Female Reproductive System

Vulva Disorders
Non-neoplastic disorders
- Leukoplakia
o Opaque, white, epithelial plaque-like thickening produce pruritus and scaling (white patch)
- Bartholin cyst and abscess:
o Bartholin cyst Sac contains at least 1ml of fluid and has epithelial lining
 Duct cysts obstruction of duct by inflammation
 Lining is transitional or squamous epithelium
o Bartholin gland abscess polymicrobial infection (Most often caused by Neisseria gonorrhoeae)
o Ex. A 25-year-old woman has experienced discomfort during sexual intercourse for the past month. On physical examination, there are no lesions of
the external genitalia. Pelvic examination shows a focal area of swelling on the left posterolateral inner labium that is very tender on palpation. A 3-cm
cystic lesion filled with purulent exudate is excised. In which of the following structures is this lesion most likely to develop? Bartholin gland
- Lichen sclerosus et atrophicus (Benign but Premalignant)
o Epidermal thinning
 Lichen band-like lymphocyte infiltrates
 Sclerosus hardening due to scarring of fibrosis (collagen fibers)
 Atrophicus decrease in size
o Porcelain, parchment or pale skin
o Increased risk of Squamous cell carcinoma
o Ex. A 53-year-old postmenopausal woman is concerned about pale areas on her labia that have been slowly enlarging for the past year. The areas
cause discomfort and become easily irritated. Physical examination shows pale gray to parchment- like areas of skin that involve most of the labia
majora, labia minora, and introitus. The introitus is narrowed. A biopsy specimen is taken and microscopically shows thinning of the squamous
epithelium, a dense band of upper dermal hyaline collagen, and scattered upper dermal mononuclear inflammatory cells. What is the most likely
diagnosis? Lichen sclerosus et atrophicus
- Lichen simplex chronicus (Benign)
o Squamous cell hyperplasia (hyperplastic dystrophy)
o From rubbing or scratching of skin to relieve pruritus
o Ex. A 40-year-old woman has noted pruritic patches on her vulva for the past 4 months. On physical examination there are multiple 1.5- to 3-cm white,
scaly plaques on the vulva. A biopsy of one lesion is taken, and on microscopic examination, it shows epidermal thickening with hyperkeratosis and
intense dermal inflammation. Mitoses are seen in keratinocytes, but they exhibit no atypia. What is the most likely diagnosis? Squamous cell
hyperplasia
- Condyloma acuminatum (Benign)
o Genital warts by HBV (6,11)
o Papillary exophytic stroma covered by thick squamous epithelium
o Koilocytic atypia, Acanthosis, hyperkeratosis & parakeratosis
o Ex. A 36-year-old sexually active woman has noticed that warty vulvar lesions have been increasing in size and number over the past 5 years. On
physical examination, there are multiple 0.5- to 2-cm, red-pink, flattened lesions with rough surfaces present on the vulva and perineum. Which of the
following infectious agents is most likely to produce these lesions? HPV
Pre-malignant lesions and Neoplasms (tumors)
- Papillary Hidradenoma (benign)
o tumor of apocrine sweat gland, presents as a painful nodule on the labia majora or interlabial folds
o Confused clinically with carcinoma because of its tendency to ulcerate
- Vulvar Intraepithelial Neoplasia (VIN)
o Classic Vin HPV (16,18,31.33)
 Discrete white or raised, pigmented lesion
 Warty, basaloid and mixed subtypes of Squamous cell carcinoma
 Basaloid vulvar carcinoma: (HPV positive), composed of small, immature (basaloid) cells with an area of central necrosis
 Warty vulvar carcinoma: superficial (exophytic) portion resembles a Condyloma while the deep (endophytic) portion is
characterized by invasive, and usually well differentiated squamous cell carcinoma
 Epidermal thickening, lack of maturation with full thickness nuclear atypia, high mitoses
 Ex. A 57-year-old woman recently noticed a pale area of discoloration on the labia. Pelvic examination shows the presence of a 0.7-cm flat,
white area on the right labia majora. A biopsy specimen is obtained and on microscopic examination shows dysplastic cells that occupy half
the thickness of the squamous epithelium, with minimal underlying chronic inflammation. In situ hybridization shows human
papillomavirus type 16 DNA in the epithelial cells. What is the most likely diagnosis? Vulvar Intraepithelial Neoplasia
o Differentiated VIN Long standing Lichen sclerosis
 Squamous carcinoma (keratinizing type)
 Differentiated vulvar intraepithelial neoplasia (HPV negative) - maturation of the superficial layers, hyperkeratosis, and basal cell
atypia, in-situ lesion; no invasion
o Extramammary Paget Disease of the Vulva
 Pruritic, red, crusted, map-like area (rash), usually on the labia majora
 Typically, NOT associated with underlying cancer, confined to the epidermis
 Paget cells Larger than keratinocytes, seen singly or in small clusters within the epidermis
 Pale cytoplasm containing mucin
 Express cytokeratin 7, EMA, CEA
 Ex. A 52-year-old woman has noted increasing size of a red, pruritic lesion on her left labium over the past 7 months. On physical
examination, this rough, scaly lesion is 0.4 Å~ 0.9 cm. The perineum appears normal; there is no lymphadenopathy, and there are no rectal
lesions. A Pap smear shows no abnormal findings. The lesion is excised and on microscopic examination shows large atypical cells lying
singly or in small clusters within the epidermis. These cells have abundant cytoplasm that stains with periodic acid–Schiff (PAS). What is the
most likely diagnosis? Extramammary Paget Disease
o Malignant Melanoma
 Occurs on the vulva must be differentiated from lentigo simplex
 Positive for S-100 protein & HMB-45, Does not stain with PAS
Vagina Disorder
- Rokitansky-Küster-Hauser (RKH) syndrome
o Anatomic cause of primary amenorrhea
o Congenital absence of the upper part of the Vagina and uterus are underdeveloped or absent
- Gartner duct cysts (benign)
o Cysts of the lateral wall of the vagina due to the persistence of a mesonephric (Wolffian duct remnant)
- Squamous cell carcinoma
o Arises from a premalignant lesion, vaginal intraepithelial neoplasia (VaIN), associated with HPV
