Module 4 Path Flashcards
What are the cellular adaptations to stress?
Atrophy, hypertrophy, hyperplasia, metaplasia and dysplasia
A neoplasm can be classified as what two things?
Benign
Malignant: sarcoma, carcinoma. other (mixed, teratoma, etc)
What are some general characteristics of tumors?
Differentiation Anaplasia Rate of Growth Invasion Metastasis
The phases of malignant tumor growth, each card will go into details of these phases. 1st phase is transformation
- Transformation: monoclonal proliferation
- additional mutations over time can lead to subclones –> increases resistance to chemo
The next phase is tumor growth, explain some characteristics
- Tumor Growth- requires 30 doubling times for clinical significance
- Angiogenesis via FGF,PDGF,VEGF to maintain blood supply
The third phase of malignant tumor growth is local invasion, explain some characteristics
- Local Invasion -resistant tissues -mature cartilage and elastic tissue in arteries
What are the steps to local invasion
- Detachment of tumor by downregulating E-cadherin and mutation of catenins
- Attachment of ECM proteins - laminins, integrins, fibronectin
- ECM protein degradation -type IV collagenase
- Generation of new sites -MMP2 and MMP9 secreted by the tumor
- Movement through ECM proteins -autocrine motility factors
The fourth and final step in malignant tumor growth is distant metastasis, what are some features?
via lymphatics, hematogenously or seeding
what is atrophy?
Decrease in size and function of cell; decreased size of whole organ
if persistent: cell death
What is hypertrophy?
Increase in size and augmented function of cell
What is hyperplasia?
Increase in number of cells
What is metaplasia?
Conversion of one differentiated cell type to another
both types of cells are normal
What is dysplasia?
Alteration in size, shape, organization of cells
What is aplasia, hypoplasia and agenesis?
Aplasia: absence of an organ (only rudiment present)
Hypoplasia: decrease size due to incomplete development
Agenesis: complete lack of organ
What is a neoplasm?
Abnormal mass of tissue
growth exceeds and is uncoordinated with that of normal tissue
persists in the same excessive manner after cessation of the stimulus which evoked the change
How are neoplasms named?
- type of neoplastic cells:indicate tissue of origin
2. nature of tumor (Whether benign or malignant)
In regards to classifying tumors there are two ways in which this is done, grading and stage. How are tumors graded?
Level of differentiation (well, moderately, or poorly differentiated), mitoses and character of tumor
Grade based on I-IV on histological appearance
Problems with variation of histology of various areas and observer variation
How are tumors staged?
Extent of spread (more important then grade)
- clinical staging: based on evidence acquired before treatment
- Pathological staging- obtained at surgery via examination tissues
In regards to staging, what does T,M and N stand for?
Size of the primary tumor = T
Extent of spread to regional lymph nodes (N)
Presence or absence of metastases (M)
What are the two major systems of categorization?
TNM: Union Internationale Contre Cancer
-clinical staging:based on evidence acquired prior to decision of definitive trust
-pathological staging: includes info obtained at surgery and from examination of tissue by pathologists
American Joint Committee (AJCC): divides tumors into stages 0-IV-factors similar to TMN
What is cervical intraepithelial neoplasia (CIN) aka Cervical dysplasia?
-Potentially pre-malignant transformation and abnormal growth (dysplasia) of squamous cells on surface of cervix
What is the etiology of CIN?
HPV infection
What is the pathogenesis for CIN?
Squamous dysplasia from HPV 16 and 18 strains incorporating in host genomes –> express E6 and E7; E6 inactivates p53 and E7 inactivates Rb
There are three stages of CIN –all of which are asymptomatic. Each card will go through one. First –>
CIN I (mild/flat condyloma) -lower 1/3 of epithelium is dysplastic and upper 2/3 has koilocytic change -Koilocytic change=perinuclear halo and nuclear hyperchromasia
What is the second stage of CIN ?
CIN II (moderate) -lower 2/3 is dysplastic and upper 1/3 has koilocytic change
What is the third stage of CIN?
CIN III (severe dysplasia/carcinoma in situ) - entire epithelium is dysplastic –> no koilocytic change, basement membrane is intact ( not carcinoma yet)
For screening it is recommended to do a yearly pap smear, what does a normal pap smear look like?
- Superficial cells located at the top of the stratified squamous epithelium; very small nucleus –> non-mitotically active; mature cells
- Intermediate cells: are in b/t the parabasal and superficial layers
- Parabasal cells: near the BM; will show expanded nucleus –mitotically active
What does an abnormal pap smear look like?
- Increased nuclear/cytoplasmic ratio; disproportionately large nuclei (not round); deep basophilic nuclei (mitotically active), disorganized cellular arrangement
- occurs at squamo-column junction (transformation zone)
What is Schillers Test?
test for non-glycogen containing areas of the cervix, which may be a site of early carcinoma; uses iodine
- Mitotic cells = glycogen absent (Being used) =fails to stain
- Non-mitotic cells=glycogen =stains brown
What are the 5 features of dysplasia/atypica?
- Increased nucleus to cytoplasmic ratio
- Nuclear hyperchromasia (blue/basophilic)
- Nuclear Pleomorphism (different sizes and shapes)
- Cellular pleomorphism
- Enlargement, irregularity and loss of polarity (orientation of cells doesnt make sense)
Naturally in the cervix, squamous cells mature from bottom to top as they accumulate what?
glycogen
What cells do you want to do a pap smear on?
Superficial cells
What two HPV strains do not incorporate in the host genome –> do not cause dysplasia or carcinoma
6 and 11
What do HPV 6 and 11 strains lead to?
Genital Warts (totally benign) -> but can still do koilocytic change (indicates the presence of HPV)
When does CIN become cancer?
Invades the BM
What is the most important predisposing factor for cervical cancer?
History of multiple sexual partners
What is the most common symptom of cervical carcinoma?
Post-coital bleeding (also have dyspyrunia which is painful intercourse), white vaginal discharge (leukorrhea)
How do the malignant cells present on histological slide?
Malignant squamous cells with keratin pearls = well differentiated in function b/c making keratin pearls
What is Anaplasia?
De-differentiated or lack of differentiation in structure and function
Rapid cell growth and hallmark of malignancy
How does Anaplasia appear on histological image?
Epithelial Origin -Carcinoma- cytokeratin stain (disseminate via lymphatics)
Mesenchymal origin-sarcoma-vimentin stain
(disseminate hematogenously via venous drainage) (liver and lungs frequent sties)
Muscle Origin - desmin stain
What are the black areas of anaplasia on histological image?
Tumor giant cells (multinucleated) b/c anaplastic tumors divide at a very fast rate
-K167 is the stain for rapidly dividing tumor cells
What age do women start getting pap smears?
21
A pap smear is a screening test for cervical cancer, what are other screening tests commonly used?
Mammogram (breast cancer)
Digital Rectal Exam (prostate cancer)
Colonoscopy (colon cancer)
PSH is considered a tumor marker, what is the role of a tumor marker enzyme?
To monitor response to treatment not
to diagnosis
If a patient has an abnormal pap smear, what is the next recommended investigation?
Colposcopy and then biopsy (these will allow you to see the basement membrane)
