Lecture 7.1: Vulva, Vagina, and Cervix Flashcards

1
Q

Which descriptive clinical term refers to opaque, white, plaquelike epithelial thickening that may produce pruritus and scaling?

A

Leukoplakia

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2
Q

Which cause of leukoplakia presents as smooth, white plaques of macules on the vulva that in time may enlarge and coalesce, producing a surface that resembles porcelain or parchment?

A

Lichen Sclerosus

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3
Q

What is seen histologically with Lichen Sclerosus?

A
  • Marked thinning of epidermis (parchment paper) + fibrosis/sclerosis of superficial dermis
  • Excessive keratinization (hyperkeratosis)
  • Chronic inflammatory cells in deeper dermis = band-like infiltrate
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4
Q

Who is lichen sclerosus most commonly seen in; what are the risks of cancer?

A
  • All ages, but most common in post-menopausal women
  • NOT a premalignant lesion
  • Slightly ↑ risk of developing SCC of the vuvlva
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5
Q

Pathogenesis of Lichen Sclerosus is uncertain, but there is a higher frequency in association with what?

A

Autoimmune disorders

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6
Q

Squamous cell hyperplasia (aka lichen simplex chronicus) results from what and how does it present?

A
  • Presents as leukoplakia w/ leathery, THICK vulvar skin w/ enhanced skin markings
  • Due to chronic rubbing or scratching
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7
Q

Histological examination of Squamous cell hyperplasia (aka lichen simplex chronicus) will show what?

A

Thickening of the epidermis (acanthosis) and hyperkeratosis

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8
Q

Is squamous cell hyperplasia (aka lichen simplex chronicus) pre-malignant?

A

Not premalignant; sometimes present at the margins of vulvar cancer

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9
Q

Condyloma acuminatum are benign genital warts caused by what; are they pre-malignant?

A
  • LOW oncogenic risk HPV, mainly types 6 and 11
  • NOT pre-malignant
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10
Q

What is seen on histological examination of condyloma acuminatum; which characteristic cytopathic change is seen in the surface epithelium?

A
  • Papillary, exophytic, tree-like cores of stroma covered by thickened squamous epithelium
  • Surface epi. shows koilocytic atypia = nuclear enlargement + hyperchromasia and a cytoplasmic perinuclear halo
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11
Q

What are the 2 groups of SCC of the vuvla; which is related to HPV and what age group is more commonly affected by each?

A
  • Basaloid and warty carcinomas related to HPV-16; less common and occur in younger women (peak in 50’s)
  • Keratinizing SCC unrelated to HPV; more common; occur in older women (peak in 70’s)
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12
Q

Basaloid and warty carcinomas and keratinizing SCC of the vulva arise from what precursor lesions?

A
  • Basaloid and warty = classic vulvar intraepithelial neoplasia (VIN)
  • Keratinizing = differentiated vulvar intraepithelial neoplasia (aka VIN simplex)
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13
Q

The risk of progression from VIN to invasive basaloid and warty carcinomas is higher in whom?

A
  • Women older than 45 y/o
  • Immunosuppressed
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14
Q

Keratinizing SCC of the vulva occurs most often in women with what underlying condition?

A

Older women w/ long-standing lichen sclerosus or SCC hyperplasia

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15
Q

Higher frequency of what type of mutations are seen in differentiated VIN leading to keratinizing SCC of the vulva?

A

TP53

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16
Q

What is the morphology upon presentation of classic VIN; what is seen microscopically?

A
  • Presents as a discrete white (hyperkeratotic) or slightly raised, pigmented lesion
  • Microscopically, shows epidermal thickening, nuclear atypia + ↑ mitoses and lack of cellular maturation
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17
Q

Which carcinoma of the vulva is characterized by nests and cords of small, tightly packed cells that lack maturation often with a foci of central necrosis?

A

Basaloid carcinoma (HPV-16 assoc.)

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18
Q

Which vulvar carcinoma is exophytic w/ papillary architectureand prominent koilocytic atypia?

A

Warty carcinoma

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19
Q

Which carcinoma of the vulva is characterized by nests and tongues of malignant squamous epithelium w/ prominent central keratin pearls?

A

Keratinizing SCC

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20
Q

Which type of VIN is characterized by marked atypia of the basal layer of the squamous epithelium and normal-appearing differentiation of the more superficial layers?