o Mostly upper part of vagina, posterior wall at junction with ectocervix and spreads to regional iliac nodes (lesions in lower 1/3rds metastasize to the
inguinal nodes)
- Vaginal adenosis
o During embryonal development, the vagina is initially covered by columnar, endocervical-type epithelium, which is normally replaced by squamous
epithelium advancing upwards from the urogenital sinus
o Small patches of residual embryonic endocervical-type glandular epithelium may persist into adult life
o Seen in 35% to 90% of women exposed to Di-Ethyl Stilboestrol (DES) in utero
o Clear cell carcinoma arising in DES related adenosis in teenagers and young adult women (1970s and 1980s)
o DES inhibits normal differentiation of paramesonephric structures
o Ex. An 18-year-old sexually active woman has had dyspareunia followed by vaginal bleeding for the past month. On pelvic examination, a red, friable,
2.5-cm nodular mass is seen on the anterior wall of the upper third of the vagina. The microscopic appearance of a biopsy specimen is shown in the
figure. Which of the following conditions is likely to have contributed most to the origin of this neoplasm? Diethylstilbestrol (DES) exposure
- Embryonal Rhabdomyosarcoma, Sarcoma botryoides
o Infants and children < 5 years of age
o polypoid, rounded, bulky masses with appearance and consistency of grapelike clusters
o Malignant embryonal rhabdomyoblasts
 Small cells with oval nuclei, small protrusions of cytoplasm from one end (tennis racket)
 Striations (indicative of muscle differentiation) may be seen within the cytoplasm
 Beneath vaginal epithelium, tumor cells are crowded in a so-called “cambium layer”
 Stain positive for Desmin, MyoD1, Smooth Muscle Actin, Muscle Specific Actin
o Tend to invade locally and cause death by penetration into the peritoneal cavity or by obstruction of the urinary tract
o Ex. A 4-year-old girl is brought to the physician by her parents, who noticed bloodstained underwear and “something” protruding from her external
genitalia. On physical examination, there are polypoid, grapelike masses projecting from the vagina. Histologic examination of a biopsy specimen from
the lesion shows small, round tumor cells, some of which have eosinophilic straplike cytoplasm. Immunohistochemical staining shows desmin,
vimentin, and myogenin in these cells. What is the most likely diagnosis? Sarcoma botryoides

Cervix Disorders
- Endocervical Polyp
o Composed of a dense fibrous stroma covered with endocervical columnar epithelium
o Non-neoplastic polyp, arises within the endocervical canal
o Loose fibromyxomatous stroma covered by mucus-secreting endocervical glands
o Irregular vaginal “spotting” or bleeding can arouse suspicion of malignancy
o Simple curettage or surgical excision is curative
- High-risk HPVs (16,18)
o Infect immature basal cells, areas of epithelial breaks, or immature metaplastic squamous cells at squamo-columnar junction
o Viral replication occurs in maturing squamous cells
o Viral DNA is integrated into the host genome
o E6 inhibits p53, up-regulates the expression of telomerase
o E7 inhibits RB, p21, p27
- Cervical Intraepithelial Neoplasia CIN (Squamous Intraepithelial Lesions)
o Occurs commonly at the squamocolumnar junction (transformation zone)
o Peak incidence is 35 years of age
o Risk factors
 Early age of onset of sexual intercourse
 Multiple, high-risk partners
 High-risk types of HPV in a biopsy
 Smoking, oral contraceptive pills, immunodeficiency
o Morphology
 Nuclear atypia, perinuclear cytoplasmic “halos”, Koilocytic atypia
o LSIL (Low grade Squamous Intraepithelial Lesion)
 immature cells confined to the lower 1/3rd of epithelium
 Ki-67 and p16 staining
 CIN I Most cases regress spontaneously; only a small percentage progress to HSIL
 Ex. A healthy 30-year-old woman comes to the physician for a routine health maintenance examination. No abnormalities are found on
physical examination. A screening Pap smear shows cells consistent with a low-grade squamous intraepithelial lesion (LSIL). Subsequent
cervical biopsy specimens confirm the presence of cervical intraepithelial neoplasia (CIN) I. Which of the following risk factors is most likely
related to her Pap smear findings? Multiple sexual partners
o HSIL (High grade Squamous Intraepithelial Lesion)
 High risk for progression to carcinoma
 immature cells in upper 2/3rds of epithelium
 CIN II moderate dysplasia
 CIN III severe dysplasia
 Ex. A 42-year-old woman has a Pap smear as part of a routine health maintenance examination. There are no remarkable findings on
physical examination. The Pap smear shows cells consistent with a high-grade squamous intraepithelial lesion (HSIL) with human
papillomavirus type 18. Cervical biopsy specimens are obtained, and microscopic examination confirms the presence of extensive
moderate dysplasia (CIN II) along with intense chronic inflammation with squamous metaplasia in the endocervical canal. What is the most
likely explanation for proceeding with cervical conization for this patient? Risk for invasive carcinoma
  Ex. A 28-year-old sexually active woman comes to her physician’s assistant for a routine health maintenance examination. There are no
abnormal findings on physical examination. She has been taking oral contraceptives for the past 10 years. A Pap smear shows a high-grade
squamous epithelial lesion (HSIL), also termed moderate dysplasia, or cervical intraepithelial neoplasia (CIN) II. What is the most likely
molecular pathogenesis for this finding? Viral inactivation of the RB1 gene product
 Ex. A 34-year-old woman has a routine Pap smear for the first time. The results indicate that dysplastic cells are present, consistent with a
high-grade squamous intraepithelial lesion (HSIL), also called cervical intraepithelial neoplasia (CIN) III. She is referred to a gynecologist,
who performs colposcopy and takes multiple cervical biopsy specimens that all show CIN III. Conization of the cervix shows a focus of
microinvasion at the squamocolumnar junction. Based on these findings, what is the next most likely step in treating this patient? No
further therapy
 Microinvasive squamous cell carcinomas of the cervix are stage I lesions that have a survival rate similar to that of in situ lesions.
