Chapter 22: Female Genital Pathology

Welcome to Last Minute Lecture.

This free chapter overview is designed to help students review and understand key concepts.

These summaries supplement not replaced the original textbook and may not be redistributed or resold.

For complete coverage, always consult the official text.

Welcome back to The Deep Dive.

Today we are tackling a beast of the topic.

We really are.

It's something that I think a lot of medical students and honestly just anyone interested in how the human body can go wrong,

finds equal parts fascinating and terrifying.

That's a good way to put it.

We are doing a specialized review session diving specifically into chapter 22 of the USMLE step one lecture notes on pathology.

That's right.

We are decoding female genital pathology.

And look, I know pathology can sound dry, it conjures up images of endless slides and memorizing lists of protein markers.

But this chapter, this chapter is actually structured beautifully because it tells the story of anatomy.

It really does.

And our mission today is pretty straightforward, but it's I'd say ambitious.

We are going to decode this massive topic by strictly following the flow of the chapter.

No jumping around.

No jumping around.

We are going to move anatomically just like a surgeon or maybe an infection would move through the body.

Exactly.

We're going to take a journey from the outside in.

We'll start with the vulva, the skin and external structures.

Then we move up through the canal of the vagina, hit the gateway of the cervix, enter the uterus itself and then float out to the ovaries.

And finally the placenta.

And finally we'll finish up with the pathology of pregnancy and the placenta.

So if you are a medical student prepping for boards or just a learner who wants these high yield concepts translated into plain English,

you are in the right place.

But here is the deal.

We want to avoid that exam panic mode, you know, where you just frantically memorize 46XX or Kruckenberg without knowing what it actually means.

Panic helps no one learn.

We want to focus on the logic of the diseases.

If you understand the mechanism, why a cell changes the way it does or why a specific bacteria targets a specific tissue, you don't have to memorize nearly as much.

The facts just stick.

They just stick because they make sense.

I love that.

Logic overwrote memorization.

And we're going to stop and visualize the specific figures and break down those dense tables found in the text as we go.

Yeah, some of those tables can be real walls of text.

Exactly.

They're intimidating until you actually read them.

So let's not waste any time.

Let's start at the beginning.

Section one, the vulva.

The vulva.

So anatomically we're talking about the external structures, the skin, the labia.

And because it's skin, the text starts us off with non -neoplastic disorders, specifically dermatological issues.

Right.

And immediately the text throws two terms at us that sound frustratingly similar.

Lichen sclerosis and lichen simplex chronicus.

They both start with lichen.

They both affect the vulva, but they seem to be opposites.

Let's unpack lichen sclerosis first.

So lichen sclerosis is really defined by thinning.

That is your anchor concept here.

It's an epidermal thinning.

The top layer of skin gets thin.

Right.

But it's not just getting thin.

There is a change in the dermis underneath, specifically a sclerosis or

that results in this pale parchment -like skin.

Parchment -like.

That's a key visual.

Like old crinkled paper.

Exactly.

Imagine paper that is so thin, it's brittle and white.

That's the leukoplakia, the white patch you see clinically.

Now, why does this happen?

The text points toward an autoimmune etiology.

Wow.

The body is essentially attacking the interface between the epidermis and the dermis.

And because it's autoimmune related, does that give us a clue about the demographic?

It does.

We typically see this in postmenopausal women.

And the clinical relevance here, aside from the discomfort and the itching, is the long -term risk.

Right.

There's a big one.

There is a small but very real risk of this progressing to squamous cell carcinoma or SCC.

OK.

So let's lock that in.

Lichen sclerosis, thinning, parchment paper skin, autoimmune postmenopausal, and a cancer risk.

Now, contrast that with lichen simplex chronicus.

Lichen simplex chronicus is almost the reverse in terms of the tissue change.

It's not an autoimmune attack.

It's a mechanical issue.

It's caused by a chronic scratch itch cycle.

A scratch itch cycle.

You mean the patient does it to themselves?

Essentially, yes.

It starts with an itch, maybe from an infection, maybe from detergent irritation, and the person scratches.

The scratching irritates the skin, which makes it itch more.

So they scratch more.

So they scratch more.

Over time, what does skin do when you constantly rub it?

It gets calloused.

It gets thicker.

Precisely.

That is the hallmark.

Thickening of the epidermis, which we call squamous cell hyperplasia.

So clinically, you still see white plaques, which is why it's confusing.

But the texture is leathery and thick, not thin and parchment -like.

And the million -dollar question.

Does this one cause cancer?

Generally, no.

That is a crucial distinction the text makes.

Lichen simplex chronicus is inflammatory and reactive, not neoplastic.

It doesn't carry that same risk of progression to carcinoma that sclerosis does.

That is definitely a distinction that sounds like a board question trap.

Okay, moving on from skin conditions to infections of the vulva, the text lists quite a few, but we have to start with the big one, the one that dominates this entire chapter, HPV.

Human papillomavirus.

It's unavoidable in genital pathology.

