Female Reproductive Pathology Flashcards
Bacterial cause of amnionitis that may result in abortion, stillbirth, or neonatal sepsis
Listeria monocytogenes
Cause of PID with rare complication of Fitz Hugh Curtis syndrome (violin string adhesions around diaphragm and/or liver)
Neisseria gonorrheae
STIs caused by chlaymida trachomatis serovars D-K and L1-L3
D-K = often present with watery vaginal or urethral discharge, may lead to PID, may be transmitted vertically causing conjunctivitis or PNA
L1-L3 = lymphogranuloma venereum — painful inguinal lymphadenopathy
Triad of Reiters syndrome associated with chlamydia trachomatis
Uveitis
Urethritis
Arthritis
Dx of tuberculous endometritis is based on identification of ____________ on biopsy
Plasma cells in the stroma (not seen in normal endometrium)
Clinical manifestations of Haemophilus ducreyi
Chancroid (soft chancre) — acute ulcerative STI most common in tropical and subtropical areas among lower SES groups
In females, most lesions occur in the vagina or periurethral area 4-7 days after inoculation as tender erythematous papule. Over several days, the surface of the primary lesion erodes to produce an irregular, painful ulcer (distinguish from primary chancre of syphilis because it is not indurated and multiple lesions may be present)
Clinical manifestations of Klebsiella granulomatis
Granuloma inguinale — begins as raised papular lesion on the moist stratified squamous epithelium of genitalia. Lesion eventually ulcerates and develops abundant granulation tissue, which manifests grossly as a protruberant, soft, painless mass. As the lesion enlarges, its borders become raised and indurated.
Untreated cases are characterized by extensive scarring, often associated with lymphatic obstruction and lymphedema of external genitalia, sometimes with associated strictures
Describe diagnostic steps for treponema pallidum
Dark-field microscopy for direct visualization
VDRL = screening test
Fluorescent treponemal Ab absorption test (FTA-ABS) = confirmatory test
Stages of syphilis
Primary syphilis — chancres (painless)
Secondary syphilis — systemic disease with maculopapular rash and condyloma lata
Tertiary syphilis — gummas, syphilitic aortitis, argyll robertson pupils
Describe bacterial vaginosis
Caused by gardnerella vaginalis
May present with thin, grey-white “fishy” smelling vaginal discharge with pH >4.5
Dx by the whiff test (KOH prep) or wet mount prep showing clue cells
Dx and clinical manifestations of HSV-2
Dx by Tzanck smear — used to visualize multinucleated giant cells infected with HSV
Presents with painful inguinal LAD; lies dormant in sacral ganglia
Actions of E6 and E7 protein associated with high risk HPV
E6 destroys p53 tumor suppressor protein
E7 destroys RB tumor suppressor protein
Both lead to unchecked cell replication
STI caused by HPV 6 and 11
Condyloma acuminata
Poxvirus that causes flesh-colored, dome-shaped, umbilicated skin lesions that may indicate immunosuppressed state when present diffusely on an adult
Molluscum contagiosum
What would you see on microscopic exam when diagnosing candida albicans via KOH mount?
Budding yeast and pseudohyphae
Clinical manifestations of trichomonas vaginalis
Cervicitis with “strawberry cervix” appearance
Symptoms may include genital burning, itching, and malodorous vaginal discharge that is frothy and yellow-green, usually pH >4.5
Dx based on motile organisms seen on wet mount with characteristic trophozoite shape
Compare classic VIN vs. differentiated VIN
Classic VIN = precursor lesion for basaloid/warty type of vulvar SCC — characterized as epidermal thickening, nuclear atypia, increased mitoses, and lack of cell maturation
Differentiated VIN = precursor lesion for keratinizing type of vulvar SCC — characterized by marked atypia of the basal layer and normal appearing differentiation of more superficial layers
Which type (basaloid/warty or keratinizing) of vulvar SCC is related to high risk HPV infection, is less common, and develops from classic VIN?