Such minimal invasiveness does not warrant more aggressive therapies. The likelihood of metastasis or recurrence is minimal.
o Carcinoma in situ (CIS) has not gone beyond basement membrane
o Invasive squamous cell carcinoma broke through basement membrane and spreads to the surrounding tissues
 A 45-year-old woman has had a small amount of vaginal bleeding and a brownish, foul-smelling discharge for the past month. On pelvic
examination, there is a 3-cm lesion on the ectocervix, shown in the figure. Microscopic examination of the lesion is most likely to show
which of the following? Squamous cell carcinoma
o Carcinoma cervix
 3rd MC cancer in women worldwide
 mortality reduced due to pap smear and colposcopy
 Squamous cell carcinoma
 Post-renal azotemia leading to renal failure is a common cause of death
 Adenocarcinoma
 Proliferation of glands composed of malignant endocervical cells
 Large, hyperchromatic nuclei
 Relatively mucin-depleted cytoplasm
 Early invasive cancers (micro-invasive) – cervical cone excision alone
 Invasive cancers - hysterectomy with lymph node dissection
 Advanced lesions - radiation and chemotherapy
 5-year survival rate
o 100% for micro-invasive carcinomas
o < 50% for tumors extending beyond pelvis
 Ex. A 62-year-old childless woman noticed a blood-tinged vaginal discharge twice during the past month. Her last menstrual
period was 10 years ago. Bimanual pelvic examination shows that the uterus is normal in size, with no palpable adnexal masses.
There are no cervical erosions or masses. Her body mass index is 33. Her medical history indicates that for the past 30 years she
has had hypertension and type 2 diabetes mellitus. An endometrial biopsy specimen is most likely to show which of the
following? Adenocarcinoma

Uterus disorders
- Dysmenorrhea painful menses
o Primary type
 Only in ovulatory cycles, due to ↑ prostaglandin F2α
o Secondary type, associated with other disorders
 Endometriosis (most common cause)
 Adenomyosis
 Leiomyomas, cervical stenosis
- Functional Endometrial disorders (dysfunctional uterine bleeding)
o Anovulation (failure to ovulate)
 Excessive endometrial stimulation by estrogens, unopposed by progesterone
 Hormonal disturbances (menarche/postmenopausal period)
 Abnormal uterine bleeding with no anatomic cause
 Ex. A 13-year-old girl began menstruation 1 year ago. She now has abnormal uterine bleeding, with menstrual periods that are 2 to 7 days
long and 2 to 6 weeks apart. The amount of bleeding varies from minimal spotting to a very heavy flow. On physical examination, there are
no remarkable findings. A pelvic ultrasound scan shows no abnormalities. Which of the following is most likely to produce these findings?
Anovulatory cycles
o Endometrial biopsy
 Lacks progesterone-dependent morphologic features (pseudostratified glands with no secretory activity and absence of stromal
predecidual change)
 Shows stromal condensation and eosinophilic epithelial metaplasia similar to menstrual endometrium
 Ex. A 69-year-old woman has passed blood per vagina for a month. On pelvic examination no abnormal findings are noted. Which of the
following diagnostic procedures should be performed next? Endometrial biopsy
- Inadequate Luteal Phase (Ovulatory DUB)
o Presents as infertility with either increased bleeding OR amenorrhea
o Inadequate progesterone production during the post-ovulatory period
- Endometritis
o Inflammation of epithelial lining in the uterus
 Acute Endometritis caused by bacterial infections after delivery or miscarriage (retained products of conception) and is promptly cleared
by removal of the retained fragments + antibiotic therapy
 Ex. A 41-year-old G5, P5 woman has noticed lower abdominal pain with fever for the past 2 days. She delivered a normal term
infant 1 week ago. On examination, she has a temperature of 37.4 degrees C. There is a foul-smelling vaginal discharge. Which
of the following pathologic findings is she most likely to have? Endometrial neutrophilic infiltrates
 Chronic Endometritis caused by PID, retained gestational tissue (postpartum/postabortion), intrauterine devices (actinomycosis)
 Plasma cells in stroma
 Severe dysmenorrhea, Dyspareunia (pain with intercourse), pelvic pain, pain on defecation, dysuria, infertility
- Endometrial Polyps
o Maybe associated with tamoxifen
o Polyp stroma is neoplastic, and the associated glands are reactive
o Rarely, adenocarcinomas arise within endometrial polyps
o Ex. A 52-year-old perimenopausal woman has had vaginal bleeding for a week. She has no medical problems and takes no medications. Hysteroscopy
is performed and there is a single, 2-cm, smooth, soft mass protruding into the endometrial cavity. Biopsies are taken. What is microscopic
examination of this lesion most likely to show? Endometrial glands resembling stratum basalis
- Endometrial Hyperplasia
o Important cause of abnormal bleeding
o Precursor to endometrial carcinoma
o Increased gland-to-stroma ratio
o Associated with prolonged estrogenic stimulation of the endometrium (too much estrogen)
 Obesity (peripheral conversion of androgens to estrogens)
 Early menarche or late menopause, nulliparity
 Polycystic ovarian syndrome
 Ex. A 21-year-old woman experienced menarche at age 14 years and had regular menstrual cycles for the next 3 years. For the
past year, she has had oligomenorrhea and has developedbhirsutism. She has noticed a 10-kg weight gain in the past 4 months.
