Exam 3 Diseases

Psoriasis

Noninfectious causes of vaginal discharge and discomfort Precipitants: Stress, trauma, dry skin, strp Autoimmune Skin esp elbows, knees or scallop and joints. Red, raised scaley/silver plaques. "Auspitz Sign": Pinpoint bleeding spots from exposure of dermal papillae when scales are scraped off. Psoriatic arthritis. Chronic/recurring UV therapy, immune modulators, topical emollients

Natural progression and regression of Cervical cancer

*important because it takes up to 10 years for the dysplasia to progress to cervical cancer. - Note in ASCUS, 68% would regress back to normal in 12 months, depending on HPV status. (7% progress to higher grade over 24 months) - For CIN1 (LGSIL), 50-80% will regress back to normal in 12 months (4-13% progress to higher grade over 24 months) - For CIN2-3 (HGSIL), 32-58% will regress back to normal in 12 months. (22% progress to higher grade over 24 months)

Management after initial testing and/or treatment of cervical cancer

- Depends on disease severity - Follow up may be as minimal as repeating the pap or an HPV test in 1 year w/ no treatment or may be as aggressive as surgical treatment w/ followup paps every 3-6 months, or even hysterectomy if cancer is present - Consider patient compliance w/ the follow-up plan - Consider treatment risks and the patient's future fertility desires.

Diagnostic and treatment excision procedures (cervical cancer)

- Performed following colposcopy study results - Obtaining a specimen from the lesion, transformation zone, and endocervical canal for further histological evaluation and treatment - Treatment procedures for cervical dysplasia: *Loop electrosurgical excision procedure (LEEP), cold-knife conization, laser conization, cryotherapy - Dilation and curettage for endometrial cells - Treatment and follow-up vary by situation

Possible harm from pap screens

1. Anxiety 2. Stigma from detected STI 3. Pain and bleeding from testing and tx procedures 4. Overtreatment of findings causing complications (short cervix ⇒ preterm births; stenotic cervix ⇒ C-section from failure to dilate in labor; pain, bleeding, infection)

Further evaluation of dysplasia (cervical cancer)

1. Repeat Pap test: w/ or w/o HPV testing 2. Colposcopy: up close microscopic eval of cervix to visualize and sample abnormal cells of the cervix (diagnostic) Examination of cervix, vagina, or vulva with an instrument that illuminates and magnifies these tissues; may involve biopsy. Usually performed in response to an abnormal pap test Attempt to visualize the abnormal cells that alerted the cytologist 3. Endocervical sampling: obtaining a specimen from the inner cervical canal 4. Endometrial sampling: obtaining a specimen of the uterine lining. *never do a endocervical curettage or endometrial biopsy on a pregnant women

Epidemiology of Cervical cancer

500K new cases annually and 240K deaths from cervical cancer per year. 3.5 million women have abnormal pap in the US and 7% are cervical cancer. 4.4% are atypical squamous cells of undetermined significance (ASUS) 50% of women in US with cervical cancer have never been screened 5-year survival rate for local disease is 92% 5-year survival for distant metastasis is 13% Screening = reduces incidence of cervical cancer.

Endometrial Carcinoma Type I

55-65 years old Genetics: PTEN Most common - 80% 2 familial cancer syndromes with increased risk of endometrioid type: 1. Hereditary nonpolyposis colon cancer syndrome (inherited genetic defect in DNA mismatch repair gene) 2. Cowden's syndrome (mutations in PTEN, tumor suppressor gene) Both mismatched genes and PTEN mutations are early events in endometrial carcinogenesis, occurring in progress from abnormal proliferation to atypical hyperplasia. Pathogenesis: Precursor: hyperplasia Indolent behavior; spreads to lymphatics Normal gland ⇒ PTEN mutation ⇒ latent precancer ⇒ EIN ⇒ adenocarcinoma (endometrioid, type 1) Develops with prolonged estrogen stimulation and endometrial hyperplasia Clinical setting: unopposed estrogen, obesity, hypertension, diabetes Endometrioid morphology (well, differentiated, mimic proliferative endometrial glands) - Grossly localized polypoid or diffuse - Spread usually via direct myometrial invasion - Dissemination to nods and late stage hematogenous spread (lungs, liver, bones) Histologically: most are adenocarcinomas (well-defined gland patterns lined by malignant stratified columnar epithelial cells) - 2-20% are squamous Grades: - Well differentiated, moderately differentiated, and poorly differentiated 90% 5 year survival for stage 1 or 2 with radiation and surgery 50% 5 year survival for stage 2 or 3

Endometrial Carcinoma Type II

65-75 years old Genetics: p53 mutation (90%) Serous carcinoma is most common subtype Precursor: serous endometrial intraepithelial carcinoma (EIC) Aggressive behavior; intraperitoneal and lymphatic spread Adenocarcinoma (endometrioid, type 1) ⇒ p53 mutation, mixed tumor into Serous EIC ⇒ serous adenocarcinoma (non-endometrioid, type II) OR from normal gland ⇒ Serous EIC ⇒ serous adenocarcinoma (non-endometrioid, type II) due to P53 mutation or ER/PR loss. Clinical setting: atrophy of endometrium, thin physique No screening test Irregular postmenopasual bleeding with excessive leukorrhea Labs: Serous, clear cell, and/or mixed mullerian tumor morphology - Papillary structures and psammoma body formation Poorly differentiated (grade 3) - solid sheets of cells with barely recognizable glands Morphology: Arise in small atrophic uteri; large bulk tumors, deeply invasive. - May be associated with extensive peritoneal disease Diagnosis depends on biopsy or curretate and histologic evaluation 50% alive after 3 years. If peritoneal cytology and adnexal histologic exam are negative, much better survival

Bacterial vaginosis (Gardnerella)

Gram-neg coccobacillus that doesn't penetrate the mucosa, nor elicits an inflammatory reaction (hence vaginosis) -Caused mainly due to dysbiosis Clinical: No inflammation Burning or pruritis of labia Thin, white or gray discharge w/ fish odor Labs: Clue cells in wet mount (squamous epithelial cells w/ a lot of bacteria/coccobacilli attached) pH > 4.5 pos KOH pos whiff test No neutrophils in discharge Treatment: Metronidazole (oral or vaginal cream) or clindamycin (vaginal cream) (Can use Tinidazole - fewer adverse effects)

Atypical glandular Cells of Undetermined Significance (AGUS)

Glandular cells = columnar epithelium - AGUS pap smear is benign abnormalities that include reactive endocervical cells, glandular metaplasia, endometriosis, endocervical polyps, and Arias-Stella reaction of the endometrium associated w/ pregnancy - Significant abnormalities include cervical dysplasia associated with squamous lesions, endocervical adenocarcinoma in-situ, and invasive endocervical adenocarcinoma - Incidence of AGUS is 0.18-0.74% of PAP smears.

Chlamydia Trachomatis Cervicitis

Obligate intracellular Elementary bodies (entering) Reticulate bodies (replicating) NAAT for detection Female: Cervicitis w/ watery vaginal discharge. Can progress to salpingitis and PID. (Repeated episodes can lead to infertility and ectopic pregnancy). Can have urethritis w/ dysuria. 1 drug therapy: Azithromycin (or can give tetracycline like doxycycline) - If there is co-infection with gonorrhea, give ceftriaxone (cephalosporin)

Allergic Vulvitis

Specific etiologies of irritants causing vaginal discharge/discomfort *Local allergic response Can be an allergic response to: topicals, soaps, feminine products, latex, bike or horseback riding, wet bathing suits, sanitary napkins Sx: Itching, redness, swelling, blisters, scales Avoid precipitants. Cool compresses, astroglide, topical medications, well balanced diet, rest, stress reduction, complementary or alternative medicine

Genital Herpes (HSV-2)

Typically presents as grouped blisters on the vulva or the perineal skin - Initial vesicular lesions appear on the vagina, cervix, vulva, and perineum - Vesicles are painful with burning and itching often associated with urination - Virus then travels up the axon and becomes latent in sensory (lumbar or sacral) ganglion cells - Recurrences may be induced by stress and pregnancy with the possibility of neonatal infection. (refer to micro for more details) - Cervical and vaginal cells exhibit large nuclei with acidophilic inclusions (ground glass nuclei)

