Vaginal Cancer

Anatomy

  • Muscular dilatable tubular structure
  • 7.5 cm
    • From the cervix to the vulva
  • Location:
    • Dorsal to the base of the bladder and urethra
    • Ventral to the rectum
    • Upper posterior wall is covered by a peritoneal reflection = Pouch of douglas
  • Embryology:
    • Developed from urogenital sinus
      • Fused with mullerian ducts at mullerian tubercle
      • The hymen marks the tubercle
  • Attachment of vagina to uterus —> pos is higher than ant
  • A circular groove, formed at the juncture of the vagina and the cervix, is called the fornix.

Histology

  • Vaginal wall
    • Mucosa
      • thick, nonkeratinizing, stratified squamous epithelium overlying a basement membrane
      • no gland
        • lubricated by mucous secreted in the cervix
    • Muscularis
      • Elastin and a double muscularis layer
      • Highly vascularized
      • Rich innervation and lymphatic
      • Smooth muscle fibers
        • Arranged circular on inner side
        • Longitudinal on outer side
        • Make a vaginal sphincter at introitus
    • Adventitia
      • Thin, outer connective tissue
      • Merges with that of adjacent organs
  • Veins ultimately drains into the internal iliac vein
  • Innervation:
    • Lumbar plexus
    • Pudendal nerve
      • S2-S4
  • Lymphatic
    • Upper part: via the lymphatics of the cervix
      • Upper ant: int iliac & parametrial nodes
    • Upper and Lower posterior: inferior gluteal, presacral, and anorectal nodes
    • Distal vagina: follow patterns of the vulva
      • Inguinal and femoral nodes —> pelvic nodes
    • Mid-vagina may drain either way
    • External iliac are always at risk

Bilateral pelvic nodes should be considered at risk

Bilateral groin nodes are at risk in lesions involving the distal third of the vagina.

Gyn%20LN.gif

Epidemiology

  • Elderly women
    • >60
  • It is increasingly being seen in younger women <— STD and HPV
  • Primary Vaginal Ca —> Rare
    • 1-2% of Gyn Ca
  • 80% to 90% —> metastatic (direct extension or lymph/hem mets)
    • From other primary gynecologic (cervix or vulva)
    • Other non-Gyn sites

If tumour extending to cervix —> It is a cervical ca and if extending to vulva —> It is a vulvar ca

  • Risk factors:
    • Smoking
    • >5 lifetime partners
    • Early onset at intercourse (<17)
    • Current smoking
    • Immunosuppression
    • HPV
      • Similar mechanism as Cervical Ca
      • Vagina doesn't have a transformation zone of immature epithelial cells —> Less HPV induces Ca in Vagina
      • HPV-induced vaginal lesions —> areas of squamous metaplasia that develop during healing of mucosal abrasions caused by coitus, tampon use, chronic pessary use, or other trauma
      • Vaginal Intraepithelial Neoplasia
  • Metastasis to Vagina
    • Uterus
    • Colon
    • Ovary
    • Kidney
    • Breast

Pathology

Epithelial Neoplasms

  • SCC
    • Vaginal Intraepithelial Neoplasia
      • Precursor of SCC
      • Graded from I to III
      • Higher grade —> more thickness involved
      • Associated with HPV
  • 90% SCC
    • Grossly:
      • Nodular
      • Ulcerative
      • Exophytic
      • Plaques
    • Keratinizing, well diff (30%)
      • Squamous pearl formation and intercellular bridges
    • Non-keratinzing, moderately differentiated (>50%)
    • Verrucous carcinoma
      • Rare
      • Variant of well-diff SCC
        • Large, well-circumscribed, soft, cauliflowerlike
        • Papillary growth
        • Pushing borders
        • Little or no atypia
        • Parakeratosis and hyperkeratosis, without koilocytosis
        • May recur locally after surgery, but rarely, if ever, metastasizes
  • Adenocarcinomas: ~5%
    • Clear cell Ca <— Exposure into DES in Utero
      • Younger age (15-22)
      • Better prognosis
  • Melanomas: 4%
    • Second most common cancer of the vagina
    • Lower third and the anterior vaginal wall, although often multifocal
    • Epithelioid cells, spindle cells, or nevuslike cells
    • Melanin pigment is often present
    • Junctional activity is usually present
    • Immunohistochemical stains:
      • S-100 protein
      • Tyrosinase and MART-1 are useful markers when S-100 is negative or only focally positive
      • HMB-45
      • Melan A
      • Tumor thickness correlates with prognosis and may be measured by the methods of Breslow
  • Sarcomas: 3%
    • Leiomyosarcoma the most common
    • Interlacing bundles of spindle-shaped cells, with blunt-ended nuclei and fibrillar cytoplasm
    • condensed round, or spindle, cells (the cambium layer) immediately beneath the intact vaginal epithelium
    • small, dark, spindle-shaped cells, sparsely distributed in a myxoid stroma
    • May show skeletal muscle differentiation, evidenced by intensely eosinophilic cytoplasm with cross striations.
    • Embryonal rhabdomyosarcoma (sarcoma botryoides)
      • Highly malignant
      • Girls <6yr
      • Multiple gray-red, translucent, edematous, grapelike masses
      • Nodules that fill and protrude from the vagina
      • IHC:
        • Actin
        • Desmin
        • Myoglobin
    • Lymphoma
    • Small neuroendocrine cell
      • IHC
        • strongly stain for cytokeratin, neuron-specific enolase, chromogranin A, and serotonin
    • Adenosquamous carcinoma
      • Rare

Vaginal Adenosis & Clear-Cell Adenocarcinoma

Vaginal adenosis is a condition in which mullerian-type glandular epithelium is present after vaginal development is complete.