On pelvic examination, there are no vaginal or cervical lesions, the uterus is normal in size, and the adnexa are prominent. A
pelvic ultrasound scan shows that each ovary is twice normal size, whereas the uterus is normal in size. Magnetic resonance
imaging is shown in the figure. Which of the following conditions is most likely to be present in this woman? Polycystic ovarian
syndrome
o Inactivation of the PTEN tumor suppressor gene
o Morphology
 Non-atypical hyperplasia
 Some intervening stroma is usually retained Rarely progress to adenocarcinoma
 Atypical hyperplasia (Endometrial Intraepithelial Neoplasia)
 Complex proliferating glands with nuclear atypia, back-to-back arrangement
 Ex. A 40-year-old nulliparous woman has had menorrhagia for the past 6 months. On physical examination, her blood pressure
is 154/93 mm Hg, there are no cervical lesions or adnexal masses, and the uterus is normal in size. She is 155 cm (5 feet 1 inch)
tall and weighs 74.5 kg (body mass index 38). A Pap smear shows atypical glandular cells of uncertain significance. Hemoglobin
A1c concentration is 9.8%. Endometrial biopsy shows complex hyperplasia with atypia; molecular analysis detects loss of PTEN
gene heterozygosity and enhanced AKT phosphorylation. Which of the following metabolic pathways is most likely to be
activated in this tumor? Increased aerobic glycolysis
o Ex. A 49-year-old perimenopausal woman has had menometrorrhagia for the past 3 months. On physical examination, there are no remarkable
findings. The microscopic appearance of an endometrial biopsy specimen is shown in the figure. The patient undergoes a dilation and curettage, and
the bleeding stops, with no further problems. What condition is most likely to produce these findings? Repeated failure of ovulation
o Ex. A 42-year-old woman has had menometrorrhagia for the past 2 months. She has no history of prior irregular menstrual bleeding, and she has not
yet reached menopause. On physical examination, there are no vaginal or cervical lesions, and the uterus appears normal in size, but there is a right
adnexal mass. An abdominal ultrasound scan shows the presence of a 7-cm solid right adnexal mass. Endometrial biopsy shows hyperplastic
endometrium, but no cellular atypia. What is the most likely lesion that underlies her menstrual abnormalities? Granulosa-theca cell tumor
 The mass is probably producing estrogen, which has led to endometrial hyperplasia. Estrogen-producing tumors of the ovary are typically
sex cord tumors, such as a granulosa-theca cell tumor or a thecoma-fibroma, the former more often being functional.
o Ex. A 62-year-old obese, nulliparous woman has an episode of vaginal bleeding, which produces only 5 mL of blood. On pelvic examination, there is no
enlargement of the uterus, and the cervix appears normal. A Pap smear shows cells consistent with adenocarcinoma. Which of the following
preexisting conditions is most likely to have contributed to the development of this malignancy? Endometrial hyperplasia
o Ex. A 52-year-old woman has had dull pain in the lower abdomen for the past 6 months and minimal vaginal bleeding on three occasions. Her last
menstrual period was 2 years ago. Pelvic examination shows a right adnexal mass, and the uterus appears normal in size. An abdominal ultrasound
scan shows an 8-cm solid mass, a small amount of ascites, and a right pleural effusion. A total abdominal hysterectomy is performed, and the mass is
determined to be an ovarian fibrothecoma. Which of the following additional lesions is most likely to be found in the excised specimen? Endometrial
Hyperplasia
- Adenomyosis
o presence of endometrial glands in the myometrium
o Ex. A 36-year-old woman has had menorrhagia and pelvic pain for six months. She had a normal, uncomplicated pregnancy 10 years ago but has failed
to conceive since then. She has been sexually active with one partner for the past 20 years and has had no dyspareunia. On pelvic examination she has
a symmetrically enlarged uterus, with no apparent nodularity or palpable mass. A serum pregnancy test result is negative. What is the most likely
diagnosis? Adenomyosis
- Endometriosis
o Presence of “ectopic” endometrial tissue at a site outside of uterus
 Regurgitation theory Retrograde flow of menstrual endometrium
 High estrogen production by endometriotic cells (high levels of aromatase)
o Infertility, dysmenorrhea (painful menstruation), pelvic pain
o Endometrial glands + stroma (may consist only of stroma)
o Ovaries, ovarian and uterine ligaments, pouch of Douglas, serosa of bowel and urinary bladder and peritoneal cavity
 Ovaries chocolate cysts (endometriomas)
o Ex. A 35-year-old woman presents with infertility. She has had dysmenorrhea, dyspareunia, and pelvic pain on defecation for 4 years. Laparoscopic
examination reveals red-blue nodules on the surface of the uterus and extensive adhesions between ovaries and the fallopian tubes. Histologic
examination of a biopsy from one of the nodules shows hyperplastic endometrial glands and hemorrhage in the stroma. Molecular analysis of the
biopsy material reveals hypomethylation of the promoter regions of the genes that encode steroidogenic factor 1 and estrogen receptor beta. There
are no mutations in the PTEN, KRAS, and MLH1 genes. Which of the following is an appropriate treatment modality in this case? Aromatase inhibitors
o Ex. A 32-year-old woman has cyclic abdominal pain that coincides with her menses. Attempts to become pregnant have failed over the past 5 years.
