Female Reproductive Pathology

Question 1

Bacterial cause of amnionitis that may result in abortion, stillbirth, or neonatal sepsis

Answer 1

Listeria monocytogenes

Question 2

Cause of PID with rare complication of Fitz Hugh Curtis syndrome (violin string adhesions around diaphragm and/or liver)

Answer 2

Neisseria gonorrheae

Question 3

STIs caused by chlaymida trachomatis serovars D-K and L1-L3

Answer 3

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

Question 4

Triad of Reiters syndrome associated with chlamydia trachomatis

Answer 4

Uveitis
Urethritis
Arthritis

Question 5

Dx of tuberculous endometritis is based on identification of ____________ on biopsy

Answer 5

Plasma cells in the stroma (not seen in normal endometrium)

Question 6

Clinical manifestations of Haemophilus ducreyi

Answer 6

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)

Question 7

Clinical manifestations of Klebsiella granulomatis

Answer 7

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

Question 8

Describe diagnostic steps for treponema pallidum

Answer 8

Dark-field microscopy for direct visualization

VDRL = screening test

Fluorescent treponemal Ab absorption test (FTA-ABS) = confirmatory test

Question 9

Stages of syphilis

Answer 9

Primary syphilis — chancres (painless)

Secondary syphilis — systemic disease with maculopapular rash and condyloma lata

Tertiary syphilis — gummas, syphilitic aortitis, argyll robertson pupils

Question 10

Describe bacterial vaginosis

Answer 10

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

Question 11

Dx and clinical manifestations of HSV-2

Answer 11

Dx by Tzanck smear — used to visualize multinucleated giant cells infected with HSV

Presents with painful inguinal LAD; lies dormant in sacral ganglia

Question 12

Actions of E6 and E7 protein associated with high risk HPV

Answer 12

E6 destroys p53 tumor suppressor protein

E7 destroys RB tumor suppressor protein

Both lead to unchecked cell replication

Question 13

STI caused by HPV 6 and 11

Answer 13

Condyloma acuminata

Question 14

Poxvirus that causes flesh-colored, dome-shaped, umbilicated skin lesions that may indicate immunosuppressed state when present diffusely on an adult

Answer 14

Molluscum contagiosum

Question 15

What would you see on microscopic exam when diagnosing candida albicans via KOH mount?

Answer 15

Budding yeast and pseudohyphae

Question 16

Clinical manifestations of trichomonas vaginalis

Answer 16

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

Question 17

Compare classic VIN vs. differentiated VIN

Answer 17

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

Question 18

Which type (basaloid/warty or keratinizing) of vulvar SCC is related to high risk HPV infection, is less common, and develops from classic VIN?

Answer 18

Basaloid/warty type

Question 19

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?

Answer 19

Keratinizing type

Question 20

Clinical manifestations of extramammary paget disease (of the vulva)

Answer 20

Presents as pruritic, red, crusted, maplike area, usually on labia majora

NOT typically associated with underlying cancer, confined to the epidermis of vulvar skin

Question 21

Clinical presentation of papillary hidradenoma

Answer 21

presents as sharply circumscribed nodule, most commonly on labia majora or interlabial folds, and has tendency to ulcerate

Question 22

What is uterus didelphys?

Answer 22

Double uterus due to failure of mullerian duct fusion; may be caused by genetic syndromes or in utero exposure to DES

Question 23

______ ______ presents clinically as red, granular areas that stand out from surrounding normal pale-pink vaginal mucosa d/t residual glandular epithelium in those areas

Answer 23

Vaginal adenosis

Question 24

Vaginal adenosis is more common in women exposed to DES, some of whom go on to develop _________

Answer 24

Clear cell carcinoma

Question 25

1-2 cm fluid-filled cysts that occur in submucosal location d/t remnants of mesonephric (wolffian) ducts in the cervix or vagina

Answer 25

Gartner duct cyst

Question 26

3 types of benign vaginal tumors

Answer 26

Stromal tumors Leiomyomas Hemangiomas

Question 27

Uncommon vaginal tumor usually found in infants and kids <5; tends to grow as polypoid, rounded, bulky masses that resemble grape clusters

Answer 27

Embryonal rhabdomyosarcoma [histologically characterized by small tumor cells with oval nuclei and small protrusions of cytoplasm that may show cross striations]

Question 28

Histology of the cervix

Answer 28

Ectocervix = mature squamous epithelium Endocervix = columnar, mucus-secreting epithelium Between them = transformation zone — unique epithelial environment renders cervix highly susceptible to infections with HPV

Question 29

Histology and clinical significance of endocervical polyps

Answer 29

Histo: loose fibromyxomatous stroma covered by mucus-secreting endocervical glands, often accompanied by inflammation Main clinical significance is as source of irregular vaginal “spotting”

Question 30

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

Answer 30

Basal

Question 31

Both _____ and _____ staining are highly correlated wtih HPV infection and are useful for confirmation of the diagnosis in equivocal cases of squamous intraepithelial lesions

Answer 31

Ki-67; p16

Question 32

Grading of CIN

Answer 32

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

Question 33

Compare features of LSIL vs. HSIL

Answer 33

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

Question 34

General staging of cervical carcinoma

Answer 34

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

Question 35

Histologic changes throughout menstrual cycle including menses, proliferative phase, and secretory phase

Answer 35

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)

Question 36

Most common cause of DUB and the associated DDx

Answer 36

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

Question 37

Acute vs. chronic endometritis

Answer 37

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.

