Path for Amy Flashcards
more than 80% of LSILs and 100% of HSILs are associated with what?
- high risk HPVs
- HPV-16 being most common
Embryonal Rhabdomyosarcoma is most frequently found in who
infants and children younger than 5
Describe a condylomata acuminatum
- exophytic proliferations covered by nonkeratinized squamous epithelium
- Viral cytopathic changed termed “koilocytic atypia” characterized by typical enlarged hyperchromatic nuclei with perinuclear halo
Age group for Lichen sclerosus
occurs in all but most common post menopausal women
due to fusion of fimbriae and the accumulation of tubal secretions and tubal distension
Hydrosalpinx
Describe the temperature and forms of candida
- Dimorphic but different than most: mold in heat and yeast in cold
- Psuedohyphae and budding yeast at 20C
- germ tubes hyphae molds at 37C
small flat papule due to chronic rubbing or scratching to relieve pruritus
Squamous cell hyperplasia
Neuroendocrine carcinoma of the cervix looks like what?
neuroendocrine carcinoma of other sites (lungs)
describe the Whiff Test
- Gardnerella vaginalis
- Add KOH to sample and it produces the fishy amine odor
Paget cells display what differentiation
apocrine, eccrine, and keratinocyte
Morphology of classic VIN
either discrete white (hyperkeratotic) or a slightly raised, pigmented lesion
-epidermal thickening, nuclear atypia, increased mitoses, and lack of cellular maturation
are condylomata accuminatum precancerous
no
Staging of cervical carcinoma
- 0: carcinoma in situ (CINIII, HSIL)
- 1: confined to cervix
- II: beyond cervix but not to pelvic wall; involved vagina but not lower 1/3
- III: extended to pelvic wall; rectal exam no cancer free space beween tumor and pelvic wall; involves lower 1/3 of vagina
- IV: beyond pelvis or involves mucoas of bladder or rectum; also cancers with metastatic dissemination
Most common STD in the world
Chlamydia trachomatis
Koilocytes
HPV
pathogenesis of Lichen sclerosus
Activated T cells in subepithelial inflammatory infiltrate
Describe lymphogranuloma venereum
- Serotype L1-L3 chlamydia trachomatis
- STD in Africa, Asia and South America
- Painless ulcer at site of contact then progresses to swollen lymph nodes leading to genital elephantiasis in late stage
- Tertiary stage presents with ulcers, fistulas, and genital elephantiasis
Main significance of endocervical polyps
-irregular vaginal spotting or bleeding in POSTMENOPAUSAL women
What is the most common cause of opportunistic mycosis
Candida
lesion from molluscum contagiosum affect what body areas
- genitals
- lower abdomen
- butocks
- inner thighs
What are the risk factors for vulvar VIN
same as those associated with cervical squamous intraepithelial lesions (younger age at first intercourse, multiple sex partners, male partner with multiple sex partners) as both are related to HPV infection
Describe structure of Treponema pallidum
thin spirochete, poorly visible on gram stains but has a gram negative envelope
- outer membrane has endotoxin like lipids, axial filaments=endoflagella=periplasmic flagella allows for motility
- Obligate pathogen but not intracellular
Histology of endocervical polyps
-loose fibromyxomatous stroma covered by mucus secreting endocervical glands, often accompanied by inflammation
HPVs infect what cells
immature basal cells of the squamous epithelium in areas of epithelial breaks, or immature metaplastic squamous cells present at the squamocolumnar junction
Describe CIN classification of cervical premalignant lesions
- cervical intraepithelial neoplasia
- based on degree of dysplasia
- CIN I: mild
- CIN II: moderate
- CIN III: severe or carcinoma in situ
high risk HPV strains for genital cancer
16, 18, 31, and 33
histologically what is lichen sclerosus characterized by
- marked thinning of the epidermis
- Degeneration of the basal cells
- excessive keratinization (hyperkeratosis)
- Sclerotic changes of the superficial dermis
- bandlike lymphocytic infiltrate in underlying dermis
Average age for cervical carcinoma?