There are no abnormal findings on physical examination. Laparoscopic examination shows numerous hemorrhagic 0.2- to 0.5-cm lesions over the
peritoneal surfaces of the uterus and ovaries. Which of the following ovarian lesions is most likely to be associated with her findings? Endometriotic
cyst
 - Carcinoma of the endometrium
o Most common invasive cancer of the female genital tract
o Postmenopausal women 55 to 65 years
o Type I (Endometrial) Carcinoma More common (80% of cases)
 Arise in the setting of endometrial hyperplasia, associated with
 Obesity, Diabetes, Hypertension, Infertility, Unopposed estrogen stimulation
 Ex. A study of patients with postmenopausal uterine bleeding reveals that some of them have malignant neoplasmsthat arise from prior
atypical hyperplastic lesions. The peak incidence is between 55 and 65 years of age in women who have obesity, hypertension, and/or
diabetes mellitus. Molecular analysis reveals mutations of the PTEN tumor suppressor gene in most of them. Their malignancies tend to
remain localized for years before spreading to local lymphatics. Which of the following neoplasms is most likely to have these
characteristics? Endometrioid carcinoma
 Most endometrial cancers have the endometrioid pattern and are classified as type I endometrial carcinomas. They arise in the
setting of unopposed estrogen stimulation and may also have PTEN mutations as well as microsatellite instability. In contrast,
type II endometrial carcinomas occur at an older age in the background of atrophic endometrium; they usually have a serous
carcinoma pattern, but may also exhibit clear cell and müllerian mixed patterns, and TP53 mutations are common.
 Increased signaling through the PI3K/AKT pathway
 PTEN tumor suppressor gene mutations (30 to 80%)
 PIK3CA oncogene activating mutations (40%)
o Type II (Serous) carcinoma In women 10 years older than those with type I carcinomas
 Arise in the setting of endometrial atrophy
 Poorly differentiated (grade 3) tumors
 15% of cases of endometrial carcinoma
 Mutations in TP53 in 90% of cases
o Leiomyomas “fibroids”
 MC tumor in women MED12 gene
 Sharply circumscribed, discrete, firm, gray-white tumors (No Capsule)
 Cut surface: characteristic whorled appearance
 Bundles of smooth muscle cells that resemble normal myometrium
 Characteristic oval nucleus and long, bipolar cytoplasmic processes
 Estrogen-dependent growth
 Abnormal bleeding, Urinary frequency (compression of the bladder), Sudden pain from infarction of a large or pedunculated tumor,
Impaired fertility
 In pregnant women: spontaneous abortion, fetal malpresentation, uterine inertia and postpartum hemorrhage
 Malignant transformation to Leiomyosarcoma is extremely rare (de novo)
 Ex. A healthy 59-year-old woman has had a feeling of pelvic heaviness for the past 11 months. There is no history of abnormal bleeding,
and her last menstrual period was 8 years ago. Her physician palpates an enlarged nodular uterus on bimanual pelvic examination. A Pap
smear shows no abnormalities. Pelvic CT scan shows multiple solid uterine masses; there is no evidence of necrosis or hemorrhage. A total
abdominal hysterectomy is performed. Based on the gross appearance of the mass shown in the figure, what is the most likely diagnosis?
Leiomyomas
o Leiomyosarcoma
 Arise ‘de novo’ from the myometrium or endometrial stromal precursor cells, not from leiomyomas
 Chromosomal deletions, MED12 mutations
 Gross: bulky, fleshy masses that invade the uterine wall or polypoid masses that project into the uterine lumen
 Microscopic: extremely well differentiated to highly anaplastic
 Histologic examination shows pleomorphic spindle cells with cigar-shaped nuclei in interwoven fascicles
 Ex. A 53-year-old woman whose last menstrual period was 3 years ago notes vaginal bleeding for a week. On physical examination, her
uterus is markedly enlarged, but there are no adnexal masses. CT imaging reveals an irregular 8-cm mass in the body of the uterus. A total
abdominal hysterectomy is performed, and microscopic examination of the soft, hemorrhagic mass shows spindle cells with atypia and
numerous mitoses. There is coagulative necrosis of tumor cells. Which of the following is the most likely cell of origin for this mass?
