10. Vulvar, Vaginal Cervical Uterine Path Flashcards
1
Q
Embryonically, there are mesonephric ducts (wolffian duct) and paramesonephric ducts (mullerian duct) which form many things. Unfused upper portion of mullerian ducts form the fallopian tubes, fused lower portions make the uterus, cervix and upper vagina, endometriosis is derived from which duct?
A
Mullerian derived lesion
2
Q
Urogenital sinus forms the lower vagina, mesonephric ducts USUALLY regress, gartner duct cysts occur when remnamts of the mesonephric duct remain as epithelial includsions adjacent to the ovaries, tubes and uterus, in the cervic and vagina these rest may be cystic… Coelomic epi (mesothelium) becomes the lining of the female gential ttract as well as the?
A
ovarian surface
3
Q
Chlaymdia trachomatis is associated with pelvic inflammatory disease (PID)/serous discharge, what is associated with PID, purulent discharge, gram negative diplococci within neutrophils?
A
Neisseria Gonorrhea
4
Q
Trichomonas vaginalis is large flagellated ovoid protozoan , yellow frothy vaginal discharge, strawberry cervix, ureaplasma urealyticum and mycoplasma hominis is most commonly associated with?
A
pre term deliveries
5
Q
What infection/STI is a gram negative bacillus, main cause of bacterial vaginosis, thin grey-green malodorous fishy vaginal discharge, assoc w premature labor?
A
Gardnerella Vaginalis
6
Q
what infection is common and involves the cervix >vagina> vulva, by age 40, 30% of females present with antibodies to type 2, presents as newly infected females w painful lesions 3-7 days post infection w fever, malaise and tender inguinal LN?
A
HSV
7
Q
HSV has red papules that progress to vesicles and then to painful coalescent ulcers, present with purulent discharge and pelvic pain, lesions around urethra can cause pain and urinary retention, all males are?
A
Asymptomatic
8
Q
Herpesvirus family is large linear dsDNA, enveloped, icosahedral, derives envelope from nuclear membrane w intranuclear inclusion bodies known as *COWDRY bodies, infection remains latent in the ?
A
lumbosacral nervous ganglion
9
Q
HSV on histo see multinucleated squamous cell with eosinophilic to basophilic viral inclusions w a ground glass appearance, HSV2 infection enhances acquisition and transmission of?
A
HIV1
10
Q
HSV is diagnosed clinically*,aspiration of exudate shows viral cytopathic effect (ground glass appearance) in 48-72 hours, there is no current treatment but acyclovir shortens the active phase… what special stain is used?
A
Tzank Smear
11
Q
Molluscum Contagiosum (POXVIRUS) is skin or mucosal with 4 subtypes, MCV1 most common, MCV2 MC sexually transmitted, dsDNA,with guarnieri bodies (inclusion) which are sites of viral replication w *dumbbell core, clinically will see a pearly, dome shaped papule with a?
A
dimpled center
(1-5mm in diameter)
-central waxy core w cytoplasmic viral inclusion bodies
12
Q
What infection is an opportunistic yeast due to disturbance of microbial ecosystem, increased in DM, abx, preg, burn pts, MCC of mycosis, they are dimorphic (mold in heat, yeast in cold), and forms pseudohyphae and budding yeast at 20C and germ tubes hypahe molds at 37?
A
Candida (Moniliasis)
13
Q
Candida presents with intense vulvovaginal pruritis, erythema, and swelling with a thick white curdlike/cottage cheese like discharge, dx via fungal hypahe on *wet KOH mounts or pap smear, it is not considered a?
A
STI
14
Q
What infection is large flagellated ovoid protozoan w sexual transmission 4-14 days to develop and MC curable STI, presents w yellow frothy discharge, discomfort, dysuria, dyspareunia, fiery red mucosa of vagina/cervix, dilation of cervical vessels = straberry cervix.. dx via motile trophozoites in methylene blue wet mount, present with corkscrew motility?
A
Trichomonas Vaginalis
15
Q
What infection is gram- bacillus, main cause of vaginitis (bacterial), present w thin green-grey malodorous fishy discharge, may cause premature labor, pap smear shows superficial intermediate squamous cells covered by a shaggy coating of coccobacilli = CLUE cells?
A
Gardberella Vaginalis
16
Q
Gardberella Vaginalis cultures contain anaerobic pepto-streptococci and aerobic a-hemolytic streptocicci, need to differentiate it from candidi and trichomonas by examining a slide to look for clue cells, what test is when there is a fishy amine oder when KOH is added?
A
Whiff Test
17
Q
What 2 infections may cause vaginitis and cervicitis, implicated in chorioamnionitis and premature delivery in preg patients, one is urease positive and the otther has no cell wall, FRIED EGG APPEARANCE?
A
Ureaplasma Urealyticum
Mycoplasma Hominis
18
Q
What is the MC STI in the world, one of the main causes of PID, small gram - obligate intracelliular bacteria, w two forms including elementary body (metabolically inactive- infectious form in endosome), and reticulate body (metabolically active form)?
A
Chlamydia Trachomatis
19
Q
Chlamydia Trachomatis is usually asymptomatic or presents similar to ghonorreah w a mucopurulent discharge of neutrophils, (gonorrhea=serous thin watery), may ascend from cervix, diagnosed with what test?
