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PATHOLGY LEC. 17

In the last lecture, I started to talk about a very important point which is

Differentiation and Dysplasia, and I said that the tumor loses its differentiation

and gradually base features of dysplasia and when the features are completely

lost this is Anaplasia.

Now, what is really meant by that ?

Dysplasia is a cytological or microscopic change, it has nothing to do with size ,

growth , anti by the grows of (****) appearance , its really something you

assess by looking down a microscope and dysplasia can occur in both :

epithelial cells and connective tissue cells , keep that in mind.

It indicates theres increase in the nuclear size , this is N/C nuclear cytoplasmic

ratio is increased because the nucleus starts to take up more space , theres

also variation in the shape and size of the nuclear and cell which we call it (

Pleomorphism) , its not that large whereas it has different sizes and shapes ,

there is loss of differentiating features which i talked about last lecture and

also there is increase in the nuclear DNA content which means if you look at it

under microscope and the section stained by ( H&E) stain which you look at inyour lab. , then the nucleus becomes very loobed which is called (

Hyperchromatism) . its dark loop and it has a higher DNA content , thats why

its hyperchromatic ( alot of staining ) deep blue. Whereas the cytoplasm is

always pink in the skin. The nucleoli in many cases are not really seen clearly in

the benign or normal condition. In the malignant ones frequently but again not

always they appear prominent and sometimes we see more than one

nucleolus. Sometimes the nucleolus is quite big and become sort of reddish in

appearance ( very recognizable ) but its not always seen in malignancy.

Mitotic figures , remember theyre seen in many normal tissues, where canwe find them?

The whole GI tract , BM. But the GI tract , the mucosal cells frequently change

this thing . any replicated tissue can show mitotic figures. But these mitotic are

really within normal , the uterine endometrium ( its continually changing

every month ) , so during menstrual cycle is replicating. So, mitosis is notabnormal .

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But in malignant conditions you see that the mitotic figures are increased and

the important point is that in many malignant processes you get:

abnormal mitosis, What is meant by that?The normal : is bipolar division, if its abnormal you may see a huge mitotic

figure : double, triple the normal. So, theres sometimes four or five duplicates

( very huge ). The presence of abnormal mitosis means definitely that the

tissue is malignant.

A bipolar mitosis : may exceed in benign or malignant or normal but frequently

its increase in number. So, the presence of bipolar mitosis is not exclusive of a

benign process. Its seen in either but when its abnormal, its malignant.

Loss of polarity: what do we mean about it ?Always in the lecture I give an example of this (fens= el 7ajz ely 3la el stage)

which is very straight, the lines are put parallel, very well arranged. This is

polarily arranged, when you come to a malignant process and you imagine that

this part is the basement membrane. When you come to a proliferating

malignant process, this is gradually lost. Why? Because the cells increase in

number in a very disorder deflation, exactly when you are walking in a queue

and then the bus comes, all of you come together to the door ( ttl5b6 el

entrance ). So, the cells become jumbled up as we shall see in the picture.

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Now here, you have severe Dysplasia or anaplasia.

I cant say whether the tissue is a carcinoma , lymphoma , melanoma or

whatever but look at this mitotic figure which is (Y) shaped: its tripolar.

Some of the cells are irregular and the nucleus is quite dark, look at it in the

figure. So, theres hyperchromatism , pleomorphism , mitosis , abnormal

mitosis and so on.

When you come to the process ofintraepithelial neoplasia, which is beingtalked about now in many tissues.

For example: tissues of the breast in the ducts , in the prostate again ducts and

in gastric epithelium always when you have epithelial surface. The

intraepithelial starts inside the epithelial. All this dysplastic features and then itprotrudes destroy the basement membrane and goes outside and filtrate. So,

many cancers start many carcinoma not sarcoma, start inside the epithelium

which becomes thicker and loses its polarity with a lot of mitosis and then

extends.

Ahmad Tamimi asked: whats the difference between sarcoma and carcinoma?

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Ans: basically sarcoma is originate from connective tissue and mesenchymal

cells rather than the epithelial, other than that for example: dysplasia occurs in

both.

Theres no intraepithelial neoplasia in sarcoma. Sarcoma spreads differently

which is more in different each group. For example: we dont have carcinoma

in a muscle unless its metastatic from let us say breasts. Sarcoma is

completely different from carcinoma but both are types of cancer.

Intraepithelial neoplasia is dysplasia involving an epithelial surface and it could

be graded either low grade or high g rade and I will discuss that: high grade

dysplasia limited by the epithelial basement membrane which is now called

carcinoma in situ which means limited in its place, and ones the basementmembrane is disrupted or broken then its an infiltrative or invasive carcinoma.