Specifically for the vulva, the text focuses on a condition called

condylamata acuminata.

Which is a very fancy Latin way of saying genital warts.

It is.

But we need to be specific about what these look like.

If we look at Figure 22 -1 in the chapter, it gives us a very clear, maybe slightly disturbing visual of a severe case.

Yeah, paint that picture for us.

Because warts sounds like a little bump on your finger.

This is different.

It is distinct.

Figure 22 -1 shows these extensive clustered lesions.

The classic description used in pathology is cauliflower -like.

Caulicolor -like.

They are raised, they are bumpy, and they have this textured surface.

In severe cases, they can cover a significant portion of the vulva area.

And when we talk about the cause here, we need to talk numbers.

HPV has so many subtypes.

Which ones are building these cauliflower cities on the vulva?

For condylamata acuminata, the warts, we're usually looking at HPV subtypes 6 and 11.

Here's where students get confused.

Are 6 and 11 the dangerous ones?

Are these the ones that are going to cause major problems down the line?

Generally, no.

That's a really important point the text makes.

HPV 6 and 11 have low oncogenic potential.

They are very good at making warts, which are distressing and unsightly, but they aren't the high -risk types associated with high -grade invasive cancer.

Got it.

We'll see the dangerous ones later when we get to the cervix.

Okay.

6 and 11 give you warts, but usually not cancer.

Low numbers, low risk.

Now, let's run through the other infections quickly, because there are some distinct clinical clues here.

Let's talk about herpes.

HSV2 is the usual culprit for genital herpes.

The key here for diagnosis is the progression of the lesion.

It doesn't just appear as an ulcer.

It starts as vesicles,

little fluid -filled sacs.

They are painless at first, but then they become pustules, and finally they break open into painful ulcers.

Painful is the key word there, because if I have a patient who comes in with ulcer down there, but they tell me, hey doc, it looks bad, but it doesn't hurt at all, I shouldn't be relieved.

No, you should not be.

I should be worried about syphilis, right?

Exactly.

That is the classic presentation of primary syphilis caused by the Spearishet treponema pallidum.

The hallmark lesion is the chancre.

The chancre.

And a chancre is a hard, painless ulcer.

And why is it dangerous?

Because if it doesn't hurt, people ignore it.

And the text notes that the chancre eventually heals on its own without scarring.

So the patient thinks it's over.

The patient thinks, oh great, the infection is gone, but it's not.

The bacteria has just gone systemic, and secondary or tertiary syphilis can be devastating years later.

That is sneaky.

Okay, two more quick ones.

Molluscum contagiosum.

That sounds like a spell from Harry Potter.

It does, it's a poxvirus infection.

The visual buzzword here is smooth papules.

They aren't warty like HPV, they are smooth and dome shaped, often with a little dimple in the center.

Okay, a central umbilication.

Exactly.

And if you look under a microscope, you'd see cytoplasmic viral inclusions inside the cells.

And finally, the Bartholin gland abscess.

This is more mechanical in a way.

The Bartholin glands are located on the side of the vaginal opening.

If the duct gets blocked, fluid builds up.

And then it gets infected.

Then it gets infected.

Usually polymicrobial, lots of different bugs.

It causes a large painful mass that needs to be surgically drained.

Okay, let's shift gears to vulvar tumors.

We have benign and malignant ones here.

Let's start with one that sounds scary but isn't.

Pepillary hydrodinoma.

Right, this is a benign tumor of the sweat glands.

Specifically, the modified apocrine glands found in the vulva usually pops up on the labia majora.

Why does it confuse people?

Why is it in the text if it's benign?

Because it can ulcerate.

And in the world of pathology, when you see a mass that ulcerates and bleeds, your brain immediately goes to cancer.

Right, that's a red flag.

It's a huge red flag, but this is benign.

Histologically, it looks very similar to an intraductal papilloma of the breast, which makes sense, right?

How so?

The breast and the vulva both have these modified glandular tissues.

They're embryologically related in a way.

That leads us to another breast -related confusion, extramammary pageant disease.

This is fascinating and a very high -yield distinction.

So clinically, you see a red crusted rash on the labia majora.

It looks like dermatitis or eczema.

It might itch.

But it's not.

It's not.

Under the microscope, you see these large malignant cells spreading through the epidermis.

We call that paigetoid spread.

Now in the breast, if a woman has pageant disease of the nipple, that is bad news.

It almost always indicates a cancer underneath, deeper in the breast tissue.

Is that true for the vulva?

No, and that is the crucial distinction you have to make.

Extramammary pageant disease of the vulva is usually not associated with an underlying invasive tumor.

So it's just on the surface?

It's strictly confined to the epidermis.

So it has the same name and looks the same on the skin.

But the implications are totally different.

In the breast, it's the tip of the iceberg.

In the vulva, it's usually the whole iceberg.

That is definitely something to highlight.

Okay, let's talk about the actual cancer.

Squamous cell carcinoma of the vulva.

This is the most common vulvar malignancy, and the text describes a really interesting concept here.

