Pathology of the Female Reproductive Tract 2 Flashcards
For some malignant neoplasms, a ‘pre-malignant state is identified
- This state is termed dysplasia
- There is an accumulation of cells which look somewhat like malignant cells but do not invade the basement membrane
- Dysplastic lesions may (but don’t always) progress to invasive malignancy
- Recognising dysplastic lesions allows early treatment before invasion occurs
-the epithelium of the normal cell shows the accumulation of the nucleus as the cell don’t have much cytoplasm at the bottom. As the cells are pushed up the upper layer of the epithelium as they differentiate, the nuclei shrink and they accumulate cytoplasmic volume.
Dysplasia
disordered growth and differentiation characterised by;
1. increased proliferation (more mitoses)
2. atypia of cells
3. decreased differentiation.
-In squamous cell epithelium, proliferation is normally confirmed to the basal and epibasal layer. so we ould only expect to see mitosis down in the bottom of the stratified epithelium, but in the dysplastic cell, you can see that there are mitotic figures in 2/3 in places where proliferation would have ordinarily been turned off.
-Atypia ; the nuclei have got this angulated margins instead of being smooth and round like normal nuclei. The chromatin which is the purple staining stuff inside the nucleus is gritty, so instead of being divided inside the nucleus its got this gritty appearance.
Atypia is a histopathologic term for a structural abnormality in a cell, i.e. it is used to describe atypical cells.
Dysplasia has lots of different terminology for the same process
Eg for the cervix:
•Generic: Dysplasia
•UK: Cervical intra-epithelial neoplasia (CIN)
•US: Squamous intra-epithelial lesion (SIL)
-In dysplasia, there is no invasion through the basement membrane into the stroma. the abnormal proliferation remains in the epithelium.
Different degrees of dysplasia may be recognised microscopically
- The image shows the different degrees of dysplasia within the squamous cervix.
- The stages of dysplasia is divided into 3 stages;
1. CIN1
2.CIN2
3. CIN3
_*the normal one is showing;_ the normal process of maturation with shrinkage of the nuclei, increased volume of cytoplasm and mitosis.
The degree of dysplasia may predict the likelihood of developing invasive malignancy
Cervical intraepithelial neoplasia (CIN)
- For CIN1, the risk of progressing to a squamous cell carcinoma over a period of 10 yrs is low. (1%)
- For CIN3, the risk of progression over 10 yrs is very high (40%)
Dysplasia often occurs in sites where there is metaplasia
•squamous metaplasia of the cervical transformation zone. it is in the zone of squamous metaplasia where the columna cells of the endocervix is being converted to stratified squamous epithelium, this is where we often see Dysplasia occur. this process is physiological.
-squamous metaplasia of the bronchial epithelium; The process of metaplasia can also be pathological. i,.e in smokers where the tobacco injures the epithelium which normally lines the upper part of the airways (trachea and bronchi) which normally form from the epithelial cells with cilia on its surface but in response to the injury of cigarette smoke, may undergo metaplasia to inform more durable squamous epithelia.
•glandular metaplasia of the distal oesophagus; In reflux, the distal oesophagus which is normally lined by squamous stratified squamous epithelium, in response to the effect of the acid, can undergo metaplasia to form glandular epithelium which is more like the normal lining of the stomach (the non-mucosal lining). The metaplasia can progress to dysplasia and invasive malignancy and when this happens, the dysplasia forms in the epithelium with the metaplastic phenotype.
In the bronchus for example, the pre-existing epithelium is columnar, can undergo squamous metaplasia and form squamous epithelium and the tumour that you see arise here is squamous cell carcinoma.
In the distal oesophagus/barret oesophagus , the metaplasia is columna , and the dysplasia we see is columna glandular epithelium and the tumour that we see is an adenocarcinoma (malignant tumour of glandular epithelium).
Cells at the surface of dysplastic epithelium are different from those at the surface of normal epithelium
- The cells at the surface of the epithelium of a dysplastic cell are different from those seen in normal epithelium and this is true regardless of the maturation that occurs in the dysplasia.
- Even in the CIN1 (early stages), the surface of the epithelium cells are different from those in the normal epepythelium.
PAP smear/ The Papanicolaou test
Samples the cell from the cervical transformation zone. The cells are then rinsed off the surface of the brush into a liquid which is then used to prepare a slide so that the cells can be stained and examined.
-The PAP is the name of the stain used to stain the cells . its called Papanicolaou stains.
Normal constituents of a smear
-The squamous cell staining pink and blue but it doesn’t matter
Normal surface cells have a small nucleus and lots of cytoplasm
These are normal cells from the surface of the epithelium of the cervix.
- They have a large surface area and are very thin.
- with lots of pink staining cytoplasm
- the nucleus is quite uniform, they look like each other
Dysplastic cells of the cervix
Dysplastic cells have a higher ratio of nuclear size to cytoplasmic volume, and the nuclei show the same features that we associate with malignancy.
- you can see how the nucleus is still big and the cytoplasm is small.
- nuclear atypia, the changes in the nucleus in malignancy like irregularities. they have nuclear which are bigger, irregular nuclear margin and gritty chromatin, unevenly spread through the middle of the nucleus.
What is the difference between dysplasia and carcinoma.
The difference between dysplasia and carcinoma is invasion through the basement membrane
-In the cancer image, you can see the invasion through the basement membrane into the stroma. it still has the feature of a dysplastic epithelium but it has an increasing cytoplasmic volume. the increase in cytoplasmic volume is caused by a contractile protein that accumulates inside the cell. we’ve also got some scattered blue dots which is the nuclei of inflammatory cells in this case (lymphocytes).
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What is the causer of CIN/ cervical cancer
HPV infection causes CIN and cervical cancer
Human Papillomavirus
- Human Papillomaviruses (HPVs) infect epithelium
- Confined to local site of infection without viraemia (spreading via blood stream)
- Over 130 HPV types, some of which infect the anogenital mucosa
- Double stranded DNA virus 7.9Kbp
HPVs may be grouped according to risk association with malignancy
•High Risk HPV 16,18,31,33,35,39,45,51,52,56,58,59,68 (associated with high risk of malignancy)
•Low Risk HPV 6,11,40,42,43,44,54,61,72,81 (associated with low risk of malignancy), they re associated with benign warts etc.
-HPV 16 and 18 are those highly associated with squamous cell carcinoma. the ones associated with urogenital warts are HPV 6 and 11..
- The virus is infecting epithelial cells locally, somehow finds its way to the cells of the base of the epithelium. it does not affect cells of the surface of the epithelium, it has to infect the basal type epithelial cells.
- The life cycle of the virus is intimately pegged to the life cycle of the squamous epithelial cells.
-In warts, for example, the virus replicates itself as the epithelial cells move their way up thought he epithelium, eventually manufacturing more viral particles which are liberated in the surface of epithelium, the viral cell burst open and the viral particles are released and this will be a productive viral infection. this is what happens in warts and verucas, and some of the lower grade dysplasia that we see in the cervix.
-In higher-grade dysplasia/cancer, the virus becomes integrated into a host genome and when this happens, the normal control mechanisms which control the way the viral proteins are manufactured particularly the viral proteins which subvert the ordinary cellular machinery in order to stimulate proliferation.
-the control mechanism is disrupted when the circular DNA virus becomes incorporated int he linear fashion into the host DNA and manufactures the protein which drives cellular proliferation and that is what leads to the full thickness dysplasia and then eventually the development of invasive squamous cell carcinoma.
