Block 4 - Reproductive Flashcards

Question

What is HIV? How does it present clinically? What are the signs of subsequent immunodeficiency?

Answer 1

**HIV** * Infection with human immunodeficiency virus. * Presents with acute fever, rash, lymphadenopathy, pharyngitis, myalgia, diarrhoea two weeks after exposure, and will then be asymptomatic for several years following infection. * Signs of subsequent immunodeficiency include oral thrush, diarrhoea, weight loss, skin infections and herpes zoster.

Answer 2

**Pubic Lice** * Infestation of the small ectoparasite *Phthirus* pubis (can occur also at eyebrows, beards and armpits). * Presents with pubic or genital itch and/or rash, and debris in underwear.

Answer 3

**Diagnostic Criteria for STIs: ASYMPTOMATIC FEMALE** 1. Self-Obtained Low Vaginal Swab (SOLVS) for PCR (CT/NG) 2. First Void Urine (FVU) for PCR (CT/NG) 3. Serology (HIV, HBV, Syphilis +/- HCV) 4. +/- Rectal or throat swabs for PCR (CT/NG)

Answer 4

**Diagnostic Criteria for STIs: ASYMPTOMATIC MALES** 1. First Void Urine (FVU) for PCR (CT/NG) 2. Serology (HIV, HBV, Syphilis +/- HCV) 3. +/- Rectal or throat swabs for PCR (CT/NG)

Answer 5

**Diagnostic Criteria for STIs: SYMPTOMATIC FEMALES** 1. Endocervical Swab (ECS) for PCR (CT/NG) 2. ECS for PCR (MG) 3. ECS for MC&S (NG) 4. HVS for MC&S (BV/Candidia/Trichomonas) + pH 5. Bimanual Pelvic Examination 6. Serology (HIV, HBV, Syphilis +/- HCV) 7. +/- Genital Ulcer Multiplex PCR (GUMP) for PCR 8. +/- Rectal or throat swabs for PCR

Answer 6

**Diagnostic Criteria SYMPTOMATIC MALES** 1. Urethral Swab for PCR (CT/NG) 2. Urethral Swab for PCR (MG) 3. Urethral Swab for MC&S (NG) 4. Serology (HIV, HBV, Syphilis +/- HCV) 5. +/- Genital Ulcer Multiplex PCR (GUMP) for PCR 6. +/- Rectal or throat swabs for PCR

Answer 7

**Diagnostic Criteria - Gonorrhoea** _Females:_ 1. Self-collected lower vaginal swab for PCR and MC&S if not examined 2. First pass urine for PCR only if ECS or vaginal swab cannot be taken 3. Endocervical swab for PCR and MC&S if discharge or dysuria present 4. Pharyngeal swab for PCR and MC&S if patient had oral sex 5. Ano-rectal swab for PCR and MC&S if patient had anal sex or ano-rectal symptoms _Males:_ 1. First pass urine for PCR always 2. Urethral swab for PCR and MC&S if discharge or local symptoms present 3. Ano-rectal swab for PCR and MC&S in MSM even if asymptomatic 4. Pharyngeal swab for PCR and MC&S in MSM even if asymptomatic

Answer 8

**Herpes** * Swab of base of ulcer or de-roofed vesicle for PCR (requires visible lesions to be present)

Answer 9

**Diagnostic Criteria - Syphilis** 1. Blood serology via enzyme immunoassay (EIA), Treponema pallidum Particle Agglutination Assay (TPPA), Treponema pallidum Hemaglutination Assay (TPHA) or Rapid plasma reagin (RPR) laboratory tests 2. Swab of ulcer for PCR to directly detect pathogen 3. Diagnosis is by a combination of serology, history and clinical assessment 4. If serology is negative, repeat testing after 2 weeks if clinical suspicion of syphilis

Answer 10

**Diagnostic Criteria - HIV** 1. Blood test for HIV Ag/Ab, Western blot (confirmatory test), HIV p24 antigen (high during primary illness), CD4 lymphocyte (marker of immune function), HIV RNA (viral load, marker of HIV level in serum) 2. Blood or saliva sample for HIV rapid point of care test (result in 10 – 20 minutes but less sensitive or specific than standard test)

Answer 11

**People at the highest risk of STIs include:** 1. Sexually active males and females who are 35 years or younger, and not in a stable, long-term relationship. 2. Those who are from a high prevalence country or have a sexual partner who is from a high prevalence country. 3. People who are experiencing homelessness. 4. People who have recently changed sexual partner. 5. People who frequently change their sexual partners. 6. Men who have sex with men (MSM) and women who have sex with MSM. 7. Aboriginal people 8. People who use methamphetamine and/ or inject drugs.

