Female Genital System Flashcards
Contact Dermatitis
Pruritus due to allergen/irritant
Well-defined erythematous weeping and crusting papules and plaques
Lichen Sclerosus
“Atrophy”
- Thinning of epidermis
- Disappearance of rete pegs
- Hydropic degeneration of basal cells
- Superficial hyperkeratosis
- Dermal fibrosis
Postmenopausal women (autoimmune)
Squamous Cell Carcinoma Increased 15% Risk
Lichen Simplex Chronicus
“Hypertrophy”
- Epithelial thickening
- Expansion stratum granulosum
- Surface hyperkeratosis
Condyloma
Anogenital warts on multiple sites
Lata - flat, moist, minimally elevated lesions occuring in secondary syphilis
Acuminata - papillary, distinctly elevated, somewhat flat and rugose.
Red-pink to pink-brown on vulva
Perinuclear cytoplasmic vacuolization with nuclear angular pleomorphism and koilocytosis
Hallmarks of HPV6 and 11 infection
Not precancerous
Vulvar Intraepithelial Neoplasia
Mostly in women > 60 yrs
~90% are squamous cell carcinomas
2 biologic forms:
- Young, cigarette smokers with HPV 16, coexisting vaginal/cervical carcinoma, carcinoma in situ, or condylomata acuminata.
- Older women, not associated with HPV, preceded by years of non-neoplastic epithelial changes, mainly lichen sclerosus. Tumors are well-differentiated and highly keratinizing.
VIN and early vulvar carcinomas appear as leukoplakia (epithelial thickening).
1/4 are pigmented with melanin.
These are transformed into overt exophytic or ulecerative endophytic tumors.
HPV+ neoplasms are usually poorly differentiated squamous cell carcinoma
<2cm tumor have 75% 5-yr surivavl after radical excision, only 10% of those w/ larger lesions survive 10 yrs
Paget disease of the vulva
A form of intraepithelial carcinoma. No underlying carcinoma.
Presents as a red, scaly, crusted plaque and may appear as an inflammatory dermatosis.
Occasionally there is an accompanying subepithelial or submucosal tumor from sweat glands.
Scattered large, clear tumor cells within the squamous epithelium, with abundant granular cytoplasm and occasional cytoplasmic vacuoles containing mucin (periodic acid-Schiff +).
Vaginitis
Produces vaginal discharge (leukorrhea)
Normal commensals that become pathogenic in conditions such as diabetes, systemic antibiotic therapy, after abortion or pregnancy, or in elderly person with compromised immunity, and AIDS.
Candida albicans - curdy white discharge
Trichomonas vaginalis - watery, copious gray-green discharge
Nonspecific atrophic vaginitis in postmenopausal women with preexisting atrophy and thinning of squamous vaginal mucosa
Vaginal Intraepithelial Neoplasia
Extremely uncommon, women > 60
Preexisting, concurrent cervical intraepithelial neoplasia or carcinoma of the cervix is frequently present.
VIN is a precursor lesion associated with HPV infection.
>50% of invasive SCC is associated with HPV.
Vaginal clear cell adenocarcinoma (young women in their late teens- early 20s whose mothers took diethylstilbestrol during pregnancy).
In 1/3 of at risk population, small glandular or microcystic inclusions appear in vaginal mucosa. Benign lesions, vaginal adenosis, appear as red granular foci and lined by mucus-secreting or ciliated columnar cells. Clear cell adenocarcinomas arise from this.
Sarcoma Botryoides
Soft polypoid masses
In infants and children < 5 yrs
Can occur in urinary bladder and bile ducts
Nabothian cysts
Overgrowth of the regenerating squamous eptihelium blocks orifices of endocervical glands in transformation zone to produce these cysts lined by columnar mucus-secreting epithelium.
Cervicitis
Extremely common, associated with a mucopurulent to purulent vaginal discharge.
White cells and inflammatory atypia of shed epithelial cells, as well as possible microorganisms.