Uterus Adenomyosis

Unknown cause - 15-20% of uteri Basal layer of endometrial glands grow deep within myometrium ⇒ expands uterine wall Hemorrhage within cysts leads to menorrhagia, dysmenorrhea, dyspareunia, pelvic pain Irregular nests of endometrial stroma +/- glands, 2-3 mm below basalis

Carcinoma of Vagina

Vagina cancer (arising from squamous epithelium lining the vaginal mucosa) Epidemiology: -2% of all GYN cancers -Carcinoma of older women -90% of all primary malignant tumors of vagina Cause: HPV (16, 18) ⇒ Vaginal intraepithelial neoplasia (VAIN) ⇒ vaginal carcinoma Detected only upon GYN examination Cancer from lower 1/3 ⇒ inguinal nodes Cancer from upper 2/3 ⇒ regional iliac nodes 5 yr survival for tumors confined to vagina (Stage I) is 80% whereas it is only 20% if extensive spread (IV)

Vulva/Vagina anatomy

Vulva = includes the skin, mucosa of the female genitalia external to the hymen. (labia majora, labia minora, mons pubis, and vestibule). Lined by squamous epithelium Vagina = canal leading to cervix. The mucosa is lined by NON-KERATINIZING squamous epithelium. During development, the lower ⅓ of vagina (from urogenital sinus - UGS) is squamous epithelium and the upper ⅔ of vagina (from Mullerian ducts) is columnar epithelium. As you grow, the squamous epithelium takes over the columnar epithelium. Thus, the vagina overall becomes squamous epithelium.

Syphilis

Presents as vulvar ulcers, chancres, or as cervicitis, or vaginal lesions that if left untreated, can progress to secondary or tertiary form. (refer to micro for more details)

Pap screening errors

*1. Inadequate sample collection - most common 2. Abnormal cells not identified or inaccurately reported 3. Small amount of water-soluble lubricant on the speculum doesn't reduce the quality of pap tests and probably doesn't affect microbiologic results

When to do a pap smear screening?

According to Sackett lecture: 1. Start at age 21+ REGARDLESS of age of sexual onset (meaning, don't screen anyone under 21 even if they are sexually active) 2. End after age 65 with adequate prior screening. Screen for a minimum of 20 years after dx of CIN2 or higher or through age 65, whichever is later. Can end after total hysterectomy for benign disease. 3. Special considerations: supracervical hysterectomy, risk factors, vaginal pap smears - in utero diethylstilbestrol exposure 4. ASCCP recommendations for conservative approach for young women under 21 b/c cancer is rare. Dysplasia is common and dysplasia commonly regresses. Want to prevent future cervical insufficiency due to excessive surgical interventions for dysplasia. 5. Adequate prior screens: 2 negative consecutive co-tests or 3 negative pap tests within the past 10 years, with the most recent test within the previous 5 years. 6. Continue to offer screening to women w/ good life expectancy who have risk factors for cervical cancer until about age 80, but upper age limits vary with risk factors. Age 21-29 = every 3 years with cytology alone Age 30-64 = every 3 years or every 5 years with HPV or cotesting. *special considerations are prior abnormal results on pap or HPV testing; prior treatment for CIN; and hx of HIV. Summary: - pap smears to screen for cervical cancer are done every 3 years from age 21-65 unless risk requires more frequent or extended testing. - Adding HPV testing to a pap smear in those age 30-65 can extend testing interval to every 5 years

Risk factors for cervical cancer

Age, HPV infection (type 16/18), early age intercourse (<16), multiple sexual partners, chlamydia infections, low SES, poor nutrition, cigarette smoking, heredity, lack of regular pap smears, race and immigrant status (African American and Hispanics)

Premenopausal AGTB - Anovulatory causes

Age-related subcause = Endometrial hyperplasia/cancer - Highest risk: advanced age, obesity, nulliparity, infertility, DM, FHx colon cancer, long-term unopposed estrogen therapy, Hx of tamoxifen use - Anovulation ⇒ increased risk of endometrial cancer - Abnormal uterine bleeding Endocrine subcause - Causes of anovulatory bleeding that is endocrine related is PCOS, uncontrolled DM, hypo- or hyper-thyroidism, hyperprolactinemia, intense exercise or stress, ovarian follicle decline (perimenopause), and starvation (including eating disorders) Iatrogenic subcause Causes of anovulatory bleeding that is iatrogenic: 1. Antiepileptics = Valproic acid 2. Typical antipsychotics = Haloperidol, chlorpromazine, thiothixene - These raises prolactin 3. Atypical antipsychotics = Clozapine, risperidone - These raises prolactin Anovulatory bleeding description - Anovulatory bleeding is characterized by irregular or infrequent periods, with flow ranging from light to excessively heavy - At extremes of reproductive years, irregular cycles resulting from anovulation can occur. - NORMAL TIMEFRAME: Following menarche, the immature hypothalamic-pituitary-ovarian axis may result in anovulatory cycles for 2-3 years. Up to 8 years before menopause, women may have intermittent anovulatory cycles. - ABNORMAL TIMEFRAME: During the rest of reproductive years, recurrent irregular cycles may be caused by anovulation and considered abnormal. - Dysfunctional uterine bleeding = anovulatory bleeding of unknown etiology Anovulatory bleeding workup 1. History 2. Physical exam = obesity, hirsutism 3. Labs = pregnancy test, TSH, prolactin 4. Endometrial biopsy = women <35 with prolonged unopposed estrogen stimulation; women >35 with suspected anovulatory bleeding; women unresponsive to medical therapy Anovulatory bleeding treatment Depends on underlying etiology. In general, OCPs or cyclic progestin induce routine withdrawal bleeding, decrease risk of hyperplasia or cancer, and correct any related excessive menstrual bleeding.

Endocervical adenocarcinoma in situ (AIS)

Also called cervical glandular intraepithelial neoplasia or CGIN (last stage before it becoming invasive) - Generally arises in the region of the squamocolumnar junction and extends into the endocervical canal - Displays tall columnar cells with abundant mucinous cytoplasm, resembling goblet cells. It is an intraepithelial neoplasm w/ normal underlying endocervical glands. In 40% of cases, high grade CIN also occurs.

Definition of terms for abnormal genital tract bleeding

Amenorrhea = absence of menses Oligomenorrhea = menstrual cycle length >35 days Polymenorrhea = menstrual cycle length <21 days Menorrhagia = heavy menstrual bleeding during menses Metrorrhagia = irregular intervals of menses Hypomenorrhea = light flow during menses Menometrorrhagia = heavy bleeding and irregular timing

Vagina/Vulva Atrophy (Postmenopausal AGTB - anatomical)

Atrophy = most common cause of postmenopausal bleeding Note other causes of vagina/vulva bleeding = trauma/abuse (damage to susceptible tissue), vaginitis (increased pH), and lichen sclerosis Menopause leads to natural decline in estrogen, causing thinning of epithelium, loss of elasticity, shortening and narrowing of vaginal canal with loss of distensibility, decrease in vaginal secretions, increase in vaginal pH Vaginal dryness, dyspareunia, post-coital bleeding Exam: pale, dry, smooth, shiny vaginal epithelium *MOST IMPORTANT DX TO EVALUATE FIRST IS ENDOMETRIAL CANCER

HPV testing as screening tool

Benefits: - Since HPV prevalence decreases with age, presence in older populations is a marker for progressive disease - Helps minimize number of colposcopies and reduces harm - If pap and HPV are negative, extend screening interval to every 5 years Drawbacks: access - financial or logistical. There are differences in guidelines in screening. Board questions more reliant on USPSTF recommendations (which is what Dr. Sackett listed) (She uses USPSTF and ACOG)

Endometrial Polyps

Benign, localized overgrowths that project from the endometrial surface into the endometrial cavity - Most arise in the fundus, usually solitary, and vary in size - Not believed to be pre-neoplastic, but up to 0.5% harbor adenocarcinoma - Can arise as a side effect of tamoxifen, which has anti-estrogenic effects on breast but weak pro-estrogenic effects on the endometrium. Pathogenesis: Thought to arise from endometrial foci that are hypersensitive to estrogen stimulation or unresponsive to progesterone that in either cause would not slough during menstruation and would continue to grow. Clinical: Presents with intermenstrual bleeding, owing to surface ulcerations (the overgrowth of endometrium due to estrogen leads to overgrowth of blood supply ⇒ eventual degeneration = bleeding) Microscopically: consists of endometrial glands, cystically dilated and hyperplastic, with rick endometrial stroma

Vulvodynia

Chronic pain and discomfort of the vulva. Can lead to dyspareunia and vaginismus Unknown cause(s) → Spasms, allergies, hormonal changes, genetics, infection, abuse, over-use of topicals, trauma Sx: Burning, itching, throbbing, swelling H&P, colposcopy, cultures Avoid tight clothing, douching, deodorized pads or tampons, vulvar pressure (bike riding). Cleanse with mild soap and water. Use lubricants during intercourse. Dietary modifications, steroids, anticonvulsants. Biofeedback, surgery.

