vulva, cervix, and disorders of sexual development

Question 1

what is lichen sclerosis?

Answer 1

thinning of the epidermis and fibrosis of the dermis that presents as a white patch (leukoplakia) with parchment-like vulvar skin. most commonly seen in postmenopausal women; possible autoimmune etiology. benign but associated with a slightly increased risk of squamous cell carcinoma

Question 2

what is lichen simplex chronicus?

Answer 2

hyperplasia of the vulvar squamous epithelium
presents as leukoplakia with thick, leathery vulvar skin
associated wtih chronic irritation and scratching. benign- no risk of squamous cell carcinoma

Question 3

what are precursors for HPV related vulvar carcinoma?

Answer 3

vulvar intraepithelial neoplasia, a dysplastic precursor lesion characterized by koilocytic change, disordered cellular maturation, nuclear atypia, and increased mitotic activity

Question 4

what are causes of non-hpv related vulvar carcinoma?

Answer 4

usually from long-standing lichen sclerosis. chronic inflammation and irritation eventually cause carcinoma. usually seen in women older than 70.

Question 5

extramammary paget disease

Answer 5

malignant epithelial cells in the epidermis of the vulva that presents as erythematous pruritc, ulcerated vulvar skin. this is carcinoma in situ without an underlying carcinoma. must be distinguished from melanoma (paget cells are PAS+, keratin +, S-100 -; melanoma is PAS-. keratin -; S100 +

Question 6

How does high risk HPV promote cancer?

Answer 6

type 16, 18, 31, 33 produce E6 and E7 proteins that result in increased destruction of p53 and Rb, respectively. loss of tumor suppressors increases the risk of cancer.
remember, we detect type of HPV by DNA typing.

Question 7

How does cervical cancer present? types of cancer? causes of death?

Answer 7

vaginal bleeding, esp. post-coital bleeding or cervical discharge. most common type is squamous cell carcinoma, but 15% of cases are adenocarcinoma. advanced cases invade throug hte anterior uterine wall into the bladder, blocking the ureters. hydronephrosis with postrenal failure is a common cause of death.
Pap smears don’t detect adenocarcinoma well.

Question 8

What are the features of klinefelter? hormonal abnormalities?

Answer 8

XXY karyotype
features include testicular atrophy, tall, long extremities, gynecomastia, female hair distribution. may present with developmental delay. patient will have barr body (inactivated X chromosome). common cause of hypogonadism.
dysgenesis of seminiferous tubules causes decreased inhibin and increased FSH.
abnormal leydig cell function causes decr. testosterone, incr LH, increased estrogen

Question 9

turner syndrome features and chromosomal abnormalities

Answer 9

short stature, ovarian dysgenesis, bicuspid aortic valve, preductal coarctation (femoral < brachial pulse, notched ribs), lymphatic defects (webbed neck, lymphedema), horseshoe kidney, most common cause of primary amenorrhea.
menopause before menarche: low estrogen, high LH and FSH.

Question 10

XYY people

Answer 10

phenotypically normal, very tall, severe acne, antisocial behavior in 1-2%. normal fertility. small percentage have autism spectrum disorders

Question 11

true hermaphroditism

Answer 11

ovotesticular disorder of sex development. both ovary and testicular tissue is present with ambiguous genitalia. very rare. 46XX or 47 XXY

Question 12

schematic for diagnosing disorders of sex hormones

Answer 12

high testosterone and high LH: defective androgen receptor
high testosterone and low LH: testosterone-secreting tumor or exogenous steroids
low testosterone and high LH: primary hypogonadism
low testosterone and low LH: hypogonadotropic hypogonadism

Question 13

female pseudohermaphrodite

Answer 13

ovaries present but external genitalia are virilized or ambiguous. due to excessive and inappropriate exposure to androgenic steroids during early gestation (congenital adrenal hyperplasia or exogenous administration of androgens during pregnancy

Question 14

male pseudohermaphrodite

Answer 14

testes present but external genitalia are female or ambiguous. most common type is androen insensitivity syndrome

Question 15

aromatase deficiency

Answer 15

inability to synthesize estrogens from androgens. masculinization of female infants (ambiguous genitalia) and increased serum testosterone and androgstenedione. can present with maternal virilization during pregnancy

Question 16

kallman syndrome

Answer 16

failure to complete puberty. form of hypogonadotropic hypogonadism. defective migration of GnRH cells and formation of the olfactory bulb’ decr. synthesis of GnRH in the hypothalamus; anosmia; decr. GnRHm FSH, LH, testosterone, and infertility (low sperm count in men; amenorrhea in women)

Question 17

5-alpha reductase deficiency

Answer 17

autosomal recessive. limited to 46XY. inability to convert testosterone to DHT. ambiguous genitalia until puberty, the incr. testosterone cuases masculinization and growth of the external genitalia. testosterone/estrogen levels are normal; LH is normal or increased. internal genitalia are normal.

Question 18

androgen insensitivity syndrome

Answer 18

defect in androgen receptor resulting in a normal appearing female. extrernal genitalia with rudimentary vagina. uterus and gallopian tubes generally absent. presents with scant sexual hair. develops testes (often in labia major- surgically removed to prevent malignancy). incr testosterone, estrogen, LH (vs. sex chromosome disorders).