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6. HDS GI Repro > Female GU Disorders > Flashcards

Female GU Disorders Flashcards

1
Q

Cervix

Anatomy

A
  • Endocervix ⇒ columnar epithelium w/ glands
  • Ectocervix ⇒ ∆ in mucosa in response to hormonal influences
    • At birth: squamocolumnar junction @ ectocervix
    • In a young adult:
      • Ectocervix is everted
      • Exposes glandular columnar endocervical mucosa to the vagina
      • Undergoes squamous metaplasia
        • Metaplastic region = Transformational zone
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2
Q

Transformational Zone

A
  • Area of cervical metaplasia
  • Extends from the _farthest area glandular mucosa reach_ed to where it is now
  • Origin of most squamous cell carcinomas of the cervix
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3
Q

Acute Cervicitis

A
  • Acute inflammation of the cervix
  • Sx: abnl vaginal bleeding, abnormal vaginal discharge, dyspareunia
  • Etiologies:
    • Post-partum
    • Staph or Strep
    • Gonococcal infection
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4
Q

Chronic Cervicitis

A
  • More common
  • Non-infectious etiologies:
    • Chemical irritant, foreign bodies, IUD
  • Infectious etiologies:
    • Non-specific ⇒ vaginal flora
      • Predisposing factors include childbirth, surgery, hormone flux
    • Specific
      • Bacterial: Chlamydia trachomatis
        • Produces follicular cervicitis
      • Fungal: Candida albicans
        • ↑ incidence in DM, abx therapy, pregnancy, alkaline vaginal pH
        • See pruritis and discharge
      • Protozoal and parasitic: Trichomonas vaginalis
        • Foamy green-gray discharge, seen on wet mount or pap
      • Viral: HPV, Herpes
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5
Q

Endocervical Polyp

A
  • Benign lesions
  • Common in 4th to 6th decade
  • Can cause postmenopausal bleeding
  • Arise in endocervical canal
  • Soft lesions, contains endocervical glands
  • Rarely become neoplastic
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6
Q

Microglandular Endocervical Hyperplasia

A

Benign lesions

↑ Glandular proliferation

Usually seen in pregnant or post-partum pts or those w/ hx of OCP use

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7
Q

Cervical Neoplasms

Overview

A
  • Most common are squamous cell disorders
  • Preceded by an identifiable precursor lesion that may progress to invasive cancer
  • Very preventable
    • Sign. ↓ incidence since Pap smear screening
    • Most cases ⇒ never screened or inadequately screened
  • Average age is 40-45 y/o
  • HPV is the most important factor in cervical oncogenesis
    • Detected in > 75% of cases
    • Also seen in pre-malignant conditions (dysplasia)
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8
Q

Cervical Carcinoma

Risk Factors

A
  • High risk sexual behavior
    • Early age at first intercourse (< 18 y/o)
    • Multiple sexual partners
    • High risk male sexual partners
  • Smoking
  • HIV infection
  • Organ transplant
  • STI infection
  • DES (diethylstilbestrol) exposure
  • Hx of cervical cancer or HGSIL
  • Infrequent or absent Pap screening tests
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9
Q

Human Papillomavirus (HPV)

Characteristics

A
  • dsDNA virus
  • Causes proliferative squamous lesions
  • Low risk types: 6 and 11
    • Cause condyloma acuminatum
  • High risk types: 16,18, 31,33, 35
    • Cause high grade lesions and cervical cancer
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10
Q

Human Papillomavirus (HPV)

Natural History

A
  • HPV is a necessary but not sufficient factor for development of squamous cervical neoplasia
  • Most infections transient w/ little risk of progression
  • Persistent infection @ 1-2 yrs strongly predicts risk of CIN 3 or cancer regardless of age
    • Carcinogenic potential:
      • HPV-16 > HPV-18 > 31, 33, 35
    • Persistent HPV infection risk factors
      • Cigarette smoking
      • Compromised immune system
      • HIV infection
  • Most common in teenagers to early 20s
  • Pts < 21 y/o have an effective immune response that clears the infection
    • Most cervical neoplasia also will spontaneously resolve in this population
    • Newly acquired HPV infection ⇒ same low chance of persistence regardless of age
  • HPV detection in pts > 30 y/o more likely to reflect persistent infection
  • HPV related cervical CA are very slow to progress
    • 3-7 yrs for severe dysplasia → invasive cervical cancer
    • Squamous epithelium origin ⇒ squamous cell carcinoma
    • Columnar epithelium origin ⇒ adneocarcinoma
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11
Q

Condyloma Accuminatum

A

“Genital Warts”

  • Can see in many sites ⇒ vulva, vagina, cervix, perineum
  • On cervix, tends to see acanthosis and hyperkeratosis
  • Koilocytes ⇒ transformation of squamous cell, indicative of HPV
    • Clearing of cytoplasm next to nucleus (where viral particles are)
    • Multinucleation
  • Usually caused by HPV 6 and/or 11
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12
Q

Squamous Intraepithelial Lesion (SIL)

Overview

A
  • Spectrum of progressive intraepithelial changes:
    • Minimal atypia → mild dysplasia → moderate dysplasia → severe dysplasia → carcinoma in situ → invasive squamous cell carcinoma
    • Most lesions will not progress but cannot know which will ⇒ must screen and tx everyone
  • HPV 16 and 18: commonly causes precursor dysplastic lesions → cancer
  • Characteristic changes:
    • Loss of basal polarity, crowded overlapping basal growth pattern, generalized disorientation
    • Nuclear hyperchromaticity, pleomorphism, ↑ N:C ratio
    • Mitotic activity at all epithelial levels
    • Morphologically abnormal mitotic figures
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13
Q

Squamous Intraepithelial Lesion (SIL)

Histologic Classification

A

Abnormal (immature) cells have ↑ N/C ratio, hyperchromatic nuclei, mitoses

Based on cervical biopsy results:

  • Mild dysplasia = Low Grade SIL = Cervical Intraepithelial Neoplasia I (CIN I)
    • Abnormal cells in bottom ⅓ of cervical squamous epithelium
  • Moderate dysplasia = High grade SIL = CIN II
    • Abnormal cells in lower ⅔ of epithelium
  • Severe dysplasia = High grade SIL = CIN III
    • Abnormal cells in top ⅓ of epithelium
  • CIS (carcinoma in situ) = high grade SIL
    • Abnormal cells extend to the top of epithelium
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14
Q

Squamous Intraepithelial Lesion (SIL)

Bethesda System Classification

A

Low Grade Intraepithelial Lesion (LGSIL)

CIN I or HPV infection (koilocytes, etc.)

High Grade Intraepithelial Lesion (HGSIL)

CIN II or CIN III or CIS

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15
Q

Squamous Intraepithelial Lesion (SIL)

Cytologic Classification

A

Based on squamous cell characteristics via pap-smear:

  • ASCUS: atypical squamous cells of undetermined significance
  • ASC-H: atypical squamous cells, cannot exclude high grade
  • LGSIL: low grade squamous intraepithelial lesion
    • Includes HPV (koilocytes), mild dysplasia, and CIN I
  • HGSIL: high grade squamous intraepithelial lesion
    • Includes moderate and severe dysplasia, CIN II, CIN III, and CIS
  • Squamous cell carcinoma
    • Look for features suspicious of invasion
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16
Q

Management of SIL

A
  • 3 components:
    1. Rule out invasive cancer
    2. Determine extent and distribution of non-invasive lesions
    3. Eradicate lesions by the easiest, cost effective method available while preserving reproductive capacity when and where possible
  • Testing sequence:
    • Pap test for cytologic diagnosis
    • If abnormal, proceed to:
    • Colposcopy w/ acetic acid application (abnormalities include mosaicism, and punctation) and punch biopsy of abnormal areas found on colposcopy
    • If biopsies show SIL ⇒ diagnostic excisional procedure (ex. electro-loop excision) of transformation zone
    • Endocervical curettage to evaluate lesion distribution
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17
Q

Papanicolaou test

“Pap smear”

