Bartholin gland cancer is a rare malignant neoplasia affecting the tissues of the large gland of the vestibule of the vagina. The main sign of the disease is a growing sedentary formation of elastic consistency in the lower third of the labia majora. The growth of the tumor may be accompanied by pain, an increase in body temperature, an increase and soreness of the inguinal lymph nodes. Diagnostic measures include anamnesis collection, clinical examination, biopsy of the neoplasm. The leading method of treatment is surgical, in addition, radio and chemotherapy can be prescribed.
Cancer (carcinoma) of the bartholin gland is a malignant tumor process, the source of which is the epithelial cells of the large vestibular gland located in the thickness of the large labrum at the base and named after Kaspar Bartholin, a Danish anatomist who described it in the XVII century. This localization accounts for 3% of all vulvar carcinomas, which account for 3-5% of cases of gynecological cancer. Unlike vulvar cancer of a different localization, usually registered in deep postmenopause, the tumor is more common in women of reproductive age (up to 45 years). Morphologically, up to 60% of neoplasms are represented by adenocarcinoma.
The etiology of bartholin gland cancer is unknown. The multifactorial nature of the disease is assumed, where a special role is assigned to a decrease in local (cellular) immune activity, spontaneous mutations of epithelial cells. Some aspects of the pathology are well studied and justified only for squamous cell carcinoma, which accounts for less than 20% of all cases. Currently , two theories of the occurrence of this type of epithelial tumor prevail:
- Viral-infectious. It is associated with infection with a high oncogenic risk papillomavirus (mainly HPV-6, HPV-16 types). When viral DNA is integrated into the genome, the synthesis of proteins responsible for cellular apoptosis is disrupted. The result of the changes is the dysplasia of the squamous epithelium, which develops over time – a precancerous condition of the vulva.
- Neuroendocrine. According to this theory, changes in the epithelium of the vulva are associated with a violation of feedback between the hypothalamic-pituitary system, ovaries. Due to a violation of the regulation of hormone production, hypoestrogenemia occurs. Estrogen deficiency leads to dystrophic vulvar disease, which increases the risk of dysplasia, cancer.
Thus, the main risk factors for squamous cell carcinoma are transferred condylomatosis of the vulva, long–term background diseases – kraurosis (lichen sclerosis), hyperplastic dystrophy (leukoplakia). The probability of malignant transformation increases sharply with the development of epithelial dysplasia against the background of these processes. Severe dysplastic changes in HPV infection are usually detected after 35-40 years, in dystrophic processes – after 50.
Predisposing conditions create pathologies such as diabetes mellitus, thyroid dysfunction, ovarian insufficiency. Dystrophic and precancerous changes of the vulva are often observed in women with signs of metabolic syndrome – obesity, hypertension. Hypothetically, the probability of both squamous cell and other histological types of epithelial neoplasia of the vestibular gland may increase local chronic inflammatory processes.
The pathogenetic links of the tumor process have been poorly studied. Most often, cancer develops from glandular cells that produce a specific secret (adenocarcinoma). Less often, the tumor originates from the epithelium of the mouths of the excretory ducts (squamous cell carcinoma) or the mucous lining of the ducts themselves (transitional cell carcinoma). A rare, difficult-to-diagnose type of neoplasia of the vestibule glands is small cell carcinoma originating from diffuse cells of the neuroendocrine system and similar to a similar histotype of a malignant neoplasm of the lung.
Due to the close proximity of the vestibular gland with other anatomical structures, a growing tumor can infiltrate the paravaginal and pararectal tissue, and then the vagina, urethra, anus. Neoplasms associated with HPV often have multifocal beginnings, which explains their tendency to local relapses. The rich provision of external genitals with lymphatic vessels is due to the fairly rapid involvement of lymph nodes in the tumor process – first superficial inguinal, then deep (femoral), later pelvic.
Hematogenous metastasis transfer is less common. Metastatic tumors can develop in the lungs, liver, brain. Germination into neighboring structures, metastasis to lymph nodes and distant organs as a whole is observed less frequently than with damage to other areas of the vulva, since the node is often delimited by a pseudocapsule formed by a stroma, thickened and compacted due to compression by an overgrown neoplasm.