Basaloid/warty type
Which type (basaloid/warty or keratinizing) of vulvar SCC is unrelated to HPV, but is more common and usually results d/t long-standing lichen sclerosus or squamous cell hyperplasia, and may be associated with high frequency of TP53 mutations?
Keratinizing type
Clinical manifestations of extramammary paget disease (of the vulva)
Presents as pruritic, red, crusted, maplike area, usually on labia majora
NOT typically associated with underlying cancer, confined to the epidermis of vulvar skin
Clinical presentation of papillary hidradenoma
presents as sharply circumscribed nodule, most commonly on labia majora or interlabial folds, and has tendency to ulcerate
What is uterus didelphys?
Double uterus due to failure of mullerian duct fusion; may be caused by genetic syndromes or in utero exposure to DES
______ ______ presents clinically as red, granular areas that stand out from surrounding normal pale-pink vaginal mucosa d/t residual glandular epithelium in those areas
Vaginal adenosis
Vaginal adenosis is more common in women exposed to DES, some of whom go on to develop _________
Clear cell carcinoma
1-2 cm fluid-filled cysts that occur in submucosal location d/t remnants of mesonephric (wolffian) ducts in the cervix or vagina
Gartner duct cyst
3 types of benign vaginal tumors
Stromal tumors
Leiomyomas
Hemangiomas
Uncommon vaginal tumor usually found in infants and kids <5; tends to grow as polypoid, rounded, bulky masses that resemble grape clusters
Embryonal rhabdomyosarcoma [histologically characterized by small tumor cells with oval nuclei and small protrusions of cytoplasm that may show cross striations]
Histology of the cervix
Ectocervix = mature squamous epithelium
Endocervix = columnar, mucus-secreting epithelium
Between them = transformation zone — unique epithelial environment renders cervix highly susceptible to infections with HPV
Histology and clinical significance of endocervical polyps
Histo: loose fibromyxomatous stroma covered by mucus-secreting endocervical glands, often accompanied by inflammation
Main clinical significance is as source of irregular vaginal “spotting”
HPV infects the immature ____ cells of the squamous epithelium in areas of tissue breaks or immature metaplastic squamous cells present at the squamocolumnar junction. It matures in MATURE squamous cells
Basal
Both _____ and _____ staining are highly correlated wtih HPV infection and are useful for confirmation of the diagnosis in equivocal cases of squamous intraepithelial lesions
Ki-67; p16
Grading of CIN
CIN I = mild dysplasia
CIN II = moderate dysplasia
CIN III = severe dysplasia
CIN I has been renamed LSIL, while CIN II and III have been combined and are called HSIL
Compare features of LSIL vs. HSIL
LSIL reflects a productive HPV infection with high viral replication but only mild growth alterations of cells. If the immature squamous cells are confined to the lower 1/3 of the epithelium, the lesion is graded as LSIL. Only a small percentage progress to HSIL.
