Adenoma of the salivary gland

The adenoma of the salivary gland in the row of benign tumors takes first place. The term "mixed tumor", proposed by R.Virkhov in 1863, reflects the opinion held by many pathomorphologists, advocates of epithelial and mesenchymal development of the tumor. At the present time, 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 it reflects the diversity of its structure. The same applies to the term "pleomorphic adenoma", used in European and American literature.

[1], [2], [3], [4], [5], [6], [7]

Pleomorphic adenoma of the salivary gland

The macroscopic picture of the tumor is quite typical: the tumor node in the capsule is clearly delineated from the SC of the round or oval shape, but can be lobate. The tumor capsule can be of different thicknesses, partially or completely absent. In small SL, the capsule is more often mildly expressed or absent. On the cut, the tissue of the tumor is whitish, shiny, dense, sometimes with cartilaginous, gelatinous-looking 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 expressed, especially when the myxoid and chondroid parts are located at the periphery of the tumor. The thickness of the capsule varies between 1.5-1 7.5 mm. In predominantly mucoid tumors, the capsule can not be detected at all and then the tumor borders on the normal tissue of the gland. Often identified areas that in the form of processes penetrate the capsule. Sometimes the adenoma of the salivary gland protrudes through the capsule and forms as it were some pseudo-satellite nodes. There is a tendency to form gaps parallel to and close to the capsule. Slots in the tumor itself push the tumor cells to the wall of the capsule. The ratio of cellular and stromal elements can vary considerably. The epithelial component includes basaloid, cuboidal, squamous, spindle cell, plasma-cytopoid, and light-cell types. Slimy, sebaceous and serous acinar cells are more rarely detected. They cytologically usually have vacuolated nuclei without visible nucleoli and low mitotic activity. Epithelial cells can have a different size, shape, correlation of the nucleus and the cytoplasm. The epithelium usually forms structures in the form of wide fields or like ducts. Sometimes the epithelial component forms a large part of the tumor - the so-called cellular pleomorphic adenoma of the salivary gland. This phenomenon has no prognostic significance. The glandular lumens can be formed by small cubic or larger cylindrical cells with an eosinophilic granular cytoplasm resembling the epithelium of the salivary tubes. Often seen glandular tube with a two-layer arrangement of cellular elements. Cells of the basal layer and surrounding the glandular, microcystic structures may resemble myoepithelium, which creates difficulties in interpreting their nature. The shape and structure ratio vary considerably: small, with large rounded nuclei and larger, light, with optically "empty" cytoplasm, reminiscent of epidermoid, forming horny pearls. There are large, light cells containing lipid complexes. Differential diagnostic difficulties arise with adenocystic or epithelial-myoepithelial cancer, with a small amount of the investigated material, if the myoepithelial cells morphologically similar to luminal cells are found in the ducts, or they have a light cytoplasm and hyperchromic, angular shape of the nucleus. The presence of squamous cell metaplasia with the formation of keratin pearls, sometimes observed in ductal and solid structures, is less common - mucous metaplasia and clear cell changes can be mistakenly interpreted as mucoepidermoid cancer. Myoepitheliocytes can form a gentle network type of structure or wide fields of spindle-shaped cells resembling a shvannoe. They can be a plasmacytoid or hyaline species. Oncocyte changes, if they occupy the entire tumor, can be treated as oncocytoma.

The stromal component of the tumor is represented by a different ratio of myxoid zones to cells of stellate, elongated form, and chondroid parts with a cartilaginous dense substance, with single round cells similar to chondrocytes, and fibroblast-like cell sites. All components: epithelial and stromal without any boundaries, are intermixed, sometimes epithelial cell complexes are surrounded by a massive intercellular base. Sometimes a mesenchymal component can occupy most of the tumor. The cells inside the mucosal material are of myoepithelial origin and their periphery tends to mix with the surrounding stroma. The cartilage-like component appears to be a true cartilage, it is positive for collagen type II and keratin sulfate. Occasionally, it is the main component of the tumor. Bone can form within this cartilage or through bone metaplasia of the stroma. The deposition of a homogeneous eosinophilic hyaline material between tumor cells and in the stroma can be a pathognomonic sign of this tumor. Tumors often form bundles and masses in the form of globules, positive when staining for elastin. This material can push back the epithelial elements, giving a picture reminiscent of a cylinder or crooked structures, as in adenocystic cancer. In some long-term tumors, progressive hyalinosis and a gradual disappearance of the epithelial component are seen. Nevertheless, 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. The adenoma of the salivary gland with a prominent lipomatous stromal component (up to 90% and above) is called lipomatous pleomorphic adenomas.

After a biopsy with a fine needle, more pronounced inflammation and necrosis after spontaneous infarctions can be observed. In such tumors, there is increased mitotic activity and some cellular atypia. In addition, squamous cell metaplasia can be observed. All these changes can be mistaken for malignancy. Some tumors show signs of cystic degeneration with the formation of a "frame" of the tumor elements around the central cavity. Occasionally, tumor cells can be seen in the vascular lumens. This is seen within the tumor and on its periphery, which is considered to be an official change. Sometimes tumor cells are seen in vessels far from the main tumor mass. Nevertheless, these findings should not be regarded as relevant in the biological behavior of the tumor, especially in terms of the risk of metastasis.