Smooth muscle cells
 Leiomyosarcomas arising in the uterine corpus account for about 5% of all GYN malignancies, and is most often present in
postmenopausal women

Genital tract infections

- Herpes simplex infection (HSV-2)
o Painful papules and ulcers
o Multinucleated squamous cells with intra-nuclear viral inclusions (cowdrey type A), “ground-glass” appearance (Tzanck preparation)
o Latent in lumbosacral nerve ganglia
- Molluscum contagiosum
o DNA poxvirus (MCV-1 most prevalent, MCV-2 most sexually transmitted)
o Pearly, dome-shaped smooth papules with dimpled center
o Central waxy core contains cells with cytoplasmic viral inclusions
- Candidiasis
o 2nd MC vaginitis in United States
o Diabetes mellitus
o Curd-like vaginal discharge (cottage cheese appearance)
o Yeast and pseudohyphae
o Ex. A 31-year-old woman has had vulvar pruritus along with a thick, whitish, odorless, globular vaginal discharge for the past week. On pelvic
examination, the cervix appears erythematous, but there are no erosions or masses. A Pap smear shows budding cells and pseudohyphae. No
dysplastic cells are present. Which of the following infectious agents is most likely to produce these findings? Candida albicans
- Trichomoniasis
o Yellow, frothy (white bubbly) vaginal discharge, dysuria (painful urination), dyspareunia (painful intercourse)
o “strawberry cervix”
- Bacterial vaginosis
o MC vaginitis in United states
o Gardnerella vaginalis
o Vaginal discharge pH greater or equal to 4.7
o Whiff test Discharge has an amine-like (fishy) odor when mixed with 10% potassium hydroxide
o Clue cells
- Pelvic Inflammatory Disease (PID)
o Ascending infection from cervix to the endometrium, fallopian tubes and pelvic cavity
o Pelvic pain, adnexal tenderness, fever, vaginal discharge
 Cervicitis  Vaginal discharge
 Endometritis Vaginal bleeding and midline abdominal pain
 Salpingitis Bilateral lower abdominal and pelvic pain
 Peritonitis Abdominal tenderness and peritoneal signs
 Perihepatitis Pleuritic right upper quadrant pain (Fitz-Hugh-Curtis syndrome, “violin-string” adhesions between fallopian tube and liver
capsule)
o Complications: tubo-ovarian abscess, tubal scarring, infertility, ectopic tubal pregnancies, intestinal obstruction secondary to fibrous adhesion
o Neisseria gonorrhoeae, Chlamydia
o Puerperal infections (staph, strep, coliforms, C. perfringens)
- Neisseria gonorrhoeae
o Fallopian tubes involvement (Acute suppurative Salpingitis → Salpingo-oophoritis → Tubo-ovarian abscesses → Pyosalpinx → Chronic salpingitis →
Hydrosalpinx), can lead to Infertility or Ectopic pregnancy
o Neonates blindness and sepsis, Males: urethritis
o Adolescents: common cause of septic arthritis, disseminated infection in young females with MAC deficiency (C5b-9)
o Ex. A 17-year-old sexually active girl has had pelvic pain for 1 week. A pelvic examination shows mild erythema of the ectocervix and pain on palpation
of right adnexa. A Pap smear shows many neutrophils, but no dysplastic cells. A cervical culture grows Neisseria gonorrhoeae. If the infection is not
adequately treated, she will be at increased risk for which of the following complications? Ectopic pregnancy
o Ex. A 22-year-old woman experiences sudden onset of severe lower abdominal pain. Physical examination shows no masses, but there is severe
tenderness in the right lower quadrant. A pelvic examination shows no lesions of the cervix or vagina. Bowel sounds are detected. An abdominal
ultrasound scan shows a 4-cm focal enlargement of the proximal right fallopian tube. A dilation and curettage procedure shows only decidua from the
endometrial cavity. Which of the following laboratory findings is most likely to be reported for this patient? Detection of human chorionic
gonadotropin in serum
- Chlamydia trachomatis
o MC STD in the world
o Urogenital infections and inclusion conjunctivitis
o Lymphogranuloma venereum
 Initially small papule on genital mucosa or skin
 Swollen, tender lymph nodes with stellate abscesses, may coalesce and rupture
 Untreated - fibrosis and strictures in the anogenital tract, lymphatic obstruction
o Infections in males: NSU (sterile pyuria), epididymitis, proctitis
o Infections in females: urethritis (sterile pyuria), cervicitis, PID, perihepatitis (Fitz-Hugh-Curtis syndrome: scar tissue between peritoneum and surface
of liver from pus from PID), proctitis, Bartholin gland abscess
o Infections in newborns: conjunctivitis (ophthalmia neonatorum), pneumonia
o Nucleic acid amplification test on genital swabs or urine specimens has the highest sensitivity and specificity
o Ex. A 31-year-old, sexually active woman has had a mucopurulent vaginal discharge for 1 week. On pelvic examination, the cervix appears reddened
around the os, but no erosions or mass lesions are present. A Pap smear shows numerous neutrophils, but no dysplastic cells. A cervical biopsy
specimen shows marked follicular cervicitis. Which of the following infectious agents is most likely to produce these findings? Chlamydia trachomatis
o Ex. A 28-year-old woman has had fever, pelvic pain, and a feeling of pelvic heaviness for the past week. Pelvic examination shows a palpable painful
left adnexal mass. Laparoscopy shows an indistinct left fallopian tube that is part of a 5-cm circumscribed, red-tan mass involving the left adnexal
region. Which of the following infectious agents is most likely to produce these findings? Chlamydia trachomatis
- Syphilis
o STD caused by Treponema pallidum
o Primary hard red chancre, painless ulcer that does not scar after healing
 Plasma cells, scattered macrophages, proliferative endarteritis (small arteries showing proliferation of epithelium)
o Secondary Mucocutaneous lesions (oral cavity, palms of hands and solves of foot)
 Anogenital region, inner thighs, and axillae, may have condylomata lata (broad-based, elevated plaques)
o Tertiary gummas, aortitis and neurosyphilis
- Chancroid
o STI caused by Haemophilus ducreyi
o Painful ulcers, soft chancre
o Regional lymph nodes enlarged and tender in about 50% of cases within 1 to 2 weeks after primary infection
- Granuloma inguinale (Donovaniosis)
o Chronic STI caused by Klebsiella granulomatis (C. donovani)
