Reproductive - Pathology (1)

Question 1

Klinefelter syndrome

• Type of disorder
• Due to…
• Findings
• Hormones

Answer 1

• Type of disorder
  
  • Sex chromosome disorder of sexual development
  • [male] (XXY), 1:850
• Due to…
  
  • Presence of inactivated X chromosome (Barr body).
• Findings
  
  • Testicular atrophy, eunuchoid body shape, tall, long extremities, gynecomastia, female hair distribution [A].
  • May present with developmental delay.
  • Common cause of hypogonadism seen in infertility work-up.
• Hormones
  
  • Dysgenesis of seminiferous tubules –> decreased inhibin –>Ž increased FSH.
  • Abnormal Leydig cell function Ž–> decreased testosterone –>Ž increased LH Ž–> increased estrogen.

Question 2

Turner syndrome

• Type of disorder
• Findings
• Hormones
• Due to…

Answer 2

• Type of disorder
  
  • Sex chromosome disorder of sexual development
  • [female] (XO)
    
    • “Hugs and kisses” (XO) from Tina Turner.
• Findings
  
  • Short stature (if untreated), ovarian dysgenesis (streak ovary), shield chest, bicuspid aortic valve, preductal coarctation (femoral < brachial pulse, notched ribs), lymphatic defects (result in webbed neck or cystic hygroma; lymphedema in feet, hands), horseshoe kidney [B].
  • Most common cause of 1° amenorrhea.
  • No Barr body.
  • Menopause before menarche.
  • Pregnancy is possible in some cases (oocyte donation, exogenous estradiol-17β and progesterone)
• Hormones
  
  • Decreased estrogen leads to increased LH, FSH.
• Due to…
  
  • Can result from mitotic or meiotic error.
  • Can be complete monosomy (45,XO) or mosaicism (e.g., 45,XO/46,XX).

Question 3

Double Y males

• Type of disorder
• Findings

Answer 3

• Type of disorder
  
  • Sex chromosome disorder of sexual development
  • [male] (XYY), 1:1000
• Findings
  
  • Phenotypically normal, very tall, severe acne, antisocial behavior (seen in 1–2% of XYY males).
  • Normal fertility.
  • Small percentage diagnosed with autism spectrum disorders.

Question 4

True hermaphroditism

• Type of disorder
• Findings

Answer 4

• Type of disorder
  
  • Sex chromosome disorder of sexual development
  • (46,XX or 47,XXY)
• Findings
  
  • Also called ovotesticular disorder of sex development.
  • Both ovary and testicular tissue present (ovotestis);
    
    • Ambiguous genitalia.
  • Very rare.

Question 5

Diagnosing disorders of sex hormones

• For each (increased/decreased)
  
  • Testosterone
  • LH
• Defective androgen receptor
• Testosterone-secreting tumor, exogenous steroids
• 1° hypogonadism
• Hypogonadotropic hypogonadism

Answer 5

• Defective androgen receptor
  
  • Testosterone: Increased
  • LH: Increased
• Testosterone-secreting tumor, exogenous steroids
  
  • Testosterone: Increased
  • LH: Decreased
• 1° hypogonadism
  
  • Testosterone: Decreased
  • LH: Increased
• Hypogonadotropic hypogonadism
  
  • Testosterone: Decreased
  • LH: Decreased

Question 6

Disorders of sex development

• Definition
• Terms

Answer 6

• Definition
  
  • Disagreement between the phenotypic (external genitalia) and gonadal (testes vs. ovaries) sex.
• Terms
  
  • Pseudohermaphrodite
  • Hermaphrodite
  • Intersex​

Question 7

Female pseudohermaphrodite

• Type of disorder
• Findings
• Due to…

Answer 7

• Type of disorder
  
  • Disorders of sex development
  • (XX)
• Findings
  
  • Ovaries present, but external genitalia are virilized or ambiguous.
• Due to…
  
  • Due to excessive and inappropriate exposure to androgenic steroids during early gestation
  • e.g., congenital adrenal hyperplasia or exogenous administration of androgens during pregnancy)

Question 8

Male pseudohermaphrodite

• Type of disorder
• Findings

Answer 8

• Type of disorder
  
  • Disorders of sex development
  • (XY)
• Findings
  
  • Testes present, but external genitalia are female or ambiguous.
  • Most common form is androgen insensitivity syndrome (testicular feminization).

