Tumor of the salivary gland

Epidemiological and statistical information concerning a disease such as a salivary gland tumor has not been registered until recently. The main reasons for this fact were: the absence of a separate statistical record; association with other malignant neoplasms of the upper part of the digestive tract, as well as statistical errors, demographic differences and other local factors.

Thus, according to the combined data of Oxford University, in 1963-1980, a salivary gland tumor occurs at a frequency of 0.4 to 13.5 per 100 000 population of Uganda, Malaya, Malawi, Scotland and Greenland. Malignant swelling of the salivary gland varies from 0.4 to 2.6 per 100 000 population. In the US, the malignant tumor of the salivary gland has up to 6% of all cancers of the head and neck area and up to 0.3% among all malignant tumors.

The main morphological form among benign tumors is a benign salivary gland tumor - ppeomorphic adenoma (85.3%), with 86% of pleomorphic adenomas localized in the parotid, 6% in the submandibular jaw, 0.1% in the sublingual, 7.8% in the sublingual small glands. The second place in the frequency is adenolymphoma (9.2%), the rest of the morphological types of adenomas account for 5.5%. Among the carcinomas, adenoid-cystic (33.3%) predominate, with 59.4% developing in small, 29% in the parotid, 10% in the submandibular jaw, and 1.6% in the sublingual gland.

According to the National Cancer Registry of the United States, a malignant tumor of the salivary gland is 6 cases per 1,000,000 population.

What causes a swelling of the salivary gland?

What causes the swelling of the salivary gland is not known, however, as for other neoplasms, the role of environmental hazards and genetic anomalies is considered. Tumor of the salivary gland is associated with inflammatory diseases, nutritional factors, hormonal and genetic disorders. There are data on the role of mumps, factors that confirm the transfer of inherited changes in the parenchyma of the LJ as well as changes in the process of embryogenesis.

Among harmful environmental factors affecting the swelling of the salivary gland, a prominent role is played by high-dose radiation exposure. Negative influence is exerted by frequent radiographic examination, therapy with radioactive iodine, excessive ultraviolet radiation. The influence of radiation was studied in the inhabitants of Hiroshima and Nagasaki 13-25 years after the atomic explosion. There was a higher incidence of benign and malignant salivary gland tumors in this population, especially such as mucoepidermoid carcinoma. Studies conducted to study the causes of lymphoepithelioma showed that 11.4% of patients had previously been exposed to radiation, and 9.8% of patients had a salivary gland tumor entering the field of radiation exposure. Many authors point to the potential risk of ultraviolet radiation. An increase in the incidence of salivary gland tumors was observed, which received an ionizing effect earlier in connection with various head and neck tumors, including in children due to dermatomycosis of the head, as well as in individuals treated with radioactive iodine for hyperthyroidism. A frequent X-ray examination of the head and neck organs also contributes to the onset of the tumor process.

Viruses

The reports on the role of oncogenic viruses convincingly testify only to the role of the Epstein-Barr virus in this virus. The role of cytomegalovirus and human herpes virus was also studied. In tumors with a lymphoid stroma, there is a correlation between the amount of the Epstein-Barr virus and the undifferentiated nasopharyngeal carcinoma. This ratio is fixed among residents of North America, Greenland and South China. Lymphoepithelial carcinoma and undifferentiated carcinoma of the salivary glands in these populations had similar pathogenetic connections with the Epstein-Barr virus. The action of the virus consists in the introduction of the product of its vital activity (oncoprotein) into the epithelial neoplastic cells of these tumors. The high frequency of these tumors in Eskimos and Southern Chinese is the result of an increase in the oncogenic potential of the virus or genetic susceptibility. The connection of undifferentiated carcinoma of the parotid salivary glands and the virus in patients of Caucasian nationality was also confirmed. Data on the effect of the virus on the incidence of benign neoplasms are also confirmed. Under the influence of the virus in the epithelial cells of the salivary glands, there are changes in the form of lymphoepithelial proliferation and inflammatory changes, especially duct cells and B-lymphocytes. Tumor of the salivary gland, especially adenolymphoma, which is characterized by lymphoepithelial proliferation, develops as a result of the virus. In 87% of cases of multiple or bilateral adenolymph in the cytoplasm of neoplastic oxyphilic cells, the altered genome of the Epstein-Barr virus was found in comparison with the solitary adenolymphome in which the genome of the virus was detected in 17% of cases (the Epstein-Barr virus was detected in the cytoplasm of the duct cells bilateral adenolymph in 75% of cases, in 33% of cases solitary adenolymph and a small amount of it is found in acinar cells. Adenolymphomas are often combined with some autoimmune diseases leading to and to the development of infection and the state of immune depression.The studies show a high level of O-antibodies to the capsid and early antigens of the Epstein-Barr virus, and the connection between H1-A-DR6 antigens is also statistically significant.In the population of Chinese with high lymphoepithelial frequency, infection caused by the Epstein-Barr virus (25% among parotid tumors) .The presented data confirm the role of the Epstein-Barr virus in the pathogenesis of adenolymphoma.