45
what does HPV infect
the stem cells basal keratinocytes of the mucosal (genital) epithelium and delevers the genome to the nucleus
Describe Trachoma
- Serotypes A-C
- leading cause of preventable infectious blindness
- follicular conjunctivitis leading to conjunctival scarring . . corneal scarring
A papillary Hidradenoma presents as what?
-a sharply circumscribed nodule, most commonly on the labia majora or interlabial folds
marked cervical inflammation can produce what changes detectable by pap smear
shedding of atypical appearing squamous cells
an uncommon anomaly of the vagina that arises from a failure of mullerian duct fusion and is accompanied by a double uterus (uterus didelphys)
septate or double vagina
name the stages of syphilis
- primary
- secondary
- latent
- tertiary
- congenital
Immature squamous metaplastic epithelial cells in the transformation zone are most susceptible to what infection
HPV
PID due to gonococcus involves what
mucosa
What are the nonneoplastic epithelial disorders of the Vulva
- Lichen sclerosus
- Squamous cell hyperplasia
What to know about Mycoplasma and ureaplasma
- Mycoplasma: no cell wall
- Ureaplasma: urease positive
- both: Chorioamnionitis and premature delivery in pregnant patients and urethritis
- fried egg appearance
what are the 2 glandular neoplastic lesion of the vulva
- papillary Hidradenoma
- Extramammary Paget Disease
uncommon vaginal tumor composed of malignant embryonal rhabdomyoblasts
Embryonal Rhabdomyosarcoma
Lichen sclerosus and cancer?
- not itself a premalignant lesion
- slightly increased chance of developing squamous cell carcinoma of the vulva
Squamous cell hyperplasia and cancer?
not considered premalignant but sometimes presents at the margins of squamous cell carcinomas of the vulva
What is the most common histologic subtype of cervical carcinoma?
2nd most?
- squamous cell carcinoma (80%)
- adenocarcinoma (15%)
Describe what PID is
an infections that begins in the vulva or vagina and spreads upward to involve most of the structures in the female genital system resulting in pelvic pain, adnexal tenderness, fever, and vaginal discharge
invasive keratinizing squamous cell carcinomas that arise in differentiated VIN contain what morphologically
nests and tongues of malignant squamous epithelium with prominent central keratin pearls
what is the main cause of bacterial vaginosis
Gardnerella vaginalis
Describe the stratified squamous nonk-eratinized epithelium of the cervix
- continuous with the lining of the vagina
- secretes more viscous mucus for fertilization
morphology of acute suppurative salpingitis
Neutrophils, plasma cells, and lymphocytes resulting in epithelial injury and sloughing of plicae
Basaloid and warty carcinomas develop from an in situ precursor lesion called what?
CLASSIC vulvar intraepithelial neoplasia (VIN)
Describe the progression of LSIL
LSIL does not progress directly to invasive carcinoma and in fact most cases regress spontaneously
- only small percent progress to HSIL
- not treated like a premalignant lesion
- High level of viral replication and only mild alterations in growth of host cells
Clinical symptoms of vaginal candidiasis
- vulvovaginal pruritis
- erythemia
- swelling
- curd like vaginal discharge
- Severe infection may result in mucosal ulcerations
- AIDS defining illness
Chlamydia trachomatis infections mainly take the form of what?
- cervicitis
- urethritis
- proctitis
Extramammary Paget Disease presents as what in the vulva
pruritic red crusted maplike area usually on the labia majora
scarring of the fallopian tubes creating gland like spaces and blind pouches
Chronic salpingitis
All subtypes of cervical carcinoma are caused by what
high risk HPVs
Candida is ______ postitive
catatlase +: people with chronic granulomatous disease are especially susceptible to these
What cures endocervical polyps
simple curettage or surgical excision
Most of the benign tumors of the vagina occur in reproductive age women and include what?
