P53 and cyclin D1 staining patterns of malignant and premalignant oral lesions in age-dependent populations.

OBJECTIVE: Recent epidemiologic studies have identified a trend of increasing cancer incidence in younger patients. The purpose of this study was to determine whether this might be reflected by different molecular mechanisms for tumor development. STUDY DESIGN: Dysplastic and malignant oral lesions from age-distinct patient populations were immunohistochemically analyzed for expression of p53 and cyclin D1. Chi-square analysis was used to determine statistical significance. RESULTS: Eighty-two percent of "older" and 75% of "younger" carcinomas stained positively with p53; 63% of carcinomas in the older population and 55% of carcinomas in the younger population showed cyclin D1 positivity. Dysplasias showed similar cyclin D1 staining in both groups. Interestingly, 100% of "younger" dysplasias stained positively for p53, whereas 35.3% of "older" dysplastic lesions showed immunoreactivity. Staining of carcinomas was not statistically significant, whereas p53 staining of dysplasias proved highly significant (P < .025). CONCLUSIONS: p53 immunoreactivity is detectable at an earlier stage of carcinogenesis in younger patients than in the traditional risk population for oral cancer.

Mucoepidermoid carcinoma of the major salivary glands: clinical and histopathologic analysis of 234 cases with evaluation of grading criteria.

BACKGROUND: The authors had previously conducted an investigation of minor salivary gland mucoepidermoid carcinoma, in which they demonstrated that certain clinical and histopathologic features were useful in predicting biologic outcome. The current study investigated the usefulness of these features in determining the prognoses of patients with mucoepidermoid carcinomas of the major salivary glands. METHODS: Clinical data and 15 histopathologic features were compared in 4 patient groups based on outcome after initial treatment. The outcome groups were 1) survival without disease, 2) survival with tumor recurrence only, 3) survival with metastasis, and 4) death related to tumor. A numeric score was assigned to each unfavorable histopathologic feature. Low grade tumors had scores of 0-4. Intermediate grade tumors scored 5 or 6. High grade tumors had scores higher than 6. RESULTS: Most patients (75%) were tumor free after the initial treatment. Twenty-one patients (9%) had local recurrence only, 12 (5%) demonstrated metastasis and survived, and 25 patients (11%) died of their disease. CONCLUSIONS: Clinical features associated with metastasis or death were more advanced age, tumor size, and preoperative symptoms. Histopathologic features that correlated with poor outcome were cystic component less than 20%, 4 or more mitotic figures per 10 high-power fields, neural involvement, necrosis, and anaplasia. All five of these histopathologic features demonstrated statistical prognostic significance when parotid gland tumors from Groups 1 and 4 were compared (P < 0.001). The point-based grading system demonstrated a statistically significant correlation with outcome for parotid tumors but not for submandibular tumors. The authors' findings indicate that patients with tumors of equal histopathologic grade have a better prognosis when their tumors are in the parotid gland than when their tumors are in the submandibular gland. Six of eight submandibular tumors that metastasized or resulted in death were low grade lesions, and none were high grade.

Salivary gland cystadenocarcinomas. A clinicopathologic study of 57 cases.

