What parts of the female gential tract are most commonly affected by herpes (in order)?
cervix, vagina, and vulva
How does herpes present?
The earliest lesions usually consist of red papules that progress to vesicles and then to painful coalescent ulcers. During latency, the virus migrates to the regional lumbosacral nerve ganglia and establishes a latent infection
NOTE: There is a high transmission rate during active infection
These characterizations are similar regardless of where the infection occurs
What is this?
Molluscum contagiosum is a self-limiting Poxvirus common in young children between 2 and 12 years of age and is transmitted through direct contact or shared articles (e.g., towels) or can be sexually transmitted in adults
NOTE: MC lesions tend to be mutliple, raised, and punctuated in the center so that they dip down characteristically (below)
Describe cervical candida infections
These are very common and is commonly the result of a disturbance in the patient's vaginal microbial ecosystem (Not sexually transmitted). They present with lumpy cottage-cheese like discharge.
Describe what is being shown
Candida cervical infection- hyeast hyphae and pseudo-hyphae and shishkabob appearance with squamous cells
Describe Trichomonas vaginalis
This is a Protozoan that infects the vagina and cervix and presents as Asymptomatic or may complain of yellow, frothy vaginal discharge, vulvovaginal discomfort, dysuria (painful urination), and dyspareunia (painful intercourse).
What is this?
Trich- Marked dilatation of cervical mucosal vessels resulting in characteristic colposcopic appearance of “ strawberry cervix .”
Describe what is seen here
Cytology: oval shaped with red-granules in it (left),
Trich halos in squamous cells - seen in low grade cervical lesions as well (right, two arrows)
What is the main cause of bacterial vaginosis?
Gardnerella vaginalis- Gram-negative bacillus
How does GV present?
Patients typically present with thin, green-gray, malodorous (fishy) vaginal discharge.
Describe what is being shown here and what a clue cell is
In GV cause bacterial vaginosis, GV allows for overgrowth of normal flora, resulting in complete covering of squamous cells by bacteria to produce 'clue cells'
What is pelvic inflammatory disease?
Infection of the lower genital tract that spreads upward to result in a ergional infection. It can be venerial or endogenous (after surgery or delivery), and the most common venerial cause is chlaymdia trachomatis (although this infection typically only causes cervicitis) and some Neisseria gonorrhoeae resulting in pelvic pain, adnexal tenderness, fever, and vaginal discharge
How is Chylamydia trach diagnosed?
histology is non-specific so the diagnosis is made on molecular tests (same for gonorrhoeae)
How do venerial diseases progress?
Usually begin as a salpingitis and progress to abscess formation, and even periteonitis (called Fitz-Hue-Curtis Syndrome) and then bacteremia leadingt o septic arthritis. Fortunately, most infections are aymptomatic.
What are the potential complications of chronic PID?
infertility or ectopic pregnancy
What is a Bartholin Cyst?
Obstruction of a bartholin gland that causes abscess formation that needed to be excised or permanently drained. Can occur in any age group but most common in reproductive yrs.
Most irritations of the vulva are the result of ______
inflammatory and thus are harmless generally. (NOTE that malignant tumors of the vulva do exist but are rare)
Vulvitis can also be caused by infections, the most important in North America being what?
HPV, the causative agent of condyloma acuminatum and vulvar intraepithelial neoplasia (VIN)
What is lichen sclerosis? When does it occur most often? What causes it?
A condition that peaks in childhood and ***post-menopausal*** women marked by thinning of the epidermis, diasppearance of rete pegs, degeneration of basal cells, dermal fibrosis, and deeper mononuclear infiltrate of the vulva.
The cause is unknown but may be autoimmune
How does lichen sclerosus present clinically?
There is the appearance of white parchment-like skin (aka leukoplakia) with dermal fibrosis and complaints of dyspareunia
How does lichen sclerosus present histologically? What is the prognosis?
There is marked thinning of the epidermis, sclerosis of the superficial dermis and chronic inflammatory cells in deeper
The prognosis is benign, BUT it is associated with a slightly increased risk for squamous cell carcinoma
What is this?
Condyloma Accuminatum, or benign genital warts, caused by low oncogenic risk HPVs, mainly types 6 and 11 (90%).
What is a condyloma? Progression?