A
  • Liquid-based and conventional methods
    • Exfoliated cells are collected from transformation zone of cervix
    • Contaminating blood, discharge, and lubricant may interfere w/ specimen interpretation
  • Liquid based has advantages
    • Cytology, HPV testing, evaluate ASCUS, test for gonorrhea and chlamydia
    • No difference in sensitivity or specificity for detection of CIN
  • Ancillary Testing ⇒ other infections such as Candida can be seen
    • Can also add on testing for HPV, Gonorrhea, Chlamydia, and Trichomonas
  • Results:
    • ~50 mil Pap tests performed yearly
    • 3.5 mil (7%) reported as abnormal
    • 800k reported as LSIL (1.6%)
    • 250k reported as HSIL
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18
Q

High-Risk HPV

Testing

A
  • Only test for high-risk HPV (HPV-16/18)
    • Adjunct to cytology for cervical CA screening in pts 30-65 y/o
    • Used in some pts w/ hx of prior ⊕ HPV result
    • 2 FDA approved HPV DNA genotyping tests (one for HPV-16 and one for HPV-16 and 18)
    • No role for testing for low-risk HPV genotypes
  • Reflex Testing
    • High-risk HPV testing performed in response to abnl biopsy result
    • Used to determine need for colposcopy in pts 21-29 y/o w/ an ASCUS cytology result
  • Co-testing
    • HPV testing is performed at the same time as cervical cytology
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19
Q

Human Papillomavirus (HPV)

Vaccination

A
  • Recommended vaccine schedule
    • Ideally given prior to sexual activity
    • Females and males
    • Routinely should be offered at 11-12 y/o
    • Catch up offered at 13-26 y/o in girls, 13-21y/o in boys (unless MSM or immune compromise)
    • Can administer as early as 9 y/o
  • Dosing: different dosing regimens based on age @ time of vaccination
    • Use the CDC Vaccine app for specifics
  • Cervical screening recommendations unchanged based on vaccination
  • Long term efficacy of the vaccine has not been established ⇒ booster?
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20
Q

Cervical Cancer

Screening Guidelines

A
  • Age to start screening
    • Start at age 21 for everyone
      • Regardless of age of sexual initiation or other high-risk behaviors
      • Earlier screening ⇒ ↑ anxiety, morbidity, and expense
  • Initiation of reproductive health care should not be predicated on cervical cancer screening
  • Younger patients who are sexually active need STI screening and discussion of birth control
  • Screening Recommendations will be different for special populations including:
    • HIV ⊕
    • Immunocompromised
    • DES exposed individuals
    • Previously treated for CIN 2, CIN 3, or cervical cancer
  • Discontinuation of Screening
    • Specific recommendations to stop screening in pts > 65 y/o or those s/p hysterectomy
  • Annual well visits are recommended even if cervical cancer screening is not performed at each visit
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21
Q

Abnormal Cytology

Management

A

Follow-up depends on cytology results:

  • ASCUS
    • Perform HPV DNA testing for ‘high risk’ HPV types
      • If ⊖ HPV ⇒ repeating cytology testing in 3 yrs
      • If ⊕ HPV ⇒ repeat cytology at 6 and 12 months
  • Higher grade lesions ⇒ colposcopy
  • LSIL ⇒ colposcopy
  • Exception is pts 21-24 y/o ⇒ repeat cytology in 12 months b/c many will have resolution in a year
  • HSIL or ASC-H ⇒ colposcopy always (no age difference)
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22
Q

Colposcopy

A
  • Magnification of the cervix to allow for visualization of the transformation zone
    • Also look in lateral fornices and upper vagina
  • Identify areas of abnormality
    • Can use green filter, acetic acid, or Lugol’s iodine to better differentiate
  • Colposcopy directed biopsy: will give you a histological dx of CIN
  • Follow-up will depend on the results
    • Normal histology or CIN: repeat co-test in 1 year (cytology w/ high-risk HPV testing)
    • CIN 2 or 3: recommend excision
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23
Q

Cervical

Excisional Procedures

A
  • Loop electrosurgical excision procedure (LEEP)
    • Uses cautery to excise transformation zone and lesion
    • Can be done in the office under local anesthesia
    • Allows for new growth of cells
  • Cold Knife Cone (CKC)
    • Uses a scalpel to excise the transformation zone and lesion
    • Done in the OR
    • Higher risk of bleeding
    • Allows for a larger specimen w/o cautery artifact for pathology
    • Better look at the margins
    • Esp. for glandular lesions
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24
Q

Squamous Intraepithelial Lesion (SIL)

Progression

A

Once full thickness dysplasia is present (CIS) ⇒ break through BM ⇒ invasive squamous cell carcinoma

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25
Q

Microinvasive Squamous Cell Carcinoma

A

Only a small area of invasive disease is seen (< 5x7 mm)

Term ‘microinvasive’ is used

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26
Q

Invasive Squamous Cell Carcinoma

Clinical Characteristics

A
  • Presents as abnormal vaginal bleeding usually following intercourse or douching
  • 10-20% of pts report:
    • Bloody malodorous discharge
    • Pain often radiating to the sacral region
  • Sx of locally advanced or metastatic disease: weight loss, pallor, BLE edema, rectal pain, hematuria
  • Gross examination: Ulcerative, exophytic (fungating) or infiltrative patterns of growth
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27
Q

Invasive Squamous Cell Carcinoma

Modes of Spread

A
  • Spreads by direct local invasion to the adjacent tissues
    • Lateral spread may reach bony pelvis
      • Can encompass and obstruct one or both ureters
      • Most common cause of death in these pts
  • Lymphatic spread late
  • Hematogenous spread even later
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28
Q

Verrucous Carcinoma

A
  • Variant of squamous cell carcinoma
  • Well-differentiated
  • Can get very large
  • Does not invade ⇒ won’t metastasize
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29
Q

Cervical Glandular Cell

Abnormalities

A
  • Atypical
    • Glandular cells
    • Endocervical cells
    • Endometrial cells
  • Endocervical adenocarcinoma in situ (AIS)
  • Adenocarcinoma
    • Endocervical
    • Endometrial
    • Extrauterine
    • Not otherwise specified (NOS)
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30
Q

Cervical Adenocarcinoma

A

Originate from glandular columnar epithelium.

  • In situ adenocarcinoma (AIS)
    • Only affects glands
    • No stromal response to indicate invasion
  • Invasive adenocarcinoma
    • Incidence ↑
      • May be up to 25% of cervical CA
    • Also associated w/ HPV
    • Some secrete mucin
    • Some are associated w/ DES (clear cell carcinoma)
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31
Q

Granuloma Inguinale

(Donovanosis)

A
  • Organism: Calymmatobacterium granulomatis
  • Clinical and histology:
    • Large ulcerated lesions contain inflamed granulation tissue and numerous MΦ
    • Bacteria are found in the cytoplasm of neutrophils, histiocytes and plasma cells (Donovan bodies)
      • Assumes the shape of a safety pin
  • Infection is more common in the tropics
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32
Q

Lymphogranuloma Venereum (LGV)

A
  • Caused by Chlamydia trachomatis
  • Clinical::
    • Transient vesicles on penis or vagina that are often unnoticed
    • Followed by inguinal lymphadenopathy w/ formation of “bubos”
      • Inflamed lymph nodes esp. in the groin area
      • Bubos contain infected, purulent material
        • Must be aspirated or they may rupture
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33
Q

Vulvar Dystrophy

A
  • Many different types referred to by many different names
  • Lesions are usually white, scaly and fissured (leukoplakia)
  • Two main types:
    • Lichen sclerosis (most common type)
    • Squamous hyperplasia
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34
Q

Benign Vulvar Lesions

A
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35
Q

Vulvar Intra-epithelial Neoplasia (VIN)

A
  • Spectrum of dysplastic changes ranging from mild to severe
    • Characterized by nuclear and epithelial atypia
    • Similar to SIL of the cervix
  • Clinical presentation: pts may be asymptomatic or have pruritis
  • Gross appearance:
    • ⅓ of pts ⇒ lesions are hyperpigmented
    • Remainder are pink, white, grey or red
    • Can be macular or papular, single or multiple
  • Microscopic appearance: dyskeratotic cells scattered throughout lesion
    • VIN I (mild dysplasia): changes confined to lower ⅓
    • VIN II (moderate dysplasia): changes in lower ⅔
    • VIN III (severe dysplasia and CIS): full thickness
    • CIS: also referred to as Bowen’s disease
  • Caused by HPV, usually seen in young women 20-35 y/o
  • Progression to invasive carcinoma is rare (6%)
    • If it occurs, usu. in postmenopausal women or immunosuppressed pts
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36
Q

