Herpes Simplex Virus (HSV)

Infections of the Lower Genital Tract

• Herpes Simplex Virus is a common infection that involves the cervix, vagina, and vulva
• It is a DNA virus with two serotypes: HSV-1 and HSV-2
• HSV-1 typically causes oropharyngeal infections
• HSV-2 typically affects the genital mucosa and skin
• Lesions typically develop 3 to 7 days after transmission
• Viral latency is when infections persist indefinitely, and any decrease in immune function can trigger reactivation
• In the ulcer phase epithelium is desquamated, and marked acute inflammation is present at the ulcer bed
• Multinucleated squamous cells contain eosinophilic to basophilic viral inclusions with a "ground-glass" appearance
• Transmission mainly occurs during the active phase, but can also occur during the latent phase due to subclinical virus shedding
• The gravest consequence of infection is neonatal transmission during birth
• HSV-2 infection enhances HIV-1 acquisition and transmission
• For diagnosis, purulent exudate is aspirated from the lesions and inoculated into a tissue culture
• The cytopathic effect of the virus can be seen after 48 to 72 hours
• Diagnosis can also be achieved via polymerase chain reaction, enzyme-linked immunosorbent assays, and direct immunofluorescent antibody tests
• There is no effective treatment for latent HSV
• Acyclovir or famciclovir may shorten the length of the initial and recurrent symptomatic phase

Molluscum Contagiosum

• Molluscum contagiosum presents as a skin or mucosal lesion caused by poxvirus
• MCV-1 is the most prevalent type, while MCV-2 is most often sexually transmitted
• It is common in young children between 2 and 12 years of age, transmitted through direct contact or shared articles
• In adults, molluscum infections are typically sexually transmitted and affect the genitals, lower abdomen, buttocks, and inner thighs
• The average incubation period for molluscum contagiosum is 6 weeks
• Diagnosis involves observing pearly, dome-shaped papules with a dimpled center; their central waxy core contains cells with cytoplasmic viral inclusions

Fungal Infections (Candida)

• Candida infections are extremely common, and yeast are part of many women's normal vaginal microflora
• Symptomatic candidiasis develops due to disturbance in the patient's vaginal microbial ecosystem, which can be caused by diabetes mellitus, antibiotics, pregnancy, or compromised neutrophil or TH17 T-cell function
• Symptoms include marked vulvovaginal pruritus, erythema, swelling, and curdlike vaginal discharge
• Diagnosis of Candida involves identifying pseudospores or filamentous fungal hyphae in wet KOH mounts of the discharge or on Papanicolaou (Pap) smears
• Candidiasis is not considered a sexually transmitted disease

Trichomonas Vaginalis

• Trichomonas vaginalis is a large, flagellated ovoid protozoan that is usually transmitted by sexual contact, developing within 4 days to 4 weeks
• Individuals may experience yellow, frothy vaginal discharge, vulvovaginal discomfort, dysuria, and dyspareunia
• Strawberry cervix involves vaginal and cervical mucosa typically exhibiting a fiery-red appearance due to marked dilatation of cervical mucosal vessels

Gardnerella Vaginalis

• Gardnerella vaginalis is a gram-negative bacillus that is the main cause of bacterial vaginosis (vaginitis)
• It presents with a thin, green-gray, malodorous (fishy) vaginal discharge
• Pap smears reveal superficial and intermediate squamous cells covered with a shaggy coating of coccobacilli
• Implicated in premature labor

Ureaplasma Urealyticum and Mycoplasma Hominis

• In some cases, cause vaginitis and cervicitis
• Implicated in chorioamnionitis and premature delivery in pregnant patients

Chlamydia Trachomatis

• Chlamydia trachomatis mainly manifests as cervicitis
• Can ascend to the uterus and fallopian tubes, resulting in endometritis and salpingitis

Pelvic Inflammatory Disease

• PID is an infection that begins in the vulva or vagina and spreads upward, involving most of the structures in the female genital system
• Results in pelvic pain, adnexal tenderness, fever, and vaginal discharge
• Neisseria gonorrhoeae is a common cause of PID
• Polymicrobial infections, including staphylococci, streptococci, coliforms, and Clostridium perfringens, can cause PID
• Gonococcal infections often involve the endocervical mucosa initially but can also start in the Bartholin gland and other vestibular or periurethral glands
• The infection may spread to the ovary, creating a salpingo-oophoritis
• Chronic salpingitis (scarring process) forms glandlike spaces and blind pouches
• Non-gonococcal bacterial infections spread upwards from the uterus through lymphatics or venous channels, rather than mucosal surfaces
• They produce more inflammation within the deeper layers of organs
• These infections often spread throughout the wall to involve the serosa and broad ligaments
• Bacteremia is a more frequent complication of streptococcal or staphylococcal PID than of gonococcal infections
• Peritonitis and bacteremia, which may result in endocarditis, meningitis, and suppurative arthritis, are acute complications
• Chronic complications include infertility and tubal obstruction, ectopic pregnancy, pelvic pain, and intestinal obstruction due to adhesions between the bowel and pelvic organs

Vulva - Bartholin Cyst

• Infection of the Bartholin gland produces acute inflammation (adenitis) and may result in an abscess
• It results from obstruction of the duct by an inflammatory process
• Usually lined by transitional or squamous epithelium
• Either excised or opened permanently via marsupialization