In relation to the surrounding tissues, intraepithelial (affecting only the epithelium within the basement membrane) and invasive (germinating the basement membrane, neighboring tissues) carcinomas are distinguished. The degree of malignancy of the process is indicated by gradations of histological differentiation: G1 – highly differentiated, least aggressive tumors; G2 – moderately differentiated; G3 – low-differentiated or undifferentiated neoplasia with the worst prognosis.
Of great importance in practical oncogynecology for determining the prognosis, developing treatment tactics is the classification of a tumor according to the TNM system (the state of the primary focus, regional lymph nodes, distant organs), according to the sequential stage development (according to FIGO, UICC) of the tumor process. According to these criteria, the characteristics of carcinoma of the vestibular glands correspond to those of carcinomas of other parts of the vulva and are presented below (UICC, seventh edition, 2010):
- Stage 0 (TisN0M0). There is a lesion within the epithelium.
- Stage I (T1a-bN0M0). The tumor does not grow beyond the vulva, perineum. The size of the primary focus does not exceed 2 cm. The magnitude of propagation beyond the basement membrane is up to 1 mm for stage IA and more than 1 mm for stage IB.
- Stage II (T2N0M0). The criteria are similar to stage I except for the size of the tumor exceeding 2 cm.
- Stage III (T1-2N1-2M0). It differs from the I-II stages by the presence of metastatic lesions of lymph nodes. Stage IIIA – one affected node with a size of 5 mm or more or 1-2 nodes with metastases less than 5 mm in size. Stage IIIB – from three affected nodes not exceeding 5 mm, or from two larger ones.
- Stage IV (T1-2N3M0, T3N1-2M0, T1-3N1-3M1). Stage IVA is characterized by the germination of the anus, vagina, urethra with an increase in regional lymph nodes or vulva lesion with a pronounced metastatic change in at least one node – lack of mobility, ulceration. A distinctive criterion of stage IVB is the defeat of distant organs with any degree of local spread.
Symptoms of Bartholin gland cancer
In the early stages, cancer of the bartholin gland develops almost asymptomatically, it is a painless seal that is not soldered to the skin, located in the depth of the labia near the perineum. As the tumor grows, the duct of the gland undergoes obstruction, which is accompanied by symptoms characteristic of the Bartolin pseudoabcess: local pain radiating into the thigh, general and local hyperthermia, soreness and enlargement of the inguinal lymph nodes. There may be bloody, purulent discharge from the duct of the gland.
Spontaneous or surgical autopsy does not bring long–term relief – the drained cavity closes quickly, the growth of neoplasia continues. Over time, the increased neoplasm leads to difficulty in the discharge of urine and feces, begins to cause pronounced discomfort when walking, sitting. An advanced tumor can reach significant (10 cm or more) sizes. Necrotic decay is accompanied by copious fetid secretions, external bleeding.
The local spread of cancer can lead to compression or germination of the rectum and urethra with the development of intestinal obstruction, acute renal failure, the formation of genitourinary and rectovaginal fistulas. The defeat of peripheral lymph nodes often provokes lymphadenitis, swelling of the hip, accompanied by pain syndrome. As a result of hematogenous metastasis, secondary lung tumors most often occur. The cause of death is often the germination by metastasis of a large vessel with perforation of its wall, the development of massive bleeding.
The diagnosis of a tumor is associated with certain difficulties due to the similarity of the clinical picture with other nosological units of pathology of the vestibular glands. The gynecologist of the antenatal clinic may suspect neoplasia, but further research with the establishment of a final diagnosis is in the competence of the oncogynecologist. Diagnostic search consists of several stages:
- Clinical examination. The preliminary diagnosis is established based on the analysis of anamnestic data, the results of examination of the vulva in a gynecological chair. Late cancer may be indicated by the significant size of the formation, progressive growth in spite of the treatment, ulceration and low mobility of the inguinal lymph nodes. Diagnosis of early stages of cancer by visual and manual methods is impossible.
- Verification of the diagnosis. To accurately identify the nature of the volume formation, a biopsy of the gland is performed, followed by a morphological examination of the sample. The method allows to determine the histological type of tumor, the degree of its differentiation. To detect small cell carcinoma of this localization, microscopy is supplemented by immunohistochemical analysis.
- Assessment of the prevalence of the process. The most accurate and reliable method of determining the lymphonodal status is lymphoscintigraphy, contrast radiography is also used. The study makes it possible to identify fairly small metastases in the lymph nodes, to differentiate them with inflammatory changes. To detect distant metastases, CT scans of the thoracic cavity and ultrasound of the abdominal cavity are used.