A
NAAT
Nucleic Acid Amplification Test
20
Q
What is an infection that begins in the vulva or vagina and spreads upward to involve most of the female genital system, causing pelvic pain, adnexal tenderness, fever and vaginal discharge, travel via lymph or venous systems rather than the mucosal route (except gonorrhea)?
A
Pelvic Inflammatory Disease PID
21
Q
PID is MC caused by neisseria gonorrhea and chlamydia trachomatis, acute complications invlude peritonitis and bacteremia, chronic sequale include infertility, tubal obstruction, ectopic preg, pelvic pain and what syndrome, which is a rare complication involving liver capsule inflammation leading to creation of adhesions? (gonorrhea)
A
Fitz-Hugh Curtis Syndrome
22
Q
Lymphogranuloma venereum from chlamydia* types L1-3 is prevalent in africa, asia and south america, tertiary stage presents with ulcers, fistulas, and genital elephantiasis, initially presents with what at the site of contact and then progresses to swollen lymph nodes?
A
PAINLESS UCLER
23
Q
What is from chlamydia serotypes A,B,Ba,and C and is the leading cause of preventable infectious blindness, follicular conjunctivitis leading to conjunctival scarring- in turned eyelashes leading to corneal scarring and blindness?
A
Trachoma
24
Q
Treponema pallidum (syphilis)is a thin spirochete, poorly visible on gram stain, outer membrane has endotoxin like lipids - serodiagnosis, transmitted sexually, characterized by endarteritis resulting in lesions, visualized on?
A
dark field microscopy
25
Jarisch-Herxheimer reaction starts in the first 24 hours of abx treatment and presents with temp, dec BP, rigors and leukopenia (syphilis), in the primary stage there is what, which is clean, indurated edge and contagious heals in 3-6 weeks?
**NON-tender painless chancre (wart)
26
The secondary stage of syphilis is maculopapular (copper colored) rash that is diffuse and includes palms and soles, patchy alopecia and condyloma lata (highly infectious), during the latent stage, what are the symptoms?
NO SYMPTOMS during latent
27
Tertiary stage of syphilis is assoc w gummas or syphilitis granulomas that are soft growths w firm necrotic centers, aortitis and aneurysms associated with tree barking appearance of the ascending aorta, CNS inflammation occurs- damage to posterior column of spinal cord and ocular defect called?
Argyll Robertson (prostitutes) - pupils which reacto accommodation but has no rxn to light
28
In congenital syphilis, there is a desquamating maculopapular rash and *tabes dorsalis, can have saber shins or anterior bowing of the tibia, saddle nose, hutchinsons notched teeth and what in the teeth in which the enamel has outgrowths?
Mulberry Molars
| Tx: Penicillin G
29
Neisseria Gonorrhea is an ascending infection that causes PID, shows marked acute inflammation of mucosal surfaces w acute suppurative salpingitis, as well as salpingo-oophritis, and tubo-ovarian abscesses, and may lead to what which is scarring of denuded tubal plicae causing gland like spaces and blind pouches?
Chronic Salpingitis
30
Neisseria Gonorrhea dx via detection of DNA/RNA, culture or NAAT, **Thayer-Martin Agar**, treat with abx, what is a common syndrome this can lead to?
Fitz-Hugh Curtis Syndrome
31
HPV presents as multiple warty lesions on the perineum and around the anus in low risk types 6/11, is non-enveloped, double stranded, circular DNA virus w icosahedral capsid, infected epithelial cells are call what, and have a *krinkled* nucleus that looks like a raisin?
Koliocytes
32
HPV has high risk types which includes 16, 18, 31, 35 and has oncogenic potential explained by two viral genes E6 and E7, E6 degrades p53 and E7 binds to and degrades what?
RB, allowing cells to speed through the G-S cell cycle checkpoint
33
What infection can cause stillbirth, neonatal sepsis or abortion, in infants can lead to widespread dz w exudative meningitis, is a facultative intracellular bacillus, *loook for gram - intracellular bacilli in CSF***?
Listeriosis / Listerio Monocytogenes
34
Haemophilus ducreyi is an acute ulcerative infection that leads to what, which is tender and erythematous on the external genitalia, and may have multiple, regional LN enlarged 1-2 weeks after *buboes*, prevalent in tropical africa/ SE asia- cofactor in HIV infection, sometimes seen on silver stain?
PAINFUL CHANCROID (soft chancre (remember firm chancre is syphilis) )
35
Klebsiella can cause *granuloma inguinale* (aka donovanosis) which is a raised papular lesions on the moist stratified squamous epithelium of the genitalia, ulceration w lots granulation tissue, endemic in rural developing countries, untreated could lead to lymph obstruction = elephantiasis, look for encapsulate coccobacilli in macrophages, aka?
Donovan Bodies! (giemsa stain)
36
The follows are all STIs with what in common?
HSV
Syphilis
Chancroid (haemophilus Ducreyi)
LGV-lymphogranuloma venereum (Chlamydia trachomatis (L1-3)
Klebsiella
STIs WITH ULCERS!
37
What is a cyst associated with the vulva due to acute inflammation (adenitis) that can create an abscess, occurs at all ages, due to obstruction of duct by inflamm, lined w transitional or squamous epithelium, 3-5cm in diameter, w pain and local discomfort, tx w excision?
