Vaginal and vulvar disorders: Pathology review

Definitions & Key takeaways

Vaginal and vulvar disorders refer to a wide range of conditions affecting the female reproductive system. Common vaginal and vulvar disorders include bartholin's cysts, where a blockage of the bartholin's gland duct results in cystic dilation and may lead to an abscess; lichen sclerosus which is a benign condition characterized by thinning of the epidermis and sclerosis of the dermis. There's also imperforate hymen which classically presents as primary amenorrhea with hematocolpos.

Other conditions include vaginal cancers, like squamous cell carcinoma, and clear cell adenocarcinoma, and vulvar cancers like melanomas and adenocarcinomas. There may also be infections like vaginal yeast infections, bacterial vaginosis, and genital warts. Diagnosis of these disorders involves a physical examination, medical history review, and potentially laboratory tests or biopsies. Treatment depends on the underlying cause and can range from topical creams and medications to surgery. Regular gynecological exams and good hygiene practices can help prevent and detect these conditions early.

Chapters:

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Case Study0:00–1:02

62-year-old Tess comes to the emergency department with vaginal bleeding for the past couple of hours. She also mentions that she has occasionally noticed some watery, foul-smelling vaginal discharge.
After ensuring that she is hemodynamically stable, history reveals that her last menstrual period was about 10 years ago and she has had multiple sexual partners.
On speculum examination, a suspicious-looking mass is identified in the upper third of the posterior vaginal wall. Later that day, 69-year-old Oshun comes to the physician's office complaining of an intense burning sensation, itching and pain in her genital region.
Her last menstrual period was at the age of 48. On further history, she has been smoking 1.5 packs daily for 40 years.
On examination, a white, asymmetrical lump with irregular borders and 1.2 cm in size is seen in the right labia majora.All right, both Tess and Oshun have some type of vaginal or vulvar condition.

Anatomy1:02–1:46

Let’s take a look at the Anatomy real quick. The external sex organs, together referred to as the vulva, contain the labia majora, which cover the labia minora, and between the two labia minora there is a space called the vulvar vestibule that includes the opening of the vagina and the the urethral opening.
Now, vaginal and vulvar conditions are classified into non- neoplastic ones including bartholin cyst, lichen sclerosus, lichen simplex chronicus, and imperforate hymen and neoplastic ones, which are relatively rare cancers of the female genital tract.
Okay, let’s start with the first non-neoplastic condition, which is the Bartholin cyst. The Bartholin glands are two small glands that lie underneath the vestibule and on each side of the vaginal opening.

Bartholin cyst1:46–3:02

Normally, they secrete a mucus- like fluid that drains through ducts into the vestibule in order to lubricate the vagina.
But when their ducts get blocked, the fluid builds up, causing cystic dilation of the gland. For your exams, remember that blockage typically occurs in females of reproductive age as a result of a mucus plug or a sexually-transmitted infection, and especially, Neisseria gonorrhoea.
If the cyst itself gets infected, an abscess occurs.Now, in a test question, a Bartholin cyst typically presents as a unilateral cystic lesion at the lower vestibule adjacent to the vaginal canal.
Most small cysts are not painful, but very large cysts can cause significant pain. And in the case of an abscess, the site will be red, warm, swollen and extremely painful.
Diagnosis is clinical and treatment is drainage of the cyst or opening the cyst to create a pouch, called marsupialization.Next, there’s lichen sclerosus.

Lichen sclerosus3:02–4:05

What’s high-yield about this is that there’s thinning of the epidermis with sclerosis or fibrosis of the underlying dermis.
This usually occurs in the genital or anal regions and is more common in postmenopausal individuals.Now, the reason why lichen sclerosis develops is unknown.
A key principle is that although it is benign, for unclear reasons, it’s associated with a slightly increased risk for squamous cell carcinoma.
It classically presents with leukoplakia, which is a porcelain-white plaque with a red or violet border. And the epidermis is so thin that examiners often like to describe it with the phrases like “cigarette paper or parchment-like.” That thin epidermis is also very fragile, so skin erosions can be present.
Symptoms typically include vulvar itching, and sometimes dyspareunia or painful sexual intercourse. Diagnosis is clinical and treatment may include steroid ointments to reduce itching.
A sort of opposite condition is lichen simplex chronicus. In this case, there’s hyperplasia of the vulvar squamous epithelium as a result of chronic irritation or scratching.

