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[Clinical aspects of salivary gland tumors].

This paper reports on epithelial tumours arising primarily in the major and minor salivary glands. The purpose of this presentation is to summarize our experience of salivary gland tumours on the basis of a material comprising of approximately 3000 salivary gland tumours as well as a review of the literature to date. The tumours are classified according to the classification recommended by WHO 1972. The incidence, location, symptomatology, grade of malignancy and treatment of the different tumour types in this classification are reviewed. Diagnostic procedures are discussed and a scheme for surgical treatment and radiotherapy of the different types of salivary gland tumours is proposed.

Adenocarcinoma↗

[Morphology of salivary gland diseases].

The human salivary glands represent a functional system with manifold responsibilities and interactions to the organism. The major and minor salivary glands show a common construction schedule consisting of an acinar functional system for the production of an enzyme- and mucin-containing primary saliva and a ductal functional system with manifold secretory, resorptive and regulatory responsibilities for the transport and the definitive composition of the saliva. The cyclic AMP and calcium iones localized in the glandular acini have an exceptional importance for the course of the secretory process. The neurohormonal control of the salivary secretion results by adrenergic and cholinergic transmitter substances. Moreover the secretory process shows a daily cycle combined with morphological alterations of the glandular cells (so called circadian structures). The fluid secretion of the salivary duct system (the output of sodium-, potassium- and chlorine-iones) represents an active energy-consumed transport process which will be regulated by several factors (autonomic nervous system, quantity of perfusion, hydrostatic pressure in the blood capillaries, transepithelial active transport by ATP-consumed pump systems). The striated ducts are the functional most important sector of the duct system for a rapid fluid- and electrolyte excretion. The terminal axons of the postganglionic sympathic and parasympathic neurits are characterized by spindle-shaped enlargements (varicosities) which contain neurosecretory granules. In the region of the acinar and intercalated duct cells a direct synaptic contact exists for the stimulation transmission, in the course of which the terminal axon contacts immediately with the effector cell by penetration of the basement membrane. The salivary glands form a part of the stabil tissues with reversible postmitotic cells in regard of the tissue regeneration. Under pathological conditions (inflammations, impediment of secretion fluid, radiation effects etc.) metaplasias and proliferations of the duct system arise with development of indifferent duct formations analogous to the type of an embryonal salivary gland. The terminal zone between intercalated and striated ducts represents an indifferent zone with large regeneratory potency. A special behaviour shows the myoepithelial cells which are developed as well to the outside of primitive embryonic duct buds as differentiated intercalated and striated ducts. Morphologically three types of diseases can be classified in the salivary glands: sialadenosis, sialadenitis and tumours.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

Mucus-producing adenopapillary carcinoma of minor salivary gland origin with signet ring cells and intracytoplasmic lumina. A light and electron microscopic study.

A histological and subcellular study of a mucus-producing adenopapillary carcinoma of a minor salivary gland is presented. The tumor was located on the buccal mucosa of a 36-year-old white man. Microscopic examination showed that the tumor was an invasive papillary growth with numerous signet-ring cells and mucous production. When viewed under the electron microscope, the tumor exhibited clusters of cells showing intracellular lumina and finely dispersed chromatin.

Adenocarcinoma, Papillary↗

Basal cell adenomatosis of minor salivary glands of the upper lip.

The basal cell adenoma is one of the more commonly occurring types of salivary tumors in the upper lip. A case with multiple (five) tumors is presented and the literature reviewed. This lesion would be more correctly designated as an adenomatosis. In spite of its frequent multicentricity, recurrence is unusual following surgical removal.

Adenoma↗

Distribution of S-100b protein in normal salivary glands and salivary gland tumors.