Chlamydia trachomatis, Ureplasma urealyticum, T. vaginalis, Candida spp., Neisseria gonorrhoeae, herpes simplex II, and HPV.
Sexually transmitted: 40% by C. trachomatis
Herpetic infections transmitted to infants during birth can cause systemic infection.
Acute vs chronic
Acute - postpartum women, by staphylococci or streptococci
Chronic - nonspecific cervicitis - herpesvirus and C. trachomatis
Cervical Intraepithelial Neoplasia
Precancerous epithelial changes
Low-grade and high-grade squamous intraepithelial lesions (SIL).
Low-grade - CIN I or flat condylomas
High-grade - CIN II or III
Peak age: 30 yrs
Peak age of invasive carcinoma: 45 yrs
Risk factors: Early age at first intercourse, multiple sexual partners, male partner with multiple sexual partners, persistent infection by “high-risk” papillomaviruses, cigarette smoking, immunodeficiency
High-risk HPV 16, 18, 31, 45
Low-risk HPV 6, 11
High-risk HPV integrate into host genome and express large amts of E6 and E7 proteins, which block or inactivate tumor suprressor genes p53 and RB = trasnformed cell phenotype, capable of autonomous growth and susceptible to acquisition of further mutations.
CIN I - mild dysplasia - koilocytotic (nuclear hyperchromasia and angulation with perinuclear vacuolization).
CIN II - more severe dysplasia, maturation of keratinocytes delayed into middle 1/3rd of epithelium.
CIN III - greater variation in cell and nuclear size, marked chromatin heterogeneity, disorderly orientation of the cells, and normal/abnormal mitoses
Alterations are confined to epithelial layer and its glands - carcinoma in situ
Cervical cytology and cervical examinations (colposcopy) remain the method for cerical cancer prevention
Invasive Carcinoma of the Cervix
75% Squamous Cell Carcinoma
20% Adenosquamous carcinoma/adenocarcinoma
SCC = 45 yrs
White areas on colposcopic exam after dilute acetic acid application.
Most advanced stages in women who have never had a Pap smear - unexpected vaginal bleeding, leukorrhea, painful coitus, and dysuria.
Eradication by laser vaporization or cone biopsy of precursors is best method of prevention.
Outlook depends on stage.
Endocervical Polyp
Protrude (sometimes through the exocervix)
No malignant potential
Polypoid masses with smooth, glistening surface with underlying cystically dilated spaces filled with mucinous secretion.
Edematous stroma with scattered mononuclear cells.
Superimposed chronic inflammation may lead to squamous metaplasia of covering epithelium and ulcerations.
Endometritis
Part of PID
Retained products of conception subsequent to miscarriage or delivery, or a foreign body such as an intrauterine device. They act as nidus for infection by flora ascending from vaginal and intestinal tract.
Acute vs chronic based on predominant neturophilic or lymphoplasmacytic response.
Acute - N. gonorrhoeae or C. trachomatis. - Neutrophilic infiltrate in superficial endometrium and glands with stromal lymphoplasmacytic infiltrate.
Chlamydial infection - prominent lympohoid follicles
Mycoplasma - subtle lymphocytic stromal infiltrate.
Presentation: Fever, abdominal pain, menstrual abnormalities, infertility and ectopic pregnancy (due to damage to tubes).
In endemic areas, tuberculosis may present with granulomatous endometritis.
Adenomyosis
Growth of basal layer of endometrium down into myometrium.
Thickened uterine wall, enlarged uterus
May produce menorrhagia, dysmenorrhea, and pelvic pain before onset of menstruation.
Endometriosis
FUNCTIONING Endometrial glands and stroma in a location outside the endomyometrium.
Occurs in 50% of women with infertility.
Common cause of dysmenorrhea, pelvic pain, present as chocolate cyst.
Multifocal, may involve tissue in pelvis, less frequently around umbilicus, lymph nodes, lungs, and even heart, skeletal muscle, or bone.