Lichen simplex chronicus4:05–5:54

It’s more common in individuals between the age of 30 and 50. For your exams, what’s high- yield is that it’s totally benign, and, unlike lichen sclerosus, carries no risk for squamous cell carcinoma.
Presentation is again with leukoplakia, but, in this case, the key is that the vulvar skin is thick and leathery. For symptoms, there’s an itch-scratch vicious cycle where itching leads to scratching and hyperplasia, which results in more itching.
Diagnosis is clinical and treatment may include steroid ointments to reduce itching. The last non-neoplastic condition is an imperforate hymen, which is a congenital disorder where a hymen without an opening completely blocks the vaginal opening.
This is caused by a failure of the hymen central epithelial cells to degenerate during fetal development. At birth, it may cause vaginal mucus to build up, causing the hymenal membrane to bulge outwards.
That’s usually self resolving, though. So for your exams, it’s important to know that imperforate hymen typically presents in adolescent females when menstrual blood accumulates in the vagina, which is also known as hematocolpos.
A test question might sometimes also show a characteristic picture of a bulging, bluish hymenal membrane. And since menstrual blood can’t go through, there’s primary amenorrhea.
However, these individuals do have recurring menstrual cramps and abdominal or pelvic pain, without any outward signs of bleeding.
On ultrasound, hematocolpos will be visible. Treatment is with surgical incision of the hymen.Okay, now, moving on to neoplastic conditions, let’s begin with vaginal cancer.

Vaginal Cancer5:54–11:47

There are three main histologic subtypes, the most common is squamous cell carcinoma, which develops from the squamous epithelium of the vagina.
A very high yield fact to know is that it’s linked to HPV infection. Particularly high risk strains include HPV 16, 18, 31 and 33.
It’s also helpful to remember these can also cause cervical cancer. In fact, vaginal squamous cell carcinoma is frequently secondary to metastasis from cervical squamous cell carcinoma.
And just like cervical cancer, vaginal cancer can start out as vaginal intraepithelial neoplasia, and it may take many years for it to even progress to cancer.
So, it predominantly occurs in postmenopausal females over the age of 60. Now, for your test, it’s important to know that the strongest risk factor is multiple sexual partners, followed by early age at first sexual intercourse, smoking, and immunocompromising conditions, like an HIV infection.The second, more rare type is clear cell adenocarcinoma, which develops from the glandular cells of the vagina.
A high-yield fact is that unlike squamous cell carcinoma, it most commonly affects young individuals under the age of 20 and it’s almost always linked to in utero exposure to a medication called diethylstilbestrol, or DES for short, which is no longer in use.
So, the test question will typically describe a female whose mother was prescribed DES during her pregnancy to prevent premature labor or misscarriage.Next, there’s botryoid rhabdomyosarcoma of the vagina, also known as sarcoma botryoides.
This is extremely rare, but high-yield for your exams and develops from rhabdomyoblasts or immature skeletal muscle cells lining the walls of the vagina.
It most commonly affects individuals under the age of 4. For symptoms, vaginal cancer most often cause postcoital or postmenopausal vaginal bleeding.
A watery, blood-tinged or foul-smelling vaginal discharge might also be present. Now, in the later stages, when the cancer has spread further and invade into organs like the bladder, there may also be symptoms like urinary frequency, dysuria and hematuria.
If the cancer has spread to the rectum, there may be constipation. The cancer cells can also metastasize to the lymph nodes, in which case pelvic pain can be present.
Very important to know for examination purposes is that the region of lymph nodes where cancer spreads depends on the location of the tumor in the vagina.
So, tumors from the lower two thirds of the vagina will go to the inguinal lymph nodes, while tumors from the upper one third will go to the nearby iliac nodes.
Now, diagnosis starts with the speculum examination. Most commonly, vaginal cancer looks like a mass, but it can also look like a white plaque or an ulcer.
In the case of sarcoma botryoides, it’s important to know that the mass is polypoid and protrudes through the vagina. The key phrase here is that this mass resembles “a bunch of grapes”.
In all cases, remember that vaginal cancer typically originates from the upper third of the posterior vaginal wall. To confirm the diagnosis, when there’s a vaginal mass, a biopsy is done.
When there is no mass, vaginal cytology can be done. This is frequently combined with HPV genotyping, meaning the vaginal cytology sample is analyzed for the presence of high risk HPV DNA.
Now, the biopsy results can differentiate between squamous cell carcinoma, clear cell adenocarcinoma and sarcoma botryoides.
For squamous cell carcinoma, the biopsy can also distinguish between precancerous lesions, like vaginal intraepithelial neoplasia, or invasive vaginal cancer.
Vaginal intraepithelial neoplasia, or VAIN for short, is classified based on how much of the vaginal epithelium is affected.
VAIN 1 is when only the lower one third of the epithelium contains cancer cells, VAIN 2 is when the lower two thirds are affected, and VAIN 3 involves more than two thirds of the epithelium.
Carcinoma in situ is when the entire epithelium is made up of cancer cells, and it’s included in the VAIN 3 category. And invasive vaginal cancer is when the cancer cells have breached through the basement membrane.Now, for sarcoma botryoides, what’s important to remember is that biopsy will reveal rhabdomyoblasts, usually described as “spindle-shaped cells with cytoplasmic cross-striations”.
And on immunohistochemistry staining, these cells will stain positive for desmin and myoglobin. Finally, imaging with CT or MRI scan can then be done to look for evidence of metastasis.
Now, treatment usually consists of local surgical excision or ablation of the lesion or, in more advanced cases a radical hysterectomy and vaginectomy, or surgical removal of the whole uterus and vagina along with the associated lymph nodes, might be necessary.
This is followed by chemotherapy and radiotherapy if the tumor has metastasized. Moving on to vulvar cancer, there are three main histologic subtypes.

