Early infiltrative squamous cell carcinoma of the vulva

　　1. Etiology

　　Early infiltrative squamous cell carcinoma of the vulva often develops from vulvar intraepithelial neoplasia (VIN), which is closely related to hyperplastic vulvar dystrophy. Patients with viral infectious diseases such as human papillomavirus (HPV) infection in the female lower genital tract and herpes simplex virus type 2 (HSV-2) infection are prone to vulvar squamous epithelial carcinoma. The HPV subtypes associated with vulvar squamous cell invasive carcinoma mainly include types 6, 11, 16, 18, and 33, among which types 16 and 33 can be detected in 90% of VIN sections. Individuals with long-term immune suppression are prone to multicentric vulvar squamous cell invasive carcinoma. The relationship between smoking and vulvar squamous cell invasive carcinoma is under attention.

　　2. Pathogenesis

　　In addition to most originating from the vulvar skin and mucosa, vulvar squamous cell carcinoma can also occur in the epithelium of the large excretory ducts outside the vestibular gland. Such cancer foci are located in the vulvar fatty tissue, and continuous pathological sections can show the relationship between the cancer focus and the gland duct.

　　The tumor resembles the gross changes of in situ carcinoma. Small superficial, elevated hard ulcers or small hard nodules and other foci may appear on the vulva. Due to itching, the vulva may have scratch marks, damage, and other symptoms. The surrounding area of the cancer focus is often accompanied by white lesions or proliferative inflammatory changes.

　　Under the microscope, most vulvar squamous cell carcinomas are well differentiated, with keratinization pearls and intercellular bridges. Lesions in the vestibule and clitoris tend to be poorly differentiated or undifferentiated, often with lymphovascular and perineural invasion. Attention should be paid to the following during microscopic pathological observation: the size and number of the cancer foci, the depth of invasion into the stroma, pathological grading, whether there is involvement of lymphovascular or blood vessels, and the presence of other vulvar diseases. These factors are extremely important for guiding clinical treatment and estimating the prognosis. The histological types of vulvar squamous cell carcinoma can be divided into the following types:

　　1. Keratinizing squamous cell carcinoma:

　　The most common, accounting for 85%. It often occurs in elderly women. The cancer cells are well differentiated, with characteristics of hyperkeratosis and keratin formation, also known as differentiated or grade I squamous cell carcinoma, but with high invasiveness.

　　The tissue morphology: The arrangement of cancer cells has layers, the cells are large and polygonal, more mature, with abundant cytoplasm and eosinophilia. The nuclei are large, round or irregular, with deeper staining, and the nucleoli are visible in the lighter ones. The structure of intercellular bridges can be seen between cells. At the base, the length, size, and growth direction of the needle-like projections are uneven, numerous, and disordered, invading the stroma to form many nests of cancer cells. The nests contain keratinized cells and keratinization pearls, and sometimes the keratinization pearls occupy the entire cell nest, with keratin structures resembling whirlpools or onion skin. There is very little fibrous stroma between the cancer cell nests. Nuclear division is most frequent around the edges of the cell nests and needle-like projections.

　　2. Non-keratinizing squamous cell carcinoma:

　　This type occurs more frequently in the squamous epithelium of the vulvar mucosa, while the squamous epithelium of the vulvar skin is mainly keratinizing squamous cell carcinoma.

　　The tissue morphology: The cancer tissue is composed of polygonal large cells. The cells gather into broad bands, with unclear layers and disordered arrangement. Although the cells are large, the nuclei are also enlarged, with a high degree of atypia, uneven nuclear staining, and a large nucleo-cytoplasmic ratio. Nuclear division is frequent, without keratinization pearls, and keratinized cells are occasionally seen. This type of cancer is equivalent to moderate differentiation or a five-grade degree of malignancy. HPV DNA detection is often negative.

　　3. Basaloid cell carcinoma:

　　It is composed of similar squamous epithelial basal cells. Cells are arranged in sheets, strips, or巢状. Cancer cells are small, immature, and have little cytoplasm. The nucleus is elongated oval or short fusiform, deeply stained, with uniform size and staining, and an increased nucleus-cytoplasm ratio. Keratinocytes are occasionally seen or not seen. This type is equivalent to poorly differentiated or subgrade squamous cell carcinoma. In a few cases, there are nuclear indentation and hollow-like cells with perinuclear halos; VIN lesions can be found near the cancer tissue; HPV DNA detection is positive in 75%. This type should be distinguished from vulvar skin tissue, such as basal cell carcinoma of the labia majora, and also from basal-squamous cell carcinoma, which is a part of basal cell carcinoma that differentiates into squamous cell carcinoma, and basaloid cell carcinoma is a subtype of squamous cell carcinoma.