Answer 12

**Pharmacological Treatment for Gonorrhoea** 1. Ceftriaxone 500mg IMI, stat in 2mL 1% lignocaine PLUS 2. Azithromycin 2g PO, stat Alternative treatments are not recommended because of high levels of resistance, EXCEPT for some remote Australian locations and severe allergic reactions

Answer 13

**Pharmacological Treatment for Chlamydia** * Doxycycline 100mg PO, BD (twice a day) 7 days (21 days if symptomatic ano -rectal infection) OR * Azithromycin 1g PO, stat (will not clear rectal infection)

Answer 14

**Pharmacological Treatment of Herpes** * Valaciclovir 500mg PO, BD for 5 - 10 days (for initial episode), 3 days (for episodic therapy) or 6 months (for suppressive therapy) * Alternative treatment includes Aciclovir 400mg PO, TDS for 5 - 10 days (for initial episode), Famciclovir 1g PO, BD for 1 day (for episodic therapy) or Famciclovir 250mg PO, BD for 6 months (for suppressive therapy)

Answer 15

**Pharmacological Treatment of Syphilis** * Benzathine penicillin 1.8g IMI, stat (for infectious syphilis) or weekly for 3 weeks for non-infectious syphilis * Alternative treatment includes Procaine penicillin 1.5g IMI, for 10 days (for infectious syphilis) or 15 days (for non-infectious syphilis)

Answer 16

**Pharmacological Treatment of HIV** First-line initial HIV therapy is currently a combination of two nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) and an integrase strand transfer inhibitor (INSTI). * Highly active antiretroviral therapy (HAART) * 2 x Nucleoside Reverse Transcriptase Inhibitors (emtricitabine and tenofovir) PLUS * 1 x Non-NRTI (efavirenz) OR 1 x Protease Inhibitor (atazanavir plus ritonavir) OR 1 x Integrase Inhibitor (dolutegravir)

Answer 17

**Principles of Management and Treatment of STIs** 1. Antibiotic therapy (treat early on suspicion i.e. ceftriaxone and azithromycin can treat chlamydia and gonorrhoea) 2. Advise no sexual contact for 7 days after treatment is administered 3. Advise no sex with partners from the last 6 months until the partners have been tested and treated if necessary 4. Notify the state health department (notification form) 5. Contact tracing 6. Follow up with patient 7. Provide patient with STI factsheet, education, risks and post-test counselling 8. Provide patient with education on safe sex and prevention measures 9. People should have regular STI tests (screening) if they think they might have an STI, they have had unprotected sex, they have had a condom break or it has fallen off during sex, their partner has another sexual partner or has had previous sexual partners, they have shared injecting equipment and they are starting a new sexual relationship

Answer 18

**Who Should Be Offered HIV Testing** Unprotected sexual contact, particularly contact that took place in a country with a high prevalence of HIV, or with a person who has recently travelled to or migrated from a high prevalence country Travel within a country with a high prevalence of HIV Unprotected male to male sex Presence of a sexually transmitted infection Sharing injecting equipment or the use of unsterile tattooing or body piercing equipment Exposure to unscreened blood or blood products through medical procedures Anyone who is subjected to sexual assault

