cell receptors by cytokines and growth factors
Are HSC normally quiescent?
YES
-This protects multipotency and acquisition of mutations that could lead to malignant transformation
True or False: In extreme circumstances, HSC can leave marrow and migrate to other organs
TRUE
What is the first commitment step resulting in lymphoid or myeloid progenitor cell (from a HSC)?
Lineage commitment
What is further differentiation of a committed progenitor cell?
Differentiation commitment
What has the capacity to self-replicate, proliferate, and differentiate to increasingly specialized progenitor cells which in turn generate the mature cells of the peripheral blood?
Common primitive stem cell
What do progentior cells resemble?
Lymphocytes (they are difficult to recognize morphologically and proliferate in culture and form colonies)
What is hematopoeisis regulated by?
Growth factors that usually act synergistically
Early lineage division is between what?
Lymphoid and myeloid cells
The early stages of hematopoeisis is confined where for both myeloid and lymphoid cells?
Bone marroe
Where do myeloid cells undergo almost the entire maturation process?
Inside the BM
Where to lymphoid cells undergo functional maturation?
Lymph nodes, thymus, and other sites
What are the 4 WHO Classifications of Myeloid Neoplasms?
- Acute Myeloid Leukemia (AML)
- Myelodysplastic Syndromes (MDS)
- Myelodysplastic/Myeloproliferative Neoplasms (MDS/MPN)
- Myeloproliferative Neoplasms (MPN)
Which myeloid neoplasm is mostly a problem of abnormal differentiation (qualitative)?
MDS
Which myeloid neoplasm is excessive proliferation with normal differentiation (quantitative)?
MPN
Which myeloid neoplams is excessive proliferation and maturation arrest (qualitative and quantitiative)?
AML
Weight loss, night sweats, splenomegaly, leukocytosis with mature and immature granulocytes, BM biopsy 100% cellular, BM aspirate shows increase in granulocytic and eosinophilic precursors?
Chronic myelogenous leukemia
Had large B cell NHL, high-dose chemo and autologous stem cell trasnplant, complete remission….now has pneumonia, pancytopenia, 2% blasts, and BM with abnormal granulocytic maturation with hyposegmentation of nuclei and increases blasts?
Myelodysplastic syndrome, refractory anemia with excess blasts
What is a combination of neutropenia with thrombocytopenia and anemia/reticulicytopenia?
Pancytopenia
What is required to establish diagnosis of pancytopenia?
BM examination
What causes hypercellular BM?
Usually hematologic malignancy, rarely a B12 deficiency
What causes hypocellular BM?
BM failure disorder
- PBS with immature monocytes and blasts
- Hypercellular marrow (95% cellular)
- Myeloblasts = 25%
- Monoblasts, immature monocytes, and mature monocytes = 42%
- Abnormal eosinophils
Acute myeloid leukemia
What do pro-B cells do first in the BM to rearrange their germline immunoglobulin genes?
Re-arrange the heavy chain genes
What do pro-B cells do after rearranging their heavy chains?
Rearrange the light ones
Once they rearragnce heavy and light chains, what are pro-B cells?
Immature B cells that have a unique IgM or IgD immunoglobulin that is expressed on the cell survace
Were do immature B cells live for a long time and are quiescent?
Lymph Nodes
Resting B cells are stimulated by what to develop into a plasma cell or memory B cell?
Antigen via APC with help from a T-cell
When antigen-stimulated B cells eventually enter the germinal center what do they do?
Somatic hypermutation of the variable region genes
The germinal center B-cells that survive can do what?
Heavy chain class switching to be IgG, IgA, IgD, or IgE
What do plasma cells do once they move to the BM?
Produce highly specific immunoglobulin
Where do pre-T-CElls undergo T-Cell receptor gene rearrangement?
Thymic cortex
T cells that express high-affinity receptors for self-antigens undergo what?
Negative selection (clonal deletion) by apoptosis
Where do T-cells undergo further maturation to become either a CD4 or CD8 Tcell?