　　The measurement of the maximum diameter of the cancer does not include the in situ cancer or atypical hyperplastic lesions around the cancer. The depth of cancer invasion is measured from the junction of the epithelium and stroma or from the nearest dermal papilla at the junction of the epithelium and stroma next to the cancer, to the deepest point of invasion. The thickness of the cancer refers to the distance from the outermost layer of the cancer to the deepest point of invasion. The difference between the two is that the depth of invasion starts from the junction of the epithelium and stroma, while the thickness starts from the surface of the tumor including the surface epithelium. To obtain accurate measurement data, the specimen must be properly fixed, cut continuously for sampling, and should be cut vertically rather than diagonally.

　　Early invasive vulvar squamous cell carcinoma can be complicated with the following diseases:

　　1. As the cancer focus gradually increases in size, it can spread to the urethra, perineal body, and vagina, leading to the complication of perineal cancer.

　　2. Some advanced patients may experience lung metastasis of cancer cells, therefore early invasive vulvar squamous cell carcinoma can be complicated with lung cancer.

　　3. Due to decreased body resistance, it can lead to imbalance of flora both inside and outside the body, eventually leading to infection.

　　1. Symptoms

　　About 10% of early invasive vulvar squamous cell carcinomas may be asymptomatic, while the common symptoms include vulvar itching, which usually has a long course. The cause of itching is mainly due to chronic vulvar lesions, such as vulvar malnutrition, vulvovaginitis, etc., rather than the tumor itself. Nearly half of the patients have a history of vulvar itching for more than 5 years. Itching is more severe at night, and scratching can cause vulvar epidermal damage, exacerbating this symptom. If there is an ulcer locally, it is often accompanied by vulvar pain, increased discharge, and sometimes bleeding. Due to the presence of chronic diseases that cause itching in many vulvar squamous cell carcinoma patients, it is difficult to determine the duration of pre-malignant symptoms.

　　2. Signs

　　Lesions can occur at any part of the vulva, but they are most commonly located on the labia majora, followed by the labia minora, clitoris, and posterior commissure. Early invasive cancer signs are not obvious, usually presenting as local papules, nodules, or small ulcers, often coexisting with precancerous vulvar lesions. The cancer focus can be solitary or multiple, and bilateral inguinal lymph node metastasis is extremely rare.

　　3. Metastatic pathways

　　Early infiltrative squamous cell carcinoma of the vulva rarely occurs metastasis. If there is metastasis, it is mainly through the lymphatic transfer pathway, so its metastatic sites are mainly determined by the characteristics of lymphatic drainage. The anterior part of the labia minora is drained by the lymphatic trunk that goes around the clitoris to the mons pubis. In the adipose tissue of the mons pubis, the lymphatic vessels turn laterally and terminate in the upper inner group of the femoral lymph nodes. The posterior part of the labia minora diffuses laterally and merges with the lymphatic drainage of the labia majora, which drains into the perineal褶 and enters the upper group of the femoral lymph nodes from the head and sides. The posterior part of the labia majora has its lymphatic drainage into the perineal褶 and reaches the fascia lata and the adductor longus tendons, terminating in the central group of the femoral lymph nodes. The lymphatic drainage of the posterior symphysis and perineum extends to the posterior lateral side to the perianal area, then forward to the perineal褶; merges with the lymphatic vessels of the labia majora and terminates in the superficial inguinal lymph nodes.

　　The lymphatic drainage of the clitoris is divided into two main pathways. The first is the lymphatic drainage of the prepubic lymphatic plexus, which drains the prepuce of the clitoris towards the head into the mons pubis, then laterally into the superficial inguinal lymph nodes, and then through the sieve-like fascia to the deep inguinal lymph nodes. The second is the lymphatic vessels from the clitoris to the posterior pubic region, parallel to the urethra, reaching the anterior wall of the bladder or directly draining into the obturator and iliac lymph nodes. Therefore, the lymphatic vessels of the clitoris can bypass the femoral lymph nodes to reach the deep pelvic lymph nodes.

