Female GU, Breast, & Gestation Flashcards
Condyloma = warty neoplasm of vulvar skin, often large. Most commonly due to HPV types ___ or ____ and characterized by _______ change. These rarely progress to carcinoma
6; 11; koilocytic
Thinning of epidermis and fibrosis of dermis characterized by leukoplakia with parchment-like vulvar skin; most commonly seen in postmenopausal women
Lichen sclerosis
Lichen sclerosis of the vulva is benign, but associated with slightly increased risk of _______
SCC
Hyperplasia of vulvar squamous epithelium characterized by leukoplakia with thick, leathery vulvar skin; associated with chronic irritation and scratching
Lichen simplex chronicus
T/F: Lichen simplex chronicus is associated with increased risk for SCC
False — lichen simplex chronicus is benign and there is NO increased risk of SCC
Vulvar cancer arises from the squamous epithelium of the vulva and is relatively rare. It presents as leukoplakia, so biopsy may be required to distinguish carcinoma from other causes of this lesion. What are the 2 pathways by which this type of cancer can develop?
HPV-related — types 16, 18, 31, 33 —> Vulvar intraepithelial neoplasia (VIN) [can occur at younger ages]
Non-HPV-related — long-standing lichen sclerosis [typically older age >70]
Disease characterized by malignant epithelial cells in the epidermis of the vulva presenting as erythematous, pruritic, ulcerated skin that represents carcinoma in situ, usually with no underlying carcinoma
Extramammary Paget Disease
[Contrast with Paget disease of the breast which typically represents underlying carcinoma]
Extramammary paget disease of the vulva must be distinguished from melanoma. What cellular markers allow this differentiation?
Paget cells: PAS+, keratin+, and S100-
Melanoma: PAS-, keratin-, S100+
Focal persistence of columnar epithelium in the upper vagina
Adenosis
Adenosis is focal persistence of the columnar epithelium in the upper vagina. There is increased incidence of this condition in females exposed to ______ in utero
DES
[Diethylstilbesterol — also causes increased risk of breast cancer in mom]
Rare complication of DES-associated vaginal adenosis characterized by malignant proliferation of glands with clear cytoplasm (discovery of this and other complications led to cessation of DES usage)
Clear cell adenocarcinoma
Rare, malignant mesenchymal proliferation of immature skeletal muscle presenting as bleeding and grape-like mass protruding from vagina or penis of child, usually <5 yrs of age
Embryonal rhabdomyosarcoma
[aka sarcoma botryoides]
Key cell of rhabdomyosarcoma is rhabdomyoblast, which is characterized by cytoplasmic cross-striations and stains positive for _____ and ______ on immunohistochemistry
Desmin; myogenin
Vaginal carcinoma arises from squamous epithelium lining the vaginal mucosa and is usually related to high-risk HPV. The precursor lesion is vaginal intraepithelial neoplasia (VAIN).
This type of carcinoma spreads to regional LNs depending on location. Cancer from the lower 1/3 of the vagina goes to the _____ nodes, while cancer from the upper 2/3 goes to the _______ nodes
Inguinal; regional iliac
The cervix is divided into the exocervix and endocervix, what is the difference in their epithelial lining?
Exocervix = squamous epithelium
Endocervix = columnar epithelium
[division between the two is the transformation zone]
HPV is a sexually transmitted DNA virus that infects the lower genital tract, especially the cervix in the transformation zone. Persistent infection leads to risk for CIN. High risk HPV factors E6 and E7 increase destruction of _____ and _____, respectively
p53; Rb
CIN is characterized by ________ change, nuclear atypia, and increased mitotic activity. It is divided into grades based on extent of immature, dysplastic cells. CIN progresses stepwise from I to II to III to carcinoma in situ to invasive carcinoma. This is not inevitable, as up to _______ still has some potential for regression/reversibility.
Koilocytic; CIN III
[Note that carcinoma in-situ has lost potential for reversibility]
Cervical carcinoma is an invasive carcinoma that arises from cervical epithelium, most commonly seen in middle-aged women (age 40-50) and presents as vaginal bleeding. What are some key risk factors for cervical carcinoma?
Key risk factor = HIGH RISK HPV!
