df Flashcards
1
Q
The __________ can be affected by psoriasis, eczema, allergic dermatitis and is more prone to superficial infections because it is constantly exposed to secretions
A
Vulva
2
Q
What vulvar disorders do we discuss?
A
- Bartholin cyst
- Non-neoplastic epithelial disorders (Leukoplakia, lichen sclerosis, squamous cell hyperplasia = lichen simplex chronicus)
- Benign exophytic lesions (condyloma acuminatum/condylomas latum)
3
Q
What is a Bartholin Cyst?
A
Obstruction of the Bartholin gland causes infection and inflammation (adenitis), forming a painful cyst that can get large (3-5cm)
4
Q
Bartholin Cyst
- What lines the cyst?
- Most often seen when?
- Treatment?
A
- Lined with transitional or squamous epithelium
- All ages
- Excised or opened permanently (marsupialization)
5
Q
What non-neoplastic epithelial disorders can cause leukoplakia on the vulva?
A
- Lichen sclerosis
- Squamous cell hyperplasia (lichen simplex chronicus)
6
Q
What is leukoplakia?
A
Opaque-white, plaquelike epithelial thickening that can cause pruritus and scaling.
7
Q
Leukoplakia can also be caused by what?
A
- Vulvar intraepithelial neoplasia (VIN)
- Paget disease
- Invasive carcinoma
8
Q
Lichen Sclerosis
- Presentation:
- Occurs in who?:
- Risk of cancer:
A
- Presentation: Smooth, white plaques macules on the vulva that can enlarge, coalesce and have porcelain/parchment surface.
- Occurs when: Any age, MC in post-menopausal W.
- Risk of cancer: Not a premalignant lesion, but have an increase risk of developing vulvar carcinoma
9
Q
What is seen histologically with Lichen Sclerosus?
A
- Thinning of epidermis (parchment paper) + fibrosis/sclerosis of superficial dermis
- Excessive keratinization(hyper-keratosis)
- Chronic inflammatory cells in deeper dermis = band-like infiltrate
10
Q
Pathogenesis of Lichen Sclerosus is uncertain, but there is a higher frequency in association with what?
A
Autoimmune disorders
11
Q
Lichin Simplex Chronicus
- Other names:
- Presentation:
- Occurs in who?:
- Risk of cancer:
A
- Squamous cell hyperplasia/hyperplastic dystrophy
- Presentation: leukoplakia w/ thick, leathery skin on vulva w/ enhanced skin markings due to chronic rubbing or scratching
- Occurs in who: chronic rubbers or scratchers
- Risk of cancer: Not premaligant, but can be on the margins of vulvular cancer
12
Q
What is seen histologically with Lichen Simplex Chronicus?
A
- Hyperkeratosis
- Thick epidermis (acanthosis) = squamous cell hyperplasoa
- Lymphocytes in dermis
13
Q
What are benign exophytic lesions?
A
Benign raised (exophytic) lesions = wart-like lesions
- Condyloma Acuminatum (genital warts) due to HPV
- Condyloma Latum due to syphilis
14
Q
Condyloma Acuminatum
- Presentation:
- Cancer risk:
A
- Presentation: Benign genital warts, which can be multiple, due to low oncogenic risk HPV (6 & 11).
- Cancer risk: Not a precancerous lesion
15
Q
What is seen histologically with Condyloma Acuminatum (genital wart)?
A
- Exophytic papillas, tree-like cores of stroma covered by thick squamous epithelium
- Surface epithelium has koilocytic atypia = large nuclei + hyperchromasia + cytoplasmic perinuclear halo
16
Q
Squamous neoplastic lesions of the vulva: VIN and vulvar carcinoma
2 groups of squamous cell carcinoma of the vuvla?
- How are they different
A
-
Basaloid & warty carcinoma related to HPV 16
- (younger age, 50’s)
-
Keratinizing SCC not related to HPV
- (older age; 70’s )
17
Q
Precursor lesions in:
- Basaloid and warty carcinomas of the vulva
- Keratinizing SCC of the vulva
A
- Basaloid & warty carcinoma of the vulva: Classic vulvar intraepithelial neoplasia (VIN)
- Keratinizing = Differentiated vulvar intraepithelial neoplasia (aka VIN simplex)
18
Q
What is VIN?
Who is it most commonly seen in?
A
- Precursor lesion that progresses to [Basaloid & warty cancers] of the vulva, often caused by HPV 16.
