Pathology of Reproductive Tract Hillard LO's Flashcards
1
Q
What is uterus didelphys and septate vagina, what causes these underlying embryological defects?
A
- Uterine didelphys is 2 separate uterine cavities and cervix’s caused by failure of the mullerian ducts to fuse
- vaginal septum is present in some cases of this
- may need C-section
2
Q
What are the clinical features and pathological features of Mayer-Rokitansky-Kuster- Hauser syndrome?
A
- Mullerian agenesis
- Presence of ovaries but no uterus vagina or fallopian tubes
- undergo normal puberty, but without menses
3
Q
Pathologic/clinical features of Bartholin cysts?
A
- posterior to the vaginal opening, these glands normally produce mucuous and when the duct is obstructed a cyst forms
- cyst is non tender U/L soft mass
- if infected the cysts is red painfulu and warm +/- edema
4
Q
- Lichen sclerosis:
- who does it occur in
- what is it
- risk for what cancer
- histo
A
- occurs in low estrogen states such as postmenopause
- Inflammatory disorder with white plaques, prurutis, dysparenuia and dysuria
- high risk for TP53 keratinizing SCC
- thinning of epithelium and hyperkeratosis edematous band and lymhocytic infiltrates
5
Q
- Lichen Simplex Chronicus (Squamous cell hyperplasia)
- what causes it
- what is it assoc. with
- appearance
- histo
A
- chronic rubbing or scratching
- associated with contact drmatitis, lichen sclerosus, SCC
- thickened reddend surface that can whiten over time
- thickened epidermis (compared to lichen sclerosus with a thinned epidermis)
6
Q
- Condyloma Acuminatum
- what causes it
- whats it look like
A
- caused by HPV 6 or 11
- anogenital wart that is a skin colored, exophytic cauliflower like papule
7
Q
Basaloid/Warty SCC age predisposing lesion associated with it and risk factors?
A
- 60 yo
- Classic VIN lesion
- High risk HPV types 16 and 18 are risk factors as well as high numbers of sex partners and low age of onset for sex
8
Q
Keratinizing SCC age, predisposing lesion, causes/risks, mutation driver? (Know how to compare/contrast to basaloid warty)
A
- 75 yo
- differentiated VIN lesion
- Chronic irritiation from long standing lichen sclerosis or squamous cell hyperplasia
- TP53 mutation
9
Q
- Papillary Hidradenoma
- Embryologic origin
- Histo features
- Gross features
A
- It is a benign neoplsm with columnar and myoepithelial cells with apocrine differentiation arises from mammary type glands along the milk line
- On gross appearance it is a solitary well circumscribed vulvar dermal or subcutaneous nodule
10
Q
- Extramammary Paget’s Disesase
- histo
- gross appearance
- staining pattern
- increased risk for?
A
- It’s an intraepithelial adenocarcinoma with cells that show sweat gland and keratinocyte differentiation
- Prurutic ill defined red area +/- white crusted plaque
- Stains with immunostain CK7
- Increased frisk for synchronous carcinoma
11
Q
- Gartner duct cyst vs Mullerian duct cyst
- embryo origin
- clinical features
A
- Gartner duct is of mesonephric (wolffian duct) remnant origin
- Mullerian is from paramesonephric (mullerian) duct
- BOTH are found on the anterolateral wall of the vagina and can protrude
- usually asx, but can cause vaginal pressure and pain with sex
12
Q
Possible long term effects of Diethylstilbestrol exposure?
A
Women who were exposed to DES in utero are at higher risk of clear cell adenocarcinoma, they have increased patches of adenosis that is predisposed to develop into cancer
ONLY transplacental carcinogen in humans
13
Q
- Embryonal Rhabdomyosarcoma
- clinical presentation
- tumor cell type
A
- Protruding polypoid mass from the vagina (grape like) usually in infants and children <5 yo
- death can occur if it invades peritoneal cavity or bladder
- Malignant cells are embryonal rhabdomyoblasts
14
Q
Vaginal SCC is similar to what other type of cancer? Compare.