Secondary risk factors include SMOKING and IMMUNODEFICIENCY
What are the most common subtypes of cervical carcinoma?
Squamous cell carcinoma
Adenocarcinoma
[note that BOTH types are related to HPV]
Advanced cervical cancer often invades through what?
Often invades through anterior uterine wall into bladder
[presents as hydronephrosis and post-renal failure — common cause of death in late cervical cancer!]
An abnormal pap smear is followed by confirmatory _____ and ______
Colposcopy; biopsy
2 major limitations of pap smear
Inadequate sampling of transformation zone resulting in false negative screening
Limited efficacy in screening for adenocarcinoma
Quadrivalent vaccine against HPV cover which 4 subtypes?
6, 11, 16, 18
The endometrium is hormonally sensitive and growth is ______ driven. Preparation of the endometrium for implantation is ______-driven. Shedding occurs with loss of _______ support
Estrogen; progesterone; progesterone
Secondary amenorrhea due to loss of basalis (regenerative layer) and scarring; often the result of overaggressive dilation and curettage (D and C)
Asherman syndrome
[loss of basalis = loss of stem cells, can regenerate endometrium]
Anovulatory cycle is a lack of ovulation. This results in estrogen-driven proliferative phase without progesterone-driven _______ phase. This is a common cause of dysfunctional uterine bleeding, especially during menarche and menopause
Secretory
Bacterial infection of endometrium usually due to retained products of conception; presents as fever, abnormal uterine bleeding, and pelvic pain
Acute endometritis
Chronic endometritis is chronic inflammation of the endometrium characterized by _____ cells (these cells are required to classify as chronic!!). Common causes include retained products of conception, chronic PID, IUD, and TB. This presents as abnormal uterine bleeding, pelvic pain, and infertility
Plasma
Endometrial polyps are hyperplastic protrusions of endometrium which present as abnormal uterine bleeding. These can arise as a side effect of the drug _____
Tamoxifen
[tamoxifen is antiestrogenic on breast, but weakly pro-estrogenic on endometrium]
Endometriosis = endometrial _____ and ______ outside the uterine endometrial lining; presents as dysmenorrhea and pelvic pain and may cause infertility
Glands; stroma
Common sites of involvement of endometriosis
Ovary — chocolate cyst
Uterine ligaments — pelvic pain
Pouch of douglas — pain with defecation
Bladder wall — pain with urination
Bowel serosa — abdominal pain and adhesions
Fallopian tube mucosa — scarring (increased risk of infertility and ectopic pregnancy)
_______ = Endometrial glands and stroma within the uterine myometrium
Adenomyosis
T/F: there is increased risk of carcinoma at the site of endometriosis
True! — especially the ovary
Endometrial hyperplasia = hyperplasia of endometrial _____ relative to the _____. This is often a consequence of unopposed _______ and presents as postmenopausal uterine bleeding
Glands; stroma; estrogen
Endometrial hyperplasia is classified histologically, based on architectural growth and cellular atypia. What is the most important predictor for progression to carcinoma in this condition?
Cellular atypia
Endometrial carcinoma is a malignant proliferation of endometrial glands that typically presents as postmenopausal bleeding. This arises via what 2 distinct pathways?
Pathologic hyperplasia d/t unopposed estrogen —> endometrioid carcinoma [resembles normal endometrium, average age is 60 yrs]
Sporadic — cancer results from atrophic endometrium (no evident precursor lesion) —> papillary serous carcinoma [typically occurs in the elderly; driven by p53 mutations, psammoma bodies present]
Benign proliferation of smooth muscle arising from myometrium related to estrogen exposure; presents as multiple, well-defined white whorled masses [grow during pregnancy, shrink during menopause]
Leiomyoma
[important that there are multiple, because distinguishes from leiomyosarcoma which would be single lesion. White whorled masses are also benign features, because malignant would show necrosis, hemorrhage, etc.]
Leiomyomas are usually asymptomatic, however what are some ways in which pts may present?