Vulvar Cancer11:47–15:44

So, for your test, remember that over 90% of vulvar cancers are squamous cell carcinomas, which develop from the squamous epithelium of the vulva.
Just like cervical and vaginal squamous cell carcinomas, these are usually linked to high-risk HPV strains like 16 and 18.
It can start out as vulvar intraepithelial neoplasia and most commonly present in postmenopausal females. Risk factors for HPV-related squamous cell carcinomas, once again, include multiple lifetime sexual partners, early age at first sexual intercourse, smoking, and immunocompromising conditions.
Rarely, squamous cell carcinomas are not related to HPV infection and in this case, they usually arise from long-standing lichen sclerosus.
Now, the other 10% of vulvar cancers are melanomas and vulvar adenocarcinomas. Melanomas develop from melanocytes and risk factors include a family history of melanoma, or a personal history of melanoma or dysplastic nevi, which are atypical moles, in other locations on the body.
Vulvar adenocarcinomas, on the other hand, develop from glandular cells, like those that make up Bartholin’s glands on either side of the vaginal opening.
Next, we have Paget disease of the vulva which is a particular type of intraepithelial or in situ adenocarcinoma, meaning that cancer cells have not invaded the basal membrane.This is a type of cancer that usually develops in the ducts of the breast, but can rarely develop in other locations, such as the vulva.
Now, a key difference is an individual with Paget disease of the breast will almost always have cancer somewhere else in the body.
In contrast, in Paget disease of the vulva, there’s usually no other cancer.For symptoms, vulvar cancer most often presents as an itchy leukoplakia, but may also look like a wart and vary in color, shape and size, or an open sore that doesn’t heal.
A clue examiners often like to use is that the lesion is asymmetric, has irregular borders and large size. Sometimes there may also be associated pain, bleeding or discharge.
In the case of Paget disease of the vulva, the test question will typically describe an erythematous, pruritic, crusting ulcer.
In later stages, if the cancer has metastasized to lymph nodes in the groin, these might also be enlarged and, sometimes, cause pelvic pain.To diagnose vulvar cancer, a biopsy is done.
This can confirm the malignant character of the lesion, and also differentiate between the different histologic subtypes.
Immunohistochemistry is also frequently performed. So, for example, Paget disease of the vulva will stain positive for PAS and keratin, which are specific for epithelial cells, and negative for S100.
In contrast, melanoma will stain negative for PAS and keratin, and positive for S100, which is specific for melanocytes.
And that’s a popular way for examiners to clue you in these particular types of tumors. Treatment usually involves local surgical excision or ablation of the lesion or, in more severe cases, surgical removal of the vulva, or radical vulvectomy, is required.
This is followed by chemotherapy and radiotherapy if the tumor has metastasized.All right, as a quick recap... non-neoplastic vaginal and vulvar conditions include bartholin’s cysts, where a blockage of the bartholin’s gland duct results in cystic dilation and may lead to an abscess, lichen sclerosus which is a benign condition characterized by thinning of the epidermis and sclerosis of the dermis.

Review15:44–17:23

It also increases the risk of developing squamous cell carcinoma. Lichen simplex chronicus is hyperplasia of the vulvar epithelium but it doesn’t raise the risk of carcinoma.
Finally, there’s imperforate hymen which classically presents as primary amenorrhea with hematocolpos. Now, for vaginal cancers there’s squamous cell carcinoma, which is the most common type.
It’s usually HPV-related and affect postmenopausal females. Clear cell adenocarcinoma is caused by in utero exposure to diethylstilbestrol.
Sarcoma botryoides consist of grape-like tumors and are usually present in individuals under the age of 4.Next, over 90% of vulvar cancers is squamous cell carcinoma, which are also HPV-related and affect postmenopausal females, but can be also secondary to lichen sclerosus.
The other 10% of vulvar cancers are either melanomas or adenocarcinomas, and a particular type of intraepithelial adenocarcinoma is vulvar Paget disease.
Unlike Paget disease of the breast, it’s usually the only cancer found in the individual unless there’s metastasis.Okay, back to our cases.

Summary17:23–18:27

Tess presented with abnormal postmenopausal vaginal bleeding along with occasional watery, foul-smelling vaginal discharge.
This is a classical presentation of vaginal cancer. Other clues include her age and the fact that she’s had multiple sexual partners, which are strong risk factors for this type of cancer.
On speculum examination, a mass was identified in the upper third of the posterior vaginal wall, which is the number one location for vaginal cancer.
Biopsy of the mass revealed a squamous cell carcinoma, which is the most common type of vaginal cancer.On the other hand, Oshun came in with vaginal burning, pruritus, pain and an asymmetric, irregular, large lump in her vulva, which all make us suspicious of vulvar cancer.
Her age and heavy smoking history are also risk factors. The lesion was biopsied and results came back with a diagnosis of squamous cell carcinoma of the vulva, the most common type of vulvar cancer.
Vaginal and vulvar disorders: Video and Causes | Osmosis