Immunohistochemical studies were performed for the presence of S-100b protein in non-neoplastic and neoplastic salivary gland tissues by the peroxidase anti-peroxidase (PAP) method. Some cases of pleomorphic adenoma were investigated by immuno-electron microscopy. S-100b protein could not be detected in epithelial cells of intercalated ducts, acini, striated ducts and excretory ducts of non-neoplastic salivary gland. However, myoepithelial cells surrounding the acini and intercalated ducts were specifically stained by S-100b protein. In pleomorphic adenomas, S-100b protein-positive cells could be mostly observed in the myxoid and chondroid areas, and the basal layer cells of the double-layered ductal cells were also positive. In clear cell adenoma, the clear cells were also S-100b protein positive. In adenoid cystic carcinomas, S-100b protein-positive cells could be found in trabecular areas, but not in tumor cells showing cribriform-pattern. In other tumors (Warthin's tumor, oxyphilic adenoma, basal cell adenoma, mucoepidermoid tumor and acinar cell carcinoma), S-100b protein positive cells were seldom observed. Immuno-electron microscopically, S-100b protein was diffusely distributed in the cytoplasm of myoepithelial cells as well as of tumor cells of pleomorphic adenoma, being distributed especially on the membrane of endoplasmic reticulum and the outer nuclear membrane.

Adenoma, Pleomorphic↗

Immunohistochemical localization of alpha 1-antitrypsin and alpha 1-antichymotrypsin in salivary pleomorphic adenomas.

Immunohistochemical identification of alpha 1-antitrypsin (alpha 1-AT) and alpha 1-antichymotrypsin (alpha 1-ACh) in pleomorphic adenomas of salivary glands is reported in order to compare their distribution profiles with those of lysozyme and lactoferrin, already described elsewhere. Normal salivary glands indicated positive alpha 1-AT staining in ductal segments and had no alpha 1-ACh in any glandular cell. Pleomorphic adenomas displayed moderate positivity to alpha 1-AT staining in duct-like, tubular and glandular epithelia which was particularly intense in luminal cells. The limited number of tumour cells which showed duct-like structures with a single cellular layer arrangement, displayed the highest staining to alpha 1-ACh. Strongly alpha 1-AT positive tumour cells located on the inner side of luminal cavities were also markedly positive to alpha 1-ACh. Spindle shaped tumour cells existed outside tubular and ductal structures and were negative to alpha 1-AT and alpha 1-ACh. Distribution of alpha 1-AT in salivary glands was similar to that of lysozyme as is usual in ductal segments or their transformed cells, and occurrence of alpha 1-ACh localization rather resembled that of lactoferrin, with occurrence in acinar compartments and changed epithelia within acini. The biological role of a specific immunohistochemical distribution of alpha 1-AT and alpha 1-ACh in pleomorphic adenomas may be associated with a self regulating mechanism which inhibits degradation by tissue proteinases.

Adenoma, Pleomorphic↗

Immunohistochemical expression of epidermal growth factor receptor in salivary gland tumours.

Immunohistochemical localization of epidermal growth factor receptor (EGFR) in normal salivary glands and tumours (108 cases) was studied using a monoclonal antibody. In the normal salivary glands, EGFR was occasionally detected in ductal segments of intercalated, striated, and excretory ducts, but not in acinar cells. The frequency of positive EGFR staining in salivary gland tumours was not high: pleomorphic adenoma, 33.8%; mucoepidermoid tumour, 25.0%; adenolymphoma, 44.4%; and sialoadenocarcinoma, 66.6%. Pleomorphic adenomas showed positive staining for EGFR on the luminal side of luminal cells and in squamous metaplastic cells of tumour tissue. Some modified myoepithelial cells were also reactive whereas outer spindle tumour cells were unstained. Adenolymphomas regularly exhibited positive EGFR staining in the cell membrane; mucoepidermoid carcinoma displayed positive staining in cell membranes in epidermoid tumour cells and cytoplasmic staining in mucous-secreting tumour cells. Sialocarcinomas revealed cell membrane staining and whole cytoplasmic staining for EGFR. The immunohistochemical localization of EGFR could be classified into two types, one the cell membrane-positive type found in epithelial tumour cells, and the second the cytoplasmic positive type seen in normal ductal cells, the luminal tumour cells of pleomorphic adenomas and mucous-secreting tumour cells.