A
- Vaginal SCC shares commonalities with Vulvar SCC
- Similar to Basaloid/Warty vulvar SCC in that vaginal also starts with HPV 16 or 18 leading to a premalignant lesion (VAIN) vaginal intraepithelial neoplasia
15
Q
Vaginal SCC spread pattern?
A
- Lower ⅔ of vagina will spread to the inguinal and femoral canal LN’s
- Upper vagina will spread to the regional iliac LN’s
16
Q
Most prevalent high risk HPV subtypes and how do they drive carcinogenesis?
A
- HPV 16 and 18 are the most common high risk (16 is first)
- HPV intergrates into squamous cell genome impacting proteins E6 and E7
- E6 increases telomerase and degrades p53
- E7 drives cell proliferation and inactivates p21 and RB
17
Q
Low grade Squamous Intraepithelial Lesion (LSIL) progression to HSIL and regression likelihood? What does it mean to have LSIL? Tx?
A
- Only 10% progress to HSIL after 2 yrs and 60% regress
- LSIL is mild dysplasia in the cervix and encompases Cervical intraepithelial neoplasia I (CIN I)
- Observation is the management
18
Q
High grade Squamous Intraepitheial Lesion (HSIL) likelihood to progress to cervical carcinoma, persist, and regress? What does it mean to have this and how is it treated in general?
A
- 10% progress to carcinoma, 60% persist, 30% regress
- Encompases CIN II and III
- moderate dysplasia, severe dysplasia, and carcinoma in situ
- Surgery is tx
19
Q
When do pap smears start, how often do they occur?
A
- Begin at 21 usually and do every 3 years if normal results
- from 30-65 co test with high risk HPV molecular test every 5 yrs if normal
- Stop screening at 65 (unless at high risk) if they have had 3 negative pap smears for the last 10 years
20
Q
What does acetowhite and abnormal vessels in the cervix raise concern for? (when using acetic acid to help visualize)
A
- Acetowhite raises conern for dysplasia
- abnormal vessels concern for carcinoma
21
Q
What is Gardasil?
A
HPV vaccine that protects against most types and should be given to males and females around 11 or 12 years old
22
Q
Endocervical polyps clinical and path features? Tx?
A
- benign common lesion less than 3cm seen during reproductive years
- spotting is commmon with these
- Fibrovascular core and endocervical glands are seen on the epithelium
- Excision is cure
23
Q
What happens during the follicular (proliferative) phase of the menstrual cycle? (what hm’s are high)
A
- It is estrogen driven and the follicle is growing so FSH is also high
24
Q
What happens midpoint the menstrual cycle?
A
LH surge (and FSH) causes release of the egg
25
What happens in the early secretory ( Luteal) phase?
* LH and FSH are dropping while progesterone is increasing
* the corpus luteum is present
* histology looks like piano keys
26
What happens in late secretory (luteal) phase?
* Corpus albicans forms and progesterone and estrogen are decreasing
* Menses occurs
* histology has tortuous serrated glands with secretory material inside
27
Abnormal Uterine Bleeding causes in:
* Adolescence
* reproductive age
* perimenopausal
* postmenopausal
* Adolescence: anovulatory cycle
* Reproductive: DUB, anovulatory cycle, anatomic lesions
* Perimenopausal: DUB anovulatory cycle, anatomic lesions such as carcinoma polyps or hyperplasia
* Postmenopausal: anatomic lesions **need to make sure it is not carcinoma**
28
What causes Dysfunctional Uterine Bleeding (DUB)?
* PCOS
* Obesity
* Endocrine DO's
29
Acute Endometritis histo features and causes?
* neutrophils destroy the epithelium and may or may not have a microabscess
* caused by bacterial infection after delivery
* post partum fever, uterine tenderness, abdominal pain
* also assoc. with PID caused by chlymadia
30
Chronic Endometritis causes and histo?