A

Differentiated VIN

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21
Q

Which lesions of invasive carcinoma of the vulva are associated with an excellent prognosis (90% at 5-years)?

A

Lesions <2 cm

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22
Q

What sharply circumscribed nodule most commonly presents on the labia majora or interlabial folds, and is often confused clinically w/ carcinoma due to its tendency to ulcerate?

A

Papillary Hidradenoma

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23
Q

Papillary hidradenomas are histologically identical to what other tumor; what are the 2 layers of cells seen on the papillary projections?

A
  • Identical to intraductal papilloma of the breast
  • Upper layer = columnar secretory cells covering
  • Deeper layer = flattened myoepithelial cells
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24
Q

How does extramammary paget disease of the vulva typically present?

A

Itchy, red, crusted, maplike area usually on labia majora

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25
Q

What do the cell of Paget disease of the vulva express which allows for immunostaining?

A

Cytokeratin 7

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26
Q

Paget cells have pale cytoplasm containing mucopolysaccharide that can be stained with what 3 stains?

A

PAS, Alcian blue, or macicarimine stains

27
Q

How does Paget disease of the nipple differ from extramammary Paget disease in terms of underlying cancer association?

A
  • 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
28
Q

Septate, or double, vagina is accompanied by a double uterus (uterus didelphys) and is due to failure of what?

A

Failure of müllerian duct fusion

29
Q

What is vaginal adenosis and who is it most commonly seen in?

A
  • Small patches of residual glandular epithelium from the developing vagina which persist into adult life and are seen as red, granular areas
  • Women exposed to DES in utero
30
Q

Where are gartner duct cysts found and what are they derived from?

A
  • Lateral walls of the vagina and derived from wolffian (mesonephric) duct rests
  • Fluid-filled cysts occurring in submucosal location
31
Q

In rare instances DES-related vaginal adenosis has been associated with what type of cancer?

A

Clear cell carcinoma

32
Q

What is the greatest risk factor for SCC of the vagina?

A

Previous carcinoma of the cervix or vulva; associated w/ high-risk HPVs

33
Q

List 3 benign tumors of the vagina that most often occur in women of reproductive-age.

A
  • Stromal tumors (stromal polyps)
  • Leiomyomas
  • Hemangiomas
34
Q

In which location of the vagina are invasive tumors most often seen?

A

Upper vagina along the posterior wall at the junction with the ectocervix

35
Q

Embryonal rhabdomyosarcoma (aka sarcoma botryoides) arises where in the female genital tract and most often in what age group?

A
  • Rare vaginal tumor
  • Most often in infants and children <4 y/o
36
Q

How do embryonal rhabdomyosarcoma (aka sarcoma botryoides) appear on presenation?

A

Clear, polypoid, round, grape-like mass emerging from vagina

37
Q

How do the tumor cells of embryonal rhabdomyosarcoma (aka sarcoma botryoides) and tumor appear histologically?

A
  • Small and have oval nuclei, w/ small protrusions of cytoplasm from one end, resembling a tennis racket
  • Tumor cells beneath vaginal epi. = crowded in a cambium layer
  • Deep regions lie in loose fibromyxomatous stroma that is edematous
38
Q

What is the prognosis and complications associated with embryonal rhabdomyosarcoma (aka sarcoma botryoides)?

A
  • Tend to invade locally = death by penetration into peritoneal cavity or by obstruction of the urinary tract
  • Surgery + chemotherapy offer best hope in cases diagnosed early
39
Q

What is the “transformation zone” of the cervix and why is this area clinically significant?

A
  • Area where columnar epithelium (endocervix) meets the squamous epithelium (ectocervix) = Squamocolumnar Jct.
  • Contains area of immature squamous metaplatic epithelial cells which are highly susceptible to infections with HPV
40
Q

In which location do cervical precursor lesions and cancer develop?

A

“Transformation zone” = Squamocolumnar Junction

41
Q

What is the dominant microbial species found in the normal vagina and what is its function?

A
  • Lactobacilli
  • Produce lactic acid, which maintain vaginal pH <4.5
  • Produce bacteriotoxic hydrogen peroxide (H2O2)
42
Q

What are endocervical polyps, where do they arise and how do they appear?