Abnormal uterine bleeding
Infertility
Pelvic mass
Malignant proliferation of smooth muscle arising from the myometrium. This tumor arises de novo, usually in postmenopausal women. Commonly appears as single lesion with necrosis and hemorrhage, mitotic activity, and cellular atypia
Leiomyosarcoma
The functional unit of the ovary is the follicle, which consists of an _____ surrounded by ______ and ______ cells
Oocyte; granulosa; theca
After ovulation, the residual follicle becomes the _____ _____, which primarily secretes ________. This prepares the endometrium for maintenance of a possible pregnancy
Corpus luteum; progesterone
[hemorrhage into corpus luteum can result in hemorrhagic luteal cyst]
Degeneration of follicles results in follicular cysts. Multiple follicular cysts results in polycystic ovarian syndrome, which is an issue of hormone imbalance. PCOS is characterized by increased ____ and low ______
LH; FSH
[LH:FSH ratio > 2]
The classic presentation of PCOS is an obese young woman with infertility, oligomenorrhea, and hirsutism. Some patients have insulin resistance as well. Pts with high circulating _____ levels are at an increased risk for endometrial carcinoma
Estrone
The ovary is composed of what 3 cell types?
Surface epithelium
Germ cells
Sex-cord stroma
[tumor can arise from any of these cell types or from metastasis]
What is the most common type of ovarian tumor?
Surface epithelial tumors
Surface epithelial tumors of the ovary are derived from coelomic epithelium that lines the ovary. The 2 most common subtypes of surface epithelial tumors are _____ and _____, both are usually cystic
Serous; mucinous
Benign tumors (cystadenoma) are composed of a single cyst with simple, flat lining and most commonly arise in premenopausal women (30-40 y/o).
How does the benign form differ from a malignant cystadenocarcinoma?
Malignant cystadenocarcinomas are composed of complex cysts with THICK SHAGGY lining and most commonly arise in POST-menopausal women (60-70 y/o)
______ mutation carriers have increased risk for serous carcinoma of the ovary and fallopian tube
BRCA1
Type of surface tumor of the ovary that is usually malignant, may be associated with endometriosis, and 15% will have separate carcinoma of uterine lining as well
Endometrioid carcinoma
Type of surface tumor of the ovary that usually contains urothelium
Brenner tumor
Surface tumors of the ovary usually present _____, thus leading to a _____ prognosis
Late; poor
[Surface tumors present late with vague abdominal symptoms like pain or fullness as well as possible signs of compression like urinary frequency]
Epithelial surface tumors of the ovary tend to spread locally, especially to the _______
Peritoneum
[presents as omental ‘caking’]
2nd most common ovarian tumor (15% of cases) usually occurring in women of reproductive age
Germ cell tumors
[tumor subtypes mimic tissues normally produced by germ cells]
Germ cell cystic tumor composed of fetal tissue derived from 2-3 embryologic layers and is the most common germ cell tumor in females; bilateral in 10% of cases
Cystic teratoma
T/F: cystic teratomas are benign
True — however, presence of immature tissue or somatic malignancy indicates malignant protential
Most common type of immature tissue in cystic teratomas indicating malignant potential
Neural ectoderm
Most common somatic malignancy arising in cystic teratoma indicating malignant potential
Squamous cell carcinoma of the skin
Cystic teratoma composed primarily of thyroid tissue
Struma ovarii
[presents as hyperthyroidism]
Most common malignant germ cell tumor; composed of large cells with clear cytoplasm and central nuclei. Its testicular counterpart is a seminoma
Dysgerminoma
Dysgerminomas have a good prognosis as they respond to radiotherapy. What lab value may be elevated in dysgerminoma?
Serum LDH
Most common germ cell tumor in children; classified as malignant tumor that mimics yolk sac
Endodermal sinus tumor
Endodermal sinus tumors are malignant tumors that mimic the yolk sac. Serum ____ is often elevated and __________ are characteristic findings on histology
AFP; Schiller-Duvall bodies
[Schiller-Duvall bodies are “glomeruloid-like” bodies]
Germ cell tumor composed of trophoblasts and syncytiotrophoblasts (villi are absent); described as small, hemorrhagic tumor with early hematogenous spread and beta-hCG is characteristically high
Choriocarcinoma
T/F: the germ cell variant of choriocarcinoma responds well to chemotherapy
False — the germ cell variant of choriocarcinoma has a poor response to chemotherapy
[Note: Choriocarcinoma may also arise as a complication of gestation (i.e., molar pregnancy, spontaneous abortion, normal pregnancy) — in THAT case it DOES respond well to chemotherapy]
Germ cell tumor composed of large primitive cells that is aggressive with early metastasis
Embryonal carcinoma
Sex-cord stromal tumors resemble sex cord-stroma tissues of the ovary. Which type of sex cord stromal tumor often produces estrogen and presents with signs of estrogen excess (sxs vary with age)?