Answer 19

**Information For Patients Before an HIV Test** 1. Talk to patient about patient confidentiality and legal responsibilities, such as the need to notify the Department of Health about any HIV diagnosis 2. Informed patient consent is always required 3. Discuss that HIV is a virus that is predominantly transmitted through blood-to-blood contact, or contact with sexual secretions. 4. Discuss possible transmission routes of HIV, e.g. unprotected sex, sharing of injecting equipment 5. Explain what an antibody test is and what the test involves 6. Explain that there is a 3-month window period, and follow up testing may be needed depending on the patient's circumstances 7. Ensure your patient is aware of the possibility of a positive result 8. Explain that positive results are reported to the Department of Health 9. Explain that for positive results there is a requirement for contact tracing, and explain ways this can be done 10. Be aware of cultural understandings of sickness and wellbeing, and whether language is a barrier for understanding 11. Check that the patient knows they have to return to collect the test results in person and organise a follow-up appointment 12. Discuss that, in the event of a positive result, HIV can be treated with ongoing daily medication, and that although HIV is a chronic condition, people who live with HIV can expect to lead long healthy lives and enjoy healthy family life

Answer 20

**Conveying a Negative HIV Result:** * Ensure the name, result, date of birth and postcode are correct before seeing patient * Check that patient understands how to minimise risk of acquiring HIV (e.g. safer sex and safer injecting practices) * Review the window period and consider the need to retest

Answer 21

**Conveying a Positive HIV Result:** * Should always be provided in person except in extenuating circumstances * Ensure the name, result, date of birth and postcode are correct before seeing your patient * Give the test result in person, and in a manner that is sensitive and appropriate to the patient’s gender, culture, behaviour, and language * Organise onwards referral to a HIV specialist, and answer questions about the referral process and indicate in referral that patient has been recently diagnosed with HIV * Confirm that HIV is a condition which can be treated, but not cured and that people living with HIV can live long and healthy lives when on treatment * Assess any immediate known support (family/friend/partner) who may provide any needed emotional support * Organise onwards referral to a support agency, to be accessed at the patient’s discretion * Perform contact tracing and partner notification * Discuss transmission of HIV, and how onwards transmission may be prevented * Discuss legal obligations and considerations, for example using condoms and practising safer sex

Answer 22

**Clinical Presentation - Acute PID** * Variable presentation! * Many asymptomatic early in disease! * Severe lower abdominal/pelvic pain (usually bilateral and rarely more than two weeks' duration) * Abnormal vaginal discharge * Abnormal uterine bleeding (intermenstrualbleeding, post-coital bleeding or menorrhagia) * RLQ pain or low back pain * Urinary frequency and dysuria * Fever * Abdominal tenderness * Acute cervical motion, uterine, and adnexal tenderness on bimanual pelvic examination * Purulent endocervical discharge and/or vaginal discharge

Answer 23

**Clinical Presentation - Chronic PID** * Abdominal/pelvic pain * Heavy and painful menstrual periods * Dyspareunia * Low-grade fever * Weight loss * Infertility

Answer 24

**Clinical Presentation - General STI** * Can be asymptomatic! * Sores or bumps on the genitals or in the oral or rectal area * Skin itch, rash, erythema, blisters or ulcers * Abnormal vaginal or urethral discharge * Dysuria * Dyspareunia * Abnormal uterine bleeding * Sore, swollen lymph nodes, particularly in the groin * Lower abdominal pain * Fever * Rash over the trunk, hands or feet * Painful defecation

Answer 25

**Trilaminar Embryo:** Reproductive system develops from mesoderm (and some endoderm)

Answer 26

**Before 6 Weeks (Indifferent Stage):** Gonadal ridge formation (why males and females both have nipples)

Answer 27

**At 6 Weeks:** SRY (sex-determining region on the Y chromosome) gene stimulates the development of the primitive sex cords to form testes, giving rise to the male gender. Absence of SRY gene promotes ovary and female development.

Answer 28

**At 8 Weeks:** Leydig cells begin to produce testosterone which maintains and drives differentiation of Wolffian duct. Sertoli cells begin to produce Mullerian Inhibiting Substance or Anti-Mullerian Hormone which causes the degeneration of the paramesonephric ducts in males (may leave remnant on testes).

Answer 29

**8 to 10 Weeks:** Mesonephric (Wolffian) duct differentiates into male internal genitalia, by forming the efferent ductules and epididymis, the vas deferens and the ejaculatory duct. The seminal vesicles form as an outgrowth from the ductus deferens, and the prostate gland arises from numerous outgrowths from the urethra.

Answer 30

**9 to 12 Weeks:** Androgens (dihydrotestosterone) from the testes promotes the development of male external genitalia. * The primordial phallus grows to form the penis. * From week 12 gender can be identified, but gender normally identified at 20-week scan to avoid mistakes.