Vulvar Paget’s Disease

Characteristics

A
  • Slowly growing intra-epithelial multi focal neoplasm
  • Arises de novo in the epidermis from totipotent intra-epithelial precursor cells
  • Can involve the dermis
  • Occurs in genital, perianal and axillary regions
  • Lesion may be pruritic
  • Usu. seen in post-menopausal Caucasian women
  • Rarely associated w/ underlying sweat gland adenocarcinoma
  • Unlike Paget’s disease of the nipple (100% of cases show underlying ductal breast carcinoma)
  • Treatment is wide local excision
  • Recurrences are common b/c Paget cells extend beyond confines of visible gross lesion
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37
Q

Vulvar Paget’s Disease

Morphology

A
  • Gross:
    • Has a red, eczematoid appearance
    • Tends to occur on the labia majora
  • Microscopic appearance:
    • Paget’s cells often occur in nests surrounded by small hyperchromatic basaloid cells
    • Isolated Paget cells may file upward in the epithelium
    • Cytoplasm is pale and occasionally vacuolated
    • Nuclei are vesicular w/ finely distributed chromatin
    • Nucleoli are prominent
    • Mitotic figures are infrequent
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38
Q

Vulvar Invasive Squamous Cell Carcinoma

Characteristics

A
  • Incidence in U.S. is 1.5/100k, represents 3% of all genital carcinoma
  • Seen in older women, usually > 60 y/o
  • Gross Appearance & Clinical Presentation
    • Pain, discomfort, itching and exudation
    • Tumor is usually an exophytic or endophytic ulcer located on labia majora or labia minora
  • Microscopic appearance
    • Usually well-differentiated
  • Pattern of Spread:
    • Inguinal nodes
    • LN w/in the pelvis, rectum
    • Parailiac nodes
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39
Q

Squamous Carcinoma of the Vulva

Staging

A
  • Stage I: Tumor confined to vulva, 2 cm. or less in diameter. No suspicious groin nodes.
  • Stage II: Tumor confined to vulva > 2 cm. w/o suspicious groin nodes.
  • Stage III: Extension beyond vulva. No suspicious groin nodes.
  • Stage IV: Grossly positive groin nodes, regardless of size of 1° tumor
    • Likelihood of regional node metastases most related to size of 1° tumor
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40
Q

Squamous Carcinoma of the Vulva

Management

A
  • Microinvasive Vulvar Squamous Carcinoma
    • Depth of invasion < 1 mm. and not associated w/ inguinal LN metastasis
    • Stage IA
    • Treatment is local excision
  • Invasive carcinoma
    • If lesion has a depth > 1 mm. ⇒ groin node dissection is done
  • Other prognostic factors include diameter of lesion, tumor ulceration, grade and confluent growth
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41
Q

Verrucous Carcinoma of Vulva

A
  • Distinct variant of squamous carcinoma w/ a unique biologic course
  • Resembles a large condyloma acuminatum
  • Usually seen in post-menopausal women
  • Very well-differentiated squamous lesion
  • Usually no nodal metastasis
  • Tx w/ wide local excision
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42
Q

Adenocarcinoma of the Vulva

A

Similar to adenocarcinoma seen in the cervix

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43
Q

Infectious Vaginitis

A
  • Bacteria
    • Garderella vaginalis (Hemophilus vaginalis)
      • Accounts for 90% of nonspecific infections
      • See clue cells on pap smear
  • Fungal
    • Candida
  • Parasite
    • Trichomonas vaginalis
  • Virus
    • HPV
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44
Q

Benign Vaginal Lesions

A
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45
Q

Vaginal Intra-epithelial Neoplasia (VAIN)

A
  • Less common than VIN and CIN
  • Annual incidence is 3/100k
  • Epidemiology is same as for cervical intra-epithelial neoplasia (CIN) i.e. exposure to HPV
  • VAIN most often affects the upper vagina
  • Multi-focal in > 50% of pts
  • Asymptomatic, can be detected on colposcopy
  • Microscopic changes are same as for CIN
  • Many pts have other lower genital tract neoplasms (cervix, vulva)
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46
Q

Vaginal Squamous Cell Carcinoma

A
  • Most common carcinoma of vagina
  • Infrequent, accounts for 1% of all gynecologic malignancies
  • Seen mostly in older women (60-70)
  • Must be differentiated from vaginal extension of cervical or vulvar cancer and from metastatic tumors
    • Valid dx of 1° vaginal CA requires no cervical or vulvar CA @ time of dx and for ≥ 10 years before dx
  • Commonly occurs in upper portions of posterior wall
  • Can spread dorsally to the parametrium, bladder and rectum
  • Most often metastasizes to pelvic lymph and inguinal nodes
  • May be silent lesions, or present as vaginal bleeding or discharge (leukorrhea)
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47
Q

Embryonal Rhabdomyosarcoma

“Sarcoma Botryoides”

A
  • Most common neoplasm of lower genital tract in girls
    • Seen in those < 5 y/o
  • Originates from undifferentiated mesenchyme w/ striated muscle differentiation (embryonal rhabdomyoblasts)
  • Grossly distinctive: polypoid grape-like mass, may be seen at introitus
  • Prognosis is poor
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48
Q

Diethylstilbestrol (DES)

A
  • Synthetic, estrogen administered to women w/ high-risk pregnancies in 1940’s-1960’s
  • Prenatal Diethylstilbestrol (DES) exposure results in:
    • Vaginal adenosis
    • Atypical adenosis
    • Dysplasia
    • Clear cell adenocarcinoma of vagina and cervix
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49
Q

Vaginal Adenosis

A
  • Related to prenatal Diethylstilbestrol (DES) exposure
  • Involves upper ⅓ of the vaginal anterior wall
  • Mucosa is replaced by glandular epithelium
    • Can then undergo squamous metaplasia
  • Similar changes can occur in the cervix
  • Pathogenesis:
    • Adenosis develops from persistent residual embryonic glandular epithelium
    • May be a precursor lesion for clear cell adenocarcinoma of the vagina
      • Adenosis → atypical adenosis → dysplasia → clear cell adenocarcinoma
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50
Q

Clear Cell Adenocarcinoma

Vagina and Cervix

A
  • Related to prenatal Diethylstilbestrol (DES) exposure
    • < 14% w/ DES exposer develop adenocarcinoma
  • Seen in young women (average age 19 years)
  • Tumor may be large or small
  • Usually asymptomatic
  • Located in the upper ⅓ of anterior vaginal wall
  • Microscopically, resembles clear cell carcinoma of uterus and ovary
  • It spreads locally and later metastasizes to pelvic LNs and blood stream
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51
Q

Uterine & Adnexal

Embryology & Anatomy

A
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52
Q

Uterine

Size Variation

A
  • Continuously grows in size from birth → puberty
  • Signficant growth during pregnancy
  • Does not revert to nulliparous size until menopause
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53
Q

Menstrual Cycle

Phases

A
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54
Q

Menstrual Endometrial Changes

A
  • D__ay 1-14 ⇒ proliferative endometrium
    • Preovulatory
    • Simple glands
    • Mitotic figures within endometrial glands
  • Day 14 ⇒ ovulation
    • Post-ovulatory
  • Day 17 ⇒ subnuclear vacuoles
    • Presence means that ovulation has occurred
  • Day 21 ⇒ secretory endometrium
    • Gland complexity
    • Stromal edema
    • Secretions in glands
  • Day 23 ⇒ pre-decidua around vessels
  • Day 26 ⇒ entire stroma now decidualized
  • Day 28 ⇒ menstrual endometrium
    • Structure breaks down
    • Endometrial balls
    • “Crumbling”
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55
Q

Menstrual Cycle

Summary Chart

A
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56
Q

Endometrium of Pregnancy

A
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57
Q

Dysfunctional Uterine Bleeding (DUB)

A
  • Abnormal bleeding w/o lesion of the endometrium
  • Very common
  • Seen most often around menarche and menopause
  • Etiologies:
    • Anovulatory Bleeding
    • Inadequate luteal phase
    • Irregular shedding
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58
Q

