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.

Effects of herpes simplex virus on human oral cancer cells, and potential use of mutant viruses in therapy of oral cancer.

The herpes simplex virus type-1 (HSV-1) might be useful in treatment of oral cancer because it is strongly cytolytic, and its natural target tissue is the source of oral squamous cell carcinomas. Use of a wild-type virus would be limited by its spread and neurotoxicity, but it might be possible to develop mutants whose range could be restricted to oral cancers. Thus we have investigated the effects of HSV-1 on human oral cancer cells and have used both wild-type virus and a mutant that lacks UL42--an essential gene of the virus. Growth of the oral cancer cell line 686LN was readily inhibited by wild-type HSV-1, with only 10(2) plaque forming units (pfu) per milliliter required for 50% inhibition. In contrast, the mutant HSV-1 required a titer of 10(6) pfu/ml for 50% inhibition of growth. The mutant virus did, however, inhibit cell growth through the activation of ganciclovir and thus might be able to amplify its cytotoxicity through a bystander effect. When wild-type HSV-1 was injected into 686LN cells which were growing as tumors in nude mice, the virus spread through the tumor. Treated tumors were smaller, of lower weight, and significantly more necrotic than either untreated tumors or tumors which had been treated with the mutant virus. The wild-type virus spread to the skin and nervous system of most animals causing zosteriform skin rash, neurological symptoms and death, while the mutant virus produced none of these side-effects. These results show that HSV-1 might be used to treat oral cancer if its replication could be limited to the tumor cells, and that controlled expression of the UL42 gene would be one way to obtain that limitation.

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.

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.

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.

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.

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.

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.

Clinico-pathological conference 2002.

INTRODUCTION: Six cases are reported, each presented at the 11th Biennial Congress of the International Association of Oral Pathologists as an instructive case for differential diagnosis on the basis of clinical, imaging or histological features. CLINICAL PICTURE: Case diagnoses included a large, possibly intraosseous, myofibroma presenting with an oral mass; Langerhans cell histiocytosis with facial skin lesions; an intraosseous vascular hamartoma of the maxilla with worrying radiological features; an unusual mixed radiolucency of the jaw caused by cemento-ossifying fibroma; an osteosarcoma of the posterior mandible causing a well-defined radiolucency and an intraoral squamous cell carcinoma in a child.

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.

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.

Microgenomics of ameloblastoma.

Gene expression profiles of human ameloblastoma microdissected cells were characterized with the purpose of identifying genes and their protein products that could be targeted as diagnostic and prognostic markers as well as for potential therapeutic interventions. Five formalin-fixed, decalcified, paraffin-embedded samples of ameloblastoma were subjected to laser capture microdissection, linear mRNA amplification, and hybridization to oligonucleotide human 41,000 RNA arrays and compared with universal human reference RNA, to determine the gene expression signature. Assessment of the data by Significance Analysis of Microarrays (SAM) and cluster analysis showed that 38 genes were highly expressed (two-fold increase) in all samples, while 41 genes were underexpressed (two-fold reduction). Elements of the sonic hedgehog pathway and Wingless type MMTV integration site family were validated by immunohistochemistry. We have identified the expression of multiple genes and protein products that could serve as potential diagnostic, prognostic, and therapeutic targets.

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.

Abnormal binding of negatively charged serum proteins to diabetic basement membranes is largely a systemic phenomenon.

Direct immunofluorescence employing goat anti-human IgG, IgA, IgM, C3 component of complement, fibrinogen, albumin, and polyvalent immunoglobulins was performed on postmortem samples of gingiva, parotid gland, thyroid, kidney, and pancreas tissue of 15 diabetic and 15 control patients. Basement membrane thickness quantification of kidney tubules, gingival capillaries, and parotid gland ducts and acini was also done utilizing a calibrated magnifier on uniformly enlarged photomicrographs which had been specially stained to highlight basement membranes. Results revealed binding of IgG, albumin, and polyvalent immunoglobulin to kidney glomerular and tubular basement membranes and parotid ductal and acinar basement membranes in all diabetic subjects. Thyroid follicular basement membranes were positive in 8 of 15 diabetic patients for the same antisera. All gingival and pancreatic tissue from diabetic and control patients was negative for binding of all serum proteins tested. Basement membrane thickening in kidney tubules and gingival capillaries was observed in diabetic subjects; however, there was no apparent difference between diabetic and control patients in thickness of ductal or acinar basement membranes of the parotid gland.

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).

Parotid gland basement membrane variation in diabetes mellitus.

Post-mortem samples of parotid gland were obtained from 15 patients with a history of diabetes mellitus for a minimum of 5 years, and from 15 age- and sex-matched controls. The tissue was studied by direct immunofluorescence for abnormal binding of selected serum proteins, including IgG, IgM, IgA, C3, fibrinogen, polyvalent immunoglobulin and albumin, to acinar and ductal basement membranes of the gland. Thickness of these basement membranes was also assessed using a calibrated magnifier on uniformly enlarged photomicrographs of the tissue which had been stained by the chromotrope silver methenamine method to highlight basement membranes. Results of this investigation revealed parotid gland basement membrane abnormalities in all diabetic subjects as indicated by the binding of IgG, albumin and polyvalent immunoglobulins to ductal and acinar basement membranes. These basement membranes were uniformly negative in control subjects for the binding of all serum proteins tested. Binding of IgA was also noted in 7 of 15 experimental subjects, with 6 of these representing Type I diabetics. Basement membrane measurements revealed no difference in thickness between diabetic and non-diabetic subjects. Variations in parotid diabetic basement membranes evidenced in this study further substantiate the idea that membranopathy in this disease is systemic in nature.

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.

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.