Now, if you look at this picture:

Here: this is the basement membrane and the whole thing is epithelial, and

you can see its full of cells, the polarity is assist here, you can see that

although theres some degree of polarity, its still in many areas ( its jumbled

up ) , theres some loss of polarity and mitosis if you have a normal process.Mitosis is usually limited for example in the skin ( the epidermis ) , mitotic

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figure maybe seen here but theyre not seen here. Why therere seen here

sometimes in malignancy? Because this is proliferating so fast and the mitosis

are pushed up and theyre increased. When you look at a higher power, look at

these all are mitotic figures. ( arrows )

So, this whole thickness is dysplasia or intraepithelial high grade dysplasia or

carcinoma in situ. If this process is broken down here and extend you will see

malignant cells here, this is dysmelium inflamed reserve. But if the process

extends in sub epithelial tissue then this is invasive carcinoma, as I said

dysplasia occurs in sarcoma or connective tissue but not intraepithelial or

carcinoma in situ. You dont get in situ lesions in sarcomas. Its either benign or

malignant.

Now, remember that not all dysplasia progress to high grade. If we look to the

thickness in the previous figure, if the dysplasia is only here this is low grade. If

it extends to the top, imagine an imaginary line here is high grade dysplasia

and here low grade.

Previously, we use to have low, intermediate and high which is lower third,

middle third, upper third and some people use that. In many cases it can be

graded.

Not all carcinomas in situ progress to invasive cancer. For example: if you have

the cervix, you may have carcinoma in situ for 10 years before its invasive or

some doesnt spread. So, not all of them spread and in some cases it may

regress : the process may stop if its treated. I mean some maybe due to

certain agents and if you remove the agent it maybe stopped. Some really are

not true dysplasia : if theres a lot of inflammation, the cells start to show

mitosis but this we call reactive process rather than actual dysplasia.

A student asked: if the dysplasia reversible ?

Ans: yes, but not all of them.

2-Rate of growth:

Usually benign tumor grow very slowly, its usually correlate with the level of

differentiation.

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Now, usually in the benign processes: tumors are pro-differentiated and they

may get a cursive with a lipoma which is a subcutaneous mass of a fatty tissue,

this is remain just a small polyp under the skin ( mass under the skin ) for 30

years then gradually slowly grow into instead of this side become to this side.

some of them do *** but still remain benign. But this process is very slow.

However, if this for example an adenoma in the thyroid , it may show bleeding

in side. The bleeding shows that the tumor mass have increased in size or for

example: a fibroadenoma in the breast where they should becomes pregnant,

the breast as a whole enlarges and the fibroadenoma itself enlarges. The rate

of growth in malignancy usually the more poorly differentiated tumors are

usually larger than the well differentiated but this is not a rule, it maybe rapid

in some benign tumors as : haemorrhage , pregnancy and leiomyoma in the

uterus may become very big. And some tumors may shrink in size even if they

are malignant, why? Sometimes, newly processes in the body can destroy

tumors cells, this is especially seen in melanoma , sometimes melanomas may

disappear but the metastasis in the lymph node is present.

Sorry, didnt hear the question very well but I think its, Can malignant tumors

outgrow their blood supply?? :P

answer: yes , as you look here some malignant tumors may outgrow their

blood supply, they grow so rapidly that the blood muscles are not sufficiently

fed, they become infracted ( they shrink ). Sometime fibroadenomas in the

breast of a female who are not removed and the patient is now 50 or 60 it may

shrink because of (melapose). So, there maybe variation but its not really an

important feature in assessing whether a tissue is benign or malignant.

Now, some tumors are hormone dependent and this is especially seen inbreast cancer, thyroid cancer and prostatic cancer. And this hormone

dependent is through receptors or surface of tumor cells. Why is that an

important fact?

Ahmad Tamimi ans: you can inhibit hormone production and cause shrinkage

on the tumor ( quite right :P ). Because theyve receptors and this in the

breasts when you have a breast cancer, its diagnose in the lab. , we do a study

for the presence or absences of hormone receptors, and if its present you giveanti-hormone therapy which in the case of the breasts called ( thamoxycal )

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which is anti-estrogens and the patient is advised to take (thamoxycal) for 5

years to depress the tumor cells that maybe present in that patient. The same

applies on the case of prostate. You get estrogens for example or you castrate

the patient ( remove the testis ). Males can have breasts cancer ( rare concept )

especially in older males but you can get it even in young people but its rare. It

depends on the hormones but not all breasts cancer depend on estrogens.

Some, especially the high grade ones in the younger people they dont have

good receptors for estrogens and progesterone and these hormones anti-

hormones are not useful for treatment, theyre given something else which is

herceptin , well talk about that in the future.

3-Local invasive & Encapsulation:

Local invasive means: spread of the tumor within short distant surrounding it.