Anovulatory Bleeding

A
  • Most common cause of DUB
  • No corpus luteum ⇒ excess estrogen, no progesterone
  • Then estrogen declines and get bleeding
  • Bleeding variable in amount and erratic
  • Most are d/t subtle hormonal imbalances
  • Some cases 2/2 obesity, malnutrition, chronic systemic disease, endocrine disorders, polycystic ovaries, etc.
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59
Q

Inadequate Luteal Phase

A

Inadequate progesterone secretion from corpus luteum

See menstruation 6-9 days after LH surge

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60
Q

Irregular Shedding

A
  • Heavy bleeding d/t extended secretion of progesterone from corpus luteum
  • See secretory and proliferative phases together on biopsy
    • Proliferative endometrium with stromal breakdown
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61
Q

Uterus

Congenital Abnormalities

A

Fusion defects & Atresias

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62
Q

Endometritis

A

Inflammation of the endometrium

  • Acute Endometritis
    • Usually near time of delivery or miscarriage
    • Caused by retained products of conception (POC)
    • Infection by Strep or Staph
  • Chronic Endometritis
    • See plasma cells in endometrium
    • Risk factors include IUD, PID, retained POC
  • Special forms of endometritis
    • TB, Mycoplasma, Chlamydia, fungi, Herpes simples, CMV, Parasites, sarcoid
63
Q

Uterine

Drug Effects

A
  • Estrogens
    • Stimulates the endometrium
    • Duration of exposure more important than dose
    • Can get hyperplasia or carcinoma from prolonged administration
  • Oral Contraceptives
    • Shortens proliferative phase, secretory changes develop slowly
    • After a few cycles, atrophied endometrium w/ decidualized stroma
  • Known adverse reactions d/t oral contraceptives:
    • Thromboembolism w/ sudden death
    • Hepatic adenoma that can present as sudden intraperitoneal bleeding, jaundice
    • Intimal fibrosis and luminal narrowing of small arteries
64
Q

Intrauterine Device (IUD)

A

Induce acute and chronic inflammation and decidual reaction

↑ incidence of infections, particularly actinomycosis

65
Q

Endometriosis

Characteristics

A
  • Endometrial glands and stroma outside the uterus
    • ‘Ectopic endometrial tissue’
  • Most common sites of occurrence:
    1. Ovary
    2. Uterine ligaments
    3. Rectovaginal septum
    4. Cul de sac and pelvic peritoneum
    5. Intestine and appendix
    6. Mucosa of cervix, vagina, fallopian tubes
    7. Laparotomy scars
  • Seen in women of reproductive age (6-10%)
  • Clinical manifestations:
    • Pelvic pain, dysmenorrhea, infertility, dysuria, rectal pain
66
Q

Endometriosis

Pathogenesis

A
  • Regurgitation theory
    • Retrograde flow of products of menstruation
    • 90% of women have this and most don’t have endometriosis
  • Benign metastasis theory
    • Spread by vessels or lymphatics
  • Extrauterine stem/progenitor cell theory
    • Cells @ ectopic locations that differentiate into endometrium
67
Q

Endometriosis

Molecular Findings

A

Endometriotic implants show:

  • Release of proinflammatory and other factors
  • Endometriotic stromal cells contain aromatase ⇒ ↑ estrogen production
    • Not in normal endometrial stromal cells
    • Conveys a survival advantage
    • Ass. w/ endometrioid and clear cell ovarian CA
68
Q

Endometriosis

Morphology

A
  • Gross:
    • Dark, ‘powder burns’ on laparoscopy, undergoes cyclic bleeding
    • Ovaries can have large cysts containing degenerated bloody material (chocolate cysts)
    • Uterus does not enlarge (in contrast to adenomyosis)
  • Microscopic:
    • Endometrial glands and stroma
    • May be difficult to identify d/t surrounding hemorrhage and fibrosis
    • Sometimes just see hemosiderin-laden MΦ
      • MΦ + correct clinical sx ⇒ dx of ‘presumptive endometriosis’
    • Atypical endometriosis shows cytologic atypia and/or glandular crowding
      • Looks like atypical endometrial hyperplasia
      • May be precursor to endometriosis-related ovarian CA
69
Q

Adenomyosis

A
  • Presence of endometrial glands and stroma within the myometrium
  • Common, benign
  • Most often seen in peri-menopausal women
  • Present w/ bleeding and dysmenorrhea
  • Uterus can become enlarged w/ thickened myometrium
  • Can respond to hormones and cycle
  • Treatment: hysterectomy
  • Does not have malignant potential
70
Q

Endometrial Polyp

A
  • Common cause of abnormal bleeding
  • Seen in women in 40s and 50s
  • Can be sessile or pedunculated
  • Polypoid fragments of tissue w/ epithelium on three sides
  • Stromal cells contain chromosomal rearrangements similar to other benign mesenchymal tumors
  • Glands are ‘along for the ride’
    • Can become hyperplastic but very rarely become malignant
71
Q

Endometrial Hyperplasia

Overview

A
  • Another cause of abnormal bleeding
  • Precursor to endometrial adenocarcinoma (most common type)
  • 1% becomes malignant
    • Simple (non-atypical) → atypical (EIN) → carcinoma
  • Morphologically:
  • ↑ Gland to stroma ratio
  • Abnl epithelial growth relative to normal endometrium
  • Vary in size and shape
72
Q

Endometrial Hyperplasia

Pathogenesis & Risk Factors

A
  • Linked to prolonged estrogen stimulation of the endometrium
    • Anovulation
    • ↑ Estrogen production
    • Exogenous estrogen
  • Conditions promoting hyperplasia include:
    • Obesity
      • Peripheral conversion of androgen to estrogen
    • Menopause
    • Polycystic ovarian disease (including Stein-Leventhal syndrome)
    • Functioning granulosa cell tumors of the ovary
    • Excessive cortical function (cortical stroma hyperplasia)
    • Prolonged admin of estrogenic substances (estrogen replacement therapy)
  • Same influences pathogenetic in some endometrial CA
73
Q

Endometrial Hyperplasia

Genetics

A
  • Inactivation of the PTEN tumor suppressor gene
    • Via deletion and/or inactivation
  • Plays a role in development of hyperplasia and endometrial carcinoma
    • Seen in 20% of hyperplasia, 30-80% of endometrial carcinomas
74
Q

Endometrial Hyperplasia

Grading

A
  • Historically used 4 categories:
    • Based on simple vs. complex architecture & no atypia vs. atypia
    • Low-grade hyperplasia ⇒ no or minimal atypia
    • High-grade hyperplasia (aka atypical hyperplasia) ⇒ has characteristics of intraepithelial neoplasia
      • Morphologic features ⇒ gland crowding and cytologic atypia
      • Genetic characteristics ⇒ PTEN mutations
  • Now WHO uses only two categories:
    • Non-atypical hyperplasia
    • Atypical hyperplasia aka “Endometrial Intraepithelial Neoplasia (EIN)”
75
Q

Non-Atypical Endometrial Hyperplasia

A
  • ↑ Gland-to-stroma ratio but retain intervening stroma
  • Rarely progress to adenocarcinoma
  • May evolve into cystic atrophy when estrogen stimulation is withdrawn
  • Management:
  • If no further fertility desired ⇒ hysterectomy
  • If fertility desired ⇒ trial of progestin therapy and follow up
76
Q

Atypical Endometrial Hyperplasia

“Endometrial Intraepithelial Neoplasia (EIN)”

A
  • Complex patterns of proliferating glands w/ nuclear atypia
  • Glands are complex w/ branching and may be ‘back-to-back’
    • Approaches appearance of adenocarcinoma
  • Cells are rounded instead of elongated and poorly oriented to BM
  • Hysterectomy in these pts shows adenocarcinoma in 23-48%
77
Q

Atypical Endometrial Hyperplasia

With Metaplasia

A
  • Some endometrial hyperplasia can show altered cellular differentiation (metaplasia)
    • Including presence of squamous, ciliated cell, and mucinous metaplasia
  • May result from ∆ in epithelial-stromal relationships
    • Induces basal endometrial cells to follow different differentiation pathways
  • Less easily classified
78
Q

