Vaginal cancer

A young woman with vagina cancer exposed to clinical case diethylstilbestrol and review of the literature. We analyzed the case of a 20-year-old patient, who was exposed in utero to diethylstilbestrol, as a probable predisposing factor to manifest vaginal cancer. The diagnostic pillar, in addition to the family history, was the taking of incisional biopsy, with histopathological report of clear cell carcinoma, stage III, extended to the pelvic wall, with metastasis to the lymph nodes. regional and absence of distant metastasis. Surgical management was decided with protocolized laparotomy, peritoneal lavage, retroperitoneal biopsies and radical hysterectomy, Piver III, with involvement of two thirds of the vagina. Factors of poor prognosis were coadjuvant management with systemic chemotherapy.

The objectives of this article are: to analyze the case of a patient with vaginal cancer who was exposed in utero to diethylstilbestrol, as a probable predisposing factor, and discuss the treatment, aggressive but necessary, for a young woman with a high risk of relapse adenocarcinoma of clear vaginal cells.

CLINICAL CASE

A 20-year-old female patient who started her condition three months before her first medical visit. She manifested opsomenorrheal menstrual cycles and moderate intensity abdominal pain, colic, of a month of evolution. It was attended by a particular gynecologist, who detected a profuse tumor that was seen in the vaginal introitus. His gynecological and obstetric history were: menarche at 12 years of age, rhythm 30 x 3, dysmenorrheic, amenorrhea of two months of patient evolution.

Laboratory studies were taken: biometrics blood count, blood chemistry, liver function tests, coagulation times, general urinalysis, all with results within normal parameters. Tumor markers: CA-125 and beta fraction of chorionic gonadotropin, both negative. The chest radiograph showed no findings of pulmonary or mediastinal metastases.

In abdominal-pelvic ultrasound, a normal image of the uterine body was seen, although displaced to the left of the midline. The right ovary had simple cysts. A solid tumor, perhaps of vaginal or adnexal origin, of 10 x 7 x 5 cm was observed. The Liver, kidneys, pancreas and bile ducts were normal (Figures 1 and 2).

Abdominal-pelvic computed tomography showed left ganglionar growth of the aorta at the height of L3, approximately 2 cm in diameter greater, lobed, with heterogeneous enhancement, which gave a topographic appearance of ganglionic conglomerate. The left ovary was enlarged and had small hypodense images in the parenchyma, less than 1 cm. In the right ovary a heterogeneous image with mixed density was observed, a mixed solid component of 7 x 6 cm in the major axes and free liquid in the bottom of bag (figures 3 and 4). In the office an incisional biopsy of the tumor was taken, which was observed in the vaginal introitus. The histopathological report confirmed moderate adenocarcinoma and little differentiated,

With clear cell component, compatible with papillary serous adenocarcinoma. The preoperative diagnosis was solid tumor, probably originated in the ovary. Due to the above, and in view of the suspicion of adnexal tumor, laparotomy was performed protocolized, peritoneal lavage, retroperitoneal biopsies and radical hysterectomy, without annexes, which were sutured above the true pelvis; Piver III, with two thirds of the vagina. The retroperitoneal lymph nodes were sent for a transoperative study and were reported as positive for malignancy.

The histopathological report was a solid tumor originating in the upper third of the vagina, which corresponded to clear cell adenocarcinoma, moderately little differentiated from it. The neoplasm formed glandular, papillary structures and small solid nests of polyhedral cells, with loss of the nucleus-cytoplasm relationship (Figures 5 and 6). The nuclei were large, there were apparent nucleoli and multiple atypical mitoses. In the study corresponding to the retroperitoneal, para-aortic and iliac ganglia ganglia left, malignant metastatic neoplasm of the vagina was observed (figure 7). The uterus was reported normal and the cytological diagnosis of the peritoneal lavage fluid was negative to malignancy. Healthy cervix.

The neoplasm was classified in stage III. Due to poor prognostic factors (locally advanced stage, retroperitoneal metastasis and tumor greater than 5 cm), he received coadjuvant treatment based on chemotherapy. Systemic: cisplatin: 60 mg x m2 body surface, days 1 and 2; epirubicin: 75 mg x m2 body surface, day 1; and cyclophosphamide: 750 mg x m2 body surface, six cycles in total. Currently, after two years of treatment, the patient is asymptomatic, with no findings of Tumor activity demonstrated by computed tomography of the thorax, abdomen and pelvis.

DISCUSSION

The presented case is of great importance and implies a great challenge for the obstetrician-gynecologist, since timely diagnosis is difficult in the case of a cancer that was considered primary at the beginning of the study and after surgery it was confirmed as the primary of the vagina. The objective is to offer a young and nubile patient an optimal treatment.

Vaginal carcinoma is an infrequent gynecological neoplasm, accounting for only 1% of neoplasms of the female genital tract.1-4 In the United States only 2,100 cases have been diagnosed and 600 patients died from this tumor in the year 2000. Clear cell carcinoma of the vagina has been related to maternal exposure to diethylstilbestrol, with a high degree of histological and manifestation in young women; its incidence peak is at 19 years of age.5-7 This was observed in a healthy woman exposed in utero to diethylstilbestrol, as the only risk factor.

