Minor salivary glands of the lips: a novel, easily accessible source of potential stem/progenitor cells.

OBJECTIVES: Cells with stem/progenitor properties have been detected in major salivary glands, but no data are available on their presence within minor salivary glands (MSGs). This study aimed to isolate and characterize potential stem/progenitor cells from human MSGs. MATERIALS AND METHODS: MSGs of the lower lip were surgically obtained during biopsy for Sjogren's syndrome investigation that finally proved to be histologically normal. The established MSG cultures were assessed for morphology, proliferation, colony-forming-unit efficiency, multipotentiality, and immunophenotypic characteristics. RESULTS: A mixed population of fibroblast-like and a few flat-shaped epithelial-like cells was obtained. These cells were capable for osteogenic, adipogenic, and neurogenic differentiation. Evidence for strong stem cell potency was observed by the detection of early stem cell markers, like Nanog, Oct-3/4, and SSEA-3. These cells also expressed characteristic mesenchymal stem cell markers, including CD90-Thy1, CD105, CD49f, CD81, nestin, CD146, and Stro-1, but were negative for CD117/C-KIT, CD45, and CD271/NFG. In addition, positivity for keratins 7/8 in part of the population was indicative of an epithelial phenotype, whereas these cells were negative for aquaporin-1 expressed in acinar/myoepithelial cells during development. CONCLUSIONS: Based on these data, a cell population with stem/progenitor characteristics was primarily isolated from labial MSGs. The morphologic and immunophenotypic features indicated that this population is mixed with mesenchymal (mainly) and epithelial characteristics. CLINICAL RELEVANCE: Due to their large number and superficial distribution in labial mucosa, MSGs may be proposed as a potential easily accessible source of adult stem/progenitor cells for regenerative therapies of glandular organs with parenchymal pathology.

Expression of N-cadherin in salivary gland tumors.

OBJECTIVE: To detect immunohistochemically the N-cadherin expression in different types of benign and malignant salivary gland tumors in an attempt to note any possible correlation to their development, stage and invasive properties. MATERIALS AND METHODS: N-cadherin expression was examined in tissue specimens from 49 salivary gland tumors including: pleomorphic adenomas (4), Warthin's tumors (10), and myoepitheliomas (4) (benign tumors), as well as adenoid cystic carcinomas (14), mucoepidermoid carcinomas (4), polymorphous low-grade adenocarcinomas (6), and adenocarcinomas not otherwise specified (5) (malignant tumors). Twelve specimens of normal salivary glands were used as control. The perineural invasion and stage of malignant salivary gland tumors were evaluated. Immunohistochemical procedure was performed automatically using the Bond Polymer Refine Detection Kit. RESULTS: N-cadherin expression was not found in normal salivary glands. In benign salivary gland tumors, N-cadherin along membranes of neoplastic cells as well as in centrocytes of lymphoid germinal centers was seen in 1 and 4 cases of Warthin's tumors, respectively. Varied degree of N-cadherin expression was found in 13 (45%) cases of malignant salivary gland tumors. N-cadherin expression was significantly correlated with perineural invasion (χ(2) = 11.7, p < 0.0001), but not with stage of malignant salivary gland tumors. CONCLUSION: N-cadherin expression was observed in malignant salivary gland tumors and could be an indicator of potentially aggressive behavior. N-cadherin expression by tumor cells could be attributed to perineural invasion.

Myofibroma of the oral mucosa: a case report.

OBJECTIVE: To report a case of coexisting irritation fibroma and myofibroma in oral mucosa. CLINICAL PRESENTATION AND INTERVENTION: One case with two painless, nodular masses, adjacent to each other in the buccal mucosa, was clinically examined with a provisional diagnosis of irritation fibroma, salivary gland tumors, neurofibroma and schwannoma. Histological examination of the smaller swelling showed features of irritation fibroma, while the features of the other mass were compatible with myofibroma or leiomyoma. Additional immunohistochemical examination established the diagnosis of myofibroma. CONCLUSION: This was a case of a myofibroma that was clinically similar to an adjacent irritation fibroma, which highlights the possibility of misdiagnosis of a myofibroblastic tumor and underlines the importance of histologic examination together with immunohistochemical and/or histochemical analysis if necessary to establish the accurate diagnosis.