There are two distinct pathways to getting this same cancer.

Two roads to the same bad destination.

Exactly.

Road number one is HPV related.

This tends to happen in younger women, relatively speaking, maybe 40s or 50s.

It's linked to the high -risk serotypes, 16 and 18.

The bad ones.

The bad ones.

And it arises from a precursor lesion called VIN, or vulvar intrapathelial neoplasia.

It basically acts like cervical cancer, but on the skin.

And road number two.

The non -HPV pathway.

This is usually seen in older women, typically over 60 or 70.

It's not viral.

Instead, it's related to chronic inflammation or long -standing leg and sclerosis.

The one we started with.

The one we talked about at the very start of the show.

So that chronic irritation eventually causes the DNA to break.

It's a p53 mutation, right?

Correct.

It's a p53 mutation pathway, usually, driven by age and chronic turnover of cells.

Okay.

And finally, for the vulva, melanoma.

It can occur here.

It's rare.

The main teaching point is distinguishing it from extramary pageant disease, which we just discussed.

Both can look like pigmented or red lesions.

So you need special stains?

You absolutely need special stains to tell them apart.

Melanoma stains for S100, pageant stains for PAS, and keratin.

All right.

We've cleared the vulva.

Let's move inward.

Section two.

The vagina.

The vagina is actually a relatively rare site for primary pathology compared to the cervix or uterus.

It's a tough squamous line tube, but there are some specific high -yield conditions.

And one of them is a history lesson, as much as a pathology lesson.

Let's talk about adenosis in DES.

This is a classic clinical correlate.

DES, or Diclostylbestrol, was a synthetic estrogen.

It was given to women with high -risk pregnancies, women who had previous miscarriages between roughly 1940 and 1970.

Why?

What was the thinking?

The idea was that low estrogen caused miscarriages, so giving more would help.

And the tragedy wasn't necessarily for the mothers taking it, but for their daughters.

Correct.

The female offspring exposed to DES in utero had a developmental error.

Normally, the vagina is lined by squamous epithelium -tough skin -like cells, but in these women, the upper part of the vagina retained glandular epithelium.

And that's adenosis.

That's called vaginal adenosis.

So they have glands in the vagina where they should have squamous cells.

Is adenosis itself cancer?

No.

Adenosis is benign.

However, it is unstable tissue.

It increases the risk of developing a very specific, very rare cancer called clear cell adenocarcinoma.

So if you see a board question about a young woman with clear cell adenocarcinoma of the vagina,

you practically don't even need to read the rest.

No.

You have to look for that maternal DES history.

100%.

It's a buzzword association.

There's another developmental issue mentioned.

The Gardner duct cyst.

Yes.

This is a cyst on the lateral wall of the vagina.

It helps to remember your embryology here.

In the fetus, you have the Wolfian ducts, mesonephric, and the Malarian ducts, parameconephric.

The Wolfian duct is usually the male duct system, right?

It makes the vas deferens and epididymis.

Exactly.

In females, the Wolfian duct should degenerate and disappear.

But sometimes, biology is messy.

If a piece of that male duct stays behind in the vaginal wall, it can form a fluid -filled cyst.

And that's the Gardner duct cyst.

That's the Gardner duct cyst.

It's benign, but it explains why you might find a cyst there.

Now let's talk about a tumor that affects children.

This one is heartbreaking but distinct.

Sarcoma boteroids.

This is a form of embryonal rhabdomial sarcoma.

Rhabdo means skeletal muscle.

So this is a malignant tumor of skeletal muscle cells.

It affects infants and young children, usually under age five.

And the visual here is iconic.

I think once you hear it, you never forget it.

Grape -like.

That is the buzzword.

The tumor grows as a polypoid soft tissue mass that literally looks like a bunch of grapes protruding from the vagina of a child.

That is a visceral image.

And what does it look like under the microscope?

You see spindle cells.

But there's a specific feature.

The cells crowd just underneath the epithelium, forming a dense zone called the cambium layer.

Cambium, like in a tree.

Exactly.

In botany, the cambium is the layer where growth happens.

Here, it's a dense layer of malignant cells.

And because it's a rhabdomial sarcoma, meaning it's trying to muscle,

the cells are positive for desmin, which is a muscle marker.

You can even see striations.

You might even see cross -striations in the cytoplasm, mimicking actual muscle fibers.

Moving to adults, what about vaginal carcinoma?

Primary vaginal cancer is extremely rare.

Usually, if you find squamous cell carcinoma in the vagina, it didn't start there.

It's spread from somewhere else.

It's spread there from the cervix.

We call that secondary carcinoma.

But if it is primary?

If it is primary, it's usually linked to high -risk HPV infections, similar to the cervix.

But again, you have to rule out cervical cancer first.

That's job one.

Before we leave the vagina, we have to cover the swab diagnoses.

Vaginitis.

This is huge in primary care.

The text breaks down three common causes.

Let's do a rapid -fire comparison to help listeners keep them straight.