This is the name given to any warty lesion of the vulva
NOTE: Vulvar condylomas do not typically progress to carcinoma!!
What is Condyloma lata?
More rare today, but are flat, moist lesions that occur in secondary syphilis.
What are the main types of vulvar carcinoma? What pts most commonly get this?
This is a rare genital tract cancer, occurring mostly in women older than 60. Approximately 90% of vulvar carcinomas are squamous cell carcinomas, with the remaining 10% being mainly adenocarcinomas or basal cell carcinomas
What are the main forms of vulvar squamous cell carcinoma?
1) The less common form related to high-risk (16/18) HPV, common in middle-aged cig smokers
2) A form occurring in older women, often preceded by years or reactive epithelial changes marked by basal layer keratinization, commonly lichen sclerosus, and not related to HPV
Women with the form of vulvar squamous cell carcinoma assoicated with HPV tend to have what precede the onset of their cancer? What tends to promote the progression to cancer?
vulvar intraepithelial neoplasia (VIN) that typically progresses to carcinoma (but not 100%). Cig smoking and immunosuppression tend to increase the risk of progression
Describe what is being shown here
Left: VIN3 or carcinoma in situ in which there is no maturity toward the peithelial surface
Right: Invasive vulvar carcinoma marked by the lack of a basement membrane
What is this?
HPV negative VIN
How does vulvar carcinomas typically progress?
Both forms of vulvar carcinoma tend to remain confined to their site of origin for a few yrs but ultimately invade and spread, first to regional nodes.
What is the prognosis of vulvar carcinomas?
Women with tumors less than 2cm in diameter have a 90% 5 yr survival rate after excision, whereas only 20% of those with advanced-stage lesions survive 10+ yrs
What is extramammary paget disease?
an intraepidermal proliferation of malignant epithelial cells that occur in the skin of the vuvla or the nipple. However, in the vulva, there is hardly ever an assoication with an underlying ductal breast carcinoma, as is the case in nipple Paget disease
How does Paget disease present clinically?
Presents as a red, scaly, crusted plaque that may mimic the appearance of an inflammatory dermatitis
How does Paget disease present histologically?
Within the epithelium there are pale cytoplasm cells- be cautious, melanoma can look like this. The presence of mucin, at detected with a PAS stain, is also useful in distinguishing Paget disease from vulvar melanoma, which lacks mucin
How does Paget disease of the vulva progress?
It may persist for yrs without invasion, but when it does, the prognosis is poor
T or F. In adult females, the vagina is rarely a site of primary disease
T. More often it's invovled secondary by cancer or infection arising in the cervic, vulva, bladder, or rectum
What is vaginitis?
A common condition that is usually transient and is not concerning but is commonly associated with production of vaginal discharge (Leukorrhea). Commonly caused by infection
What are common infectious causes of vaginitis?
Many are due to normal commensals that become pathogenic in the setting of diabetes, ABX therapy, immunodeficiency, pregnancy, or abortion. In adults, primary gonorrheal infection of the vagina is uncommon.
Other frequent offenders- Candida albicans (below) and Trichomonas
What are the most common cancers of the vagina?
Squamous cell carcinoma
clear cell adenocarcinomas
Describe squamous cell carcinomas of the vagina
It is an extremely uncommon cancer that occurs in women over 60 in the setting of risk factors. VAIN is a precursor lesion that is nearly always associated with HPV infection.
Describe clear cell adenocarcinomas of the vagina
rare, but common in women who take diethylstillbestrol (a synthetic estrogen) during pregnancy to prevent abortion
What is sarcoma botryoides?
Aka embryonal rhabdomyosarcoma- An uncommon vaginal tumor composed of malignant embryonal rhabdomyoblasts in children under 5.
How do sarcome botyroides typically progress?
They tend to invade locally and cause death by penetration into the peritoneal cavity or by obstruction of the urinary tract,. Conservative surgery coupled with chemo offer the best prognosis
How common is cervical carcinoma?
While most cervical lesions are benign, cervical carcinomas is the 3rd most common female cancer with an estimated 530K cases/yr, of which 50+% are fatal
What is the most important cause of cervical cancer?
High risk HPV (name HPV-16 causes 60% and HPV-18 causes 10%)
___________ is the major risk for the deaths associated with cervical cancer
Lack of screening
Why are HPV 16/18 high risk for cervical cancer while HPV 6/11 are not?
