Salivary gland adenoma

Adenoma of the salivary gland ranks first among benign tumors. The term "mixed tumor" proposed by R. Virchow in 1863 reflects the opinion held by many pathomorphologists, supporters of epithelial and mesenchymal tumor development. At present, complex morphological studies allow us to speak about the epithelial genesis of the neoplasm, and the term "adenoma of the salivary gland" is used only conditionally, as reflecting the diversity of its structure. The same applies to the term "pleomorphic adenoma" used in European and American literature.

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Pleomorphic adenoma of the salivary gland

The macroscopic picture of the tumor is quite typical: the tumor node in the capsule, clearly delimited from the tissue of the SG, round or oval in shape, but can be lobular. The tumor capsule can be of different thickness, can be partially or completely absent. In small SG, the capsule is often poorly expressed or absent. On the section, the tumor tissue is whitish, shiny, dense, sometimes with cartilaginous, gelatinous areas, with large sizes - with hemorrhages and necrosis.

Microscopically, pleomorphic adenoma of the salivary gland demonstrates morphological diversity. The tumor capsule is not always well defined, especially when myxoid and chondroid areas are located along the tumor periphery. The thickness of the capsule fluctuates in the range of 1.5-17.5 mm. In predominantly mucoid tumors, the capsule may not be detected at all, and then the tumor borders on normal gland tissue. Often, areas are detected that penetrate the capsule in the form of processes. Sometimes, adenoma of the salivary gland protrudes through the capsule and forms separate pseudosatellite nodes. There is a tendency to form cracks parallel to and close to the capsule. Cracks in the tumor itself push tumor cells to the wall of the capsule. The ratio of cellular and stromal elements can vary significantly. The epithelial component includes basaloid, cuboid, squamous, spindle, plasmacytoid, and clear cell types. Less common are mucous, sebaceous, and serous acinar cells. Cytologically, they usually have vacuolated nuclei without visible nucleoli and low mitotic activity. Epithelial cells may vary in size, shape, and nucleus-to-cytoplasm ratio. The epithelium usually forms structures in the form of wide fields or ducts. Sometimes the epithelial component forms the majority of the tumor, the so-called cellular pleomorphic adenoma of the salivary gland. This phenomenon has no prognostic significance. Glandular lumens may be formed by small cubic or larger cylindrical cells with eosinophilic granular cytoplasm, resembling the epithelium of the salivary tubes. Glandular tubes with a two-layer arrangement of cellular elements are often visible. The cells of the basal layer and the surrounding glandular, microcystic structures may resemble myoepithelial cells, which creates difficulties in interpreting their nature. The shape and proportions of the structure vary significantly: small cells with large round nuclei and larger, light cells with optically "empty" cytoplasm, resembling epidermoid cells that form horny pearls. Large, light cells containing lipid complexes are encountered. Differential diagnostic difficulties arise with adenoid cystic or epithelial-myoepithelial cancer, with a small amount of material to be examined, if myoepithelial cells are found in the ducts, morphologically similar to luminal cells, or they have light cytoplasm and hyperchromatic, angular nuclei. The presence of squamous cell metaplasia with the formation of keratin pearls, sometimes observed in ductal and solid structures, less often - mucinous metaplasia and clear cell changes can be mistakenly interpreted as mucoepidermoid carcinoma. Myoepitheliocytes can form a delicate mesh type of structure or wide fields of spindle-shaped cells, reminiscent of schwannoma. They can be of plasmacytoid or hyaline type. Oncocytic changes, if they occupy the entire tumor,may be interpreted as oncocytoma.