* Caused by retained conception products, PID, IUD with actinomyces
* See plasma cells with perinuclear hoff
31
Pathogenesis of Endometriosis? (3 theories)
* Persistent survival via release of proinflammatory and inflammatory factos
* Increase in aromatase enzyme producing more estrogen
* Mutations in general that allow extra uterine endometrial tissue to survive
32
What is endometriosis and where is it commonly found?
* ectopic endometrial tissue commonly found on ovaries and pelivc tissue presenting with severe dysmenorrhea and potential ovarian mass if there
33
Gross and histo of endometriosis?
* Redish-Brown or Blue-black powder burn appearance in serosa or peritoneum
* Chocolate cyst on ovary
* Histology **diagnosis needs 2 of 3**:
* Endometiral glands
* Endometrial stroma
* Hemosiderin laden macrophages (evidence of hemorrhage)
34
Clinical and pathological features and risks for developing endometrial polyps.
* exophytic benign hyperplasitic polypoid neoplastic like mass
* Proestrogenic factors increases polyp risk especially Tamoxifen
* Most common cause of vaginal bleeding
35
What are the two types of endometiral hyperplasia and what does it put the patient at risk for?
1. Typical: glands have crowding and +/- cystic change, NO atypia, slight risk for carcinoma progression
2. Atypical: complex glandular proiferation WITH nuclear atypia, substantial risk for carcinoma
36
Risk factors for endometrial hyperplasia?
* Chronic unopposed estrogen is major risk factor
* Obesity
* DM
* PCOS
* Tamoxifen
* Estrogen replacement therapy
37
Compare contrast endometrial carcinoma types 1 and 2
38
What does Endometrioid Carcioma of the Uterus (Type 1) mimic and how do you tell them apart histologically?
* mimics normal endometrium but you see back to back glands with no stroma
39
Lynch syndrome mutations primary tumor location and risk for what gynecological cancers?
* AD mutations in MLH1 and MSH2
* primary tumors are carcinoma in the colon and puts women at risk for endometrial endometriod carcinomas and ovarian carcinomas
40
Malignant Mixed Mullerian Tumor demographics, prognosis, and histo?
* Rare seen in post menopausal atrophic women also more common in African American women
* Aggressive tumor especially if heterologous component is present, then it is poor prognosis
* (when malignant stroma forms sarcomatous elements not normally found in other uterine sarcomas)
* Made of malignant glandular and malignant stromal components
41
Adenosarcoma histology and how does it present?
* **BENIGN** glands and **MALIGNANT** stroma
* Often large polypoid mass that can be mistaken for a polyp
* This is a rare low grade malignany
42
What is associated with a JAZF1 mutation? Describe what it is, how it presents, and histo.
* Low grade endometrial stromal sarcoma
* this invades the myometrium, lymph nodes, or vasculature
* presents with AUB and abdomen pain
* see small blue cells with little cytoplasm
43
How do you differentiate the histology of Leiomyosarcoma from Leiomyoma?
* Leiomyosarcoma histology has Atypia, Mitoses, and Tumor necrosis
* Leiomyoma histology shows fasciciles of benign smooth muscle cells
44
What are paratubal cysts? What are Hydatid cysts of morgagni?
* Cysts on fallopian tubes that originate from embryological ducts or mesothelium, they are generally small
* Hydatid cysts of morgagni are a subcategory of paratubal cysts that afre usually larger and come from mullerian duct remnants
* Both are usually asx unless they rupture or have a torsion
45
What is an adenomatoid tumor? where does it originate where is it found? Presentation?
* Rare benign tumor from mesothelial origin
* Most common tumor of fallopian tubes
* Usually asx incidental finding in middle aged women
46
Follicular vs Luteal cyst origination and presentation?
* Follicular cysts come from ovarian follicle and have inner granulosa cells and outer follicular cells
* Luteal cysts forms when corpus luteum fails to regress and is lined with inner granulosa cells and outer thecal cells
* both are usually asx but pain if rupture or torsion
47
PCOS pathogenesis?