HSIL reflects a progressive deregulation of cell cycle by HPV but lower viral replication; All are considered high risk for progression to carcinoma
General staging of cervical carcinoma
Stage 0 = carcinoma in situ (CIN III/HSIL)
Stage I = carcinoma confined to cervix
Stage II = carcinoma extends beyond cervix but not to pelvic wall; involves vagina but not the lower 1/3
Stage III = carcinoma has extended to pelvic wall with no cancer-free space between; tumor involves lower 1/3 of vagina
Stage IV = carcinoma has extended beyond true pelvis or has involved mucosa of the bladder or rectum; also includes metastatic dissemination
Histologic changes throughout menstrual cycle including menses, proliferative phase, and secretory phase
Menses: superficial (functionalis) layer of endomedtrium is shed
Proliferative: rapid growth of glands and stroma arising from endometrium basalis; numerous mitotic figures. Glands appear as straight tubular structures lined by regular tall pseudostratified columnar cells. Stroma consists of spindle cells with scant cytoplasm
Secretory: appearance of secretory vacuoles beneath nuclei in glandular epithelium, by week 4 the glands become tortuous and serrated (“sawtooth”). The late secretory phase is characterized by stromal changes including prominent spiral arterioles, stromal cell hypertrophy, eosinophilia, sparse infiltrate of lymphocytes and neutrophils (normal in this scenario)
Most common cause of DUB and the associated DDx
Anovulation
Endocrine disorders: thyroid disease, adrenal disease, pituitary tumors
Ovarian lesions: functioning ovarian tumor (granulosa cell tumor), polycystic ovaries
Generalized metabolic dz: obesity, malnutrition, other chronic systemic dz
Acute vs. chronic endometritis
Acute: uncommon and limited to bacterial infection arising after delivery or miscarriage, usually d/t retained products of conception. Inflammatory response is limited to stroma
Chronic: occurs in association with PID, retained gestational tissue, IUDs, or TB. May present with abnormal bleeding, pain, discharge, and/or infertility. Histology reveals plasma cells in stroma.
Most common site of involvement for endometriosis
Ovary
Histologic features of atypical endometriosis
Cytologic atypia of epithelium lining the endometriotic cyst
Glandular crowding d/t excessive epithelial proliferation
____ = presence of endometrial tissue within uterine wall (myometrium)
Adenomyosis
2 types of endometrial polyps
Hyperplastic polyps — arise in association with generalized endometrial hyperplasia and are responsive to estrogen (seen with tamoxifen use)
Atrophic polyps — postmenopausal women (likely represent atrophic remnants of previously hyperplastic polyps)
______ inactivation is present in 20% of cases of endometrial hyperplasia. Its inactivation may stimulate estrogen-dependent gene expression leading to overgrowth of cells dependent upon estrogen (endometrium, mammary tissue)
PTEN
[pts with Cowden syndrome who have germline mutation in PTEN have high incidence of endometrial and breast carcinoma]
Type I vs. type II endometrial carcinoma
Type I: mean age 55-65, occurs in the setting of unopposed estrogen, obesity, HTN, DM; Has precursor lesion of hyperplasia and endometrioid morphology; runs more indolent course
Type II: mean age 65-75, occurs in the setting of atrophy and thin physique, has serous endometrial intraepithelial lesion as precursor and serous clear cell morphology; runs more aggressive course
Endometrial adenocarcinomas with malignant mesenchymal component, of which the vast majority are carcinosarcomas; morphologically bulky, polypoid, with elements of adenocarcinoma and sarcoma. occur in postmenopausal women and present with bleeding
Malignant mixed mullerian tumors (MMMT)
Staging criteria for endometrial cancer
Stage I = carcinoma is confined to body of uterus
Stage II = carcinoma involves uterus and cervix
Stage III = carcinoma extends outside uterus but not outside true pelvis
Stage IV = carcinoma extends outside the true pelvis or involves the mucosa of the bladder or rectum
2 types of tumors of endometrial stroma
Adenosarcomas — most commonly present as broad based endometrial polypoid growths but may prolapse through os; Dx based on malignant appearing stroma which coexists with benign endometrial glands. Estrogen-sensitive.