Bartholin Cyst
38
What is a nonneoplastic epithelial DO which is a descriptive clinical term for opaque white plaque like epithelial thickening that may produce pruritis and scaling, commonly d/t inflamm dermatoses, lichen sclerosis/ squamous cell hyperplasia and neoplasia?
Leukoplakia
39
What is smooth, white plaques or macules seen on the vulva which may enlarge and coalesce forming a porcelain/parchment surface v, v thin plaque, occurs at any age but MC in post-menopausal females, labia become atrophic and agglutinated and the vag orifice constrict when entire vulva is involve- AI like: activated T cells present in subepithelial inflam infiltrate and inc. frequency of AI disorders in affected women?
Lichen Sclerosis
40
Lichen Sclerosis is NOT a premalignant lesion, women with symptomatic lichen sclerosis have a slightly increased risk of developing SCC of the vulva, patients have inc risk of autoimmune AI disorders*, on morphology what is the key finding in the epidermis?
*Marked thinning of the epidermis (parchment paper)
41
Lichen Sclerosis histologically will also show degeneration of basal cells, excessive keratinization, sclerotic changes of the superfificial dermis and activated T cells are seen in the subepi inflammatory infiltrate also called what kind of infiltrate?
Band-like infiltrate
42
What nonneoplastic epithelial DO is nonspecific condition resulting from rubbing or scratching of the skin to relieve pruritus, presents as leukoplakia- histo reveals acanthosis (thickening of epidermis) and hyperkeratosis, NOT premalignant?
Squamous Cell Hyperplasia (hyperplastic dystrophy or lichen simplex chronicus)
*morph: thickening of epiderm and hyperkeratosis
43
What is a b9 exophytic genital wart due to HPV 6/11, usually multifocal involving vulvar, perineal and perianal areas, NOT precancerous lesions?
Condyloma Acuminatum (genital wart d/t HPV)
44
Condyloma Acuminatum has papillary exophytic tree-like cores of stroma covered by thickened squamous epi, with *koilocytic atypia in epithelium (atypical, enlarged hyperchromatic nuclei w perinuclear halos).. What is a benign raised leasion due to syphilis/treponema pallidum?
Condyloma Latum
45
Carcinoma of the vulva is MC, 2/3 in females >60, and has two types, basaloid and warty carcinoma related to HPV 16 (younger age~ 50) and *keratinizating SCC not related to HPC which is seen in?
Older aged women (MORE COMMON)
46
What carcinoma is the following morphology?
Exophytic or indurated and ulcerated
Small tightly packed basaloid cells
foci of central necrosis
Basaloid Carcinoma
47
What carcinoma is the following morphology?
Exophytic, papillary architecture
prominent koilocytic atypia
Warty Carcinoma
48
CLASSIC Vulvar intraepithelial neoplasia (VIN) is a precursor lesion to basaloid and warty carcinoma of the vulva, MC in females of reproductive age- HPV16 related, presents as multicentric around the vuvla, 10-30% also have vag or cervical HPV, most likely to progress to invasive carcinoma in females?
older than 45, or immunocompromised
49
Vulvar intraepithelial neoplasia (VIN) on histo will see discrete white or slightly raised pigmented lesions, epidermal thickening, nuclear atypia, increased mitoses/ lack cellular maturation, will see nests and cords of small, tightly packed cells that lack maturation and resemble the?
basal layer of normal epi
50
What carcinoma occurs in ODLER women with long standing lichen sclerosis or squamous cell hyperplasia, not related to HPV, *arises from precursor lesion called differentiated vulvar intraepithelial neoplasia?
Keratinizing SCC
51
Differentiated VIN is caused by increased freq of TP53 mutations, may be assoc w chronic epithelial irritation, on histo see marked atypia of basal layer of squamous epi, normal differentiation of superficial layers, invasive keratinizing SCC and will see PROMINENT central?
Keratin pearls !! yay
52
Summary:
30% vulvar cancers cause by HPV (16) develop from in situ lesion called classic VIN
70% vulvar cancers not related to HPV, develop d/t lichen sclerosus or squamous cell hyperplasia which causes differentiated VIN
MEOW
53
What is a glandular neoplastic lesion of the vulva that is a sharply circumscribed nodule, MC on the labia majora or inter-labial folds, tends to ulcerate so clinically confused w carcinoma, histo identical to intraductal papilloma of the breast, projections w two layers: columnar secretory cells and flattened myoepithelial cells?
Papillary Hidradenoma
54
Extramammary Paget Disease is a pruritic, red, crustedm map-like area usually on the labia majora, not associated with underlying cancer (like breast pagets-100% assoc w ductal breast carc), typically not assoc w underlying cancer and is confined to the?
Epidermis of the vulvar skin
55
Extramammary Paget Disease is intraepithelial proliferation of malignant cells, cells larger than keratinocytes, may be single or small clusters, express apocrine, eccrine and keratinocyte differentiation, have pale cytoplasm w mucopolysaccharide that stains PAS, Alcian blue or mucicarmine stains, expresses ? **
Cytokeratin 7
56
Extramammary Paget Disease is located intraepithelially, confined to *epidermis* of vulvar skin and spreads laterally within the epidermis, tx w wide excision, mets usually do not occur and remains in the epidermis, if invasion occurs then prognosis is?