Question 9

Aromatase deficiency

• Definition
• Findings

Answer 9

• Definition
  
  • Inability to synthesize estrogens from androgens.
• Findings
  
  • Masculinization of female (46,XX) infants (ambiguous genitalia), and increased serum testosterone and androstenedione.
  • Can present with maternal virilization during pregnancy (fetal androgens cross the placenta).

Question 10

Androgen insensitivity syndrome

• Definition
• Findings

Answer 10

• Definition
  
  • Defect in androgen receptor resulting in normal-appearing female
  • (46,XY)
• Findings
  
  • Female external genitalia with rudimentary vagina
  • Uterus and fallopian tubes generally absent
  • Presents with scant sexual hair
  • Develops testes (often found in labia majora; surgically removed to prevent malignancy).
  • Increased testosterone, estrogen, LH (vs. sex chromosome disorders).

Question 11

5α-reductase deficiency

• Definition
• Findings

Answer 11

• Definition
  
  • Autosomal recessive
  • Sex limited to genetic males (46,XY).
  • Inability to convert testosterone to DHT.
• Findings
  
  • Ambiguous genitalia until puberty, when increased testosterone causes masculinization/increased growth of external genitalia.
  • Testosterone/estrogen levels are normal
  • LH is normal or increased.
  • Internal genitalia are normal.

Question 12

Kallmann syndrome

• Definition
• Definition
• Findings

Answer 12

• Definition
  
  • Failure to complete puberty
  • A form of hypogonadotropic hypogonadism.
• Due to…
  
  • Defective migration of GnRH cells and formation of olfactory bulb
  • Decreased synthesis of GnRH in the hypothalamus
• Findings
  
  • Anosmia
  • Decreased GnRH, FSH, LH, testosterone, and infertility
    
    • Low sperm count in males
    • Amenorrhea in females

Question 13

Hydatidiform mole

• Definition
• Treatment
• Types

Answer 13

• Definition
  
  • Cystic swelling of chorionic villi and proliferation of chorionic epithelium (only trophoblast).
• Treatment
  
  • Dilation and curettage and methotrexate.
  • Monitor β-hCG.
• Types
  
  • Complete mole
  • Partial mole

Question 14

Hydatidiform mole:
Complete

• Karyotype
• hCG (increased/decreased/no effect)
• Uterine size (increased/decreased/no effect)
• Convert to choriocarcinoma (%)
• Fetal parts (yes/no)
• Components
• Risk of complications
• Symptoms
• Imaging

Answer 14

• Karyotype
  
  • 46,XX; 46,XY
• hCG
  
  • Really increased
• Uterine size
  
  • Increased
• Convert to choriocarcinoma
  
  • 2%
• Fetal parts
  
  • No
• Components
  
  • Enucleated egg + single sperm (subsequently duplicates paternal DNA)
  • Empty egg + 2 sperm is rare
• Risk of complications
  
  • 15–20% malignant trophoblastic disease
• Symptoms
  
  • Vaginal bleeding, enlarged uterus, hyperemesis, preeclampsia, hyperthyroidism
• Imaging
  
  • Honeycombed uterus or “clusters of grapes” [A]
  • “Snowstorm” on ultrasound [B]

Question 15

Hydatidiform mole:
Partial

• Karyotype
• hCG (increased/decreased/no effect)
• Uterine size (increased/decreased/no effect)
• Convert to choriocarcinoma (%)
• Fetal parts (yes/no)
• Components
• Risk of complications
• Symptoms
• Imaging

Answer 15

• Karyotype
  
  • 69,XXX; 69,XXY; 69,XYY
• hCG
  
  • Increased
• Uterine size
  
  • No effect
• Convert to choriocarcinoma
  
  • Rare
• Fetal parts
  
  • Yes
  • Partial = fetal parts
• Components
  
  • 2 sperm + 1 egg
• Risk of complications
  
  • Low risk of malignancy (< 5%)
• Symptoms
  
  • Vaginal bleeding, abdominal pain
• Imaging
  
  • Fetal parts

Question 16

Hypertension in pregnancy:
Gestational hypertension (pregnancy-induced hypertension)

• Definition
• Treatment

Answer 16

• Definition
  
  • BP > 140/90 mmHg after the 20th week of gestation.
  • No pre-existing hypertension.
  • No proteinuria or end-organ damage.
• Treatment
  
  • Antihypertensives (α-methyldopa, labetalol, hydralazine, nifedipine)
  • Deliver at 39 weeks.