Answer 31

**7 Weeks to 9 Months (Testes Descent)** * The gonads develop retroperitoneally (near kidneys), moving into the abdomen and eventually into the scrotal sacs. * Between the 7th and 12th weeks, the gubernaculum shortens and pulls the testes down to the vicinity of the deep inguinal ring. * The testes remain in the vicinity of the deep ring from the 3rd to about the 7th month. * At around 6 months, testes descend and pass through the abdominal wall and deep inguinal ring into inguinal canal. * At 8 months, testes descend and pass through superficial inguinal ring. During the last month of development, the testes descend into the scrotum. * Transversalis Fascia becomes Internal Spermatic Fascia * Internal Obliques become Cremaster muscle * External Obliques become External Spermatic Fascia

Answer 32

**Birth to 3 Months:** Processus vaginalis (outpouching of parietal peritoneum) closes off and the remaining portion around the testes becomes the tunica vaginalis. Some individuals have a patent processus vaginalis (opening between peritoneum and scrotum).

Answer 33

**Biological Basis of Gender and Sexual Development:** * **Sex Chromosomes:** Males (XY) and Females (XX) * **The SRY Gene:** Sex‐determining region of the Y chromosome. SRY gene acts as a transcription activator which binds to DNA and initiates male sex determination and testes development. In females, (absence of Y chromosome and SRY gene), the transcription factor is absent and female development occurs. * **Internal Genitalia:** The presence of testosterone (Leydig cells) drives maintenance and differentiation of Wolffian duct and Mullerian Inhibiting Substance (Sertoli cells) drives degeneration of the paramesonephric ducts in males, producing the male internal genitalia. The absence of testosterone allows for the development of the Mullerian duct and regression of the Wolffian duct, producing the female internal genitalia. * **External Genitalia:** The presence of dihydrotestosterone (DHT) drives the development of male external genitalia. The absence of DHT drives the development of female external genitalia.

Answer 34

* **Brain**: Responsible for sexual/gender identification, orientation, proception, gratification and procreation, under hormonal influence. * **Sexuality**: Combination of genotype expression, gonadal expression, genital expression and brain expression.

Answer 35

**Penile Erection—Role of the Parasympathetic Nerves.** Erection is caused by parasympathetic impulses that pass from the sacral portion of the spinal cord through the pelvic nerves to the penis. These parasympathetic nerve fibers, in contrast to most other parasympathetic fibers, are believed to release *nitric oxide* and/or *vasoactive intestinal peptide* in addition to acetylcholine. Nitric oxide activates the enzyme *guanylyl cyclase,* causing increased formation of *cyclic guanosine monophosphate* (GMP). The cyclic GMP especially relaxes the arteries of the penis and the trabecular meshwork of smooth muscle fibers in the *erectile tissue* of the *corpora cavernosa* and *corpus spongiosum* in the shaft of the penis. As the vascular smooth muscles relax, blood flow into the penis increases, causing release of nitric oxide from the vascular endothelial cells and further vasodilation. The erectile tissue of the penis consists of large cavernous sinusoids, which are normally relatively empty of blood but become dilated tremendously when arterial blood flows rapidly into them under pressure while the venous outflow is partially occluded. Also, the erectile bodies, especially the two corpora cavernosa, are surrounded by strong fibrous coats; therefore, high pressure within the sinusoids causes ballooning of the erectile tissue to such an extent that the penis becomes hard and elongated.

Answer 36

When the sexual stimulus becomes extremely intense, the reflex centers of the spinal cord begin to emit *sympathetic impulses* that leave the cord at T-12 to L-2 and pass to the genital organs through the hypogastric and pelvic sympathetic nerve plexuses to initiate *emission,* the forerunner of ejaculation. Emission begins with contraction of the vas deferens and the ampulla to cause expulsion of sperm into the internal urethra. Then, contractions of the muscular coat of the prostate gland followed by contraction of the seminal vesicles expel prostatic and seminal fluid also into the urethra, forcing the sperm forward. All these fluids mix in the internal urethra with mucus already secreted by the bulbourethral glands to form the semen. The process to this point is *emission.* The filling of the internal urethra with semen elicits sensory signals that are transmitted through the pudendal nerves to the sacral regions of the cord, giving the feeling of sudden fullness in the internal genital organs. Also, these sensory signals further excite rhythmical contraction of the internal genital organs and cause contraction of the ischiocavernosus and bulbocavernosus muscles that compress the bases of the penile erectile tissue. These effects together cause rhythmical, wavelike increases in pressure in both the erectile tissue of the penis and the genital ducts and urethra, which “ejaculate” the semen from the urethra to the exterior. This final process is called *ejaculation*.

