Pathology-Female GU Path Flashcards
A 22 year old woman present with a unilateral painful lesion at the lower vestibule adjacent to the vaginal canal. What is the most likely cause of her condition?
Bartholin cyst. This is a cystic dilation of the Bartholin gland that arises due to inflammation and obstruction of the gland; commonly in women of reproductive age.
A 34 year old woman presents with a large warty lesion of the vulvar skin. Biopsy of the lesion is shown below. What is causing her condition?
Condylomas are most commonly due to HPV 6 or 11. They are characterized by koilocytic change (crinkled or raisinoid nucleus) on biopsy. Note that these rarely progress to carcinoma because HPV 6 and 11 are low risk infections.
Typical areas affected by HPV 6 or 11 in females
Vulvar, vaginal canal and cervical (lower genital tract) condylomas
How do you know whether a woman is infected with high risk or low risk HPV infection?
DNA sequencing (because HPV is a DNA virus). Low risk are serotypes 6 and 11. High risk are serotypes 16, 18, 31 and 33
Typical areas affected by HPV 16, 18, 31 and 33 in females
Dysplasia over time that can eventually become carcinoma in the cervix, vagina and vulva.
A 60 year old post-menopausal woman presents with parchment-like (very thin) leukoplakia on the vulvar skin. What is likely causing her condition?
Lichen sclerosis. This is a thinning of the epidermis and fibrosis of the underlying dermis. This is a benign lesion but has a SLIGHT increased risk of squamous cell carcinoma.
A 60 year old post-menopausal woman presents with thick leathery leukoplakia on the vulvar skin. What is likely causing her condition?
Lichen simplex chronicus. This is hyperplasia of vulvar squamous epithelium due to chronic irritation and scratching. Note that these are benign and have NO increased risk of squamous cell carcinoma as Lichen Sclerosis does.
A patient presents with leukoplakia on the vulvar skin. Biopsy shows cancer. What is the most likely diagnosis?
Vulvar carcinoma. This arises from the squamous epithelium lining the vulva. Note that it is rare and accounts for a very small percentage of female genital cancers.
What are the two etiologies of vulvar carcinoma?
HPV-related (40-50 year old patient has high risk HPV which results in vulvar intraepithelial neoplasia that progresses to carcinoma) and non-HPV-related (elderly patient has long-standing lichen sclerosis, chronic inflammation and irritation leads to carcinoma).
A patient presents with erythematous, pruritic and ulcerated skin around the nipple and vulva. The biopsy is shown below. How would you narrow your diagnosis?
Paget Disease of the nipple and vulva (carcinoma) or malignant melanoma. Note the malignant epithelial cells present in the epidermis of the vulva. If the cells were PAS+, keratin+ and S100- it is Paget Disease of the nipple and vulva (carcinoma) If it is PAS-, keratin- and S100+, it is melanoma. Note that this represents carcinoma in situ, with no underlying carcinoma in the vulva.
Why are you more concerned about a patient with Paget Disease of the nipple vs a patient with Paget Disease of the vulva?
Nipple usually means there is underlying cancer in the breast. Vulva usually means no underlying carcinoma.
Where does the lower 1/3 of the vagina originate from? The upper 2/3?
Lower 1/3 = Urogenital sinus. Upper 2/3 = Mullerian duct.
What drug can cause a woman to have this vaginal biopsy?
She has adenosis. Normally, the stratified squamous epithelium from the lower 1/3 of the vaginal canal proliferates and replaces the columnar epithelium in the upper 2/3 of the vagina. Adenosis is a focal persistence of columnar epithelium in the upper vagina, with increased incidence in females exposed to DES in utero. Note the two glands persisting with columnar epithelium.
Why is exposure to DES in utero such a big deal that people stopped using it?
A rare complication of DES-associated vaginal adenosis is clear cell adenocarcinoma.
Aside from adenosis and/or clear cell adenocarcinoma, what other complications may arise from DES?
Abnormal smooth muscle formation in the uterine tube carries a complication of ectopic pregnancy and infertility. Mothers who took DES is related to increased estrogen and increased risk for breast cancer.
A <5 year old girl presents with bleeding and a grape-like mass protruding from the vagina. What is the most likely diagnosis?