Cervical Intraepithelial neoplasia (CIN)

CIN is characterized by koilocytic change (keyword for HPV = the hallmark of infection), disordered cellular maturation, nuclear atypia, and increased mitotic activity within cervical epithelium. Cervical cancer progression (from neoplasia ⇒ invasive carcinoma) = SQUAMOUS CELLS: CIN I: Involves <1/3 of the thickness of the epithelium CIN II: Involves <2/3 of the thickness of the epithelium CIN III: Involves slightly less than the entire thickness of epithelium Carcinoma in situ (CIS): Involves entire thickness of the epithelium Invasive carcinoma: Last stage in which the cancer invades through the basement membrane Lower CIN grades can regress. However, higher the grade of dysplasia, more likely it is to progress to carcinoma and less likely it is to regress to normal Cervical dysplasia is squamous cell cancer that originates in the transformational zone, marked by intense cell proliferation - This zone may be widened after cervical trauma, which typically occurs during a vaginal delivery when the cervix widens to allow the birth. - Chronic inflammation also causes its widening (as from infection) - Women who have numerous vaginal deliveries or those that are infected may have altered transformation zones. - These altered, proliferating cells are increasingly susceptible to viral infections so exposure to an oncogenic virus, such as HPV could induce neoplastic transformation of this zone. - These transformed cells don't respond to normal regulatory stimuli in the tissue (no maturation) = remain undifferentiated and proliferate uncontrollably. - Lack of normal maturation of squamous epithelium = "Dysplasia" = CIN-I, II, or III. It may progress to the point it reaches the basement membrane (doesn't pass it though) = Carcinoma In-Situ. If it crosses, then it is invasive carcinoma, which can spread locally or invade lymphatics and metastasize to distant sites. *Note that the readings for specifically an abnormal glandular (columnar cell result) will be AGUS, AIS (or CGIN), and invasive adenocarcinoma. (otherwise, CIN, CIS, and invasive cervical carcinoma refers to squamous)

HPV

Can result in formation of venereal warts on the vulva, vagina, or cervix, called Condyloma accuminatum (now most common venereal disease in US) (refer micro for more details)

Ovary, Fallopian Tube (Postmenopausal AGTB - anatomical)

Cancer of fallopian tube, ovarian cancer

Cervicitis in general

Caused by Gonorrhea or Chlamydia Inflamed cervix appears red, swollen, and has yellow mucopurulent endocervical discharge. Infection can spread upwards to involve the uterus, fallopian tubes, and ovaries (PID) and cause abnormal vaginal discharge, or uterine bleeding, dyspareunia, N/V, and fever. Most common symptom = lower abd pain

Cervical carcinoma (squamous) (if it was glandular, it would be named as cervical adenocarcinoma)

Cervical carcinoma is the last stage of cervical cancer progression = invading through the basement membrane. Epidemiology Middle-aged women (40-50 y/o) ~20% of all malignant tumors in the female repro tract but accounts for more deaths than cancer of the uterus, vagina, and vulva together. Cause High risk HPV infection (16, 18) Secondary risk: smoking and immunodeficiency (AIDS) Other Risks: sex at early age, multiple sex partners (prostitutes), other venereal diseases like Herpes or Syphilis (environmental causes) Clinical and complications Vaginal bleeding, especially postcoital bleeding or cervical discharge (as tumor develops, the discharge becomes more purulent and foul-smelling) - Pain is not a feature unless it spreads beyond the cervix. Advanced tumors invade through the anterior uterine wall into the bladder, blocking ureters. Hydronephrosis with postrenal failure is a common cause of death in advanced cervical carcinoma. Metastases tend to follow the lymph node drainage of the cervix and typically involve pelvic lymph nodes. Distant mets to the abdominal and thoracic organs may occur in terminal stages. Labs Colposcope = used to identify mucosal abnormalities (mosaic pattern) and tortuosity of the vessels. Mucosa changes from a smooth, shiny contour to an exo- or endophytic invasive tumor that either protrudes into the vagina or grows inside the cervix (crater-like ulceration) Staging and Tx Stage 0 = no gross lesions. Carcinoma limited to mucosa (CIS) Stage 1 = invasive but confined to cervix Stage 2 = extends beyond cervix, not reaching pelvic wall or upper vagina Stage 3 = reaches pelvic wall and invades lower third of vagina Stage 4 = spread beyond pelvis and infiltrated adjacent organs. CIS or other forms of CIN can be restricted surgically with a scalpel or laser ablation, cryotherapy, or electrocautery. - Stage I or II lesions have been treated surgically or by irradiation. - Advanced lesions are treated surgically in combo with radiation and chemo but results are not too encouraging.

Gonococcal Urethritis

Clinical: Dysuria - chief complaint (almost all cases of gonorrhea, ½ pts NGU) Pruritus, burning, discharge (discharge features like cervicitis) - 5-10% gonorrhea = no symptoms -Mucoid, mucopurulent, or purulent discharge on examination -Large % of women asymptomatic -Other complaints: lower abdominal discomfort, pain with sexual intercourse (dyspareunia). -Both asymptomatic and symptomatic women can transmit infection. Males: Symptomatic = primarily urethritis: - Dysuria, purulent discharge (much more purulent than Chlamydia) Epididymitis can occur (later in reproduction). Labs: Easy to see on Gram-stain. Gram-stain shows gram-negative diplococci and WBCs GC urethritis also infects columnar epithelium of vagina and cervix, which becomes reddened and friable, with purulent exudate Positive leukocyte esterase "dipstick" or the presence of >10 WBCs per high power field of the first void or first catch spun urine

Non-gonococcal urethritis (NGU)

Clinical: Dysuria - chief complaint (almost all cases of gonorrhea, ½ pts NGU) Pruritus, burning, discharge (discharge features like cervicitis) If dysuria is the only symptom, most likely chlamydia. -40% NGU = no symptoms. Male: Nongonococcal urethritis (NGU) = dysuria, water, nonpurulent discharge (sometimes might not be enough to even see). Can progress to epididymitis, prostatitis, or proctitis. Labs: CAN'T be seen on gram-stain: Chlamydia trachomatis (most common cause of NGU) and mycoplasma genitalium. PCR/NAAT for NGU Positive leukocyte esterase "dipstick" or the presence of >10 WBCs per high power field of the first void or first catch spun urine

Endocervical polyps

Common Arise in endocervical canal Irregular vaginal bleeding Loose fibromyxomatous stroma, mucin secreting endocervical glands and inflammation

Sexually active adolescents (under 21) cervical cancer screening guideline

Counsel regarding safe sex and contraception; counsel and test for STIs (HIV, gonorrhea, chlamydia through urine specimen; if asymptomatic, no speculum for STI testing) Pap/cervical cytology NOT necessary (even to rx OCP's)

Endometriosis Labs and imaging

Cystic lesions measuring 1-5 cm in diameter. (can be red, white, brown, yellow, translucent) - Superficial implants - Adhesions - filmy or dense - Endometriosis cysts are filled with brown-red viscous fluid derived from decomposed blood "Chocolate cyst" = Endometrioma: Classic chocolate cyst from ectopic endometrial stroma and glands on ovary Histology needs 2/3 components: - Endometrial type glands - Endometrial type stroma - Evidence of chronic hemorrhage (hemosiderin laden macrophages) Labs are typically not useful. CA-125 can be elevated, but this is not specific. Imaging is mainly useful only in the presence of a pelvic or adnexal mass. Ultrasound is modality of choice. Ovarian endometriomas on ultrasound appear as cysts with low-level, homogeneous internal echoes like old blood. Can also view rectovaginal/bladder nodules. Imaging along has high predictive accuracy in differentiating endometriomas from other adnexal masses. - Mass usually in pelvis but can occur as far away as lungs and diaphragm (catamenial hemoptysis) - Can't see small lesions/nodules - Unable to detect adhesions, but can assess mobility and fixation *Laparoscopy with Biopsy = gold standard (histology) - Exceptions to surgery: if you can visualize the mass/lesion and biopsy without needing laparoscopy - Exceptions to surgery: Endometrioma on ultrasound: if it's clear and dark, it's a sign it's just a regular fluid-filled cyst. If there's graininess, and has smooth borders, it's consistent with stagnant blood that might have formed a clot.