Immunohistochemically, the internal cells of the ducts in the tubular and glandular structures are positive for cytokeratins 3, 6, 10, 11, 13 and 16, while the neoplastic myo-epithelial cells are focal positive to cytokeratins 13, 16 and 14. Neoplastic myoepithelial cells co-express vimentin and pancitokeratin , are unstable to the B-100 protein, smooth muscle actin, CEAP, calponin, NNP-35 and FRY. The altered myoepithelial cells are also positive for p53. Non-lacunar cells in the chondroid parts are positive for both pancitokeratin and vimentin, while lacunar cells are only for vimentin. The spindle-shaped tumor myoepithelial cells around the chondroid regions express the bone morphogenetic protein. Collagen type II and chondromodulin-1 are present in the cartilage matrix.

Agtrekan is found not only in the cartilaginous matrix, but also in the myxoid stroma, and in the intercellular spaces of the tubular-ferruginous structures. Actively conducted cytogenetic studies showed karyotype disorders in approximately 70% of pleomorphic adenomas. There are four main cytogenetic groups:

• Tumors with translocations t8q 12 (39%).
• Tumors with perestroika \ 2q \ 3- 1 5 (8%).
• Tumors with sporadic clonal changes, except 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 with t8q 12 (51.1 years versus 39.3 years) and that adenomas with normal karyotypes have a more pronounced stroma than with t8q 12.

Clinico-morphological studies undertaken by the author to elucidate the relationship between the clinical course and the predominant structure in a mixed tumor did not reveal this dependence.

Electron microscopic studies have established the epithelial and myoepithelial nature of tumor components. The cells of the epithelial component differentiate in the direction of the flat epithelium, the elements of the salivary tubes, the ducts, sometimes the secreting epithelium of the acini, myoepithelium; there are low-grade epithelial cells. Myoepithelial cells are found in glandular tubes, strands and cluster clusters. Low-differentiated cells of the epithelial component, in the absence of them in the stromal component, give grounds to consider them as 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 toward flat epithelium. The signs of flat-epithelial differentiation in chondroid sections and areas from elongated fibroblast-like cells, in the absence of elements of the fibroblastic series, give grounds to consider epithelial cells with flat-epithelial differentiation and myoepithelial elements forming mesenchymal regions of the tumor. Polymorphism and proliferation of epithelial cells are not criteria of malignancy. Pleiomorphic adenoma of the salivary gland has the ability to recur and 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 ranges from 1 to 50%. Differences in relapse statistics are most likely due to the inclusion of non-radical operations in studies, until subtotal resection has become the main treatment for pleomorphic adenoma. Relapses often develop in young patients. The main causes of relapse are:

• predominance of the myxoid component in the tumor structure;
• a difference in the thickness of the capsule, together with the ability of the tumor to germinate the capsule;
• individual tumor nodes, immured within the capsule;
• "Experiencing" of tumor cells.

Many recurrent pleomorphic adenomas have a multifocal type of growth, sometimes so common that surgical control in such a situation becomes quite complicated.

Basal cell gland adenoma

A rare benign tumor characterized by a basaloid cell species and the absence of a myxoid or chondroid stromal component present in pleomorphic adenoma. The code is 8147/0.

Basal cell gland adenoma was first described in 1967 by Kleinsasser and Klein. In our material, basal cell adenoma enters the group sometimes can be a cystic type. The membrane variant of the neoplasm (a tumor similar in skin type) can be multiple and coexist with skin cylinders and trichoepitheliomas.

Macroscopically in most cases, the adenoma of the salivary gland is a small, clearly delimited, encapsulated node, measuring 1 to 3 cm in diameter, except for the membrane variant, which can be multifocal or multinodular. On the surface of the incision the neoplasm has a dense and homogeneous consistence, a grayish-whitish or brownish color.

Basal cell gland adenoma is represented by basaloid cells with eosinophilic cytoplasm, fuzzy boundaries and oval-rounded nucleus forming solid, trabecular, tubular and membranous structures. However, a tumor can consist of more than one of these histological types, usually with a predominance of one of them. A solid type consists of bundles or islands of various sizes and shapes, usually with palisade cubical or prismatic cells around the periphery. The islands are separated from each other by strips of tight connective tissue, rich in collagen. Trabecular type of structure is characterized by narrow strips, trabeculae or bundles of basaloid cells separated by a cellular and vascularized stroma. A rare but distinctive property is the presence of a cell-rich stroma consisting of altered myoepithelial cells. Channel ducts are often seen among the basaloid cells, and in such cases they speak of the tubulo-trabecular type. The membrane type of basal cell adenoma has thick bundles of hyaline material along the periphery of the basaloid cells and in the form of intercellular droplets. In the tubular type, duct structures are the most conspicuous feature. In all cases, there may be cystic changes, signs of squamous cell differentiation in the form of "pearls" or "whirlpools" or rare cribrous structures. In rare tumors, especially the tubular structure, there may be extensive oncocyte changes.