POOR
57
Common symptoms of PID caused by N. Gonorrhea and C. Trachomatis include pelvic pain, adnexal tenderness, fever and?
vaginal discharge
58
What presents with severe RUQ pain, fever chillls, headaches, and general feeling of poor health (malaise), due to gonorrhea, characterized by peritonitis and peri-hepatitis and see 'violin strings' on liver?
Fitz-Hugh Curtis Syndrome
59
HPV virus infects what cells of the mucosal epithelium and delivers the genome to the nucleus?
Basal keratinocytes
60
Risk of metastasis of vulvar carcinomas include size of primary tumor, depth of invasion and lymphatic envolvement. Vulva and distal 1/3 vagina drain to inguinal nodes while proximal 2/3 of vagina and uterus drain to?
Internal nodes
61
Septate/double vagina is due to failure of the mullerian duct fusion and is accompanied by a dobule uterus known as?.. Either caused by genetic syndromes or in utero exposure to DES (diethylstilbestrol) which is used to prevent threatened abortions
Uterus Didelphys
62
Embryonal epi is columnar, endocervical type and is replaced w squamous epithelium ascending from the urogenital sinus. Small patches of residual glandular epithelium which persists into adult life is known as?
Vaginal Adenosis
63
Vaginal Adenosis is red glandular areas that stand out from normal pale pink vaginal mucosa, MC in females exposed to DES in utero, rarely will see what carcinoma arising?
Clear cell carcinoma
64
What is a common lesion found along the lateral vaginal walls derived from wolffian-mesonephric duct rests, 1-2cm fluid filled cysts found in the submucosa?
Gartner Duct Cyst
65
Virtually all primary carcinoma of the vagina are SCC associated with high risk HPVs, increased risk if previous vulvar/cervical carcinoma, arises from premalignant lesion = vaginal intraepithelial neoplasia VIN, most invasive tumors affect the posterior wall of the upper vagina at the junction of?
*the ectocervix
66
What is a rare tumor of malignant embryonal tissue in infants and children <5years, tumors invade locally and cause death via penetration into the peritoneal cavity and obstruction of the urinary tract?
Embryonal Rhabdomyosarcoma (Sarcoma Botryoides)
67
Embryonal Rhabdomyosarcoma have small cells with oval nuclei and cytoplasmic protusions (tennis racket shape), tumor cells crowded in a cambium layer beneath vaginal epi, grow as polypoid, rounded, bulky masses from vagina and appear as what clusters?
Grapelike clusters
surgery+chemo
68
The cervix has external vaginal portion known as the ectocervix which is visible on exam w/ mature squamous epithelium, endocerivcal canal is columnar mucus secreting epi that converges with ectocervix to form?
Squamocolumnar Junction = transformation zone
69
SCJ or transformation zone is location where squamous and columnar epi meet. In the transformation zone, metaplastic epithelial cells are most susceptible to HPV infection, which is the leading cause of cervical cancer, Transformation zone is where cervical ?
precursor lesions and cancer will develop**
70
During reproductive years, the SCJ moves out onto the ecotcervix and as a woman ages, the SCJ retreates back up into the endocervical canal. HPV infects WHICH cells of the squamous epithelium in areas of epithelial break?
***Immature basal cells
| **HPV cannot infect mature* superficial squamous cells
71
What is the dominant microbial species of the normal vagina, gram- non-spore forming bacillus, which produce lactic acid and maintains a ph of less than 4.5 which suppresses growth of other saprophytic and pathogenic organisms, at low pH produce H2O2 which is bacteriotoxic?
Lactobacilli in the vagina
72
When the pH in the vagina is increased due to bleeding, sex or antibiotics, leads to decreased H202 and promotes overgrowth of other organisms leading to cervicitis or?
Vaginitis
73
What is a common, benign exophytic growth within the endocervical canal, has loose fibromyxomatous stroma covered by mucus secreting endocervical glands +/- inflammation, varies from small sessile bumps to large polypoid masses, *may be source of irregular vaginal spotting?
Endocervical Polyps
74
Cerivcal carcinoma is the 3rd MC cause of cancer in women worldwide, progress slowly, allowing screening and detection, PAP smears detects precursor lesions and low-stage, and has a strong associated with HPV, which HPV strain accounts for 60% of cervical cancers?
HPV 16 (HPV18 is 10%)
75
HPV is a DNA virus, viral DNA remains extrachromosomal, alone is not sufficient to cause cervical cancer, progression to carcinoma is influenced by exposure to what, along with host immune status?
Cocarcinogens
76
HPV infections are extremely common and are asymptomatic, do not cause tissue changes and are no detected on pap tests, peak HPV positivity is 20-24, most infections are transient and 50% are cleared in 8 months, 90% by?
24 months
| persistent infection inc risk of cervical cancer
77
HPV can ONLY infect immature squamous cells while it REPLICATES in ?
*MATURE squamous cells
78
Squamous intraepithelial lesions (SIL) are classified into two tier system and are most commonly caused by HPV16... LSIL is low grade squamous intraeptihelial lesion, previously CIN1 (mild cervical intraepithelial neoplasia), 80% of LSILs are associated with?
high risk HPVs
79
HSIL: high grade squamous intraepithelial lesions, previously CIN2/3/CIS (moderate dysplasia/severe/carcinoma in situ) is caused 100% of the time by?