Neonatal withdrawal bleeding (AGTB - premenarchal)

Premenarchal AGTB - Hormonal causes: Normal physiologic process in newborn females Maternal estrogen stimulates growth of the female fetus' endometrium. Then the lack of estrogen after birth leads to endometrial slough Few days of light vaginal bleeding (scant blood seen on diaper) No treatment needed

Normal vagina

Description: Lactobacillus is part of the normal flora and if we take antibiotics, we can inhibit normal flora Signs and symptoms: Doesn't cause symptoms of pruritus, pain, or irritation - Pools in fornices of vagina - Increases during sexual excitement - What effects? Diet, sexual activity, meds, stress, pregnancy, ovulation, menopause, hormonal use Leukorrhea = excessive amount of discharge Lab findings: - 1-4 mL of fluid/24 hours, white or transparent - vaginal pH = 3.8-4.2 - Absent amine odor (KOH whiff test) Treatment: Reassure pt that the discharge is physiologic. Review hygiene with pt.

Pap smear

Developed in 1941 by Georgios Nikolaou Papanikolaou and it is the single-most effective cancer screening test. Purpose: detect premalignant changes (dysplasia) in cervical cells Ultimate goal: prevention of cervical cancer via early treatment of abnormalities. PAP =/= Pelvic Exam (Pelvic exam contains 4 components = examination of external genitalia, Pap test, bimanual exam (check uterus and ovaries), and rectovaginal exam)

Endometrial and myometrial pathology

Endometrium = mucosal lining of uterine cavity that is hormonally sensitive *Growth of endometrium = estrogen driven (proliferative) *Preparation of endometrium for implantation = progesterone driven (secretory phase) Myometrium = smooth muscle wall underlying the endometrium

Benign and malignant neoplasm (AGTB - premenopausal - menorrhagia)

Etiologies: uterine polyps, fibroids Endometrial Polyps: prevalence 8-35%, increases with age. Most common presenting symptom is intermenstrual bleeding. Polyps may prolapse through cervix. Adenomyosis: endometrial tissue in myometrium. Enlarged uterus. Symptoms: painful, heavy, prolonged menstrual bleeding. Leiomyoma (fibroids): benign uterine tumors; prevalence increases with age. Symptoms of heavy or prolonged menses. Evaluation with transvaginal ultrasound. - If normal, if bleeding doesn't respond to pharmacology, or risks for endometrial cancer: evaluate with biopsy or hysteroscopy Tx: - Reduce flow volume - Correct anemia - Hormonal tx (progestins, OCP) - Non-hormonal tx (NSAIDs) - Surgery (polypectomy, resection of fibroids) - Endometrial ablation - Hysterectomy

Infection (AGTB - premenopausal)

Premenopausal AGTB - Ovulatory causes - intermenstrual subcause: Pelvic inflammatory disease Note that hormonal contraception is the most common cause of iatrogenic uterine bleeding (breakthrough bleeding)

Vaginal adenosis due to DES

Failure of the normal glandular (columnar) epithelium that lines the embryonic vagina to be replaced by squamous epithelium during fetal development Cause/Epidemiology: Occurs in daughters exposed in utero to DES Diethly-stilbesterol (DES) = synthetic estrogen used in 1940's and 1950's for high risk pregnancies. (used to prevent miscarriages) Noticed in 1970's that there was a substantial increase in incidence of this disease in young daughters of women who received DES during pregnancy Pathogenesis: Normally, 10th week of gestation: upgrowth of squamous epithelium derived from urogenital sinus (lower 1/3 vagina) replaces the glandular (Mullerian) epithelium lining (upper 2/3 vagina) the vagina and exocervix. -DES exposure anywhere from 10th to 18th week of gestation arrests this transformation process and glandular tissue remains within vagina (adenosis) Clinical: Manifests as red, glandular patches on the vaginal mucosa which usually disappear as women gets older. -Rare cases of clear cell adenocarcinoma of the vagina have also occurred in the daughters of women treated w/ DES Microscopically: mucinous columnar cells, similar to the endocervix, along with ciliated cells with eosinophilic cytoplasm, similar to the lining cells of the fallopian tube and endometrium. - Glandular cells ultimately undergo squamous metaplasia

Trichomonas vaginitis

Flagellated protozoan that is the most common non-viral STI -Sexually transmitted disease -Infection typically limited to vagina and cervix, which may give changes to PAP smear. - Common infection (25-50% of women in U.S) - Symptomatic pt's are highest amount sexually active women in their 30's and lowest in postmenopausal. Clinical: Inflammation (strawberry cervix) Frothy, yellow-green, foul-smelling discharge accompanied by itching and burning. - Infection in men = usually asymptomatic but 10% have urethritis Labs: Motile pear-shaped trophozoite with central nucleus and 4 anterior flagella seen on Pap. (exists only as trophozoite with no cyst form) pH > 4.5 Treatment: Motile pear-shaped trophozoite with central nucleus and 4 anterior flagella seen on Pap. (exists only as trophozoite with no cyst form) pH > 4.5 Treatment: Metronidazole (Flagyl). Treat sexual partner(s) (can use tinidazole - fewer adverse effects) *Alcohol abstinence after completion of tx b/c of potential disulfiram-like reaction.

Endometriosis pathogenesis

Foci are composed of endometrial glands and stroma, responding to estrogenic stimulation and proliferating with normal endometrium. - At the time of menstruation, glands degenerate and bleeding occurs, and the blood cannot be discharged because the endometriosis foci are encased by normal connective tissue and peritoneum Key components in development of endometriosis = local overproduction of prostaglandins by ↑ in COX-2 activity and prostaglandins and overproduction of local estrogen by ↑ aromatase activity. - Progesterone resistance (changes in steroid hormone receptor expression) dampens the antiestrogen effect of progesterone and amplifies local estrogenic effect. -Implants further lead to ↑ TNF-α, IL-1, 6, 8 secreted from peritoneum. Also, leads to nerve growth factor, fibrosis, adhesions, changes to nerve innervation of the uterus, and altered immune function. Pathogenesis: 1. Regurgitated theory = endometrial tissue is regurgitated during normal menstruation and instead of entering vagina, it is transferred upstream where it enters the abdominal cavity through fallopian tubes. Glands implant on the serosa of the ovary or peritoneum, forming typical red-brown nodules or plaques - Reversed menstrual flow occurs in 70-90% of women and is thought to be more common in women with endometriosis, but many don't develop this dz. 2. Vascular-lymphatic theory = lymph system or blood vessels (vascular system) is the vehicle for the distribution of endometrial cells out of the uterus. 3. Coelomic metaplasia theory = Remnants of tissue from embryological development of the woman's reproductive tract transforms into endometrial cells throughout the body. 4. Induction theory = Postulates that an unidentified substance found in the body forces cells from the lining of the body cavity to change into endometrial cells ⇒ stem cell transformation

Candida vulvovaginitis

Fungal infections typically cause a vulvovaginitis and includes Candida albicans which lives on the moist surface of vagina and doesn't invade deeper into tissue -Pregnant women are more susceptible and 10% symptomatic. Increased incidence in diabetes and BCP. -Antibiotics inhibit normal flora and predisposes to Candida vaginitis (normal flora but low #s) Clinical: Inflammation White, thick, "cottage cheese" discharge Vulvar and vaginal itching, leading to bleeding Labs: Pseudohyphae in wet mount prep pH normal Pos KOH test, but Neg whiff test (meaning when KOH is added, the KOH kills the bacteria and leaves only the yeast behind. But there is no fishy odor in comparison to BV) Treatment: Azoles (ex: oral fluconazole, or vaginally admin miconazole/butoconazole) *Pregnant women = only topical conazoles and avoid fluconazole. - Not all "-azole" are antifungals like metronidazole and tinidazole. - "-conazole" are antifungal.