Current classification schemes for salivary gland neoplasms categorize cystadenocarcinomas on the basis of a recurring histomorphologic pattern of cystic, and often, papillary growth without features of other specific types of salivary gland tumors. To ascertain the clinicomorphologic spectrum and biologic behavior of this tumor, the clinicopathologic features of 57 cystadenocarcinomas from the files of the Armed Forces Institute of Pathology were studied. Excluding five Veterans Administration military cases, men and women were equally affected. Patients ranged in age from 20 to 86 years (mean, 58.8; median, 64), and patients aged over 50 years accounted for 71% of cases. Thirty-seven tumors (65%) occurred in major salivary glands, 35 in the parotid, and two in the sublingual glands. The 20 minor salivary gland tumors (35%) involved, in descending order, the lips, buccal mucosa, palate, tongue, retromolar area, and floor of mouth. Grossly, the lesions were cystic or multicystic masses that ranged in size from 0.4 to 6.0 cm. Microscopically, all tumors demonstrated an invasive, cystic growth pattern, and 75% had a conspicuous papillary component. The predominant cell type varied among tumors and included small cuboidal cells (35 cases), large cuboidal cells (nine cases), and tall columnar cells (seven cases). Six cases exhibited an admixture of cell types. Ruptured cysts with hemorrhage and granulation tissue were common. All 40 patients with follow-up data were either alive or had died of other causes and were free of tumor a mean interval of 59 months after their initial surgery. Three tumors recurred locally (mean interval, 76 months). Three tumors were metastatic to regional lymph nodes at the time of diagnosis, and one patient developed a regional lymph node metastasis after 55 months. Salivary gland cystadenocarcinomas represent a distinct group of malignancies that have an indolent biologic behavior.

An immunohistochemical analysis of anti-amylase antibody reactivity in acinic cell adenocarcinoma.

In many salivary acinic cell adenocarcinomas, well-differentiated serous acinar-type cells may be few and inconspicuous. In these cases it may be difficult to distinguish acinic cell adenocarcinoma from other types of salivary gland neoplasms such as cystadenocarcinoma. The usefulness of antisalivary amylase antibody immunohistochemical staining as a diagnostic aid was assessed on paraffin-embedded tissue sections from 27 typical acinic cell adenocarcinomas. Only 4 of 27 tumors showed reactivity in tumor cells. We conclude that anti-amylase antibody is of limited value in the recognition of acinic cell adenocarcinoma when light morphologic features are insufficient for diagnosis.

Atypical features in salivary gland mixed tumors: their relationship to malignant transformation.

Although criteria for distinction between the benign and malignant elements in carcinoma ex mixed tumor have been adequately described, there have not been any attempts to identify clinical or histologic features in benign mixed tumors that indicate increased risk of malignant change. For this reason, 65 mixed tumors of the major and minor salivary glands that exhibited atypical histologic features were examined in an attempt to analyze which, if any, of these features might indicate a greater likelihood of malignant transformation. The atypical features evaluated were hypercellularity, capsule violation, hyalinization, necrosis, and cellular anaplasia. The mitotic rate was also analyzed. The age of the patient, and the site, size, and prediagnostic duration of the tumor were recorded and, together with the histologic findings, were correlated with follow-up information. Nine (13.8%) of the 65 tumors underwent malignant transformation. Five of these patients died of the tumor, two others had distant metastases and were alive with the disease, and two were free of disease. Benign mixed tumors that showed prominent zones of hyalinization or at least moderate mitotic activity were more likely to develop carcinoma than those that did not. chi 2 analysis indicated that only hyalinization was significant (P < 0.05), but, with Fisher's exact test (two-tailed), this and all of the other features evaluated revealed a P value greater than 0.05. The other atypical features failed to correlate with malignant change. Clinical findings at the initial diagnosis that indicated a greater likelihood of malignant transformation were occurrence in the submandibular gland, older patient age, and large tumor size.

Tumor-associated lymphoid proliferation in the parotid gland. A potential diagnostic pitfall.

A substantial proportion of neoplastic and nonneoplastic parotid diseases have a prominent lymphoid component. The lymphoid element in lesions such as papillary cystadenoma lymphomatosum, sebaceous lymphadenoma, and lymphoepithelial carcinoma are readily recognized as a required diagnostic element. However, when other types of benign and malignant salivary gland neoplasms demonstrate tumor-associated lymphoid proliferation, the tumor may be either misclassified or misinterpreted as metastatic disease. Examples of primary benign and malignant parotid neoplasms exhibiting tumor-associated lymphoid proliferation are documented and illustrated. Other parotid lesions that may have a lymphoid element include sialadenitis, cysts with associated lymphoid tissue, parenchymal neoplasms with an expected lymphoid component or those that arise within an intraparotid lymph node, autoimmune disease, malignant lymphoma, and metastatic disease. An approach to recognition and separation of these entities is discussed.