High risk HPVs
80
LSIL is associated with HPV infection, high level of viral replication, mild alteration in growth of host cells, does NOT progress directly to invasive carcinoma, 60% regress spontaneously, 10% go to HSIL, not treated as a premalignant lesions, they are how much more common than HSIL?
10x more common
81
HSILs have progressive dregulation of the cell cycle by HPV, increased cellular proliferation, decreased epithelial maturation, lower rate of viral replication, 80% develop from LSIL, derangements may become irreversible- ALL HSILs are considered to be?
high risk for progression to carcinoma (SCC)
82
Diagnosis of HSIL/LSIL is based on ID of nuclear atypia with nuclear enlargement, hyperchromasia (dark staining), coarse chromatin granules, variation in nuclear size and shape, may have cytoplasmic halos which are perinuclear vacuoles due to E5 protein localization to the ER which is = to?
KOILOCYTIC ATYPIA
83
Aids in diagnosis include highest viral loads in upper 1/2 of epithelium, Ki67 marker of actively dividing cells usually restricted to basal layer (seen in upper layers where should be), and overexpression of what due to increased CDK4?
p16***
*Ki-67/p16 staining are highly correlated with HPV infection and are useful for confirmation of the diagnosis of SIL*
84
If there are atypical cells confined to the lower 1/3 it is considered LSIL (CIN1), if there is expansion into the upper 2/3s then it is considered?
HSIL (CIN2/3)
85
Lesion: LSIL
Regress: 60%
Persist: 30%
Progress: ?
10% to HSIL
86
Lesion: HSIL
Regress: 30%
Persist: 60%
Progress: ?
10% to carcinoma in 2-10 years
87
Cervical carcinoma average age is 45, due to high risk HPVs, 80% are SCC, 15% are adenocarcinomas (all histological types caused by HPV), and 5% are what kind, which are the worst w shorter progression from insitu to invasive, *more likely advanced disease w less favorable prognosis?
Mixed Adenosquamous / neuroendocrine
88
The following is describing what cervical carcinoma morphology?
nests and tongues of malignant epi
keratinizing/non-keratinizing
invade underlying cervical stroma*
Squamous Cell Carcinoma
89
The following is describing what cervical carcinoma morphology?
Proliferation of glandular epi composed of malig endocervical cells w large, hyperchromatic nuclei and mucin depleted cytoplasm = dark appearance of glands
Adenocarcinoma
90
The following is describing what cervical carcinoma morphology?
Intermixed malignant glandular and squamous epithelium
Adenosquamous Carcinoma
91
The following is describing what cervical carcinoma morphology?
appears similar to small cell caricnoma of the lung but is positive for HPV 16/18/31/33/45, v poor prognosis
Neuroendocrine Carcinoma
92
The following is describing what cervical carcinoma morphology?
spreads via direct extension to contiguous tissues, paracervical soft tissue, urinary bladder, ureters, rectum, vagina, lymphovascular invasion leads to local and distant LN mets in liver, lungs, bone
Advanced Cervical Carcinoma
93
A pap smear has 75% sensitivity, 95% specificity while testing for HPV DNA has a higher what?
Sensitivity and lower specificity
94
Early invasive cervical carcinoma is treated with a cervical cone excision, invasive cancer is treated w hysterectomy and LN dissection, and advanced cancer is treated with?
Radiation and chemotherapy
95
Primary pelvic nodes are first metastasized to for cervical cancer, then paraaortic nodes, distant mets MC lungs, liver, bones, death is usually due to complications related to ?
Local tumor invasion rather than distant mets
96
The HPV vaccine is recommended for all girls and boys 11-12 and up, up to 26, provides complete protection agains 16/18/6/11 for up to 10 years, what is the name of the Vax?
Gardisil or Gardisil 9 (9 serotypes)
97
The myometrium is tightly interwoven bundles of smooth muscle that form the wall of the uterus- hormonally responsive to oxytocin during parturition. What is the lining of the internal cavity of the uterus, composed of glands embedded in a cellular stroma - responsive to sex steroid hormones?
Endometrium
98
Dissolution of the Corpus Luteum
• Leads to ↓ progesterone
• Functionalis degeneration + bleeding into the stroma occurs
• Stromal breakdown → onset of the next menstrual cycle
** What drives proliferation of glands and stroma during the proliferative phase?
Estrogen
99
Dissolution of the Corpus Luteum
• Leads to ↓ progesterone
• Functionalis degeneration + bleeding into the stroma occurs
• Stromal breakdown → onset of the next menstrual cycle
** What drives proliferation of glands and stroma during the proliferative phase?
Estrogen
100
Menstrual phase days 1-5, initiated when corpus luteum involutes if no fertilized egg, progesterone drops causing shedding of what layer?
Functionalis Layer (tortuous glands)
101
During the proliferative/estrogenic phase, stromal cells are proliferating and releasing growth factors, numerous mitotic figures are in the glands and stromal cells, what type of glands are seen?
Straight tubular glands
102
The secretory/progesterone/luteal phase has a key feature of what at day 16-17, which progress to supranuclear vacuoles, the glands will dilate at days 18-24 and become tortuous/serrated or sawtooth like by week 4?