Type I Endometrial Adenocarcinoma

Pathogenesis & Genetics

A
  • Atypical hyperplasia precursor lesion
    • Both show PTEN mutations
      • ↑ signaling via PI3K/AKT pathway
      • ∆ Expression of estrogen receptor-dependent target genes
    • Can see also activating mutations in KRAS
  • PIK3CA mutations in CA, but not hyperplasia
    • May relate to ability to invade
  • 20% of sporadic tumors show DNA mismatch repair gene defects
    • Also seen in women from HNPCC families
  • 50% of poorly diff CA shows TP53 mutations
  • Links demonstrating estrogen-dependence:
    • Ovarian estrogen-secreting tumor & HRT ⇒ ↑ risk of endometrial CA
    • Extremely rare in women w/ ovarian agenesis and those castrated early in life
79
Q

Type I Endometrial Adenocarcinoma

Risk Factors

A
  • Obesity
  • DM
    • Abnl glucose tolerance in > 60%
  • HTN
  • Infertility
    • Pts are often nulliparous w/ hx of functional menstrual irregularities consistent w/ anovulatory cycles
  • Unopposed estrogen stimulation
80
Q

Type I Endometrial Adenocarcinoma

Morphology & Behavior

A
  • Localized polypoid tumor vs diffuse tumor involving entire endometrial surface
  • Usu. spreads by myometrial invasion → periuterine structures
  • Can spread into broad ligaments ⇒ palpable mass on pelvic exam
  • Eventually, tumor disseminates to regional LNs
  • Later, may metastasize to lungs, liver, bones, and other organs
  • Histology:
    • Tends to be well-differentiated and mimic normal endometrial glands (85%)
      • Called endometrioid endometrial adenocarcinoma
    • Others may show mucinous, tubal, or squamous differentiation
81
Q

Endometrioid Endometrial Adenocarcinoma

Grading

A

3-step grading system for endometrioid tumors:

  • Grade 1: Well-differentiated, easily recognizable glandular patterns
  • Grade 2: Moderately-differentiated, well-formed glands mixed w/ solid sheets of malignant cells
  • Grade 3: Poorly-differentiated, solid sheets of cells w/ few glands, more nuclear atypia and mitotic activity
82
Q

Type I Endometrial Adenocarcinoma

Other Elements

A
  • Endometrial adenocarcinomas may show mucinous, tubal, or squamous differentiation
  • Up to 20% contain foci of squamous differentiation
    • Squamous elements may be benign-appearing
    • Some moderately or poorly differentiated endometrioid CA contain squamous elements that are malignant
  • Previously called adenoacanthoma and adenosquamous carcinoma
  • Now just grade carcinomas based on glandular differentiation alone and use the term squamous differentiation
83
Q

Type II Endometrial Adenocarcinoma

Characteristics

A
  • Less estrogen-dependent and less often preceded by hyperplasia than Type I
  • Often arise in setting of endometrial atrophy
  • Pts are usu. older @ time of dx
  • Accounts for 15% of endometrial carcinoma
  • All non-endometrioid carcinomas classified as grade 3 (poorly differentiated) regardless of histologic pattern
  • Subtypes:
    • Serous adenocarcinomas
      • Resemble subtypes of ovarian CA
    • Clear cell carcinoma
    • Malignant Mixed Muellerian Tumor (MMMT)
84
Q

Type II Endometrial Adenocarcinoma

Pathogenesis and Genetics

A
  • 90% of Type II w/ mutations in tumor suppressor, TP53
    • 1° missense mutations ⇒ accumulation of altered protein
    • Same mutation seen in EIN
  • Most common subtype is serous carcinoma
    • Suggests that serous CA starts as surface epithelial neoplasm → adjacent gland structures → endometrial stroma
  • Poor prognosis
    • Tends to exfoliate
    • Undergo transtubal spread
    • Implant on peritoneal surfaces like ovarian CA
  • Often beyond uterus at dx
85
Q

Non-Endometrioid Endometrial Carcinomas

Serous Carcinomas

A
  • Arise in small atrophic uteri (post-menopausal women)
  • Tumors usu. large bulky tumors or deeply invasive into myometrium
  • Invasive lesions can show papillary growth pattern ⇒ papillary serous carcinoma
  • Marked cytologic atypia including high N/C ratio, atypical mitotic figures, and prominent nucleoli
  • Relatively superficial endometrial involvement may be ass. w/ extensive peritoneal disease
    • Suggests spread by routes other than direct invasion ⇒ tubal or lymphatic transmission
    • More common Type II
  • Can also have a predominantly glandular growth pattern w/ marked cytologic atypia
  • Poor prognosis
86
Q

Non-Endometrioid Endometrial Carcinomas

Clear Cell Carcinomas

A
  • Commonly Type II Endometrial CA
  • Vacuolated spaces within cells
  • Very poor prognosis
87
Q

Endometrial Adenocarcinoma

Staging and Grading

A

Applies to Type I and Type II

  • Staging based on extension:
    • Stage I: confined to the corpus uteri itself
    • Stage II: involves corpus and cervix
    • Stage III: extended outside the uterus but not outside the true pelvis
    • Stage IV: extended outside the true pelvis or obviously involves mucosa of bladder or rectum
  • Cases in various stages can also be sub-grouped into 3 grades:
    • G1: well-differentiated adenocarcinoma
    • G2: differentiated adenocarcinoma w/ partly solid (< 50%) areas
    • G3: predominantly solid or entirely undifferentiated carcinoma or serous or clear cell carcinoma
      • Includes all Type II CA
88
Q

Endometrial Tumors w/ Stromal Differentiation

A
  • Carcinosarcomas ⇒ Malignant Mixed Mullerian Tumor (MMMT)
  • Adenosarcomas ⇒ composed of stromal neoplasias in association w/ benign glands
  • Pure stromal (mesenchymal) neoplasms ⇒ ranges from benign (stromal nodule) to malignant (stromal sarcoma)

Together, these tumors comprise < 5% of endometrial malignancies

89
Q

Malignant Mixed Mullerian Tumor (MMMT)

(Carcinosarcoma)

A
  • Endometrial adenocarcinoma w/ stromal differentiation
  • Consists of adenocarcinoma mixed w/ stromal (sarcoma) elements
    • Arising from the same cell type
    • Sarcomatous components may include striated muscle cells, cartilage, adipose tissue, and bone
  • Bulky, polypoid tumors, can protrude through cervical os
  • Outcome is determined by depth of invasion and stage
  • Grade and type of adenocarcinoma matters too
    • Poorest outcome w/ serous differentiation
  • Tumors are highly malignant
    • 5-yr-survival rate 25-30%
  • MMMTs occur in postmenopausal women and present w/ postmenopausal bleeding
  • Many have hx of previous radiation therapy
90
Q

Endometrial Adenosarcomas

A

Benign epithelial component w/ malignant mesenchyme

  • Large broad-based endometrial polypoid growths
    • May prolapse through cervical os
  • Dx based on malignant appearing stroma + benign but abnormally shaped endometrial glands
  • Presents w/ abnormal bleeding
  • Women in 4th to 5th decade
  • Low grade malignancy
    • 25% recur
    • Rarely spread beyond pelvis
  • Estrogen-sensitive
91
Q

Pure Mesenchymal (Stromal) Tumors

A

Neoplasms that resemble normal stromal cells:

  • Stromal Nodule (Benign Mesenchymal Endometrial Tumor)
    • Well-circumscribed aggregates of endometrial stromal cells in the myometrium
    • Mean age 47 yrs
    • Presents w/ abnormal bleeding
  • Stromal Sarcoma (Malignant Mesenchymal Endometrial Tumor)
    • Neoplastic endometrial stroma lying between muscle bundles of the myometrium
      • Can infiltrate myometrial tissue OR penetrate lymphatic channels (old term: endolymphatic stromal myosis)
    • ~50% of these tumors recur
    • Distant metastases can occur decades later
      • ~15% of pts die from metastatic tumors
    • 5-yr-survival rate 50%
    • Often ass. w/ chromosomal translocations that create fusion genes (like other sarcomas)
92
Q

Leiomyoma

Overview

A

Benign tumor of myometrium

  • Most common uterine neoplasm
    • Maybe the most common tumor in women
  • Commonly known as ‘fibroids’
  • Present in 20-30% of women over age 30
    • Usu. found in middle aged women
  • Most leiomyomas regress after menopause
  • Very common in black women
  • Estrogen can make leiomyomas larger
  • Progesterone and pregnancy ⇒ ± rapid ↑ in size and hemorrhagic degeneration
93
Q