- Pre-menopausal F
19
Q
Presentation & Histology of VIN
A
- Presents: discrete white (hyperkeratotic) or slightly raised, pigmented lesion
- Histologically:
- Epidermal thickening,
- Nuclear atypia + ↑ mitoses
- Lack of cellular maturation
20
Q
Presentation and Histology of Basaloid Carcinoma
A
-
Presentation:
- Exophytic or indurated/ulcerated
-
Histology
- Small, tightly packed basaloid cells that lack maturation (look like basal layer of NL epithlelium
- Central necrosis
21
Q
Presentation and Histology of Warty Carcinoma of the Vulva
A
- Presentation: Exophytic and papillary
- Prominent koilocytic atypia
22
Q
Progression from [VIN => invasive basaloid and warty carcinomas] is higher in whom?
A
- Women older than 45YO
- Immunosuppressed
23
Q
Keratinizing Squamous Cell Carcinoma
- Occurs more in?
- Precursor lesion?
A
- Older women (70s) with long-standing lichen sclerosus or squamous cell hyperplasia
- VIN simplex/differentiated VIN
24
Q
Histology of Keratinzing Squamous Cell Carcinoma
A
Malignant squamous epithelium with keratin pearls
25
**Histology** of Diffentiated VIN/ VIN simplex
1. Basal layer atypia
2. Normal-appearing differentiation of superficial layers
3. Hyperkeratatosis
26
Which precursor lesion has a higher frequency of **TP53 mutations?**
**Differentiated VIN**
27
When **Differeniated VIN** becomes invasive, where does it spread?
* **LN**: Inguinal, pelvic, iliac and periaortic lymph nodes
* **Lympho-hematogenously:** lungs, liver and other organs
28
How many v**ulvular cancers** are caused by high-risk HPV?
What are the others caused by?
* 30% = HPV 16 and 18; VIN
* 70% = not HPV-related and develop in background of lichen sclerosus or squamous cell hyperplasia; Differentiated VIN
29
What **glandular neoplastic lesions** occur in the vulva (has apocrine sweat glands)?
1. **Papillary Hildradenoma**
2. **Extramammary Paget Disease**
30
Which lesions of **invasive carcinoma of the vulva** have an excellent prognosis (90% at 5-years)?
**Lesions \<2 cm**
31
**_Papillary Hidradenoma_**
* Presentation:
* Often confused with:
* Histology:
* **Presentation**: Sharply, circumscribed nodule of the apocrine sweat gland, most often on labia major or interlabial folds that tends to ulcerate
* **Often confused with:** Invasive carcinoma bc ulcerates
* **Histology:**
* Same as intraductal papilloma of the breast:
* 1. Papilloma covered by 2 cells: columnar and flat myoepthial cells of sweat glands.
32
**_Extramammary Paget Disease_**
* Presentation
* Associated with cancer?
* Cell of Paget disease of the vulva express \_\_\_\_\_\_\_, which allows for immunostaining
* **Itchy**, red, **crusty**, maplike area confined to the epidermis of vulva (mainly **labia majora)**
* **No**
* **Cytokeratin 7**
33
**Histology** of Extramammary Paget Disease
* **Epidermis**: Large cells with pale-pink cytoplasm (mucopolysaccharide) with apocrine, eccrine and keratinocyte differentiation
* **Dermis**: inflammation
34
**Paget cells** have pale cytoplasm containing mucopolysaccharide that can be stained with what 3 stains?
1. **PAS**
2. **Alcian blue**
3. **Macicarimine stains**
35
How does **Paget disease of the nippl**e differ from **extramammary Paget disease** in terms of underlying cancer association?
* **Paget of the nipple** =\> 100% of pt's have underlying ductal breast carcinoma
* **Extramammary** =\> typically not associated w/ underlying cancer and is confined to the epidermis of vulvar skin
36
**Treatment** of Extramammary Paget Disease
**Wide local excision** because cells spread laterally within the epidermis and can be present beyond the borders of the visible lesion
37
What part of the female genital tract is a **RARE** site of primary disease?
Vagina
38
Most vaginal cancers are what kind?
**Squamous cell carcinomas** due to **high-risk HPV**
39
What developmental anomalies occur in the vagina?
1. **Septate (double) vagina**
2. **Vaginal adenosis**
3. **Gartner duct cyst**
40
**Septate**, or **double, vagina** is accompanied by a **double uterus (uterus didelphys**) and is due to failure of what?
