Polymorphous low-grade adenocarcinoma versus pleomorphic adenoma of minor salivary glands: resolution of a diagnostic dilemma by immunohistochemical analysis with glial fibrillary acidic protein.

OBJECTIVES: Differentiating polymorphous low-grade adenocarcinoma (PLGA) from pleomorphic adenoma (PA) in salivary gland biopsy specimens from the palatal region might be a diagnostic dilemma for the pathologist when tumors are cellular with minimal matrix material. Glial fibrillary acidic protein (GFAP), expressed by a number of cells in the mature central nervous system, is also expressed in tumors not generally considered to be of glial origin. PAs have previously been reported to strongly express GFAP. PLGAs have been examined for the expression of this protein only in small group studies with variable results. The objective of this study was to determine whether differential expression of GFAP in these 2 tumors could be diagnostically significant. STUDY DESIGN: A total of 42 PLGAs and 36 PAs, formalin-fixed and paraffin-embedded, were immunostained with rabbit polyclonal antibodies to GFAP. CNS tissue was used as a positive control. RESULTS: Results showed the 36 cases of PA to be strongly positive for GFAP. Of PLGAs, 31 were negative and 11 showed faint patchy reactivity in luminal cells. CONCLUSIONS: The results strongly support a role for GFAP as a diagnostic adjunct in the microscopic differential diagnosis of PLGA versus PA. This study is the largest investigation with consistent results to date addressing the application of this antibody to the diagnostic problem of PA versus PLGA.

Establishment of a human polyclonal oral epithelial cell line.

OBJECTIVE: To develop a human oral epithelial cell line to constitute a continuous source of cells readily available for human oral epithelial cell research. STUDY DESIGN: Oral epithelial cells from a 30-week gestational, stillborn male fetus were grown in serum-free medium and transfected by lipid-mediation with the shuttle vector plasmid, pZ189, containing the T-antigen coding region and replication origin from the SV40 virus. RESULTS: Resulting cultures produced foci of rapidly multiplying cells that failed to senesce, in contrast to controls. The transformed culture, designated GMSM-K, was polyclonal. The original culture possessed a normal human male karyotype, and the transformed line was largely hypotetraploid. Multiple clones, isolated from soft agar studies and low density plating, showed decreased doubling times. Electron microscopy and immunohistochemistry confirmed an epithelial phenotype. Cells did not generate tumors in nude mice. CONCLUSION: Few human epithelial cell lines are available to investigators and most are tumor-derived. The nontumor-derived GMSM-K line has value as a resource for human oral epithelial cell research.

Adenomatoid odontogenic tumor presenting as periapical disease.

Adenomatoid odontogenic tumor commonly occurs in association with the crowns of unerupted teeth. An extrafollicular variant, radiographically in relationship to root apices, has been reported. However, clear association with the root apices at surgery has not been demonstrated. We report a case of adenomatoid odontogenic tumor in the anterior mandible in a 21-year-old woman that presented radiographically at the root apices and at surgery as a radicular cyst. We believe this represents the first reported case of adenomatoid odontogenic tumor presenting as periapical disease both clinically and radiographically. The diagnosis of adenomatoid odontogenic tumor should be considered when the clinician is presented with a corticated radiolucency in the anterior jaw, especially in teens and young adults.

Oral lichen planus: parameters affecting accurate diagnosis and effective management.

Oral lichen planus is one of the most common mucosal diseases that require management by the dental practitioner. The gingival presentation of this disease can be particularly problematic. Accurate diagnosis is of paramount importance for effective management, and tissue specimens are often required to distinguish this disease from other vesiculo-ulcerative diseases. The lichen planus patient can generally be managed with topical steroids. The use of antibiotics may be an important adjunctive consideration for patients with a concurrent significant periodontal condition. The possibility of carcinoma arising in lichen planus lesions is addressed. The learning objective of this article is to define specific parameters that contribute to the definitive diagnosis in order to promote objective, rather than empirical, treatment and to delineate specific points to address in patient education.

Trichilemmal cyst of the upper lip.

