Week 4 - Breast Mass Flashcards
State the basic breast imaging principles and procedures to evaluate symptomatic women
Available modalities (imaging):
- Mammography
- Ultrasound
- MRI
Biopsy (ultrasound guided)
Describe the cutaneous innervation of the skin overlying the breast
Nerve Supply for skin that covers breast:
- 2nd to 6th intercostal nerves
Nipple: by the 4th intercostal N.
Describe the vascular supply and lymphatic drainage of the breast
Vascular supply Blood supply - Axillary (artery) - Internal thoracic (artery) (also Ant. intercostal)
Lymphatic drainage
Axilla lymph nodes - vessels - parasternal lymph nodes communicate with the other side of the sternum (cancer can spread from one breast to the other this way)
List key components of a patient-centred medical interview
?
List the mechanisms of protein synthesis, modification and targeting within a cell
The life cycle of proteins - summary
(Didn’t include synthesis)
- Protein targeting signals are zip codes that determine the targeting of proteins to various organelles
- Proteins are translated directly into the ER lumen following SRP dependent targeting of ribosomes to the ER membrane
- Chaperones help protein folding and prevent the accumulation of protein aggregates
For transmembrane protein - stop transfer sequence in the middle
Explain the various ways that proteins may be degraded within a cell
Ubiquitin proteasome pathway
- proteins tagged with ubiquitin will be degraded by proteosomes
ER associated degradation (ERAD)
- misfolded/mislocalized substrates recognized and extracted through the ER membrane, also ubiquitinated
Lysosomal pathways
- Endocytic vesicle and autophagosomes can target proteins to lysosomal degradation
*need to know details?
Describe the fate of (some) mutant/variant proteins and some examples of links between mutation and disease
Leigh syndrome - neurometabolic disorder - can be caused by mutations of the mitochondrial genome
Cystic fibrosis - mutation in CFTR gene, plasma membrane channel, protein misfolding and degradation
Gaucher’s disease - mutation in b-glucosidase, lysosomal enzyme responsible for degradation of lipids
Multiple Myeloma - cancer, relies on ubiquitin pathway (how?)
Describe checkpoints in the cell cycle and their regulators
Cell cycle)
G0: Mitogens induce G1 (macaroni linker molecules)
G1: Mitogens induce Cyclin formation, Cyclin/CDK complexes form to progress the cell through the cell cycle
S: more cyclin/cdks
G2: more cyclin/cdks
M: Prophase, Metaphase, Anaphase, Telophase/Cytokinesis (Mitosis is your dog: Please don’t Pee on the MAT)
3 DNA checkpoints. One before S, one after S, one before M
Identify the 3 major components of the cytoskeleton, and their distinct functions
Microfilaments: dynamic, important in cell adhesion, contractile force, cell shape, surface projections (e.g. microvilli)
Intermediate filaments: more stable, tensile strength within cells and across tissues (cell-cell/cell-ECM), maintain cell and nuclear structure, **helpful markers of specific tissues in histopathology, determining origin of tissue
Microtubules: cylinders of tubulin, polar, grow from + end, held in position by microtubule organizing centre, motors move along bringing cargo
Recognize the structure and function of 4 major cell-cell junctions
“Cell-cell:
(Zonula = belt)
- Zonula adherens** (Need to know names of junctional molecules) - belt around cell, lateral adhesion
- Tight Junctions (Zonula Occludens) - apical, forms barrier and regulates the movement of macromolecules between cells
- Desmosomes (Macula Densa) - not a belt, spots (appear on electron micrographs), link to intermediate filaments increase tensile strength; physically link cells together (prominent in skin)
- Gap junctions - channels that link cells and allow for the passage of small molecules and ions between cells
Recognize the structure and function of 2 major cell-extracellular matrix (ECM) junctions
Cell-ECM
Hemidesmosomes - heterophilic (bind to ECM proteins), intermediate filaments
Focal Adhesions - heterophilic, actin filaments, contractile force, highly dynamic, critical for cell migration
What are the components of Zonula adherens?