* Hyperandrogenism leading to hirtuism and male pattern baldness
* Hormonal imbalances (high estrogen, low FSH, and high LH) resulting in decreased fertility
* Insulin resistance (again leading to incresed estrogen due to obesity)
* Polycystic ovaries
48
What are patients with PCOS at increased risk for and why?
Increased risk for endometiral hyperplasia and carcinoma due to the increased estrogen
49
What are the epithelial tumors of ovaries? When do they occur?
* Serous
* Mucinous
* Endoometrioid
* Clear cell
* Transitional (Brenner)
Occurs 20+ yo and this type makes up 65-70% of ovarian tumors
50
Ovarian Serous tumor? (2 types)
* Low grade cystic tumor with tubal like epithelium and papillary growth
* High grade is a soid tumor with marked atypia, associated with BRCA1 and BRCA2 mutations with breast cancer and P53
51
Ovarian Mucinous tumor?
* Epithelial tumor made of columnar epithleium derived from intestines or mullerian ducts
* usually unilateral and large cystic like with thick mucinous fluid
* **KRAS** mutation
52
Endometrioid Ovarian tumor?
* Epithelial origin
* most ar carcinomas similar to endometrial endometriod carcinoma
* Endometriosis can be a precursor
53
CLear cell ovarian?
* epithelial derived
* vast majority are carcinomas
* histology shows large epithelial cells with clear cytoplasm
54
Transitional Ovarian tumor?
* benign unilateral mass made of transitional epithleium
55
What are the ovarian germ cell tumors? When do they occur?
* Teratoma
* Dysgerminoma
* Yolk sac
* Choriocarcinoma
Occur from 0-25 yo and makes up 15-20% of ovarian tumors
56
Mature cystic teratoma vs Immature Malignant Teratoma?
Mature Cystic:
* **benign** mature tissue from all embryo layers
* most common type of GCT usually a u/l cystic mass
Immature Malignant:
* Prepubertal females
* histology is like mature but it has immauture neurepithelium and the amount of this determine prognosis
57
Dysgerminoma?
* Most common **malignant** GCT
* Counterpart in ovary to testicular seminoma
* **KIT** mutation
58
Yolk sac tumor?
* 2nd most common **malignant** GCT
* Produces AFP
* See Schiller Duval bodies on histo
59
Ovarian choriocarcinoma?
* Aggressive malignant GCT with placental differentiation
* Produces B-HCG
60
Monodermal (specialized) teratoma?
1. Struma Ovarii: made of mature thyroid folicles rarely can cause hyperthyroidism
2. Carcinoid: can cause carcinoid syndrome (diarrhea flushing hypotension)
61
What are the sex chord tumors and when do they occur?
* Granulosa cell
* Fibroma/ Thecoma
* Sertoli Leydig
occurs at all ages and makes up 5-10% of ovarian tumors
62
Granulosa cell tumor?
* Low grad emalignancy 2 types
* 1.) adult granulosa occuring in peri and post menopausal women resulting in an increased risk for endometrial hyperplasia and carcinoma bc of increased estrogen release
* 2.) Juvenile Granulosa occurin in kids resulting in precocious puberty
* Hormonally active tumors are yellow
63
Differentiate Fibroma, Thecoma, and Fibrothecoma?
* Fibroma is made of fibroblasts
* Thecoma is made of thecal cells
* Fibrothecoma is a mix
64
What syndrome is associated with Fibroma of the ovary?
* Meigs syndrome: a triad of ascites, pleural effusion and benign ovarian tumor
65
What do thecoma's put patients at risk for?
Endometrial hyperplasia and carcinoma due to increased estrogen release
66
Sertoli-Leydig cell tumor? mutation?
* Low malignant potential
* Seen in reproductive age women due to **DICER1** mutation
* secretes testosterone resulting in defeminization and severe virulization
* can stop female dev if in kids
* Reinke crystals seen with leydig cells tumors
67
What is a Krukenberg tumor?
