Apparent inhibition of apoptosis by polyamines and aminothiols in DNA fragmentation assays is artifactual.

We report that, in commonly used DNA fragmentation assays, polyamines and the radioprotective aminothiol WR1065 artifactually depress the degree of spontaneous or induced cellular apoptosis in two distinct ways. Firstly, in assays utilizing Hoechst 33258 dye to measure apoptotic DNA, both amines quench the fluorescence of low affinity dye/DNA binding resulting in preferential underestimation of DNA in the apoptotic DNA fraction and a resultant underestimation of the extent of DNA fragmentation. Secondly, these amines can cause aggregation and condensation of apoptotic DNA, causing anomalous sedimentation under conditions universally employed to separate apoptotic from intact DNA in cell lysates. This anomalous sedimentation of apoptotic DNA leads to underestimation of fragmentation in fluorescence assays as well as in agarose gel assays. We demonstrate that manipulation of the ionic strength of the lysis buffer or lowering the dye concentration ameliorates the effects of dye quenching in the Hoechst assay. Alternatively, this effect is alleviated by substituting DAPI for Hoechst in this assay. Inclusion of a polyanion to the lysis buffer antagonizes the condensation and anomalous sedimentation of apoptotic DNA observed regardless of which dye is used in the assay. These studies call into question the validity of previously reported studies suggesting that polyamines and the radioprotective aminothiol, WR1065, inherently suppress the apoptotic process and underline the need to consider alternative endpoints of apoptosis such as morphology in order to assess effects on cellular apoptosis of exogenously added agents, particularly di- or polycations.

Neuroepithelial hamartoma of the oral cavity.

We report a previously undescribed gingival lesion composed of squamous epithelial islands in close association with bundles of nonmyelinated nerves. A review of the pertinent literature is presented and the histologic differential diagnosis is discussed. We suggest the term neuroepithelial hamartoma for this lesion.

Leiomyoma of the oral cavity: a light microscopic and immunohistochemical study with review of the literature from 1884 to 1992.

Leiomyoma is the most common benign neoplasm in the uterus and stomach but is rare in the oral cavity. There were only 5 oral cases in a series of 7748 leiomyomas of all sites. Benign smooth muscle neoplasms are classified into leiomyoma (solid leiomyoma), angiomyoma (vascular leiomyoma) and epithelioid leiomyoma (leiomyoblastoma). 6 cases diagnosed as leiomyoma were retrieved from the files of two oral biopsy services over the past 25 years. A light microscopic study including trichrome and phosphotungstic acid haematoxylin (PTAH) stains, and an immunohistochemical study with the following markers: desmin, muscle specific actin, myoglobin, vimentin, S-100 protein, neuron-specific enolase, factor VIII and Ulex europeus were done with suitable controls. The haematoxylin and eosin and Masson's trichrome stains supported a diagnosis of leiomyoma in all 6 cases but PTAH was positive in only 3 of them. The immunohistochemical study confirmed the diagnosis of leiomyoma in 3 cases. The other 3 were identified as granular cell tumour, myofibroma and neurofibroma, respectively. The review of the literature contributed the following data: mean age was 41 and median age 39 in 134/142 patients. A male sex prevalence 72/137 patients (54.0%) was noted. The lips were the most common site with 39 cases (27.46%) followed by the tongue 26 (18.30%), cheeks and palate 22 (15.49%), gingiva 12 (8.45%), and mandible 8 (5.63%). Prognosis of oral leiomyomas is excellent. Immunohistochemistry is a precise and reliable method for definitive diagnosis of oral leiomyoma.

Squamous odontogenic tumor. Report of three cases including the first extraosseous case.

Squamous odontogenic tumor is a distinct entity-separate from the more aggressive ameloblastoma. Only 33 squamous odontogenic tumors have been reported since the first description in 1975. We report three additional cases including the first completely extraosseous case.

Malignant transformation of peripheral ameloblastoma.

A peripheral (extraosseous) ameloblastoma was excised from the maxillary left tuberosity of an 82-year-old man. It recurred twice over a 5-year period, once as squamous cell carcinoma and again as undifferentiated carcinoma. Analysis of the literature suggests that peripheral ameloblastomas may have the same potential for malignant transformation as intraosseous ameloblastomas.

Metastatic papillary endometrial carcinoma of the tongue. Case report and review of the literature.