Answer 37

**Somatic Nervous System:** Moderates Ejaculation (Pudendal Nerve S2-S4) Semen in the urethra triggers a spinal reflex through somatic motor neurons. The bulbospongiosus muscles of the penis undergo a rapid series of contractions via the pudendal nerve, propelling semen from the urethra at a speed of up to 500 cm/s. These rhythmic contractions are accompanied by intense pleasure and many systemic changes, such as generalized muscle contraction, rapid heartbeat, and elevated blood pressure.

Answer 38

**Key Hormones:** 1. **GnRH:** Stimulates release of FSH and LH from anterior pituitary 2. **FSH:** Stimulates Sertoli cells to release ABP, thereby stimulating spermatogenesis 3. **LH:** Stimulates Leydig cells to secrete testosterone (and some estrogen) 4. **Testosterone:** Triggers spermatogenesis, maturation of sex organs, development/maintenance of secondary sexual characteristics and sexual behaviour and libido. When levels are high, has negative feedback on hypothalamus to inhibit the release of GnRH and on the anterior pituitary to inhibit release of gonadotropin (FSH and LH) 5. **ABP:** Released by Sertoli cells to allow for high concentration of testosterone in lumen of seminiferous tubules 6. **Inhibin:** Released by Sertoli cells when sperm count is high to inhibit the release of FSH from anterior pituitary and GnRH from hypothalamus

Answer 39

**Definition of Erectile Dysfunction:** The consistent or recurrent inability to attain and/or maintain a penile erection sufficient for sexual performance

Answer 40

**Causes of Erectile Dysfunction:** 1. Psychological 2. Vascular 3. Neurological 4. Hormonal 5. Drug-Induced 6. Anatomic 7. Trauma

Answer 41

_Causes of_ _Erectile Dysfunction - Drug-Induced_ **Examples** → Antihypertensives, antidepressants, antipsychotics, alcohol, tobacco and street drugs (cocaine, heroin and methadone) 1. **Antihypertensives (β-blockers and Thiazide Diuretics):** Diuretics can decrease forceful blood flow to the penis and β-Blockers cause peripheral vasoconstriction. 2. **Antidepressants (SSRIs):** Increased serotonin causes anorgism and decreased libido. 3. **Antipsychotics (Dopamine Antagonists):** Increases prolactin and decreases GNRH, LH and testosterone causing hypogonadotropic hypogonadism. * *Alcohol:** CNS depressant and peripheral neuropathy. 4. **Tobacco:** Contributes to vascular disease. 5. **Street Drugs:** Acts on the CNS, impairing the body’s ability to respond sexually.

Answer 42

_Anatomic causes of_ _Erectile Dysfunction_ **Examples** → Peyronie's disease and phimosis. **Mechanisms** → May cause pain

Answer 43

_Traumatic causes of_ _Erectile Dysfunction_ * **Examples** → Pelvic fracture, urethral injury, perineal injury, spinal cord injury, vascular injury, head trauma or genital injury. * **Mechanisms** → May cause pain and nerve or artery damage.

