A United States Army Medical Department 

continuing Education program,

the 24 th annual Armed Forces seminar on 

obstetrics and gynecology,

clinical management of lower generative 

tract pre malignant pathology 

with John JM MD,

Professor OBGYN Department,

University of Pennsylvania at Philadelphia.

The previous discussions 

have brought into focus 

in a very fine way,

the present status of thinking about 

the early lesions,

particularly those that apply to 

the cervix.

And I would like to cover 

some points again,

that has been or have been brought 

out by these speakers.

First,

as Doctor Roberts showed the 

important aspect with regard to 

scientology and its clinical 

application in the management of a patient 

is communication.

And unless the clinician 

has an ongoing line 

of communication with 

his cy pathologist,

I think he can be misled into doing 

things that may not be in the best interest of the patient.

Secondly,

with regard to the utilization of 

colposcopy as 

doctor O has demonstrated,

and as Dr Fenoglio has demonstrated 

that the utilization of colposcopy 

as a an additive 

method of clinical estimation of what is going 

on in a particular patient's cervix 

is a very,

very important feature 

in a step that can be now 

used in the management of patients with 

premalignant uh cervical pathology.

First of all,

it is important that when a 

patient has an abnormal 

cytologic smear from the cervix and 

endocervix,

I would like to stress again that a single 

sample of material taken 

from the cervix should be considered 

inadequate.

Those studies show that if you take this sample from 

the endocervix,

either with aspiration or by a 

moisten cotton tip applicator.

And I might add that our cytologist does not 

like the moistened cotton tip applicator.

And I think most cytologists do not,

but the aspiration technique appears to 

be probably the best method of 

obtaining a good sample that we 

should be in a position to pick up most of the 

abnormalities present in a particular patient,

the vaginal pool as a method 

of screening,

I think has been largely discarded.

And we may use this in our discussion.

Our first step is usually to have the patient 

return for a repeat smear 

examination.

And I think this is this gives us some 

idea as to whether perhaps in the 

first sampling,

we may have missed a lesion that was 

more extensive by our cytology.

And secondly,

we may find that occasionally the second 

sampling will show no abnormality 

whatsoever suggesting perhaps that there may 

have been a mix up in the slides or that something 

else may have happened in 

between that may have altered the 

pathologic process.

The next step is to have the patient 

evaluated colposcopic if you 

have a colposcopy available to do 

this.

And again,

I would like to stress the fact that a single 

uh course,

the evaluation of a few patients in your 

practice is usually not 

sufficient to make you be 

able to be comfortable to 

rely on.

Using this as the only method of 

following a patient.

I think in the studies that have been done uh 

primarily by Doctor Richard,

by Kaufman Townsend and 

others,

where patients have been observed colposcopic 

where they were a part of a 

well designed program and where 

the patients were liable,

such things can be done and have been done 

to the great advantage of patients who are going to 

come after them in order to be able 

to pick out those patients that perhaps can 

be treated by a lesser method of treatment than we have 

used in the past.

I think that the reliability of the patient is a 

very important aspect of what we're 

talking about today.

If you're dealing with a typical patient who 

has a ac in 

lesion,

if you're dealing with a patient who is 

in the lower socioeconomic group,

who has begun her sexual life early,

who may already have been divorced and remarried a couple of 

times or has 

had several Children.

This type of patient not only is 

epidemiologically at risk for the development of 

these lesions.

She also is probably the kind of 

individual who is going to be somewhat 

unreliable in follow up.

And I think a part of your total assessment of the patient 

has got to include whether or not this patient 

is going to come back and have done to her 

what you plan to do and that she 

understands thoroughly what you are trying to 

accomplish uh with 

the colposcopic examination.

Again,

utilizing the concepts that have been 

presented today,

it may be possible for the colposcopy 

to identify and even 

remove the entire lesion 

provided it is within the transformation 

zone and such can be accomplished.

On the other hand,

if the lesion is not totally visible 

or if there are extensions that go up into 

the endocervix,

where we begin to get into the complicated 

anatomy of the endocervix where it grooves and 

clefts and other 

indentations are available 

for this epithet to become hidden 

somewhat.

It may be more difficult using 

colposcopy in order to determine what is 

going on in those areas.