Let's do it.

First up, candidiasis.

Yeast.

Candida albicans.

It often follows antibiotic use, because antidiotics kill the good bacteria that keep yeast in check.

The classic cottage cheese discharge.

Exactly.

The text implies that.

On the scope, you see yeast cells and pseudohypha.

Next,

bacterial vaginosis or BV.

This is interesting because it's not just one bug.

It's a shift in the ecosystem.

The good lactobacilli decrease, and anaerobes like Gardnerella vaginalis overgrow.

Associated with a fishy smell.

Yes, especially after intercourse.

And the microscopic hallmark.

The clu cell.

The clu cell.

This is a squamous cell from the vaginal wall that looks fuzzy or stippled, because it is absolutely coated in bacteria.

The bacteria are sticking to the surface, giving it a clu appearance.

And finally,

trichomonas.

This is a parasite.

Trichomonas vaginalis is a protozoan.

It is sexually transmitted.

The bug is motile.

If you look at a wet mount under the microscope, you can actually see it swimming around.

That would certainly be a diagnosis you wouldn't miss.

No, you wouldn't.

And clinically, it can cause a strawberry cervix, which is a very inflamed red punctate appearance on the cervix, though that's not present in every case.

Perfect.

Speaking of the cervix, let's move up to the gateway of the uterus.

Section three, the cervix.

The cervix is huge for pathology.

It is the battleground between the external world and the sterile uterus.

Let's start with inflammation.

Pelific inflammatory disease or PID.

This is usually an ascending infection, right?

It starts low and climbs high.

Yes.

It usually begins in the cervix, typically from a sexually transmitted infection like Neisseria gonorrhea or Chlamydia trachomatis.

Oh.

But it doesn't stay there.

It keeps going.

It climbs up into the endometrium, endometritis, through the fallopian tubes, salpingitis, and potentially out into the pelvic cavity, euphoritis and peritonitis.

And there's a specific syndrome mentioned when it gets all the way up to the liver.

Sounds crazy from the pelvis to the liver.

It is a long journey for bacteria.

This is Fitzhugh -Kurtis syndrome.

It's a perihepatitis.

The inflammation creates scar tissue between the liver capsule, glistens capsule, and the peritonium.

And the description is?

The text describes them as violin string adhesions.

That's such a vivid image.

Thin, tight strings stretching across the liver surface.

But let's talk about the real damage.

What are the long -term consequences of PID?

They are severe and permanent.

The main issue is scarring in the fallopian tubes.

If the tubes are scarred, the egg can't travel normally.

So infertility?

This increases the risk of infertility significantly.

It also increases the risk of ectopic pregnancy, where the egg gets stuck and implants in the tube.

You can also get intestinal obstruction from adhesions, binding the loops of bowel together.

Okay, let's get to the big topic.

Cervical carcinoma.

This is one of the biggest success stories in pathology history, but it's still a major disease.

It is.

The text provides a table.

Table 22 to 1 comparing the big three female genital cancers.

I think it's worth breaking this down because students mix them up constantly.

It is crucial.

We need to distinguish between incidence, how common it is, and mortality, how deadly it is.

So who wins the prize for most common in the US?

Endometrial cancer is number one in incidence.

It's linked to obesity and estrogen, which are, you know, common issues.

Ovarian is number two.

Cervical is number three.

So cervical is the least common of the three.

But if we look at mortality, the deadliest.

The order changes.

Ovarian cancer is number one for mortality.

It's the silent killer because it presents late.

Endometrial is number two.

Cervical is number three.

So cervical is number three for both.

Why is that?

Why is it less deadly than the others?

Screening.

The pap smear.

Because of the pap smear, we catch cervical changes before they become cancer, or when the cancer is very early.

We don't have that for ovarian cancer.

Ovarian cancer has no effective screening test, which is why it kills more women despite being less common than endometrial cancer.

Let's talk about the driver of cervical cancer.

It's almost entirely viral.

Yes.

HPV.

Human papilloma virus.

Specifically, high -risk types 16, 18, 31, and 33.

The text explains the molecular mechanism here.

And it's fascinating.

It's like a heist movie inside the cell.

The virus produces these two proteins, E6 and E7.

What exactly are they doing?

They're disabling the cell's security guards.

Think of P53 and RB as the security team protecting the genome.

E6 is the assassin for P53.

P53 is the guardian of the genome.

Exactly.

Normally, if DNA is damaged, P53 stops the cell and says, repair this or die, you know, apoptosis.

Right.

HPV E6 binds to P53 and destroys it.

So now the cell accumulates mutations and doesn't die.

And E7.

What's its job?

E7 takes out RB.

RB, the retinoblastoma protein, is the brake pedal on the cell cycle.

It holds a molecule called E2F to stop the cell from dividing.

E7 binds to RB and releases E2F.

So it's basically cutting the brake lines.

It's cutting the brake lines.

So E6 stops the cell from dying and E7 hits the gas pedal on division.

That is a perfect recipe for cancer.

