Female Reproductive Tract Pathology Part 1 Flashcards
what type of tissue lines the vagina?
squamous mucosal lined space
what type of tissue is the outside dome of the the cervix (ectocervix)?
squamous mucosa
what tissue lines the internal endocervix?
columnar mucosa
what is important about the transition zone?
human papillomavirus causes squamous dysplasia and carcinoma has predilection to this area
Germ cells in the embryo migrate by the 5th or 6th week from the yolk sac to an area comprised of mesoderm called the genital ridge to form the gonads. During the 6th week of gestation what forms?
bilateral ducts form called the Mullerian ducts (aka paramesonephric ducts) and later the bilateral ducts called the Wolffian ducts (aka the mesonephric ducts)
what is the primary driver of anatomic sex?
the SRY or sex determining region on the Y chromosome
What happens if an embryo has an SRY gene?
it will drive the development of the testis which will produce testosterone and Mullerian inhibiting factor, which will drive the creation of male internal and external genitalia while inhibiting the development of female structures
what happens if an embryo lacks an SRY gene?
an ovary will be created, which will produce estrogen driving the creation of the female organs
what do the Mullerian ducts eventually become?
fallopian tubes, uterus, and upper portion of the vagina
Uterine didelphys is caused by what?
the failure of fusion of the mullerian ducts during embryologic development
What is Mayer-Rokitansky-Kuster-Hauser syndrome?
Uterine/vaginal absence or underdevelopment due to Mullerian agenesis
what occurs in Mullerian agenesis?
uterine/vaginal absence or underdevelopment
-amenorrhea but normal breast, pubic hair, vulvar development
What is a Bartholin Cyst?
What do they result from?
How do they present?
Bartholin cyst results from obstruction of the duct
Cysts present as a non-tender, unilateral soft mass (3-5 cm) in the posterior aspect of vaginal introitus
if infected (abscess) becomes painful, warm, +/- surrounding edema and cellulitis
what is the most common organism to cause an bartholin abscess?
e. coli
What is Lichen Sclerosus?
inflammatory disorder (with activated T cells) which typically affects the vulvar and anogenital skin
which population of patients does Lichen Sclerosus most commonly affect?
How does it present?
affects all ages, but most common in post-menopausal women
Presents: pruritus, dyspareunia, dysuria, anal discomfort, white plaques on skin
What are patients at increased risk of developing if they have lichen sclerosus?
***Importantly, although lichen sclerosus itself is not a premalignant lesion, with active symptomatic disease, there is an increased risk of squamous cell carcinoma, particularly squamous cell carcinoma driven by TP53 mutation
What does histology show in a patient with lichen sclerosus?
thinning (atrophy), hyperkeratosis, edematous band, with underlying lymphocytic infiltrate
What is Squamous cell hyperplasia (aka Lichen Simplex Chronicus)?
thickening of the skin due to chronic, habitual rubbing or scratching
What does physical examination show on a patient with lichen simplex chronicus?
thickened, reddened surface which can whiten over time
what is lichen simplex chronicus associated with?
contact dermatitis, psoriasis, lichen sclerosus, or squamous cell carcinoma
How do you make the diagnosis of lichen simplex chronicus?
***it should be noted that biopsy is rarely needed for diagnosis, as the clinical history and physical exam findings are often conclusive
What is Condyloma Acuminatum?
What causes it?
Anogenital warts
caused by HPV
often due to low risk HPV (6, 11)
How does condyloma acuminatum present?
skin colored, exophytic papules and plaques
can be present in the vulvar, perineal, perianal, vaginal, or cervical area
what are the histologic findings of condyloma acuminatum?
hyperplastic papillary projections comprised of squamous cells with parakeratosis
Most vulvar carcinomas are of what type?
squamous cell carcinoma
What categories can squamous cell carcinomas of the vulva be divided into?
- Basaloid/warty SCC
- keratinizing SCC
Both types of SCC of the vulva arise from what?
from a precursor squamous lesion called vulvar intraepithelial neoplasia (VIN)
The risk of vulvar cancer development depends on not only the duration and extent of disease but also what?
the immune status of the patient
*individuals who are immunosuppressed are much more predisposed to develop invasive carcinoma from a precursor VIN
What is the average age of onset of the basaloid/warty SCC of the vulva?
60 (younger)
what is the average age of onset of the keratinizing SCC of the vulva?
75 (older)
What is a major risk factor for developing the basaloid/warty SCC of the vulva?
infection with high risk HPV (16, 18)
what is the precursor lesion (VIN) associated with the basaloid/warty SCC of the vulva?
“classic VIN”
what is the precursor lesion associated with keratinizing SCC of the vulva?
differentiated VIN
what are the risk factors associated with the keratinzing SCC of the vulva?
chronic irritation: long standing lichen sclerosus or Squamous cell hyperplasia
What is a key factor to know for keratinizing squamous cell carcinoma?
its association with TP53 mutations, which causes the creation of an abnormal p53 tumor suppressor protein
Which VIN type can present with white plaques?