Immunohistochemical analysis of basal cell adenocarcinoma.

Basal cell adenocarcinoma is a recently defined category of salivary gland neoplasms. As the terminology implies, this group of tumors has many histopathologic features that are similar to the more well-known basal cell adenomas. To better characterize these tumors, 23 basal cell adenocarcinomas were reviewed and compared with 11 basal cell adenomas with the use of light microscopic and immunohistochemical methods. Evaluation of cytokeratin, S-100 protein, glial fibrillary acidic protein, carcinoembryonic antigen, epithelial membrane antigen, smooth muscle actin, vimentin, B72.3, Ber-EP4, and milk fat globulin immunoreactivity was performed. Parallel to the morphologic similarity, the immunoprofiles of the basal cell adenocarcinoma and basal cell adenoma were quite similar. Both tumors showed reactivity patterns indicative of ductal epithelial and myoepithelial differentiation. In addition, reactivity to some polymorphic epithelial mucins was observed, which suggested glandular differentiation. The identification of antigens found normally in myoepithelial and epithelial cells supports the concept that these tumors are derived from pluripotential salivary gland epithelial cells. The comparable immunohistochemical profiles imply evolvement from similar cell lines and lead us to conclude that distinction between the two is not possible on the basis of these findings.

Mucoepidermoid carcinoma of intraoral salivary glands. Evaluation and application of grading criteria in 143 cases.

The histopathologic criteria most useful for grading of mucoepidermoid carcinomas are controversial. To identify those histologic features most important in the grading of intraoral mucoepidermoid carcinomas, 143 cases of this disease with clinicopathologic correlations were studied. Twelve histopathologic features of each tumor and their clinical presentation were correlated with patient outcome. Seven patients died of disease, 5 had regional metastases only, 10 had recurrences only, and 121 had no additional problems. Clinical features suggesting aggressive behavior were short duration, presence of clinical symptoms, and location of tumor in the tongue and floor of the mouth. The histopathologic features that indicated high-grade behavior were an intracystic component of less than 20%, four or more mitotic figures per ten high-power fields, neural invasion, necrosis, and cellular anaplasia. The simultaneous assessment of these features showed improved prognostic correlation over individual parameters. A quantitative grading system was devised using these features. Tumors with a point score of 0 to 4 were considered low grade, and none of 122 patients with scores in this range died of their tumor, although 9 had recurrences only and 3 had regional metastases. Point scores of 7 or above indicated highly aggressive behavior. Six of ten patients with these high scores died of tumor. Most of these six patients had recurrences and regional metastases, and all had distant metastases. Two other patients had regional metastases only. Scores of 5 to 6 were considered intermediate between low-grade and high-grade scores because only 1 of 13 patients with these scores died of disease. Three of the five patients with regional metastasis had low-grade tumors, indicating the inability of the grading system to identify them. Nonetheless, with an average follow-up on these patients of 10 years after treatment of the metastasis, no patient had additional problems. The relative objectivity of our proposed grading system for intraoral mucoepidermoid carcinomas may help achieve more accurate and consistent grading of these rare tumors.

Diagnosis of oral hairy leukoplakia by ultrastructural examination of exfoliative cytologic specimens.

Lingual exfoliative cytologic specimens (scrapings) were obtained from 18 patients positive for human immunodeficiency virus with clinical oral hairy leukoplakia. Buccal mucosal scrapings were obtained from 12 of these patients. The specimens were processed for examination by transmission electron microscopy (TEM). Sixteen (89%) of the lingual specimens revealed infection of keratinocytes by herpes-type virus. There was no evidence of virus infection in the 12 buccal mucosal scrapings. Fungal hyphae were seen by TEM in 14 (78%) of the lingual scrapings and two (17%) of the buccal scrapings. One exfoliative specimen and two biopsy specimens were stained for Epstein-Barr virus DNA with a DNA probe. The demonstration of herpes-type virions by TEM in keratinocytes from a lesion clinically suspected to be hairy leukoplakia provides direct, objective diagnosis. Furthermore, use of exfoliative cytologic specimens provides a clinically simple, noninvasive technique.