It really is.

And this happens at a very specific geography.

The transformation zone of the cervix.

The T zone, yeah.

This is where the squamous epithelium of the outside meets the columnar epithelium of the inside.

That border is where the virus likes to strike.

And we can see this on a slide.

We have a figure for this too, a figure 22 -22.

It shows the hallmark change.

The coilocyte.

This is the cellular fingerprint of HPV.

If you look at the figure, you see squamous cells, but the nucleus looks wrong.

How so?

It's dark and crinkled.

We call that nuclear hyperchromesia and angulation.

The description is raisinoid, looking like a raisin.

And around that, raisin nucleus.

A clear halo.

A perinuclear vacuole.

That halo is the cytopatic effect of the virus.

If you see coilocytes on a pap smear, you know HPV is present.

And the progression is logical.

It doesn't go from normal to cancer overnight.

No, it steps up.

It goes from low -grade SIL or squamous intraepithelial lesion, which is just CIN1 to high -grade CIL, which is CIN2 and 3, then to carcinoma in situ.

Full thickness dysplasia.

Full thickness dysplasia.

And finally, if the basement membrane is breached, invasive squamous cell carcinoma.

What are the symptoms of invasive cancer?

If a woman misses her screenings.

The classic sign is postcoital bleeding after sex.

Also, dyspareunia, which is painful sex, and malodorous discharge.

But remember, the goal is to catch it way before symptoms appear.

Before we leave the cervix, the text mentions cervicitis.

Just general inflammation.

Right.

Acute or chronic.

It can be infectious or non -infectious.

But one specific note in the text is vital.

Follicular cervicitis caused by chlamydia.

Why is that one highlighted?

Because of the risk to the newborn.

If a baby is delivered vaginally through a cervix infected with chlamydia, the baby can develop conjunctivitis, an eye infection, or pneumonia shortly after birth.

That's why we give the eye ointment.

That's exactly why we treat the eyes of newborns with erythromycin ointment to prevent gonococcal and chlamydial eye infections.

All right.

Let's open the door and enter the uterus proper.

Section 4.

We have the endometrium, the lining, and the myometrium, the muscle.

Let's start with the lining.

Inflammation here is endometritis.

We have acute versus chronic.

How do we tell them apart?

Is it just time?

Not just time.

It's about the cell type.

Acute endometritis is usually neutrophilic and happens after a delivery or abortion where some tissue is left behind.

It's an ascending infection.

But chronic is distinct because of what you see on biopsy.

Yes.

Plasma cells.

This is a hard rule in pathology.

Lymphocytes are normal in the endometrium, but plasma cells are not.

If you see a single plasma cell in the endometrium, the diagnosis is chronic endometritis.

That is a great absolute rule and what causes it.

Often it's retained products of conception, chronic PID, or a foreign body like an IUD, an intrauterine device.

Now, a condition that affects so many women and is often misunderstood,

endometriosis.

This is defined as endometrial glands and stroma located outside the uterus.

Basically, the lining of the womb is growing places it shouldn't be.

Like where?

The ovaries, the uterine ligaments, the pouch of Douglas behind the uterus, even on the bowel or bladder.

And the problem is, this tissue still thinks it's in the uterus.

Exactly.

It responds to hormones.

So when the woman has her period, this ectopic tissue bleeds too.

But the blood has nowhere to go.

It causes intense irritation, inflammation, and scarring.

The text lists the four Ds of symptoms.

Right.

Dysmenorrhea, which is painful periods.

Dysperunia, painful sex.

Dyskesia, which is painful defecation or rectal pain.

And chronic pelvic pain.

It's also a major cause of infertility because the scarring can kink the tubes.

And visually, this has some vivid descriptions.

In the ovary, the bleeding accumulates over months and years.

It forms a cyst filled with old hemolyzed blood that looks thick and brown.

We call it an endometrioma, or famously, a chocolate cyst.

Right, and elsewhere.

On the peritoneum, you see small red -brown nodules.

The text calls them gunpowder nodules because they look like someone sprinkled gunpowder burns inside the pelvis.

Wow.

Now what if the endometrium dives into the muscle of the uterine wall?

Not outside the uterus, but deep into its own wall.

That's adenomyosis.

Adeno for gland.

Myo for muscle.

It causes the uterus to become boggy, enlarged, and globular.

It leads to heavy, painful periods.

But you don't get the cyclic bleeding outside the uterus like in endometriosis.

Moving to the muscle itself,

the myometrium.

We have the most common tumor of the female tract here.

I feel like everyone knows someone who has these.

The leomyoma, or as everyone calls them fibroids.

Benign.

Yes, benign, smooth muscle tumors.

They are extremely common, especially in African -American women.

And they respond to hormones, which is why they change size during life events.

They are estrogen -dependent.

So the text notes, they tend to grow during pregnancy when estrogen is high, and they shrink during menopause when estrogen drops.

What do they look like if you were a surgeon holding one?

Grossly, they are well -circumscribed rubbery white tan masses.

