54. Pathology of the vulva and vagina. Sexually transmitted diseases

Page created on April 23, 2019. Last updated on May 3, 2020 at 20:28

Lesions of the vulva

The vulva is the external female genitalia and includes the most hair-bearing skin and mucosa in that region. It involves the labia majora and minora. Most pathologies of the vulva are more annoying than serious.

A Bartholin cyst is a cyst that occurs when the Bartholin glands that lubricate the vaginal vestibule becomes obstructed, causing the gland to enlarge. It usually occurs unilaterally and is painful. It can be caused by local infection. If the Bartholin cyst becomes infected it can become an abscess.

Condyloma acuminatum or genital wart is a warty neoplasm of the vulva, vaginal canal or cervix. They are associated with HPV types 6 and 11. It rarely progresses into carcinoma. Histopathologic features are acanthosis, hyperkeratosis and koilocytosis.

Lichen sclerosus is a chronic inflammatory condition of the skin with characteristic leucoplakias (white plaques). It causes a thinning of the epidermis and fibrosis of the dermis, causing the skin to be almost parchment-like. It most commonly affects genital regions, the vulva included. It’s most commonly seen in postmenopausal women but can occur in any age. It is a precancerous lesion and therefore slightly increases the risk of squamous cell carcinoma.

Lichen simplex chronicus is similar to lichen sclerosus in some ways. A major difference is that the epidermis is thickened rather than thinned due to hyperplasia. Leucoplakia is characteristic also for lichen simplex chronicus. Lichen simplex chronic is caused by chronic irritation, often due to scratching. Unlike lichen sclerosus there is no increased risk for cancer here.

Vulvar squamous cell carcinoma is relatively rare compared to other female genital tract cancers. It also presents as a leucoplakia and must therefore be biopsied to be differentiated from lichen sclerosus or lichen simplex chronicus. We distinguish two “forms” of vulvar squamous cell carcinoma: HPV-positive tumors and HPV-negative tumors.

HPV-positive vulvar carcinoma is related to high-risk HPV strains like subtypes 16, 18, 31 and 33. In this form, vulvar intraepithelial neoplasia (VIN, which is similar to CIN in the cervix) develops. This precancerous lesion often progresses to greater degrees  of atypia, carcinoma in situ and invasive carcinoma. Progression is however not inevitable and may occur only after several years. Smoking and immunodeficiency may contribute to this progression. It’s most commonly seen in middle-aged women.

The HPV-negative vulvar squamous cell carcinoma is not related to HPV but rather following long history of reactive epithelial changes, principally lichen sclerosus. They develop a subtle lesion called differentiated vulvar intraepithelial neoplasia (dVIN), characterised by cytological atypia confined to basal layer and abnormal keratinization.  As these are associated with long-standing lichen sclerosus it’s most commonly seen in postmenopausal woman.

When Paget disease affects the vulva, it’s called extramammary Paget disease or Paget disease of the vulva. Unlike Paget disease of the nipple, extramammary Paget disease is most frequently not associated with an underlying carcinoma. Instead the Paget cells arise from epidermal progenitor cells. Extramammary Paget disease manifests as a red and scaly plaque on the vulvar skin.

Extramammary Paget disease resembles melanoma. Differentiation of the two can be done with PAS staining. Melanoma cells are not stained with PAS while Paget cells are.

Neoplasms of the vagina

Vaginal cancer is associated with symptoms like vaginal bleeding and smelly discharge 🐟🐟

Vaginal adenosis refers to the persistence of embryonic columnar epithelium in the upper vagina. In healthy people this columnar epithelium is replaced by stratified squamous cells. If this replacing process is disrupted there is vaginal adenosis. It is associated with a now-obsolete drug called DES, but it can occur in anyone. This drug was taken during pregnancy to treat pregnancy-related complications, but it turned out that it crosses the placenta and causes several complications, like vaginal adenosis. Adenosis is important as it may lead to clear cell adenocarcinoma.

Sarcoma botryoides (= embryonal rhabdomyosarcoma) is a rare form of vaginal cancer that manifests as soft polypoid, grape-like masses in children < 5 years old. These tumors produce cross-striations that look like muscle on histology.