HPV vaccination

Gardasil 9 valent (only one used now in the US) - Contains HPV 6, 11, 16, 18, 31, 33, 45, 52, 58 - Males and females age 9-26, and possibly up to 45 depending on risk - 2 doses spaced 6 months apart for those under age 15 (3 doses for those who initiate vaccine after age 15)

Neisseria gonorrhoeae Cervicitis

Gram-negative diplococci Facultative intracellular (PMNs) Oxidase positive Glucose fermentation positive Thayer-Martin agar Discharge more purulent NAAT for detection GC infection of cervix can progress to PID, an infection of uterus (endometritis), fallopian tubes (salpingitis) and/or ovaries (oophoritis) Females: mainly Asymptomatic - Endocervix infection, mucopurulent vaginal discharge & intermenstrual bleeding (cervicitis). Common complication (asymptomatic, no treatment) ascending infection into uterus and fallopian tubes (PID and salpingitis), infertility, ectopic pregnancy. 2 drug therapy: Cephalosporin (Ceftriaxone) + azithromycin (<-- this one helps covers for Chlamydia co-infection)

Non-atypical endometrial hyperplasia

IT is hyperplasia of endometrial glands relative to stroma. Linked to prolonged estrogen stimulation: obesity, menopause, PCOD, functioning granulosa cell tumors of the ovary, excessive ovarian cortical function, estrogen replacement therapy Estrogen effect leads to the hyperplasia (estrogen = growth of endometrium) Postmenopausal bleeding It is benign. Diffuse endometrial topography Classified histologically based on architectural growth pattern (simplex or complex) and presence or absence of cellular atypia. Tx: Hormonal therapy

Urethritis

Inflammation of urethra - most common in males Gonorrhea and chlamydia can be present at the same time - Urethritis is basically cervicitis but has additional dysuria and in males. Then to distinguish between gonorrhea vs chlamydia, look at the discharge description (mucopurulent vs watery) (also if dysuria alone = definitely chlamydia)

Atypical endometrial hyperplasia (Endometrial intraepithelial neoplasia = EIN)

It is monoclonal neoplastic growth of genetically altered cells with greatly increased risk of endometrial carcinoma. Focus of cytologically altered glands becomes diffuse later. Shift in gland morphology from benign to precancerous often accompanied by loss of PTEN expression. This is precancerous. *Most important predictor for progression to carcinoma is present cellular atypia. - Simple hyperplasia with atypia often progresses to cancer (30%) - Complex hyperplasia without atypia rarely doesn't (<5%) Focal progresses to diffuse (clonal) endometrial topography Tx: Endometrial intraepithelial neoplasias managed by hysterectomy or in young women, a trial of progesterone.

Bethesda system vs CIN system and its equivalent names

Low Grade Squamous Intraepithelial lesion (LSIL) includes changes associated with HPV (koilocytic atypia) = CIN-I or mild dysplasia High-grade Squamous Intraepithelial Lesion (HSIL) = CIN-II (moderate dysplasia), CIN-III (severe dysplasia) and Carcinoma In-Situ (CIS) Atypical Glandular Cells of undetermined significance (AGUS) = Borderline changes in glandular cells Unspecified endocervical or endometrial cells or endocervical adenocarcinoma in-situ (AIS) or adenocarcinoma = Glandular neoplasia

Embryonal Rhabdomyosarcoma

Malignant mesenchymal proliferation of immature skeletal muscle CHILDREN (<5 y/o) Rare **Sarcoma Botryoides = rare vaginal tumor in children that appears as confluent polypoid masses that extend from introitus of the vagina Detected due to spotting on diaper + grape-like mass protruding from vagina or penis of child (sarcoma botryoides) "BOTRYOID = BUNCH OF GRAPES AND CHILDREN EATS GRAPES" Tumor is composed of primitive spindle rhabdomyoblasts in a dense zone beneath the vaginal epithelium called the Cambium layer Rhabdomyoblast = exhibits cytoplasmic cross creations and + immunohistochemical staining for desmin and myogen. Wide excision of tumor and chemo

Endometrial Carcinoma in general

Malignant proliferation of endometrial glands. Most common invasive cancer of the female genital tract. Used to be less common than cervical but earlier detection and eradication of CIN and increase in endometrial carcinoma in younger age groups has reversed ratio - Arise mainly in postmenopausal women, causing abnormal bleeding, which permits early detection and cure at early stage - Uncommon in women under 40, peak 55-65 years Pathogenesis: 1. Hyperplasia pathway (75%) = (type I) = carcinoma arises from endometrial hyperplasia. - Increased Estrogen exposure = increased growth of endometrium - Other risk: early menarche/late menopause, nulliparity, infertility with anovulatory cycles, and obesity - Histology = endometrioid (normal endometrium-like) -Avg age is 60 y/o 2. Sporadic pathway (25%) (type II) = carcinoma arises in an atrophic endometrium with no evident precursor lesions. - Avg age is 70 y/o. - Histology = serous and characterized by papillary structures with psammoma body formation; p53 mutation common and tumor is aggressive. Clinical: Postmenopausal bleeding This is cancer! Focal progresses to diffuse (clonal) endometrial topography Surgical stage-based Stage 1: confined to endometrium (90% survival) Stage 2: extend into cervix and invading into myometrium (50% survival) Stage 3: extend through wall of uterus, but not outside pelvis (20% survival) Stage 4: infiltrate the bladder or rectum, or extend outside the pelvis. Can go to lymph nodes (5% survival)

Abnormal menstrual cycle definition

Menstrual bleeding is heavy if it: - Interferes w/ quality of life = changing pads or tampons frequently, staining clothing or bedding, or making pt avoid activities. - Or causes anemia Intermenstrual bleeding occurs between menses, minimal blood loss.

Normal menstrual cycle definition

Menstrual cycle = average 28-35 days - 14-21 days in follicular phase and 14 days in luteal phase. - cycle varies most at onset of puberty and perimenopause - Menarche average age is 12 years and Menopause average age is 51 years.

Hidradenitis Suppurativa

Noninfectious causes of vaginal discharge and discomfort Blockage and inflammation of the hair follicles, leading to painful bumps, scarring and fistulas. Begins as pimple-like bumps on the skin, commonly mistaken for pimples. Boils can grow deep into the skin, becoming painful. They can also rupture and leak bloodstained pus, emitting foul odor. Remaining scars can thicken, and if scar is at the underarm, it can be hard to move the arm. If in the groin area, hard to walk. *Associated with a risk of becoming squamous cell carcinoma (SCC). Often affects underarms, goin, and buttocks. Inflammation of the sweat glands. [G. hidrōs, sweat, + adēn, gland, + -itis, inflammation]

Polymyositis

Noninfectious causes of vaginal discharge and discomfort Chronic inflammatory disease of muscle Muscle weakness affecting both sides of body.

SLE

Noninfectious causes of vaginal discharge and discomfort Chronic multisystem disorder Malar or "butterfly rash"

Behcet's Disease

Noninfectious causes of vaginal discharge and discomfort Chronic vasculitis. Rare in the USA. < 200,000 Autoimmune. Oral/Genital ulcers. Arthritis, blood clots, CNS and Gi symptoms. Mistaken for HSV Supportive care, possible immunosuppressive medications.