Coexistence of mucous retention cyst and basal cell adenoma arising from the lining epithelium of the cyst. Report of two cases.

OBJECTIVE: To report 2 cases of coexisting mucous retention cyst and basal cell adenoma arising from the lining epithelium of the cyst. CLINICAL PRESENTATION AND INTERVENTION: Two cases of painless swellings, well-demarcated, soft to palpation, and located in the submucosa of the upper lip were clinically examined with the provisional diagnosis of mucocele or salivary gland tumor. Histological examination showed the presence of a large unilocular cystic cavity in many parts surrounded by single or bilayered lining epithelium composed of flattened to cuboidal cells, and in other parts surrounded by projections of cells arranged in a trabecular pattern far into the cystic cavity. The trabeculae were composed of basal and low columnar cells that sometimes formed small duct-like structures. Immunohistochemistry showed that the lining epithelium of the cystic cavity and the cells of the projections expressed cytokeratin 7 and high-molecular-weight cytokeratins. The cells of the projections were weakly positive for S-100 protein and negative for vimentin and alpha-smooth muscle actin. Based on the results, a diagnosis of coexisting mucous retention cysts and basal cell adenomas arising from the lining epithelium of cysts was made. CONCLUSION: The coexistence of mucous retention cysts and basal cell adenomas arising from the lining epithelium of the cyst is reported.

Immunohistochemical study of fibroblasts and mast cells in chronic submandibular sialadenitis.

AIM: To further our understanding of the processes involved in fibrosis that occurs in chronic submandibular sialadenitis by investigating the distribution of myofibroblasts, CD34-positive fibroblasts and tryptase-containing mast cells. MATERIALS AND METHODS: Thirty specimens of chronic submandibular sialadenitis with varying degrees of fibrosis and five normal submandibular glands were examined immunohistochemically for the presence of CD34, alpha-smooth-muscle-actin, desmin and tryptase. RESULTS: Myofibroblasts were not demonstrated by the techniques for alpha-smooth-muscle-actin or desmin. CD34-positive fibroblasts were found around normal and moderately atrophic acini, but were not found around extremely atrophic acini and duct-like structures or in periductal and interlobular fibrous tissue. Tryptase-containing mast cells were found around vessels in normal submandibular glands. They were found in increased numbers in chronic submandibular sialadenitis, particularly in glands with widespread fibrosis, in which they were found in the fibrous tissue, and in which the increase was statistically significant. CONCLUSIONS: The results of this investigation suggest that tryptase-containing mast cells are likely to be involved in the fibrosis of chronic submandibular sialadenitis, but myofibroblasts and CD34-positive fibroblasts are not.

The role of Candida in inflammatory papillary hyperplasia of the palate.

The objective of this study was to investigate the expression by immunohistochemistry of the major basement membrane (BM) components (laminin, collagen type IV, fibronectin) in specimens from the palatal mucosa lesions of patients with complete dentures and diagnosis of inflammatory papillary hyperplasia of the palate (IPHP). Furthermore to evaluate the potential role of candidal infection in patients with IPHP. Biopsies of palatal mucosa were obtained from patients with IPHP, generally healthy/orally healthy patients with dentures, and healthy subjects. Immunohistochemical studies performed with specific antibodies to BM proteins. Scrapings and swaps of oral lesions from all patients and control groups were taken from the palate, and Candida species colonization was assessed with mycology tests. Immunohistochemical expression of BM components revealed thin linear staining in the BM of healthy palatal mucosa. In IPHP discontinuities or disruptions in BM were observed at the interface between epithelium and the underlying connective tissue in the areas of severe inflammatory response. Our findings suggest an interaction between the expression of BM components and Candida involvement in the development of IPHP, a disorder involving inflammatory reaction and modification of soft tissues.

Verruciform xanthoma coexisting with oral discoid lupus erythematosus.

We describe an unusual case of verruciform xanthoma on the lingual surface of the gum that coexisted with oral discoid lupus erythematosus.

Immunohistochemical detection of E-cadherin in certain types of salivary gland tumours.