ErbB Receptors↗

Ultrastructural study of glycogen-rich oxyphilic adenoma of the nasopharyngeal minor salivary gland.

A glycogen-rich adenoma occurring in the minor salivary gland of the nasopharynx in a 41-year-old woman was studied ultrastructurally. The cytoplasm of the tumour cells was abundantly filled with glycogen particles. The tumour cells possessed many mitochondria, a great number of microvillous processes and microvilli and were joined to each other by desmosomes. These findings suggest that this adenoma is of salivary duct epithelial origin most probably from storing striated ductal cells, and is a variant of monomorphic oxyphilic adenoma.

Adenoma↗

Mast cells in cystadenolymphomas.

Cystadenolymphomas are a special kind of salivary gland tumours with an epithelial and a stromal part. Mast cells, which in this tumour were only rarely mentioned, were observed in large amounts in the stroma and in the epithelium. This type of cell is present especially in those cystadenolymphomas rich in epithelial parts. The possible significance of this observation is discussed.

Adenolymphoma↗

Multiple expression of keratins, vimentin, and S-100 protein in pleomorphic salivary adenomas.

Immunohistochemical staining for S-100 protein and the intermediate filaments keratin and vimentin, was made in 41 salivary adenomas. In pleomorphic adenomas, great heterogeneity in the staining, as well as multiple and co-expressions of these proteins were found in the outer tumor cells of tubulo-ductal structures and modified myoepithelial cells, but not in the luminal tumor cells. All the outer tumor cells stained for S-100 protein, 97% for K8.12 keratin and 85% for vimentin. Of these cells, 29% showed multiple expression of K8.12 keratin, vimentin, and S-100 protein, and 17% showed co-expression of K8.12 and S-100 protein. Modified and neoplastic myoepithelial cells showed similar expressions of these proteins to those of outer tumor cells; myoepithelioma cells displayed the most complicated pattern, being positive for KL1, PKK1, and K8.12 keratins, vimentin and S-100 protein. In luminal tumor cells there was a heterogeneous expression of KL1 and PKK1 in 82%, and of KL1, PKK1, and K8.12 in only 14.7%. Based on the immunohistochemical findings obtained with different monoclonal antibodies in pleomorphic salivary adenomas, outer tumor cells may be derived from ductal basal cells and luminal tumor cells from intercalated duct cells.

Adenoma, Pleomorphic↗

Comparison of CEA distribution in lesions and tumors of salivary glands as determined with monoclonal and polyclonal antibodies.

Immunohistochemical localization of carcinoembryonic antigen (CEA) with conventional antibody to CEA (anti-CEA), nonspecific crossreacting antigen (NCA)-absorbed polyclonal antibody to CEA (NCAa-CEA), and monoclonal antibody to CEA (Mono-CEA) have been compared in obstructive lesions and salivary gland tumors. Normal salivary glands gave strong staining of the luminal borders of acinar cells with anti-CEA, whereas no staining occurred with Mono-CEA. Obstructive lesions showed occasionally marked staining with anti-CEA in some acinar cells, but there was no reaction with Mono-CEA. Of 69 pleomorphic adenomas examined, 34 were positively stained with anti-CEA, 18 with NCAa-CEA and 8 with Mono-CEA along the luminal borders of the tumor cells. The frequency of positive staining of material within tubular lumina was similar with all three immunoreagents. Neoplastic cells were positive with Mono-CEA in only three cases, while eight cases were positive with NCAa-CEA and 11 cases with anti-CEA. In salivary gland tumors true CEA is be found mainly at the border of tumor cells, but the frequency of positive reactions is low.

Adenolymphoma↗

Immunohistochemical evaluation of cartilage-derived morphogenic protein-1 and -2 in normal human salivary glands and pleomorphic adenomas.