However,

where directed localized biopsy can be 

carried out either utilizing this method of 

approach or in the hands of experienced 

colposcopy,

utilizing a biopsy of the 

area that appears to have the most advanced 

lesion followed by local 

treatment to the cervix,

either in the form of cryosurgery or in 

the form of cauterization may be all that 

is necessary to accomplish the 

destruction of the abnormal epithelium,

allowing normal meta plastic epithelium to 

take its place.

Huh last 

year at this meeting,

Dr Upton,

formerly of Portsmouth presented the use of 

the laser beam in which 

directed very,

very minutely measured 

approaches to epithelial 

neoplasia were applied.

I think this is still in a very 

experimental 

area.

But there may be a possibility that utilizing 

such instrumentation and 

techniques may be helpful in 

localizing very strictly the lesion 

and not to have to apply 

freezing or burning to large areas of the 

cervix.

This would reduce the 

possibility of stenosis of the cervix that 

sometimes occurs even after simple 

cauterization.

Uh And uh I think improve the possibility of 

pregnancy and those girls who are interested in that particular 

area.

Here we have the first slide,

please just to 

review briefly,

the pathogenesis progressing 

from the normal cervix through 

the chronic citti,

which is essentially typical of just about any cervix 

that you look at under the microscope.

We may exclude this term because according to 

Dr Fenoglio,

this morning reserve cells probably are not a 

significant part of this process.

So let's delete this line and go on to 

dysplasia and carcinoma.

And two,

the important thing clinically is that 

the median age of 

patients in any screen group who will 

demonstrate dysplasia is somewhere in the 

twenties.

Therefore,

it suggests that this process probably 

begins sometime after the 

initial pregnancy or after the 

changes that occur with adolescents 

coupled with sexual activity.

The carcinoma in C two group again is 

about five or so years 

older.

And the invasive carcinoma group is about 10 

years older than the carcinoma in C two 

group,

the important thing to remember.

However,

again,

in the clinical management of these patients is 

that the time at which any 

CIN lesion may go on to 

invade is absolutely unknown.

It may happen back in here.

It may happen here.

It may happen here and therefore the age at which 

this occurs and the predictability 

as to what is going to happen if a 

lesion is allowed to go untreated is 

open to question.

May we have the next slide,

please?

We didn't mention much in the 

evaluation of some of these uh 

patients about the utilization of 

other methods of approach.

We've talked about colposcopy.

Uh We haven't talked about the old,

tried and true or at least tried method of the 

Schiller test to determine the 

degree of epithelial abnormality that 

may exist in the cervix.

I think it is also very important to stress at 

this time that in doing either 

the Schiller's test if you don't have colposcopy 

available or in doing colposcopy,

that attention be paid to areas of the upper 

vagina.

At the same time.

I think that two things will happen.

First,

it will tell you whether there are any epithelial 

abnormalities in the or at any 

part of the vagina which should be removed or 

treated at the same time that you're going to treat whatever is 

on the cervix.

Secondly,

uh I think that uh if we take a look 

at uh the extent of our 

dissection in terms of removal of the 

vaginal cuff.

The best time to determine this is prior 

to any type of definitive treatment such as 

Hysterectomy.

And uh as you know,

approximately one or 2% of patients uh 

will have some type of epithet 

abnormality out on the vagina 

years ago.

Uh Stanley,

we said that in evaluating 

patients with cervical intra epithelial 

carcinoma and then studying they removed 

vaginal cuff that they found as high 

as 21% had microscopic 

areas uh that were present on the vagina.

This has not held up clinically either with 

colposcopic examination or in 

recurrences of the lesion in patients who did 

not have the vaginal Cuffy remove.

It appears that the risk of a patient developing 

something in that vagina after 

she's had a carcinoma of the cervix as Dr 

Fino pointed out earlier is about 1 to 2 or 

perhaps 3%.

It means however,

that once a patient has had definitive treatment for her 

carcinoma in C two,

that she should be followed very carefully.

And that the upper vaginal and and uh 

vaginal cuff area be carefully 

evaluated on a periodic basis for the rest of her 

life.

Here,

you can see again,

the typical nonstaining area that would mark 

both the transformation zone as well as the end of cervical 

canal where the glandular epithelium does not 

take up the stain.

Now,

may we have the next slide please?