  • DES in utero
  • Red, velvety, grapelike clusters in vagina
  • Associated with 97% of vaginal and 52% of cervical CA
  • Glandular epithelium may replace the surface epithelium, and undergoes progressive squamous metaplasia
  • Upper third
  • Exophytic
  • Superficially invasive
  • Mainly composed of clear and hobnail-shaped cells
    • Clear cells:
      • Cuboidal or columnar
      • Abundant glycogen-rich cytoplasm
    • Hobnail cells:
      • Large atypical protruding nuclei
      • Small amount of cytoplasm

Natural History

  • Majority —> Upper third (57% to 83%)
    • apex of the vault
    • Posterior wall —> most common
  • Lower third (30%)
  • Local Invasion:
    • Along the vaginal wall
      • Cervix
      • Vulva
    • Anterior wall
      • Vesicovaginal septum
      • Urethra
    • Posterior wall
      • Rectovaginal septum
    • Lateral extension(not common)
      • Parametrium & paracolpal tissues
    • In more advance cases:
      • Obturator fossa
      • Cardinal ligaments
      • Lateral pelvic walls
      • Uterosacral ligaments.
  • Regional nodal metastasis:
    • Risk varies with stage and location of the primary tumor
    • Involvement of inguinal nodes is most common when the lesion is located in the lower third of the vagina
  • Distant metastasis
    • Lungs
    • Supraclavicular LN
Stage Risk of DM
I 15%
II 30%
III 50%
IV 60%

Work-Up

History

  • PMHx:
    • VAIN: asymptomatic
    • Any abnormal pap smear?
      • Any previous treatment?
    • Last Pap Smear
  • General questions:
    • In a young lady always ask about Pregnancy related questions:
      • LMP and Mensturation History
      • Any chance of pregnancy
      • Previous pregnancies/ number of children
      • Desire for future pregnancy
  • Invasive Ca:
    • Irregular vaginal bleeding
      • Postcoital
      • Most common presenting symptom
    • Vaginal discharge
    • Dysuria
    • Pruritis
    • Dysparaunia
    • Pelvic pain —> late symptom
      • Tumor extent beyond the vagina
  • Physical Exam:
    • Start with general Exam
      • General Status
        • Cachectia
        • Fatigue
        • Weakness
      • Anemia
      • Jaundice
      • Lymphadenopathy
        • Cervical/Axillary
        • Supraclavicular
          • Left —> Virchow Node
        • Inguinal
      • Abdominal Exam
        • Mass
        • Tenderness
    • Complete Gyn Exam
      • Bimanual
      • Vaginal Exam
        • Inspection through speculum
          • Total vaginal wall should be visualized
        • Digital vaginal exam
          • Check Cervical OS
          • Fornix
      • Rectal Exam (DRE)
        • Do not forget this! Patient with a vaginal bleeding may actually have an Anal Ca
      • Gyn Exam Under Anesthesia
      • Colposcopy
  • Investigation
    • Cytology and Biopsy
      • Forget to mention biopsy and confirmation of diagnosis will FAIL you!
      • Application of the acetic acid —> then place half-strength Schiller's iodine to determine if the Schiller positive (nonstaining) areas
        • These areas correspond with the involved areas —> to be biopsied
    • Biopsy of the cervix is recommended to rule out primary cervical ca
  • Staging investigation:
  • Vaginal Ca is staged clinically.
  • Blood work:
    • CBC
      • Anemia
      • Need for transfusion
    • KFT
      • Cisplatin toxicity —> Kidney failure
    • LFT
  • FIGO allowed staging work-up:
    • CXR
    • Cystoscopy
    • Proctoscopy/ Proctosigmoidoscopy
    • IVP
  • Other tests ( not changing FIGO staging)
    • Pelvic CT
      • Inguinofemoral and/or pelvic LN
      • Extent of local disease
    • Chest Abdo CT
      • Vaginal melanoma or sarcoma
    • Pelvic MRI
      • Helpful in differentiate recurrence from fibros tissue in F/U

Staging

FIGO Staging
Stage Description
0 Carcinoma in situ, intraepithelial neoplasia grade III
I Limited to the vaginal wall
II Involvement of the subvaginal tissue but without extension to the pelvic side wall
III Extension to the pelvic side wall
IVA Spread to adjacent organs and/or direct extension beyond the true pelvis
IVB Spread to distant organs

Prognostic Factors Influencing Choice of Treatment

Invasive Squamous Cell Carcinoma

  • Stage: Most significant prognostic factor
Stage 10yr OS after defenitive RT
I 70%
IIA 50%
IIB 40%
III 30%
IV None
  • Probable prognostic factors:
    • Size (>5mm)
    • Location
      • proximal half —> better(?)
  • Histlogical grade
  • Overexpression of HER-2/neu
    • rare ==> aggressive
  • More favorable prognosis if overexpression of wild-type p53 protein than in tumors containing mutated p53 genes.
  • Age
    • >60 do worse
  • AdenoCa and Melanoma
    • More metastases to the lung and SCN
  • Depth of invasion and size of lesion (>3 cm) in melanoma —> adversely impacted survival
  • Malignant mesenchymal tumors —> do worse
  • Vaginal sarcoma poor prognostic factors:
    • Infiltrative worse than pushing borders
    • High mitotic rate ≥5 mitoses per 10 HPF
    • Size >3 cm in diameter
    • Cytologic atypia

Treatment of Vaginal Ca