The annual incidence of cases associated with this hormone decreased in 1979, compared to 1973, and has continued in this line; However, in 1987 there were more than 500 cases of adenocarcinomas of clear cells of the vagina and cervix since this control began in 1971. The annual rate of new cases dropped from 25-30 in the early 1970s to 10 to 15 in the 1980s.8

In 1998, the National Health System in Mexico reported the hospital death of 13 people with malignant tumors of the vulva and vagina, without reporting their age; Of these, eight belonged to the rightful population and five to the open population.9 In 1999, the National Health System reported 136 hospital discharges of cases with malignant tumors of the vulva and vagina; 7, 2, 43, 25 and 59 cases in patients from 1 to 4, 5 to 14, 15 to 44, 45 to 64 and 65 or more years of age, respectively. There were no specific reports of the causes.

It is estimated that the incidence of   Clear cell denocarcinoma in women exposed in utero to diethylstilbestrol is 1 in 1,000; It has been observed that the risk is higher in those that the exposure occurred in the first 18 weeks in utero. 11 Other factors, such as the dose and duration of treatment with said hormone, could not be related to the frequency and location of clear cell adenocarcinoma.

In the presented case it was of sum importance to know the clinical history of the patient, who was exposed in utero to diethylstilbestrol in the year of 1984 before the threat of abortion of her mother. Before the era of diethylstilbestrol, vaginal adenocarcinoma was rare; it was believed to be caused by Gartner's vaginal adenosis, endometriosis and remnant ducts. However, from the description of Herbst and Scully of clear cell adenocarcinoma in 197012 and the subsequent relationship with prenatal exposure to said hormone, the diagnosis in stages early stages has been increased by biopsies, the Pap test result and colposcopy.

Since 1938, when it was first synthesized, until 1971

In the United States it was prescribed in pregnant women to prevent the risk of spontaneous abortion. The drug was used freely in patients who had a history of threatened abortion or diabetes mellitus, sometimes even administered only to achieve a healthy pregnancy. In 1971 the FDA contraindicated its use in pregnant women. Its exposure in young patients (late adolescence and early 20 years of age) age) has been related to the clear cell adenocarcinoma of the vagina, as the clinical case of study. Before his prescription, this cancer was rarely seen in women under 20 years of age. The studies carried out show the possibility of lasting effects until the third generation.

found that the risk of intraepithelial neoplasia cervical and vaginal in the daughters of mothers exposed to diethylstilbestrol was doubled, compared to not exposed. The histological findings indicated, also, as a causative factor in utero exposure to diethylstilbestrol.

 

In women exposed to said hormone increases the risk of breast cancer in 25 to 30%, those exposed in utero are at higher risk of manifesting multiple abnormalities in the genital tract and infertility, and the estimated risk for trigger clear cell adenocarcinoma is observed in 1: 1,000 and 1: 1,500 patients.8,14 Diethylstilbestrol has effects similar to those of natural estrogens, uses hormonal secretion of luteinizing inhibitors of the pituitary and inhibits the secretion of testosterone

Its side effects are: a) cardiovascular: elevation of blood pressure, thromboembolism (when administration is greater than 3 mg / day), edema due to sodium retention; b) central nervous system: headache, migraine exacerbation and depression; c) dermatological: chloasma; d) endocrinological: impotence, gynecomastia, sensory disorders of the nipple, feminization in males, urinary incontinence, amenorrhea and dysmenorrhea; and) gastrointestinal: nausea, vomiting and intestinal colic; f) genitourinary: pain, itching in the genitoanal area, only during administration; g) hepatic: elevation of liver function tests; h) ophthalmic: keratoconus, lens intolerance; i) renal and metabolic: alteration in the metabolism of carbohydrates and hypercalcemia

It also causes structural abnormalities in the cervix, such as: hypoplasia, papilloma and cervical pseudopolyps, and in the vagina, such as: adenosis and clear cell adenocarcinoma. In men, children of mothers exposed to diethylstilbestrol, studies show an increase in prostate and testicular cancer.

The initial symptom is abnormal vaginal bleeding, as in the clinical case study. The tumor biopsy reported clear cell adenocarcinoma without knowing the original site. Then surgical management was performed with protocolized laparotomy when suspected of primary ovarian cancer; in this way it was classified as stage III according to the AJCC / UICC / IFGO Federation of Gynecology and Obstetrics) (table 1.

Adenocarcinoma of clear vaginal cells in young patients can be found in any area of the same. However, it has been noted that most tumors originate in the upper third of the anterior wall of the vagina, followed by the anterior face of the lower third of the vagina.18 The prognostic factor more important is the clinical stage of the neoplasm, which reflects the size and depth of the infiltration in the vaginal wall or adjacent tissues. The The age of the patient, the macroscopic aspect of the lesion and the degree of differentiation do not seem to influence the prognosis.

Before a patient exposed in utero to the diethylstilbestrol the explorations by obstetrician gynecologists they must be frequent, since adenocarcinoma of clear cells can appear at any time, even after a negative scan. Around 10 to 20% of patients with invasive disease are asymptomatic. In these cases it is mandatory to perform: cytology, colposcopy, biopsy and touch rectal or vaginal, for the timely diagnosis of the disease.  

In a comparative study of patients exposed and not exposed to diethylstilbestrol, performed by Wagoner et al, it was observed that patients younger than 15 years exposed in utero have poor prognosis compared to the older ones 19 years old not exposed. The tumor diameter was also considered as prognostic factors. the existence of lymph nodes, at the risk of recurrence and low survival Table 2.

The risk of distant metastasis increases according to the stage of the disease; the frequency goes from 13 to 30% in tumors with stages I and II, and from 47 to 52% in stages III and IV. Most recurrences appear in the pelvis before two years, after of the treatment. Other prognostic factors are the depth of penetration of the tumor into the stroma underlying and lymphatic metastases