Answer 44

**_Assessment of Patient with Erectile Dysfunction:_** **History:** * **International Index of Erectile Function (IIEF):** Five-item questionnaire to evaluate male sexual function * **Sexual History:** Sexual function, erection history, libido, ejaculation, sexual lifestyle or partner issues * **General Medical History:** Cardiovascular, neurologic, psychiatric, metabolic, trauma, surgery and respiratory (COPD or sleep apnoea) history * **Medication History:** Antihypertensives, antipsychotics, antidepressants or other drugs with erectile dysfunction side effects * **Social History:** Stress, job and social position, relationships status and history, economic position, education level, religion, sexual abuse or trauma

Answer 45

**_Assessment of Patient with Erectile Dysfunction:_** **Examinations:** Focus on the genitourinary (features of hypogonadism), vascular (abnormal pulses), and neurological (neurogenic dysfunction) exams * **Cardiovascular:** Pulse and BP, heart, peripheral pulses and peripheral venous status * **Secondary Sex Characteristics:** Male hair pattern, fat distribution and gynecomastia * **Genito-Urinary:** Penis for fibrosis, nodules, functional length and hygiene, and testicles for size, symmetry, nodules and tenderness

Answer 46

1. **Primordial follicle** - single layer of flattened follicle cells around ovum 2. **Primary follicle** - Follicle cells convert to cuboidal granulosa cells 3. **Early secondary follicle** - Multiple granulosa cell layers emerge 4. **Late Secondary/Antral Follicle** - Emergence of thecal cell layers, granulosa cells secrete fluid that forms the antrum 5. **Mature/Graafian Follicle** - Ovum eccentrically positioned, surrounded by granulosa cell layer (corona radiata). 6. **Follicle rupture & Ovulation** 7. **Corpus Luteum** - Granulosa cells convert to luteal cells that secrete progesterone and estrogen, prepare endometrium 8. **Corpus Albicans** - Produced when corpus luteum undergoes apoptosis after 12 days, hormone production stops, triggers menstruation.

Answer 47

**Definition**: the absence of menarche at 15 years of age despite normal development of secondary sexual characteristics, or absence of menses at 13 years of age in female individuals with no secondary sexual characteristics

Answer 48

**Secondary Amenorrhea:** The absence of menses for three consecutive cycle in the absence of pregnancy, lactation, cycle suppression with systemic hormonal contraceptive (birth control) pills, or menopause. **Definition**: the absence of menses for more than 3 months in individuals with previously regular cycles, or 6 months in individuals with previously irregular cycles.

Answer 49

Anatomical Causes of Abnormal Uterine Bleeding: 1. Leiomyoma (Fibroids) 2. Endometrial Polyps 3. Adenomyosis 4. Endometrial Hyperplasia 5. Malignancy

Answer 50

**Infectious Causes of Abnormal Uterine Bleeding:** Inflammation causing increased vascularisation (vascular dilation and congestion), as well as local cell damage due to host immune reaction, leading to abnormal bleeding (as described above). 1. Endometritis 2. Pelvic Inflammatory Disease 3. Cervicitis

Answer 51

**Hormonal Changes in Menopause: ** 1. Combined ovarian and hypothalamic aging. 2. Desynchronised GnRH release from hypothalamus 3. Decline in ovarian follicles producing anovulatory cycles. 4. Decline in estrogen levels associated with decline in available follicles. 5. Decline in inhibin B levels and AMH with decline in available follicles. 6. FSH and LH levels rise in the absence of negative feedback from ovarian follicles (estrogen, AMH, inhibin B) 7. Anovulatory cycles don't produce a corpus luteum, decreasing progesterone levels associated with lighter bleeds.

Answer 52

**Urogenital Symptoms: **Estrogen withdrawal leads to decreased collagen synthesis and subsequent weakening of vaginal walls and urinary structures. It also causes decreased blood flow to vaginal epithelium and subsequent epithelial atrophy and decreased glycogen production, decreased lactobacilli and increased vaginal pH.

Answer 53

- **Vasomotor Symptoms**: Estrogen withdrawal leads to peripheral vasodilation, blood flow and sweating (estrogen administration abolishes hot flashes) though exact mechanism poorly understood. - **Cardiovascular Disease:** Estrogens are highly vasoactive, promote vascular remodelling, elasticity, regulating dilation and inflammation. Estrogen withdrawal has indirect effects on cardiovascular risk factors (visceral adiposity, dyslipidaemia, increased TGLs, insulin resistance and increased BP) and direct vasoconstrictive effects on vasculature (activation of RAAS, increased endothelin and decreased NO synthase). Estrogen decline increases risk of atherosclerosis and ischaemic heart disease and stroke.