Stromal tumors — benign stromal nodules and endometrial stromal sarcomas (can be subdivided in to low grade [characterized by JAZF1-SUZ12 fusion] or high grade)
Clinical presentation and morphology of leiomyoma
May be asymptomatic or present with abnormal bleeding, urinary frequency, sudden pain d/t infarct of large pedunculated tumor, and impaired fertility. In pregnancy, there is increased risk of spontaneous abortion, fetal malpresentation, uterine inertia, and postpartum hemorrhage
Morphology: sharply circumscribed, discrete, round, firm, gray-white tumors that vary in size; found in myometrium of corpus. Characteristic whorled pattern of smooth muscle bundles with low mitotic index (distinguishes them from leiomyosarcomas)
Clinical presentation and morphology of leiomyosarcomas
Occur both before and after menopause, with peak incidence of 40-60y. Often recur, and metastasize hematogenously or via abdominal cavity. Typically arise de novo, not from leiomyomas
Morphology: grow in 2 patterns: bulky fleshy masses that invade uterine wall OR polypoid masses that project into uterine lumen. Display nuclear atypia, higher mitotic index, and zonal necrosis
Pyogenic inflammation of the fallopian tube; usually a manifestation of PID caused by gonococcus or chlamydia
Suppurative salpingitis
Cysts lined by serous epithelium found near fimbriated end of fallopian tube or in the broad ligaments; presumed to arise from mullerian remnants
Hydatid of morgagni
Mesothelioma which occurs subserosally on the fallopian tube or sometimes in the mesosalpinx
Adenomatoid tumor
Differentiate follicle cysts from luteal cysts clinically and morphologically
Follicle cysts — common, may be associated with increased estrogen production and endometrial abnormalities. Usually multiple, filled with serous fluid, and lined by gray glistening membrane, granulosa cells, and theca cells.
Luteal cysts — present in normal ovaries of women of reproductive age. Lined by bright yellow tissue containing luteinized granulosa cells; occasionally rupture and cause a peritoneal reaction
Polycystic ovarian syndrome increases the risk for _______ hyperplasia and carcinoma due to increases in free _______ levels
Endometrial; estrone
3 overall types of ovarian tumors
Surface epithelial tumors (most common)
Germ cell tumors
Sex-cord stromal tumors
Surface epithelial tumors are derived from _____ epithelium that lines the ovary. The 2 most common subtypes are ______ and ______ — both are usually cystic, and can be further categorized as benign, malignant, or borderline
Coelomic; serous; mucinous
Compare features of benign, malignant, and borderline tumors arising from surface epithelium in ovary
Benign = cystadenoma — compoased of single cyst with simple, flat lining. Most commonly arises in premenopausal women (age 30-40)
Malignant = cystadenocarcinoma — composed of complex cysts with thick, shaggy lining. Most commonly arises in postmenopausal women (age 60-70)
Borderline = features between benign and malignant. Better prognosis than malignant but still carry metastatic potential
_____ mutation carriers have increased risk for serous carcinoma of the ovary and fallopian tube
BRCA1
_______ is a type of surface epithelium ovarian tumor that is usually malignant and may be associated with endometriosis and a similar tumor located in the endometrium
______ is a type of surface epithelium ovarian tumor that usually contains urothelium
Endometrioid
Brenner
Clinical presentation and prognosis of surface epithelial cancers of the ovary
Typically present LATE with vague abdominal symptoms (pain, fullness) and/or signs of compression (i.e., urinary frequency)
Since they present late, they have poor prognosis; tend to spread locally, especially to peritoneum — may see omental “caking”
Useful serum marker for monitoring tx response and screening for recurrence
CA-125
Germ cell ovarian tumors are the second most common type, usually occurring in women of reproductive age. Tumor subtypes mimic tissues normally produced by germ cells. What are the 5 primary types of germ cell ovarian tumors?
Cystic teratoma Dysgerminoma Endodermal sinus tumor (yolk sac) Choriocarcinoma Embryonal carcinoma
Features of cystic teratoma germ cell ovarian tumors
Cystic tumor composed of fetal tissue derived from 2-3 embryologic layers
Most common germ cell tumor in females
Bilateral in 10% of cases
Usually benign. Malignant potential is indicated by presence of immature tissue (usually neuroectoderm) or somatic malignancy (usually SCC in skin contained in tumor)
Cystic teratoma in ovary composed primarily of thyroid tissue, possibly manifesting as hyperthyroidism
Struma ovarii
Features of dysgerminoma germ cell tumor in ovary
Composed of large cells with clear cytoplasm and central nuclei
Most common malignant germ cell tumor
Good prognosis; responds to radiotherapy
Serum LDH may be elevated
Features of endodermal sinus tumor
Malignant tumor that mimics the yolk sac; most common germ cell tumor in children
Serum alpha-fetoprotein is often elevated
Schillar duvall bodies seen on histology (glomeruloid appearance)
Features of choriocarcinoma
Composed of trophoblasts and syncytiotrophoblasts (villi are absent)
Small hemorrhagic tumor with early hematogenous spread
High beta hCG
Poor response to chemotherapy
3 types of sex cord-stromal tumors are granulosa-theca cell tumors, sertoli-leydig cell tumors, and fibromas.