Regurgitation theory - menstrual backflow through fallopian tubes with subsequent implantation.
Vascular/lymphatic dissemination theory
Find 2 of 3 features: endometrial glands, stroma, or hemosiderin pigment.
Severe dysmenorrhea and pelvic pain as a result of intrapelvic bleeding and periuterine adhesions.
Dysfunctional Uterine Bleeding
Abnormal bleeding in the absence of well-defined lesion
- Failure of ovulation: Anovulatory cycles due to excess estrogen (relative to progesterone) - poorly supported endometrium collapse and rupture of spiral arteries.
- Inadequate luteal phase: Failure for corpus luteum to mature normally leads to relative lack of progesterone.
- Contraceptive-induced bleeding: older oral contraceptives
- Endomyometrial disorders: chronic endometritis, endometrial polyps, submucosal leiomyomas
Endometrial Hyperplasia
Excess estrogen relative to progestin will induce hyperplasia.
Simple hyperplasia - Complex hyperplasia - Atypical hyperplasia
Failure to ovulate (menopause), prolonged use of estrogenic steroids, estrogen-producing lesions (polycystic ovaries), cortical stroma hyperplasia, granulosa-theca cell tumors of the ovary.
Common risk factor: OBESITY, adipose tissue processes steroid precursors into estrogens.
Atypical hyperplasia with cellular atypia: 25% risk of endometrial cancer.
Endometrial Polyps
Abnormal Uterine Bleeding
Fixed, hemispheric lesions (.5-3cm diameter)
Cystically dilated glands
Stromal cells are monoclonal, 6p21 rearrangement (the neoplastic component of the polyp)
Commonly develop at time of menopause
Rare risk of cancer
Leiomyoma
Menorrhagia, w/ or w/o metrorrhagia. Women complain of dragging sensation.
Benign tumor arising from smooth muscle cells of myometrium AKA fibroids b/c they’re firm.
Most common benign tumor (30-50% of all females)
No real risk of malignancy
Blacks > whites
Estrogens, oral contraceptives stimulate their growth, shirnk postmenopausally
Monoclonal. Nonrandom chromosomal abnormalities found in 40% of tumors
Sharply circumscribed, whorled cut surface.
Most often multiple tumors (can be bigger than uterus)
Intramural, submucosal, subserosal locations, can attach to surrounding organs and free themselves to become parasitic.
Histologically: whorling bundles of smooth muscle cells with possible foci of fibrosis, calcification, ischemic necrosis, cystic degeneration, and hemorrhage.
Endometrial Carcinoma
Presentation: Marked luekorrhea, irregular bleeding - cause of concern in postmp women, since it reflects erosion and ulceration of endometrial surface. Over time, uterus may be palpable.
Most frequent cancer occuring in female GT
Age: 55 - 65
- Endometroid* - Perimenopausal women with estrogen excess
- Serous* - Older women with endometrial atrophy
Risk Factors for endometroid carcinoma - obesity (increased synthesis of estrogens in fat depots and from adrenal and ovarian precursors), diabetes, hypertension, and infertility (nulliparous women)
Increased estrogen stimulation (prolonged estrogen replacement therapy and estrogen-secreting ovarian tumors increase risk of this cancer)
Similar R.F. as endometrial hyperplasia - endometrial carcinoma often arises on background of endometrial hyperplasia.
Endometroid - similarity to normal endometrial glands.