**Failure of müllerian duct to fuse**
41
What can cause **septate (double) vagina?**
Exposure to **DES** (diethylstilbestrol) in **utero.**
* Used to **prevent threatened abortions** (vaginal bleeding during the first 20 weeks)
42
What is **vaginal adenosis** and who is it most commonly seen in?
* Persistance of small patches of residual glandular epithelium from the developing vagina =\> create **red, granular areas**
* Women exposed to DES in utero
43
What was a **RARE complication** seen in *vaginal adenosis?*
**Clear cell carcinoma** can arise from DES-related adenosis
44
Where are **gartner duct cysts** found and what are they derived from?
**Fluid-filled cysts i**n the submucosa of lateral walls of vagina, derived from **wolffian (mesonephric) duct rests**
45
What is the greatest risk factor for SCC of the vagina?
Cervical or vulvular carcinoma due to high-risk HPV
46
List **3 benign tumors** of the **vagina** that most often occur in **women of reproductive-age.**
1. Stromal tumors (stromal polyps)
2. Leiomyomas
3. Hemangiomas
47
**_Vaginal Squamous Cell Carcinoma_**
* Premalignant lesion:
* What part of the vagina is most commonly affected?
* What LN does it metasasize?
* VaIN
* Posterior wall of the upper vagina, at the junction of the ectocervix
* Metastasize
* Upper 1/3 of vagina: iliac LN
* Lower 2/3 of vaina: inguinal LN
*
48
What is **embryonal rhabdomyosarcoma (sarcoma bortyoides)?**
- Rare, *malignant vaginal tumor* most often in *infants and children \<4 y/o*
49
How do **embryonal rhabdomyosarcoma (aka sarcoma botryoides)** appear on presenation?
**Clear, polypoid, round, grape-like mass** emerging from vagina
50
**Histology** of Embryonal Rhabdomyosarcoma (aka sarcoma botryoides)
1. Tumor cells are small, oval nuclei, w/ smallcytoplasmic protrusions from one end, resembling a tennis racket
2. Tumor cells beneath vaginal epi. = crowded in a cambium layer
3. Tumor cells in deep regions = lie in loose, edematous fibromyxomatous stroma
51
Risk of metatsis of the **invasive** **VULVAR cancer** depends on what?
* **1. Size of the tumor** (\<2cm =\> 90% chance of survival in 5 years)
* **2. Depth of invasion**
* **3. Lymphatic involvement**
52
What is the **prognosis** and **complications** associated with **embryonal rhabdomyosarcoma** (aka sarcoma botryoides)?
- Tend to invade locally = death by penetrating into peritoneal cavity or by obstructing urinary tract
- Surgery + chemotherapy offer best hope in cases diagnosed early
53
Describe the anatomy of the **cervix** (& cell type)
1. **Ectocervix** (external vaginal part) = part seen on vaginal exam
1. Squamous epithelium
2. Converges at the external os
2. **Endocervix** (endocervical canal)
1. Columnar, mucus secreting epithelium that begins at the external os
3. **Squamocolumnar junction (transformation zone)** = where both meet
54
What is the **"transformation zone"** of the cervix and why is this area clinically significant?
* Area where columnar epithelium (endocervix) meets the squamous epithelium (ectocervix)
* Area has **immature squamous metaplatic epithelial cells,** which are highly susceptible to HPV.
55
Where do **cervical precursor lesions** and **cancer** develop?
**Transformation zone**
56
How does the **transformation zone** of the cervix change over time?
Location depends on age and hormones.
Overtime, **moves upward** into the endocervical canal.
57
What is the **dominant microbial species** found in the **normal vagina** and what is its function?
**Lactobacilli**
1. Produce **lactic acid**, which maintain vaginal pH \<4.5
2. Produce **hydrogen peroxide** (H2O2), which is bacteriotoxic when pH gets too low.
58
Physiologically, what causes ***cervicitis*** or **_vaginitis_**?
1. Vaginal pH becomes alkaline (\> 7) due to bleeding, sex, ABX\*, douching
2. Decreases H2O2 production
3. Overgrowth of other microorganisms
59
What can cause **cervicitis** or **vaginitis**?
1. Gonorrhea
2. Chlamydia
3. Mycoplasma
4. HSV
60
Why is it important to ID the causes of cervicitis or vaginitis?
They can be associated with a upper genital tract disease, pregnany complication, STI, PID (=\> Fitz-Hugh Curtis Syndrome).