Cartilage-derived morphogenic protein (CDMP)-1 and -2 belong to the bone morphogenetic protein (BMP) family in the transforming growth factor (TGF)-beta superfamily. CDMP-1 and CDMP-2 were reported to play essential roles in limb cartilage and limb-joint formation in developing mice. Although pleomorphic adenoma of the salivary glands is an epithelial tumor, it frequently shows ectopic cartilaginous formation. These findings suggested that CDMP-1 and -2 may play essential roles in chondroid formation in salivary pleomorphic adenoma. To evaluate this hypothesis, we examined the expression and localization of CDMP-1 and -2 immunohistochemically in 20 normal human salivary glands and 35 pleomorphic adenomas. CDMP-1 was immunolocalized in the striated ducts and the intercalated ducts in the normal salivary glands. CDMP-1 was immunolocalized in the cuboidal neoplastic myoepithelial cells around the chondroid areas of the pleomorphic adenomas, whereas these molecules were not localized in the spindle-shaped neoplastic myoepithelial cells of the myxoid element or the lacuna cells of the chondroid element in these tumors. CDMP-2 was expressed neither in normal salivary glands nor any of the elements of the pleomorphic adenomas. Type-II collagen and aggrecan were immunolocalized throughout the matrix around the lacuna cells of the chondroid element, whereas type-X collagen was not immunolocalized in any epithelial or stromal elements, including the chondroid elements. Aggrecan was deposited not only on the chondroid matrix, but also on the myxoid stroma and intercellular spaces of the tubulo-glandular structures, whereas chondromodulin-I was deposited on the chondroid matrix. These results indicated that the cuboidal neoplastic myoepithelial cells around the chondroid areas expressed CDMP-1 and suggested that this molecule may play a role in the differentiation of neoplastic myoepithelial cells in pleomorphic adenoma. The phenotype of the lacuna cells was similar to that of mature to upper hypertrophic chondrocytes of the authentic cartilage. In conclusion, pleomorphic adenoma expressed CDMP-1 but not CDMP-2.

Adenoma, Pleomorphic↗

Sarcomatoid salivary duct carcinoma of the oral cavity.

This report recounts a new case of sarcomatoid variant of salivary duct carcinoma in a 45-year-old woman. The 1.5-cm polypoid mass protruded from the retromolar area and focally extended into the pharyngeal wall. The patient was free of disease for 11 years. The tumor showed a biphasic malignancy; nondescript sarcomatous proliferation predominated over ductal carcinoma population, with perceptible blending of the two components. The sarcomatoid areas had no heterologous properties. Discohesive pleomorphic cells were immunopositive for vimentin, epithelial membrane antigen and AE1/AE3 at a significant rate. A dual expression of AE1/AE3 and vimentin was also evident in enmeshed foci of conventional cribriform adenocarcinoma. Thus, the sarcomatoid histology represents a dedifferentiated phenotype of salivary duct carcinoma.

Biomarkers, Tumor↗

Plasmacytoid cells in salivary-gland pleomorphic adenomas: evidence of luminal cell differentiation.

To determine the cellular origin of plasmacytoid cells in salivary gland adenomas, immunohistochemistry was performed on sections from 12 pleomorphic adenomas rich in these cells. In normal salivary glands included in these sections, the myoepithelial cells (MECs) expressed alpha-smooth muscle actin (alphaSMA) and smooth muscle myosin heavy chain (SMMHC), whereas the duct luminal cells expressed keratins 19, 18 and 8. Some of the salivary duct basal cells expressed these keratins, and the acinar cells expressed keratins 18 and 8. The expression profile was similar in rat salivary glands not only after but also during development. The immature MECs never expressed the keratins nor did the immature duct cells express alphaSMA. In seven cases, up to 60% of the plasmacytoid cells expressed keratin 19. In three of these cases, about 10% of the plasmacytoid cells expressed keratin 18. No plasmacytoid cells expressed alphaSMA, SMMHC or keratin 8. These results indicate that plasmacytoid cells originate from luminal cells and not from MECs. Furthermore, in addition to the luminal tumor cells, the non-luminal cells could express keratins 19, 18 and 8. Therefore, it is necessary to re-evaluate the prevailing notion that non-luminal cells are modified MECs. Keratin 14, basic calponin, vimentin and p63 were bi-specific for the MECs and the duct cells. Therefore, expression of these proteins by significant numbers of the non-luminal tumor cells and the plasmacytoid cells never denied the above notion.