Leiomyoma

Pathogenesis

A

40% have abnormal karyotype

Simple chromosomal abnormality

  • Rearrangement of chromosomes 12q14 and 6p
    • Involves HMGIC and HMGIY genes
      • Encode DNA-binding factors that regulate chromatin structure
  • Up to 70% of leiomyomas have mutations in MED12 gene
    • Ultimately stimulates gene expression
94
Q

Leiomyoma
Clinical Manifestations

A
  • Many asymptomatic
  • Sx include: pain, pressure sensation, bladder compression → urinary frequency, sudden pain if disruption of blood supply occurs
  • Submucosal leiomyomas are most responsible for abnormal bleeding and infertility
  • Cause uterine enlargement
  • Complications: spontaneous abortion, DIC, dystocia, postpartum hemorrhage
  • Malignant transformation (leiomyosarcoma) is extremely rare
95
Q

Leiomyomas

Morphology

A
  • Gross pathology:
    • Sharply circumscribed, discrete, round, firm, gray-white tumors w/ ‘whorled’ appearance
    • Usu. seen in myometrium of uterine corpus
    • Can occur within the:
      • Myometrium (intramural)
      • Just beneath the endometrium (submucosal)
      • Beneath the serosa (subserosal)
      • Rarely can involve uterine ligaments, lower uterine segment, or cervix
    • Large tumors may develop areas of yellow-brown to red softening (red degeneration)
  • Histology:
    • Whorled bundles of smooth muscle cells that resemble uninvolved myometrium
    • Usu. individual muscle cells are uniform in size and shape and have characteristics of nl SM (oval nucleus and long, slender ‘cigar-shaped’ cytoplasm)
    • Should not see many mitotic figures
96
Q

Leiomyoma

Variants

A
  • Common:
    • Atypical or bizarre (symplastic) tumors
      • See nuclear atypia and giant cells
    • Cellular leiomyomas
  • Rare:
    • Benign metastasizing leiomyoma
      • Uterine tumor that extends into vessels and migrates to other sites, most commonly the lung
    • Disseminated peritoneal leiomyomatosis
      • Presents as multiple small nodules on the peritoneum
97
Q

Leiomyomas

Management

A
  • Uterine leiomyomas, even when extensive, may be asymptomatic
    • If asymptomatic, don’t need to treat
  • If symptomatic, treatment options include:
    • Hysterectomy
    • Myomectomy
    • Embolization of vessels to the leiomyoma
    • Endometrial ablation (if bleeding is the major sx)
98
Q

Leiomyosarcoma

Overview

A
  • Rare
    • 1.3% of uterine malignancies, 25% of uterine sarcomas
    • 1/800 tumors of uterine smooth muscle
  • Peak incidence 40-60 y/o
  • Pts usu. present w/ vaginal bleeding, pelvic pain
  • Leiomyosarcomas are not thought to originate from an existing leiomyoma
  • Diagnosis:
    • Main criterion is ↑ mitotic figures
      • Need 10 mitoses per 10 HPF
    • Moderate-marked nuclear or large (epithelioid) cells & 5 mitoses/10 HPF ⇒ ± leiomyosarcomas dx
    • Cellular tumors w/ 5-9 mitoses /10 HPF and minimal atypia ⇒ ‘tumors of uncertain malignant potential’
  • Treat w/ TAH-BSO
    • May recur after surgery
  • > 50% metastasize → lungs, bone, brain
  • 5-yr-survival 40%
99
Q

Leiomyosarcoma

Morphology

A
  • Gross:
    • Most leiomyosarcomas are intramural and fairly large (average size 9 cm)
    • Soft, gray, fleshy mass w/ necrosis, hemorrhage
  • Microscopic:
    • Cells are spindled, can show pleiomorphism/atypia
    • ± Moderate-marked nuclear or large (epithelioid) cells
    • ± Hypercellularity
100
Q

Reproductive vs Post-Menopausal

TAH-BSO

A
101
Q

Ovarian

Morphology

A
102
Q

Ovarian

Non-Neoplastic and Functional Cysts

A

Most common lesions of the ovary

  • Surface inclusion cysts
    • Secondary to invagination of surface epithelium
  • Follicle cysts (aka Cystic follicles)
    • Arise from unruptured follicles or follicles that rupture
    • Seal and undergo atresia
    • Lined by surface epithelium that may be luteinized
    • Often multiple
    • ± ↑ estrogen ⇒ endometrial hyperplasia
    • May rupture and cause abd pain
  • Corpus luteum cysts
    • Seen in ovaries of repro age women
    • May rupture
103
Q

Polycystic Ovarian Syndrome (PCOS)

A
  • Affects 6-10 % of reproductive age women
  • Clinical manifestations:
    • Hyperandrogenism, menstrual abnl, polycystic ovaries, chronic anovulation, ↓ fertility
    • Insulin resistance and ∆ adipose tissue metabolism
      • Ass. w/ obesity and Type 2 DM
      • Ass. w/ premature atherosclerosis
  • ↑ Risk for endometrial hyperplasia and carcinoma
  • Pathogenesis:
    • Dysregulation of androgen biosynthesis
    • Insulin resistance
      • Admin of insulin mediators ass. w/ resumption of ovulation
  • Morphology of ovary:
    • Numerous cystic follicles or follicle cysts that enlarge the ovaries
      • Isolated cysts seen in 20-30% of all women
104
Q

Stromal Hyperthecosis

(Cortical Stromal Hyperplasia)

A
  • Usually in postmenopausal women
  • Present w/ sx similar to PCOS
  • Gross: uniform enlargement of both ovaries w/ white/tan appearance on sectioning
  • Microscopic: hypercellular stroma w/ luteinization of stromal cells
105
Q

Ovarian Tumors

Overview

A
  • 80% of ovarian tumors are benign
    • Benign tumors more common in young women (20-45)
    • Malignant tumors more common at later age (45-65)
  • Ovarian CA is 3% of all cancer in females
  • 5th most common cause of CA death in US women
  • Higher mortality rate than other genital CA
  • Often dx after spread beyond the ovary
  • Most are non-functional
  • Some tend to be bilateral
  • Large tumors ⇒ abd distension and discomfort, GI and urinary sx
106
Q

Ovarian Carcinoma

Risk Factors

A
  • ↑ Risk of ovarian CA:
    • Nulliparous or low parity
    • BRCA1 or BRCA2 mutation
      • 20-60% risk of ovarian CA by age 70
      • Most are serous cystadenocarcinomas
  • ↓ Risk of ovarian CA:
    • Oral contraceptive use
107
Q

Ovarian Tumors

Classification

A

WHO Classify according to cell type of origin:

  • Surface/fallopian tube epithelium & endometriosis (most common)
  • Germ cells
    • Pluripotent
    • Migrate to ovary from yolk sac
  • Ovarian stroma
  • Can also see metastatic tumors to the ovary
108
Q

Surface (Muellerian) Epithelium Tumors

Overview

A

Most common cell of origin for ovarian tumors

  • 3 major histologic types of epithelium:
    • Serous
    • Mucinous
    • Endometrioid
  • Each can be benign, borderline or malignant
    • Depends on whether epithelial tumor cells invade ovarian stroma
  • Next can subclassify by other components:
    • Cystic areas ⇒ cystadenomas
    • Cystic and fibrous areas ⇒ cystadenofibromas
    • Mostly fibrous areas ⇒ adenofibromas
109
Q

Surface (Muellerian) Epithelium Tumors

Benign vs Malignant vs Borderline

A
  • Benign lesions
    • Usually show flat epithelium and cystic areas
  • Malignant lesions
    • Usually show papillary projections and solid areas
    • Carcinomas can extend through tumor capsule & seed peritoneal cavity
      • Resulting in ascites
    • Tumors grow slowly
      • Tumors usu. large & has spread beyond the ovary @ dx
    • CA-125 is a marker for some ovarian CA
  • Borderline lesions
    • Neither clearly malignant nor clearly benign
    • Are in a ‘borderline’ category
110
Q

