Vaginal adenocarcinoma

　　Firstly, etiology

　　The etiology of vaginal adenocarcinoma is not yet clear. The vagina itself does not have glands, and vaginal adenocarcinoma can come from remnants of the mesonephric duct, paramesonephric ducts, and ectopic endometrial tissue in the vagina.

　　Humans reach maturity in the fetal vaginal development in the late stages of pregnancy. The use of diethylstilbestrol during pregnancy has a certain effect on the fetal reproductive tract. Diethylstilbestrol causes the retention of vaginal glandular epithelium, leading to vaginal adenosis. The increased incidence of vaginal clear cell carcinoma in women who used diethylstilbestrol in early pregnancy is partly due to a large area of ectopic glandular epithelium in the vagina, and the vaginal clear cell carcinoma is related to the fallopian tube endometrial cells in vaginal adenosis. The area of fallopian tube endometrial-type epithelium in women who used diethylstilbestrol in early pregnancy increases, providing more opportunities for interaction with unknown cocarcinogens. These women have estrogen in their bodies as a starting factor promoting cancer after menarche. Diethylstilbestrol passes through the placental barrier into the fetal body after being used by the mother, and the fetus already has estrogen receptors developed in the vaginal area in early pregnancy. Diethylstilbestrol is not a steroid hormone, and it cannot be metabolized in the fetal body like steroid estrogens, so it will affect the development of the fetal vagina.

　　Secondly, pathogenesis

　　1. Primary vaginal adenocarcinoma:The histogenetic mechanism of diethylstilbestrol-induced vaginal clear cell carcinoma: the vagina originates from the Müllerian duct and the urogenital sinus, with a pair of paramesonephric ducts causing the body cavity epithelium to sink near the urogenital ridge, extending tailward continuously, and then fusing at the urogenital sinus. The columnar epithelium originating from the Müllerian duct is replaced by flat epithelial tissue originating from the vaginal plate, which forms the cavity of the vagina, and the vagina is covered with flat epithelium.

　　Vaginal adenocarcinoma can originate from remnants of the mesonephric duct, the paramesonephric ducts that have not been transformed into vaginal mucosa, the glands around the urethra, and ectopic endometrial lesions. Vaginal adenocarcinoma associated with intrauterine diethylstilbestrol exposure can develop from vaginal adenosis. Vaginal adenocarcinoma without intrauterine diethylstilbestrol exposure appears similar to adenocarcinoma in other parts under the microscope. Clear cell carcinomas associated with diethylstilbestrol exhibit three basic histological features: cystic tubular, papillary, and solid. The tumor cells are in a lentil shape and columnar, with transparent cytoplasm and clear cell membranes, or they may be in a coarse, short, nail-like shape, with large, atypical, prominent nuclei and a small amount of cytoplasm around them.

　　(1) Vaginal clear cell carcinoma:

　　① Gross: 2/3 occur at the upper end of the vagina, most are polypoid, can also be nodular, some are flat spots or ulcerative, hard in texture, with granulation tissue on the surface.

　　② Microscopy: Under the microscope, the cancer cells are translucent, the cell structure is arranged in a solid mass, and can be tubular, cystic, papillary, and cystadenoid. Under electron microscopy, the cancer cells contain granules of glycogen in the cytoplasm, have microvilli that are short and obtuse, and are rich in mitochondria and Golgi apparatus.

　　(2) Vaginal mesonephric adenocarcinoma: located in the path of the mesonephric duct in the vaginal part, that is, the lateral and roof walls of the vagina. The tumor grows deeper in the location, covered with vaginal mucosal epithelium. The cancer cells are tubular or papillary, and the cells are typical of tumbler-shaped, deeply stained nuclei, large and atypical. Histological examination shows negative staining for PAS and mucopolysaccharide staining.

　　(3) Endometrioid adenocarcinoma: derived from ectopic endometrium, the cancer cells can be similar to clear cell carcinoma, or non-mucin-secreting glandular epithelial cells, showing obvious atypia.

　　(4) Rare adenocarcinoma: such as mixed intestinal adenocarcinoma and argentaffin cell carcinoma. Under light microscopy, the cancer cells have pseudostratified columnar cells and mucin secretion, and there are undifferentiated small cell nests below the adenocarcinoma. The small cells show positive staining for argentaffin staining, and the histochemical examination shows positive reaction for 5-hydroxytryptamine antibody. Electron microscopy shows neurosecretory granules in small cells.

　　2. Histopathological examination of secondary vaginal adenocarcinoma:The appearance of the vaginal lesion is generally polypoid, papillary, or cauliflower-like, and the vaginal wall presents irregular nodular infiltration. Under the microscope, the recurrent lesions in the vagina are more poorly differentiated than the primary tumor, often forming solid areas and showing more obvious atypical cells and epithelial hyperplasia, and often surrounding blood vessels with vigorous growth. The histological type of secondary adenocarcinoma is mainly mucinous adenocarcinoma, which mainly originates from the metastasis of gastrointestinal tract, cervix, and ovarian tumors.