Adenoma, Pleomorphic↗

Differential expression of basement membrane type-IV collagen alpha1, alpha2, alpha5 and alpha6 chains among the histological subtypes of adenoid cystic carcinoma.

Six distinct alpha(IV) chains in the basement membrane (BM) of adenoid cystic carcinoma (ACC) of the salivary gland were immunohistochemically examined by anti-alpha(IV) chain-specific antibodies, and their expressions were compared with the histological subtypes and the expressions of cytokeratin 19 (CK19), cytokeratin 14 (CK14) and alpha-smooth muscle actin (alpha-SMA) and Ki-67. In the BM of normal salivary ducts, alpha1(IV), alpha2(IV), alpha5(IV) and alpha6(IV) chains were continuously stained, but alpha3(IV) and alpha4(IV) chains were negative. In the tubular and cribriform subtypes of ACC, tubules with continuous staining of alpha5(IV) and alpha6(IV) chains showed the biphasic-staining pattern among the expressions of CK19, CK14 and alpha-SMA. However, in cancer-cell nests with discontinuous or negative staining of alpha5(IV) and alpha6(IV) chains, the biphasic pattern was ambiguous. In the solid subtype, the staining of alpha1(IV) and alpha2(IV) chains was discontinuous, the staining of alpha5(IV) and alpha6(IV) chains was negative and the biphasic-staining pattern was unclear. The mitotic activity of cancer cells analyzed by the Ki-67 labeling index was significantly related to the expression of alpha5(IV) and alpha6(IV) chains in the cribriform subtype. These results suggest that BM irregularity with the differential expression of alpha(IV) chains in ACC closely relates to cell proliferation, cell differentiation and histological structure.

Adult↗

Melanin bearing myoepithelial cells in a pigmented salivary gland carcinoma: a new avatar of myoepithelial cell? A case report.

Melanocytes can be found in the stroma of salivary glands and their tumors. However, the presence of melanin pigment in the tumor cells of salivary gland origin is exceedingly rare. A 42-year-old man presented with a nasal tumor that was black in color. The histology was that of a minor salivary gland carcinoma with foci resembling an adenoid cystic carcinoma. The myoepithelial cells of this tumor contained melanin pigment. The possible histogenesis of this lesion and an explanation for the occurrence of melanin pigment in a salivary gland tumor are discussed.

Adult↗

[Diagnostic pitfalls in benign and malignant salivary gland diseases. Their significance for prognosis and therapy].

Diagnostic pitfalls exist when benign salivary gland diseases are mistakenly classified as malignant, with consequences for treatment and prognosis. Examples are necrotizing sialometaplasia, metaplastic Warthin tumour and sclerosing polycystic sialadenopathy. The proper diagnosis is of eminent importance to distinguish cases of primary tumours that have developed in salivary glands or their lymph nodes from cases of extraglandular tumours with metastases in these glands or their nodes. In these cases clinical data and additional immunocytochemical methods are necessary to clarify the exact diagnosis, especially when the primary salivary gland tumours have a structure largely identical to the metastases (e.g. squamous cell carcinoma). Nasopharyngeal or cervical chordomas can be mistaken for pleomorphic adenoma or mucinous adenocarcinoma. The initial stage of malignant MALT lymphomas in association with Sjögren's syndrome demands identification of clonal rearrangement for therapeutic implication. The diagnostic criteria for proper classification are analysed in detail.

Diagnosis, Differential↗