Surface (Muellerian) Epithelium Tumors

Histological Subtypes

A
  • Serous tumors (30% of all ovarian tumors)
    • Benign ⇒ serous cystadenoma
    • Borderline (low malignant potential)
    • Malignant ⇒ serous (+/- papillary) cystadenocarcinoma
      • Most common ovarian CA (40%)
      • 65% are bilateral
  • Mucinous tumors
    • Benign ⇒ mucinous cystadenoma
    • Borderline (low malignant potential)
    • Malignant ⇒ mucinous cystadenocarcinoma
  • Endometrioid tumors
    • Clear cell adenocarcinoma
    • Brenner Tumor
111
Q

Ovarian Carcinoma

Types

A
  • Type I
    • Low grade tumors
    • Often arise in ass. w/ borderline tumors or endometriosis
    • Many histologic subtypes:
      • Low grade serous
      • Endometrioid
      • Mucinous
  • Type II
    • High grade serous carcinoma
    • Arises from serous intraepithelial carcinoma
112
Q

Ovarian Serous Tumors

Characteristics

A

Surface (Muellerian) Epithelium Tumors

  • 30% of all ovarian tumors
    • 40% of all ovarian malignancies
    • # 1 ovarian malignancy (50% if we count borderline)
  • 25% are malignant
    • Benign and borderline most common ages 20-45
    • Malignant later (unless familial)
  • Often large
  • Many are bilateral
    • Especially if malignant
  • Lined by serous (tubal-like) epithelium
    *
113
Q

Ovarian Serous Tumors

Grading and Origin

A
  • Low grade serous ovarian CA
    • Less nuclear atypia and better survival
    • May arise in ass. w/ serous borderline tumors
  • High grade serous ovarian CA
    • Arises from in situ lesions in fallopian tube fimbriae or from serous inclusion cysts in ovary
      • BRCA1/2 women s/p prophylactic BSO had marked epithelial atypia in tubes
        • Named ‘Serous Tubal Intraepithelial Carcinoma’ (STIC)
      • Atypia also seen in sporadic high grade serous ovarian tumors
    • Others arise from cortical inclusion cysts of ovary or implantation of detached fallopian tube epithelium where ovulation has disrupted ovarian surface
114
Q

Ovarian Serous Tumors

Risk Factors

A
  • Unsure of risk factors for benign and borderline
  • Risk factors for malignant serous tumors:
    • Nulliparity
    • Family hx
    • Heritable mutations
      • BRCA1 (5% of ovarian CA pts under 70)
      • BRCA2
      • Women w/ either of these have 20-60% ovarian CA risk by age 70
115
Q

Benign Ovarian Serous Tumors

Features

A
  • Serous cystadenoma
    • Composed of one or several cysts w/ smooth inner & outer surfaces
    • Cysts are lined by a layer of tall columnar, serous secreting, ciliated or non-ciliated cells w/ no atypia
    • Occasional short papillary projections, lined by same kind of cells
    • Outer surface of tumor is covered by mesothelial cells
  • When there is abundant fibrous stroma, benign serous tumor called a cystadenofibroma
116
Q

Borderline Ovarian Serous Tumors

Features

A
  • Not clearly malignant or benign
  • See surface proliferation
  • No definite invasion into stroma
  • Concerning for invasive disease ⇒ must watch after removal
117
Q

Malignant Ovarian Serous Tumors

Features

A

Depends of degree of differentiation

  • Composed of numerous cysts w/ many papillary projections and solid areas
  • Epithelium piles up ⇒ > 1 layer over the surface of the cysts
  • Solid masses of epithelial cells that invade into wall of the cysts
  • Cells are atypical w/ features of malignancy
  • Can see psammoma bodies
    • Also seen in papillary thyroid CA and meningiomas
118
Q

Ovarian Serous Tumors

Clinical Course

A

Depends on degree of differentiation: low grade vs high grade

Even if it has extended to the peritoneum

  • Borderline serous tumors
    • May arise from or extend to peritoneal surfaces as non-invasive implants
    • Possible behaviors:
      • Remain localized ⇒ asymptomatic
      • Slowly spread ⇒ intestinal obstruction or other complications after many yrs
      • Develop into low-grade carcinoma
        • Even then will usu. progress slowly
  • High-grade serous tumors
    • Often widely metastatic throughout abd @ presentation
    • Pts can experience rapid clinical deterioration
119
Q

Ovarian Serous Tumors

Prognosis

A

5-yr survival rate from diagnosis of:

  • Borderline serous tumor
    • Confined to ovary: 100%
    • Involving peritoneum: 90%
    • May have protracted course and recur so 5-yr survival ≠ cure
  • Malignant serous tumor
    • Confined to ovary: 70%
    • Involving peritoneum: 25%
120
Q

Ovarian Mucinous Tumors

Overview

A
  • 20-25% of all ovarian tumors
  • Mid adult life
  • Few are malignant
    • 3% of all ovarian CA
  • Only 5% are bilateral, < serous tumors
  • Rarely involve surface of ovary
  • Many show mutations of KRAS proto-oncogene
  • Tall columnar, mucin-secreting cells
  • Often very large tumors
  • Can be malignant, benign or borderline
  • Pseudomyxoma peritoneii is a complication in 2-5% of pts
    • Mucinous, jelly-like, material throughout abdomen
    • Tends to reaccumulate after removal
    • Also seen w/ mucinous tumors of appendix and colon
121
Q

Ovarian Mucinous Cystadenoma

A

Benign

80% of ovarian mucinous tumors

122
Q

Borderline Ovarian Mucinous Tumors

A
  • Distinguished from cystadenomas by:
    • Epithelial stratification, tufting, and/or papillary intraglandular growth
    • May look similar to adenomas or villous adenomas of the intestine
  • Low malignant potential
123
Q

Ovarian Mucinous Carcinoma

A
  • Malignant growth
    • Confluent glandular growth ⇒ “expansile” invasion
  • Tumors w/ marked epithelial atypia but no invasive features ⇒ “intraepithelial carcinomas”
    • 95% 10-yr survival rate if Stage I
  • Stage I ⇒ 90% 10-yr survival rate
    • Even if invasive
  • Mucinous carcinomas that have spread beyond the ovary ⇒ usually fatal, but rare
124
Q

Endometrioid Ovarian Tumors

Overview

A
  • 10-15% of all ovarian cancer
  • Most are malignant
  • See solid and cystic growth
  • 40% are bilateral
  • Histologically similar to endometrial carcinoma
  • 5-yr survival for Stage I is 75%
  • ~15-20% of pts also have endometriosis
    • Present ~10 yrs earlier than w/o endometriosis
  • Up to 30% of pts also have an independent endometrial carcinoma in the uterus
    • Still a good prognosis, likely not a metastasis
  • Subtypes: Clear cell adenocarcinoma, Brenner tumors
125
Q

Endometrioid Ovarian Tumors

Genetics

A

See similar molecular similarities to endometrial endometrioid carcinoma

  • Mutations in PTEN, PIK3CA, ARIDIA and KRAS ⇒ ↑ PIEK/AKT pathway signaling
    • PTEN mutations also seen in atypical endometriosis
  • Mutations in mismatch DNA repair genes and CTNNB1 (Beta-catenin)
  • TP53 mutations in poorly differentiated tumors
    • Just like in endometrioid CA of endometrium
126
Q

Ovarian

Clear Cell Adenocarcinoma

A
  • Uncommon variant of endometrioid carcinoma
  • Can see similar neoplasm in endometrium, cervix, uterus and vagina
  • May be solid or cystic
  • Microscopic:
    • Large cells w/ clear cytoplasm or hobnail type cells
    • Arranged in solid, tubular or papillary configuration
  • Aggressive tumor
    • Poor prognosis if beyond ovary
127
Q

Brenner Tumor

A
  • Transitional cell tumors
  • Subtype of endometroid tumors
  • 10% of ovarian epithelial tumors
  • Most are benign; usually unilateral
  • Usually solid and firm, 1-20 cm in diameter
  • Fibrous stroma containing scattered groups of transitional epithelial cells
128
Q

Ovarian Cystadenofibroma

A
  • Uncommon variant
  • Pronounced proliferation of fibrous stroma underlying columnar lining epithelium
  • Benign tumor
  • Usually small and multilocular
  • May have mucinous, serous, endometrioid or transitional epithelial components
129
Q