The classic description is a whirled appearance on the cut surface.

Like a fingerprint or a galaxy.

Yeah, that's a good way to think of it.

And location matters for symptoms.

A subcerosal fibroid on the outside might just press on the bladder.

An intramural one is in the wall.

But a submucosal one, just under the lining, can cause severe bleeding and infertility because it disrupts the cavity.

Is there a malignant version?

Can a fibroid turn into cancer?

Generally, no.

Leomyosarcomas exist, but they are rare and usually arise de novo from scratch.

They don't typically come from an existing benign fibroid.

So having fibroids doesn't mean you are pre -cancerous for sarcoma.

Back to the lining for the scary stuff.

Endometrial hyperplasia and cancer.

Hyperplasia is proliferation of the glands relative to the stroma.

It's a ratio problem.

You have too many glands.

Okay.

It can be benign, which is simple hyperplasia, or it can have atypia, which is complex atypical hyperplasia.

And that atypia is the red flag.

Yes.

Endometrial intrapathelial neoplasia with atypia is a direct precursor to cancer.

And then we have adenocarcinoma, the most common invasive cancer of the female tract in the U .S.

It typically affects postmenopausal women presenting with abnormal bleeding.

Postmenopausal bleeding is endometrial cancer until proven otherwise.

The text lists a huge block of risk factors.

Obesity, early menarche, late menopause, nulliparity, which is never being pregnant.

What ties these all together?

It's all about estrogen,

specifically unopposed estrogen.

Progesterone protects the endometrium by thinning it.

Estrogen builds it up.

If you have high estrogen without the progesterone break, the lining grows out of control.

Why does obesity cause high estrogen?

Adipose tissue, fat, contains an enzyme called aromatase.

Aromatase converts androgens into estrone, which is an estrogen.

So more body fat equals more estrogen factory, which equals a higher risk of cancer.

We have figure 22 .3 showing this cancer.

What are we seeing there?

It shows the adenocarcinoma invading down into the myometrium.

The depth of that invasion is the most important prognostic factor.

Shallow invasion is good.

Deep invasion is bad.

Now, I want to clarify something here.

The text mentions two genetic pathways for endometrial cancer.

This seems like a detail that separates the average student from the top student.

It is.

Pathway one is the endometrioid type.

This is the classic one we just discussed, related to estrogen and hyperplasia.

The genetic mutation here is usually in the PTN gene.

And pathway two.

The cemerus type.

This is different.

It occurs in older women, like in their 70s versus their 50s.

It is not necessarily driven by estrogen hyperstimulation.

It arises in a trophic or thin endometrium.

And the mutation is different.

The mutation is TP53.

So endometrioid equals estrogen plus PTN plus good prognosis.

Cemerus equals aggressive plus TP53 plus bad prognosis.

You got it.

And serous tumors have a specific histology.

They form papillary structures.

And crucially, they often have somoma bodies.

And that's a perfect lead -in.

Which leads us nicely to the next organ.

OK.

We are moving out to the adnexa.

Section five, the ovary.

Ovarian pathology is tricky, I'm not going to lie.

The ovary is a complex organ because it has three totally different cell types living together.

And tumors can arise from any of them.

Before we classify the tumors, let's hit a very common non -tumor condition.

PCOS or polycystic ovarian disease.

Also known as Stein -Leventhal syndrome.

It's an endocrine disorder affecting 5 to 10 percent of women.

The text emphasizes a triad of features.

One, androgen excess, so hirsutism or acne.

Two, oligo or anovulation, so irregular or no periods.

And three, polycystic ovaries on ultrasound.

And the labs reflect that mechanism.

You see high LH, luteinizing hormone, and low FSH, follicle stimulating hormone.

The high LH drives the ovary to make androgens or testosterone, causing the hirsutism.

The low FSH means follicles never mature, so they turn into cysts instead of ovulating.

Clinically, this presents in young women with infertility, obesity, and hair growth.

And there is a metabolic component too, right?

Yes.

Insulin resistance.

These patients are at high risk for type 2 diabetes.

Now for the tumors,

the text uses table 2222 to classify them.

This is the roadmap for ovarian cancer.

Everything comes from one of three origins.

Right.

Think of the anatomy of the ovary.

You have one, the covering,

surface epithelium.

Okay.

Two, the egg itself, germ cells.

And three, the structural support and hormone cells,

sex cord stroma.

Which is the most common.

Surface epithelial tumors are by far the most common, accounting for about 65 to 70 % of cases.

Why the surface?

Think about ovulation.

Every month, the surface of the ovary ruptures to release an egg and then has to repair itself.

That constant trauma and repair break fix, break fix increases the chance of a mutation.

So anything that stops ovulation is protective.

That's why things like pregnancy, breastfeeding, or oral contraceptives are actually protective against ovarian cancer.

They give the surface a break.

That makes total sense.

Yeah.

Let's drill down into epithelial tumors.

We have serotonin mucinous.

Cirrus tumors are the most common malignant type.