Smoking

The effect of smoking on etiology is confirmed by many authors. The link between smoking and adenolymph is indicated, for example, by Italian and American researchers. They note the presence of adenolymphoma in 87% and pleomorphic adenoma in 35% for a long time and many smoking patients. However, smoking does not cause a malignant tumor of the salivary gland.

Profession

The influence of some professions on the swelling of the salivary gland is shown. They are employees of the rubber, metallurgy, woodworking, automotive industry, asbestos mines, chemical laboratories, beauty salons and hairdressers. They are exposed to lead, nickel, silicon, chromium, asbestos, cement dust components during the production process.

Food

Possible risk factors for salivary gland tumors include the use of kerosene in the process of cooking, high cholesterol in food and low levels of vitamins. The small consumption of yellow vegetables, fruits and plant food has a harmful effect.

[1], [2], [3], [4], [5]

Hormones

Endogenous hormonal activity is found in normal and tumor tissue of the SC. In normal tissue, SS estrogen receptors are found in 80% of cases in women and men, and in half of the cases of salivary gland tumors in women, expression of estrogens has been detected both in hormone-dependent breast cancer. Publications indicate the presence of a small number of estrogen receptors in the acinosis-cell, mucoepidermoid carcinoma, they occur in adenoid cystic carcinoma and are absent in tumors from the ducts of the SC. Progesterone receptors are detected in normal SJ tissue in some pleomorphic adenomas, but this fact has no prognostic significance. Androgen receptors are found in more than 90% of ductal carcinomas. Immunoreactivity for androgen receptors is characteristic for all cancers of the salivary glands from the ducts, carcinoma from pleomorphic adenoma and basal cell adenocarcinomas. Positive to androgen receptors are about 20% of mucoepidermoid, acinosis-cell and adenoid-cystic carcinomas.

Gene mutations of salivary oncogenes

Cytogenetic and molecular studies of chromosomal and gene mutations in benign and malignant tumors of the salivary glands conducted in recent years have extended the possibilities for successful diagnosis, therapy and prognosis of the course of the tumor process. Specific structural chromosomal changes in various histological types of salivary gland tumors are the result of the movement of genetic material involving chromosome 8 in pleomorphic adenoma, chromosome 11 in mucoepidermoid carcinoma and translocation on chromosome 6 in adenoid cystic carcinoma.

The most studied in a series of alternating chromosomes is the Y-chromosome in adenocarcinomas. In mucoepidermoid carcinoma of the root of the tongue, the trisomy 5 gene is described as an abnormal karyotype. Polysomal chromosomes 3 and 17 are significant for adenoid cystic carcinoma; the tumor suppressor gene located on this chromosome is also of interest.