Breast cancer ~ Endometrial cancer (frequently)
Increased Risk for:
2nd most common cancer associated with hereditary nonpolyposis colon cancer syndrome (inherited genetic defect of DNA mismatch repair gene) - endometrioid endometrial carcinoma have high frequency of inactivation of these genes by methylation of promoter, and thus unstable genomes (microsatellite instability)
Cowden’s syndrome - multiple hamartoma syndrome w/ inc. risk of breast, thyroid, and endometrium carcinoma - mutations in PTEN (tumor suppressor gene)
Serous carcinoma - background of atrophy, sometimes in endometrial polyp - p53 tumor suppressor gene mutation
Endometroid carcinoma - resembles normal endometrium, range of patterns, including mucinous, tubal, and squamous differentiation. Originate in the mucosa and may infiltrate myometrium and enter vascular space (metastases to regional lymph nodes). Stage I - confined to corpus, Stage II - involvement of cervix, Stage III - beyond uterus but w/i true pelvis, Stage IV - distant metastases or involvement of other viscera. Synchronous endometrioid tumors in uterus and ovary - two separate primary neoplasms, so favorable prognosis.
Serous carcinoma - small tufts and papillae rather than glands, and much greater cytologic atypia, more aggressive.
Ovarian cancer
Risk factors:
- Nulliparity and Family History
- BRCA1 (30% inc. risk of ovarian cancer) and BRCA2 gene mutations
- HER2/NEU overexpressed in 35% of ovarian cancers (poor prognosis)
- K-RAS in 30% of tumors (mucinous cystadenocarcinomas)
- p53 in 50% of cancers
Pose clinical challenges because they produce no symptoms or signs until they are well advanced. When mature and large enough - they cause local pressure symptoms. They may (esp. the common epithelial tumors) may cause an increase in abdominal girth. Smaller masses, like dermoid cysts, can torse, producing acute abdomen. Malignant serous tumors and fibromas cause ascites (serous tumors seed metastatically of the peritoneal cavity).
No real improvement in treatment.
Protein CA-125 elevated (but also in benign conditions, so not a good screening marker). It’s useful as a screenting test in asymptomatic postmenopausal women because there are less confounding variables. Greatest value in monitoring response to therapy.
Surface Epithelial-Stromal Ovarian Tumors
-
Serous Tumor
- Most frequent ovarian tumor, 60% of all ovarian tumors
- Benign in 30 - 40 yrs old
- Malignant in 45 - 65 yrs old
- 60% benign, 15% low malignant potential, 25% malignant
Most are large cystic structures (30-40cm in diameter) - about 25% of benign forms are bilateral (serosal cover is smooth and glistening). Cystadenocarcinomas have nodular irregularities (penetration). On transection, multiple septa with cystic spaces filled with clear, serous fluid (mucus as well). Polypoid/papillary projections jut into the cystic cavities.
Benign tumors - single layer of tall columnar epithelium (part ciliated, part dome-shaped secretory cells) that line the cysts.
Psammoma bodies common in tips of papillae.
Carcinoma - anaplasia of lining cells, invasion of stroma. Complex, multilayred papillary formation, with invasion of axial fibrous tissue. p53 and BRCA1 mutations.
Tumors of low malignant potential - milder cytologic atypia, little or no stromal invasion. Some have BRAF and K-RAS mutations.
Distant metastases infrequent (regional lymph nodes common)
Prognosis for clearly invasive serous cystadenocarcinoma (after chemo, surg, radiation) = Poor
Surface Epithelial-Stromal Ovarian Tumors
-
Mucinous
- Differ from serous in that epithelium consists of mucin-secreting cells (like endocervical mucosa).
- MUCH LESS LIKELY to be malignant
- 80% benign, 10% low malignant, 10% malignant
USUALLY unilateral. VS SEROUS - larger, multilocular, papillary formations less common, no Psammoma bodies. Prominent papillation, serosal penetrationa, and solidifed areas -> malignancy.
3 types of mucin-producing epithial cells: endocervical, intestinal-type (almost always low malignant potential), and mullerian mucinous cystadenoma (associated with endometriotic cyst).
Mucinous deposits in peritoneum with production of copious amounts of mucin - psudomyxoma peritonei. Mainly from metastasis from GI tract (appendix mainly). Metastasis from GI tract to ovaries - Krukenberg tumor - BILATERAL involvement, infilfration of strom by small glands and individual cells, and “dirty” necrosis of tumor (necrosis associated with cellular debris).