o extensive scarring can cause lymphatic obstruction and lymphedema (elephantiasis) of the external genitalia
o Regional lymph nodes typically are spared (unlike chancroid)
o Donovan bodies ends have chromatin condensation
Placental Disorders
- Single Umbilical artery Associated with ↑ incidence of congenital anomalies
- Spontaneous abortion “miscarriage”
o Fetal chromosomal anomalies
 Aneuploidy, polyploidy, and translocations
o Ex. A 17-year-old girl missed a menstrual period, and her pregnancy test is positive. A month later, she notes suprapubic pain and passing blood clots
from her vagina. She passes a small amount of tissue 3 days later. Pathologic examination of this tissue shows products of conception. Which of the
following is the most likely cause for her pregnancy loss? Fetal trisomy 16
- Ectopic Pregnancy
o Implantation of the fetus in a site other than the normal intrauterine location
o MC site Extrauterine fallopian tube
- Tubal pregnancy
o MC cause of hematosalpinx
o Medical emergency
o Rupture of tubal pregnancy Moderate to severe abdominal pain and vaginal bleeding 6 to 8 weeks after last menstrual period
 Hemorrhagic shock with signs of an acute abdomen
- Placental abruption
o placenta tears from the uterus (right before or during delivery) released in maternal circulation activate clotting cascade causes DIC
- Placenta previa
o Placenta implants in the lower uterine segment or cervix
o Often leads to serious third trimester bleeding
o Complete previa covers the internal os and requires delivery via C-section
- Placenta accrete
o Placental villous tissue adheres directly to the myometrium
o Severe, potentially life threatening postpartum bleeding
o May require hysterectomy
- Preeclampsia
o Widespread maternal endothelial dysfunction
o Presents during pregnancy with hypertension, edema, and proteinuria
o 3 to 5% of pregnant women, usually last trimester and primiparas
o Risk factors: women <20 years of age and >35 years of age, previous history, multiple gestations, blacks > whites
 May be associated with hydatidiform moles
o Ex. A 36-year-old primigravida develops peripheral edema late in the second trimester. On physical examination, her blood pressure is 155/95 mm Hg.
Urinalysis shows 2+ proteinuria, but no blood, glucose, or ketones. At 36 weeks, she gives birth to a normal viable but low-birth-weight infant. Her
blood pressure returns to normal, and she no longer has proteinuria. Which of the following pathologic findings is most likely to be found on
examination of the placenta? Multiple Infarcts
 Causes for postmenopausal uterine bleeding include endometrial atrophy, carcinoma, hyperplasia, and polyps. An early potentially curable
endometrial carcinoma should
- Eclampsia more severe form with convulsions (CNS involvement)
o HELLP syndrome - 10% develop Microangiopathic Hemolytic Anemia, Elevated Liver Enzymes, and Low Platelets
o Ex. A 35-year-old primigravid woman at 30 weeks' gestation develops worsening headaches along with a 3-kg weight gain over 1 week. This morning
she had a generalized seizure. On physical examination, she is afebrile, but her blood pressure is 190/115 mm Hg (it was 120/80 mm Hg at a prenatal
visit 1 month ago). She has peripheral edema involving her head and all extremities. Fetal heart tones of 140/min and fetal movement are present.
Laboratory studies show hemoglobin, 12.5 g/dL; hematocrit, 37.6%; MCV, 92 μm3; platelet count, 199,000/mm3; serum creatinine, 1 mg/dL;
potassium, 4.2 mmol/L; and glucose, 101 mg/dL. Urinalysis shows 2+ proteinuria, but no hematuria, RBCs, WBCs, or casts. Which of the following is
the most likely underlying factor in the causation of her disease? Placenta ischemia
 Classic features of eclampsia are defined by hypertension, edema, and proteinuria, typically with onset in the third trimester. The addition
of seizures defines eclampsia. Primigravid women are at greater risk. There is no evidence in this case that primary renal disease could
cause her hypertension, and the onset was sudden. Although the precise cause of preeclampsia/eclampsia is unknown, placental ischemia
is believed to be the underlying mechanism. This is associated with shallow placentation and incomplete conversion of decidual vessels
into high-volume channels required to perfuse the placenta adequately. Untreated patients may go on to disseminated intravascular
coagulation.
- Hydatidiform mole (molar pregnancy)
o Tumor of trophoblastic tissue
o 2 types of benign, non-invasive moles: complete and partial
o Increased risk of persistent trophoblastic disease (invasive mole) or choriocarcinoma
o Complete mole
 Fertilization of an egg that has lost its female chromosomes
 Genetic material is completely paternally derived (male)
 Karyotype is diploid (46, XX)
 Embryo does not develop
 2.5% risk of choriocarcinoma, 15% risk of persistent or invasive mole
 Chorionic villi are enlarged, scalloped with central cavitation (cisterns), and covered by extensive trophoblast proliferation that involves the
entire circumference of the villi
 Symptoms
 Vaginal bleeding, Severe vomiting, Preeclampsia is present in 1% of patients, Uterus is too large for gestational age
 Elevated (+) beta-hCG
 “Snowstorm appearance” with ultrasound
 Successfully removed by curettage
 Ex. A 21-year-old G2, P1 woman is in the early second trimester. She has noted a small amount of vaginal bleeding for the past week and
has had marked nausea and vomiting for 3 weeks. On physical examination, the uterus measures large for dates. An ultrasound
examination shows intrauterine contents with a “snowstorm appearance,” and no fetus is identified. The gross appearance of tissue
obtained by dilation and curettage is shown in the figure. Which of the following substances is most likely to be greatly increased in her
serum? Human chorionic gonadotropin
  The figure shows a hydatidiform mole, or complete mole, with enlarged, grapelike villi that form the tumor mass in the
endometrial cavity. These trophoblastic tumors secrete large amounts of human chorionic gonadotropin (hCG). Molar
pregnancies result from abnormal fertilization, with only paternal chromosomes present.