16/18 integrate into the host DNA by infecting the basal cells through micro-tares,
while 6/11 remain extra-chromosomal and, thus, many regress (70%). Of the 30% that persist, only about 10% go on to be a high-grade lesion (and even some of those may regress). Of the high-grade lesions, 60% persist and 10% transform to carcinoma.
How does HPV prevent cell-cycle arrest?
Through virally-dervied E6 and E7 action which have the effect of inhibiting p53 and Rb respectively, as well as both inhibiting p21 and p27, two important cyclin-dependent kinase inhibitors.
NOTE: this requires insertion of viral DNA into the host genome to promote cancer
Most tumors of the cervix are of epithelial origin and are caused by oncogenic strains of HPV.
How does the cervix develop?
During development, the columnar, mucus secreting epithelium of the endocervix is joined to the squamous epithelial covering of the exocervix at the external os. At puberty, the squamocolumnar function becomes more columnar, and eventually the most external columnar cells undergo squamous metaplasia to form the transformation zone
Where does HPV like to infect the cervix?
the immature squamous cells of the transformation zone (basal layer).
NOTE: Replication of HPV DNA takes place in more differentiated overlying squamous cells
Describe the progression of HPV infections
Most are transient and are cleared within months. A subset can persist, however, and some of these can progress to CIN, a percursor to invasive cervical carcinoma.
T or F. HPV alone is sufficient to drive neoplastic development
F. Other factors, such as compromised immune status or co-infection with other STDs must be present
How long does the onset of CIN precede the onset of carcinoma if its going to occur?
How is CIN classified?
Mild cervical dysplasia is classified as CIN I (aka low-grade squamous intraepithelial lesion- LSIL)
Moderate dysplasia is CIN II, and Severe dysplasia is CIN III (Note CIN II and III are both grouped into high-grade squamous intraepithelial lesion- HSIL)
The decision to treat HSIL and to observe LSIL is based on differences in the natural histories of these groups
What stage of CIN is this?
Normal cervical epithelium
What Stage of CIN is this?
I- there is dysplastic changes in the lower third of the squamous epithelium
What Stage of CIN is this?
II- dysplasia extends to the middle third
What Stage of CIN is this?
III- there is no maturation during ascent and this atypia would be considered a carcinoma in situ
What changes are seen in HPV?
Best seen in LSIL caused by HPV- can see halos around the squamous cells (cytology left), binucleation and raisinoid nuclei (these are caused hoylocytic changes)
What tools can be used to diagnose HPV?
Ki-67 (proliferation) and p16 (needs to be strong and diffuse to classify as a high grade lesion)
What are the most common cancers of the cervix?
squamous cell carcinoma (75%)
All caused by high-risk HPV
T or F. You typically have to be either a heavy smoker or immunocompromised to progress to cervical cancer from CIN
Most pts. with advanced cervical carcinoma die of ______ rather than distant metastasis
local invasion. In particular, renal failure stemming from bladder and ureter obstruction is a common cause of death
What are these?
Adenocarcinoma in situ (left)- glands that provide mucin and
adeno invasive (right)
Staging of adenocarcinomas
Stage 0— Carcinoma in situ (CIN III, HSIL)
Stage I— Carcinoma confined to the cervix
Ia—Preclinical carcinoma, that is, diagnosed only by microscopy
Ia1—Stromal invasion no deeper than 3 mm and no wider than 7 mm (so-called microinvasive carcinoma)
Ia2—Maximum depth of invasion of stroma deeper than 3 mm and no deeper than 5 mm taken from base of epithelium; horizontal invasion not more than 7 mm
Ib—Histologically invasive carcinoma confined to the cervix and greater than stage Ia2
Stage II— Carcinoma extends beyond the cervix but not to the pelvic wall. Carcinoma involves the vagina but not the lower third.
Stage III— Carcinoma has extended to the pelvic wall. On rectal examination there is no cancer-free space between the tumor and the pelvic wall. The tumor involves the lower third of the vagina.
Stage IV— Carcinoma has extended beyond the true pelvis or has involved the mucosa of the bladder or rectum. This stage also includes cancers with metastatic dissemination.