OBJECTIVES: To investigate the topography of E-cadherin and its possible correlation with the histological phenotype of salivary gland tumours. MATERIAL AND METHODS: Archival formalin-fixed, paraffin-embedded sections of 54 benign and 56 malignant tumours and 24 samples of normal and inflamed salivary gland tissue were studied immunohistochemically using an Envision/horseraddish peroxidase (HRP) technique. RESULTS: In normal and inflamed salivary gland samples, E-cadherin was expressed at the membrane of acinar, myoepithelial and ductal cells located at cell-cell contact points. Reduction and/or absence of E-cadherin was only observed in pleomorphic adenoma at the peripheral cells of the duct-like or island structures, or in the cells exhibiting plasmacytoid or stromal differentiation. Neoplastic epithelium in Warthin's tumours and in myoepithelial and oncocytic adenomas was strongly positive. Furthermore, a weak to moderate loss of expression which was related to tissue tumour subtype was seen in malignant tumours such as: adenoid cystic carcinomas; polymorphous low-grade adenocarcinomas; acinic cell carcinomas; and mucoepidermoid low-grade, epithelial-myoepithelial, lymphoepithelial and squamous low-grade carcinomas. Moderate to extreme loss or alternative cytoplasmic non-functional expression were observed in cases of salivary ductal carcinoma, carcinosarcoma, myoepithelial carcinoma, oncocytic adenocarcinoma, unspecified adenocarcinoma and squamous high-grade carcinomas. CONCLUSION: This study suggests a direct association of E-cadherin expression with neoplastic histologic phenotype, which is lost in the more undifferentiated and invasive epithelial salivary gland tumours.

Coexistence of lymphoepithelial and epidermoid cysts on the floor of the mouth: report of a case.

Lymphoepithelial and epidermoid cysts in the oral cavity are uncommon. The coexistence of lymphoepithelial and epidermoid cysts in the oral cavity is extremely rare. Only one case of lymphoepithelial cyst associated with two epidermoid cysts on the floor of the mouth has been reported in the literature and the present report describes a second case where a lymphoepithelial cyst coexisted with an epidermoid cyst on the floor of the mouth. It is likely an accidental trauma that was accompanied by inflammation produced the development of implantation-keratinizing epidermoid and lymphoepithelial cysts.

Adenoid cystic carcinoma and polymorphous low-grade adenocarcinoma of minor salivary glands: a comparative immunohistochemical study using the epithelial membrane and carcinoembryonic antibodies.

OBJECTIVE: The purpose of this study was to investigate immunohistochemically the expression of epithelial membrane antigen (EMA) and carcinoembryonic antigen (CEA) in adenoid cystic carcinoma (AdCC) and polymorphous low-grade adenocarcinoma (PLGA) in an attempt to assess the ability of these markers to distinguish AdCC from PLGA when the histological features on routine hematoxylin and eosin are equivocal. MATERIALS AND METHODS: Fourteen specimens of AdCC, 10 PLGA, and five normal minor salivary glands fixed in 10% formalin and embedded in paraffin, were retrieved from the files of our department and were retrospectively studied with the streptavidin-biotin complex method using the epithelial membrane and carcinoembryonic antibodies. RESULTS: The immunoreactivities and the expression patterns of EMA and CEA in AdCC and PLGA were similar. CONCLUSIONS: The results of this study suggest that the immunostaining of AdCC and PLGA with EMA and CEA could not offer an adjunctive aid in differential diagnosis between these two tumors.

Osteoma of the ethmoidal sinus: a rare case of recurrence.

Osteomas are slow growing bony tumours that may form in the sinuses of the skull. Presenting complaints include headaches, cerebral symptoms, or visual disturbances, depending on the site of the tumour. We describe an unusual case of an osteoma in the ethmoid sinus that recurred 5 years after its resection at another hospital. The patient presented with proptosis, epiphora, and headaches. We approached the lesion and removed it through a lateral nasal incision. Two years later the patient was free of symptoms.

Benign tumors of adipose tissue of the oral cavity: a clinicopathologic study of 13 cases.