Question 17

Hypertension in pregnancy:
Preeclampsia

• Definition
• Due to…
• Findings
• Complications
• Treatment

Answer 17

• Definition
  
  • Defined as hypertension (> 140/90 mmHg) and proteinuria (> 300 mg/24 hr) after 20th week of gestation to 6 weeks postpartum (< 20 weeks suggests molar pregnancy).
• Due to…
  
  • Caused by abnormal placental spiral arteries
  • Incidence increases in patients with preexisting hypertension, diabetes, chronic renal disease, or autoimmune disorders
• Findings
  
  • Results in maternal endothelial dysfunction, vasoconstriction, or hyperreflexia.
  • Severe features include BP > 160/110 mmHg with or without end-organ damage, e.g., headache, scotoma, oliguria, increased AST/ALT, thrombocytopenia.
• Complications
  
  • Placental abruption, coagulopathy, renal failure, uteroplacental insufficiency, or eclampsia.
• Treatment
  
  • Antihypertensives
  • Deliver at 34 weeks (severe) or 37 weeks (mild)
  • IV magnesium sulfate to prevent seizure.

Question 18

Hypertension in pregnancy:
Eclampsia

• Definition
• Findings
• Treatment

Answer 18

• Definition
  
  • Preeclampsia + maternal seizures.
• Findings
  
  • Maternal death due to stroke –>Ž intracranial hemorrhage or ARDS.
• Treatment
  
  • Antihypertensives, IV magnesium sulfate, immediate delivery.

Question 19

Hypertension in pregnancy:
HELLP syndrome

• Definition
• Treatment

Answer 19

• Definition
  
  • Hemolysis, Elevated Liver enzymes, Low Platelets.
  • A manifestation of severe preeclampsia, although may occur without hypertension.
• Treatment
  
  • Immediate delivery.

Question 20

Pregnancy complications:
Placental abruption (abruptio placentae)

• Definition
• Risk factors
• Presentation

Answer 20

• Definition
  
  • Premature separation (partial or complete) of placenta from uterine wall before delivery of infant.
  • Life threatening for mother and fetus.
• Risk factors
  
  • Trauma (e.g., motor vehicle accident), smoking, hypertension, preeclampsia, cocaine abuse.
• Presentation
  
  • Abrupt, painful bleeding (concealed or apparent) in third trimester
  • Possible DIC, maternal shock, fetal distress.

Question 21

Pregnancy complications:
Placenta accreta / increta / percreta

• Definition
• Risk factors
• Placenta accreta
• Placenta increta
• Placenta percreta
• Presentation

Answer 21

• Definition
  
  • Defective decidual layer –>Ž abnormal attachment and separation after delivery.
  • Life threatening for mother.
• Risk factors
  
  • Prior C-section, inflammation, placenta previa.
  • Three types distinguishable by the depth of penetration:
• Placenta accreta
  
  • Placenta attaches to myometrium without penetrating it
  • Most common type.
• Placenta increta
  
  • Placenta penetrates into myometrium.
• Placenta percreta
  
  • Placenta penetrates (“perforates”) through the myometrium and into uterine serosa (invades entire uterine wall)
  • Can result in placental attachment to rectum or bladder.
• Presentation
  
  • No separation of placenta after delivery Ž–> massive bleeding.

