Merkel cell carcinoma of the vulva is a rare aggressive malignant tumor affecting the external female genitals. It is manifested by a rapidly increasing painless node of reddish coloration in the thickness or on the surface of the skin of the labia. The diagnosis is established on the basis of a patient’s survey, visual examination data, and biopsy. It is possible to distinguish Merkel cancer from other types of carcinoma only with the use of an immunohistochemical method of research. The treatment is combined, includes surgery, radiation therapy. Sometimes antitumor drugs are prescribed.
General information
Merkel cell carcinoma of the vulva is a malignant neuroendocrine tumor of the dermis formed by cells that are similar to the “tactile” epidermal, first described by the German morphologist Friedrich Sigmund Merkel in 1875. There are mentions of several dozen cases of this carcinoma, every year the disease is registered more often, which is associated with the introduction of modern diagnostic methods. Women of the Caucasian race 50-70 years old are most susceptible to the disease. Merkel cancer differs from other forms of cutaneous carcinomas by rapid local growth and early metastasis.
Causes
The etiopathogenesis of Merkel cell carcinoma of the vulva has been little studied. It is believed that the initiation of the development of a neoplasm can be provoked by either one or several unfavorable factors at once. The main causes of the disease are considered to be:
- Poliomavirus infection. In 80% of patients with neoplasia, human polyomavirus 5 (Merkel cell polyomavirus) is isolated. The virus does not cause the development of infection, accompanied by visible manifestations, but its DNA is embedded in the cellular genome, which leads to malignant transformation.
- Suppression of the immune system. Pronounced weakening of the immune response is more often associated with a severe chronic disease, HIV infection, taking immunosuppressants. In women with the immunodeficiency virus, the risk of neoplasia is increased by 13 times, in patients after transplantation – tenfold.
- The presence of other oncopathology. Malignant neoplasm of another type and localization increases the likelihood of the disease due to possible common etiological factors, impaired immune response, pathological skin changes associated with antitumor therapy. Thus, in chronic lymphocytic leukemia, Merkel’s carcinoma is detected 30-50 times more often.
The provoking factors are related to each other, the weakening of the immune response leads to oncogenic activation of the polyomavirus. Other predisposing conditions of malignant transformation of cells include permanent injury to the skin (for example, when wearing tight synthetic underwear), excessive exposure to ultraviolet light (addiction to tanning without a swimsuit).
Pathogenesis
In modern oncogynecology, Merkel’s viral theory of cancer development is the most widespread. Infection with poliomavirus occurs more often in children and adolescents, transmission routes and risks are not precisely established. Then the virus is eliminated or latently exists in the body for decades. The occurrence of cancer is preceded by a mutation of viral DNA under the influence of adverse factors, its integration into the genome of host cells.
The result of the association are chromosomal abnormalities and gene mutations of the affected cells, affecting the suppression of apoptosis, uncontrolled division. Previously, due to the phenotypic similarity, it was believed that cancer originates directly from cells discovered by Merkel. However, healthy Merkel cells are part of the epidermis, and tumor cells affect the dermis and deeper layers, but not the epidermal.
This fact, as well as some differences in the chemical composition and various differentiation options (glandular, squamous, melanocytic) of tumor cells suggested the origin of Merkel cancer from stem cells. The source of carcinoma is the polypotent cells of the dermis, which acquire the phenotype and specialization of neuroendocrine cells during malignant transformation.
Classification
To assess the local lesion, possible involvement of regional lymph nodes and distant organs, the international classification TNM is used. The severity of the disease is determined by the stage:
- Stage I (T1Nx-0M0). It is characterized by a local process without the involvement of distant organs, the absence of visible metastases in regional lymph nodes, the size of the focus is no more than 2 cm. Stage IA is established only after histological confirmation of the integrity of the lymph nodes. Without morphological examination, the distribution corresponds to IA.
- Stage II (T2-3Nx-0M0 and T4N0M0). Stages IIA-B differ from IA-B only in the size of the primary cancer (more than 2, but less than 5 cm). At stage IIC, the size of the primary focus is more than 5 cm, regional lymph nodes and distant organs are not affected.
- Stage III (T0-4N1a,b-2M0). It is characterized by any tumor size, absence of distant metastases, lesion of regional lymph nodes. At stage IIIA there are microscopic metastases (determined by histological examination of the removed node), at stage IIIB – macroscopic, visible on ultrasound and CT.
- Stage IV (T0-4N0-2M1). It is diagnosed in the presence of distant metastases with any size of primary neoplasia and the condition of regional lymph nodes. Distant metastases to lymph nodes, skin, soft tissues are designated M1a, lungs – M1b, other organs – M1c.
Letter (A, B, C) gradations of stages affect the prognosis – an increase in the prevalence of the process by one such “step” reduces the five-year survival rate by 2-5%. Unlike other types of carcinomas, histological determination of the degree of malignancy in the diagnosis of neoplasia is not provided.
Symptoms
Merkel’s cancer manifests itself in the form of a dense painless rounded nodule in the area of the pubic skin, vulva. The skin above the formation is smooth, sometimes with a visible vascular pattern. The color can vary from pink to red and red-purple. In two-thirds of patients, the tumor is represented by a single node, in the remaining patients there are satellites (daughter or primary multiple nodules) nearby.