***KEY FEATURE = Subnuclear Vacuoles
103
The late secretory phase is manifested by stromal changes: prominent sprial arteries (21-22) increased ground substance and edema, along with what change?
decidual change (24-28) w increased stromal mitoses
104
Functional endometrial disorders aka dysfunctional uterine bleeding is uterine bleeding that lacks and underlying abnormality and is most commonly due to ?
hormonal distrubances
105
dysfunctional uterine bleeding may also be due to apthologies such as chronic endometriosis, endometrial polyps, submucosal leiomyomas, and endometrial neoplasms, MCC of uterine bleeding is?
ANOVULATORY CYCLE (failure to ovulate) which causes excessive endometrial stimualtion by estrogens that is UNOPPOSED by progesterone*
106
dysfunctional/abnormal uterine bleeding (AUB) may also be due to apthologies such as chronic endometriosis, endometrial polyps, submucosal leiomyomas, and endometrial neoplasms, MCC of uterine bleeding is?
ANOVULATORY CYCLE (failure to ovulate) which causes excessive endometrial stimualtion by estrogens that is UNOPPOSED by progesterone*
107
AUB due to anovulatory cycle is MC at menarche and perimenopausal periods, MC due to subtle hormonal imbalances assoc w endocrine DOs, ovarian lesions like polycystic, and metabolic distrubances like obesity, malnutrition and chronic?
Systemic disease
108
Structural Causes of AUB = PALM
| Nonstructural cuases of AUB= COEIN
```
Polyps
Adenomyosis
Leiomyoma
Malignancy/hyperplasia
__________________________________
Coagulopathy
Ovulatory dysfunction
Endometrial
Iatrogenic
Not yet classified
```
109
AUB due to anovulatory cycle is MC at menarche and perimenopausal periods, MC due to subtle hormonal imbalances assoc w endocrine DOs, ovarian lesions like polycystic, and metabolic distrubances like obesity, malnutrition and chronic?
Systemic disease
| endometrium shows pseudostratified glands w scattered mitotic figures
110
Structural Causes of AUB = PALM
| Nonstructural cuases of AUB= COEIN
```
Polyps
Adenomyosis
Leiomyoma
Malignancy/hyperplasia
__________________________________
Coagulopathy
Ovulatory dysfunction
Endometrial
Iatrogenic
Not yet classified
```
111
Prepuberty: Percocious pubertty
Adolescence: anovulatory/coag DOs
Reproductive Age: preg complication, anatomic lesions, AUB,
Perimenopausal: AUB d/t anovulatory or anatomic lesions
Postmenopausal: endometrial hypertrophy or antomic lesions
Causes of AUB by Age group
112
Prepuberty: Percocious pubertty
Adolescence: anovulatory/coag DOs
Reproductive Age: preg complication, anatomic lesions, AUB,
Perimenopausal: AUB d/t anovulatory or anatomic lesions
Postmenopausal: endometrial hypertrophy or antomic lesions
Causes of AUB by Age group
113
What type of endometritis is uncommon, limited to bacterial infections that arise after delivery or miscarriage, d/t retained products of conception, due to group A hemolytic strep/ staph, nonspecific inflammation of the stroma.. tx w curettage of fragments and abx?
Acute Endometritis
114
Chronic endometritis is MC form, typically caused by an ascending infection (especially *chlamydia*), sometimes idiopathic, if you see one plasma cell on bx then it is CHRONIC endometritis until proven otherwise, dx is made on the identification of what?
plasma cells in the stroma of endometrium
115
Chronic endometritis is associated with PID, retained gestational tissue, UID, Tb, Chlamydia, and presents with abnormal bleeding, pain, discharge and?
infertility
116
What would involve both fallopian tubes, infects the endometrium 50% of the time, rarely infects the cervix/vagina, seen with multinucleated giant cells, histiocytes and visualized with Kinyoun/Ziehl-Neelsen Acid fast stain?
Pelvic Tb (1/3 of patient shave Tb elsewhere before)
117
What is ectopic endometrial tissue outside of the uterus, tissue usually includes stroma/endometrial glands, causes infertility, dysmenorrhea, and pelvic pain, complications can occur if invasion present, most common in 30s-40s?
Endometriosis
118
Endometriosis is MC in OVARIES, uterine ligament, rectovaginal septum, cul de sac, pelvic peritoneum, large and small bowel and appendix, mucosa of cervix, vagina, fallopian tubes and laparotomy scars. What is the theory of the pathogenesis which states that retrograde flow of menstrual endometrium thru the fallopian tubes (occurs in 90% of women)?
Regurgitation Theory
119
Endometriosis is caused by a release of proinflammatory factors such as VEGF/PGE2/ TNFa/ IL1B/ IL8 / IL6, increase estrogen production by endometriotic stromal cells, all contribute to invasion and establishment of neurovascular networks and decreased immune clearance allowing?
Survivial of ectopic tissue
120
The increase in estrogen production seen in Endometriosis is associated with high levels of aromatase*, epigenetic alterations increase response to estrogen and decrease response to?
PROGESTERONE
121
Endometriosis causes an increased risk of 3x for ovarian cancer (endometrioid/clear cell types), endometrial cysts/endometriosis with PTEN and ARID1A mutations also increases risk of carcinoma, formation of what kind of cysts is seen?