Analysis of genetic abnormalities reveals the microsatellite duplication of most chromosomal zones and the situation in which the reaction with the polymerase (PCR) intensifies. This is a sensitive marker that identifies replication errors and genomic mutations. There is a loss of the allelic gene in chromosome 12p (35% of cases) and chromosome 19q (40% of cases) in pleomorphic adenoma, adenoid cystic carcinoma. Mucoepidermoid carcinoma shows 50% and a large loss of 2q, 5p, 1 2p, 16q. Most pleomorphic adenomas lose the allele gene on chromosome 8, which is observed in 53% of malignant and 41% of benign tumors. Malignant tumors that have lost a heterozygous gene acquire aggressive properties, and the transformation of benign pleomorphic adenoma into a malignant tumor is associated with changes in the surface of the chromosome 17.

Thus, loss of the allele gene and heterozygous gene (LOH) causes changes in chromosomes of 1 2p and 19q in mucoepidermoid carcinoma, chromosome 8 in adenoid cystic carcinoma and LOH - in many chromosomal zones of malignant tumors, which confirms the significance of genetic changes in tumor genesis for salivary glands. Modern studies have made it possible to identify genes involving salivary glands in the tumor process. There is an activation of oncogenes and inactivation of suppressor genes.

The most famous suppressor gene p53 is located on chromosome 17 (p 13) and is often detected in some benign and especially malignant tumors of the salivary gland. The mutational product of the p53 gene accumulates in the nucleus of the neoplastic cell and is found in 3 (1 1%) of 26 benign and 31 (67%) of 46 malignant tumors of the parotid salivary gland. The researchers' reports indicate that abortions of p53 were associated with regional and distant metastases. P53 mutations and / or p53-protein expression occur in most salivary gland tumors, including adenoid cystic carcinomas, adenocarcinomas and salivary duct carcinomas, pleomorphic adenomas and carcinomas, as well as in mucoepidermoid and squamous cell carcinomas. There is a transformation of SLE cells into tumor cells. The increase in p53 expression affects factors that contribute to angiogenesis. The absence or decrease in E-cadherin expression is a sensitive prognostic marker for adenoid cystic carcinoma, which confirms the role of tumor suppression of the gene.

The study of oncogenes c-erbB-2 (HER-2, pei) confirms the analogy that exists between tumors of the salivary gland and mammary tumors. The increase in proto-oncogenes, the complication of their structure, the expression of their proteins were detected in 35% of patients with a salivary gland tumor and correlated with tumor aggressiveness, especially in adenoid cystic carcinomas and adenocarcinomas of large SJ. Overexpression of c-erb-B2 is found in 47% of Wartin tumors and in 33% pleomorphic adenomas.

Expression of the proto-oncogene C-Kit encoding the transmembrane type of tyrosine kinase receptor was detected in adenoid-cystic and myoepithelial carcinoma of the SS and is absent in other morphological types by carcinoma. None of the tumor-expressing tumors had gene mutations in exons 11 and 17. The results of the studies emphasize the possible important role of gene activation mechanisms and other genetic disorders. Further studies of this gene have revealed its high expression in some other salivary gland tumors (including monomorphic adenomas). 

Tumor of the salivary glands: species

The tumor of the salivary gland represents a diverse and complex group of tumors, so their classification is difficult. Morphological signs of malignancy are not always reflected in the clinical manifestation of the neoplasm. To express clinico-morphological features of each nosological unit and to present it in a single classification is almost impossible. That is why the salivary gland tumor, studied by pathomorphologists, as the modern data accumulated, was improved and formed into the international histological classification adopted by WHO in 1972, which was supplemented and approved by the WHO in 1991. However, this does not mean that the pathomorphology of tumors has been thoroughly studied. Modern ultrastructural studies help not only to present the morphological nature of the tumor, but also to determine the degree of malignancy, the response to ongoing treatment.

The classification used by domestic oncologists included three groups of tumors:

1. Benign tumor of the salivary gland:
   • epithelial (adenoma adeno-lymphoma, mixed tumor);
   • connective tissue (fibroma, hemangioma, chondroma, etc.);
2. Local-destructive swelling of the salivary gland:
   • mucoepidermoid tumor, cylinder.
3. Malignant tumor of the salivary gland:
   • epithelial (cancer);
   • connective tissue (sarcoma, etc.);
   • Malignant, developed from benign neoplasms;
   • secondary (metastatic).