Question 22

Pregnancy complications

• Placenta previa
  
  • Definition
  • Findings
  • Risk factors
• Retained placental tissue

Answer 22

• Placenta previa (image)
  
  • Definition
    
    • Attachment of placenta to lower uterine segment.
  • Findings
    
    • Lies near (marginal, not shown), partially covers (partial), or completely covers internal cervical os.
  • Risk factors
    
    • Multiparity, prior C-section.
• Retained placental tissue
  
  • May cause postpartum hemorrhage
  • Increased risk of infection

Question 23

Pregnancy complications:
Ectopic pregnancy

• Definition
• Findings
• Diagnosis
• Risk factors

Answer 23

• Definition
  
  • Most often in ampulla of fallopian tube ([A] shows 10-mm embryo within oviduct at 7 weeks’ gestation).
• Findings
  
  • Suspect with history of amenorrhea, lower-than-expected rise in hCG based on dates, and sudden lower abdominal pain
  • Often clinically mistaken for appendicitis
  • Pain with or without bleeding
• Diagnosis
  
  • Confirm with ultrasound.
• Risk factors
  
  • ƒƒHistory of infertility
  • Salpingitis (PID)
  • Ruptured appendix
  • Prior tubal surgery

Question 24

Amniotic fluid abnormalities

• Polyhydramnios
  
  • Definition
  • Associations
• Oligohydramnios
  
  • Definition
  • Associations
  • Can cause…

Answer 24

• Polyhydramnios
  
  • > 1.5–2 L of amniotic fluid
  • Associated with fetal malformations (e.g., esophageal/duodenal atresia, anencephaly; both result in inability to swallow amniotic fluid), maternal diabetes, fetal anemia, multiple gestations.
• Oligohydramnios
  
  • < 0.5 L of amniotic fluid
  • Associated with placental insufficiency, bilateral renal agenesis, or posterior urethral valves (in males) and resultant inability to excrete urine.
  • Any profound oligohydramnios can cause Potter sequence.

Question 25

Cervical pathology: Dysplasia and carcinoma in situ * Definition * Associations * Findings * Risk factors

Answer 25

* Definition * Disordered epithelial growth * Begins at basal layer of squamocolumnar junction (transition zone) and extends outward. * Classified as CIN 1, CIN 2, or CIN 3 (severe dysplasia or carcinoma in situ), depending on extent of dysplasia. * Associations * Associated with HPV 16 and HPV 18, which produce both the E6 gene product (inhibits p53 suppressor gene) and E7 gene product (inhibits RB suppressor gene). * Findings * May progress slowly to invasive carcinoma if left untreated. * Typically asymptomatic (detected with Pap smear) or presents as abnormal vaginal bleeding (often postcoital). * Risk factors * Multiple sexual partners (#1), smoking, early sexual intercourse, HIV infection.

Question 26

Cervical pathology: Invasive carcinoma

Answer 26

* Often squamous cell carcinoma. * Pap smear can catch cervical dysplasia (koilocytes [A]) before it progresses to invasive carcinoma. * Lateral invasion can block ureters, causing renal failure.

Question 27

Endometritis * Definition * Treatment

Answer 27

* Definition * Inflammation of the endometrium (with plasma cells and lymphocytes) [A] associated with retained products of conception following delivery (vaginal/C-section)/miscarriage/abortion or foreign body such as an IUD. * Retained material in uterus promotes infection by bacterial flora from vagina or intestinal tract. * Treatment * Gentamicin + clindamycin with or without ampicillin.

Question 28

Endometriosis * Definition * Locations * Findings * Due to... * Treatment

Answer 28

* Definition * Non-neoplastic endometrial glands/stroma outside of the endometrial cavity [A]. * Locations * Can be found anywhere * Most common sites are ovary, pelvis, and peritoneum. * In the ovary, appears as an endometrioma (blood-filled “chocolate cyst”). * Findings * Characterized by cyclic pelvic pain, bleeding, dysmenorrhea, dyspareunia, dyschezia (pain with defecation), infertility; **normal-sized** uterus * Due to... * Can be due to retrograde flow, metaplastic transformation of multipotent cells, or transportation of endometrial tissue via the lymphatic system. * Treatment * NSAIDs, OCPs, progestins, GnRH agonists, surgery.