Eczema

Noninfectious causes of vaginal discharge and discomfort General term for types of rashes. Atopic dermatitis is the most common type. IgE-mediated allergic reactions play a pathophysiological role in many. "Itch that rashes". Intense itching. **Unilateral vulvar itching particular needs biopsy to rule out cancer

Crohn's

Noninfectious causes of vaginal discharge and discomfort Inflammatory bowel disease Pain/diarrhea, malnutrition, mouth-to-anus lesions (perineal skin tags, fistulas, and fissures), skip lesions. "Knife Cut Sign": Deep sloughy linear erosions (nonspecific) Immune modulators

Dermatomyositis

Noninfectious causes of vaginal discharge and discomfort Polymyositis with skin involvement Late 40s to early 60s but can also occur in children. Females most affected Violaceous color and periorbital edema = heliotrope rash *Dusky red rash on face and eyelids, and in areas around the nails, knuckles, elbows, knees, chest, and back. Muscle weakness frequent

Polyarteritis Nodosa

Noninfectious causes of vaginal discharge and discomfort Vasculitis of medium and small-sized arteries PAN = multisystem disease that may present w/ fever, sweats, weight loss, and severe muscle joint aches/pains. -Develop in a subacute fashion, over several weeks or months -Malaise, weight loss, anorexia, abd pain. -Can affect any site in the body but predisposition to skin, kidney, nerves, and GI. -High blood pressure and elevated erythrocyte sedimentation rates (ESR)

Normal Cervix

Normal Cervical transformation zone: anatomical junction of squamous and the mucinous epithelia and the external os is the macroscopically visible junction between the exocervix and endocervix. *With age, mucinous columnar epithelium of exocervix undergoes squamous metaplasia. I.e. columnar epithelium ⇒ stratified squamous epithelium. - As a result, the new squamocolumnar junction is located at the internal os. - Area between the original squamocolumnar junction on exocervix and the new squamocolumnar junction at the internal os is termed the "Transformation zone" (it is the area where 2 types of cells meet - endocervix w/ glandular and exocervix w/ squamous)

Acanthosis Nigricans

Not a cause of vaginitis, but a common finding. Can also be seen in pregnancy Velvety hyperpigmentation. Groin and skin folds. Has an endocrine link to insulin resistance.

Endometriosis Clincial

Often located on the pelvis but can be on the ovary, fallopian tube, or pelvic peritoneum. Occasionally outside the pelvis (umbilicus, appendix, and colon). - Most foci of endometriosis are located close to orifice of fallopian tubes which support the regurgitated theory. - Lesions expand during the menstrual cycle and are infiltrated with blood at the time of menses. = peritoneal irritation and pain. Benign = doesn't lead to cancer CHRONIC PAIN + INFERTILITY = endometriosis. - Recurrent disease 2nd look at laparoscopy 6-12 months after the first. Progression up to 35% of the time in untreated women. Regression 30%. Stable 35% Pregnancy and nursing = symptoms can improve Long term effects unknown Presentation of symptoms: 1. Dysmenorrhea (79%) 2. Chronic pelvic pain (69%) 3. Dyspareunia (painful intercourse) (45%) 4. Infertility (26%) 5. Bowel upset/pain (30%) 6. Uterosacral ligament nodularity 7. Adnexal mass (either symptomatic or asymptomatic) are among the well-recognized manifestations. Physical exam: - Often normal but can get tenderness in posterior vaginal fornix, posterior cul-de-sac, palpable nodules, pain with movement of uterus, and thickened uterosacral ligaments. The more severe the disease, the harder it is to have a successful pregnancy

Pap smear procedure

Old method: conventional pap smear = 60-80% sensitive for detecting a high grade lesion New method: Liquid based pap and computerized re-screening showed higher sensitivity but lower specificity. Benefits include GC/Chlamydia/HPV screening on same sample. Proper speculum placement: 1. Separate the labia w/ the opposite hand before inserting the speculum 2. Angle the speculum downward toward the posterior fornix 3. Backup and re-advance if needed to center the cervix between the blades of the speculum 4. Lock the speculum in place The sample of cervix cells are taken from the transformation zone (junction of endocervix and ectocervix). Sample is sent to cytology for review of cells - Sample collected by the cytobrush (most effective for nulliparous or stenotic cervical os) or the spatula/broom (cervex brush) (more effective for the large cervix or cervix w/ ectopy

Cervix (Postmenopausal AGTB - anatomical)

Post-menopausal changes increase vulnerability to inflammation and infection; stenosis. Cervical cancer = mean age 52.2 years old Foreign bodies can cause bleeding. Uterine/pelvic organ prolapse: risk factors include parity, advanced age, and obesity Bulge, pressure, and bleeding symptoms Treatment: depends on severity and symptoms

Exogenous estrogen (AGTB - premenarchal)

Premenarchal AGTB - Hormonal causes: Caretakers use topical estrogen which unintendedly transfer to children's skin, leading to feminization Estrogen may also been in food or other products Exposure to androgen-containing cream Feminization

Precocious puberty (AGTB - premenarchal)

Premenarchal AGTB - Hormonal causes: Onset of secondary sexual characteristics before age 8 in girls, 9 in boys (compared to normal 10.5 in girls and 11.5 in boys) Prevalence varies by race/ethnicity: - At 8 y/o (48% AA girls, 15% white girls) - At 7 y/o (27 AA girls, 7% white girls) Factors: overweight, obese, family hx 1. Central precocious puberty: "true" = gonadotropic-dependent = early maturation of hypothalamic-pituitary gonadal axis - Causes of central: idiopathic (80-90% girls, 25-60% boys); CNS lesion (hamartomas - benign and most common; astrocytomas, optic gliomas, CNS radiation); genetics (KISS1); sex steroid exposure; pituitary gonadotropin tumors 2. Peripheral precocity: gonadotropin-independent = excess sex hormones from peripheral source (gonads, hormone secreting tumor, etc). - Causes: CAH, granulosa cell tumor (estrogen-secreting ovarian tumor), Leydig cell tumors (produce testosterone), McCune-Albright syndrome 3. Benign or nonprogressive pubertal variants: require close monitoring Treatment of central: GnRH agonist Treatment of peripheral: treat underlying cause

Hypothyroidism (AGTB - premenarchal)

Premenarchal AGTB - Hormonal causes: Pubertal development is delayed in most adolescents or children with hypothyroidism. However, some children with primary hypothyroidism have sexual precocity, characterized by breast development and vaginal bleeding in girls and enlarged testes in boys. Bone age may not be delayed (in contrast to central precocious puberty) due to effect of sex steroid production Rarely, pts may present with galactorrhea secondary to hyperprolactinemia associated with hypothyroidism. Slightly increased FSH concentration

Trauma (AGTB - premenarchal)

Premenarchal AGTB - NON-Hormonal causes: In girls, most genital trauma is blunt (non-penetrating) There can also be penetrating trauma Blunt trauma = minor injury. - Bathroom most common place - Bruising of labia majora - Lacerations anterior or lateral to hymen Penetrating trauma: - Lacerate vaginal wall, leading to hemorrhage - Rectal injury Vulvar trauma: - Significant bleeding - Increased risk b/c immature labia without fat pads Non-sexual (accidental) trauma: - Associated with anterior vulvar structures - Need to assess ability to urinate - Straddle injury = anterior area of vulva, including mons, clitoral hood, and anterior aspect of labia. TX: Ice, bladder drainage, pain medication Most vulvar hematomas will resolve spontaneously

Foreign body (AGTB - premenarchal)

Premenarchal AGTB - NON-Hormonal causes: One of the most common causes of vaginal bleeding in prepubertal girls Most common foreign body = toilet paper Light bleeding +/- odor PE: Knee to chest position to examine the vaginal vault and see the foreign body -Sometimes need anesthesia to establish diagnosis Removal with methods include irrigation and/or exam under sedation

Sexual abuse (AGTB - premenarchal)

Premenarchal AGTB - NON-Hormonal causes: >60,000 children are sexually abused annually - Victims of sexual abuse include children from all social, cultural, and economic backgrounds Injury to posterior fourchette and hymenal area - Ex: laceration to lower half of hymenal area is consistent with a penetrating injury Suspicious findings: - Intravaginal bleeding - Injury to hymen - Injury to posterior fourchette - Perineal lacerations/tears Tx: Victims may present with a variety of medical complaints. Don't hesitate to include experienced child abuse teams and/or experts in care/evaluations. *mandated reports of suspected child abuse

Infectious vaginitis (AGTB - premenarchal)

Premenarchal AGTB - NON-Hormonal causes: Bacteria that cause bleeding in prepubertal girls is: 1. Streptococcus pyogenes 2. Shigella Strep. Pyogenes = fiery-red, beefy skin appearance Shigella = bloody vaginal discharge. (⅓ have history of recent or concurrent diarrhea)

Genital warts (AGTB - premenarchal)

Premenarchal AGTB - NON-Hormonal causes: Condylomata acuminata caused by HPV Children <3 years old, maternal-child transmission most common Skin-colored or pink lesions that may be warty or smooth flattened papules. HPV testing of mothers doesn't exclude sexual abuse and therefore is not generally performed. If sexual abuse suspected, evaluation needed No therapy needed, but some families choose treatment with laser therapy, trichloroacetic acid, imiquimod cream Tx can also be electrocautery, liquid nitrogen, or surgical excision Spontaneous resolution within 5 years in more than 50% of patients.