Granulosa-theca cell tumor
[in a young child - precocious puberty, in a middle aged woman - DUB, in an older woman - postmenopausal bleeding]
Sex-cord stromal tumor of the ovary that may produce androgen and is associated with hirsutism and virilization
Sertoli-leydig cell tumor
In sertoli-leydig cell tumors of the ovary, the sertoli cells form _____ while the leydig cells contain characteristic _____ _____
Tubules; Reinke crystals
Fibromas are sex cord stromal tumors that are a benign tumor of fibroblasts. These are associated with ________ syndrome, which is characterized by accompanying symptoms of _______ and ________
Meigs; pleural effusion; ascites
Classic example of mucinous tumor that metastasizes to both ovaries, typically from diffuse subtype of gastric carcinoma (signet ring cells) but can also come from other sites (lobular breast carcinoma, colon, etc)
Kruckenberg tumor
[if mucinous tumor only involves 1 ovary — it is most likely a primary mucinous surface epithelial tumor; if bilateral — it is more likely kruckenberg tumor]
Classic example of mucinous metastasis to the ovary from appendix
Pseudomyxoma peritonei
Spontaneous abortions are most commonly due to what?
Chromosomal anomalies
[other causes include hypercoagulable state, congenital infection, and exposure to teratogens]
Implantation of placenta in lower uterine segment in which placenta overlies cervical os; presents as third trimester bleeding
Placenta previa
[requires C section to avoid compression of baby’s blood source during delivery]
Separation of placenta from decidua prior to delivery of fetus; common cause of stillbirth that presents with 3rd trimester bleeding and fetal insufficiency
Placental abruption
Improper implantation of placenta into myometrium with little or no intervening decidua; presents with difficult delivery of the placenta with postpartum bleeding. Often requires hysterectomy
Placenta accreta
Abnormality of maternal-fetal vascular interface in placenta leading to pregnancy-induced HTN, proteinuria, and edema arising in 3rd trimester
Preeclampsia
[seen in 5% of pregancies, high blood pressure results in fibrinoid necrosis in vessels of placenta]
Eclampsia is defined as preeclampsia with _______
Seizures
Features of HELLP syndrome
Preeclampsia with thrombotic microangiopathy involving the liver
Hemolysis, Elevated Liver enzymes, Low Platelets
Sudden infant death syndrome is defined as death of a healthy infant between 1 month to 1 year of age. Infants usually expire during sleep. What are the 3 major risk factors?
Sleeping on stomach
Smoking in household
Prematurity
Abnormal conception characterized by swollen and edematous villi with proliferation of trophoblasts; uterus expands as if normal pregnancy is present
Hydatidiform mole
[uterus is larger than expected for gestational age; beta hCG will be higher than expected for gestational age]
Hydatidiform mole classically presents in 2nd trimester in the absence of prenatal care with what finding?
Passage of grape-like masses through vaginal canal
Genetics, fetal tissue present/absent, villous edema, trophoblastic proliferation, and risk for choriocarcinoma associated with partial mole
Genetics: normal ovum fertilized by 2 sperm (or one sperm that duplicates chromosomes); 69 chromosomes
Fetal tissue present
Villous edema: some are hydropic, some are normal
Focal trophoblastic proliferation present around hydropic villi
Minimal risk for choriocarcinoma
Genetics, fetal tissue present/absent, villous edema, trophoblastic proliferation, and risk for choriocarcinoma associated with complete mole
Genetics: empty ovum fertilized by 2 sperm (or one sperm that duplicates chromosomes); 46 chromosomes
Fetal tissue absent
Most villi are hydropic
Diffuse, circumfirential trophoblastic proliferation
2-3% risk for choriocarcinoma
The treatment for molar pregnancy is ________ while monitoring ______ to ensure adequate mole removal and to screen for development of choriocarcinoma
D and C; beta hCG
Functional unit of the breast
Terminal duct-lobular unit (TDLU)
[lobules make milk that drains via ducts to nipple]
The lobules and ducts of the breast tissue are lined by what 2 layers of epithelium?