What are features of granulosa-theca cell tumors?
Neoplasm of granulosa and theca cells
Often produces estrogen; elevated tissue and serum levels of inhibin; FOXL2 mutations
Presents with signs of estrogen excess (sx vary with age)
Associated with call-exner bodies
Features of sertoli-leydig cell tumors of the ovary
Sertoli cells form tubules
Leydig cells contain characteristic Reinke crystals
May produce androgen; associated with hirsutism or virilization
Associated with DICER1 mutations
Features of ovarian fibroma (sex cord-stromal tumor)
Benign tumor of fibroblasts
Associated with pleural effusion and ascites (Meigs syndrome)
A ______ tumor of the ovary consists of a mucinous carcinoma from another site, they are often bilateral
Kruckenberg
Classic primary site causing a kruckenberg tumor
Diffuse gastric carcinoma (signet ring cells)
Other primary sites include breast or colon cancer
Condition resulting in abundent mucin in the abdomen, primary source is usually cancer of the appendix
Pseudomyxoma peritonei
Type I vs type II ovarian carcinoma
Type I = low-grade tumors arise in association with borderline tumors or endometriosis
Type II = high-grade serous carcinomas that arise from serous intraepithelial carcinoma
Condition in which placenta implants in lower uterine segment or cervix, often leading to serious 3rd trimester bleeding
Placenta previa [when complete/covering cervical os, it requires C section]
Condition caused by partial or complete absence of decidua, such that placental villous tissue adheres directly to the myometrium —> failure of placental separation at birth
Placenta accreta
[important cause of severe life-threatening postpartum bleeding; common predisposing factors = placenta previa, hx of previous C section]
Systemic syndrome characterized by widespread maternal endothelial dysfunction that presents during pregnancy with HTN, edema, and proteinuria
Preeclampsia (other complications include hypercoagulability, acute renal failure, pulmonary edema)
10% of pts with preeclampsia develop ______
HELLP — hemolytic anemia, elevated liver enzymes, low platelets
Eclampsia exhibits the features of pre-eclampsia + ________
Seizures (and/or coma)
Role of placenta in pathogenesis of preeclampsia and eclampsia
Abnormal placental vasculature sets placenta up for ischemia
Endothelial dysfunction and imbalance of angiogenic and anti-angiogenic factors results in inadequate placental vascularization, vasoconstriction, HTN, and hypoperfusion (roles of sFlt1 and endoglin)
Coagulation abnormalities include hypercoagulability d/t inadequate production of PGI2
Cystic swelling of chorionic villi, accompanied by variable trophoblastic proliferation
Hydatidiform mole
Features of complete hydatidiform mole
Results from fertilization of egg that lost its female chromosomes — karyotype 46,XX
No fetal tissue present
Increased risk of choriocarcinoma
HCG greatly exceeds that of a normal pregnancy
Features of partial hydatidiform mole
Results from fertilization of egg with 2 sperm — karyotype 69,XXY
Fetal tissue usually present
Not associated with choriocarcinoma
Features of invasive hydatidiform mole
Mole penetrates or perforates uterine wall/myometrium; hydropic villi may embolize
Manifestations include vaginal bleeding and abnormal uterine enlargement with persistent elevation of HCG