PURPOSE: The purpose of this study was to determine the clinical and histologic features of 9 simple lipomas, 2 fibrolipomas, and 2 infiltrating lipomas of the oral cavity. In addition, 10 cases of infiltrating lipoma of the oral cavity previously reported in the literature were reviewed. MATERIALS AND METHODS: All cases were retrieved from the archives of the Department of Oral Medicine/Pathology of the University of Thessaloniki, Greece. Data on age, sex, location, clinical appearance, duration, recurrence, and histologic appearance were evaluated. RESULTS: This study showed that the sex distribution of the simple lipomas was approximately equal, and the mean age of patients was 60.2 years. The buccal mucosa was the most frequent location of the tumors. Their size ranged from 0.2 to 1.5 cm, with an average rate 0.8 cm. In 3 cases, the tumor was not encapsulated. The sex distribution of the infiltrating lipomas was equal, and the mean age of the patients was 36.8 years. The most frequent location was the tongue. CONCLUSIONS: Tumors of adipose tissue represent rare neoplasms of the oral cavity. The diagnosis is based on both the clinical and histologic characteristics. Caution is required during their surgical excision to avoid recurrence, especially with infiltrating lipomas.

Tumor-associated glycoprotein 72 (TAG-72) expression in salivary gland neoplasia: an immunohistochemical study using the monoclonal antibody (MAb) CC49.

OBJECTIVES: The purpose of this study was to investigate immunohistochemically the expression of tumor-associated glycoprotein 72 (TAG-72) using the monoclonal antibody (MAb) CC49 in salivary gland neoplasia and normal salivary glands in an attempt to determine the potential usefulness of MAb CC49 in diagnostic and therapeutic applications. MATERIALS AND METHODS: Eighty-six specimens (21 benign tumors, 41 malignant, and 24 normal salivary glands), fixed in 10% formalin and embedded in paraffin, were retrieved from the files of the Department of Oral Medicine and Oral Pathology at the Dental School of Aristotle University, Thessaloniki, Greece, and were retrospectively studied with hematoxylin and eosin and with the streptavidin-biotin-complex method using the MAb CC49. RESULTS: Strong immunoreactivity for TAG-72 was observed in salivary duct carcinoma, adenocarcinoma, papillary cystadenocarcinoma, low-grade mucoepidermoid carcinoma, normal submandibular, sublingual, and minor salivary glands. Weak or no immunoreactivity was found in adenoid cystic carcinoma, basal cell adenocarcinoma, polymorphous low-grade adenocarcinoma, and normal parotid gland. CONCLUSIONS: Our results suggest the potential use of MAb CC49 in the differential diagnosis of some salivary gland neoplasms in which their histopathologic features overlap, and in the radiation immunolocalization and immunotherapy of malignant tumors that are localized in the parotid gland.

Role of microliths in the aetiology of chronic submandibular sialadenitis: a clinicopathological investigation of 154 cases.

AIMS: Confusion about the aetiology and pathogenesis of chronic submandibular sialadenitis led to the present investigation of 154 cases in which many clinical and histological features were analysed. METHODS AND RESULTS: By far the greatest number of histological factors, namely liths, atrophy, fibrosis, parenchymal inflammation, lymphoid germinal centres, mucous and ciliary metaplasia, salivary extravasation and glycosaminoglycan accumulation, was related to the degree of inflammation, which appears to be of the greatest importance in the aetiology and pathogenesis. Inflammation, atrophy and fibrosis were related to duration of symptoms, which supports the concept of a chronological progression through increasingly severe histological changes. CONCLUSIONS: Inflammation possibly arises from ascending infection in a normal gland and exerts an obstructive and destructive effect on the parenchyma with the development of the related histological changes and a vicious circle involving further ascending infection. Normal glands contain microliths that possibly by localized obstruction cause atrophic foci that are reservoirs for ascending infection. Microliths and liths were unrelated: microliths were related to age as in normal glands whereas liths were related to duration of symptoms and appeared to be secondary to the sialadenitis. Many glands showed minimal changes, which raises the possibility of conservative treatment.

Tumor-associated glycoprotein (TAG-72) in chronic submandibular sialadenitis and normal minor salivary glands defined by monoclonal antibody B72.3.

Formalin-fixed, paraffin-embedded samples of three normal minor salivary glands, 10 chronic submandibular sialadenitis, and three normal submandibular glands were studied immunohistochemically using the monoclonal antibody (Mab) B72.3 in order to have a better understanding of the distribution of tumor-associated glycoprotein (TAG-72). Diffuse expression of TAG-72 was observed in the mucous cells of normal minor salivary glands, and in the ducts with goblet cell metaplasia and/or hyperplasia of chronic submandibular sialadenitis (eight of 10). Focal expression of TAG-72 was seen in the acinar mucous cells of normal submandibular gland (three of three), and in the mucous cells of normal or atrophic acini of chronic submandibular sialadenitis (eight of 10). These results should be considered in the cytologic diagnosis of the mucoepidermoid carcinoma using the Mab B72.3 as a diagnostic aid, as well as in future studies for the radiation immunolocalization and immunotherapy of submandibular gland tumors.

