patho sheet(3rd of Dr faisal) - Eman Hashem Al-Momani.

Cervix


Our lecture is about another part of the female genital tract, the cervix.
In general we are going to take its relation with the D & C (Dilatation & Curettage--كشط او جرف), sometimes physician take some part of the endometrium for diagnostic purposes and sometimes for therapeutic purposes.
Sometimes descending vulvovaginitis occurs after delivery (post partum {PP}) especially if there were endometritis.
Chronic inflammation may occur due to TB infection but it is very rare.
Almost always the inflammation is acute, sometimes and rarely chronic, with the acute inflammation mucus secretion may be present, this secretion is thick to the extent that it blocks the orifices of the endocervical glands, so small cysts may develop -few millimeters in diameter- which are called Nabothian Cysts or follicles.
To sum up:
Inflammation due to trauma or infection  thick or dry mucus is secreted  obstruction of the endocervical glands Nabothian Cysts develops.
these cysts indicate inflammations not tumors.
This was an overview of what we are going to talk about this lecture, now let's start…
The cervix in neonates then infants then about puberty develops some evolutions because of the hormones effect, these evolutions involve the enlargement of the cervix, and therefore it undergoes some sort of hypertrophy and the endocervical canal elongates, the end result is exposure of the columnar epithelium of the endocervix.
Take a look at these pictures:
The internal os is the junction between the endometrium and the endoservical canal. The external os is the junction between the endocervical canal and the exocervical canal.
What the physician sees while examining the patient is the external os.
In the first picture (at birth) you can see that sqamous cells covering the entire vagina till the exocervix, then columnar epithelium starts to appear till the end of the endocervical canal.
Physiologically -when hypertrophies of the females' organs begin including the cervix-, or sometimes with inflammation, the canal enlarges, elongates and the lips of the canal will look as if it was flipped outside, exposing the columnar epithelium. (more explanation) physiologically or when injury or infection occurs the endocervical canal elongates and the columnar epithelium over grows, leading to the exposure of columnar epithelium beyond the external os on the cervix, so as you can see in the second picture the columnar epithelium which has been lining the canal emerged outside and covered some of the cervix.
Under these one or two layers of columnar epithelium, blood vessels could be seen, this area was referred to as cervical "erosion"; because it is seen as a red-colored epithelium.
Erosion: a very small ulcer or discontinuity in the mucus membrane.
Actually this was mistakenly referred to as erosion, in fact it’s the translucency of the epithelial layer which gives it this redid color.
Now the place where the columnar epithelium emerged to has a different PH from the place where it came from (cervical canal), so for adaptation; squamous epithelium starts to creep or grow (some say metaplasia) over the columnar epithelium – you can see it in the 3rd picture- to form a stratified squamous epithelium layer which is a protective and a resistant layer to the vaginal environment.
In other words, the original squamo-columnar junction now is in the place of the external os.
This junction is referred to as functional squamo-columnar junction, this is normal.
The resulted area is a transformed area in which it has been transformed from the original squamous epithelium to columnar covered by squamous epithelium, that’s why this area is called the transformation zone, this zone is very important because mostly all of the cervical cancers develop in this region.









Another importance of this region is for pathologists, for examination a swab is taken from this region containing these transforming cells, (to insure that the swab has been taken from this zone the pathologist should look for some columnar epithelium present in the sample if he doesn't find some, then he knows that the examiner didn’t get the right swab), so this region is important for diagnostic purposes because as I said before cancer develops from there.
Are these changes in the cervix normal??? Yes they are, and they are present in all females after puberty; during and after puberty everything in the female changes including the enlargement of the cervical canal, so part of it gets outside the vagina and changes develop as we've mentioned before.
*The condition in which columnar epithelium grows distally beyond the exocervical os is called : Ectropion.

Tumors of the cervix
Endocervical polyp is very common 5-7% .
Polyps usually grow endocervicaly and rarely exocervicaly.
Polyps may be confused with cancer because most of the cancers which develop are polyploid, but usually polyps in this region are benign .
So proper diagnosis should be done in order not to miss the presence of cancer.
Sometimes the presence of bleeding may be confusing, is it normal due to menstruation or is it from the polyps itself because sometimes it might be ulcerated so infection may occur resulting in lower abdominal or back pain!
So the polyp should be sampled properly.