This is embryonal rhabdomyosarcoma. This is a malignant mesenchymal proliferation of immature skeletal muscle and is rare.
A <5 year old girl presents with bleeding and a grape-like mass protruding from the vagina. What is the key cell in this lesion? How do you distinguish them?
Rhabdomyoblasts are the key cells in defining rhabdomyosarcoma. These cells have cytoplasmic cross-striations and will stain positive for desmin (intermediate filament in muscle cells) and myogenin (nuclear transcription factor in immature muscle cells) with immunohistochemistry.
What is a patient at risk for if they have vaginal intraepithelial neoplasia?
Vaginal carcinoma. This arises from squamous epithelium lining the vaginal mucosa. It is related to high-risk HPV and the precursor lesion is vaginal intraepithelial neoplasia (VAIN).
Lower 1/3 vaginal carcinoma spreads to what nodes? Upper 2/3 vaginal carcinoma spreads to what nodes?
Lower 1/3 = inguinal. Upper 2/3 = regional iliacs.
What defines the boundary between the exocervix and the endocervix?
Exocervix = squamous epithelium. Endocervix = columnar epithelium. This division is called the zone of transition.
HPV’s favorite place to infect in the lower genital tract. What happens in the 1% of time that persistent infection occurs?
Zone of transition. With persistent infection, cervical intraepithelial neoplasia occurs and can transform to carcinoma.
What is it about HPV 16, 18, 31 and 33 that make them high risk?
They make pro-oncotic proteins: E6 increases destruction of p53 (normally promotes DNA repair & apoptotic mechanisms) and E7 increases destruction of Rb (normally inhibits E2F so transcription does not go rampant)
What checkpoint is regulated by p53?
G1 -> S phase transition via checking for DNA damage, repairing it and inducing apoptosis if repair is not possible.
What checkpoint is regulated by Rb?
G1 -> S phase transition via suppression of E2F.
How would you stage this cervical biopsy?
Note the koilocytic change, nuclear atypia and increased mitotic activity. Note that the cells no longer loose their nuclei and turn pink as the go superficial. This is characteristic of cervical intraepithelial neoplasia (CIN) III and CIS (Carcinoma in situ).
How is CIN staged? How likely is each stage to reverse?
Dysplasia of 1st 1/3 of cells = CIN I w/ 66% chance of reversal. 1st 2/3 of cells = CIN II w/ 33% chance of reversal. Most of epithelium = CIN III w/ little chance of reversal. Entire thickness of epithelium = CIS (Carcinoma in situ).
What is the key feature that differentiates CIN from CIS?
CIN has the potential to reverse. CIS cannot reverse and the next step is invasion and squamous cell carcinoma.
A 40 year old woman presents with vaginal and post-coital bleeding. She has a history of HPV infection about 20 years ago. What are secondary risk factors she may have?
Smoking and immunodeficiency increase risk of cervical carcinoma. Note that immunodeficiency results in an inability to clear the HPV infection, allowing it to become chronic and cause cervical carcinoma.
Why is cervical carcinoma an AIDS defining illness?
The body has become so immunodeficient that it cannot clear the HPV infection and allows for progression to cervical cancer.
What are the most common types of cervical carcinoma?
Squamous cell carcinoma and adenocarcinoma. Note that squamous cell is most common, but BOTH are driven by HPV.
What is a classic late finding of an advanced cervical carcinoma?
Hydronephrosis. The tumor metastasizes late but invaded through the anterior uterine wall into the bladder and causes urinary obstruction. Note that one of the most common causes of death in people with cervical cancer is renal failure, post-hydronephrosis.
Goal of screening for cervical carcinoma
Catch dysplasia before it develops into carcinoma.
How do you do a pap smear?
Scrape cells off of the zone of transition, put them under the microscope and look for atypical cells (dark nuclei, high N:C ratios).
What is your diagnosis of this pap smear?
Note the normal squamous cell on the left. Note the atypical cells with a high N:C ratio on the right, which are malignant cells and features you would expect to see in dysplasia.
What is the confirmatory test done after an abnormal pap smear?
Colposcopy. A magnifying glass is placed near the cervix, acid is placed around the cervix and areas of abnormality are biopsied.
What are limitations of a pap smear?