Luminal cell layer
Myoepithelial cell layer
The breast tissue is hormone sensitive. Development occurs after menarche and breast tenderness occurs during the menstrual cycle. Breast tissue undergoes _____ during pregnancy, and ______ after menopause. The highest density of breast tissue occurs at the _____ quadrant
Hyperplasia; atrophy; upper-outer
Acute mastitis is a bacterial infection of the breast that is usually due to ________; it is associated with breast feeding. Clinically presents as warm, erythematous breast with purulent nipple discharge. Treatment involves continued drainage (continue breastfeeding) and antibiotics — typically ________
S.aureus; dicloxacillin
[note that this can also be complicated by abscess]
The ducts of the breast are lined by ________ epithelium that is dependent on vitamin _____; a deficiency in this vitamin can lead to metaplasia into squamous epithelium and subsequent periductal mastitis
Columnar; vitamin A
Clinical presentation of subareolar mass with nipple retraction in a smoker; biopsy shows inflammation of subareolar ducts
Periductal mastitis
Inflammation with dilation (ectasia) of subareolar ducts resulting in periareolar mass with green-brown nipple discharge; rare condition that classically arises in multiparous postmenopausal women
Mammary duct ectasia
Biopsy shows chronic inflammation with PLASMA cells
The breast tissue may undergo fat necrosis which is usually related to trauma. It presents as a mass on exam or _________ on mammography.
Biopsy shows necrotic fat with associated _______ and _____ cells
Calcification
Calcifications; giant cells
Fibrocystic changes are the most common change in premenopausal breast tissue. They present as ‘lumpy’ breast, usually in upper outer quadrant. Cysts have a blue-domed appearance on gross exam. This is BENIGN, and may include fibrosis, cysts, and ______ metaplasia
Apocrine
[note that in this case, the apocrine metaplasia is not considered a precursor to malignancy like metaplasia in other areas of the body]
Fibrocystic changes of the breast are benign as long as they only contain fibrosis, cysts, and apocrine metaplasia. What findings on biopsy of fibrocystic lesions would indicate increased risk of invasive carcinoma?
Ductal hyperplasia and sclerosing adenosis (classically associated with calcification) = 2x increased risk
Atypical hyperplasia = 5x increased risk
T/F: if a biopsy in the right breast reveals worrisome features for invasive carcinoma, there is an increase in risk in the right breast only
False — the risk would apply to both breasts
Intraductal papilloma is a papillary growth, usually into a large duct, consisting of fibrovascular projections lined by epithelial and myoepithelial cells. How does this present?
Bloody nipple discharge in premenopausal woman
[must distinguish from papillary carcinoma. Intraductal papilloma is lined by the normal 2 layers of cells. Papillary carcinoma is more common in postmenopausal woman and myoepithelial cells would be ABSENT]
Most common benign neoplasm of breast; presents as well-circumscribed, mobile marble-like mass
Fibroadenoma — tumor of fibrous tissue and glands
Fibroadenomas are ______-sensitive, but also considered benign and at no increased risk for carcinoma
Estrogen
Fibroadenoma-like tumor with overgrowth of fibrous component resulting in ‘leaf-like’ projections; most commonly seen in POSTMENOPAUSAL women and CAN BE MALIGNANT
Phyllodes tumor
How does breast cancer rank in terms of incidence and mortality in women?