Chocolate Cysts/endormetriomas: 3-5cm cystic masses filled w brown fluid (hemosiderin deposit) from previous hemorrhage
122
Endometriosis morphologically may bleed in response to extrinsinc and intrinsinc hormonal stimulation = red/blue to yellow/brown nodules on or beneath the mucosal surfaces (powder burn marks), some lesions may hemorrhage and cause extensive fibrous adhesion between structures causing obliteration of the?
rectouterine pouch of Douglas (cul de sac)
123
Atypical endometriosis is the precursor to ovarian carcinoma, there is cytologic atypia of the epi lining of the cyst OR glandular crowding due to excess epi proliferation. Clinically, endometriosis presents in active reproductive/childbearing years, 30-40s, 6-10% of women are affected, sx includ dysmenorrhea, dyspareunia, and?
PELVIC pain d/t intrapelvic bleeding and periuterine adhesions
124
Endometriosis clinically may also cause menstrual irregularites, infertility, pain w pooping, and dysuria. Dx is made via presence of endometrial glands and stroma, can be obscured by secondary fibrosis, treat with?
Aromatase inhibitors or surgically
125
What is related to Endometriosis but there is presence of endometrial tissue WITHIN the uterine wall (myometrium), irregular nests of endometrial stroma, menometrorrhagia, colicky dysmenorrhea, dyspareunia, pelvic pain?
Adenomyosis
126
What is increased proliferation of the endometrial glands relative to the stroma that leads to increased gland:stroma ratio, associated w *prolonged estrogenic stimulation of the endometrium* such as anovulation, increased estrogen production from endogenous sources, or exogenous supplement (hormone replacement)?
Endometrial Hyperplasia
| obesity/PCOS too
127
Endometrial Hyperplasia is an important cause of abnormal uterine bleeding and is frequently a precursor to the MC type of endometrial cancer. What inactivating mutation of is a common genetic alteration in both endometrial hyperplasia and carcinoma?
PTEN tumor suppressor gene mutation
| CAUSES CELL GROWTH
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PTEN mutation causes overactive PI3K/AKT growth regulatory pathway which enhances ability of estrogen to stimulate gene expression, so loss of PTEN leads to overactive estrogen dependent expression. What is the syndrome for germline mut of PTEN which is a multiple hamartoma syndrome w High incidence of endometrial and breast cancer?
Cowden Syndrome
129
WHO classifies Endometrial Hyperplasia as either nonatypical or atypical which differ in appearance and propensity to progress to carcinoma. nonatypical hyperplasia has glands that vary in size/shape, may be dilated, may be back to back w some stroma, d/t endometrial response to persistent estrogen, what is the cardinal feature***?
Increase in gland to stroma ratio (more stroma than atypical)
130
nonatypical hyperplasia rarely progresses to adenocarcinoma but may evolve to what after menopause when estrogen is withdrawn?
cystic atrophy
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atypical hyperplasia is aka as endometrial intraepithelial neoplasia EIN = PRECURSOR, there are complex patterns of proliferating glands with *NUCLEAR ATYPIA*, *conspicuous nucleoli*, loss of orientation of nuclei to BM, nuclear chromatin is opne or vesicular, and the glands are?
back to back and branch (v little stroma)
| these findings overlap w well differentiated cancer
132
Tx for endometrial hyperplasia includes hysterectomy, in which up to 1/2 of pts are found to have carcinoma after hysterectomy, for those who want to remain fertile, what is given?
Progesterone therapy
133
Endometrial carcinoma is the *MC* invasive cancer of the female genital tract, bleeding is usually an early sign, with a peak age of 55-65, Uncommon under 40. there are two types, including type 1 : endometrioid (low grade, indolent, preceded by aypical hyperplasia) and type 2:?
serous (high grade, aggressive, poor prog, preceded by serous endometrial intraepithelial carcinoma)
134
Type of Endometrial Cancer:
Age: 55-65 years
Clinical Setting: unopposed estrogen, obesity, HTN, diabetes
Morphology: Endometrioid
Precursor: Hyperplasia
Mutated Genes: PTEN*, ARID1A, MSI*
Behavior: Indolent, spreads via lymphatics
Type 1: Endometrioid
*MC mutation is PTEN which increases signaling via PI3K/AKT*
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Type of Endometrial Cancer:
Age: 65-75 years
Clinical Setting: Atropy and thin physique
Morphology: Serous/Clear cell/ mixed mullerian tumor
Precursor: Serous endometrial intraepithelial carcinoma
Mutated Genes: TP53, Aneuploidy
Behavior: Aggressive, intraperitoneal, Lymphatic spread
Type 2: Serous
136
Type 1 (endometrioid) carcinoma is the MC type of endometrial carcinoma (80%), most are well differentiated and mimic proliferative endometrial glands, 55-65 coming from hyperplasia, associated with obesity, DM, HTN, infertility and?
Unopposed estrogen stimulation
137
The hallmark for Type 1 (endometrioid) carcinoma is increased signaling via PI3K/AKT pathway via PTEN mutation. MSI or microsattelite instability due to DNA MMR or mismatch repair mutations are prevelant in carcinomas in females w HPNCC, known as what ?