This just shows the extent of 

conization that we normally do at our 

institution in patients where we feel that 

we have to evaluate the cervix further.

This would be in patients who have 

either a lesion that 

cannot be totally defined colposcopic 

or patients who may have endocervical 

curettings that show abnormal cells,

even if it appears that the lesion is limited 

to the uh to the 

transformation zone.

And occasionally you may see a patient like this.

Um in doing the conization,

we take a cone that is beyond the area 

of non staining or beyond,

definitely beyond the transformation zone,

go up into the canal.

Roughly about uh 50% of 

the way or usually a couple of centimeters.

We try to uh in doing 

this at the time that the cone is done.

We do not use any kind of scrubbing or cleaning uh 

techniques to rub off uh the 

tissues because this plastic 

cells have a tendency to 

separate from one another.

And you may find that if you go in and rub 

this cervix a little too briskly with the 

usual type of vaginal preparation.

Prior to operation,

you may wipe off surface cells.

And perhaps then histologically what the 

pathologist will report to you is CN 

three or carcinoma in situ rather than 

dysplasia.

We have the next slide please.

And here is a finally uh the cervix which 

has been turned in uh after uh the cone 

specimen has been removed.

Now,

as you know,

the concept of utilizing 

conization as definitive treatment 

for CIN 

of all phases has been 

studied over roughly about 10 to 

15 years.

Now,

primarily in Australia and New Zealand,

there have been clinics in this country also that have 

practiced the use of conization only.

This is also a popular method of approach 

to this problem in Scandinavia and the United 

Kingdom.

And generally speaking,

in most reported series 

conization of the cervix apparently 

will control about 10 to 

15% all but 10 to 15% of 

patients who have conization done as 

was done in the past for abnormal cytology alone.

However,

if we take and study the hysterectomy specimens of 

some of these patients,

we find uh some interesting data.

May we have the next slide please?

Here we had we evaluated 

in patients who had ization of the cervix 

and were found to have carcinoma in C two 

as the uh as the major 

diagnosis.

When we looked at 270 patients,

we found that 151 of these 

patients also had dysplasia somewhere in the 

field.

Again,

I think demonstrating what has been brought out 

before that this is probably a continuum 

of a disease process.

And then if you study your specimens carefully,

you will find that a good number of patients will 

demonstrate certain degrees of dysplasia in 

addition to the major lesion,

which was carcinoma in situ.

And again,

looking at these,

we find that 58 of these patients 

had severe dysplasia in 

association with the carcinoma in si two again 

showing that continuum and the mild and moderate 

dysplasias were distributed roughly in the 

same manner.

We have the next slide.

Now,

in looking at the Hysterectomy specimen 

after removal and generally 

speaking,

we did the conization that I showed you here,

followed by hysterectomy,

usually within 24 to 48 hours,

we treated the hysterectomy specimen of 

the cervix area,

the same as the cone was treated.

And we found that if we looked at 

patients with carcinoma and C two 

as a major lesion that we had 

a residual rate of 36 almost 

37% in the 

Hysterectomy specimen.

And I think this is fairly much in keeping 

with the type of data that we hear from other 

clinics.

The residual carcinoma in situ after what 

is considered adequate conization varies between 

about 15 and 45%.

If we take an ad to this,

another 77 patients in whom there 

was no carcinoma in situ.

But where dysplasia was left behind in the 

hysterectomy,

we add another 28%.

So roughly 65% of our patients in this 

series had residual disease at the time 

of the conation.

It sounds as if this might be a good 

argument for the utilization 

of of conization as a fairly 

routine procedure.

However,

when we look at this type of information,

we're talking about patients who only 

have abnormal cytology as they're presenting 

a feature and therefore,

they were not evaluated,

colposcopic,

many of these lesions were much more advanced 

and therefore,

probably covered a greater geographic area on the 

cervix were up into the areas 

where the glands of the 

cervix were involved.

And therefore,

we found a good bit of residual disease in 

most reported series too.

If you look at the uh where the 

residual disease is,

you'll find that most of it is up in the canal of the 

cervix.

And I think it points out again,

the importance if you're going to use lesser 

methods of treatment that you evaluate the 

endo cervical canal.