　　As can be seen, the first group of lymphatic drainage of the vulva is the superficial inguinal lymph nodes, which are located between the superficial fascia of the abdominal wall and the sieve-like fascia covering the femoral vessels. The deep inguinal lymph nodes are located around the vessels below. The lateral group of the superficial inguinal lymph nodes penetrates the tendons of the external oblique muscle to directly drain into the external iliac lymph nodes. The deep inguinal lymph nodes are often involved only after the superficial inguinal lymph nodes are invaded by cancer. The latest deep inguinal lymph node is Cloquet's lymph node, located in the femoral canal below the inguinal ligament. If there is no metastasis to the inguinal superficial lymph nodes or Cloquet's lymph node, it is unlikely that vulvar cancer will invade the pelvic lymph nodes. According to the characteristics of vulvar lymphatic drainage, the cancer foci are often transferred to the ipsilateral lymph nodes.

　　1. Epidemiology:Invasive squamous cell carcinoma of the vulva (invasive squamous cell carcinoma of the vulva) mainly occurs in postmenopausal women, and the incidence rate increases in a logarithmic form with age. The average age at diagnosis in China is 50 years, and abroad it is 60 years. However, there has been a significant trend of youngening in the past 20 years. Al-Ghamdi (2001) reported that in patients with invasive squamous cell carcinoma of the vulva, young patients under the age of 40 accounted for about 5% of whom the youngest was only 17 years old.

　　2. Prognosis:Early infiltrative squamous cell carcinoma of the vulva can occur metastasis and recurrence.

　　1. Examination of secretions, tumor marker examination.

　　2. Cytological examination: Smears of suspicious lesions are often examined by cytology, and cancer cells can often be seen. Due to the common concurrent infection of external genital lesions, the positive rate is only about 50%.

　　3. Pathological biopsy: All vulvar neoplasms, including cauliflower-like lesions, ulcerative lesions, nodular lesions, and white lesions, should undergo histological examination. During biopsy, for lesions without obvious signs, such as extensive ulcerative lesions, to avoid inaccurate sampling and misdiagnosis, a vaginal magnifying mirror and/or 1% toluidine blue (a nuclear stain) can be used for vulvar staining. Then, 1% acetic acid is used to rinse, identify suspicious lesions, and then perform biopsy. Since both inflammation and cancer can show positive results, toluidine blue staining can only be used to select biopsy sites. When sampling from lesions with necrosis, sufficient depth should be taken, and sampling should be made at the edge of the necrotic tissue to avoid only sampling necrotic tissue, which may affect the results of the examination.

　　1. Diet Guide for Squamous Cell Carcinoma Patients: Squamous cell carcinoma patients have excessive toxins in their bodies and a lot of phlegm. They should eat more expectorant, detoxifying, and cooling foods to alleviate the symptoms of squamous cell carcinoma. Eating high-fiber foods can help the excretion of toxins. Seaweed, wakame, vegetables and fruits, Chinese cabbage, celery, and spinach are the best choices.

　　2. Diet Guide for Squamous Cell Carcinoma Patients: Foods to avoid for squamous cell carcinoma include: chili, pepper, pickled vegetables, fatty meat, overly hot or cold foods, and overly sweet foods. Cancer patients have poor digestion, and mainly consume liquid foods in the early stage. As the condition gradually improves, rich-nutritious foods should be supplemented, which are best to be colorful, delicious, and fragrant to stimulate the appetite of patients.

　　3. Diet Guide for Squamous Cell Carcinoma Patients: The hallmark symptom of squamous cell carcinoma is easy bleeding, which is the result of the spread of squamous cell carcinoma. It is necessary to eat hemostatic and blood-building foods, such as: jujube, Ganoderma lucidum, pork liver, beef, dairy products, black fungus, animal internal organs.

　　Firstly, Prevention

　　Early diagnosis, active treatment, and good follow-up.

　　Secondly, Preoperative Preparation

　　1. Vulvar cancer often occurs with infection, and it is necessary to take a potassium permanganate bath with a concentration of 1/1000 for about one week before the operation.

　　2. Increase high-protein, low-residue diet before the operation, and do not consume high-fiber foods within one week before the operation to ensure that there is no defecation within one week after the operation, and to reduce perineal wound infection caused by defecation.

　　3. Those who need to undergo rectal and anal canal resection should consume liquid food two days before the operation and take intestinal anti-inflammatory medication orally.

　　4. Those who need to undergo total cystectomy with ileal conduit for bladder substitution should prepare for urinary tract and intestinal inflammation.