We report the apparent first case of a trichilemmal cyst presenting intraorally. Trichilemmal cysts are cysts of epithelial origin with a distinctive keratinization pattern that simulates that of the human anagen hair follicle between bulge and sebaceous gland and in the sac surrounding catagen hairs. This type of keratinization of outer root sheath epithelium occurs when it is freed from its internal cover of inner root sheath. This particular case showed evidence of mild epithelial proliferation and slight foci of "metaplastic" epidermoid keratinization, possibly related to mild trauma. The rarity of intraoral hairs undoubtedly accounts for the lack of reported cases of trichilemmal cysts in oral or perioral locations.

Attenuation of the natural course of herpes simplex virus infection in human oral epithelial cell cultures by smokeless tobacco extracts suggests the possibility of a synergistic mechanism for carcinogenesis.

High prevalence of both tobacco use and latent herpes simplex virus type 1 suggests the opportunity for synergism between these agents as cocarcinogens. In this study, postprimary human oral epithelial cell cultures were infected with herpes simplex virus type 1 pretreated with 2% extracts of either loose leaf, moist, or dry snuffs. Cultures were subsequently periodically exposed to the tobacco. Parameters measured included percentage of cultures undergoing active virus production, onset and time course of cytopathic effects, and concentration of virus released into the media over time. Results showed inhibition of both herpes simplex virus-mediated cell lysis and viral replication by tobacco extracts. This is the first time that these phenomena have been demonstrated in normal human oral epithelial cells. The work described here provides evidence to support a hypothesis that herpes simplex virus type 1 and smokeless tobacco may act synergistically in oral carcinogenesis.

The effect on cell phenotype of the mutagenic peptide of herpes simplex virus type-1.

The transforming region of the genome of herpes simplex virus type-1 (HSV-1) encodes a peptide that raises the mutation frequency of cells. To find the effect of this peptide on cell phenotype, three types of cells were transfected with a shuttle vector plasmid that expressed the peptide. When immortalised rat fibroblasts were transfected they rapidly became anchorage-independent with high efficiency, but were not tumorigenic in nude mice. When monkey kidney cells were transfected, five clonal cell lines were isolated, of which one became anchorage-independent but was not tumorigenic in nude mice. When human oral keratinocytes were transfected they did not become immortalised. The peptide therefore induced some of the features of transformation in different cell types, but did not induce a malignant phenotype in any cell. This suggests that interaction with co-factors would be necessary for the peptide to contribute to the development of oral cancer.

Proliferative verrucous leukoplakia and verrucous hyperplasia.

Proliferative verrucous leukoplakia and hyperplasia are irreversible clinicopathologic lesions of the oral cavity and upper respiratory tract with considerable potential for evolving into verrucous or other forms of squamous cell carcinoma. Proliferative verrucous leukoplakia is a disease of the oral cavity in which verrucous hyperplasia is a part of its developmental spectrum. Verrucous hyperplasia, at other head and neck mucosal sites, may be associated with papillomas or be a de novo lesion. Human papillomavirus, as a cofactor, plays a role in some of the lesions. In the instance of verrucous hyperplasia, the authors consider it an early form of verrucous carcinoma and recommend it be treated accordingly.

Salivary duct carcinoma.

Salivary duct carcinoma is a high-grade neoplasm associated primarily with the parotid gland. Its abysmal prognosis demands aggressive clinical management. Initially named after its resemblance to intraductal carcinoma of the breast, this entity derives its histogenesis from the excretory duct reserve cells, which are also the source of origin of other biologically high-grade neoplasms. As this is a lesion seldom encountered by the clinician, it is important for the pathologist to clearly make the distinction between this malignancy and more indolent neoplasms, such as terminal duct adenocarcinoma.

Loss of the basement membrane matrix molecule, bamin, in diphenylamine-treated mice.

Polycystic kidney disease (PKD) is a life-threatening disease characterized by focal dilatations or cysts in certain kidney tubules. Changes (i.e. thickening) in the support structure for these tubules, the basement membrane, have been related to the development of the cysts. Analysis of changes in basement membranes of humans with PKD is difficult, however, due to the restricted amount of material available for study. Several genetic and induced animal models, including diphenylamine-treated rats, have been employed to study the effects of PKD on basement membrane synthesis. While all these studies agree that PKD has a significant influence on basement membranes, no clear understanding as to how PKD effects basement membrane composition has emerged. Here, we report our findings of the effect of diphenylamine treatment on the composition of the basement membrane. Our immunohistological studies indicate that bamin, a recently described glycoprotein associated with glomerular basement membranes (Robinson et al., 1989), is not present in the glomerular basement membranes of diphenylamine-treated mice. This finding was confirmed by analysis of the composition of the basement membrane matrix synthesized by EHS tumors grown in control and diphenylamine-treated mice. The possible role of bamin in the pathogenesis of renal cysts is discussed.