Vaginal squamous cell carcinoma is a rare occurrence. It most frequently affects women > 60 years old. It’s associated with high-risk HPV subtypes like 16, 18, 31 and 33, which leads to a precursor lesion called vaginal intraepithelial neoplasia (VAIN). From this precursor lesion squamous cell carcinoma will develop.

Vulvovaginitis

Vulvovaginitis refers to a large variety of conditions that result in inflammation of the vagina and/or vulva. The normal vaginal bacteria flora keeps the pH of the vagina low and prevents overgrowth of pathogenic organisms. Infection usually occurs when the flora is disrupted, due to immunosuppression, sexual intercourse or antibiotic treatment.

The most common causes of vulvovaginitis are:

• Bacterial vaginosis
• Trichomoniasis
• Vulvovaginal candidiasis
• Gonorrhoea
• Chlamydia
• Atrophic vaginitis

Bacterial vaginosis is caused the bacterium Gardnerella vaginalis. It is part of the normal vaginal flora but is usually kept in check by lactobacillus. If something disrupts the lactobacillus colony the Gardnerella vaginalis colony can overgrow, causing symptoms. The characteristic symptom is milky vaginal discharge with a fishy odour 🐟

Vulvovaginal candidiasis or vaginal yeast infection is caused by overgrowth of candida albicans in the vagina. It most frequently occurs due to antibiotic treatment. Symptoms include white, crumbly and sticky (cottage cheese-like🧀) vaginal discharge and burning in the vagina.

Atrophic vaginitis occurs due to atrophy of the epithelium of the vagina and vulva in postmenopausal women due to low oestrogen levels. Treatment is by topical oestrogen cream or oestrogen replacement therapy.

Sexually transmitted infections

Syphilis, sometime called lues is caused by the spirochete bacterium Treponema pallidum. The disease has four distinct clinical stages if left untreated.

Primary syphilis is characterised by a special lesion called a chancre. They occur at the place where the bacterium enters the body, and manifest as a painless ulcer.

Secondary syphilis is characterised by general flu-like symptoms and a characteristic rash. This rash is polymorphic and brownish and occurs everywhere on the body, including the palms and soles. Wart-like lesions called condyloma lata arise on the genital region.

The third period is called latent syphilis, as there are months or even years where there are no clinical symptoms. At this point the disease may resolve, reactivate or progress into tertiary syphilis.

Tertiary syphilis is characterised by a variety of symptoms:

• Gumma – destructive and ulcerative granulomatous lesions anywhere on or in the body
• Cardiovascular syphilis – aortitis with resulting aneurysm of the aorta
• Neurosyphilis
  • Early
    • Meningitis
    • Stroke
  • Late
    • Tabes dorsalis – demyelination of the dorsal column and dorsal root ganglia
    • Wide-based ataxia – ataxia with a wide gait
    • Dysesthesia – abnormal peripheral sensation
    • Widespread cerebral atrophy

Children of women who had syphilis during pregnancy develop congenital syphilis. This is associated with all kinds of birth defects, like hepatomegaly, rash, skeletal abnormalities, hearing loss and dental abnormalities.

Gonorrhoea is caused by the bacterium Neisseria gonorrhoeae. It leads to genitourinary tract infections like urethritis, cervicitis, pelvic inflammatory disease and epididymitis. It is commonly asymptomatic, which increases its spreading and risk for complications. When it does cause symptoms, it causes urethral or vaginal discharge, dysuria and pain. It may cause infertility due to scarring and deformity of the fallopian tubes and ovaries.

Chlamydia is caused by the bacterium Chlamydia trachomatis, especially serotypes D-K. It leads to genitourinary tract infections like urethritis, vaginitis, cervicitis and epididymitis. Like gonorrhoea, most cases are asymptomatic. When it does cause symptoms, it causes vaginal discharge or bleeding, dysuria and pain during sex. It may cause infertility.

Genital herpes is most frequently caused by HSV-2 but can be caused by HSV-1 as well. It causes painful erythematous vesicles on or around the genitalia. The lesions regress but frequently recur at seemingly random times.

Human papillomavirus causes condyloma acuminatum, precancerous lesions and invasive cancers, as already described.

Pelvic inflammatory disease is the inflammation of the upper female reproductive tract (uterus, tubes, ovaries) that occurs as a complication of lower reproductive tract infections. It’s most frequently caused by chlamydia or gonorrhoea. It usually causes pain, but the complications can be severe and involve chronic pain and infertility.