As compared, if you remember the diagram I showed you last lecture of the

uterus and I compared the two muscles, the one that benign was round, small

and encapsulated whereas the other one showed projections. So, the benign

tumor frequently has a capsule and this capsule could be a fibrous capsule or it

could be compress normal tissue of that organ for example ( leiomyoma ) itscapsule is also smooth muscle but its compressed around it. Malignant tumors

progressively invade and destroy surrounding tissue. Sometimes malignant

tumors also have some capsule but its not very compact which mean it can

burst through the capsule and you dont really say capsule ( we see it limited a

rounded tumor = not true capsule ). And we find that it will extend through it,

thats why in the majority of malignant processes the surgeon will try to

remove wide excision. If its in the leg here, he will amputate above the knee

amputation.

Whats meant by local invasion..?

For example: if you have a breast cancer ( la sm7 allah ) it will infiltrate the skin

and the underlying muscle. Basal carcinoma and youll hear this name again

which is type of very common skin cancer, the major features about is that: it

has a tendency to be a very invasive. Its often in the face and its may invade

the (couldnt hear) face but doesnt metastasis. But invasion itself is a sign ofcancer, it may infiltrate the nerve in the case for example: the facial nerve and

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cause facial paralysis. And you can see here its the second most important

feature distinguishing malignant tumor which is local invasion not the

capsule.

4-Metastasis: is the most important point of differentiation.

Benign tumor never metstasis.

Malignant tumor usually metastasis but not necessarily, for example: basal cell

carcinoma doesnt. Metastasis means spread of malignant tumor to distant site

not contiguous ( ( with the mean tumor. Like breast to the brain, kidney ,

bone. All tumor can potentially metastasize except basal cell CA and Glioma.

Glioma: its a tumor of glial tissue inside the brain, theyre usually inside thebrain, they dont spread outside but because of their cousins in the brain

barrier inside the skull, itll kill you very quickly. And its also depend on the

grade and the type of the tumor, but in general: Glial tumors dont spread

outside the skull. Metastasis is often proportionate to the size and the

differentiation of the primary tumor which means if you have a malignant

tumor, the bigger it is , the less differentiated it is and the more likely it is to

metastasis. You may have small tumor for example: *** carcinoma of the ** is

a very slow growing malignant tumor.

Does metastasis to the lymph node ** but its a very slow process and may not

even metastasis. And you shall see that this depend on the nature of the tumor

cells.

Lutfi asked: but unfortunately I couldnt hear it very well

But the answer is: we do radiation and chemotherapy together, if its

accessible for example: if its in the frontal lobe, its accessible and you can

remove most of the tumor but if its in the base of the brain you can hardly

touch it. Youll learn it later , we use other methods.

Quest: Is the can be large in size, less differentiated and more likely to be

metastasis?

Answer: not as the tumor that is large is poorly differentiated and will be likely

metastatic, but in general; the whole thing is proportionate. The bigger thetumor and less differentiated itll be more likely to metastasis, this doesnt

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mean that every big tumor is poorly differentiated. But if that characteristics

came together its more likely to metastasis.

Now, what are the routes of metastases? , how does it spread apart from the

local invasion?

It means apart away, it goes by the lymphatic channels , blood vessels and

seeding within the body cavity which is called Transcoelomic spread.

Where do we have coelomic surfaces?

Along the mesothelium in the pleural & peritoneal cavity. Well come to each

one.

The lymphatic spread is a feature that is seen more with carcinoma ratherthan sarcoma. However, this is not an exception, sarcoma can also go by the

lymphatic drainage but usually if you have breast cancer, the first thing it

does if its metastasis, itll go to the lymph node.

If you have a sarcoma it may go to the lymph node but frequently it goes to the

blood vessels. This is a difference between sarcoma and carcinoma.

The spread usually follows the anatomical route of drainage unless you havemetastasis. What does that mean? In the case of the breast cancer

anatomically, if you have a tumor in the left upper quadrant, then where does

it go? Itll go to the left axilla. Its depending on the anatomical route.

When I say upper left quadrant usually when we talk about breast cancer we

divide the breast theoretically into 4 quarters (quadrants) and we say the mass

in the upper left quadrant, lower left medial quadrant upper or lower.

If the cancer in the medial quadrant it will go to the internal memory chain

supra-clavicular or infra-clavicular. Always its according to the Anatomy.

However, if this patient has had for example: radiation and you have a blocked

channel which is a result of the radiation or its completely blocked by tumor,

then where does the tumor go? it will skip metastasis and ensure that itll go

to the other side.

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Lung cancer: its frequently around the peri-bronchial passages, its usually

bronchial origin. It goes to the peri-bronchial glands, trachea-bronchial lymph

nodes then the hilar lymph nodes.

