Female Genital Tract Flashcards
Name the 5 most important infectious agents in vulvitis.
- HPV (condyloma acuminata, VIN)
- HSV
- Gonococcus (gonococcal vulvovaginitis)
- Syphilis (chancre)
- Candida
Smooth white plaques or papules that extend and coalesced. Biopsy reveals: thinning of the epidermis, disappearance of the rete pegs, hydropic degeneration of the basal cells and dermal fibrosis with scant mononuclear inflammation.
Lichen sclerosus
What causes lichen sclerosus?
Unknown.
Quite possibly autoimmune.
NOT a premalignant lesion but afflicted women have a 15% lifetime risk of developing SCCA.
Biopsy of leukoplakia reveals thickened epithelium and significant surface hyperkeratosis. There is significant leukocytic infiltration of the dermis.
Lichen simplex chronicus
In lichen simplex chronicus, this layer of the epidermis is expanded.
Stratum granulosum
Hallmarks of HPV infection
Perinuclear cytoplasmic vacuolization with nuclear angular pleomorphism and koilocytosis
T/F. HPV(+) vulvar intraepithelial neoplasialeads to poorly differentiated squamous cell CA.
True!
Well-differentiated keratinizing squamous cell CA is seen in HPV(-) individuals, with lichen sclerosus.
Red, scaly plaque in the vulva microscopically characterized by the spread of malignant cells within the epithelium, occasionally with invasion of the underlying dermis
Paget Disease of the Vulva
Red granular foci lined by mucus-secreting or ciliated columnar cells in patients whose mothers took diethylstilbestrol
Vaginal adenosis!
More frequent than vaginal clear cell adenoCA
Overgrowth of regenerating squamous epithelium blocks the orifices of the endocervical glands in the transformation zone to produce ___ lined by columnar mucus secreting epithelium
Nabothian cyst
MOST COMMON cause of cervicitis encountered in STDs
Chlamydia trachomatis
Acute nonspecific cervicitis is seen in ___ and is usually caused by ____.
Postpartum women;
Staphylococci, streptococci
The most successful cancer screening test ever developed
Pap smear
High risk HPV subtypes
16, 18, 45, 31
Low risk HPV subtypes
6, 11, 42, 44
Peak age incidence of CIN? of cervical CA?
CIN: 30 years
Cervical CA: 45 (15 yrs after CIN)
5 yr survival rates of Cervical Ca by stage
Stage 0: 100% Stage 1: 90% Stage 2: 82% Stage 3: 35% Stage 4: 10%
Generally, the diagnosis of chronic endometritis requires the presence of ___.
Plasma cells
Histologic diagnosis of endometriosis depends on finding 2 of the following three features within the lesion.
- Endometrial glands
- Endometrial stroma
- Hemosiderin pigment
Peak age incidence of CIN? of cervical CA?
CIN: 30 years
Cervical CA: 45 (15 yrs after CIN)
5 yr survival rates of Cervical Ca by stage
Stage 0: 100% Stage 1: 90% Stage 2: 82% Stage 3: 35% Stage 4: 10%
Generally, the diagnosis of chronic endometritis requires the presence of ___.
Plasma cells
Histologic diagnosis of endometriosis depends on finding 2 of the following three features within the lesion.
- Endometrial glands
- Endometrial stroma
- Hemosiderin pigment
Most accepted hypothesis for the pathophysiology of endometriosis
Regurgitation theory
Endometrial CA Quiz!
A. Endometrioid
B. Serous
- Associated with increased estrogen
- Arises from atrophic endometrium
- Perimenopausal women
- PTEN / HNPCC association
- p53 mutations
- Forms tufts or papillae
- A
- B
- A
- A
- B
- B (A produces aberrant glands)
Most probable cause of abnormal uterine bleeding in prepuberty
Precocious puberty
Second most common cancer associated with HNPCC
Endometrial CA
Cowden’s syndrome is a multiple hamartoma syndrome that carries an increased risk of carcinoma in these three organs.
BET!
Breast
Endometrium
Thyroid
Endometrial CA Quiz!
