Morphological Aspects of Neoplasia Flashcards
What are the two phases in the morphological model of cancer? What is it called when you transition from one step to the next?
- Premalignant or dysplastic - accumulation of abnormal cells within an epithelium, without invasion
- Malignant - local invasion and/or distant (lymphatic or hematogenous) spread - that is, metastasis
It is called “progression” when you transition from one step to the next
What is generally the stimulus for hyperplasia?
Inflammation or hormone stimulation
-> it is reversible and subsides when the stimulus is removed
What are atypical and complex hyperplasia?
Very unfortunate terms used in uterus and breast pathology which are meant to mean premalignant states, although generally hyperplasia is meant as a reversible increase in the number of normal cells
What is Barrett’s esophagus and how can it lead to cancer?
It is when the squamous mucosa of the lower esophagus is replaced by intestinal type mucosa (replacement of fully differentiated epithelium = metaplasia).
This metaplasia can lead to dysplasia of the new columnar epithelium and ultimately invasive adenocarcinoma of the esophagus (vs squamous cell carcinoma which you would normally see without metaplasia)
How is squamous cell carcinoma likely to occur in the lung?
Pseudostratified columnar -> stratified squamous epithelium
SSE -> squamous dysplasia
Squamous dysplasia -> squamous cell carcinoma
What is an intraepithelial neoplasia or premalignancy also called? What is its defining characteristic?
Dysplasia
-> has not invaded the surrounding tissues by breaking through the basement membrane
What are the features of abnormal cells in dysplasia?
- Ratio of proliferating / differentiating cells increases
- Cells have altered polarity (may lead to stratified cells in columnar epithelium, for instance)
- Abnormal nuclear morphological features
- Increased nuclear to cytoplasmic ratio
What types of tissue are precancerous conditions found in, and how long does it take for dysplasia to progress to invasive cancer? Why is this important?
Virtually all tissues in the body, including glandular epithelium (usually non-squamous) and epithelium of exocervix, upper / low aerodigestive tract, and skin (squamous)
Takes decades for dysplasia -> invasive cancer
-> provides important opportunity for screening, i.e. PAP smears, PSA test, mammograms, colonoscopies
What is the progression of normal squamous epithelium from basal layer to surface?
No mitosis pass the basal layer, with progressive decrease in the nuclear:cytoplasm ratio, and an accumulation of intermediate filaments (keratin).
How can SSK epithelium be differentiated from SSNK?
SSNK will have small nuclei on the uppermost layer, whereas SSK (stratified squamous keratinized) will lack any nuclei
Give the three primary features of dysplastic squamous epithelium.
- Overall increased cellularity
- Mitoses and abnormal, basal-like cells everywhere in the epithelium
- High N:C ratios
What does each grade correspond to?
How far up the stratified layer the abnormal and mitotic cells reach. If it reaches all the way to the surface, it is severe dysplasia / carcinoma in situ.
-> represents increased proliferation and reduced differentation
What feature of squamous epithelium tells you the cells have abnormal polarity?
When keratinization occurs in the base or in the middle, not at the surface (keratinization can happen anywhere, and even form “keratin pearls”)
What is it called when highly dysplastic cells have variation in size / shape, and also increased density of their nuclear chromatin?
Prominent in high grade dysplasias:
Pleomorphism - variation in size and shape
Hyperchromasia - increased density of their nuclear chromatin
What are the two systems for grading dysplasia?
Four-grade system - more variability between pathologists: Mild, moderate, severe, and CIS (carcinoma in situ)
Two grade system - less variable: Low and high
What does the field effect state?
Cancer often arises in the background of MULTIFOCAL precursor lesions within an organ or anatomical system
-> if you had a cancer of the breast once, you are more likely to develop a second primary breast cancer than other people
Why does the field effect occur?
Due to widespread exposure of the organ system to a carcinogen.
I.e. if you are a smoker and you develop head and neck cancer, the rest of the epithelium in your head and neck also saw that tobacco smoke and was likely to seed a few more premalignant lesions
-> like a farmer spreading his seeds over a large area
What should be done to prevent second cancer recurrences in light of the field effect?
Use systemic chemotherapies
-> can kill other premalignant lesions at the same time as malignant cancer
What two characteristics of dysplasia are proportion to its chance of developing into cancer?
- Degree of dysplasia -> more severe = more likely
2. Extent of dysplasia -> more premalignant lesions = more likely
Are some organs more prone to aggressive cancers than others? When is detecting this impotant?
Yes. Prostate and thyroid cancers tend to be vary indolent cancers and often do not kill you.
However, even within a given organ, some cancers are more aggressive than others and require more specific treatment. Detecting specific markers which give clues into the amount of invasiveness can also guide treatment for the individual patient.