- stromal tumors (stromal polyps)
- leiomyomas
- hemangiomas
Explain Cervicitis
- At onset of menarche, estrogen from ovaries stimulates maturation of cervical and vaginal squamous mucosa and formation of intracellular glycogen vacuoles
- as they shed, glycogen is substrate for bacteria . . lactobacilli
- lactobacillia produce lactic acid to produce pH below 4.5 . . . also produce H2O2
- if pH becomes to high due to bleeding, sex, or douching, then H2O2 production stops
- antibiotics also suppress lactobacilli and cause pH to rise
- Other organisms are able to grow
Diagnosis of trichomonas vaginalis
-MOTILE trophozoites in methylene blue wet mounts; present with corkscrew motility
Paget cells express what
cytokeratin 7
whats the precursor lesion for keratinizing squamous cell carcinoma
differentiated VIN or VIN simplex
high risk HPVs are also implicated in squamous cell carcinomas arising at what other sites?
- vagina
- vulva
- penis
- anus
- tonsil
- other oropharyngeal locations
Explain role of E6 in HPV
- binds p53 and promotes its degradation by proteasome
- also up regulates expression of telomerase, leading to cellular immortalization
What are the causes of PID
- Neisseria gonorrhoeae (most common)
- Chlamydia
- infections after spontaneous or induced abortions and normal or abnormal deliveries (puerperal infections): Staph, strep, coliforms, clostridium perfringens
Histology of squamous cell hyperplasia
-hyperkeratosis and THICKENED epidermis (acanthosis) with some lymphocytic infiltration
Characteristic clinical appearance of Molluscum contagiosum
- Pearly, dome shapes papules with a dimpled center
- 1-5 mm diameter
- dimpled umbilicated center
- waxy core contains cells with CYTOPLASMIC VIRAL INCLUSION BODIES
Infections by what organisms may produce significant acute or chonic cervicitis
- gonococci
- Chlamydiae
- Mycoplasms
- HSV
What is the most common cause of PID
Neisseria gonorrhea
Embryonal Rhabdomyosarcomas tend to invade locally and cause death by what?
penetration into the peritoneal cavity or by obstruction of the urinary tract
HPVs cannot infect what?
mature superficial squamous cells that cover the ectocervix, vagina, and vulva
in rare cases, what cancer can arise in DES related adenosis
Clear cell adenocarcinoma
Describe what the E6 protein for HPV does
-binds to and mediates the DEGRADATION of p53 and stimulates expression of TERT, the catalytic subunit of telomerase
Then markers are highly correlated with HPV infections and are useful for confirmation of the diagnosis in equivocal cases of SIL
- ki-67 (usually confined to basal layer so if it’s seen in upper layers it’s helpful)
- p16 (increased CDK40
how many condyloma accuminatum are there usually
can be solitary but more likely multifocal
benign genital warts caused by low oncogenic risk HPV, mainly types 6 and 11
Condylomata acuminata
Describe the simple columnar epithelium of the cervix
- mucus secreting
- blockage of mucosal glands –> Nabothian cysts
- simple branched tubular glands
What is used to see chlamydia
NAATs: nucleic acid amplification test
Describe what the E7 protein for HPV does
- binds to RB protein and displaces the E2F transcription factors that are normally sequestered by RB, promoting progressing through the cell cycles
- also inactivates the CDK inhibitors p21 and p27
- also bind and activate cyclins E and A
Virtually all primary carcinomas of the vagina are squamous cell carcinomas associated with what/
high risk HPV
Clinical symptoms of trichomonas vaginalis
- asymptomatic in males
- females may complain of yellow, frothy vaginal discharge, vulvovaginal discomfort, dysuria (painful urination), and dyspareunia (painful intercourse)
- The vaginal and cervical mucosa typically has a fiery-red appearance, with marked dilatation of cervical mucosal vessels resulting in characteristic colposcopic appearance of “STRAWBERRY CERVIX”
Paget disease of vulva and cancer?
typically not associated with underlying cancer and confined to the epidermis of vulvar skin
-contrast to Paget disease of the nipple in which 100% have an underlying ductal breast carcinoma
Primary lesions of the vagina are rare, the most serious being what?