Answer 54

- **Psychological and Cognitive Changes:** Mood disorders often occur for the first time during menopause, but not considered to be caused by it. Menopause often occurs concurrently with significant life stressors (children leaving home, caring for elderly parents). Many symptoms of menopause can effect quality of life (sleep disturbance due to hot flushes, changes to sexual function associated with urogenital changes). - **Osteoporosis**: Estrogens couple bone formation and reabsorption. Estrogen decline leads to excessive resorption (osteoclast activity) and reduced formation of bone (osteoblast activity).

Answer 55

The focus on sexual history/menstrual history/pregnancy history will depend on the context and presenting complaint. For example a 50 year old woman with irregular bleeding - focus more on menstrual history but it is important to establish brief pregnancy and sexual history.

Answer 56

- The components of pelvic examination are inspection, speculum, Cervical Screening Test, swabs and bimanual examination. Which components are done depends on the patient clinical circumstances. - Inform patient of Cervical Screening Test registry and obtain consent - Discuss how to obtain results

Answer 57

**Squamous Cell Hyperplasia** Previously called hyperplastic dystrophy or lichen simplex chronicus, squamous cell hyperplasia is a nonspecific condi- tion resulting from rubbing or scratching of the skin to relieve pruritus. Clinically it presents as leukoplakia, and histologic examination reveals thickening of the epidermis (acanthosis) and hyperkeratosis (see Fig. 22.5B). Lymphocytic infiltration of the dermis is sometimes present. The hyper- plastic epithelium may show mitotic activity but lacks cellular atypia. While squamous cell hyperplasia is not considered premalignant, it is sometimes present at the margins of vulvar cancers.

Answer 58

- **Bartholin Cyst**: Cystic dilation of the Bartholin gland that arises due to inflammation and obstruction of gland. Usually occurs in women of reproductive age. - **Macroscopic Pathology**: Presents as a unilateral, painful cystic lesion (3 to 5cm) at the lower vestibule adjacent to the vaginal canal, which may cause abscess. - **Microscopic Pathology**: Cysts are lined by transitional or squamous epithelium.

Answer 59

Lichen sclerosis presents as smooth, white plaques or macules that in time may enlarge and coalesce, producing a surface that resembles porcelain or parchment. When the entire vulva is affected, the labia become atrophic and agglutinated, and the vaginal orifice constricts. Histologically, the lesion is characterized by marked thinning of the epidermis (Fig. 22.5A), degeneration of the basal epithelial cells, excessive keratinization (hyperkeratosis), sclerotic changes of the superficial dermis, and a bandlike lymphocytic infiltrate in the underlying dermis. The disease occurs in all age groups but is most common in postmenopausal women. It may also be encountered elsewhere on the skin. Its pathogenesis is uncertain, but the presence of activated T cells in the subepithelial inflammatory infiltrate and the increased frequency of autoimmune disorders in affected women suggest that an autoimmune reaction is involved. Although lichen sclerosus is not itself a premalignant lesion, women with symptomatic lichen sclerosus have a slightly increased chance of developing squamous cell carcinoma of the vulva.

Answer 60

**Condyloma Acuminatum** Condylomata acuminata are benign genital warts caused by low-risk HPV, mainly types 6 and 11. They may be solitary, but are more frequently multifocal, and they may involve vulvar, perineal, and perianal regions as well as the vagina and, less commonly, the cervix. The lesions are identical to those found on the penis and around the anus in males.

Answer 61

On histologic examination, they consist of papillary, exophytic, treelike cores of stroma covered by thickened squamous epithelium (Fig. 22.6A). The surface epithelium shows characteristic viral cytopathic changes referred to as koilocytic atypia, which manifest as nuclear enlargement, hyperchromasia, and a cytoplasmic perinuclear halo. Condylomata acuminata are not precan- cerous lesions. HPV vaccines (described later) provide excellent protection against infection by low-risk HPV and genital warts.

Answer 62

**Vulvar Intraepithelial Neoplasia:** Refers to particular changes that can occur in the skin that covers the vulva (in-situ precursor lesions). Can disappear without treatment. Are benign, but if the changes become more severe, risk of cancer increases. Risk factors include HPV, HSV, smoking, immunosuppression, chronic valvular irritation and conditions such as Lichen Sclerosis. - **Macroscopic pathology**: Discrete white (hyperkeratotic) or a slightly raised, pigmented lesion. - **Microscopic pathology:** - Classic VIN: Epidermal thickening, nuclear atypia, increased mitoses, and lack of cellular maturation. - Differentiated VIN: Marked atypia of the basal layer of the squamous epithelium and normal-appearing differentiation of the more superficial layers.