The stromal component of the tumor is represented by a variable ratio of myxoid zones with stellate, elongated cells, and chondroid areas with a cartilaginous dense substance, with single round cells similar to chondrocytes, and areas of fibroblast-type cells. All components: epithelial and stromal without any boundaries, are mixed with each other, sometimes epithelial cell complexes are surrounded by a massive intercellular basis. The mesenchymal-like component can sometimes occupy a large part of the tumor. The cells inside the mucous material are of myoepithelial origin and their periphery tends to mix with the surrounding stroma. The cartilaginous component, apparently, is true cartilage, it is positive with respect to type II collagen and keratin sulfate. Rarely, it is the main component of the tumor. Bone can form within this cartilage or by bone metaplasia of the stroma. Deposition of homogeneous eosinophilic hyaline material between tumor cells and in the stroma may be pathognomonic of this tumor. Tufts and masses of globules that are positive for elastin staining are often formed within the tumor. This material may push aside epithelial elements, producing a pattern resembling cylindroma or cribriform structures as in adenoid cystic carcinoma. Progressive hyalinosis and gradual disappearance of the epithelial component are seen in some long-standing tumors. However, it is important to carefully examine the residual epithelial elements in such hyalinized old pleomorphic adenomas, since the risk of malignancy of these neoplasms is significant. Adenoma of the salivary gland with a pronounced lipomatous stromal component (up to 90% and more) is called lipomatous pleomorphic adenoma.

Fine needle biopsy may show more marked inflammation and necrosis after spontaneous infarctions. Increased mitotic activity and some cellular atypia are seen in such tumors. Squamous cell metaplasia may also be present. All of these changes may be mistaken for malignancy. Some tumors show signs of cystic degeneration with a "rim" of tumor elements around a central cavity. Rarely, tumor cells may be seen in vascular lumens. This is seen within the tumor and at its periphery and is thought to be an artifactual change. Occasionally, tumor cells are seen in vessels distant from the main tumor mass. However, these findings should not be considered significant for the biological behavior of the tumor, especially with respect to the risk of metastasis.

Immunohistochemically, the inner duct cells in the tubular and glandular structures are positive for cytokeratins 3, 6, 10, 11, 13, and 16, whereas the neoplastic myoepithelial cells are focally positive for cytokeratins 13, 16, and 14. The neoplastic myoepithelial cells coexpress vimentin and pancytokeratin and are inconsistently positive for B-100 protein, smooth muscle actin, CEAP, calponin, HHP-35, and CPY. The altered myoepithelial cells are also positive for p53. Non-lacunar cells in the chondroid areas are positive for both pancytokeratin and vimentin, whereas the lacunar cells are positive for vimentin only. Spindle-shaped tumor myoepithelial cells around the chondroid areas express bone morphogenetic protein. Collagen type II and chondromodulin-1 are present in the cartilage matrix.

Agtrecan is found not only in the cartilaginous matrix, but also in the myxoid stroma and in the intercellular spaces of tubular-glandular structures. Actively conducted cytogenetic studies have shown karyotype abnormalities in approximately 70% of pleomorphic adenomas. Four main cytogenetic groups can be distinguished:

• Tumors with t8q translocations 12 (39%).
• Tumors with 2q3-15 rearrangement (8%).
• Tumors with sporadic clonal changes, other than those that include the two previous types (23%).
• Tumors with apparently normal karyotype (30%).

Previous studies have also shown that karyotypically normal adenomas are significantly older in age than those with t8q 12 rearrangement (51.1 years vs 39.3 years), and that adenomas with normal karyotype have more prominent stroma than those with t8q 12.

Clinical and morphological studies undertaken by the author to clarify the relationship between the clinical course and the predominant structure in a mixed tumor did not reveal this relationship.

Electron microscopic studies have established the epithelial and myoepithelial nature of the tumor components. The cells of the epithelial component differentiate towards squamous epithelium, elements of salivary tubes, ducts, sometimes - secreting epithelium of acini, myoepithelium; there are low-differentiated epithelial cells. Myoepithelial cells are found in glandular tubes, cords and nested clusters. Low-differentiated cells of the epithelial component, in their absence in the stromal component, give reason to consider them a zone of tumor proliferation. The "basis" of the tumor is represented by epithelial and myoepithelial cells with weakened intercellular connections, fragments of basal membranes and collagen fibers between them. Epithelial cells differentiate towards squamous epithelium. Signs of squamous epithelial differentiation in chondroid areas and areas of elongated fibroblast-like cells, in the absence of fibroblastic elements, give grounds to consider epithelial cells with squamous epithelial differentiation and myoepithelial elements as forming mesenchymal-like areas of the tumor. Polymorphism and proliferation of epithelial cells are not criteria of malignancy. Pleomorphic adenoma of the salivary gland has the ability to recur and undergo malignant transformation. Relapses occur on average in 3.5% of cases within 5 years after surgery and in 6.8% of cases - after 10 years. According to various literature data, this figure fluctuates from 1 to 50%. Differences in relapse statistics are most likely caused by the inclusion of cases with non-radical operations in the studies, before subtotal resection became the main method of treating pleomorphic adenoma. Relapses more often develop in young patients. The main reasons for relapses are:

• predominance of the myxoid component in the tumor structure;
• differences in capsule thickness together with the ability of the tumor to penetrate the capsule;
• individual tumor nodes walled up within the capsule;
• "survivability" of tumor cells.

Many recurrent pleomorphic adenomas have a multifocal growth pattern, sometimes so widespread that surgical control in this situation becomes quite difficult.

Basal cell adenoma of the salivary gland

A rare benign tumor characterized by a basaloid cell appearance and the absence of the myxoid or chondroid stromal component present in pleomorphic adenoma. Code - 8147/0.

Basal cell adenoma of the salivary gland was first described in 1967 by Kleinsasser and Klein. In our material, basal cell adenoma is included in the group can sometimes be cystic. The membranous variant of the neoplasm (a tumor similar in appearance to the skin) can be multiple and coexist with skin cylindromas and trichoepitheliomas.

Macroscopically, in most cases, a salivary gland adenoma is a small, clearly demarcated, encapsulated node, ranging in size from 1 to 3 cm in diameter, with the exception of the membranous variant, which can be multifocal or multinodular. On the cut surface, the neoplasm has a dense and uniform consistency, grayish-whitish or brownish in color.

Basal cell adenoma of the salivary gland is represented by basaloid cells with eosinophilic cytoplasm, indistinct borders and oval-round nucleus, forming solid, trabecular, tubular and membranous structures. However, the tumor may consist of more than one of these histological types, usually with a predominance of one of them. The solid type consists of fascicles or islands of various sizes and shapes, usually with palisading cuboidal or prismatic cells at the periphery. The islands are separated from each other by strips of dense connective tissue rich in collagen. The trabecular type of structure is characterized by narrow strips, trabeculae or fascicles of basaloid cells separated by cellular and vascularized stroma. A rare but distinctive feature is the presence of a cellular stroma composed of altered myoepithelial cells. The duct openings are often visible among the basaloid cells, and in such cases we speak of a tubulotrabecular type. The membranous type of basal cell adenoma has thick bundles of hyaline material at the periphery of the basaloid cells and in the form of intercellular drops. In the tubular type, the ductal structures are the most noticeable sign. In all variants, cystic changes, signs of squamous cell differentiation in the form of "pearls" or "whirlpools" or rare cribriform structures may be encountered. In rare tumors, especially those of tubular structure, there may be extensive oncocytic changes.

Immunoprofile of basal cell adenoma - keratin, myogenic markers, vimentin, p53 indicate ductal and myoepithelial differentiation. Vimentin and myogenic markers can also stain cells of palisade structures in the solid type of structure. Expression variants reflect different stages of tumor cell differentiation, ranging from the less differentiated solid type to the most differentiated - tubular.

Basal cell adenoma does not usually recur, with the exception of the membranous type, which recurs in about 25% of cases. Malignant transformation of basal cell adenoma has been reported, although this is extremely rare.

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Canalicular adenoma of the salivary gland

A tumor composed of columnar epithelial cells arranged in thin, anastomosing bundles, often in a "beaded" pattern. The tumor stroma has a characteristic multicellular and highly vascularized appearance.

Synonyms: basal cell adenoma of the canalicular type, adenomatosis of the minor salivary glands.

The average age of patients and the peak incidence of canalicular adenoma are 65 years. The age of patients in general varies between 33 and 87 years. Salivary gland adenoma is uncommon in people under 50 years of age, and the ratio of affected men to women is 1:1.8.