Components:
Cadherins - receptor, calcium dependent adherence molecules, will bind similar cadherins on other cells
Catenins - link cadherins to cytoskeletal elements
Actin - make the junction dynamic, can form/release/reform along lateral cell wall
Dysplasia vs metaplasia
Dysplasia
- A pre-malignant change in cells (usually epithelium) characterized by disordered growth and morphologic changes in the cell nucleus
- In mammary gland, same epithelium, but cells look different (dysmorphic) and epithelium is disorderly - can transform into carcinoma
Metaplasia
- a mature, differentiated cell type is replaced by another mature, differentiated cell type (doesn’t necessarily indicate cancer)
- In mammary gland, replacement of epithelium with another type of cell, but it appears normal - can transform into carcinoma
Carcinoma
Malignant epithelial neoplasm
Define cell signal transduction pathways
Involves the binding of extracellular signaling molecules and ligands to receptors located on the cell surface or inside the cell that trigger events inside the cell, to invoke a response.
Oncogene + MOA
Oncogene: Oncogenes code for proteins and factors involved in cell growth; Mutations in these genes lead to an increase cell
division (mutation turns ON - cancer)
Tumor suppressor gene + MOA
Tumor suppressor gene: prevent abnormal proliferation of cells, promote cell death (e.g. p53 gene); mutation turns OFF - cancer
Describe the Gompertzian pattern of tumor growth
Number of cancer cells by time
-Diagnostic threshold (1cm)
- Limit of clinical detection (earliest)
- Cell death (when cancer cells outgrow food source and die)
**Look at picture
What are the characteristic features of cancer development?
- Genomic instability
- Inappropriate cell proliferation, evasion of cell death
- Angiogenesis
- Invasion and metastasis
Describe inappropriate cell proliferation in cancer development
Neoplastic state, there is an imbalance (cell division>cell death)
- normal cells will reproduce until they come into contact with other cells (in malignant cells - there is a loss of contact inhibition)
- evasion of the immune system by inhibition through targeting PD1 on T cells (stops them from killing)
Describe angiogenesis in cancer development
- generally, the creation of blood vessels to provide nutrients/O2 - occurs during life and growth;
- Neoplastic tissues recruit new blood vessels from pre-existing ones, controlled by regulators secreted by the tumor and stroma (+ regulators - by oncogene, - regulators -by tumor suppressor)
Describe invasion in cancer development
- Invasion occurs when neoplastic cells show a disordered structure with piling up of cells; can be as a result of:
Imbalance between proteinases and proteinase inhibitors in ECM (the underlying basement membrane and ECM are degraded)
Alterations in Cell Adhesion Molecules (allow detachment of cancer cells, enhance cell mobility)
Describe metastasis in cancer development
- intravation of primary tumour into vessel through the basement membrane, circulates, extravation of tumor cells into new tissue at different location
Hyperplasia
- An increase in the number of cells within an organ. Occurs in response to a stimulus.
When the stimulus is removed, the cells return to normal size.
Malignant neoplasia
• Grow rapidly • Poorly circumscribed • Infiltrate and destroy adjacent tissues • Metastasize • Histologically may poorly resemble tissue of origin • Often fatal • Surgically cured only in the early stages
Neoplasm
Abnormal mass of tissue, the growth of which exceeds and is uncoordinated with that of the adjacent normal tissues. The mass persists in the same excessive manner even after the stimulus or cause is removed.
Hypertrophy
An increase in the size of cells within an organ. Occurs in response to a stimulus.
When the stimulus is removed, the cells return to normal size.
Atrophy
A reduction in either the size of cells or the number of cells within an organ.
This process is reversible when it represents part of a response to an external stimulus or it can be part of the normal aging process.
High grade dysplasia aka. Carcinoma in-situ
- High-grade dysplasia has most of the cellular morphologic changes of cancer cells but is not invasive and cannot therefore metastasize.
By molecular analysis high-grade dysplasia has fewer mutations than invasive cancer.