Lynch syndrome (60% w this mutation have endometrial cancer as well as colorectal cancer)
138
Spread of endometrial carcinomas is via infiltration of the endometrial lining, speads via myometrial invasions/direct invasion, invasion of broad ligament = palpable mass, late metastasis to lungs liver bones via lymphatics, what is given to patients w cancer spread beyond the uterus?
Chemotherapy
139
Type 1 endometrioid carcinoma can take the form of a local polypoid tumor, or a tumor that diffusely infiltrates the endometrial lining, the adenocarcinomas demonstrate glandular growth patterns w 3 histologic grades: well differentiated (grade 1), moderately differentiated (grade 2), and ?
poorly differentiated grade 3- lack stroma looks like solid growth pattern
140
**NOTE endometrial hyperplasia and type 1 well differentiated endometrioid carcincoma are distinguished from eachother lack of intervening stroma in carcinoma (there is stroma in hyperplasia)
MEOW
141
Stage I: carcinoma is confined to the corpus uteri (body of the uterus)
Stage II: carcinoma involves the copus + cervix
Stage III: carcinoma extends outside the uterus but not out of the true pelvis
Stage IV: carcinoma extends outside the true pelvis or involves the mucosa of the bladder or rectum
MEOW
142
Type II (serous) carcinoma is 15% of all endometrial cancers (more frequent in AA), most common subtype is serous carcinoma, *POORLY differentiated, patients are 10 years older than type 1 patients. Arise in the setting of endometrial atrophy, usually has spread out of the uterus at presentation, most (90%) have what mutation?
TP53 missense mutation = accumulation of altered protein
143
Type II (serous) carcinoma has a precursor lesion known as serous endometrial intraepithelial carcinoma (identical cells but lack stromal invasion = not malignant), morphologically, seen in small atrophic uteri, tumors are large, bulky or invasive into myometrium, papillary growth pattern along with what nuclear changes?
Increased nuclear: cytoplasmic ratio, atypical mitotic figures, hyperchromasia, prominent nucleoli
144
Clinically, Type II (serous) carcinoma pts have no screening availble, asymptomatic or w irregular/post-menopausal bleeding*** for serous subtype, 2x mortality in AA and MC in AA, 5 year survival of what even if it is confined to the uterus?
18-27% (BAD) - most recur
145
Malignant mixed mullerian tumors (MMMTs) (carcinosarcomas) are endometrial adenocarcinomas with a malignant mesenchymal component, mutations are same as endometrial including PTEN, TP53, PIK3CA, morphologically will see bulky polypoid and may protrude through the cervical os, mets usually only contains which component?
Epithelial component
146
Clinically with Malignant mixed mullerian tumors (MMMTs), it is seen in postmenopausal women with bleeding, resembles endometrial carcinoma genetically, there are poor outcomes, and prognosis is based on?
Depth of invasion and stage
***Heterologous mesenchymal component tumors do worse than homologous
147
What is the MC tumor in women, benign, smooth muscle neoplasms, multiple more common than single, 40% have a abnormal karyotype: T(12q14;6p) HMGIC and HMGIY which are genes that regulate chromatin structure?
Uterine Leiomyoma (Fibroids)
148
Uterine Leiomyoma (Fibroids) are located in the myometrium, usually dont involve the uterine ligaments, lower uterus or cervix, they are sharply circumscribed, firm gray white masses, subserosal, myometrial (intra) and submucosal, what is a somatic mutation that is seen in 70% of these?
MED12 gene = encodes a component of mediator which allows cells to divide in uncontrolled way
149
Uterine Leiomyoma (Fibroids) have a characteristic *whorled pattern* of smooth muscle bundles on histo, uniform size and shape, oval nucleus, long bipolar processes and can degenerate, what is rarely seen?
Mitosis (to differentiate from leiomyosarcoma)
150
clinically, Uterine Leiomyoma (Fibroids) are asymptomatic* but may have abnormal bleeding, urinary frequency d/t bladder compression, sudden pain d/t infarction of large tumor, impaired infertility and rarely will do what?
malignant transformation to leiomyosarcoma **V rare
151
In pregnancy, Uterine Leiomyoma (Fibroids) causes an increased frequency of SAB, fetal malpresentation, uterine inertia (failure to contract) and postpartum hemorrhage, benign metastasizing leiomyoma may go into blood vessels and MC mets to?
LUNG
152
What is an uncommon, malignant neoplasm that arises from myometrium or endometrial stromal precursor cells, peak age 40-60, has complex* karyotypes with MED12 mutations (unique to uterine SM tumors), recurrence is common and more than 1/2 metastasize prior to presentation?
Leiomyosarcoma
153
Leiomyosarcoma are bulky, fleshy masses that invade the uterine wall or are polypoid masses that project into the uterine lumen, microscopically, one can see nuclear atypia, *zonal necrosis, and most importantly what?
Mitotic Index of 10 or >/10hpf = malignant
| STUMP= smooth muscle tumor of uncertain malignant potention
154
50% of Leiomyosarcomas metastasize to lungs (via uterine vein), bone, and brain, local spread to abdominal cavity occurs as well, 40% 5 year survival, recur after surgery, anaplastic lesions have a 5 year survival of?
10-15% (BAD) = anaplasia