A. Endometrioid
B. Serous
- Associated with increased estrogen
- Arises from atrophic endometrium
- Perimenopausal women
- PTEN / HNPCC association
- p53 mutations
- A
- B
- A
- A
- B
Quick staging for endometrial CA:
Stage I: Confined to uterus
Stage II: Cervix
Stage III: Organs within true pelvis
Stage IV: Distant mets
Endometrioid tumor arising in the uterus and ovary. Stage?
If synchronous, signifies two separate primary neoplasms. Not necessarily Stage III endometrial disease. Has a favorable prognosis
Principal biochemical abnormality in PCOS
High androgens
High LH
Low FSH
(Androgens converted to estrone in fat; estrone exerts negative feedback on FSH secretion by pituitary.)
The surface covering epithelium of the ovary is multipotential / totipotential / pluripotential or differentiated.
Multipotential (Sex cord/stromal cells are also multipotential).
Does OCP increase or decrease the risk of ovarian CA?
Decrease
K-RAS protein is overexpressed in this subtype of ovarian tumors.
Mucinous cystadenocarcinomas
Majority of hereditary ovarian CA are due to mutations in:
BRCA genes
Most frequent of the ovarian tumors
Serous tumors
Epithelial lining of benign serous ovarian cysts
Tall columnar epithelium
How many percent of benign serous tumors are bilateral? mucinous tumors?
About 25% of benign serous tumors are bilateral. A lesser percentage - 5% - of mucinous tumors are bilateral.
What do you found in the papilla of serous tumors that you do not find in mucinous tumors?
Psammoma bodies
Implantation of mucinous tumor cells in the peritoneum with production of copious amounts of mucin. This is mostly caused by?
Pseudomyxoma peritonei.
Metastasis from the GI tract (appendix)
Three types of mucinous tumors. Which is typically associated with an endometriotic cyst?
3 is associated with an endometriotic cyst.
- Endocervical
- Intestinal
- Mullerian mucinous cystadenoma
How is the ovary different from the testes in terms of the types of tumors that arise from the organ?
In the testis, epithelial tumors are rare. Benign cystic teratomas are never seen and malignant GCTs are most common.
In the ovaries, surface epithelial cells are most common, followed by GCTs, and then sex cord-stromal tumors.
More than 90% of GCTs arising in the neoplasms are ___
Benign mature cystic teratomas
Solid gray mass in the ovary. Histology reveals anaplastic tumor cells, cords, glands, dispersed through fibrous background. Cells may be “signet ring” mucin secreting.
Metastases to the ovary
(Usual primaries are GI tract, breast and lung.)
No such thing as primary signet ring ovarian CA!
Unilateral ovarian tumor appears small, gray to yellow, and solid. Recaps development of testis with tubules. Many are masculinizing.
Sertoli-Leydig cell tumor
Unilateral, tiny or large, gray to yellow ovarian mass with cystic spaces. Composed of a mixture of (1) cuboidal cells in cords, sheets, or strands and (2) spindled or plump lipid-laden cells
Granulosa-theca cell tumor
1 - describes granulosa cells
2 - described theca cells
Ovarian tumors which may elaborate large amounts of estrogen
Granulosa-theca cell tumor
Ovarian tumors which microscopically exhibit solid gray fibrous cells to yellow plump cells
Thecoma-fibroma
(Yellow lipid laden cells are theca cells.)
Hormonally INACTIVE
Unilateral ovarian tumor. Histology reveals sheets or cords of large cleared cells separated by scant fibrous strands.
Dysgerminoma
All malignant! 80% cure with RT
Unilateral ovarian tumor; often small and hemorrhagic. Cytotrophoblasts and syncytiotrophoblasts present.
Choriocarcioma
Choriocarcinoma arising primarily from the ovary is peculiar because ___
It is resistant to chemo!
Ovarian tumor; composed entirely of mature thyroid tissue that may even cause hyperthyroidism
Struma ovarii
Dermoid cysts are commonly unilateral found on which side.
Right!
Immature teratomas of the ovary with ___ differentiation are aggressive and metastasize widely.
Neuroepithelial differentiation
CA-125 is useful as a screening test for ovarian CA in this population.