* Metastatic tumor to the ovary made of mucin rich signet ring cells
* Usually of GI origin with b/l masses
68
What is psuedomyxoma peritonei?
* “Jelly Belly” mucinous acites due to an appendiceal mucionous tumor that often involves the ovary
* Presents with nonspecific lower right quadrant pain, prognosis depends on spread
69
What is the #1 risk for ectopic pregnancy and where is #1 site? Presentation?
* PID is number one risk
* Fallopian tubes are most common site
* Presents with vaginal bleeding and abdominal/pelvic pain 6-8 weeks after last period
* Severe pain and hemorrhagic shock if ruptures
70
Most common causes of spontaneous abortions and when do these occur?
* Loss before 20 weeks
* Most are due to fetal chromosomal abnormalities
* can also be due to endocrine disorders uncontrolled, anatomic abnormalities, thrombosis, or TORCH
71
What kind of placenta do Dizygotic twins have?
* Dichorionic diamniotic placenta
72
What kind of placenta can monozygotic twiins have? (multiple)
* Di-di if splits early
* Monochorionic-diamniotic if split 4-8 days
* monochorionic monoamniotic if split 9-12 days
* if split \>13 days conjoined twins
73
What is the only type of twin and placenta that can result in twin twin transfusion syndrome and what is it?
* Monozygotic twins with a monochorionic placenta
* Donor twin will be underperfused while recepient twin will be fluid overloaded
* both twins are at risk of death due to heart failure
74
Placenta acreta spectrum?
* Placenta Acreta: absence of placental decidua allowing fetal villi to adhere to the myometrium
* can cause severe post partum hemorrhage, previoius C section increases risk
* Placenta Increta: Villi penetrate the myometrium
* Placenta Percreta: villi go all the way to the uterina serosa
75
What is placenta previa\>
* Placenta is in the lower uterine segment or cervix presents in 3rd trimester with bleeding
* Needs a C section
76
What is preeclampsia's pathogenesis?
* Trophoblasts do not enlarge causing placental ischemia which causes the release of inflammatory factors leading to maternal vasoconstriction (htn)
* these factors also lead to a hypercoaguable state increasing fibrin thrombi which when in the kidney results in proteinuria and when in the brain leads to ecpampsia
77
What is HELLP syndrome?
* Can present with features of preeclampsia in 3rd trimester and resolves after delivery
* Hemolysis with microangiopathic anemia
* ELevated liver enzymes
* Low Platelets
78
When does preeclampsia occur and what are the signs?
* After 20 weeks and coexists with proteinuria
* htn, proteinuria, potential edema
* sx include scotoma, blurred vision, epigastric or RUQ pain, headache
* Mild is \>140/90 but less than 160/110
* Severe is \>160/110 2 occasions 4 hours apart and symptomatic
79
What is eclampsia?
Preeclampsia plus a grand mal siezure
80
Compare complete and partial hydatiform mole.
Complete:
* multicystic thinned walled lesion with **NO** fetal parts
* US shows "snow storm"
* Substantial trophoblastic proliferation
* Increased risk for invasive mole and choriocarcinoma
* Paternally derived so p57 - stain
* 46 xx, xy
Partial:
* enlarged abnormal vili with some normal vili
* **has** fetal parts just abnormal
* Mild trophoblastic proliferation
* small risk for invasive mole
* both parents so p57+
* 69xxy, xxx, xyy
81
Gestational choriocarcinoma? risks, what is seen clincally, prognosis?
* Complete mole is a risk factor but it is an uncommon malignancy of trophoblastic origin
* Widespread metastasis are seen at diagnosis
* High B-HCG
* **Chemo has nearly 100% remission**
82
Placental site trophoblastic tumor?
* Very rate malignancy
* follows normal pregnancy or spontaneous abortion
* high B-Hcg
* uterine mass with abnormal uterine bleeding
83
Adenomatoid tumor gross and histo.
solid white cut surface, histo shows small spaces of different size lined by a compressed cellular lining without atypia