Most common carcinoma in women by incidence
2nd most common cause of cancer mortality
Risk factors for breast cancer are mostly related to estrogen exposure. This includes female gender, age, ______ menarche and/or _____ menopause, obesity, prior biopsy showing atypical hyperplasia, and a first-degree relative with breast cancer (sister, mother, daughter)
Early/late
DCIS is a malignant proliferation of cells in ducts of the TDLU with no invasion of the basement membrane. These are detected as ________ on mammography (it does not usually produce a mass). The ______ type has high-grade cells with necrosis and dystrophic calcification in the center of the ducts
Calcification; Comedo
[keep in mind other things that show up as calcification on mammography are fat necrosis and sclerosing adenosis]
DCIS that extends up ducts of skin of nipple, presenting as nipple ulceration and erythema and almost always associated with an underlying carcinoma
Paget disease
Most common type of invasive carcinoma of the breast
Invasive ductal carcinoma
[classically forms duct-like stsructures; presents as a MASS detected by PE or mammography (PE can detect mass at 2+ cm, while mammography can detect mass at 1+cm). Advanced tummors may result in dimpling of skin or retraction of nipple]
Invasive ductal carcinoma has what appearance on biopsy?
Duct-like structures in desmoplastic stroma
4 subtypes of invasive ductal carcinoma and their px
Tubular carcinoma — very good px
Mucinous carcinoma — very good px
Medullary carcinoma
Inflammatory carcinoma — poor px (already has access to lymphatics)
Subtype of invasive ductal carcinoma characterized by tubular structures with desmoplastic stroma and absence of myoepithelial cell
Tubular carcinoma
Subtype of invasive ductal carcinoma with excellent prognosis, particularly seen in elderly women, and characterized by malignant cells floating in pools of mucous
Mucinous carcinoma
Subtype of invasive ductal carcinoma with poor prognosis characterized by erythema and swelling of the breast that does not improve with a course of antibiotics; biopsy shows cancer in dermal lymphatics
Inflammatory carcinoma
[Requires clinical dx of INFLAMMATION and pathologic dx of cancer obstructing DERMAL LYMPHATICS]
Subtype of invasive ductal carcinoma characterized by high grade malignant cells on background of inflammatory cells, particularly lymphocytes and plasma cells
Medullary carcinoma
Which of the following subtypes of invasive ductal carcinoma arises with higher incidence in association with BRCA1 mutations?
A. Tubular carcinoma
B. Mucinous carcinoma
C. Medullary carcinoma
D. Inflammatory carcinoma
C. Medullary carcinoma
______ is a malignant proliferation of cells in breast lobules with NO invasion of the basement membrane. It is discovered incidentally; does NOT produce mass or calcification. It is characterized by discohesive cells lacking _______; they are often multifocal and bilateral
LCIS; E-cadherin
Treatment for LCIS includes _____ and close follow-up, since this cancer carries a low risk of progression to invasive carcinoma
Tamoxifen
Breast cancer that grows in single-file pattern, and exhibits no duct formation due to lack of E-cadherin
Invasive lobular carcinoma
Prognosis of breast cancer is based on TNM staging. Metastasis is the most important factor for determining prognosis. However, what is the most USEFUL factor for determine px?
Spread to axillary LNs
[Sentinel node biopsy is used to assess axillary LNs]
Predictive factors are utilized in breast cancer to predict the response to treatment. What are the most important factors, and how do they help with treatment strategy?
Most important factors = ER, PR, and HER2/neu gene amplification
ER and PR — responds to antiestrogenic agents (tamoxifen)
HER2/neu amplification — responds to trastuzumab (binds a portion of HER2 and prevents activation of a transmembrane tyrosine kinase)
[HER2/neu is a growth factor receptor (protooncogene) that when activated becomes an oncogene]
Triple-negative breast cancer means that it is negative for ER, PR, and HER2/neu. This type of cancer has a _____ prognosis, and in terms of demographics is more common in ___________
Poor; African american women
Hereditary breast cancer affects 10% of women with breast cancer. What are some features suggesting hereditary cause?
Multiple first degree relatives with breast cancer
Tumor at premenopausal age
Multiple tumors
The most important single genes regarding increased risk of breast cancer are BRCA1 and BRCA2. Which of these genes is associated with breast carcinoma in males?
BRCA2
Which BRCA gene is associated with breast and ovarian/fallopian tube cancer?
BRCA1
Male breast cancer is rare, but can occur. It usually presents as a subareolar mass under the nipple in older males. It may also produce nipple discharge. In terms of type of breast cancer, it is usually __________.
Male breast cancer is more common in the setting of _____mutation, as well as _______ syndrome
Invasive ductal carcinoma
BRCA2; Klinefelter