　　Vaginal adenocarcinoma can cause female vaginal infection and nodular masses that can ulcerate and lead to massive vaginal bleeding. Secondary cases often accompany symptoms from other primary sites. And the disease threatens the patient's life, it is necessary to seek timely treatment.

　　1. Symptoms:Early cancer may have no symptoms. As the course of the disease progresses, symptoms such as vaginal discharge, vaginal bleeding, and certain vaginal adenocarcinomas may produce mucus, making vaginal secretions thicker. When the cancer invades the bladder, symptoms such as frequent urination, urgency, hematuria, or difficulty urinating may occur; when it invades the rectum, symptoms such as tenesmus and difficulty defecating may occur; when it invades the para-vaginal area, the main ligament, the uterosacral ligament, there may be pain in the iliac or lumbar sacral area.

　　2, Signs:Vaginal lesions are mostly polypoid or nodular, can also be flat plaques or ulcerous, with a harder texture, surface with small granulation tissue, and shallow growth location, which can spread on the vaginal surface and involve most of the vagina.

　　The clinical symptoms of vaginal adenocarcinoma without a history of intrauterine diethylstilbestrol exposure are similar to those of vaginal squamous cell carcinoma, and symptoms appear at a more advanced stage, making diagnosis more difficult. It is necessary to differentiate between primary vaginal cancer and cancer metastasized from other sites. Occasionally, cancer originating in the kidney, breast, colon, or prostate may first present as vaginal cancer.

　　The age of diagnosis of vaginal clear cell adenocarcinoma with a history of intrauterine diethylstilbestrol exposure is 19 years old. Small tumors are usually asymptomatic clinically and can be detected through palpation or Pap smear. Large tumors may present with irregular vaginal bleeding or increased vaginal discharge symptoms. Vaginal clear cell adenocarcinoma can occur at any site in the vagina, primarily occurring at the upper third of the anterior vaginal wall. The size of the tumor ranges from 1 to 30 cm, most of which are exophytic and invasive in growth, with 97% of patients with vaginal clear cell adenocarcinoma having vaginal adenosis. The typical gross appearance of vaginal adenosis is red, velvety, resembling a grape-like lesion.

　　Clinical manifestations of secondary vaginal adenocarcinoma: irregular vaginal bleeding in about 58.2%; bloody leukorrhea and vaginal mass in about 18.2%; the location of recurrent vaginal lesions: 72.8% of recurrent lesions are located at the vaginal apex, posterior wall 18.2%, bilateral walls 5.4%, and anterior wall 3.6%; lesions occurring at the vaginal apex or fornix are mainly from gynecological system adenocarcinoma, accounting for about 92.5%; lesions occurring at the posterior vaginal wall are mainly from gastrointestinal tumor metastasis, accounting for about 90.0%.

　　Long-term follow-up of vaginal adenocarcinoma is necessary, as most recurrences occur within 3 years of treatment, and there are also reports of recurrence after 20 years of treatment. Approximately 1/3 of patients with recurrence first discover lesions at distant sites, most often in the lung.

　　Prognosis

　　It is generally believed that important factors determining prognosis are: ① stage of disease; ② regional lymph node metastasis; ③ degree of nuclear mitotic activity. The pelvic lymph node metastasis rate in stage I is 10% to 12.5%, and in stage II, it is 50%. Radical surgical treatment is performed for early-stage vaginal clear cell adenocarcinoma, with a 5-year survival rate of 87% in stage I, 76% in stage II, 40% in stage III, and 0% in stage IV (Herbst, 1981; John, 1982; Karol, 1990).

　　The prognosis of vaginal clear cell adenocarcinoma is related to the history of estrogen exposure. Those with a history of exposure are less likely to have distant metastasis and have a higher long-term survival rate. Among the 318 reported cases of vaginal clear cell adenocarcinoma, 18.6% had pelvic lymph node metastasis, 1.2% had para-aortic lymph node metastasis, with a 5-year survival rate of 84% and a 10-year survival rate of 78%. The tumor metastasis sites were lung (9.0%), supraclavicular lymph nodes (1.6%). Those without a history of estrogen exposure had pelvic lymph node metastasis of 17.1%, para-aortic lymph node metastasis of 8.6%, with a 5-year survival rate of 69% and a 10-year survival rate of 60%. The tumor metastasis sites were lung (24%) and supraclavicular lymph nodes (8.0%).

　　The prognosis of clear cell adenocarcinoma of the vagina is also related to the pathological type (Herbst, 1979), with a 5-year survival rate of 88% for cystic type, 73% for papillary type, solid type, or mixed type. Patients with cystic type are often older than 19 years old.

　　For young patients, after vaginal resection, the use of skin flap reconstruction of the vagina has been reported to have successful pregnancy (Hudson, 1988).

　　The prognosis of secondary vaginal adenocarcinoma is poor, with low differentiation and active invasive growth as its morphological characteristics. Therefore, strengthen postoperative examination and follow-up, especially within 3 to 5 years after surgery. Regardless of the primary tumor site, 80% of recurrences occur 3 years after the resection of primary adenocarcinoma. Studies have shown that the recurrence time of adenocarcinoma from various sources in the vagina is very similar.