Morphologic and growth effects of tobacco-associated chemical carcinogens and smokeless tobacco extracts on human oral epithelial cells in culture.

Epidemiologic studies show an increase in the use of smokeless tobacco but few in vitro studies have directly assessed the potential for smokeless tobacco-induced oral carcinogenesis. Oral keratinocytes were grown to 90% confluence from explants of human labial and gingival mucosa at 34 degrees C, 5% CO2 in defined media. Epithelial monolayers were subsequently subcultured and then treated for 1 hour with aqueous extracts of moist or leaf smokeless tobacco, or with 0.25 to 1.0 ng/ml of three common smokeless tobacco carcinogens: 4-(N-methyl-N-nitrosamino)-1-(3-pyridinyl)-1-butanone; N-nitrosonornicotine; and benzo(a)pyrene. Even though the controls and most treatment groups terminally differentiated, cells exposed to 4-(N-methyl-N-nitrosamino)-1-(3-pyridinyl)-1-butanone, N-nitrosonornicotine, and moist and dry extract continued to divide, maintained a differentiated phenotype for 8 1/2 to 10 weeks in culture, and displayed focal growth and morphologic changes suggestive of early stages in cell transformation.

Magnetic resonance spectroscopy of inflammation associated with the temporomandibular joint.

Noninvasive early recognition and treatment of temporomandibular joint dysfunction remains a diagnostic challenge. This pilot study evaluated the use of phosphorus 31 magnetic resonance spectroscopy with magnetic resonance imaging to measure alterations in pH and high-energy phosphate metabolite ratios of muscle that is adjacent to an inflamed temporomandibular joint. Ten New Zealand white rabbits were used in this study. Two animals were used to develop signal acquisition protocols and to ensure that stable baseline data could be measured. In each of the eight animals used in the experiment, one temporomandibular joint was injected with a suspension of silica particles and the contralateral joint served as a control. Data were collected from control and experimental joints on days 0, 7, 14, 21, and 28, after the injection. At the end of the study, temporomandibular joints were block resected and histologically examined to confirm the presence of an inflammatory response. Results indicated that pH and metabolite ratios could be obtained by 31P-magnetic resonance spectroscopy. Changes in pH and some metabolite ratios in experimental joints showed statistical significance (p < 0.001). Differences were seen on day 2 and day 7 (p = 0.040 and p = 0.008, respectively) in the phosphocreatine/alpha-adenosine triphosphate ratios. This contrasts with phosphocreatine/beta adenosine triphosphate ratios that showed significance that began at day 7 (p = 0.022) and continued to day 14 (p = 0.025). Histologic examination indicated that the tissue response within the joint capsule was less than the granulomatous reaction expected.(ABSTRACT TRUNCATED AT 250 WORDS)

Orofacial metastasis of pulmonary giant cell carcinoma.

A patient was admitted to the hospital with multiple skin nodules of recent origin and signs and symptoms suggestive of acute pulmonary infection. Because one of the skin masses was located overlying the left mandibular body region, the patient was referred to the hospital dentistry clinic for evaluation. Historical, clinical, and radiographic assessments were consistent with reactive lymphadenopathy, and an intraoral excisional biopsy was performed. The biopsy results were indicative of giant cell carcinoma, which was confirmed by biopsy results from a similar skin lesion on the shoulder and by malignant cells recovered in the sputum and pleural fluids. Although this carcinoma has been shown to rarely metastasize to the skin and lymphatics of the neck, this is the first case report of metastasis to facial lymphatics.

Characterization of a novel glycoprotein isolated from the basement membrane matrix of the Engelbreth-Holm-Swarm tumor.