And also if you're going to 

use the colposcope to identify the lesion that the 

lesion be totally visible within the 

transformation zone.

May I have the next slide,

please?

Here we have something just a little further showing the type 

of in the hysterectomy specimen,

the degree of dysplasia that was left behind.

And we noted that the majority of patients 

had mild dysplasia as the 

residual lesion.

You could argue about this somewhat that perhaps this was not 

going to be a significant lesion.

Perhaps again,

that the regression of these lesions might 

occur.

I think we'll have the lights,

please.

I think that if we're going to look at the,

at the possibility 

of utilizing just a lesser 

procedure,

then it is important to take into 

account the fact that perhaps some of the milder 

dysplasias may regress,

at least it appears that some might regress to a greater 

extent.

But generally speaking,

if we accept the concept that we're dealing with a 

continuum of a process that unless it is 

removed or destroyed will continue to grow,

then I think we have to be fairly aggressive in our 

approach to these patients.

I'd like to go on briefly from here to,

we can put the slides off.

Now,

I'd like to go on briefly to discuss 

the evaluation of patients 

with the 

both teratogenic and archaic effects of 

des uh as you know,

this is uh become quite an issue 

over the last five years since it was 

reported in 1970.

Uh that a certain group of adolescent 

girls were found to have um 

a rare type of clear cell 

carcinoma of the vagina uh related 

to the fact that the mothers uh took uh 

des or some other type of 

non synthetic estrogenic substance during 

pregnancy.

Since this time,

approximately 250 girls were found to 

have clear cell carcinoma.

And uh in this group,

one of the striking things was the fact that the 

cytology was not really 

helpful,

at least in these particular patients in 

detecting the presence of the clear cell 

carcinoma.

And I think it points up what was brought out earlier 

today and by Doctor Roberts and that is that 

scraping of the tissues is 

probably very,

very important in getting an adequate sample and 

I just had on Monday before I left,

I had the daughter of a gynecologist who 

refers a lot of oncology to me.

And unfortunately,

his daughter had been having abnormal bleeding for a whole 

year.

She had no history of des exposure could be 

determined from the mother's chart.

Although the doctor who delivered this child was known to 

use a lot of des but nothing was on the record.

The girl had been having post coal bleeding for a whole 

year,

had seen two or three gynecologists in an 

area that I won't mention.

Uh and uh all of these 

examinations were reported as 

showing uh very bad service 

and the the the cytology 

was uh normal.

Finally,

she discussed it with her father who had his partner 

take a look at her and lo and behold,

she had a very bad looking area involving the 

cervix as well as the right vaginal fornix.

And a biopsy showed a clear cell 

carcinoma.

And I think it points out that in the approach to 

any of these lesions,

we must maintain our clinical 

index of suspicion at all times.

We have patients who come in who have 

cytology taken and we find that 

the cytology is normal 

and a lesion,

there may be a gross lesion on the cervix.

We've all seen this in our experience,

a lesion that bleeds a lesion that looks 

angry,

a lesion that doesn't feel right.

The old crude clinical 

criteria of malignancy are 

there and yet because the smear is reported 

as class one or perhaps class 

two with some at ti you but nothing that we're going to get 

excited about this type of malignancy may be 

overlooked.

And in my own experience,

I still see too many patients who come in who 

have been having regular pap smears every 

six months or a year only to find that they 

turn up with a definite 

stage one B and occasionally stage two 

A carcinoma that for some reason 

or other was overlooked in previous 

screenings.

But in going back to the to the girls with 

des exposure,

we have about 600 girls now under surveillance in our 

clinic.

Uh these girls are examined uh 

with cytology and again scraping 

from both the cervix as well as the 

vaginal es.

In addition,

they are examined colposcopic.

Uh the solution is applied to 

determine areas that are abnormal.

And if we find areas that are 

suspicious,

then these are biopsies.

Otherwise random biopsies are done of 

areas of adinos.

And what we're finding is that approximately 

85% of these girls with a positive 

history of des exposure 

have lesions that 

are,

that are 

compatible with this 

first adinos.

Secondly,

the cox comb and incidentally,

this youngster that I 

mentioned had a typical cox 

comb of the cervix.

It's something that I think every gynecologist 

should be aware of because sometimes the 

patient will have absolutely no.