Question 38

Most common site of involvement for endometriosis

Answer 38

Ovary

Question 39

Histologic features of atypical endometriosis

Answer 39

Cytologic atypia of epithelium lining the endometriotic cyst Glandular crowding d/t excessive epithelial proliferation

Question 40

____ = presence of endometrial tissue within uterine wall (myometrium)

Answer 40

Adenomyosis

Question 41

2 types of endometrial polyps

Answer 41

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)

Question 42

______ 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)

Answer 42

PTEN [pts with Cowden syndrome who have germline mutation in PTEN have high incidence of endometrial and breast carcinoma]

Question 43

Type I vs. type II endometrial carcinoma

Answer 43

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

Question 44

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

Answer 44

Malignant mixed mullerian tumors (MMMT)

Question 45

Staging criteria for endometrial cancer

Answer 45

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

Question 46

2 types of tumors of endometrial stroma

Answer 46

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)

Question 47

Clinical presentation and morphology of leiomyoma

Answer 47

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)

Question 48

Clinical presentation and morphology of leiomyosarcomas

Answer 48

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

Question 49

Pyogenic inflammation of the fallopian tube; usually a manifestation of PID caused by gonococcus or chlamydia

Answer 49

Suppurative salpingitis

Question 50

Cysts lined by serous epithelium found near fimbriated end of fallopian tube or in the broad ligaments; presumed to arise from mullerian remnants

Answer 50

Hydatid of morgagni

Question 51

Mesothelioma which occurs subserosally on the fallopian tube or sometimes in the mesosalpinx

Answer 51

Adenomatoid tumor

Question 52

Differentiate follicle cysts from luteal cysts clinically and morphologically

Answer 52

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

Question 53

Polycystic ovarian syndrome increases the risk for _______ hyperplasia and carcinoma due to increases in free _______ levels

Answer 53

Endometrial; estrone

Question 54

3 overall types of ovarian tumors

Answer 54

Surface epithelial tumors (most common) Germ cell tumors Sex-cord stromal tumors

Question 55

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

Answer 55

Coelomic; serous; mucinous

Question 56

Compare features of benign, malignant, and borderline tumors arising from surface epithelium in ovary

Answer 56

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

Question 57

_____ mutation carriers have increased risk for serous carcinoma of the ovary and fallopian tube

Answer 57

BRCA1

Question 58

_______ 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

Answer 58

Endometrioid Brenner

Question 59

Clinical presentation and prognosis of surface epithelial cancers of the ovary

Answer 59

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”

Question 60

Useful serum marker for monitoring tx response and screening for recurrence

Answer 60

CA-125

Question 61

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?

Answer 61

``` Cystic teratoma Dysgerminoma Endodermal sinus tumor (yolk sac) Choriocarcinoma Embryonal carcinoma ```

Question 62

Features of cystic teratoma germ cell ovarian tumors

Answer 62

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)

Question 63

Cystic teratoma in ovary composed primarily of thyroid tissue, possibly manifesting as hyperthyroidism

Answer 63

Struma ovarii

Question 64

Features of dysgerminoma germ cell tumor in ovary

Answer 64

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

Question 65

Features of endodermal sinus tumor

Answer 65

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)

Question 66

Features of choriocarcinoma

Answer 66

Composed of trophoblasts and syncytiotrophoblasts (villi are absent) Small hemorrhagic tumor with early hematogenous spread High beta hCG Poor response to chemotherapy

Question 67

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?

Answer 67

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

Question 68

Features of sertoli-leydig cell tumors of the ovary

Answer 68

Sertoli cells form tubules Leydig cells contain characteristic Reinke crystals May produce androgen; associated with hirsutism or virilization Associated with DICER1 mutations

Question 69

Features of ovarian fibroma (sex cord-stromal tumor)

Answer 69

Benign tumor of fibroblasts Associated with pleural effusion and ascites (Meigs syndrome)

Question 70

A ______ tumor of the ovary consists of a mucinous carcinoma from another site, they are often bilateral

Answer 70

Kruckenberg

Question 71

Classic primary site causing a kruckenberg tumor

Answer 71

Diffuse gastric carcinoma (signet ring cells) Other primary sites include breast or colon cancer

Question 72

Condition resulting in abundent mucin in the abdomen, primary source is usually cancer of the appendix

Answer 72

Pseudomyxoma peritonei

Question 73

Type I vs type II ovarian carcinoma

Answer 73

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

Question 74

Condition in which placenta implants in lower uterine segment or cervix, often leading to serious 3rd trimester bleeding

Answer 74

Placenta previa [when complete/covering cervical os, it requires C section]

Question 75

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

Answer 75

Placenta accreta [important cause of severe life-threatening postpartum bleeding; common predisposing factors = placenta previa, hx of previous C section]

Question 76

Systemic syndrome characterized by widespread maternal endothelial dysfunction that presents during pregnancy with HTN, edema, and proteinuria

Answer 76

Preeclampsia (other complications include hypercoagulability, acute renal failure, pulmonary edema)

Question 77

10% of pts with preeclampsia develop ______

Answer 77

HELLP — hemolytic anemia, elevated liver enzymes, low platelets

Question 78

Eclampsia exhibits the features of pre-eclampsia + ________

Answer 78

Seizures (and/or coma)

Question 79

Role of placenta in pathogenesis of preeclampsia and eclampsia

Answer 79

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

Question 80

Cystic swelling of chorionic villi, accompanied by variable trophoblastic proliferation

Answer 80

Hydatidiform mole

Question 81

Features of complete hydatidiform mole

Answer 81

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

Question 82

Features of partial hydatidiform mole

Answer 82

Results from fertilization of egg with 2 sperm — karyotype 69,XXY Fetal tissue usually present Not associated with choriocarcinoma

Question 83

Features of invasive hydatidiform mole

Answer 83

Mole penetrates or perforates uterine wall/myometrium; hydropic villi may embolize Manifestations include vaginal bleeding and abnormal uterine enlargement with persistent elevation of HCG