vaginal squamous cell carcinoma
Describe Jarisch-Herxheimer reaction
starts during first 24 hours of antibiotic treatment and presents with increase in temperature, decrease blood pressure, rigors, and leukopenia
describe Gardnerella
gram negative bacillus
Which strain of poxvirus is most often sexually transmitted
MCV-2
invasive tumor of the vagina most often involves what location
upper vagina particularly posterior wall at the junction with the ectocervix
Describe the structure and features of pox virus
- dsDNA
- can makes its own envelope
- only DNA virus that replicates in the cytoplasm and has own RNA polymerase
- dumbbell shaped core
Progression to invasive carcinoma from an SIL takes how long
years to more than a decade
describe pathogenesis of Gardnerella vaginalis
-endogenous normal flora gets disturbed, increasing pH, allowing overgrowth
Describe the structure and features of Herpes virus
Large, linear dsDNA enveloped, icosahedral
Cysts that arise from remnants of mesonephric duct
Gartner duct cyst
What areas of the genital tract does herpes involve in order of frequency
- cervix
- vagina
- vulva
These are common lesion found along the lateral walls of the vagina and are derived from wolffian (mesonephric) duct rests
Gartner duct cysts
Describe the newer two tiered classification of cervical dysplasia based on patient management
- CIN I = low grade squamous intraepithelial lesion (LSIL)
- CIN II and III = high grade (HSIL)
What is the most common histologic type of vulvar cancer
squamous cell carcinoma
What serotype of chlamydia cause bacterial STD in US?
D-K
describe progression of HSIL
- progressive deregulation of the cell cycle by HPV
- lower rate of viral replication
- Derangement of cell cycle may become irreversible and lead to a fully transformed malignant phenotype
- ALL HSILS ARE CONSIDERED TO BE AT HIGH RISK FOR PROGRESSION TO CARCINOMA
what general process do proteins E6 and E7 do
speed cells through G1-S cycle checkpoint
Most important strains of HPV in cervical cancer
- HPV 16 (almost 60%)
- 18 (10%)
peak age for for basaloid and warty vulvar cancer
6th decade
Septation of the vagina can be due to exposure to what ?
in utero expoosure to diethylstilbestrol (DES)
What is the greatest risk factor for squamous cell carcinoma of the vagina
previous carcinoma of cervix or vulva
For children 2-12, molluscum contagiosum can be passed through what?
direct contact
infection of fallopian tubes
Acute suppurative salpingitis
Morphology of differentiated VIN
- marked atypia of the basal layer
- normal appearing differetiation of the more superficial layers
lesions in the lower 2/3 of the vagina metastasize where?
upper vagina?
- inguinal lymph nodes
- regional iliac nodes
Describe the mechanism by which HPV enters a cell
- binds to receptor: dependent only on CAPSID PROTEIN L1
- generally internalized via a clatherin dependent endocytic mechanism
- after getting internalized and viral coat is disassembled which allow viral genomes access to the cellular transcription and replication machinery
infection of fallopian tubes and ovary
Salpingo-oophoritis
HSV lesions typically develop 3 to 7 days after transmission and are often associated with what symptoms?
systemic such as:
- fever
- malaise
- tender inguinal lymph nodes
Cowdry bodies
INTRAnuclear inclusion bodies in Herpes
pus in tubal lumen
pyosalpinx
Morphology of herpes
multinucleated squamous cells containing eosinophilic to basophilic viral inclusions with a “ground glass” appearance
as the squamocolumnar junction moves upwards into the endocervical canal with time, the replacement of the glandular epithelium by advancing squamous epithelium is a process called what?
squamous metaplasia
Chronic salpingitis can lead to what?
infertility or ectopic pregnancy
Explain role of E7 in HPV
- binds the hypophosphorylated (active) form of RB and promotes its degradation via the proteasome pathway
- also binds and inhibits p21 and p27 . . CDK inhibitors
2 forms of chlamydia
- Elementary body: metabolically inactive and infectious
- Reticulate body: metabolically active and in the cell
Diagnosis of SIL is based on identification of what/
- nuclear atypic . . nuclear enlargement
- hyperchromasia (dark staining)
- course chromatin granules
- variation in nuclear size and shape
- nuclear changes are often accompanied by cytoplasmic “HALOS” . . created by E5 . . . called KOILOCYTIC ATYPIA
Diagnosis of herpes infection is based off clinical symptoms . .what are these?