The size of the neoplasm often does not exceed 2 cm, in 35% of cases the tumor continues to grow and can reach 20 cm. Its contours are smooth, the structure is homogeneous. The only visible evidence of the malignant nature of neoplasia is often only rapid growth – within three months, a twofold or more increase is possible.
Complications
The most dangerous complication of the neoplasm is metastases that spread through the lymphatic and circulatory system. They are found in 65-85% of patients, at the time of initial diagnosis they are registered in 15% of patients. The frequency of metastatic lesions of various localization in this form of cancer: remote skin areas – up to 30%, lungs – 10-23%, brain – 18%, bones – 10-15%, liver – 13%.
In 20% of patients, the primary tumor (usually of impressive size) ulcerates, undergoes necrotic decay. This creates favorable conditions for the development of purulent-septic complications, makes it difficult for a woman to be in society, adversely affects family relations due to an unpleasant smell, constant leakage of blood and pus. With the collapse of cancer, bleeding from damaged vessels is not uncommon, weakening the patient.
Diagnostics
Establishing a diagnosis of Merkel’s vulvar cancer is difficult. Clinically, the development of neoplasia is more like a benign process, the correct diagnosis is made only by 1% of patients with neuroendocrine carcinoma of the skin of the genitals. The examination is conducted under the guidance of an oncogynecologist or an oncologist surgeon, it necessarily includes:
- General inspection. During the examination and palpation of the external genitals, the doctor discovers a formation on the skin of the vulva. It is possible to suspect Merkel cancer in it by the rapid growth of the tumor, asymptomatic course, anamnesis data (age over 50 years, immunosuppression, concomitant lymphocytic leukemia).
- Laboratory diagnostics. A sample taken from a tumor focus is subjected to histological and immunohistochemical examination. The first allows you to determine the malignant nature of the tumor, the second – to find out its genotype and establish a final diagnosis.
To identify regional and distant macrometastases, bone scintigraphy, ultrasound of lymph nodes, abdominal and pelvic organs, CT of the chest and head are prescribed. Pathology is differentiated with benign (dermatofibroma, lipoma, atheroma) and other malignant (non-pigmented melanoma, squamous cell carcinoma of low differentiation, metastasis of small cell lung carcinoma) formations.
Treatment
Since this type of carcinoma is not widespread and poorly studied, there are no uniform standards for its treatment. The nature of therapy corresponds to the features of neoplasia – intensive, aggressive. The main method is surgery, which is often combined with radiation therapy. Antitumor drugs are used less often.
Conservative therapy
Currently, in the treatment of Merkel cell carcinoma of the vulva, along with surgery, both classical (radiation therapy, chemotherapy) and new promising methods of treatment are used, which selectively act on the tumor with minimal effect on healthy tissues. The advantages and disadvantages of the former are already well known, the latter are being studied in detail, of which photodynamic therapy has proven itself well.
- Radiation therapy. It is more often prescribed as an adjunct to surgery for irradiation of a postoperative scar. The tumor has a high sensitivity to ionizing radiation, so radiotherapy can be used as an independent method of treating the affected sentinel lymph nodes and even the primary focus.
- Chemotherapy. Carcinoma from Merkel cells is relatively resistant to antitumor drugs, moreover, the latter are poorly tolerated by age-related patients, and can cause a decrease in sensitivity to subsequent radiation treatment. Therefore, chemotherapy is prescribed if it is impossible to excise or irradiate cancer, for example, due to extensive local spread.
- Photodynamic therapy. It consists in the selective accumulation of a photosensitizing drug by cancer cells and their subsequent destruction under the influence of a laser beam. The method is recognized as effective, and has recently been included in Merkel’s cancer therapy protocols in the United States and European countries.
Surgical treatment
Surgery is the leading method of treating Merkel cell carcinoma of the vulva. When this type of carcinoma is detected, a wide excision of the tumor is performed (with an indentation of at least 2.5-3 cm from the edges). With the involvement of regional lymph nodes, resection of the primary focus is supplemented by lymph dissection. After removal of neoplasia, a histological examination of the slice is performed.
Wide excision may be the only radical method of treatment at the initial stages of neoplasm without regional spread. In the presence of tumor cells at the edges of resection, surgical intervention is necessarily supplemented with radiation therapy. Removal of the tumor is also indicated in the terminal stage – when it disintegrates. In this case, a sanitary (non-radical) operation is performed in order to improve the quality of life.
Prognosis and prevention
Merkel cell carcinoma of the vulva is more aggressive than the same tumors of a different localization. The prognosis depends on the stage of the disease: the five-year survival threshold after treatment can be overcome by 60-80% of patients with stage I carcinoma (at stage IA, this indicator is 20% higher than at IB) and 8% at the last stage. The outcome of treatment is affected by the possibility of eliminating the immunodeficiency condition – there is a known case of spontaneous resolution of Merkel’s carcinoma against the background of successful HIV therapy.
To prevent tumors, common diseases should be treated in a timely manner, do not abuse the tan, and wear comfortable underwear. Secondary prevention consists in early diagnosis of the primary tumor (oncological alertness of the doctor is necessary, a thorough examination of the skin in patients at risk) and lifelong dispensary observation of patients to detect relapses, the probability of which is 30%.