Asymptomatic postmenopausal women
Most commonly, placental infections arise by which route of infection. What are common etiologic agents?
Ascending infections by mycoplasma, Candida, and vaginal flora bacteria.
Hematogenous infection of the placenta is suggested by this histologic finding.
Villitis (villi are most commonly affected.)
Causes: syphilis, TB, TORCH
Mole Quiz!
A. Complete mole
B. Partial mole
- 69,XXY
- Circumferential trophoblast proliferation
- Absent atypia
- Greater elevation of hCG
- 2% risk of choriocarcinoma
- (+) fetal parts
- Some villous edema
- B (46,XX or 46,XY in A)
- A (focal in B)
- B
- A
- A (Rare in B)
- B
- B
How many % of complete moles are invasive?
10%
T/F. Invasive moles do NOT metastasize.
TRUE!
Although it is locally invasive, it does not have the aggressive metastatic potential of a choriocarcinoma.
Hydropic villi, however, may embolize to distant organs, but this is NOT true metastasis.
How many % of choriocarcinomas arise from complete H-moles? abortions? normal pregnancy?
Complete H-moles: 50%
Abortions: 25%
Normal pregnancy: 25%
What is the histologic hallmark of choriocarcinomas that differentiates it from H moles and invasive moles?
Absence of chorionic villi!
It is purely epithelial composed of anaplastic cuboidal cytotrophoblasts and syncytiotrophoblasts.
Most often sites of metastasis in choriocarcinomas
Lung (50%)
Vagina (30 - 40%)
Brain, liver, kidneys
Chemotherapy for placental chorioCA is exquisitely sensitive to chemo but those that arise in the gonads have a poor response. Why?
Presence of paternal antigens on placental chorioCa but NOT on gonadal lesions. Maternal immune response against paternal antigens helps.
Cell of origin of placental site trophoblastic tumors
Intermediate trophoblasts.
Does not secrete as much hCG. A large lesion with low levels of hCG.
Response to therapy of placental site trophoblastic tumors
Indolent; favorable outcome if confined to endomyometrium. But NOT as sensitive to chemo; prognosis poor with spread beyond the uterus
Underlying mechanism in all cases of preeclampsia syndromes
Inadequate maternal blood flow to the placenta due to inadequate development of spiral arteries
Why do pre-eclamptic patients have high BP?
Placental hypoperfusion leads to decreased placental production of vasodilators (prostacyclin, NO, prostaglandin E2), which oppose RAAS.
Why are pre-eclamptic patients at high risk of developing DIC?
The ischemic placenta secretes tissue factor and thromboxane.
What are the placental changes noted in patients with pre-eclampsia/eclampsia?
- Infarcts more numerous
- Retroplacental hemorrhage (15%)
- Premature aging (villous edema, hypovascularity)
- Atherosis in spiral arteries
Most common cause of breast “lumps”
Fibrocystic change
T/F. Oral contraceptives increase incidence of fibrocystic changes in the breast.
False. It decreases incidence.
Breast cyst lined by large polygonal cells with abundant granular, eosinophilic cytoplasm with round deeply chromatic nuclei. Benign or malignant?
Benign.
This is apocrine metaplasia.
Hyperplasia that cytologically resemble lobular carcinoma in situ, but do not fill >50% of the acini within a lobule
Atypical lobular hyperplasia
Breast lesion with a hard, rubbery consistency. Histology reveals proliferation of lining epithelial cells and myoepithelial cells in small ducts and ductules, yielding masses of small gland patterns within a fibrous stroma.
Sclerosing adenosis
Sclerosing adenosis may be difficult to distinguish from a ____. What histologic characteristic distinguishes sclerosing adenosis?
Invasive scirrhous carcinoma.
Presence of double layers of epithelium and myoepithelial elements suggest benign disease.
Atypical hyperplasia of ductular or lobular epithelium is associated with ____ increased risk of developing CA. With a (+) family history, this risk increases to ___.