A previously undescribed protein has been isolated and purified from the extracellular matrix of the Engelbreth-Holm-Swarm (EHS) tumor, a murine tumor that synthesizes an extensive matrix composed of basement membrane molecules. Molecular characterization of the molecule determined that it is a glycoprotein with internal disulfide bonds and an isoelectric point of 6.0. Electrophoretic mobility on sodium dodecyl sulfate-polyacrylamide gel electrophoresis indicated that the glycoprotein migrated as a diffuse band with a molecular weight of approximately 72,000-80,000. The amino acid composition was significantly different from known basement membrane components. Polyclonal antibodies that specifically recognize the glycoprotein localized it to the kidney glomerular basement membrane. These antibodies did not cross-react with either known basement membrane components (laminin, type IV collagen, and heparan sulfate proteoglycan), with 70K "culture shock" protein or with components of normal mouse serum (including mouse transferrin, albumin, or alpha-fetoprotein), when analyzed by "Western" immunoblots. Our data indicate that the glycoprotein is synthesized by the EHS tumor cells and is present at relatively high levels in the EHS tumor matrix.

Antibody testing and counseling of dental patients at risk for human immunodeficiency virus (HIV) infection and associated clinical findings.

Two hundred six dental patients were tested between 1985 and 1987 for antibodies to human immunodeficiency virus (HIV) when a review of their medical histories revealed a high risk for infection. Serologic results are correlated with soft tissue and osseous findings recorded during routine head and neck and radiographic examination. Counseling recommendations for use in association with testing are outlined. A more active role for the dentist as a preventive agent is advocated to combat the spread of acquired immunodeficiency syndrome (AIDS).

Compliance with guidelines for management of dental school patients susceptible to infective endocarditis.

The purpose of the investigation was to determine the extent to which the 1984 American Heart Association prophylaxis guidelines were adopted in a sample of dental school patients and to determine whether implementation strategies resulted in change in the management of patients at risk for infective endocarditis (IE). Dental records of 330 patients requiring medical consultation on the basis of a heart problem identified in the medical history questionnaire were reviewed. One hundred fifty-four patients required IE prophylaxis according to their physicians. Only 11 percent of IE-susceptible patient charts showed documentation of correct prophylaxis for every appointment at which a bacteremia was possible. Only 35 percent of patients receiving prophylaxis after December 1984 were covered according to the new American Heart Association guidelines.

Simultaneous occurrence of transitional cell carcinoma and urothelial adenocarcinoma associated with xanthogranulomatous pyelonephritis.

We report on a patient with xanthogranulomatous pyelonephritis, in situ transitional cell carcinoma, and focal prosoplasia revealing abrupt conversion of transitional epithelium to moderately well-differentiated adenocarcinoma. The etiology and pathogenesis of mucinous adenocarcinoma in the renal pelvis very likely involves the prosoplastic transition of pre-existing transitional carcinoma to adenocarcinoma. The urologist should be aware of the increased possibility of this tumor developing in a patient with longstanding infection, and frozen section should be performed more often because the gross structure of the tumor frequently appears normal. This permits the urologist to change his surgical strategy if frozen section is positive for tumor.

Diabetes mellitus and associated oral manifestations: a review.

Oral research concerning diabetes mellitus has revealed a number of clinical implications. These include, among others, the need for more intense management of the diabetic patient with periodontal disease because tissue destruction may be accelerated, the need for rapid control of oral infection in these patients in order to prevent exacerbation of the existing metabolic imbalance, and the desirability of performing a screening for diabetes mellitus on all patients exhibiting asymptomatic parotid enlargement. Despite the explosion of knowledge concerning diabetes mellitus that has occurred since the discovery of insulin, its definitive etiology continues to elude the scientific community and its treatment remains in the realm of clinical management rather than in that of prevention and cure. In the past, research on diabetes has focused on the role of insulin in seeking the fundamental etiology of diabetes and its complications. With the progression of research, it has become apparent that the initiation and progression of the disease probably involve the interplay of a multiplicity of factors. Hereditary and immunologic factors, as suggested earlier, appear to be operated on by environmental factors, subsequently altering the body's metabolic milieu with widespread primary and secondary effects. Fertile areas for future oral research in diabetes mellitus will include, therefore, genetics, immunology, enzymology, and basement membrane pathology. On the cellular and molecular levels, particularly, the oral cavity and associated structures comprise a somewhat under-investigated area in diabetes mellitus research and, thus, hold great promise for increasing our knowledge of this complex disease.