Why is this important to remember?
vulvar intraepithelial neoplasia of both the classic and differentiated variety can both present with raised white plaques
since both squamous hyperplasia and lichen sclerosus can also show leukoplakia, biopsy is often times necessary to rule out premalignant VIN change
What is papillary Hidradenoma?
a benign neoplasm which typically present as a solitary dermal or subcutaneous nodule
what is a papillary hidradenoma composed of?
columnar and myoepithelial cells with apocrine (sweat gland) differentiation
papillary hidradenomas are thought to arise from what?
mammary-type glands along the primitive milk-line
What is extramammary Paget’s disease (EMPD)?
an intraepithelial adenocarcinoma of unclear histogenesis
What type of differentiation do the tumor cells display in cases of extramammary Paget’s disease (EMPD)?
sweat gland (apocrine and eccrine) and keratinocyte differentiation
How does extramammary paget’s disease (EMPD) present?
pruritic, ill-defined, erythematous +/- white crusted lesion
“map like” quality to it
often found in the anogenital region, especially in the vulvar region
What are patients with extramammary Paget’s disease at risk of?
a noncontiguous synchronous carcinoma, which can involve another area such as in the bladder, urethra, or other gynecologic site
What are Gartner duct cyst and mullerian cysts?
common submucosal cysts in reproductive age women
gartner duct cyst is derived from Wolffian (mesonephric) remnants
mullerian cyst is derived from the mullerian (paramesonephric) duct
where are gartner duct and mullerian cysts located?
both types of cysts are often found on the anterior lateral walls of the vagina, sometimes protruding from the orifice
what are gartner duct cysts lined by?
a cuboidal to low columnar epithelium whereas mullerian cysts can show any epithelium seen in the female genital tract
What does in utero DES exposure predispose women to develop?
clear cell adenocarcinoma in daughters of women who had used the drug during pregnancy
vaginal adenosis
What is vaginal embryonal rhabdomyosarcoma?
sarcome botryoides
uncommon, found in infants and young girls (less than 5 years)
how does vaginal embryonal rhabdomysarcoma present?
protruding bulky, polypoid, grape-like mass
mucosanguineous discharge
what are the complications associated with vaginal embryonal rhabdomyosarcoma?
invasion can result in death by bladder obstruction, penetration to peritoneal cavity
the tumor cells of embryonal rhabdomyosarcoma are malignant cells derived from what?
embryonal rhabdomyoblasts, which are the cells within the embryo that will differentiate to eventually become mature muscle cells
What is the pathogenesis of vaginal squamous cell carcinoma?
it starts with a premalignant lesion, vaginal intraepithelial neoplasia (VAIN) caused by a high risk HPV (16 or 18)
When the vaginal squamous cell carcinoma metastasizes, what does the lymphatic pattern of spread depend?
depends on where the carcinoma starts
for vaginal squamous cell carcinoma in the lower ⅔s of the vagina: typically involves the inguinal and femoral nodes
for vaginal squamous cell carcinoma in the upper ⅓ of the vagina: typically involves the iliac lymph nodes and can later spread to periaortic lymph nodes
High risk HPV integrates into what?
into the squamous cells genome where the E6 and E7 oncogenes create proteins which promote oncogenesis
how do the high risk strains promote the formation of precancerous and cancerous lesions through E6?
E6 increases telomerase causing the cell to be able to not have a finite division limit
E6 also degrades p53 which is a tumor suppressor gene
how do the high risk strains promote the formation of precancerous and cancerous lesions through E7?
E7 drives cellular proliferation past the G1/S cell cycle point through the inhibition of p21 and RB binding
The current standard is to stratify all cervical squamous lesions into only two diagnostic categories: what are they?
low grade squamous intraepithelial lesion and high grade squamous intraepithelial lesion
Which layer does infection by HPV occur?
in the basal layer
in mild squamous dysplasia or a low grade squamous intraepithelial lesion (CIN I), what is the maturation level like?
there is a lack of maturation in the lower third of the epithelium often times with koilocytes seen in the upper laters
what happens to the level of maturation as the dysplasia becomes increasingly more and more severe?
eventually the middle third shows atypia and lack of maturation and finally with severe dysplasia in a high grade squamous intraepithelial lesion (CIN III) the entire epithelium shows atypia with lack of maturation
in a normal pap specimen, what are the nuclear to cytoplasmic and koilocytic characteristics?
there is no change in the nuclear to cytoplasmic ratio and no koilocytic changes
if there is a low grade squamous intraepithelial lesion, what are the pap findings?
koilocytes will be seen in the cytology specimen corresponding to the koilocytes present in the upper epithelium of such a lesion
if there is a severe dysplasia in a high grade squamous intraepithelial lesion, what do the dysplastic cells show on pap smear?
a high nuclear to cytoplasmic ratio in the cytology specimen, resembling basal cells
what does punctation help with?
stratifying the risk of degree of the dysplasia
What is the treatment if the biopsy shows a high grade squamous intraepithelial lesion (moderate or severe squamous dysplasia?
treated with a cervical conization or a LEEP procedure
what happens if a high grade squamous intraepithelial lesion is not removed?
it has the possibility to transform into an invasive squamous cell carcinoma
*remember, approximately 10% of high grade squamous intraepithelial lesions progress to carcinoma
Although the majority of cervical carcinomas are squamous cell carcinomas, sometimes a high risk HPV infects the endocervical mucosa. This can cause what?
a precursor glandular lesion called adenocarcinoma in situ (AIS)
how is adenocarcinoma in situ (AIS) characterized?
by hyperchromatic nuclear enlargement with pseudostratification
what can adenocarcinoma in situ progress to?
cervical adenocarcinoma
what is the average age of diagnosis of cervical carcinoma?
45-50
what is the current CDC recommendation for vaccination against HPV?
at age 11 or 12 to both males and females
what are endocervical polyps?
when do they occur
how do they present
how are they treated
benign, common lesions, typically less than 3 cms
occur during the reproductive years, especially after 40
can present with spotting (bleeding) or discharge
simple excision (polypectomy) is curative