And the awareness that such lesions may exist 

around the cervix and vagina,

I think are very,

very important.

I think it's good to have this picture in your mind.

Any time you're examining a young girl,

particularly someone who is now between the 

age of 15 and 25 

this lesion I think is going to disappear.

But in the meantime,

it may provide some sort of a hazard for the patient.

The next question that arises is Adinos,

is this a pre malignant lesion?

There's no evidence and no one has ever followed a 

patient with Adinos that has become a clear 

cell carcinoma.

Excuse me,

we've all seen patients.

However,

with uh clear cell 

carcinoma with concomitant 

fields of adinos,

this is not an uncommon finding.

The other aspect of this particular 

entity is that more and more 

since the Adinos essentially 

represents an increase in 

the transformation zone,

basically,

all of this epithelium may be considered as 

epithelium in a transformation 

zone,

which is much,

much larger than what you have on the on the normal 

cervix.

And as a result,

there may be greater potential for abnormalities to 

develop because the metas process is 

going to be spread over a greater area.

And recently,

there has been some speculation and I think there is 

some evidence uh in,

in some of the clinics,

particularly Dr Stael's Clinic.

And I think Doctor Richard also has some patients in this 

category where uh the 

uh the Adinos in 

in undergoing the meta plastic change has 

also gone on to develop the 

intraepithelial type of neoplasia,

uh which we're talking about today,

except that this appears to be occurring in the adinos 

areas in the vagina.

So I think this is another thing to remember uh in,

in terms of evaluating these patients.

Uh I think we should consider the des 

exposed girl as one who may be at 

risk,

although very small of developing 

clear cell carcinoma and she may 

after a while,

perhaps as she gets into her thirties may be at some 

greater risk of developing the typical squamous 

lesions of uh of the CIN 

type.

Finally,

just to mention the vulva,

it seems like we've been ignoring the vulva today and sort of 

spending our time up above but with 

regard to VVER lesions,

uh I think that several things are important 

clinically.

One is the importance of peritus.

And I think that most patients who develop valva 

dystrophy of some type will have peritus 

as a major presenting symptom.

I think that many times these patients are treated 

without adequate attention to what is going on in the 

vagina.

I think we should rule out or rule in the possibility 

of parasitic infections in the vagina first.

Then I think we should look at the VVER areas very 

carefully.

The utilization of colposcopy and VVER 

disease I think is still in its infancy.

But I think that as time goes on,

we may,

we may find that the colposcope or even a simple 

magnifying glass may be of help to us in 

this particular area.

We should remember too that the lesions of the 

vagina and the velvet tend to be multifocal.

And that uh in evaluating the 

vulva use of the blue 

technique that is staining and de staining with 

acetic acid may be 

helpful in identifying the 

areas of nuclear activity where 

biopsies should be taken 

in order to provide uh the uh the uh 

histologic information about uh what is 

going on with regard to the 

management of lesions of bowen's disease 

or intraepithelial neoplasia of the vulva.

Again,

if we have a localized patch or one or two 

lesions,

these can usually be handled by wide local 

excision.

Uh I think with careful postoperative 

observation,

if there is a dystrophic lesion 

present,

either of the atrophic or the 

hypertrophic type,

these can be handled with either the use of estrogen 

or testosterone.

And again,

careful observation of the patient with 

periodic staining with tau and blue,

I think is helpful in these particular 

patients.

The other aspect 

of this is that patients with valva disease may 

have lesions up in the vagina or on the 

cervix.

So that any lesions that appear on the vulva should 

be associated with careful screening of the vagina and 

cervix.

In order to be sure that lesions in those areas 

are not overlooked.

I'd like to just close.

Now by again,

re emphasizing the fact that an 

evaluation of these lesions and the clinical approach 

to their management.

We should not forget the fact that,

that we must know exactly what we're 

thinking about exactly what we're looking for.

We must take into account the 

available 

techniques that we have to work with in order to get 

the best results.

And the main thing when we're talking about pre malignant 

lesions is that we must never 

ever allow a patient to go on to 

become an invasive malignancy if we can in 

any way avoid it.

Thank you.

This program was produced through the mobile 

facilities of the television branch,

Health Sciences,

media division,

Academy of Health Sciences,

United States Army,

Fort Sam Houston,

Texas.