Question 29

Adeno- * Adenomyosis * Definition * Due to... * Findings * Treatment * Adenomyoma

Answer 29

* Adenomyosis * Definition * Extension of endometrial tissue (glandular) into the uterine myometrium. * Due to... * Caused by hyperplasia of the basalis layer of the endometrium. * Findings * Dysmenorrhea, menorrhagia. * Uniformly **enlarged**, **soft**, globular uterus. * Treatment * Hysterectomy * Adenomyoma (polyp) * Well-circumscribed collection of endometrial tissue within the uterine wall. * May contain smooth muscle cells. * Can extend into the endometrial cavity in the form of a polyp.

Question 30

Endometrial proliferation * For each * Definition * Findings * Risk factors * Endometrial hyperplasia * Endometrial carcinoma

Answer 30

* Endometrial hyperplasia * Definition * Abnormal endometrial gland proliferation usually caused by excess estrogen stimulation. * Increased risk for endometrial carcinoma. * Findings * Clinically manifests as postmenopausal vaginal bleeding. * Risk factors * Anovulatory cycles, hormone replacement therapy, polycystic ovarian syndrome, and granulosa cell tumor. * Endometrial carcinoma * Definition * Most common gynecologic malignancy. * Peak occurrence at 55–65 years old. * Increased myometrial invasion --\> decreased prognosis. * Findings * Clinically presents with vaginal bleeding. * Typically preceded by endometrial hyperplasia. * Risk factors * Prolonged use of estrogen without progestins, obesity, diabetes, hypertension, nulliparity, and late menopause. 

Question 31

Leiomyoma (fibroid) * Definition * Findings

Answer 31

* Definition * Most common tumor in females. * Increased incidence in blacks * Benign smooth muscle tumor * Malignant transformation is rare * Does not progress to leiomyosarcoma * Peak occurrence at 20–40 years old * Findings * Often presents with multiple discrete tumors [A]. * Estrogen sensitive— tumor size increases with pregnancy and decreases with menopause. * May be asymptomatic, cause abnormal uterine bleeding, or result in miscarriage. * Severe bleeding may lead to iron deficiency anemia. * Whorled pattern of smooth muscle bundles with well-demarcated borders.

Question 32

Gynecologic tumor epidemiology * Incidence * Worst prognosis

Answer 32

* Incidence * Endometrial \> ovarian \> cervical * Data pertain to the United States * Cervical cancer is most common worldwide * Worst prognosis * Ovarian \> cervical \> endometrial.

Question 33

Ovarian problems * Premature ovarian failure * Definition * Findings * Most common causes of anovulation

Answer 33

* Premature ovarian failure * Definition * Premature atresia of ovarian follicles in women of reproductive age. * Findings * Patients present with signs of menopause after puberty but before age 40.  * Decreased estrogen * Increased LH, FSH. * Most common causes of anovulation * Pregnancy, polycystic ovarian syndrome, obesity, HPO axis abnormalities, premature ovarian failure, hyperprolactinemia, thyroid disorders, eating disorders, female athletes, Cushing syndrome, adrenal insufficiency.

Question 34

Polycystic ovarian syndrome (Stein-Leventhal syndrome) * Definition * Hormones * Findings

Answer 34

* Definition * Hyperandrogenism due to deranged steroid synthesis by theca cells, hyperinsulinemia * Most common cause of infertility in women. * Hormones * Estrogen increases steroid hormone-binding globulin (SHBG) and decreases LH * Ultimately resulting in decreased free testosterone * Insulin and testosterone decreases SHBG --\>Ž increased free testosterone.  * Increased LH due to pituitary/hypothalamus dysfunction. * Increased LH, increased FSH (LH:FSH, 3:1), increased testosterone, increased estrogen (from aromatization). * Findings * Results in enlarged, bilateral cystic ovaries [A] * Presents with amenorrhea/oligomenorrhea, hirsutism, acne, infertility.