A
  • Common benign exophytic growths arising within endocervical canal
  • Vary from small, sessile “bumps” to large polypoid masses that may protrude through cervical os
43
Q

What is the clinical significance of endocervical polyps?

A

May be source of irregular vaginal “spotting” (bleeding) that arouses suspicion of some more ominous lesion

44
Q

What is the most important risk factor for the development of cervical cancer?

A

HPV especially type 16 (60% of cases) and (10% of cases)

45
Q

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?

A
  • E6 inhibits p53 and ↑ regulates expression of telomerase
  • E7 inhibits RB + p21 and p27 = impairs ability of cell to repair DNA damage
46
Q

How do the E6 and E7 proteins of low-risk HPV impact cellular growth and survival?

A
  • E7 proteins bind RB with lower affinity; E6 proteins fail to bind p53
  • Dysregulate growth and survival by interfering w/ Notch signaling pathway
47
Q

What is the position of HPV DNA in precursor lesions assoc. w/ high-risk HPVs and in condylomata assoc. w/ low-risk HPVs?

A

DNA is extrachromosomal (episomal)

48
Q

How does the squamous cell that HPV infects differ from the cell that HPV replicates in?

A
  • Infects immature squamous cells; cannot infect mature cells
  • Viral replication occurs in maturing squamous cells
49
Q

How does the position of the viral DNA of HPV change with malignant transformation?

A

Viral DNA is integrated INTO the host cell genome –> ↑ expression of E6 and E7

50
Q

How does the viral replication and cellular proliferation differ between low-grade squamous intraepithelial lesions (LSIL) and high-grade squamous intraepithelial lesions (HSIL)?

A
  • LSIL have high levels of viral replication and only mild alterations in the growth of host cells –> NOT treated as pre-malignant
  • HSIL = lower rate of viral replication w/ ↑ cellular proliferation and ↓ or arrested epithelial maturation –> high risk for progression to carcinoma
51
Q

Diagnosis of squamous intraepithelial lesions (pre-cursor lesions) is based on identification of what characteristics of nuclear atypia?

A
  • Nuclear enlargement
  • Hyperchromasia (dark staining)
  • Coarse chromatin granules
  • Variation in nuclear size and shape
52
Q

Nuclear changes seen in squamous intraepithelial lesions often accompanied by what cytoplasmic finding?

A

Cytoplasmic “halos” + nuclear alterations = koilocytic atypia

53
Q

How does expansion of the immature cell layer in the normal basal location dictate the grading of a low vs. high-grade squamous intraepithelial lesion?

A
  • LSIL = immature cells confined to the lower 1/3 of the epithelium
  • HSIL = expansion to the upper 2/3 of the epithelial thickness
54
Q

Staining for what cell markers highly associated with HPV infection is useful for confirmation of the diagnosis in equivocal cases of SIL?

A

Ki-67 (marker of actively dividing cells) and p16 (characterized high-risk infections)

55
Q

After SCC what is the second most common tumor type (15%) of the cervix and which 2 types represent only 5% of cases?

A
  • Adenocarcinoma (15%)
  • Adenosquamous and neuroendocrine carcinomas (5%)
56
Q

Advanced cervical carcinoma spreads how and to where?

A

Direct extension to contiguous tissues:

  • Paracervical soft tissue
  • Urinary bladder
  • Ureters –> hydronephrosis

- Rectum

- Vagina

57
Q

Lymphovascular invasion by advanced cervical carcinoma may cause distant metastases to what organs?

A

Liver + Lungs + Bone marrow

58
Q

Which cancer of the cervix is associated with a very poor prognosis?

A

Small-cell neuroendocrine tumors

59
Q

Most patients with advanced cervical cancer die due to what?

A

Local tumor invasion –> ureteral obstruction, pyelonephritis, and uremia

60
Q

An abnormal Pap test should be followed up with what?

A

Colposcopic exam of the cervix and vagina to identify lesion

61
Q

What % of cervical cancer arise in women who were not in a regular screening program?

A

50%

62
Q

What is the significance of persistent HPV infections?

A

Persistent infection ↑↑↑ risk for cancer

63
Q

What % of LSIL regress, persist, and progress to HSIL within 2-year follow-up?

A
  • 60% regress
  • 30% persist
  • 10% progress to HSIL