The sentinel lymph node is a special lymph node which is called sentinel. Thisis the first lymph node in the pathway of primary tumor which means the

surgeon during an operation gives a dye to the breast or it can be the same as

in the colon and the dye moves. The first lymph node that takes the dye up its

called the sentinel lymph node which means its the first defence

mechanism. Now, this sentinel lymph node shows if it doesnt contain

metastatic tumor than most likely the other lymph node, which are further

behind it are free, they dont containtumor. Its important in surgical practice

to assist the surgical if the sentinel lymph node. The surgeon sent it separately

and labels it as the sentinel lymph node. (Sentinel means which is like from

sentry= )

The tumor cells come, if theyre rejected this lymph node which is coloured

blue by the dye would not contain metastasis tumor. If its weak, the tumor

can penetrate and this mean probably other lymph nodes are involved. Now,

remember that some lymph nodes during process of surgery are also enlarge

but that doesnt mean every enlarged lymph node contains metastatic tumor.

It could be reactive to the presence of the tumor ( reactive hyperplasia ) ,

sometimes you get prominent Histiocytes again in the lymph node as type of

defence mechanism.

Blood vessels: haematogenous through the blood.Now, usually venous first allowing anatomical drainage, why its by venous?

Lutfi answers: because the arteries are thicker (has muscle). So, itll not be

easy for the cancer cell to enter an artery, its easier to penetrate vein.

Ahmad Jarrar additions: and the pressure also included.

So, the easiest thing to do is to enter a vein and through it, itll spread

throughout the body. Now, it goes to the lung and through to the liver.

Especially if we have tumor which for example: in the GI tract, it will go to the

liver.

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This is more characteristic of sarcoma that theyre spread through the blood

stream. However, it does occur in the later stages of carcinoma when it

spreads widely, parts of the poor features in the carcinoma is that it also uses

blood vessels. And always when you look at tumor whether its carcinoma or

sarcoma, we mention in our report there is (+) lympho vascular invasion.

However, although this is a late stage in carcinoma but there are certain types

of carcinoma that use blood vessels very early in their development. And that

is renal carcinoma which goes to the renal vein and the inferior vena cava

(IVC), and hepatocellular carcinoma which goes to the portal & hepatic vein.

( theyre carcinoma but they goes by the blood )

Melanoma spreads in blood & lymph node in a very wide spread.

Transcoelomic spread: this is within the peritoneal or pleural cavity, thecancer cells are shed into the fluid of the coelomic cavities and swims across

a distance. For example: If you have tumor in the upper lobe of the lung, you

may have siblings in the lower. Or: cancer of the stomach or even breasts.

Breast goes to the liver then to ovary which are in the pelvis, this is quite a

distance and a gastric cancer may present for the first time with ovarian

metastasis. ( this is Transcoelomic spread )

Also, cancer of the ovary tends to spread very widely through the peritoneal

surface, its really has a tendency to spread throughout the intestine and so on.

Cancer of the colon may go across the peritoneum to small intestine (SI) &

other lobes of colon.

This was all the examples of the Transcoelomic spread, especially here in the

ovary in the pelvis about the whole thing is blocked by tumor which is called

frozen pelvis.The surgeon cant remove anything. ( because its one mass )

Ahmad Tamimi asked: Is benign lieomyoma could be on the ovary?

Answer: Not usually, because theyre not related. Benign lieomyoma is a mass

in the uterus which may produce bleeding, may interfere sometimes with

conceptions and the lieomyoma could make obstruction to uterine cavity

depending on the site and location.

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This is a summary of benign and malignant tumors, you can see each one that

we talked about:

Summary : Differences between benign &

malignant neoplasmsBenign vs malignant

Well-differentiatedLow mitotic indexSlow GrowthWith capsuleNo invasionNo metastases

AnaplasticHigh mitotic indexRapid growthInfiltrative growth

without capsule

InvasionMetastases

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Epidemiology: is a study of a disease in community and by studying the disease

you study the different types of cancer and factors.* you can see the diagram

below: that first three cancers in males which are they: prostate , bronchial &

lung , colon & rectum while the female: breast , lung & bronchial , colon &

rectum.

And look at the cancers death diagram:

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Prognosis: how bad/good behaviour of the tumor.

Lung cancer is one of the worst cancer that you can get. So, it kills very often.

Few patients live for 5 years, thats why it has very high mortality. So, when

you end up counting the cancer deaths, lung is the most. Thats why STOP

SMOKING.

Note: they dont use lung transplant for cancer.

You can see in the figure below (from King Hussien cancer centre) the most

common cancers among Jordanian males :

And that among Jordanian females :

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Done by:

Mousa Alhokail

Note: the (*) signs means that i didnt hear the record very well, sorry.

Forgive me for any mistakes in the lecture, and wish you ALL THE BEST in your

EXAMS.

I want to thank every single person in our GREAT BATCH for their FANTASTIC

EFFORTS. :*