Vaginal Malignancy

Sareena Singh, MD, FACOG
BASICS
DESCRIPTION
Carcinomas of the vagina are uncommon\: 2-3% of gynecologic malignancies; 2,300 new cases annually.
Vaginal intraepithelial neoplasia (VAIN), de
epithelial involvement\:
VAIN 1\: 1/3 thickness
VAIN 2\: 2/3 thickness
VAIN 3\: >2/3 thickness
Carcinoma in situ (CIS)\: designating full-thickness neoplastic changes without invasion through the
basement membrane
Invasive malignancies\: Vaginal malignancies include squamous cell carcinoma (85-90%), adenocarcinoma
(5-10%), sarcoma (2-3%), and melanoma (2-3%). Clear cell carcinoma is a subtype of adenocarcinoma.
Invasive squamous cell carcinoma has the potential for metastasis to the lungs and liver.
To be classi
involved, then the tumor is classi
Additionally, if the patient has had a diagnosis of invasive cervical or vulvar cancer in the preceding 5
years, it can not be classi
Most vaginal malignancies are metastatic tumors from other primary sites (e.g., cervix, vulva,
endometrium, breast, ovary).
Most common sites of primary vaginal cancer metastases\: lung, liver, bone
Pregnancy Considerations
This malignancy is not typically associated with pregnancy.
EPIDEMIOLOGY
Incidence
Predominant age
CIS\: mid-40 to 60 yearsInvasive squamous cell malignancy\: mid-60 to 70 years
Adenocarcinoma\: any age; 50 years is the mean age. Peak incidence is between 17 and 21 years of age.
Clear cell adenocarcinoma occurs most often in females aged \<30 years with a history of exposure to
diethylstilbestrol (DES) in utero.
Mixed müllerian sarcomas and leiomyosarcomas in the adult population\: mean age is 60 years
Pediatric Considerations
Vaginal tumors are extremely rare. Rhabdomyosarcoma (botryoid and embryonal subtype) is the most
common malignant neoplasm of the vagina. Less common entities are germ cell tumor and clear cell
adenocarcinoma.
Prevalence
In the United States, it is one of the rarest of all gynecologic malignancies (3%).
ETIOLOGY AND PATHOPHYSIOLOGY
Women with a history of cervical malignancy have a higher probability of developing squamous cell
malignancy in the vagina, even after hysterectomy.
Human papillomavirus (HPV) is found in 80-93% of patients with vaginal CIS and 50-65% of the patients
with invasive vaginal carcinoma.
HPV-16 is the most common, found in 66% of CIS and 55% of invasive vaginal cancers.
Smokers have a higher incidence.
Clear cell adenocarcinoma of the vagina in young women has been associated with DES exposure. The
incidence, however, is exceedingly rare, estimated at 1/1,000 to 1/10,000 exposed females.
Metastatic lesions can involve the vagina, spreading from the other gynecologic organs.
Although rare, renal cell carcinoma, lung adenocarcinoma, GI cancer, pancreatic adenocarcinoma,
ovarian germ cell cancer, trophoblastic neoplasm, and breast cancer can all metastasize to the vagina.
Genetics
No known genetic pattern
RISK FACTORS
Similar risk factors as cervical cancer
AgeAfrican American
Smoking
Multiple sex partners, early age of
History of squamous cell cancer of the cervix or vulva
HPV infection
Vaginal adenosis
Vaginal irritation
DES exposure in utero
Immunocompromised, HIV
Prior pelvic radiation
COMMONLY ASSOCIATED CONDITIONS
Due to the
vulva and should be followed closely.
DIAGNOSIS
HISTORY
Abnormal bleeding is the most common symptom.
Postcoital bleeding can result from direct trauma to the tumor.
Vaginal discharge
Dyspareunia
Urinary symptoms, including hematuria and increased frequency
Constipation
Pain along with symptoms and signs of hydroureter are late
paravaginal tissues and extends to the pelvic sidewall.
Pediatric Considerations
In children, sarcomas can present either as a mass protruding from the vagina or as an abnormal genital
bleeding.
PHYSICAL EXAMPelvic examination
The vagina, uterus, adnexa (fallopian tubes and ovaries), bladder, and rectum should be evaluated for
unusual changes.
Vaginal malignancies are found most commonly on the posterior wall in the upper 1/3 of the vagina.
DIFFERENTIAL DIAGNOSIS
Premalignant changes\: VAIN 1, 2, and 3 and CIS
Adequate biopsies ensure that invasive lesions are not overlooked. Invasive lesions penetrate the
basement membrane and cannot be treated conservatively.
Other malignancies, such as endometrial, cervix, bladder, or colon cancer, can invade directly into the
vagina or metastasize to the vagina.
In the childbearing years, trophoblastic disease should be considered.
The vagina is a common site of metastases; however, biopsy should typically be avoided because the
implants are very vascular and may hemorrhage if sampled.
The clinical presentation is typically obvious so histopathologic con
required.
DIAGNOSTIC TESTS & INTERPRETATION
Initial Tests (lab, imaging)
Pap smear may incidentally detect asymptomatic lesions.
Biopsy suspicious lesions
Chest x-ray (CXR)\: to evaluate for metastatic disease
CT scan and/or MRI\: to evaluate the liver and retroperitoneum, especially the lymph nodes in the pelvic
and periaortic area
PET scan detects primary and secondary metastatic lesions more often than CT scan.