- 3-7 days post transmission: fever, malaise, tender inguinal lymph nodes
- Red papules that progress to vesicles and then to painful coalescent ulcers
- Cervical or vaginal lesions present with severe purulent discharge and pelvic pain
- Lesion around urethra may cause painful urination and urinary retention
The gravest consequence of HSV infection is what?
transmission to the neonate during birth
Describe secondary syphilis
- Maculopapular COPPER COLORED rash that is diffuse and includes palms and soles
- patchy alopecia
- Condyloma lata: FLAT wart like perianal and mucous membrane lesions
- Highly infectious
common benign exophytic growths that arise within endocervical canal
endocervical polyps
diagnosis of vaginal candidiasis is made by finding what?
psuedospores or filamentous fungal hyphae in wet KOH mounts of the discharge or on PAP smear
describe the pap smear in Gardnerella vaginalis
- superficial and intermediate squamous cells covered with a shaggy coating coccobacilli
- pH > 4.5
- CLUE CELLS
Vaginal adenosis is found in 35-90% of women with what
DES exposure
Describe primary syphilis
- NONtender chancre
- clean, indurated edge
- contagious
- heals spontaneously in 3-6 weeks
peak occurrence for keratinizing squamous cell carcinoma
8th decade
What is the most common malignant tumor to involve the vagina
carcinomas spreading from the cervix
-followed by primary squamous cell carcinoma
Guarnieri bodies
-CYTOPLASMIC inclusion bodies in molluscum contagiosum
clinical presentation of chlamydia
- primary infection characterized by a mucopurulent discharge containing a predominance of neutrophils
- Not visible in gram stains
- WATERY discharge
What is by far the most important factor in the development of cervical cancer
high risk HPVs
Describe an Embryonal Rhabdomyosarcoma
- polypoid, rounded, bulky masses that have the appearance and consistency of grapelike clusters
- small tumors with oval nuclei, with small protrusions of cytoplasm from one end, resembling a tennis racket
Describe the progression of adenosquamous carcinoma or neuroendocrine carcinoma
- shorter progression from in situ to invasive
- more likely advanced disease and less favorable prognosis
describe neonatal herpes infections from TORCH
- Disseminated with liver involvement and high mortality
- encephalitis, also high mortality
- affects skin, eyes, or mouth
Describe basaloid and warty carcinomas
- related to infection with high risk HPVs . . most commonly 16
- less common type of vulvar carcinoma’
- younger ages
infections that are very common and may cause significant discomfort but are without serious squelae?
- Candida
- Trichomonas
- Gardnerella
Molluscum contagiosum is from what virus
Poxvirus
What is Fitz-Hugh Curtis syndrome
violin sting adhesions due to PID
Describe congenital syphilis
- Desquamating maculopapular rash and tabies dorsalis
- Saber Shins or anterior bowing of tibia
- Saddle nose
- Hutchinson’s notched teeth
- MULBERRY MOLARS with enamel outgrowths
- Deafness
how many males and females with herpes are symptomatic
- all males
- 1/3 females
HPV alone is not sufficient for carcinogenesis. explain the other influencers
- immune status and co carcinogens are influencers
- cigarette smoking, coexisting microbial infections, hormone changes, dietary deficiencies
accumulation of pus
Tubo-ovarian Abscess
What are the two groups of types of vulvar squamous cell carcinomas
- Basaloid and warty carcinomas
- Keratinizing squamous cell carcinomas
What does the smear show for Neisseria gonorrhea
- inflammatory exudate with phagocytosed gram-negative diplococci within neutrophils (PMNs)
- definite diagnosis requires detection of gonococcal RNA or DNA
Features of Bartholin cyst
- Acute inflammation (adenitis) and may result in an abscess
- common . . all ages
- obstruction of the duct
- lined with transitional or squamous epithelium
- may become large 3-5 cm
- pain and local discomfort
- either excised or opened permanently
pregnant patients with Gardnerella vaginalis
-can lead to premature labor
Describe latent syphilis
no clinical symptoms
pathogenesis of Chlamydia
-infection of nonciliated columnar or cuboidal epithelial cells of mucosal surfaces leading to granulomatous response and damage
is candidiasis considered a sexually transmitted disease
no
describe Tertiary syphilis
- Gummas or syphilitic granulomas: soft growth with firm necrotic centers
- Aortitis and aneurysm of ascending aorta with TREE BARKING appearance: destroys vasa vasorum that supplies aorta
- CNS inflammation: damage to POSTERIOR columns of spinal cord and ocular defects of ARGYLL ROBERTSON PUPILS (react to accommodation but not light)
Advanced cervical carcinoma spreads how
by direct extension to contiguous tissues
Describe the grading of SIL based on expansion of immature cell layer from its normal basal location
- if confined to lower 1/3 of epithelium then LSIL
- if expanded to upper 2/3 then HSIL
Development of symptomtic candiciasis is typically a result of a disturbance in the patients vaginal microbial ecosystem with what?