Inadequate sampling of the transformation zone results in a false negative screening test. Also there is limited efficacy in screening for adenocarcinoma (it doesn’t go through same progression of dysplasia that squamous cell carcinoma does).
What immunizations are available for HPV? How long does it last?
Quadrivalent vaccine against HPV 6/11 (protects against condyloma), 16/18 (protects against VIN, VAIN and CIN). Protection lasts 5 years and pap smears are still necessary because there are other high-risk serotypes of HPV that can cause dysplasia.
What are the uterine divisions shown below?
The glandular mucosa of the endometrium and the muscular myometrium.
What drives the uterine proliferative phase?
Estrogen
What drives the uterine secretory phase in preparation for implantation?
Progesterone
A 34 year old woman had to come in for a D&C (dilation and curettage) because of a miscarriage at 15 weeks gestation. She now complains of amenorrhea. What is likely causing her condition?
Asherman Syndrome from overaggressive D&C. This is due to loss of the endometrial basalis, where the stem cells are. This results in inability to regenerate the functionalis, scarring and secondary amenorrhea.
When do you typically see dysfunctional uterine bleeding due to anovulatory cycles?
Menarche and menopause. Lack of progesterone-driven secretory phase causes estrogen uterine proliferation to double on top of one another. This causes proliferating cells to outgrow their blood supply, shed and cause dysfunctional uterine bleeding.
A mother of a newborn baby presents with fever, abnormal uterine bleeding and pelvic pain 2 days after giving birth. The resident informs you that the entire placenta was not delivered after the child came out. What is causing her condition?
Acute endometritis. This is a bacterial infection of the endometrium usually due to retained products of conception.
A woman presents with abnormal uterine bleeding, pelvic pain and infertility. What might you see if a patient has retained products of conception, PID, IUD or Tb?
Chronic endometritis and plasma cells in the endometrium. She would have granulomas if she had Tb.
A 35 year old woman presents with abnormal uterine bleeding. Uterine biopsy is shown below. She has been on tamoxifen for its anti-estrogen effects due to previous breast cancer. What is the likely cause?
Endometrial polyp, a hyperplastic protrusion of the endometrium. Note that although tamoxifen is anti-estrogenic on the breast, it is pro-estrogenic on the uterus promotes uterine proliferation and formation of endometrial polyps.
A 20 year old woman presents with dysmenorrhea, pelvic pain, pain with defecation, pain with urination and abdominal pain. You are worried that her current condition may cause infertility. What is likely causing her condition?
She has endometriosis. This is misplacement of endometrial glands AND stroma outside of the endometrial lining. In her case pelvic pain is caused by involvement of uterine ligaments, defecation pain from pouch of Douglas involvement, urinary pain from bladder wall involvement and abdominal pain from involvement of the bowel serosa. She is at risk for infertility due to fallopian tube scarring.
3 theories of the cause of endometriosis
1) Retrograde menstruation through fallopian tubes into peritoneal cavity 2) Endometrial metaplasia from Mullerian duct 3) Spread through the lymphatics
Most common site of endometriosis
Ovary - chocolate cyst (menstrual product accumulation from growing and shedding of tissue as the endometriosis cycles)
How does endometriosis affect soft tissues grossly?
It produces small, brown, hemorrhagic areas called gunpowder lesions.
A fat postmenopausal woman presents with uterine bleeding. Endometrial biopsy shows increased density of endometrial glands relative to endometrial stroma. What is causing her condition?
She has endometrial hyperplasia as a consequence of unopposed estrogen proliferative effects that cause endometrial gland hyperplasia and overgrowth eventually causes shedding and bleeding. Post-menopause is a risk because progesterone secretion is gone due to lack of ovulation. Being fat is a risk because androgen gets converted to estrone by aromatase in the fat.
A 50 year old postmenopausal woman presents with bleeding. Gross image of her uterus is shown below. What are the two ways this type of carcinoma can arise?
Endometrial Carcinoma, note the growth from the normal smooth endometrium. This is a malignant proliferation of endometrial glands that can arise via two distinct pathways: hyperplasia (unopposed estrogen -> hyperplasia -> carcinoma) and sporadic (arises in atrophic endometrium with no evident precursor lesion).
