The multistage process of vaginal cancer resulting from deep infiltrative endometriosis: a case report | BMC Women’s Health
Vaginal cancer accounts for 1-2% of all gynecological malignancies. The most common histologic subtype is squamous cell carcinoma, and established risk factors include HPV infection, smoking, and decreased immune function . The second most common subtype is adenocarcinoma, accounting for 15% of all primary vaginal cancers. . Most cases of adenocarcinoma correlate with benign endometriosis . In a recent comprehensive review, 37 histologically documented cases of primary vaginal cancer emerged from endometriosis . In the review, 25 tumors had epithelial histology (17 endometrioid carcinomas; 3 clear cell carcinomas; and 5 adenocarcinomas not otherwise specified), while 12 tumors had sarcomatous histology.
Sampson first established the specific criteria to define cancer resulting from endometriosis : (1) the presence of benign endometrial tissue and cancer in the same site, (2) the presence of endometrial stroma surrounding the glands, and (3) exclusion of metastases from another primary site. Based on these criteria, the vaginal mass was diagnosed as vaginal endometrioid carcinoma associated with endometriosis.
In the vaginal mass, complex hyperplasia presented synchronously with the cancer of endometriosis against the background of endometriosis. The step-by-step transformation process from typical endometriosis to atypical endometrioma and finally cancer is well documented in ovarian cancer associated with endometriosis . The case reveals the process of transition from benign endometriosis to complex hyperplasia to cancer to endometriosis in deep infiltrative endometriosis. Atypical endometriosis is considered a histologically intermediate feature between benign and malignant . This term corresponds to architecturally complex and cytologically atypical proliferative lesions that resemble atypical hyperplasia appearing in the endometrium. This sequential change from deep infiltrative endometriosis to malignancy has not been reported.
In this case study, rectovaginal endometriosis could have invaded the vaginal and rectal wall with a protruding polypoid appearance. . The main mass, located in the rectovaginal septum and cul-de-sac developed into complex hyperplasia, while vaginal endometriosis developed into endometrioid carcinoma. During this time, rectal endometriosis did not develop into hyperplasia or carcinoma. The case showed the difference in the degree of malignant change depending on the organ where the endometriosis is implanted; the result was not found in the literature.
Hyperestrogenism is associated with the malignant transformation of endometriosis, and the microenvironment provided by endometriosis facilitates the excessive accumulation of estrogen by several mechanisms. . Normally aromatase is absent in eutopic endometrial tissue, but in endometriotic tissue it is present at high levels . This enzyme catalyzes the conversion of androstenedione and testosterone to estrone and estradiol, respectively. Its presence in endometriotic tissue leads to constitutive expression of estradiol, and excess estradiol can lead to cell proliferation by inducing cytokine production. . Additionally, estradiol stimulates the production of prostaglandin E2, which promotes tumor growth and triggers aromatase activity, resulting in a positive feedback loop in favor of continued estrogen formation in endometriosis. [22, 24].
In obese women, the peripheral conversion of steroid hormones to estrone by aromatase increases, leading to a hyperestrogenic environment. Zanetta compared 31 patients with 62 controls and found that obese women using unopposed exogenous estrogen had a significantly increased risk of developing cancer from endometriosis (P= 0.05) . The patient had a BMI of 36.4 kg / m2, and hyperestrogenism linked to obesity may have been responsible for the malignant transformation of endometriosis.
Endometrial cancer is a malignant epithelial tumor that forms in the endometrium. It is the most common gynecological malignancy in the United States . Risk factors for endometrial cancer include increased estrogen levels (caused by obesity, diabetes, and a high fat diet), early age at menarche, nulliparity, age late menopause, advanced age and tamoxifen use. [27,28,29,30]. Endometriosis is linked to endometrial cancer, reflecting overlapping risk factors, such as endogenous or exogenous hyperestrogenia and ovulatory dysfunction [9, 10]. In a recent meta-analysis, the risk of endometrial cancer is 40% higher in women with endometriosis .
This patient was diagnosed with vaginal cancer associated with stage I endometriosis and stage IA1 synchronous endometrial cancer. The patient needed full treatment for vaginal cancer combined with endometriosis and endometrial cancer. Given the limited experience with vaginal carcinoma associated with endometriosis, optimal management remains poorly established. Surgical excision of malignant lesions is used consistently in most patients. However, the need and composition of adjuvant therapy is not uniform and depends on the characteristics of the patient and the tumor. . For patients with epithelial tumors, adjuvant therapy is less frequently used. The patient had residual endometriosis involving her vagina and rectum (resection margin with endometriosis). Postoperative medical treatment for rectovaginal endometriosis is important . In the case, the progestogen was treated to suppress any spread of the residual endometriosis.
This case demonstrated a multistage transformation from endometriosis to complex hyperplasia to endometrioid carcinoma. Progression was individualized between implantation sites and even within the same organ. Once surgery is indicated, complete excision of endometriotic lesions is necessary as the residual lesion may include hidden malignancy.