ALERT

PET scan correlation with CT scan lesions strongly suggests malignancy.
Follow-Up Tests & Special ConsiderationsLymphoscintigraphy (sentinel lymph node mapping) as part of the pretreatment evaluation can result in a
change in the radiation
cancer.
HPV vaccination\: Implementation of prophylactic HPV vaccination could prevent ˜2/3 of the
intraepithelial lesions in the lower genital tract but is yet to be proven.
Diagnostic Procedures/Other
Colposcopy with directed biopsies for small lesions
Wide excision under anesthesia of super
not present.
Cystoscopy to rule out bladder invasion
Proctosigmoidoscopy to rule out rectal invasion
Test Interpretation
Tumors are staged clinically\:
Stage 0\: VAIN and CIS
Stage I\: carcinoma limited to the vaginal wall (26%)
Stage II\: involves the subvaginal tissues but has not extended to the pelvic wall (37%)
Stage III\: extends to the pelvic wall (24%)
Stage IV\: extends beyond the true pelvis (13%)
IVa\: Tumor invades bladder and/or rectal mucosa and/or direct extension beyond the true pelvis.
IVb\: spread to distant organs
TREATMENT
GENERAL MEASURES
Treatment methods for VAIN and CIS include the following\:
Wide local excision
Partial or total vaginectomy
Intravaginal chemotherapy with 5%
Intracavitary radiation therapy
MEDICATION
Imiquimod
In a review of the e1), the following
results were reported\:
26-100% of patients had complete regression.
0-60% of patients had partial regression.
0-37% of patients experienced recurrence.
Contraindications
The diagnosis must be established with certainty prior to treatment.
If there is any doubt that a process beyond in situ disease exists, vaginectomy must be performed.
These patients are often elderly, and aggressive therapy is limited by the patient's performance status
and ability to tolerate radical surgery, chemotherapy, or radiation.
ISSUES FOR REFERRAL
Patients should be treated and followed by a gynecologic oncologist and/or a radiation oncologist.
ADDITIONAL THERAPIES
Treatment with radiotherapy depends on the stage of disease (2)[A]. This treatment option should be
discussed with physicians experienced with this malignancy.
It is common to use radiotherapy and sensitizing chemotherapy (chemoradiation) for better cancer
control.
Early-stage primary squamous cell carcinoma treated with radiation alone has shown good results.
Stage III vaginal cancer may bene
Patients with advanced squamous cell carcinoma or adenocarcinoma receive concurrent irradiation and
cisplatin-based chemotherapy.
Neoadjuvant chemotherapy followed by radical surgery may bene
In most tumor types, metastatic disease from the vagina to other sites is only minimally responsive to
chemotherapy.With one exception, no chemotherapeutic agents have shown a survival advantage. The exception is
childhood sarcomas, which have been treated with combinations of the following\: vincristine,
dactinomycin (actinomycin-D), cyclophosphamide (Cytoxan), cisplatin, etoposide (VP-16)
SURGERY/OTHER PROCEDURES
Whenever there is a doubt as to the presence or absence of invasive disease, vaginectomy must be
performed.
Invasive lesions usually are treated by radiation therapy, but stage I lesions can be treated with radical
hysterectomy or radical vaginectomy with pelvic lymph node dissection (2)[A].
If the lesion involves the lower vagina, inguinal node dissection also must be done because cancer
involving the lower vagina can metastasize to the groin region (inguinal-femoral nodes).
Premenopausal women who desire to retain ovarian function are better candidates for radical surgery for
early-stage disease, with vaginal reconstruction possible afterward.
Patients who have not completed their family can occasionally be treated with limited resection and
localized radiation to the area (3).
Sarcomas are treated by radiation therapy followed by pelvic exenteration if persistent disease is present.
Pediatric Considerations
The treatment of vaginal tumors today mainly consists of neoadjuvant chemotherapy followed by local
control with surgery or radiotherapy.
Geriatric Considerations
Older patients, many with a long history of smoking, are at a higher risk for malignancies requiring surgical
treatments.
ONGOING CARE
FOLLOW-UP RECOMMENDATIONS
Patients are usually ambulatory and able to resume full activity by 6 weeks after surgery.
Most patients are fully active while receiving chemotherapy and radiation therapy.
Patient Monitoring
Pelvic examination and Pap smear every 3 months for 2 years, then every 6 months for the next 3 years,
and then yearly thereafterAnnual CXR
PATIENT EDUCATION
American College of Obstetricians and Gynecologists\: http\://www.acog.org
American Cancer Society\: https\://www.cancer.org/
MedlinePlus\: http\://www.nlm.nih.gov/medlineplus/vaginalcancer.html
PROGNOSIS
Stage and 5-year survival (4)
I\: 77.6%
II\: 52.2%
III\: 42.5%
IVA\: 20.5%
IVB\: 12.9%
Stage is the most important determinant of survival.
Tumor size >2 cm, correlated with worse survival outcome