Answer 63

* Approximately 30% of vulvar cancers are caused by infection with high-risk HPVs, principally HPV-16.These cancers develop from an in situ lesion termed classic vulvar intraepithelial neoplasia (classic VIN). * Most vulvar cancers (70%) are not related to HPV and develop in a background of lichen sclerosus or squamous cell hyperplasia from the premalignant lesion called differentiated vulvar intraepithelial neoplasia (differentiated VIN).

Answer 64

- **What**: Malignant mesenchymal proliferation of immature skeletal muscle (rare). Also known as sarcoma botryoides. - **Macroscopic**: Bleeding and a grape-like mass protruding from the vagina or penis of a child (usually < 5 years of age). - **Microscopic**: Rhabdomyoblast, the characteristic cell, exhibits cytoplasmic cross- striations and positive immunohistochemical staining for desmin and myogenin.

Answer 65

1. Bartholin Cyst 2. Inflammatory Dermatoses 3. Lichen Sclerosus 4. Squamous Cell Hyperplasia / Lichen Simplex Chronicus 5. Condyloma Acuminatum 6. Vulvar Intraepithelial Neoplasia 7. Squamous Neoplastic Lesions - Basaloid and Warty Carcinoma 8. Squamous Neoplastic Lesions - Keratinizing Squamous Cell Carcinoma 9. Glandular Neoplastic Lesions - Papillary Hidradenoma 10. Glandular Neoplastic Lesions - Extramammary Paget Disease

Answer 66

1. Vaginitis 2. Vaginal Squamous Cell Carcinoma 3. Embryonal Rhabdomyosarcoma

Answer 67

1. Cervicitis 2. Endocervical Polyps 3. Cervical Ectropion 4. Cervical Intraepithelial Neoplasm 5. Cervical Carcinoma

Answer 68

1. Endometritis 2. Endometriosis 3. Adenomyosis 4. Endometrial Polyp 5. Endometrial Hyperplasia 6. Endometrial Carcinoma - Type I Endometrial Adenocarcinoma 8. Endometrial Carcinoma - Type II Endometrial Serous Carcinoma (15% of cases) 9. Uterine Leiomyoma (Fibroids) 10. Leiomyosarcoma

Answer 69

* Endometrial carcinoma is the most common malignancy of the female genital tract. * There are two major types of endometrial carcinoma: type I and type II.Type I tumors are low-grade and usually indolent; type II tumors are high-grade aggressive tumors and have a poor prognosis. * Four molecular subtypes of endometrioid and serous carcinoma are currently recognized. * Endometrioid (type I) carcinoma is often preceded by atypical hyperplasia and commonly has mutations that upregulate PI3K/ AKT signaling. * Serous (type II) carcinoma is associated with serous endometrial intraepithelial carcinoma, and the most common mutations are in TP53. TP53 mutations are also found in precursor lesions. * Stage remains the most important factor in outcome; serous tumors are much more likely to present at advanced stage and have a decidedly worse prognosis. * Carcinosarcomas are aggressive tumors that resemble endo- metrial carcinoma genetically and have poor outcomes with current therapies.

Answer 70

* Endometrial stromal tumors include stromal nodules, low-grade stromal sarcoma, and high-grade stromal sarcoma. * Stromal nodules are benign, well-circumscribed tumors. * Low-grade stromal sarcoma resembles stromal nodules but infiltrates into the surrounding myometrium. It is associated with fusion of the JAZF1 gene and various polycomb factor genes, usually SUZ12. * High-grade stromal sarcoma shows marked atypia and is associated with other gene fusions. * Both low- and high-grade stromal sarcoma are prone to late recurrences. * Leiomyomas are very common benign smooth muscle tumors that cause significant morbidity, but are not prone to malignant transformation. * Leiomyosarcoma (a malignant smooth muscle tumor) is an uncommon, highly malignant myometrial tumor that usually arises de novo.