Cervical intraepithelial neuplasia (CIN)
Premalignant, malignant, and CIN.
CIN (cervical intraepithelial neuplasia) = CIL (cervical intraepithelial lesion)
Dysplasia is not necessarily premalignant especially if it was mild, the moderate or severe dysplasia might probably be converted to pre-invasive then micro-invasive and then invasive. (cancer development).
Mostly the development of cancer is on top of CIN II or CIN III, not all the CIN II is converted to CIN III then to cancer but all the CIN III is converted most probably to cancer (30%).
CIN if detected early, treatment can be done successfully and by that the conversion of CIN I to II and III is inhibited.
How can they detect CIN ???
There are more than one method but the most comonly used one is: collecting exfoliated cells from the vagina ( it's called the vaginal pool), they collect samples of cells from the vagina and the transformational zone using certain tools like a brush for example. The person who invented this method took the Nobel price, because he saved many lives…his name was Papanicolaou (Pap).
His method is named: 1- Pap smear.
2- Pap stain.
3- Pap slide.
So the Pap method is to collect –as we said- the exfoliated cells from the transformational zone and the vagina, then stain it and under the microscope we can tell whether there is something wrong or not.
In the past endocrinology wasn’t so goodly developed, that’s why they couldn’t exactly tell the hormonal status of the female genital tract, so they used the Pap method to draw a scheme and count the types of cells presented whether columnar or squamous maturated or not …etc, and they drew a maturation index. This method is still used.
In addition to that now a vaccine has been developed, in order to avoid human papillomavirus infection, but this is not fully protective because this type of virus can change its receptors so the immune system wouldn’t recognize it –like the influenza virus- .
A mechanical device has been made to be used easily by any women called: Davis pipit, this divise is for the application of the Pap method.




Morphology
CIN I CIN II CIN III
• Mild dysplasia.
• Flat cells with peripheral nucleus.
• Small nucleus.
• Towards the surface the squamous cells are well matured. • Dysplasia is more severe.
• Some variation in the cell & nucleus size.
• In deeper two thirds the cells are irregular • Very large nuclei.
• Angulated cells.
• Cells are darkly stained.
• Named carcinoma in sito.
• Chromatin heterogeneity.
• Normal & abnormal mitosis are present.

Pathogenesis
Important risk factors for the development of CIN and invasive carcinoms:
• Squamous cell carcinoma is more common, Less common adenocarcinoma.
• Human papillomaviruse (HPV) is the most common cause of carcinoma, especially HPV 16, there are other types of HPV which contribute to cervical carcinoma like HPV 18,45,31 but the most important type is type 18.
• In many of these patents we can isolate Herpes Simplex Virus.
• Bad hi-gene can sometimes contribute to these inflammations which can lead to cancer.
• Injury to the cervix, especially in early marriages, early age at first intercourse can develop CIN.
• Repeated injury to the cervix, usually multiparous mothers; mothers who give birth to more than 15-16 children!
• A male partner with multiple previous sexual partners.
• Smoking; cigarettes contain more than 300-400 toxins some can be dissolved in the blood then circulates till it is secreted in the cervical mucus.

3/4 the cancer in the cervix is squamous cell carcinoma, 1/4 is adenocarcinoma but both of these are related to the infection by the HIV type 16 or 18.
There are other types of carcinomas but we are not concerned about them.
The peak incidence of CIN is between 30-40 years, almost roughly 35 years.
The peak incidence of invasive carcinoma of the cervix is between 40-50 years, roughly 45 years.
The CIN needs one decade (10 years) to proliferate in the cervix, if it was detected in this period by using deferent methods one of which is the Pap smear (it’s the cheapest and easiest method) it can save lives.
Morphology of the invasive carcinoma of the cervix is of many types; ulcerative, fungative… etc ---------->it's not important, the dr. mentioned them and said were not going to talk about them.
The spread of carcinoma is in three directions.
The metastasis reaches the regional lymph nodes, and it develops around the melarian duct, so the first direct spread goes to the lymph node ,,,,cervix then endometrium then the vagina, sometimes if cancer is present in the endometrium, physicians should suspect that the cervix is the source.
Usually it metastasizes to the lung and liver and sometimes to the bone.
Morphology is not important as I said.

Staging is very important:
Stage zero: carcinoma in sito or sever dysplasia.
Stage 1,2,3,4: carcinoma affecting the upper vagina stage (1),then stage (3) if it reached the lower vagina, or if it reached the remaining pelvic organ stage (4).
The importance of these stages is that when detecting the carcinoma in stage 0 or 1 the percent of five year survival is more than 90%, on the other hand in stage (4) the percent of survival is less than 5 years.
Comments on some pictures the dr. showed to us:
• A- benign cells, called waver cells, transparent, large cell body, crispy((متكسر.
The nucleus is very small, ovoid or circular in shape, the nuclear membrane is very smooth, nucleus to cytoplasm ratio is 1:6 or 1:7.
• B- opposite of these characteristics are applied on the other type of cells (cancer cells).
A B




Good luck everyone.
Done by: Eman Hashem Al-Momani.
3rd lecture for Dr. Faisal Kamal.
15/3/2011
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