Like endometrial cancer, they are split into low grade and high grade.

Low grade is linked to KRS or BRAF mutations.

High grade is linked to TP53 mutations.

And we have a visual for cirrus tumors in figure 22 to 4.

Somomabodies.

I love saying that word.

It comes from the Greek word for sand.

These are concentric laminated calcifications.

They look like little purple onion rings under the microscope.

A key buzzword.

If you see a somoma body in an ovarian mass, you should immediately think cirrus cystodendrocarcinoma.

What about risk factors?

Nulliparity, so no kids again.

And genetics.

This is where the BRCA1 and BRCA2 mutations come into play.

Also Lynch syndrome.

Women with BRCA1 mutations have a significantly higher risk of high grade cirrus carcinoma.

And mucinous tumors.

They look like intestine or endocervix.

The cells are tall and full of mucin like goblet cells.

What about the marker CA125?

I feel like patients always ask for this blood test.

Can we use it to screen everyone?

No.

The text is very clear on this.

CA125 is a nonspecific marker.

It can be elevated in endometriosis, inflammation, even pregnancy.

It has a high false positive rate.

So what's it good for?

We use CA125 to follow treatment, to see if the cancer is coming back, or to evaluate unknown mass.

We do not use it to screen the general population.

Okay, category two.

Germ cell tumors.

These are the weird ones.

These come from the egg cells.

The most famous one is the cystic teratoma or dermoid cyst.

The one that contains teeth and hair?

Yes.

It sounds like science fiction.

Because it comes from a germ cell, it is tertipotent.

It can differentiate into any tissue type.

So you open up the sovarian cyst and you find a ball of hair, skin, sebaceous material, teeth, sometimes even bone or carnilage.

The text mentions struma ovari.

That's a specific type of teratoma that is composed almost entirely of thyroid tissue.

And it functions.

It produces thyroid hormone.

No way.

So a woman can present with signs of hyperthyroidism racing heart, heat intolerance caused by a tumor in her ovary.

Are teratomas cancerous?

In the ovary, usually no.

95 % are benign, mature teratomas.

This is the opposite of the testicle, where teratomas are usually malignant.

What about a malignant germ cell tumor?

The dysgermanoma.

This is the female equivalent of the male semenoma.

It looks the same histologically as sheets of fried egg cells.

It affects younger women or children.

And it's linked to Turner syndrome.

Yes, linked to Turner syndrome, 45x.

The good news is it is extremely sensitive to radiation, so the prognosis is good.

Category 3.

Sex cord stromal tumors.

These are the hormone factories.

Exactly.

These tumors arise from the cells that support the egg and make hormones.

First, the fibroma.

It's just a firm, white mass of fibroblasts.

It's benign.

But it has a famous syndrome, Miggs syndrome.

What is Miggs syndrome?

It's a triad.

Ovarian fibroma plus ascites, which is fluid in the belly, plus a plural effusion, fluid in the lung lining, usually on the right side.

That sounds like metastatic cancer.

It looks like metastatic cancer, but it's not.

You remove the benign fibroma and all the fluid goes away.

It's like magic.

Next, the granulosa cell tumor.

Granulosa cells normally convert testosterone to estrogen.

A tumor of these cells is an estrogen factory.

In a little girl, this massive dose of estrogen causes precocious puberty.

In an older woman, it causes post -metapausal bleeding and endometrial hyperplasia.

Any microscopic buzzwords?

Call exner bodies.

These are little follicle -like structures, small spaces filled with eosinophilic fluids surrounded by granulosa cells.

They look like little rosettes.

And the sartoli -leydig tumor.

Sartoli and leydig cells are normally male cells.

So this tumor is an androgen factory.

It produces testosterone.

It causes virilization.

The patient develops a deep voice, male pattern baldness, and facial hair.

Finally, before we leave the ovary, metastasis.

Specifically, the Kruchenberg tumor.

This is a tricky one.

It presents as large bilateral ovarian masses.

But it's not ovarian cancer.

It's a metastasis from the stomach.

Specifically, a gastric signet ring cell carcinoma.

So if you find bilateral masses, look at the stomach.

Always.

The cancer cells produce mucin, pushing the nucleus to the side, creating that signet ring appearance.

All right, we are on the final leg of the journey.

Section six, the placenta and pregnancy.

Let's start with gestational trophoblastic disease.

Moles.

What is a mole, exactly?

Is it a baby?

No.

It's a tumor of the placental tissue, the trophoblasts.

It's a conception gone wrong.

We classify them as complete or partial.

We have table 22 .3 comparing them.

I feel like this is a guaranteed math question on the exam.

Let's do the genetics.

Complete and mole.

The genetics are 46xx.

But here is the kicker.

All the DNA is paternal.

It comes from the dad.

How does that happen?

An empty egg, an egg with no nucleus gets fertilized by a single sperm.

That sperm then duplicates its DNA.

So you have 46 chromosomes, but they're all dads.

No mom DNA.

So is there a fetus?

No fetus.