Argyrophilic nucleolar organizer region associated proteins in human oral normal mucosa, verrucous carcinoma, and squamous cell carcinoma.

Silver-binding nucleolar-organizer regions (AgNORs) were counted in sections from formalin-fixed, paraffin-embedded blocks of 24 cases of well-differentiated squamous cell carcinoma, 6 cases of verrucous carcinoma, and 11 cases of normal oral mucosa. Two methods of AgNORs counting were used. The mean number of AgNORs/nucleus (mAgNORs) was used as indicator of the DNA content, and the percentage of cells containing five or more AgNORs/nucleus (pAgNORs) as indicator of the proliferative activity of the cells. These two methods were used to examine their possible contributory value as a diagnostic aid to distinguish between the types of carcinoma. The pooled mean counts were: normal oral mucosa mAgNORs 2.41 +/- 0.44 and pAgNORs 3.10 +/- 2.54 (mean +/- SD); verrucous carcinoma: mAgNORs 3.55 +/- 0.39 and pAgNORs 23 +/- 6.99; squamous cell carcinoma: mAgNORs 4.74 +/- 1.04 and pAgNORs 49.88 +/- 23.41. Although the differences of mAgNORs and pAgNORs counts were statistically significant, there was overlap of the counts between verrucous carcinoma and squamous cell carcinoma. These two methods of AgNORs counting cannot be used as a diagnostic aid to distinguish between these variants of squamous cell carcinoma.

Intraoral salivary duct carcinoma: a clinicopathological study of four cases and review of the literature.

Salivary duct carcinoma (SDC) is a distinctive entity of highly malignant salivary gland tumors. We present the clinical features and outcomes of four cases in minor salivary glands and of 69 additional cases previously reported in the literature. The tumor occurs most frequently in the sixth and seventh decades of life with a 3.8:1 male preponderance. The prognosis is dismal. Sixty-one percent of patients were dead within 5 months to 10 years (mean 25 months) and the rate of lymph node metastasis was 60%. Twenty-eight percent of patients were without evidence of the disease for 13 months to 9 years (mean 33 months). The histologic features, differential diagnosis, and origin of SDC are discussed.

Salivary gland tumors studied by means of the AgNOR technique.

Silver-binding nucleolar organizer regions (AgNORs) were counted in sections from formalin-fixed, paraffin-embedded tissue blocks of 14 benign and 17 malignant tumors of minor salivary glands. The difference in the mean number of AgNORs count per nucleus between benign and malignant tumors was found to be statistically significant (p < 0.001). A positive correlation between the AgNORs count and the degree of malignancy of the malignant salivary gland tumors was generally observed. The AgNORs technique can be used as a diagnostic aid in differentiating between benign and malignant salivary gland tumors, and possibly the salivary duct carcinoma from the acinic cell carcinoma and poorly differentiated mucoepidermoid carcinoma.

Evaluation of the nucleolar organizer region associated proteins in oral squamous cell carcinoma.

Silver-binding nucleolar-organizer regions (AgNORs) were counted in sections from formalin-fixed, paraffin embedded blocks of oral squamous cell carcinoma. Twenty-four cases were histologically classified as grade 1 and fourteen cases as grade 2. In counting AgNORs two specifications were used. The mean number of AgNORs/nucleus (mAgNORs) was used as indicator of the DNA content and the percentage of tumor cells containing five or more AgNORs/nucleus (pAg-NORs) as indicator of the proliferative activity. These counts were examined with respect to their relation to the histologic grading. The pooled mean counts were: Grade 1 carcinomas mAgNORs 4.73 +/- 1.04 and pAgNORs 49.87 +/- 23.41 (mean +/- SD); Grade 2 carcinomas mAgNORs 7.04 +/- 0.95 and pAgNORs 79.14 +/- 20.14. The differences of these results between grade 1 and 2 were statistically significant. These data possibly indicate that in grade 2 oral squamous cell carcinoma there is a higher DNA content and proliferative activity of the tumor cells than in grade 1.