In studies of large series, this neoplasm occurs in 1% of cases of all tumors of the gastrointestinal tract and in 4% of cases of all tumors of the small gastrointestinal tract.

Canalicular adenoma of the salivary gland selectively affects the upper lip (up to 80% of observations). The next most common localization of canalicular adenoma is the buccal mucosa (9.5%). Rarely, canalicular adenoma occurs in large SGs.

The clinical picture is represented by an increasing node without accompanying symptoms. The mucous membrane around the tumor is hyperemic, but in some cases it may look bluish.

Of particular importance are cases of multifocal or multiple canalicular adenomas. Typically, the upper lip and mucous membrane of the cheek are involved in the process, but other localizations may be affected.

Macroscopically, canalicular adenoma of the salivary gland usually reaches 0.5-2 cm in diameter and is well demarcated from the surrounding tissues. Their color ranges from light yellow to brown.

Microscopically, at low magnification, a clear border is visible. Canalicular adenoma of the salivary gland has a fibrous capsule, while smaller tumors often lack it. Sometimes, small nodules can be seen around an adjacent large tumor. In addition, very small foci of adenomatous tissue that can be seen represent the initial stage of adenoma manifestation. In some cases, areas of necrosis may be encountered.

The epithelial component is represented by two rows of prismatic cells, which are located one after the other, at a distance from each other. This leads to the characteristic feature of this tumor - the so-called "canaliculae", where the epithelial cells are widely separated. The alternate arrangement of closely opposed and widely separated epithelial cells also leads to the characteristic "beaded" appearance of this tumor. The epithelial cells that form bundles are usually prismatic in shape, but can also be cubic. The nuclei are of regular shape, and polymorphism is not observed. Nucleoli are inconspicuous, and mitotic figures are extremely rare. The stroma has a characteristic appearance, which serves as a clue to the diagnosis. The stroma is cellular and abundantly vascularized. The capillaries often demonstrate the presence of eosinophilic "cuffs" of connective tissue.

The immunoprofile of canalicular adenoma consists of a positive reaction to cytokeratins, vimentin, and S-100 protein. Rarely, focal positivity with GFAP is detected. Canalicular adenoma of the salivary gland lacks staining for sensitive muscle markers such as smooth muscle actin, smooth muscle myosin heavy chains, and calponin.

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Sebaceous adenoma of the salivary gland

A rare, usually well-circumscribed tumor consisting of nests of sebaceous cells of varying sizes and shapes without signs of cellular atypia, often with foci of squamous differentiation and cystic changes. Code - 8410/0.

Sebaceous adenoma of the salivary gland accounts for 0.1% of all tumors. The average age of patients is 58 years, although the tumor occurs in a wide age range - from 22 to 90 years. The ratio of men to women is 1.6:1. Unlike sebaceous skin neoplasms, sebaceous adenoma of the SG does not show an increase in the incidence of cancers of various visceral localizations.

Sebaceous adenoma of the salivary gland is localized as follows: parotid sebaceous adenoma - 50%, mucous membrane of the cheeks and retromolar region - 1, 7 and 13%, respectively, submandibular sebaceous adenoma - 8%.

The clinical picture is represented by a painless tumor.

Macroscopically, sebaceous adenoma of the salivary gland has dimensions of 0.4-3 cm in the largest dimension, with clear boundaries or encapsulated, the color is from grayish-whitish to yellowish.

Histologically, sebaceous adenoma of the salivary gland consists of nests of sebaceous cells, often with foci of squamous differentiation, with no or minimal atypia and polymorphism without a tendency to locally destructive growth. Many tumors consist of multiple small cysts or are built predominantly of ectatic ductal structures. The sebaceous glands vary greatly in size and shape, and are often enclosed in fibrous stroma. Some tumors show signs of severe oncocytic metaplasia. Histiocytes and/or giant cells of foreign body resorption can be seen focally. Lymphoid follicles, signs of cellular atypia and polymorphism, necrosis and mitotic figures are not characteristic of this tumor. Occasionally, sebaceous adenoma can be part of a hybrid tumor.

Regarding the prognosis and treatment, it should be said that salivary gland adenoma does not recur after adequate surgical removal.