Thymic medulla
What is required for stimulation of T-cell receptors?
Antigen presentation on an APC via HLA
4- MHC II
8- MHC I
What happens in the presence of a co-stimulatory signal?
T-cell activation
What happens in the absence of a co-stimulatory signal?
T-cell Anergy
- Phenotype: CD10+, CD19+, CD20+, kappa +
- Genetics: t(14;18)(q32;q21)
Follicular lymphoma
What causes follicular lymphoma?
Rearragement of the Bcl-2 gene at 18q21 adjacent to IgH gene at 14q32 results in BCL-2 OVEREXPRESSION
- Phenotype: CD10+, CD19+, CD20+, kappa +, bcl-6+, Ki-67 + 100%
- Bcl-2 - , EBERs -
- Genetics: t(8;14)(q24;q32)
Burkitt Lymphoma
Bone Marrow Failure can arise as a result of disease processes that do what 2 things?
- compromise the bone marrow microenvironment
2. Injure stem cells directly
What are prototype disorders for Bone Marrow Failure?
- Myelophthisis
2. Aplastic anemia
What does myelophthisis do?
Compromises the bone marrow environment
Pancytopenia due to marrow replacement can be caused by what 4 things?
- Fibrosis
- Metastatic tumors: Breast, prostate, lung, lymphoma
- Primary tumors: Acute leukemia, myeloproliferative neoplasms
- Granulomas: Tuberculosis, fungal infections, sarcoid
What is seen in a peripheral blood smear with bone marrow failure?
-Nucleated RBCs, tear drop RBCs, myeloid precursors (leukoerythroblastic)
What results if you injure stem cell directly?
Aplastic Anemia
What are 2 causes of acquired bone marrow failure?
- Idiopathic
- Secondary to injury by radiation, drugs (chemotherapy, chloramphenicol), toxins (hydrocarbons, benzene), viral infections (non-A, non-B, non- hepatitis)
What can cause congenital bone marrow failure?
Fanconi anemia (AR, defect in DNA repair)
Others
THIS IS RARE
What is aplastic anemia?
A rare disorder with probable auto-immune etiology causing direct impairment of the ability of HSC to proliferate and differentiate
What is likely a cause of aplastic anemia?
-Induction of antigen expression triggering immune destruction by cytotoxic T-cells.
What can trigger the immune response in aplastic anemia?
Various stimuli (drugs, toxins, infections)
True or False: v) Severe AA (ANC < 0.5) and very severe AA (ANC < 0.2) have high mortality if untreated.
TRUE
What is mortality almost always due to in aplastic anemia?
Infections (fungal ones especially)
What are 2 treatment options for aplastic anemia that have a high response rate?
- Allogeneic bone marrow transplantation (young patients with HLA-identical sibling).
- T-cell immune suppressive agents like anti-thymocyte globulin and cyclosporin (older patients and patients without HLA-identical sibs).
What must you consider in treatment options for CA?
Curative or Palliative
-Surgery, Chemo, Radiation, Hormones, Immunotherapy
What are some types of supportive care for CA treatment?
Pain, nausea, infections, nutrition, psychosocial issues
-Don’t forget about end of life care
How does cancer grow?
Angiogenesis
What are some terms for vascular access?
- Mediport
- Hickman
- PICC
What is done through those vascular access sites?
- Infusions: Chemo or stem cell
- Blood draws
- Stem cell collection
When a growth factor starts the signal for a cell to divide, what can a single tyrosine kinase inhibitor do?>
Stop the signal
What can a multi-tyrosine kinase inhibitor do?
Block signal for the cell to divide (via growth factor) and block the signal for the cell to make blood vessels (via growth factor)
Novel therapies?
He put in a picture with drugs that we covered in pharm…
Why is it important to understand hemonc concepts?
So you can…
(1) Contribute to proper care
(a) Screening and Prevention
(2) Treat Complications of disease
(3) Treat Complications of treatments
(4) Contribute to your patient’s quality of life
What does cancer do?
SCARES EVERYONE…