Urethral prolapse (AGTB - premenarchal)

Premenarchal AGTB - NON-Hormonal causes: In prepubertal girls (usually 2-10), often of African descent "History of 'vaginal' bleeding with dusky red or purplish annular mass between labia majora upon examination" Bleeding, dysuria Exam: dusky red or purplish annular mass between labia majora "doughnut shape with central dimple" Tx: Topical estrogen, Sitz baths Resolves in few weeks

Hemangioma (AGTB - premenarchal)

Premenarchal AGTB - NON-Hormonal causes: Occur on the vulva as on other body surfaces. (benign vascular tumor) Rarely bleed Tx: Involute between 2-5 years of age and require no further intervention. Once involuted, remaining skin and fatty tissue can be evaluated to determine whether lesion is significant size to necessitate a surgical resection

Malignancies (AGTB - premenarchal)

Premenarchal AGTB - NON-Hormonal causes: Rare cause of vaginal bleeding in children. Endodermal sinus tumors and rhabdomyosarcomas (including sarcoma botryoides) of the vagina are rare, accounting for about 8% of pediatric germ cell tumors and about 0.3% percent of childhood malignancies. Girls <3 y/o

Benign and malignant neoplasm (AGTB - premenopausal - intermenstrual)

Premenopausal AGTB - Ovulatory causes - intermenstrual subcause: Intermenstrual bleeding often due to conditions of the cervix, including cervical cancer, cervical polyps, cervicitis, or ectropion - Each cervical cancer is frequently asymptomatic. For those symptoms, most common ones at presentation are irregular or heavy vaginal bleeding or post-coital bleeding. - Diagnosis by histologic evaluation of cervical biopsy. 1. Cervical polyps: occur during repro years after age 40. Unknown etiology. - Tear-shaped or lobular structures appear red, purple, or flesh-colored depending on vascularity and congestion present. Look succulent and glistening. - Size <3 cm in diameter. - Pedicles are long and thin but may be short and broad based. - Histologically characterized by vascular connective tissue stroma covered by epithelium, which may be columnar, squamous, or squamocolumnar - Should be removed if symptomatic, cause bleeding, excessive discharge, >3cm, or appear atypical 2. Ectropion: occurs when eversion of endocervix (cervical canal) exposes columnar epithelium to vaginal milieu. - Everted epithelium has reddish appearance similar to granulation tissue and may be covered by yellow turbid discharge - ADOLESCENTS - May be observed in women who are pregnant, taking COC, or had cervical laceration during L&D - Doesn't need to be treated except in rare occurrences of excessive mucous discharge, spotting. Malignancy need to be excluded.

Coagulopathy (AGTB - premenopausal)

Premenopausal AGTB - Ovulatory causes - menorrhagia subcause: Von Willebrand Disease (13%): - most common inherited bleeding disorder - Autosomal dominant or recessive - present any age - menorrhagia in 60-90% of women Requires eval if: - FHx bleeding disorder - Menses lasting 7+ days and impairment - prior treatment of anemia - Excessive bleeding w/ prior tooth extraction, delivery, miscarriage, surgery Von Willebrand workup for adolescents with menorrhagia CBC, PT, activated PTT vWD: abnormal aPTT, thrombocytopenia, microcytic anemia Treatment for coagulopathy: OCP, mirena IUD, antifibrinolytic agents, intranasal DDAVP, ablation **AVOID NSAIDS**

Local irritants, foreign body trauma, atrophy causes of vaginal discharge and discomfort

Prepubertal factors ENDOGENOUS: Undeveloped labia, thin mucosa, alkaline pH, poor hygiene EXOGENOUS: Perfumed products, foreign body, tight clothing OTHER: Self-exploration, sexual abuse, infection, STI, pinworms, molluscum, UTI, urinary reflux, urethral polyps, urethral prolapse Interventions: Avoid sleeper PJs, tight wet suits. Cotton crotch in underwear. Double rinse, warm water soaks, cool compresses, proper wiping Post-pubertal known irritants: Scented soaps, bubble baths, fabric softeners, detergents, perfumed/scented tampons, contraceptive gel, latex condoms, lubricants, douches, parasites, sperm Other irritants: Post-antibiotic, obesity, new sexual partner, poorly-controlled diabetes, primary vaginitis, vulvar pressure, moisture

Endometriosis description

Presence of endometrial glands and stroma OUTSIDE the endometrium and uterine musculature. UTERUS SIZE IS NORMAL. Women of repro life (3rd and 4th decades) -Higher incidence in women in higher socioeconomic groups who tend to marry later in life. 5-10% of repro age 40% of infertile women 70-90% of women undergoing surgery to determine cause of chronic pelvic pain Higher % (50%) in teenages with chronic pelvic pain Up to 50% of women have surgery for infertility. No racial predisposition *Risk factors: Nulliparous, early menarche (before 11), late menopause, short menstrual cycle (<27), prolonged menses (>7 days) *Protective factors: higher parity (more babies), increased duration of lactation, regular exercise of more than 4 hours per week.

Clear cell Adenocarcinoma

Rare tumor of vagina encountered exclusively in women exposed to Diethly-stilbesterol (DES) (complication of DES-associated vaginal adenosis) Most common between ages 17-22 Abundant glycogen account for clear nature of cytoplasm Develops most frequently on the anterior wall of upper third of vagina Essentially curable when small.

Bethesda System

Recent (2001) classification for reporting cervical/vaginal cytologic diagnoses - Reports whether the PAP is an adequate sample - Reports incidental findings such as evidence of infection - Reports of atypical squamous cells of undetermined significance ASCUS) which favors benign/inflammation (90% of cases) or atypical squamous cells higher risk (ASC-H) (10% of cases that require more invasive procedures like colposcopy.

Lichen Planus

Specific etiologies of irritants causing vaginal discharge/discomfort Affects VULVAR Cell-mediated, inflammatory, immune response. Precipitants: Chemical exposures, quinidine, post-transplant, "unknown". Female = Male, More common ages 30-60. Associated with hepatitis C, chronic active hepatitis, and primary biliary cirrhosis. DDx: Syphilis, psoriasis, graft-vs-host disease, tinea corporis Sx: Vulvar burning, soreness, dyspareunia, and increased vag Violaceous papules and scales. Involves skin, nails, and mucous membranes. *6 P's: Pruritic, purple, polygonal planar papules, plaques Tx: Steroids, retinoids, immunosuppressants. May recur spontaneously

Lichen Sclerosus (also known as lichen sclerosis)

Specific etiologies of irritants causing vaginal discharge/discomfort Benign, Chronic, mucocutaneous inflammatory dermatosis (skin condition) Unknown etiology Women > Men; children rare Middle aged to older women Uncircumcised males at risk Bimodal onset: prepubertal and postmenopausal Prevalence: 1:30-59 Loss of VULVAR architecture can occur including fusion of labia minora, phimosis of the clitoral hood, and fissures **4.5% risk of squamous cell carcinoma (SCC) of vulva Slowly development but progessive lesions Sx: Pruritus, irritation, burning, pain dyspareunia, vulvar skin tearing, itching, vulvar discomfort, bowel and bladder symptoms, discharge, and bleeding (due to fragile tissue). - Abnormal growth of the Vulvar skin characterized by ****white (leukoplakia), paper-thinned, wrinkled. (onion-skin like). Epidermal plaques and atrophy, a cigarette or parchment paper appearance Perianal involvement creates a "keyhole" or hourglass shape Biopsy required for diagnosis Histologically: hyperkeratosis, loss of rete ridges, and homogenous acellular dermal zone High potency topical steroids, retinoids, tacrolimus ointment Must monitor.