COMPLICATIONS

Those typically associated with major abdominal surgery or radiation therapy
Common complications of treatment include rectovaginal or vesicovaginal fistulas, rectal/vaginal
strictures, radiation cystitis, and/or proctitis.
Most recurrences occur within the first 2 years after initial diagnosis.
REFERENCES
1. Iavazzo C, Pitsouni E, Athanasiou S, et al. Imiquimod for treatment of vulvar and vaginal
intraepithelial neoplasia. Int J Gynaecol Obstet. 2008;101(1)\:3-10.
2. Guerri S, Perrone AM, Buwenge M, et al. De
systematic review. Oncologist. 2019;24(1)\:132-141. Full Text
3. Gadducci A, Fabrini MG, Lanfredini N, et al. Squamous cell carcinoma of the vagina\: natural history,
treatment modalities and prognostic factors. Crit Rev Oncol Hematol. 2015;93(3)\:211-224.4. Adams TS, Cuello MA. Cancer of the vagina. Int J Gynaecol Obstet. 2018;143(Suppl 2)\:14-21.
Additional Reading
Wolfson AH, Reis IM, Portelance L, et al. Prognostic impact of clinical tumor size on overall survival for
subclassifying stages I and II vaginal cancer\: a SEER analysis. Gynecol Oncol. 2016;141(2)\:255-259.
Codes
ICD10
C52 Malignant neoplasm of vagina
D07.2 Carcinoma in situ of vagina
N89.3 Dysplasia of vagina, unspeci
Clinical Pearls
Vaginal cancer is rare; 85-90% of vaginal cancers are squamous cell.
Vaginal malignancies are found most commonly on the posterior wall in the upper 1/3 of the vagina.
Most vaginal malignancies are metastatic (from cervix, vulva, endometrium, breast, or ovary).