61
**Cervicitis** can lead to what complication of the cervix?
* Reparative and reactive changes of the epithelium + shedding of atypical squamous cells → **abnormal Pap smear**
62
What is the most common **benign exophytic growth** in the **endocervical canal?**
**Endocervical polyps** = Range from [small, sessile "bumps" =\> large polpys] that may protrude through cervical os.
63
**_Endocervical Polyps_**
1. Histology
2. Symptoms
3. Treatment
1. **Loose fibromyxomatous stroma** covered by **mucus secreting endocervical glands** that can inflammed
2. Vaginal "spotting" (bleeding), makes us things something else
3. Curretege and excise via surgery
64
**Cervical cancer** is the ___ most common cancer in women in the WORLD.
**3rd**
65
What is the most important risk factor for the development of **cervical cancer?**
**High-risk HPV16** (60% of cases) and **HPV18** (10% of cases)
66
What kind of cells can HPV **NOT** infect?
**Mature superficial squamous cells** that cover the cervix, vagina or vulva.
67
Which viral protein of **high-risk HPV** impairs the ability of cells to repair DNA and which up-regulates expression of telomerase =\> leading to cellular immortalization?
- **E6** inhibits p53 and ↑ regulates expression of telomerase =\> cell immortilization
- **E7** inhibits RB + p21 and p27 = cell cannot repair DNA damage
68
How do the **E6** and **E7 proteins** of **low-risk HPV** impact cellular growth and survival?
* - **E7** proteins bind **RB** with _lower affinity_; **E6** proteins _do not bind_ to **p53**
* - Dysregulate growth and survival by interfering w/ **Notch** signaling pathway
69
1. High risk HPV strains cause =\>
2. Low risk HPV stains cause = \>
1. **Cervical cancer**
2. **Conduloma acuminta** in the vulva, perineal and perianal area
70
Alone, **HPV** is **not** **enough** to cause cervical cancer. What else influences the progression?
1. ***Carcinogens***
2. ***Host immune status***
71
What is the position of **HPV DNA** in precursor lesions assoc. w/ high-risk HPVs and in condylomata assoc. w/ low-risk HPVs?
DNA is **extrachromosomal** (episomal)
72
How does the squamous cell that **HPV** infects differ from the cell that HPV replicates in?
- **Infects** _immature_ squamous cells; cannot infect mature cells
- **Viral replication** occurs in _maturing_ squamous cells
73
How does the position of the viral DNA of HPV change **with malignant transformation?**
Viral DNA is **integrated** INTO the host cell genome --\> ↑ expression of E6 and E7
74
**Genital HPV infections** are extremely \_\_\_\_\_; most of them are _symptomatic/asymptomatic_, _do/do not_ cause any tissue changes, and therefore ______ detected on Pap test
* common
* asymptomatic
* no tissue changes =\> not detected on Pap smear
75
What makes **high-risk HPV infections** more likely to become cancer?
* **50%** of HPV infections are cleared within **8 months**, and **90%** of infections are cleared within **2 years**
* High-risk HPV infections last longer =\> more time develop precursor lesion
76
1. **Epithelial cells** in the ________ =\> ↑ risk of HPV
2. **Epithelial cells** in the ________ =\> ↓ risk of HPV
1. Cervix and anus (homosexual men)
2. Vulva and penis (except for epithelial breaks)
77
**HPV** causes 80% of ____ and 100% of ____ _precursor lesions_
**_HPV_** causes:
* **80% of LSIL** (low grade squamous intraepithelial lesions)
* **100% of HSIL** (high grade SIL)
78
_**LSIL\*\* (more common) & HSIL:**_
Differentiate the two based on
1. viral replication
2. cellular proliferation
3. progression to invasive carcinoma
* **LSIL**:
* high rate of viral replication;
* mild alterations in growth of host cells =\>
* not pre-malignant and does directly become invasive carcinoma (60% regress; 10% =\> HSIL)
* **HSIL**
* lower rate of viral replication
* ↑ cellular proliferation and ↓ arrested epithelial maturation
* ALL are high risk for progression to carcinoma
79
Diagnosis of s**quamous intraepithelial lesions (pre-cursor lesions)** is based on identification of what?
1. Atypical nuclei
1. Nuclear enlargement
2. Hyperchromasia (dark staining)
3. Coarse chromatin granules
4. Variation in nuclear size & shape
2. **Cytoplasmic halos** due to E5 protein localization to the ER = koilocytic atypia
80
How do we assign **low-grade/high-grade** to cervical precusor lesions?