Differential diagnosis of cancer of the bartholin gland is primarily carried out with diseases of inflammatory etiology – a cyst of the bartholin gland, its abscess. The main reason for the late detection of this malignant tumor (and, as a consequence, an unfavorable prognosis) is insufficient oncological alertness of district obstetricians and gynecologists, unjustifiably prolonged monitoring and treatment of patients with suspected bartholinitis.
Treatment of cancer of the bartholin gland should be carried out on the basis of specialized oncogynecological medical institutions or departments. Conservative methods – chemotherapy, radiation therapy – are used only as additional components of combined (including surgical method) or complex (combination of all methods) treatment aimed at preventing early relapses.
As independent methods, conservative therapy options can be used both individually and in combination in the presence of absolute contraindications (including the patient’s refusal) to surgery or as palliative treatment at late stages. A good therapeutic effect (in the case of carcinoma – long-term persistent remission) cannot be achieved without surgical intervention.
- Chemotherapy. Adjuvant (postoperative) treatment with antitumor drugs is recommended for all patients, regardless of the stage of the tumor. Neoadjuvant (preoperative) therapy is prescribed for advanced cancer in order to suppress tumor growth. With a marked decrease in tumor mass, the possibility of radical surgical treatment appears.
- Radiation therapy. Carcinomas of the vestibular gland in most cases are resistant to ionizing radiation, so the feasibility of using this method is considered individually. Radiotherapy can be performed for squamous cell carcinoma before or after surgery. In such cases, the probability of local and regional relapses can be reduced fourfold.
Surgical intervention is the main method of treating carcinoma. The outcome of the disease is directly dependent on the radicality of the operation performed. The scope of surgical intervention depends on the spread of the tumor process, the etiological form and degree of differentiation of neoplasia, partly on the general condition of the patient, her desire to maintain sexual activity. The choice of volume is approached individually, striving to maintain a balance between maximum conservatism and a good therapeutic effect.
- Organ-preserving treatment. Economical operations include removal of the tumor with a capsule, hemivulvectomy. Interventions in this volume are carried out with microinvasive cancer for women who are contraindicated for an extended operation due to a general somatic disease (severe obesity, arterial hypertension), as well as those interested in maintaining full sexual function.
- Radical operations. Extended vulvectomy is usually prescribed for stage IB and above, and is also preferred for microinvasive HPV-associated cancer. Patients with pre- or intraoperative regional metastatic lesion are simultaneously undergoing inguinal-femoral lymphadenectomy. With the involvement of the rectum, the urinary tract, it is necessary to resort to pelvic exenteration.
Patients after radical vulvectomy need medical rehabilitation. Due to the vastness of the wound defect, when suturing the edges of the wound, suppuration, necrosis, and healing by secondary tension are often observed, which leads to the formation of rough scars in the vulva, vaginal stenosis, and impaired urination. This becomes a source of not only physical, but also moral suffering.
In order to prevent such complications, surgical reconstruction of the external genitalia is performed. To close the wound, skin-fascial flaps are used from the back of the thighs. Reconstructive plastic surgery can achieve good functional and cosmetic results, which contributes to a significant improvement in the quality of life of patients, achieving complete social rehabilitation, especially in sexually active young women.
Prognosis and prevention
The prognosis of vestibular cancer is cautious, the five-year survival rate is 52% on average. The outcome largely depends on the stage of the disease. Among patients who started treatment at stage I, the five–year survival rate reaches 90%, at stage II, III, IV – up to 68%, 40% and 20%, respectively. Unfavorable prognostic factors include the defeat of two or more superficial inguinal lymph nodes, the spread of the process to deep inguinal and pelvic lymph nodes, a decrease in the degree of differentiation. Relapses are observed in 27-30% of patients.
Primary prevention measures have not been developed due to insufficient knowledge of etiopathogenesis. The fight against inflammatory diseases of the vestibule glands, metabolic and endocrine pathologies, and papillomavirus infection contributes to a certain decrease in morbidity. Secondary prevention includes the rejection of unreasonable wait-and-see tactics in case of ineffectiveness of the usual treatment of cysts and inflammation of the bartholin gland, consultation of such patients by an oncogynecologist; long-term follow-up of patients after removal of the tumor.