o Partial mole
 Fertilization of an egg with two sperm
 Incomplete or missed abortion
 Embryo may develop for a few weeks Fetal tissues are typically present
 Karyotype is triploid (69, XXY)
 Not associated with choriocarcinoma
 Only a fraction of the villi are enlarged and edematous
 Symptoms
 Preeclampsia in 5% of patients, Vaginal bleeding, Uterine enlargement
 Elevated (+++) beta-hCG
 Curettage because of ultrasound findings of abnormal villous enlargement.
 Ex. A 23-year-old woman, G3, P2, has a spontaneous abortion at 15 weeks’ gestation. The male fetus is small for gestational age and is
malformed, with syndactyly of the third and fourth digits of each hand. The placenta also is small, and shows 0.5-cm grapelike villi
scattered among morphologicallynormal villi. Chromosomal analysis of placental tissue is most likely to show which of the following
karyotypes? 69,XXY
 Partial hydatidiform mole develops from triploidy (69 chromosomes). In contrast to a complete mole with only paternal
chromosomes, in which no fetus is present, a partial mole has a fetus because maternal chromosomes are present. Survival of
the triploid fetus to term is rare. A partial mole may contain some grapelike villi, or none. The fetus is usually malformed, often
with 3,4 syndactyly.
- Invasive mole
o Mole that penetrates or perforates the uterine wall
o Invasion of the myometrium by hydropic chorionic villi
 accompanied by proliferation of both cytotrophoblasts and syncytiotrophoblasts
o Locally destructive and may invade parametrial tissue and blood vessels
o Hydropic villi may embolize to distant sites (lungs and brain) but do not grow in these organs as true metastases, and regress even without
chemotherapy
o Clinical presentation
 Vaginal bleeding and irregular uterine enlargement
 Persistently elevated serum HCG
 Responds well to chemotherapy but may result in uterine rupture and necessitate hysterectomy
o Differs from choriocarcinoma by the presence of villi in the invasive component
- Choriocarcinoma
o Malignant germ cell tumor derived from trophoblast that forms necrotic and hemorrhagic mass
o Gestational choriocarcinoma
 Malignant neoplasm of trophoblastic cells from a previous normal or abnormal pregnancy
 Arise from incomplete hydatidiform moles, previous abortions, follows normal pregnancies or occurs in ectopic pregnancies
 Chorionic villi are not present
 Rapidly invasive and metastasizes widely – lungs, liver, vagina, brain But responds well to chemotherapy
o Non-gestational choriocarcinoma
 From germ cells in the ovaries or the mediastinum
 Gross
 Soft, fleshy, yellow-white tumor and large areas of necrosis and extensive hemorrhage
 Microscopic
 Does not produce chorionic villi
 Consists entirely of syncytiotrophoblasts and cytotrophoblasts
 Irregular vaginal spotting of a bloody, brown fluid during normal pregnancy, after a miscarriage, or after curettage
 HCG levels Typically higher than in hydatidiform moles and Low in necrotic tumors
 More resistant to therapy
o Ex. A 23-year-old woman suddenly notices a bloody, brownish vaginal discharge. The next day she has shortness of breath. On physical examination, a
3-cm, red-brown mass is seen on the lateral wall of the vagina. A chest radiograph shows numerous 2- to 5-cm nodules in both lungs. Laboratory
studies show that her serum human chorionic gonadotropin levels are markedly elevated. A biopsy specimen of the vaginal mass is obtained and
shown in the figure. Chromosome analysis of these cells shows a 46,XX karyotype. Which the following cells is most likely present in this mass lesion?
Syncytiotrophoblast
 Choriocarcinomas are aggressive, malignant trophoblastic tumors. Some of these tumors can arise without evidence of pregnancy.
Metastases in the vaginal wall and lungs and a hemorrhagic appearance are characteristic. The large pleomorphic and hyperchromatic
syncytiotrophoblastic cells produce human chorionic gonadotropin. Treatment with agents such as etoposide, methotrexate, actinomycin
D, cyclophosphamide, and vincristine can often lead to remission and cure.
- Placental site trophoblastic tumor (PSTT)
o Neoplastic proliferations of extravillous (intermediate) trophoblasts
o Found in implantation site, within the placental parenchyma, and in the placental membranes
o Human placental lactogen is elevated, beta-hCG levels are low
o Ex. A 26-year-old woman delivered a normal neonate a month ago following an uncomplicated pregnancy. She now has vaginal bleeding.
Hysteroscopy shows a nodule in the uterine fundus. Laboratory studies show hCG level of 200 mIU/mL. She is given chemotherapy but the lesion does
not regress. Hysterectomy is performed. Microscopic examination of the nodule shows intermediate trophoblast cells. Immunostaining for which of
the following proteins is most likely to yield positive results in this nodule? Human placental lactogen