Virus-associated dysplasia (bowenoid papulosis?) of the oral cavity.

We are presenting a case of multifocal, virus-associated dysplasia of the oral cavity. We believe this case represents bowenoid papulosis, which usually is limited to the genital region. The patient, a 21-year-old white man, had recently completed therapy for Hodgkin's disease. An oral examination revealed multiple red 3 to 6 mm macules scattered over the oral mucosa, involving the buccal and labial mucosa, palate, and gingiva. The favored clinical diagnosis was candidiasis. Histologically, the biopsy specimen showed severe epithelial dysplasia. Three additional oral biopsies of different sites were performed and revealed similar histology. Immunohistochemical stains for human papillomavirus were done, and two of four lesions stained positively. Transmission electron microscopy revealed intranuclear viral particles consistent with human papillomavirus. Further questioning and examination of the patient revealed that he had lesions of the penis that were clinically and histologically bowenoid papulosis. In addition, he admitted to oral-genital sex during the period of therapy for Hodgkin's disease. This is the first reported case of oral bowenoid papulosis, and it supports a viral cause for this disease process.

Metastatic adenocarcinoma of the colon presenting as periradicular periodontal disease: a case report.

Metastases to the jaws account for only 1% of all malignant tumors of the oral cavity. Consequently the diagnosis of metastasis to the mandible requires a high degree of clinical suspicion and the use of a systematic diagnostic approach. In this case report a patient sought treatment for what appeared clinically and radiographically as periradicular periodontal disease. However, because the patient had a medical history of adenocarcinoma of the colon 5 years previously, metastasis to the jaws was included in the differential diagnosis. Metastasis to the jaws may resemble periodontal disease or many of the other benign and malignant conditions that affect the jaws, thus making the correct radiographic diagnosis difficult. Ultimately, histologic evaluation is essential to make a definitive diagnosis.

A clinical and histomorphologic comparison of the central giant cell granuloma and the giant cell tumor.

The clinical, histologic, and histomorphometric features of 42 giant cell tumors (GCT) of long bones and 49 central giant cell granulomas (CGCG) of the jaws were compared. These findings were also correlated with the clinical behavior of 25 cases of CGCG for which follow-up information was available. There was a female predilection for both lesions. The mean ages of patients with CGCG and GCT were 21 and 25 years, respectively. In contrast to CGCG, GCT rarely occurred in persons below the age of 10 years. The only statistically significant quantitative difference between the lesions at the histologic level was the greater number of nuclei in the giant cells of the GCT. There were four significant histologic differences between the two lesions, but 26% of the GCTs were histologically similar to most of the CGCGs and 10% of the CGCGs were histologically similar to most of the GCTs. Five of the 25 patients with CGCG for whom follow-up information was available had recurrences. The average age of those five patients was 11 years, compared to 29 years for those patients without recurrence. All five patients with recurrence were under 17 years of age, and they constituted 45% of the patients in this age group with follow-up. There were no quantitative or histologic differences between the recurrent and nonrecurrent CGCGs that were useful in predicting the likelihood of recurrence. Our findings suggest that the GCT and the CGCG represent a spectrum of a single disease process modified by the age of the patient and the site of occurrence.

An amalgam tattoo causing local and systemic disease?

Amalgam tattoos are common oral lesions. The case presented here involved a 33-year-old woman who had had an amalgam tattoo for 2 years and complained of localized soreness and occasional swelling as well as systemic symptoms of weight loss, fatigue, sinusitis, and headaches. After excisional biopsy of the lesion, the patient's complaints ceased dramatically. It is suggested that alterations in healing due to the presence of amalgam particles led to systemic as well as local disease.