5x. With family history, 10x
Characteristics of Strep vs Staph infection of the breast
Staph: single or multiple abscesses; heals with residual induration
Strep: generalized spread causing pain, swelling and breast tenderness; heals without residual induration
Female presents with breast mass, reports a history of antecedent trauma to the breast.
Traumatic fat necrosis
Indurated breast with retraction of the nipple in a woman who has borne children. Cross section reveals dilated ropelike ducts from which thick, cheesy secretions can be extruded.
Mammary duct ectasia
Giant fibroadenoma exceeds ____ cm in diameter.
10 cm
Breast mass biopsy reveals proliferation of intralobular stroma surrounding and distorting the associated epithelium. The border is sharply delimited from the surrounding tissue.
Fibroadenoma
Biopsy of a large breast mass reveals leaf-like clefts and slits. Treatment?
Phyllodes tumor.
Excision
Gene expression subtypes in breast CA A. Luminal A (ER/PR+) B. Luminal B (ER/PR/HER2+) C. HER2+ D. Basal like (Triple negative)
- Most common
- Best prognosis
- Worst prognosis
- A
- A
- C
How does one differentiate papillary carcinoma from intraductal papilloma?
Papillary CA appear as multiple lesions, often lacks myoepithelial component, show cytologic atypia or monotonous ductal epithelium.
Overexpression of this proto-oncogene in cases of breast CA confers a poor prognosis.
HER-2-NEU
EGF-receptor family
5 intrinsic subtypes of breast based on gene expression
Luminal A - ER/PR(+), HER2(-)
Luminal B - ER/PR(+), HER2(+)
HER2+/ER(-)
Basal-like - Triple negative (ER/PR/HER2 (-))
Which breast is more commonly affected?
Left breast (slightly)
DCIS (A) or LCIS (B)
- Breast mass, pain, calcifications
- 60 - 90% multicentricity
- Higher incidence of bilaterality
- Presents in the older age group (54-58)
- A
- B
- B
- A (44-47 in B)
This subtype of DVIS is characterized by cells with high-grade nuclei distending spaces with extensive central necrosis; subtype MOST FREQUENTLY detected as calcifications
Comedo subtype
Treatment for DCIS
Surgery and radiation
Tamoxifen may decrease recurrence.
DCIS (A) or LCIS (B)
- Mass, pain, calcifications
- 60 - 90% multicentricity
- Higher incidence of bilaterality
- Presents in the older age group (54-58)
- A
- B
- B
- A (44-47 in B)
Extension of DCIS up to the lactiferous duct. Clinically appears as unilateral crusting exudate over nipple and areolar skin
Paget disease of the nipple
Monomorphic with bland, round nuclei and occur in loosely cohesive clusters in ducts and lobules
LCIS
How many percent of patients with LCIS will subsequently develop invasive CA
1/3
How many percent of invasive ductal CA are:
a. ER/PR (+)
b. HER2/NEU (+)
a. 2/3
b. 1/3
Identify the breast CA type.
Poorly differentiated, diffusely invading breast parenchyma. Blockage of dermal lymphatics create clinical picture.
Inflammatory breast CA
Identify the breast CA type.
Rarely present as palpable masses; but rather present as irregular mammographic densities. What is the prognosis?
Tubular CA
Excellent prognosis! All express hormone receptors.
Identify the breast CA type.
Present as well-circumscribed, soft and gelatinous mass. Tumor cells with abundant quantities of extracellular mucin
Colloid (aka mucinous) CA
Identify the breast CA type.
Well-circumscribed mass; consists of sheets of large anaplastic cells. There is a pronounced lymphoplasmacytic infiltrate
Medullary CA
Identify the breast CA type.
Cells invade individually into stroma aligned in strands or chains (“indian filing.”)
More frequently metastasize; more likely to be multicentric and bilateral
Invasive lobular CA
Identify the breast CA type.
Which type uniformly lacks hormone receptor and do NOT overexpress HER2/NEU?
Medullary CA
5-yr survival of breast CA
Stage 0: 92% Stage 1: 87% Stage 2: 75% Stage 3: 46% Stage 4: 13%
Most important cause of hyperestrinisim that causes gynecomastria
Cirrhosis of the liver