Based on **expansion** of **immature cells** from its normal, basal location. If,
1. Confined to the lower 1/3 =\> **LSIL**
2. Expands to upper 2/3 =\> **HSIL**
81
Staining for what cell markers highly associated with HPV infection is useful for **confirmation of the diagnosis** in equivocal cases of SIL?
1. **Ki-67** (marker of actively dividing cells), usually restricted to basal layer. But seen in upper levels when E6 and E7 prevent arrest of cell-cycle.
2. **p16** (characterized high-risk infections) =\> increase CDK4
82
**Most (80%) HSIL** develop from \_\_\_\_\_.
How many progress to invasive cancer?
* LSIL
* 10%
83
After SCC what is the second most common cancer (15%) of the cervix and which 2 types represent only 5% of cases?
1. **Adenocarcinoma** (15%)
2. Adenosquamous and neuroendocrine carcinomas (5%) = progress quicker and pt presents with advanced disease and worse prognosis
84
Average age of cerical cancer?
**45 YO**
85
How does **_advanced_** cervical cancer spread?
**Directly** extends into tissues
1. Paracervical soft tissue
2. Urinary bladder
3. Ureters (→ hydronephrosis)
4. Rectum
5. Vagina
86
Lymphovascular invasion by **advanced cervical carcinoma** may cause distant metastases to what organs?
**Liver** + **Lungs** + **Bone marrow**
87
Which cancer of the **cervix** is associated with a very poor prognosis?
**Small-cell neuroendocrine** tumors
88
Most patients with **advanced cervical cancer** die due to what?
**Local tumor invasion** =\>
* 1. Ureteral obstruction
* 2. Pyelonephritis
* 3. Uremia
89
An **_abnormal pap test_** should be followed up with what?
**Colposcopic exam** of the cervix and vagina to ID lesion
90
What % of **cervical cancer** arise in women, who were not in a regular screening program?
**50%**
91
What is the significance of **persistent HPV infections**?
Persistent infection **↑↑↑ risk for cancer**
92
* Histology of cervical intraepithelial neoplasia
* LSIL (CIN I) =
* HSIL (CIN II) =
* HSIL (CIN III) =
* HSIL (CN IV) =
* **LSIL (CIN I)** = mild cervical intraepithelial neoplasia = koilocytic atypia in basal layer
* **HSIL (CIN II)** = moderate dysplasia = progressive atypia and expansion of immature basal cells above lower 1/3 of the epithelium
* **HSIL (CIN III)** = severe dysplasia = diffuse atypia, loss of maturation and expansion of the immature basal cells to the surface
* **HSIL (CN IV)** = CIS
93
What % of **LSIL** regress, persist, and progress to HSIL within 2-year follow-up?
* - **60**% regress
* - **30**% persist
* - **10**% progress to HSIL
94
Describe the **staging** of cervical cancer
1. **Stage 0** = CIS (HSIL CN III)
2. **Stage 1 =** confined to cervix
3. **Stage 2** = cancer goes beyond cervix, but NOT pelvic wall (involves only upper 2/3 of vagina)
4. **Stage 3=** : cancer extends beyond pelvic wall (lower 1/3 of vagina is involved)
5. **Stage 4** = cancer extends beyond pelvis or involves bladder/rectum mucosa.
95
**Treatment of:** early invasive, invasive cancer or advanced cervical carcinoma
* **Early invasive:** cervical cone excision
* **Invasive cancer**: hysterectomy + lymph node dissection
* **Advanced cancer:** + radiation + chemotherapy
96
What is a **pap smear?**
How does it affect mortality of cervical cancer?
**Pap Smear: t**ransformation zone is scraped and smeared onto a slide, fixed and stained with Papanicolaou method
* ↓ mortality of cervical cancer because most cancers arise from precursor lesions over many years
97
**_HPV vaccine_**
* Recommended for who?
* Gardasil protects agains?
* should cervical screens still be done?
* All girls and boys 11-12 years old, up to age 26
* 6, 11, 16, 18
* Yes bc does not protect against all strains
98
Describe the precursor lesions
* A = NL
* B = LSIL bc koilocytes
* C = HSIL (II)
* D = HSIL (III)
Increase in nucleus to cytplasm ratio which occurs as the grade of the lesion increases. Indicates progressive loss of cellular differentiation on the surface of the lesion.