What prognosis does the swelling of the salivary gland have?

The main prognostic and predictive factors are factors that influence survival. They include morphological criteria (histological type and degree of malignancy of the tumor), etiology, localization, prevalence of the tumor process, methods of therapeutic effect. The study of objective criteria for assessing the effectiveness of treatment can predict the outcome of the disease. The most important of these criteria are the frequency of relapses and metastases. The most pronounced is the correlation of the prognosis with the clinical stage of the tumor process, which emphasizes the importance of the earliest possible diagnosis. It is shown that the microscopic degree of differentiation ("grad") and the type of tumor are independent factors of the forecast and often play a major role in optimizing the therapeutic process. The tendency of many tumors to recur, regional and distant metastasis indicates the need in many cases to resort to more aggressive initial treatment tactics. The relationship between the clinical stage of the disease and the degree of differentiation ("grade") of the tumor indicates a biological feature of the tumor, allows you to predict the stages of the development of the disease (clinical course) and the response to the treatment methods used. The influence of prognostic factors for each morphological type of tumor has its own peculiarities. A benign salivary gland tumor has the main factor determining the prognosis, which is an adequate surgical intervention. However, the biological feature of some tumors is manifested by a tendency to relapse and malignancy. Thus, the tumor of the salivary gland basally-cellular adenoma usually does not recur, except for the membrane type, which occurs again in about 25% of cases. There are reports of malignant transformation of basal cell adenoma, although this is extremely rare. Relapses after surgical treatment (parotidectomy or enucleation) occur in 2-2.5% of cases, which is mainly due to the multifocal nature of tumor growth. Concerning prognostic and predictive factors with respect to adenolymphoma, it should be said that malignancy of adenolymphoma is observed rarely - about 1% of observations. Fertilization may affect the epithelial or lymphoid component. In some patients, there is an indication of the effect of radiation in an anamnesis. Adenolymph is sometimes found in combination with other benign salivary gland tumors, especially often with pleomorphic adenoma. There are works that indicate an increase in the frequency of "extra-salivary" tumors in adenolymphoma. Here, probably, smoking explains the general etiology for adenolymphoma and lung cancer, larynx, bladder, while other neoplasms (kidney, breast cancer, etc.) seem to represent an accidental combination.

For adenoid cystic carcinoma, the determining type is the histological type, tumor localization, clinical stage, the presence of bone damage and the condition of the surgical margins of resection. In general, tumors consisting of cribular and tubular structures have a less aggressive course than those that have solid sites occupying 30% or more of the tumor area. The clinical stage of the disease has a significant effect on the prognosis. In other studies, attempts to confirm the predictive value of "grad" failed, and the prognostic significance of the clinical stage and tumor size as the most constant factors of clinical outcome in these patients was revised. The five-year survival rate is 35%, but the more distant results are significantly worse. From 80 to 90% of patients die in 10-15 years. Local relapses, according to different data, occur in 16-85% of observations. Relapse is a serious sign of incurability. Lymph node involvement is infrequent and varies between 5 and 25%, usually more often in tumors with localization in the submandibular SJ, which is more likely due to direct spread to the lymph node, rather than to metastasis. Remote metastases are observed in 25-55% of cases of adenoid cystic carcinoma; more often than other tumors, it gives metastases to the lungs, bones, brain and liver. Only 20% of patients with distant metastases live 5 years or more. The effect of perineural infestation on survival is controversial. Widespread radical local excision with subsequent radiation therapy is the method of choice therapy. Radiotherapy alone or in combination with chemotherapy in the treatment of relapses or metastatic lesions is a limited success, but nevertheless, it improves results with local exposure to a microscopically residual tumor. The value of the chemotherapeutic method of treatment in acinar-cell carcinoma is limited and needs further study.