- antibiotics
- diabetes
- contraceptives
Clinical symptoms of Gardnerella vaginalis
-thin, green, gray, malodorous (fishy) vaginal discharge
This present as smooth white plaques or macules that in time may enlarge and coalesce, producing a surface that resembles porcelain or parchment
Lichen Sclerosus
Most HPV infections are transient and are eliminated by the immune response in the course of months. On average, 50% of HPV infections are cleared within how long?
-90% within how long?
- 8 months
- 2 years
Acute complications of PID
- peritonitis and bacteremia
- endocarditis, meningitis, and suppurative arthritis
PID due to non gonococcal bacteria following abortions or other surgical procedures spread upwards through what
lymphatic and venous channels rather than on the mucosal surfaces . . . more inflammation within deeper layers
What are the rare cervical carcinomas that make up the last 5%
- adenosquamous
- neuroendocrine
Describe a Gartner duct cyst
-1-2 cm fluid filled cysts that occur in submucosal location
Describe the HPV vaccines
- Gardasil: 6, 11, 16, and 18
- Gardasil 9: original 4 + 31, 33, 45, 52, 58
- Cervarix: 16 and 18
describe structure of HPV
- non enveloped
- double stranded
- Circular DNA virus
- icosahedral capsid
The prevalence of HPV in cervical smears in women with normal Pap test results peaks between what ages
-20 and 24, related to onset of sexual activity
Classic VIN occurs mainly in who
reproductive age women and includes lesion designated formerly as carcinoma in situ or Bowen disease
Infections that are major causes of female infertility
- Neisseria gonorrhoeae
- Chlamydia
Diagnosis of Treponema pallidum
visualized by immunofluorescence or DARK FIELD microscopy
What is the premalignant lesion of squamous cell carcinoma of the vagina
vaginal intraepithelial neoplasia
Describe the lining of the cervix
- Ectocervix (visible in the vaginal exam): nonkeratinizing squamous epithelium
- Endocervix: Single layer of columnar epithelium
- Junction between the ectocervix and endocervix is the transformation zone . . squamocolumnar junction
When residual glaandular epithelium in the vagina persists into adulthood
vaginal adenosis
Describe Trichomonas
large flagellated ovoid protozoan that is usually transmitted by sexual contact and develops within 4 days to 4 weeks
during an acute HSV infection, the virus migrates where
regional lumbosacral nerve ganglia and establishes a latent infection
The risk of classic VIN progressing to invasive carcinoma is higher in who?
women older than 45 years of age or in women who are immunosuppressed
infections implicated in preterm deliveries
- Ureaplasma urealyticum
- Mycoplasma hominis
What is a papillary hidradenoma commonly confused with
carcinoma because of its tendency to ulcerate
Neonatal chlamydia
- conjunctivitis and pneumonia . . . 1-2 weeks later
- Taccato cough
vaginal adenosis presents as what
red and glandular and stands out from surrounding pale pink vaginal mucosa
the histologic appearance of a papillary hidradenoma is identical to that of what?
Describe it
intraductal papilloma of the breast
-papillary projections covered with 2 layers of cells: an upper layer of columnar secretory cells covering a deeper layer of flattened myoepithelial cells
Describe keratinizing squamous cell carcinomas of vulva
- unrelated to HPV
- more common in older women due to long standing lichen sclerosus or squamous cell hyperplasia
Decribe how the squamocolumnar junction changes
- variable and changes with age and hormone influence
- During reproductive years it moves out into the ectocervix
- as woman ages, the transformational zone moves up into the endocervical canal