Vulva - Nonneoplastic Epithelial Disorders

• Leukoplakia is a descriptive clinical term for opaque, white, plaquelike epithelial thickening
• Lichen sclerosus presents as smooth, white plaques or macules that may enlarge and coalesce, resembling porcelain or parchment over time
• Histologically, there is marked thinning of the epidermis, degeneration of the basal cells, excessive keratinization (hyperkeratosis), sclerotic changes of the superficial dermis, and a bandlike lymphocytic infiltrate in the underlying dermis
• Squamous cell hyperplasia AKA hyperplastic dystrophy or lichen simplex chronicus
• Due to rubbing or scratching of the skin to relieve pruritus
• Histologically, there is thickening of the epidermis (acanthosis) and hyperkeratosis, with hyperplastic epithelium that may show mitotic activity but lacks cellular atypia

Vulva - Benign Exophytic Lesions

• Benign exophytic lesions may be caused by infection or be reactive conditions of unknown etiology
• Condyloma acuminatum is benign genital warts caused by low oncogenic risk HPVs, mainly types 6 and 11 and are sexually transmitted infections
• Histologically consist of papillary, exophytic, treelike cores of stroma covered by thickened squamous epithelium; koilocytic atypia shows nuclear enlargement, hyperchromasia, and a cytoplasmic perinuclear halo
• Considered to be non-precancerous lesions

Vulva - Squamous Neoplastic Lesions

• Vulvar intraepithelial neoplasia and vulvar carcinoma occur
• Uncommon malignant neoplasm
• Squamous cell carcinoma (SCC) is the most common histologic type of vulvar cancer
• Basaloid and warty carcinomas are related to infection with high-risk HPVs, most commonly HPV-16, accounts for 30% of cases
• Keratinizing squamous cell carcinomas are unrelated to HPV infection (70% of cases) and are more common, occurring in older women
• Basaloid and warty carcinomas are less common and occur at younger ages
• Develop from an in situ precursor lesion called classic vulvar intraepithelial neoplasia (VIN)
• Classic VIN occurs mainly in reproductive-age women and includes lesions designated formerly as carcinoma in situ or Bowen disease
• Risk factors include young age at first intercourse, multiple sexual partners, and male partner with multiple sexual partners
• Keratinizing squamous cell carcinoma often occurs in individuals with long-standing lichen sclerosus or squamous cell hyperplasia and is not related to HPV
• The peak occurrence is in the eighth decade, arising from a precursor lesion referred to as differentiated vulvar intraepithelial neoplasia (differentiated VIN) or VIN simplex
• Chronic epithelial irritation leads to gradual evolution to the malignant phenotype, presumably through acquisition of driver mutations in oncogenes and tumor suppressors
• Classic VIN presents as a discrete white (hyperkeratotic) or a slightly raised, pigmented lesion
• Microscopically, there is epidermal thickening, nuclear atypia, increased mitoses, and a lack of cellular maturation analogous to those seen in cervical squamous intraepithelial lesions
• Differentiated VIN involves marked atypia of the basal layer of the squamous epithelium and normal-appearing differentiation of the more superficial layers
• This can lead to Invasive keratinizing squamous cell carcinomas
• VIN contain nests and tongues of malignant squamous epithelium with prominent central keratin pearls
• The initial spread is to inguinal, pelvic, iliac, and periaortic lymph nodes
• Patients with lesions less than 2 cm in diameter have a 90% 5-year survival after treatment with vulvectomy and lymphadenectomy
• Larger lesions with lymph node involvement have a poor prognosis

Vulva - Glandular Neoplastic Lesions

• Like the breast, the vulva contains modified apocrine sweat glands
• Papillary hidradenoma is a sharply circumscribed nodule, most commonly on the labia majora or interlabial folds which may be benign
• May be confused clinically with carcinoma because of its tendency to ulcerate
• Histologically: papillary projections covered with two layers of cells: an upper layer of columnar secretory cells covering a deeper layer of flattened myoepithelial cells

Vulva - Extramammary Paget Disease

• It is similar in its manifestations to Paget disease of the breast
• Not associated with underlying cancer, and is confined to the epidermis of vulvar skin
• Paget cells are larger than surrounding keratinocytes and are seen singly or in small clusters within the epidermis
• The cells have pale cytoplasm containing mucopolysaccharide that stains with periodic acid-Schiff (PAS), Alcian blue, or mucicarmine stains and express cytokeratin 7

Vagina - Developmental Anomalies

• Developmental anomalies include septate or double vagina
• Can also be caused by manifestations of genetic syndromes, in utero exposure to diethylstilbestrol (DES, used to prevent threatened abortions in the 1940s through 1960s, or other unknown factors
• Vaginal adenosis may result
• Gartner duct cysts may develop

Vagina - Premalignant and Malignant Neoplasms

• Most benign tumors of the vagina occur in reproductive-age women
• Carcinoma spreading from the cervix, followed by primary squamous cell carcinoma of the vagina, is the most common malignant tumor
• Virtually all primary carcinomas of the vagina are squamous cell carcinomas associated with high-risk HPVs
• These are extremely uncommon cancer
• A risk factor is a previous carcinoma of the cervix or vulva
• SCCA: A premalignant lesion is VAGINAL INTRAEPITHELIAL NEOPLASIA
• Embryonal rhabdomyosarcoma is uncommon, AKA sarcoma botryoides
• It is most frequently found in infants and children younger than 5 years of age
• Presents of polypoid, rounded, bulky mass with "grapelike" clusters
• Microscopically, has small and oval nuclei, with small protrusions of cytoplasm from one end, resembling a tennis racket
• Beneath the vaginal epithelium, the tumor cells are crowded in a so-called cambium layer