Question 35

Polycystic ovarian syndrome (Stein-Leventhal syndrome) * Associations * Treatment * For hirsutism, acne * For infertility * For endometrial protection

Answer 35

* Associations * Associated with obesity.  * Increased risk of endometrial cancer 2° to increased estrogens from the aromatization of testosterone and absence of progesterone. * Treatment * For hirsutism, acne * Weight reduction * OCPs * Estrogen increases SHBG and decreases LH Ž--\> decreased free testosterone * Antiandrogens * For infertility * Clomiphene citrate * Blocks negative feedback of circulating estrogen * Decreases FSH, LH * Metformin * Increases insulin sensitivity, decreases insulin levels --\> results in decreased testosterone * Enables LH surge * For endometrial protection * Cyclic progesterones (antagonizes endometrial proliferation)

Question 36

Ovarian cysts * Follicular cyst * Corpus luteum cyst * Theca-lutein cyst

Answer 36

* Follicular cyst * Distention of unruptured graafian follicle. * May be associated with hyperestrogenism and endometrial hyperplasia. * Most common ovarian mass in young women. * Corpus luteum cyst * Hemorrhage into persistent corpus luteum. * Commonly regresses spontaneously. * Theca-lutein cyst * Often bilateral/multiple. * Due to gonadotropin stimulation. * Associated with choriocarcinoma and moles.

Question 37

Ovarian cysts * Hemorrhagic cyst * Dermoid cyst * Endometrioid cyst

Answer 37

* Hemorrhagic cyst * Blood vessel rupture in cyst wall. * Cyst grows with increased blood retention * Usually self-resolves. * Dermoid cyst * Mature teratoma. * Cystic growths filled with various types of tissue such as fat, hair, teeth, bits of bone, and cartilage. * Endometrioid cyst * Endometriosis within ovary with cyst formation. * Varies with menstrual cycle. * When filled with dark, reddish-brown blood it is called a “chocolate cyst.”

Question 38

Ovarian neoplasms * Definition * Arise from... * Risk factors * Findings * Diagnosis

Answer 38

* Definition * Most common adnexal mass in women \> 55 years old. * Can be benign or malignant. * Arise from surface epithelium, germ cells, and sex cord stromal tissue. * Majority of malignant tumors arise from epithelial cells. * Majority (95%) are epithelial (serous cystadenocarcinoma most common). * Risk factors * Risk increases with advanced age, infertility, endometriosis, PCOS, genetic predisposition (BRCA-1 or BRCA-2 mutation, HNPCC, strong family history). * Risk decreases with previous pregnancy, history of breastfeeding, OCPs, tubal ligation. * Findings * Presents with adnexal mass, abdominal distension, bowel obstruction, pleural effusion. * Diagnosis * Diagnose surgically. * Monitor progression by measuring CA-125 levels (not good for screening)

Question 39

Serous cystadenoma * Type of tumor * Definition * Findings

Answer 39

* Type of tumor * Benign ovarian neoplasm * Definition * Most common ovarian neoplasm. * Often bilateral * Findings * Thin-walled, uni- or multilocular. * Lined with fallopian-like epithelium.

Question 40

Mucinous cystadenoma * Type of tumor * Definition

Answer 40

* Type of tumor * Benign ovarian neoplasm * Definition * Multiloculated, large. * Lined by mucus-secreting epithelium [A].

Question 41

Endometrioma * Type of tumor * Definition * Findings

Answer 41

* Type of tumor * Benign ovarian neoplasm * Definition * Mass arising from growth of ectopic endometrial tissue. * Findings * Complex mass on ultrasound. * Presents with pelvic pain, dysmenorrhea, dyspareunia.

Question 42

Mature cystic teratoma (dermoid cyst) * Type of tumor * Definition * Findings

Answer 42

* Type of tumor * Benign ovarian neoplasm * Definition * Germ cell tumor, most common ovarian tumor in women 20–30 years old. * Can contain elements from all 3 germ layers * Teeth, hair, sebum [B] are common components. * Findings * Can present with pain 2° to ovarian enlargement or torsion. * Can also contain functional thyroid tissue and present as hyperthyroidism (struma ovarii) [C].

Question 43

Brenner tumor * Type of tumor * Findings

Answer 43

* Type of tumor * Benign ovarian neoplasm * Findings * Looks like **_b_**ladder. * Solid tumor that is pale yellow-tan in color and appears encapsulated. * “Coffee **_b_**ean” nuclei on H&E stain.