Without maternal DNA, you cannot make embryonic parts.

You just get a massive proliferation of placental tissue.

The villi becomes swollen and hydropic or water -filled.

And the visual.

Grape -like clusters again.

And on ultrasound, it looks like a snowstorm.

The uterus grows way too fast, size greater than dates.

And the beta HCG levels are sky high, much higher than a normal pregnancy.

Now the partial mole.

Partial is triploid.

69 ,000 XY usually.

This is a fertilization error.

One normal egg gets fertilized by two sperm or one sperm that failed to divide.

So you have 23 maternal plus 46 paternal, which equals 69 chromosomes.

Is there a fetus here?

There can be fetal parts.

Yes,

but it's not viable.

The HCG is elevated, but less so than in a complete mole.

Why do we care so much about distinguishing them, besides the math?

Malignancy risk.

A complete mole has a 10 to 15 % risk of becoming invasive and a 2 % risk of choriocarcinoma.

A partial mole rarely becomes malignant.

And the malignant form is choriocarcinoma.

Right.

This is a nasty, aggressive tumor.

It's composed of cytotrophoblasts and syncytotrophoblasts, but no villi.

It's necrotic and hemorrhagic.

It spreads very early via the blood hematogenes spread to the lungs and brain.

If you have a patient with rising HCG after a pregnancy, miscarriage or mole removal, you have to suspect this.

Yes.

Luckily, despite being aggressive, it is incredibly sensitive to chemotherapy, like methotrexate.

The cure rates are very high.

Let's run through structural issues.

Ectopic pregnancy.

Implantation usually occurs in the fallopian tube, specifically the ampulla.

Risk factors are anything that scars the tube PID, like we mentioned,

endometriosis, or surgery.

If it ruptures, it's a surgical emergency due to massive interperitoneal hemorrhage.

Placental positioning.

Previa versus abruption versus accretia.

Break them down.

Placenta previa.

The placenta implants over the cervical os.

It blocks the exit.

It presents as painless third trimester bleeding.

You cannot deliver vaginally or you'll tear the placenta.

OK.

Placental abruption.

The placenta prematurely separates from the uterine wall before the baby is born.

This cuts off oxygen to the baby and causes painful bleeding and a rigid abdomen in the mom.

Wrist factors, cocaine use, and hypertension.

Endocrine.

Placenta creta.

The placenta implants too deeply into the myometrium.

It lacks the normal separation layer, so after birth it won't detach.

It leads to massive postpartum hemorrhage and often requires a hysterectomy to stop the bleeding.

Twins.

Fraternal versus identical.

Fraternal or dizygotic means two eggs, two sperm.

They're just siblings sharing a womb.

Always two amions, two chorions.

Identical or monozygotic is one egg, one sperm that splits.

The setup depends on when it splits.

If it splits early, days zero to four, you get two sacs, two placentas.

If it splits later, days four to eight, you get one placenta, two sacs.

And that's the danger zone.

That is the risk zone for twin -twin transfusion syndrome.

Twin -twin transfusion.

If they share a placenta, a monochorionic, they can share blood vessels.

One twin can steal blood from the other.

One gets huge and fluid overloaded.

The other gets tiny and anemic.

Last topic, preeclampsia.

This is a systemic syndrome defined by new -onset hypertension plus proteinuria or end -organ damage after 20 weeks of gestation.

It's caused by abnormal placental spiral arteries leading to placental ischemia.

And if they have seizures?

That's eclampsia.

Eclampsia is preeclampsia plus seizures.

And H -E -L -L -P syndrome.

Severe variant.

H for hemolysis.

You'll see schistocytes on the smear.

E -L -L for elevated liver enzymes.

And L -P for low platelets.

And the only cure.

The only cure for preeclampsia or H -E -L -L -P is delivery of the placenta.

Wow.

We made it.

We walked from the skin of the vulva through the infections and tumors of the tract all the way to the complex physiology of twins and the placenta.

It's a huge chapter, but seeing it anatomically makes it manageable.

You can see the progression.

Let's do a quick, so what?

Why does all this matter?

Besides the board exam, these pathologies represent some of the most common issues women face.

Knowing that a painless ulcer is syphilis might save a patient from neurocyphilis years later.

Knowing that post -metapausal bleeding implies endometrial cancer leads to early detection and cure.

Understanding the HPV mechanism explains why we vaccinate and screen the way we do.

It's about catching things when they are treatable.

And my final thought for the listener.

Remember the visuals.

The parchment skin of lichen sclerosis, the grape -like mass of sarcomabotreoids, the chocolate cyst of endometriosis, the somoma bodies and the ovary.

Anchor your memory on those images.

And remember the difference between the silent killer, ovarian cancer, and the preventable one, which is cervical.

Pathology isn't just about cells.

It's about recognizing patterns to save lives.

Thanks for diving deep with us into the world of female genital pathology.

Keep looking for the logic.

A warm thank you from the Last Minute Lecture Team.

We'll see you on the next deep dive.