Immunoprofile of basal cell gland - keratin, myogenic markers, vimentin, p53 indicate ductal and myoepithelial differentiation. Vitaminen and myogenic markers can also be colored cells of palisade structures with a solid type of structure. Expression variants reflect different stages of differentiation of tumor cells, ranging from a less differentiated solid type to the most differentiated one - tubular.

Basal cell adenoma usually does not recur, except for the membrane type that occurs again in about 25% of cases. There are reports of malignant transformation of basal cell gland, although this is extremely rare.

[8], [9], [10], [11], [12], [13], [14], [15]

Canal adenoma of the salivary gland

A tumor consisting of prismatic epithelial cells, assembled into thin, anastomosing with each other bundles, often in the form of "beads". The tumor stroma has a characteristic multicellular and abundantly vascularized appearance.

Synonyms: basilar cellular adenoma of the canalicular type, adenomatosis of small salivary glands.

The average age of the diseased and the peak frequency of canalicular adenoma occur at 65 years. The age of the patients as a whole varies between 33 and 87 years. The adenoma of the salivary gland is infrequent in people under the age of 50, and the ratio of men to women is 1: 1.8.

In studies of large series, this new growth occurs in 1% of cases of all tumors of the SC and in 4% of all small SC tumors.

Kanapikular adenoma of the salivary gland selectively affects the upper lip (up to 80% of observations). The next most frequent localization of canalicular adenoma is the mucous membrane of the cheek (9.5%). Occasionally, canalicular adenoma occurs in large SJ.

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

Of particular importance are cases of multifocal or multiple canalicular adenomas. Typical is the involvement of the upper lip and mucous membrane of the cheek in the process, however, other localizations may be affected.

The macroscopically canonic adenoma of the salivary gland usually reach a size of 0.5-2 cm in diameter and is well delimited from the surrounding tissues. Their color is from light yellow to brown.

Microscopically, at a small magnification, a clear boundary is visible. The canal adenoma of the salivary gland has a fibrous capsule, while smaller tumors are often devoid of it. Sometimes you can see small nodules around a neighboring large tumor. In addition, very small foci of adenomatous tissue, which can be seen, represent the initial stage of adenoma manifestation. In some cases, there may be areas of necrosis.

The epithelial component is represented by two rows of prismatic cells, which are located one behind the other, are located at a distance from each other. This leads to a characteristic feature of this tumor - the so-called "canal", where the cells of the epithelium are widely separated. The alternate arrangement of closely opposite and widely separated epithelial cells also leads to the characteristic "bead" type of this tumor. Epithelial cells that form bundles are usually prismatic in shape, but can also be cubic. The nuclei are of regular shape, polymorphism is not observed. Nucleoli are invisible, and the figures of mitosis are extremely rare. The stroma has a characteristic appearance, which is the key to the diagnosis. The stroma is cellular and abundantly vascularized. Capillaries often demonstrate the presence of eosinophilic "cuffs" from connective tissue.

The immunoprofile of canal adenoma consists of a positive reaction to cytokeratins, vimentin and S-100 protein. Focal positive reaction with GFAP is rarely detected. The canal adenoma of the salivary gland is devoid of coloration by sensitive muscle markers, such as smooth muscle actin, heavy chains of smooth muscle myosin and calponin.

[16], [17], [18], [19], [20]

Greater adenoma of the salivary gland

A rare, usually clearly delineated tumor, consisting of different sizes and forms of nests of sebaceous cells with no signs of cellular atypia, often with foci of squamous cell differentiation and cystic changes. The code is 8410/0.

The sebaceous adenoma of the salivary gland is 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 and women is 1.6: 1. In contrast to sebaceous skin lesions, with sebaceous adenoma SJ, there was no increase in the incidence of cancers of various visceral localizations.

The sebaceous adenoma of the salivary gland is localized as follows: Parotid SJ - 50%, mucous membrane of cheeks and the retromolar region - 1 7 and 13%, respectively, subthrift SJ - 8%.

The clinical picture is presented by a painless tumor.

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

The histologically sebaceous adenoma of the salivary gland consists of the nests of the sebaceous cells, often with foci of squamous cell differentiation, without atypia, or with minimal signs of cellular atypia and polymorphism, without a tendency to local-growth growth. Many tumors consist of many small cysts or are built predominantly from ectasized duct structures. Sebaceous glands vary greatly in size and shape, often in the fibrous stroma. In some tumors, there are signs of marked oncocytic metaplasia. Focal it is possible to see histiocytes and / or giant cells resorption type of foreign bodies. Lymphoid follicles, signs of cellular atypia and polymorphism of necrosis and mitosis are not characteristic for this tumor. Sometimes, the sebaceous adenoma can be part of a hybrid tumor.

With regard to prognosis and treatment, it must be said that the adenoma of the salivary gland does not recur after adequate surgical removal.