Benign neoplasia
• Slow growing • Usually circumscribed • A mass that pushes aside adjacent tissues • Does not infiltrate adjacent tissues • Do not metastasize • Histologically resemble the tissue of origin • Good prognosis • Can be cured by surgical removal • Can be a precursor for malignant neoplasms
Malignant neoplasia
• Grow rapidly • Poorly circumscribed • Infiltrate and destroy adjacent tissues • Metastasize • Histologically may poorly resemble tissue of origin • Often fatal • Surgically cured only in the early stages
Identify the important steps required to diagnose carcinoma-in-situ and invasive cancer
History and Exam
Tissue sample - Distinguishes malignant from benign • Establishes the cancer type – e.g. lymphoma from carcinoma • Can confirm the site of origin of the cancer
Tools for tumour diagnosis and classification:
- Morphology – what the tumour looks like
- Immunophenotype – proteins expressed by the tumour
- Molecular tests - FISH for copy number changes and translocations; Sequencing for gene mutations
Predictive biomarkers
Staging investigations - where is the cancer?
Describe the development of the mammary gland
Glands made up of:
- epithelial tissue (functional unit of glands - parenchyma)
- connective tissue (supportive unit - stroma)
Dynamic organ that only develops into a mature functional state in pregnancy/lactation (look at how changes throughout life)
Describe normal breast tissue and how it changes in response to hormonal changes throughout life
Fetal:
15 - 20 or 25 ducts present at birth
Milk line that regresses to pectoral region
Puberty:
Increase in estrogen and progesterone that induces proliferation of the ducts resulting in elongation and branching
Terminal end buds (possibly 2 cell layer)
Slight increase in adipose tissue
Adult/Resting:
Continued duct elongation with each ovarian cycle
Branching also continues
Growth/branching continues until 35 years old
Pregnancy/Lactation:
Prolactin is introduced due to drop in progesterone (48 - 72 hours after delivery)
Oxytocin introduced, induces contraction of myoepithelia and lactation
Stroma reduces, parenchyma increases
Terminal ends become alveolar through morphogenesis
Involution (post-weaning):
Reverts back to adult/resting stage through apoptosis
Caused by decrease in prolactin, oxytocin, and estrogen and progesterone revert back to normal cycles
Post-menopausal Involution:
Decrease in estrogen and progesterone
Increased adipose tissue
List the different types of pre-malignant conditions and different key types of breast cancer that can occur
changes occurring gradually from normal breast tissue, to development of atypical ductal hyperplasia, then ductal carcinoma in-situ (DCIS), then invasive ductal carcinoma
invasive lobular (carcinoma?): 10-15% -atypical: 5-10%
Describe what a mammogram is and the difference between screening and diagnostic mammography
Type of low dose x-ray designed to image breast tissue.
Screening
• Asymptomatic women
• Limited views
Diagnostic • Symptomatic women or women with history of cancer or with implants • Additional views
State the basic breast screening policy in BC
Letters sent out to Women age 50-69 years (Service also available to women age 40-49 & 70+)
Every 2 years (controversial)
Two-view screening mammogram
Higher risk (one 1st degree relative with breast cancer) - every year Can be under 40 if strong family history or mutation
Define specificity vs. sensitivity
Specificity: reducing false positives
Sensitivity: reducing false negatives
How are cancers staged?
TNM (tumour, nodes, metastasis) system is universally used in solid cancers
• T - Primary tumour characteristics (Size and depth of invasion)
• N - Nodal status (Involved or not, number involved, size)
• M - Metastasis (Present or absent and extent)
TNM is specific to the individual cancer type
Describe the models for genetic counseling and genetic testing (of cancers)
Traditional Approach - referral - HCP appointment - assessment - call back
Oncologist-Led Genetic Testing - oncologist initiates testing, reduces
Group Genetic Counseling
DNA-Direct Genetic Counseling - (Call and mail in sample?)
Describe and compare different molecular methods for hereditary cancer diagnosis and tumour testing
** Skip this, need to go over lecture**
- Site specific
- Single gene
- Gene panel
- Whole exome
- Whole genome
Tumour testing - performed for diagnosis and treatment decisions
Tumour phenotype can reflect germline
First tumour approach
Explain the difference between exocrine and endocrine glands
Endocrine gland secrets chemical substances directly to the blood stream, while exocrine gland secrets its product into a duct
Indicate which cranial nerves and spinal nerves carry sympathetic and parasympathetic fibers out of the central nervous system
Sympathetic:
Parasympathetic:
Describe in general how pain from the viscera is referred to regions innervated by somatic nerves
-
Describe in general terms how parasympathetic nerves are distributed in the head
–
Describe in general terms how sympathetic nerves get into the head
-
