Pathology Thread

IV. Premalignant and Malignant Neoplasms

Objectives:

After completing this tutorial the student will be able to:

• classify the premalignant conditions and malignant tumors of the vagina
• describe epidemiologic features
• describe clinical appearance
• describe/recognize histologic features and grade lesions
• predict clinical behaviour

1. Vaginal Intraepithelial Neoplasia — VAIN ("Dysplasia")

Epidemiology

VAIN is much less common than cervical or vulvar dysplasia. It may occur as an isolated lesion but more commonly (75% of cases) a pre- or co-existing squamous carcinoma of cervix or vulva is present or VAIN may develop later. This may be due to a field effect involving the squamous epithelium of the lower genital tract (which arises from a common cloacogenic origin) that is affected by the same carcinogenic agent. Risk factors include dysplasia elsewhere in genital tract, HPV infection and in utero exposure to DES.

Question. What is the clinical implication of this "field effect"?

Clinical appearance

The lesion is asymptomatic and often no grossly identifiable lesion can be seen. Diagnosis is usually considered because of an abnormal Pap smear result in a woman with no demonstrable cervical abnormality or who has had hysterectomy. This is confirmed ultimately by colposcopy and biopsy.

Histology.

As with other intraepithelial neoplasia, there are architectural abnormalities in the form of loss of epithelial cell maturation towards the surface (loss of polarity). Cytologic abnormalities occur with dysplastic cells showing nuclear hyperchromasia and pleomorphism, undifferentiated cells resembling the basal cells scattered within the epithelium, and cellular crowding. Mitotic figures, some abnormal, are increased and may be present above the basal layer.

Grading.

The severity of VAIN is graded according the proportion, in thirds, of the total thickness of the epithelium replaced by dysplastic cells.

• VAIN 1: Mild
• VAIN 2: Moderate
• VAIN 3: Severe. Carcinoma in situ may be used when dysplastic cells involve the full thickness of the epithelium and there is no invasion of the underlying stroma.

Clinical behavior

The lesion may regress spontaneously, may recur after treatment, or progress to invasive squamous cell carcinoma if left untreated.

2. Invasive squamous cell carcinoma

Epidemiology

Invasive squamous cell carcinoma of the vagina is much, much less common than its counterpart in the cervix or vulva. Extension or metastasis from a cervical or vulvar primary must be excluded. A tumor should not be considered to be primary vaginal carcinoma unless the cervix is uninvolved or minimally involved by a tumor obviously arising in the vagina. By convention, any cancer involving both cervix and vagina that is histologically compatible with a primary in either organ is classified as cervical. Likewise, tumors involving the vulva and vagina are classified as vulvar cancers.

Most patients are postmenopausal (peaks at 60 to 70 years).

Clinical appearance.

Most tumors arise in the proximal (upper) third of the vagina. They may occur as an exophytic mass or an endophytic ulcer.

Histology.

The tumors show varying degrees of histologic differentiation ranging from well differentiated through to poorly differentiated.

Clinical behavior.

This depends on the stage of the disease. Direct extension into soft tissue of the pelvis or to the mucosa of the bladder or rectum occurs early because the wall of the vagina is thin and is separated from these structures by scant connective tissue.

3. Botryoid (Embyonal) rhabdomyosarcoma (sarcoma botryoides)

Epidemiology.

Botryoid rhabdomyosarcoma is a rare malignant tumor of mesenchymal origin that arises in the lamina propria of the vagina. Over 90% of cases occur in girls under 5 years of age.

Clinical appearance.

The patient presents with vaginal bleeding or smooth, glistening, "grape-like", polypoid masses (hence the name "botryoid"; "grape-like") that fill the vagina and often protrude through the introitus.

Smooth, glistening, "grape-like" masses protrude through the vagina and fill the introitus.

Histology.

Microscopically, the tumor, covered by intact vaginal epithelium, comprises spindled or round cells (rhabdomyoblasts) loosely dispersed in a myxoid stroma. Immediately subjacent to the surface epithelium is a dense layer of tumor cells called the cambium layer. Focal evidence of skeletal muscle differentiation, in the form of cross-striations, may be present.

Dark, small round cells loosely dispersed in myxoid stroma.

Clinical behavior.

The tumor invades extensively and metastasizes widely to regional lymph nodes and hematogenously to distant sites. Direct spread occurs into the bladder, rectum, and soft tissues of the pelvis. Historically, the prognosis after radical surgery has been very poor. However, it has improved with the introduction of adjuvant chemotherapy.