Ovarian Epithelial Tumors

Clinical Characteristics

A
  • Often presents w/ vague sx: GI complaints, urinary sx, pelvic pressure
    • Often found when large
  • Benign tumors are removed ⇒ pt recovers
  • If malignant:
    • May see ascites ⇒ can contain malignant cell
    • Tumor can spread throughout peritoneum ⇒ tiny nodules seed the serosal surface
    • May spread to liver, lungs, GI tract, opposite ovary
  • Serum CA-125
    • Good marker for known disease to monitor recurrence/progression
    • Not for screening
130
Q

Ovarian Germ Cell Tumors

Overview

A
  • 15-20% of ovarian tumors
  • Germ cells are totipotent ⇒ tumors can contain a variety of tissues
  • Most are mature teratomas (Dermoid Cysts) ⇒ benign
  • Others include:
    • Immature teratoma
    • Dysgerminoma
    • Endodermal sinus (yolk sac) tumor
    • Choriocarcinoma
    • Embryonal carcinoma
    • Mixed germ cell tumor
131
Q

Mature Ovarian Teratomas

A
  • Benign teratomas
  • Most common type of ovarian germ cell tumor
  • Usually cystic ⇒ also called “Dermoid cysts”
  • 10-15% are bilateral
  • Filled w/ sebaceous material, hair shafts, and other tissue types
  • Malignant transformation is rare
132
Q

Immature Ovarian Teratomas

A
  • Malignant teratomas
  • Usually seen in children and young adults
  • Contain immature embryonic tissues
  • Mostly solid w/ focal necrosis and hemorrhage
133
Q

Struma ovarii

A

Specialized type of monodermal ovarian teratoma

Entirely composed of mature thyroid tissue

134
Q

Ovarian Dysgerminoma

A

Ovarian counterpart of seminoma

  • Always malignant, usually unilateral
  • 50% of malignant ovarian germ cell tumors
  • 2% of ovarian tumors
  • 75% in 2nd and 3rd decades
  • Some produce gonadotropins
  • Microscopic:
    • Large cells w/ clear cytoplasm and centrally located nuclei in cords or sheets
    • Separated by thin, fibrous septa that contains lymphocytes
135
Q

Ovarian

Endodermal Sinus (Yolk Sac) Tumor

A
  • Malignant and very aggressive
  • Seen in children and young women
  • See yolk sac differentiation w/ Schiller-Duval bodies
    • Looks like a glomerulus
  • Contain intracytoplasmic hyalin droplets
  • Droplets contain Alpha-fetoprotein (AFP) and alpha-1-antitrypsin (AAT)
136
Q

Ovarian Choriocarcinoma

A
  • Rare tumor
  • Histologically identical to choriocarcinoma of placental origin
  • Much more malignant w/ early widespread metastases
  • Produce chorionic gonadotropin (hCG)
  • Often seen as a component in combo w/ other germ cell tumor types
137
Q

Ovarian Embryonal Carcinoma

A
  • Solid tumor w/ necrosis and hemorrhage
  • Micro shows solid sheets and nests of large, primitive cells
  • Can see syncytiotrophoblast-like cells
    • Secrete chorionic gonadotropin (hCG)
    • Can also see ↑ alpha-fetoprotein (AFP) levels
138
Q

Ovarian

Sex Cord Stromal Tumors

A
  • 5% of all ovarian tumors
  • Include:
    • Granulosa cell tumor
    • Thecoma and Fibroma
    • Sertoli-Leydig cell tumor (Arrhenoblastoma)
    • Leydig cell tumor (Hilus Cell Tumor)
    • Lipid cell tumor
139
Q

Ovarian

Granulosa Cell Tumor

A
  • Epidemiology:
    • 5% before puberty
    • 40% after menopause
  • 10% bilateral
  • Gross: smooth surface, lobulated, gray-yellow color
  • Micro: microfollicular w/ Call-Exner bodies
    • See coffee-bean nuclei
  • 75% associated w/ ↑ estrogen production
    • Endometrial hyperplasia/carcinoma in adults
    • Precocious puberty in children
  • ↑ tissue and serum inhibin
  • Risk of recurrence or spread is 5-25%, usually indolent
140
Q

Ovarian

Thecoma and Fibroma

A
  • 65% in post-menopausal women
  • Nearly all are benign
  • Gross: round, firm, solid
  • Micro: fascicles of spindle cells, can sometimes see fat
  • May see ↑ estrogen production in thecomas
  • Can see ascites and right sided hydrothorax (Meigs’ Syndrome) w/ fibroma
  • Can be associated w/ Basal Cell Nevus syndrome
141
Q

Virilizing Tumors

A
  • Sertoli-Leydig cell tumor
  • Leydig cell tumor (Hilus cell tumor)
  • Lipid cell tumor
    • Rare, yellow or brown
    • 25% malignant
  • Ovarian gynandroblastoma
  • Sex-cord Tumor w/ Annular Tubules
  • About 1/3 of cases are associated w/ Peutz-Jegher
142
Q

Sertoli-Leydig Cell Tumor

(Adroblastoma/Arrhenoblastoma)

A
  • Ovarian virilizing tumor
  • Rare tumor
  • Average age is 25 y/o
  • Resembles immature testis w/ Sertoli and Leydig cells
  • ~15% are malignant
143
Q

Leydig Cell Tumor

(Hilus Cell Tumor)

A
  • Ovarian virilizing tumor
  • Can see cells containing Reinke crystals
  • Benign
144
Q

Ovarian Gynandroblastoma

A
  • Ovarian virilizing tumor
  • Mix of Granulosa and Sertoli-Leydig cell tumor
  • Pts have abnl sexual development and gonads of indeterminant nature
  • 50% have a coexistent dysgerminoma
145
Q

Metastatic Ovarian Tumors

A
  • 7% of ovarian tumors are metastatic
  • 50% of these are bilateral
  • Most often originate from stomach, large bowel, appendix, breast, uterus and lungs
  • Krukenberg tumors
    • Usually bilateral and solid
    • Diffuse infiltration by signet ring cells
    • Most often from stomach
146
Q

Fallopian Tube

Histology

A
147
Q

Acute Salpingitis

A
  • Acute infection of the fallopian tube
  • Usu. caused by bacteria from uterine cavity
  • # 1 organism is Gonococcus but can also involve E. coli, bacteroides, strept, chlamydia
  • Gonococci penetrate into subepithelial connective tissue
    • Cause acute inflammation w/:
      • Pus accumulation in tube lumen w/ distension
      • Pus drains out of fimbriated end → pelvis
      • Fibrinous exudate on serosa
  • Nongonococcal bacteria can get to tubes via uterine lymphatics
  • Complications: PID, tubo-ovarian abscess (TOA)
148
Q

Chronic Salpingitis

A
  • Residual inflammation and alteration in tubes after an acute episode or repeated episodes of acute inflammation
  • Gross:
    • Adherence of mucosal plicae and/or closure of fimbriated end
    • fibrous adhesions between tubes, adjacent peritoneum and ovary
    • Can result in pyosalpinx and/or hydrosalpinx
  • Micro: lymphocytic and plasmocytic infiltration
149
Q

Granulomatous Salpingitis

A
  • Subtype of chronic salpingitis
  • l% of pts w/ infertility problem have tuberculosis of oviducts
  • 10% of women pts dying of tuberculosis have tuberculous salpingitis
    • Source is from 1° tuberculosis somewhere else in the body
    • Blood borne TB preferentially involves fallopian tubes vs other female genitalia
    • Lesion starts from the mucosa → muscular layer
150
Q

Paratubal Cyst

A

Very common and benign

151
Q

Salpingitis Isthmica Nodosa

A

Diverticular lesion of tubal epithelium in isthmus

152
Q

Endosalpinigiosis

A

Presence of tubal epithelium in sites other than fallopian tube.

153
Q

Fallopian Tube

Adenomatoid Tumor

A

“Mesothelioma”

  • Benign tumors
  • Small nodule
  • Counterpart can be seen in testis or epididymis
154
Q

Fallopian Tube

Adenocarcinoma

A
  • Very rare
  • Malignant tumors
  • 50% are stage I at dx
  • 40% of pts die w/in 5 years

6. HDS GI Repro (30 decks)

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