Classic histology of endometrial carcinoma that arises via the hyperplasia pathway. What age typically gets this type of carcinoma?
Endometriod, looks like normal endometrium (more disorganized and piled up on itself with minimal stroma). 60+.
Classic histology of endometrial carcinoma that arises via the sporadic pathway. What age typically gets this type of carcinoma? What type of mutations drive proliferation?
Serous w/fibrovascular cores (also called papillary serous that may sometimes calcify, die and form psammoma bodies). 70+. p53 mutations.
A 30 year old woman presents with abnormal uterine bleeding, infertility and a pelvic mass. Gross image is shown below. What is your diagnosis?
Leiomyoma, note the multiple well-defined white whorled masses. This is a benign proliferation of smooth muscle in the myometrium related to estrogen exposure (enlarge during pregnancy and shrink during menopause).
Cells that make up the ovarian follicle? What gonadotropins control these cells?
Oocyte (bathed in estradiol during maturation), granulosa cells (FSH controlled conversion of androgen to estradiol) and theca cells (LH controlled androgen production)
What does this structure do? How might this present as a mass?
Note the yellow color sitting on top of the ovary. The cells in the corpus luteum secrete progesterone that prepares the uterus for implantation and maintains the pregnancy. It can present as a hemorrhagic luteal cysts if blood fills the cavity of the corpus luteum.
Type of ovarian tumor that most commonly arises in premenopausal women? What would you see grossly?
Benign cystadenoma. Grossly you would see a single cyst and histologically you would see a simple flat lining of epithelial cells.
What are the 5 subtypes of the ovarian germ cell tumors?
The key is to remember that the subtypes mimic tissues normally made by germ cells. Cystic teratoma w/skin, teeth, bone, hair from 2-3 embryologic layers. Embryonal carcinoma w/primitive cells. Yolk sac tumor. Dysgerminoma: mass of germ cells. Choriocarcinoma: placental tissue.
A patient presents with an ovarian mass. On biopsy you see nests of large cells with clear cytoplasm and central nuclei (shown below). Serum LDH levels are elevated. What is the diagnosis and what is the prognosis?
Dysgerminoma. This is the most common malignant her cell tumor, with the male counterpart seminoma. This has a good prognosis and responds to radiotherapy.
A 5 year old girl presents with an ovarian mass. Labs reveal elevated serum AFP. What would you likely see on histology?
Endodermal sinus tumors mimic the yolk sac and are the most common germ cell tumor in children. You would see Schiller-Duval bodies on histology (glomeruloid structure with blood vessel in the center with cells organizing around it).
A woman presents with pleural effusion, ascites and an ovarian mass. Gross biopsy of the ovarian mass is shown below. What is causing her condition?
Meigs syndrome. This is a condition associated with pleural effusion, ascites and fibroma (note the solid tumor w/white bands of fibrosis on gross specimen) of the ovary.
Most common site of ectopic pregnancy? Key risk factor?
Lumen of fallopian. Key risk factor is scarring from PID, endometriosis etc.
What would you see grossly after you deliver the placenta of a mother who had placental abruption?
Blood on the maternal surface of the placenta with clots.
What will a pregnant woman pass if she has a hydatidiform mole pregnancy with no prenatal care?
Grape-like masses pass through the vaginal canal in the early second trimester. These “grape-like” masses are large, edematous abnormal villi surrounded by syncytiotrophoblasts.
How do you classify molar pregnancies?
Complete or partial. Complete mole occurs as a result of two sperm entering an empty ovum. (46 chromosomes). Complete moles have 0 fetal tissue. Villi will be completely edematous w/complete proliferation of trophoblasts all along villous. In complete mole beta-hCG is higher because there are more syncytiotrophoblasts. The complete mole has the higher risk for choriocarcinoma (2-3%). Partial mole occurs as a result of two sperm fertilizing a normal egg (69 chromosomes). This results in presence of fetal tissue, partial villous edema, partial trophoblast proliferation and partial risk for choriocarcinoma.
What does a biopsy of a molar pregnancy look like? How do you treat it?
Massive, edematous villi with proliferation of trophoblasts. Treated with D&C, monitor beta-hCG to ensure adequate removal of the mole and screen for choriocarcinoma development for 1 year after removal.