Sarcomas and sarcomatoid neoplasms of the major salivary gland regions. A clinicopathologic and immunohistochemical study of 67 cases and review of the literature.

Sixty-seven cases of sarcomas and sarcomatoid neoplasms of the major salivary gland regions were studied in order to determine the clinical and histomorphologic features and biologic behavior. Fifty-seven of these proved to be sarcomas and the two most common types were malignant schwannoma (11) and fibrosarcoma (9). Nine sarcomas could not be subclassified morphologically. Ten cases, originally believed to be sarcomas, proved by means of immunohistochemistry to be either carcinomas (five cases) or melanomas (five cases). Fifty-nine of the 67 cases occurred in the parotid gland regions, and the remaining eight occurred in the submandibular regions. Twenty of the 67 cases were thought to arise from within the gland, nine from paraglandular tissues, and insufficient data was present to anatomically categorize the other 38 cases. The mean age of occurrence was 42 years for men and 38 years for women. A swelling was the presenting symptom in 64 cases, with a mean duration of 4.3 months. Pain, tenderness, or paralysis were noted in 17 cases, but the swelling was painless in seven cases. Follow-up data of 42 sarcoma patients revealed that 17 experienced recurrences, 16 developed metastases, and 15 died of disease. These rates were lowest among patients with tumors arising from within the gland (Group I) and highest among those patients with tumors of paraglandular origin (Group III). Mean survival time for those dying of disease was 2.4 years, and a 5-year survival time appeared to be a significant indicator of cure. The most successful therapy was either parotidectomy (superficial or total) or a combination of surgery and radiation. The morphologic and the immunohistochemical evidence suggest that the majority of the tumors represent true sarcomas that may arise from undifferentiated pluripotential cells, but that the remainder (15%) represent epithelial malignancies.

A comparison of freeze-dried allogeneic and fresh autologous vascularized rib grafts in dog radial discontinuity defects.

The limitations of autologous vascularized grafts include morbidity at the donor site and the increased surgical time associated with graft retrieval. To overcome these limitations, freeze-dried allogeneic and fresh autologous vascularized rib grafts were compared in 6-cm mid-radial defects of dogs. There was no statistically significant difference between the two graft systems when postoperative radiographs, in vivo intraarterial angiograms, and histologic evaluation of vessel patency were compared. However, clinical assessment of graft stability favored the autologous grafts, and force deflection tests revealed that the freeze-dried grafts had only 64% of the graft strength of the fresh autologous grafts at the end of the experiment at 26 weeks.

Altered H-antigen reactivity as an early indicator of malignant transformation in oral epithelium.

This study was undertaken to determine whether or not the blood group H-antigen reactivity of oral epithelium has value in predicting malignant transformation. Tissue from 3 groups of patients was studied retrospectively, using an immunoperoxidase technique. Two biopsy specimens from each patient, obtained at different times but from the same site, were examined for the presence of H-antigen. Group I consisted of 16 patients in which the initial biopsy was histologically benign, but the subsequent biopsy revealed epidermoid carcinoma. The initial biopsies in Groups II (17 patients) and III (17 patients) revealed epithelial dysplasia. Whereas the subsequent biopsy in Group II revealed carcinoma, the subsequent biopsy in Group III remained non-invasive. Normal epithelium from 64 patients was also studied. The results showed that in normal epithelium, H-antigen-negative cells are rarely seen, but 81% of the initial benign specimens of Group I showed antigen-negative areas. Therefore, it was concluded that altered H-antigen reactivity in histologically benign epithelium may serve to predict eventual malignant transformation, and that immunologic dedifferentiation precedes histologic dedifferentiation. A comparison between the initial biopsy specimens of Groups II and III yielded nearly identical results and showed that it was not possible, on the basis of the H-antigen reactivity, to predict which dysplastic lesions would progress to epidermoid carcinoma.