Straddle Injury

Specific etiologies of irritants causing vaginal discharge/discomfort EXPECTED: Unilateral, superficial, anterior genitalia CONSIDER SEXUAL ABUSE IF: Bilateral, deeper involvement, hymen, posterior fourchette, 3-9 o' clock, perianal/rectal, abnormal secretions Tx: Ice, bladder drainage, elevation, pain medications, stool softeners. Surgery rarely required.

Foreign body

Specific etiologies of irritants causing vaginal discharge/discomfort Prepubertal: different things kids can put in their vagina. Or even can be sensitive to toilet paper Postpubertal: Tampons, condoms, etc.

Pubic Lice & Scabies

Specific etiologies of irritants causing vaginal discharge/discomfort Sx: Pruritus, eventual inflammation, excoriations Treat patient, clothing, and surroundings. Pyrethrins, permethrins, and lindane.

Atrophic Vaginitis

Specific etiologies of irritants causing vaginal discharge/discomfort Thinning of vaginal epithelium and loss of glycogen → changes in pH and flora Hypoestrogenism, overuse of topicals, trauma Sx: Pruritis, erythema, pigment loss, erosions, dyspareunia Tx: Estrogen (topical or PO), lubricants for intercourse

Exfoliative Cytology

Study of normal and disease-altered desquamated cells from various body sites - PAP smear is the cervical cytological test where the most superficial epithelial cells are exfoliated. - It is an effective screening procedure for early detection of premalignant and malignant cervical lesions

Invasive Adenocarcinoma of the endocervix

These are cancers that develop from GLANDULAR cells that begin in the endocervix. (opposed to the more common type of cervical cancer that is squamous cell carcinoma that begins in the transformation zone) - 20% of malignant cervical tumors (increasing incidence) - Shares epidemiologic factors with squamous cell cancers (HPV types 16 and 18) and spreads similarly. - Presents as a fugating or polypoid mass with malignant glandular cell proliferation. Spreads by local invasion and lymph node metastasis - Treatment similar to squamous cell variant, but prognosis is slightly better.

Bartholin Gland Cyst

These paired glands produce a clear mucoid secretion, which continuously lubricates the vestibular surface. - The fluid drains via ducts into the lower vestibule Cause/Epidemiology: Staph, Chlamydia, and anaerobes -Seen in women of reproductive age and arises due to inflammation and obstruction of gland Pathophysiology: Ducts are prone to obstruction and consequent cyst formation Clinical: Presents as a unilateral, painful cystic lesion at the lower vestibule adjacent to the vaginal canal. Infection of cyst leads to abscess formation. Tx: Incisional drainage and antibiotics

Endometriosis Treatment

Treatment: Suppression of menstruation with OCP's alleviate the symptoms - Need to decrease estrogen levels - Expectant management - Analgesia - Hormonal therapy 1. OCP's (cyclic or continuous): Estrogen and progesterone can slow disease progression. Patients can take indefinitely cyclically. Can transition to continuous if pain is not improved. 2. Progestins - Alone: Reduction in endometriosis implants at repeat LSC after progestin therapy. Equal effects to GnRH agonists in reducing pain. Side effect of GnRH agonists are similar to menopause: vasomotor symptoms and BONE LOSS. - IUD: Should improve symptoms by reducing menstruation or dysmenorrhea 3. GnRH agonists Increased menopausal side effects: vasomotor symptoms and bone loss. Can minimize side effects with add-back therapy of norethindrone. Limited duration of use, maximum 12 months 4. Surgical therapy: or - Indications based on: failure of medical therapy to relieve (appx 3 month trial); decline or have C/I to medical therapy; need for definitive dx; evaluate adnexal mass; treatment for infertility. - Conservative (keep ovaries and uterus) = ablation/destruction of endometriotic lesions or excisions of lesions. Less morbidity than definitive but rate of recurrence higher - Definitive (hysterectomy , removal of endo lesions, +/- removal of ovaries). Theory is since this is estrogen dependent dz, if we remove ovaries, we place woman in postmenopausal state. Oophorectomy likely increase potential health effects of premature menopause (osteoporosis, CVD) 5. Postoperative Medical Therapy with CONSERVATIVE Surgery Goal is to preserve the uterus and ovaries. We ablate/destroy or excise lesions. There's a smaller morbidity chance than definitive surgery, but comes with an increased rate of recurrence. OCPs or Progestins alone suppress lesions. Increased duration of pain relief and delayed recurrence. GnRH is used to take care of any microscopic lesions (short term therapy) 6. Postoperative Medical therapy DEFINITIVE surgery - Hormone replacement therapy (HRT) can be initiated immediately after surgery - Recurrence low (3.5%) - If extensive residual disease then women have increased risk of recurrent symptoms associated with estrogen therapy. Conditions and tx: 1. Mild pelvic pain = NSAIDs +/- OCP 2. Moderate pelvic pain = OCPs, GnRH agonist, +/- surgery 3. Suspected endometriomas/ advanced stage = surgery 4. Infertility = surgery *generally first line of tx = NSAIDs and OCP *Start OCP or progestin until pt can be seen by OBGYN

Carcinoma of Vulva

Vulva cancer (arising from the squamous epithelium lining the vulva) Epidemiology: 3% of all GYN cancers Carcinoma of older women, median age at dx is 60 years Etiology: HP related or non-HPV-related 1. HPV-related (16,18) ⇒ vulvar intraepithelial neoplasia (VIN) ⇒ koilocytic change (wrinkle) ⇒ carcinoma in-situ (CIS) - seen in women w/ multiple partners, early first age of sex, or reproductive age. 2. Non-HPV related ⇒ preneoplastic lesions like leukoplakia (lichen sclerosis) ⇒ CIS - seen in >70 yo -chronic inflammation and irritation leads to CIS *Leukoplakia = white patch (need to distinguish this carcinoma from other causes of leukoplakia like lichen sclerosis and lichen simplex chronicus through biopsy Clinical: Itching, discomfort, pain, bleeding. Significant number of pts are asymptomatic. Tumor can be recognized by gross inspection of the external genitalia and presents as a wart-like or slightly raised mucosal lesion or ulcers. Tumor is almost always present as squamous cell carcinoma, usually slow growing If diagnosis is made before it has metastasized to the lymph nodes, pt has 70% of 5 year survival following surgical resection. -Those that spread to lymph nodes have less favorable prognosis. Tx: surgical resection of tumor or entire vulva, supplemented w/ radiation therapy and chemotherapy.

Workup for abnormal genital bleeding

Where is the bleeding coming from? Vagina, canal, cervix, uterus, vulva, urethra, or anus 1. Heavy bleeding = likely uterine 2. Spotting = could be anywhere 3. Post-coital = likely cervix 4. Trauma = vaginal or cervical 5. Timing like after defecation = anus Complete OBGYN history including menstrual history/diary, sexual history, obstetric or gynecologic surgeries, medications (oral contraceptives, IUD, etc), risk factors for endometrial cancer (postmenopausal women) Labs include HCG (BEST FIRST TEST), CBC, PT, PTT, TSH Imaging include ultrasound (check structure), hysteroscopy +/- saline infusion to check for abnormal bleeding, endometrial thickening or polyps, submucosal fibroids, intrauterine adhesions, mullerian anomalies, foreign bodies, retained products of conception, sterilization, or endocervical lesions Biopsy if needed to evaluate for endometrial cancer, evaluate further an abnormal ultrasound, surveillance of possible or prior endometrial cancer, or assess for chronic subclinical endometritis