　　Tumor marker examination, secretion examination, all vaginal masses or obvious erosions should undergo vaginal cytology examination and biopsy for diagnosis. For lesions that are localized, superficial, and small, observation and biopsy can be performed under colposcopy, or Lugol's solution can be locally applied, and biopsy can be performed at non-staining areas for diagnosis. If necessary, fine needle aspiration or lymph node excision from the supraclavicular lymph nodes can be performed, and pathological examination can be conducted. Vaginal bimanual examination and rectal examination should also be performed.

　　Since clear cell adenocarcinoma is prone to lung and supraclavicular lymph node metastasis, chest X-ray examination should be performed for suspected patients.

　　1. Eat

　　1. Eat more foods that enhance immunity: turtle, tortoise, sea turtle, sandworm, crucian carp, shark, water snake, shrimp, white flower snake, crucian carp, mulberry, fig, lychee, walnut, loofah, soybean paste, olive, almond, luffa.

　　2. For infection and ulceration, eat shepherd's purse,螺蛳, needlefish, loach, herring, chrysanthemum, rapeseed, taro, mung bean, red bean, Malan tou.

　　3. For lymph node enlargement, eat taro, hawthorn, lily, water chestnut, mulberry seeds,螺蛳, yellow catfish, cat meat.

　　2. Avoid

　　1. Avoid smoking and alcohol.

　　2. Avoid spicy and刺激性 foods.

　　3. Avoid moldy and pickled foods.

　　4. Avoid fried, greasy, smoked, and grilled foods.

　　5. Avoid all warm foods such as lamb, dog meat, chive, etc.

　　Traditional Chinese Medicine Treatment for Vaginal Adenocarcinoma

　　1. Selecting formulas based on differentiation

　　After surgery, use 16 of Cangzhu, 20 of Danshen, 12 of Shengdi, 15 of Shanyao, 18 of Shengma, 12 of Huangqi, 16 of Longgu, 12 of Foshou, decocted in water and taken as a single dose daily to enhance immunity, promote wound healing, and improve the quality of life. After wound healing, the following can be used: 50 of Shanzhailian, 60 of Shishangbai, 16 of Yunfu, 15 of Fashenxia, 12 of Zhuru, 15 of Nuzhenzi, 12 of Shudi, 6 of Honghua, 8 of Gancao, decocted in water and taken as a single dose daily, taken for 5 consecutive days, then take the above formula for 4 more days, which is helpful to improve the efficacy.

　　Second, special formula and verified formula

　　(1) Sanpin formula: Arsenic sulfide 45g, Alum 60g, Realgar 7.2g, Myrrha 3.6g. Grind into fine powder and mix to make three-penny coin-sized Sanpin cakes (thick 2mm, weight 0.2g), disinfected with ultraviolet light and stored for use. The patient lies on the gynecological examination bed, the vagina is disinfected, and the unbroken parts of the vagina and fornix are protected with Vaseline gauze strips first. Apply the Sanpin cake to the tumor, after 5-7 days, the necrotic tissue falls off, and before the Sanpin cake is absorbed, the tissue falls off and change to traditional Chinese medicine

　　(2) Huangwu San No. 1: Huang Bai 64%, Qingfen 13%, Wugong 7%, Bingpian 3%, She Xiang 0.7%, Xiong Huang 12.3%, respectively ground into powder through a 100-mesh sieve, mixed and stored for use. Use sterile tail thread cotton balls, dip about 1g of medicine powder with long-nose forceps and send it into the damaged area of the vagina; for mild cases, once a week, for severe cases, apply medicine 2-3 times a week. Avoid sexual intercourse during treatment.

　　2. Internal treatment formula

　　(1) Antineoplastic tablet: 5 catties of Strychnos nux-vomica, Trichosanthes kirilowii, and Fritillaria thunbergii, 1 catty of Liquorice, Strychnos nux-vomica peeled, fried in sesame oil until crisp, mixed with the other three drugs into a fine powder, added with starch to make tablets, each tablet 0.3g, taken 3 times a day; initially 3 tablets per time, no adverse reactions increase 5 tablets per time, not divided into courses, continue to take medicine. Most of them have increased physical strength and appetite; symptoms such as tightness of hands and feet may occur with excessive or prolonged medication, which will disappear after stopping the medicine. This formula detoxifies, resolves swelling, and removes blood stasis.

　　(2) Pinellia pedatisecta formula: Pinellia pedatisecta in appropriate amount, made into oral tablets; taken orally, 3 times a day, the total amount is about 60g of crude drug, which has a significant effect of clearing heat, detoxifying and anti-cancer.

　　3. Formulas for preventing and treating radiotherapy and chemotherapy toxic and side effects:Chemotherapy and radiotherapy for malignant tumors often lead to a series of toxic and side effects after treatment; such as local pain, adhesion, tissue necrosis, decreased blood cells and platelets in the whole body, disordered digestive function, damage to liver and kidney function, damage to the nervous system, etc. The application of traditional Chinese medicine formulas for the prevention and treatment of these toxic and side effects has a good effect. The following formulas can be selected for use.