Tongue metastases are exceptional, with a frequency of 0.1% to 0.2% in autopsy series of patients with disseminated cancer. A case of secondary papillary endometrial carcinoma of the tongue is reported as the first sign of metastasis in a 78-year-old white woman treated 7 years before by complete hysterectomy and radiotherapy. The lesion presented as a 3 x 3-cm submucosal mass of the dorsum of the tongue. Fine-needle aspiration and excisional biopsy established the diagnosis. Metastases to the lungs, liver, and bone developed 3 months later, and she died 6.5 months after initial diagnosis. A review of reports of 77 lingual metastases showed that the mean age was 57 years, with a male predominance. The lung, kidney, and skin were the most common primary sites. The tongue was the first site of metastases in 61% and the first sign of the primary malignant neoplasm in 15% of the cases. Average survival was 10 months.

Oral and pharyngeal adenosquamous carcinoma. A report of four cases with immunohistochemical studies.

Four cases of adenosquamous carcinoma from the oral and pharyngeal cavities were analyzed by light microscopy and immunohistochemistry. Lymph node metastases were present in three cases. One patient died 2 years after treatment. All four carcinomas presented a mixture of squamous and glandular mucus-secreting neoplastic elements. Immunostaining for high-molecular-weight cytokeratins (KL1) was constantly positive in both squamous and glandular tumor cells. Antibodies against low-molecular-weight cytokeratins (K19) and carcinoembryonic antigen were positive only in the glandular component. The histological aspect and the immunohistochemical phenotype of these tumors is similar to the ordinary squamous cell carcinoma and adenocarcinoma, respectively.

Eosinophilic ulcer.

A 10-year review of biopsy accessions revealed 15 cases of eosinophilic ulcer. Six manifested recurrent or multiple lesions, and two exhibited histologic atypia. The possible relationships to other oral and systemic diseases are discussed.

Odontogenic epithelial hamartomas in periodontal structures.

4 hamartomas apparently derived from remnants of the dental lamina and enamel organ are reported in a collection of human jaw specimens. These epithelial lesions represent a transitional stage between a developmental anomaly and a distinct odontogenic neoplasm. Earlier reports indicated that such lesions with clinical symptoms are rare; however, this study suggests a more common occurrence on a microscopic level.

Sinus histiocytosis with massive lymphadenopathy (Destombes-Rosai-Dorfman syndrome) occurring as a single enlarged submandibular lymph node: a light and immunohistochemical study with review of the literature.

Sinus histiocytosis with massive lymphadenopathy (SHML) is primarily a disease of children and young adults in which there is a pronounced and persistent cervical lymph node enlargement that usually is bilateral and is accompanied by fever. The histology, which varies according to the stage of the disease, is characterized by an exuberant intrasinusoidal histiocytic proliferation. The present case involves a 4-year-old girl who had several episodes of upper respiratory infection and otitis media; subsequently, a walnut-sized enlargement developed in the left anterior portion of the neck. Results of a physical examination were essentially normal. A laboratory work-up was noncontributory. Serologic tests for toxoplasmosis, infectious mononucleosis, and cat-scratch disease were negative. Immunoelectrophoresis disclosed normal values for IgG, IgM, IgA, and IgE. The histopathology was characteristic of SHML. The lymph node demonstrated pericapsular and capsular fibrosis and widely dilated subcapsular, trabecular, and medullary sinuses packed with histiocytes and plasma cells. "Lymphophagocytosis" and large atypical histiocytes resembling Reed-Sternberg cells were noted. Immunohistochemistry demonstrated a polyclonal population of plasma cells mostly stained with rabbit anti-human igG. The cytoplasm of the histiocytes, having ingested lymphocytes, was positively stained for IgG. Other groups of lymph nodes were affected during the next several months. The patient's condition has now been followed for 2 years, and the lymphadenopathy has almost completely regressed. The site distribution of the head and neck extranodal manifestations of SHML was analyzed in 54 cases.

Hodgkin's lymphoma of the oropharyngeal region: report of four cases and diagnostic value of monoclonal antibodies in detecting antigens associated with Reed-Sternberg cells.

In a review of more than 500 cases from the Lymphoma Registry, Department of Anatomic Pathology, University Hospital Purpan, Université Paul Sabatier, Toulouse, France, four cases of primary lesions in the oropharyngeal region were found. There were two lesions in the palatine tonsil, one in the nasopharynx, and one in the parotid gland. The average age of the patients was 54.5 years (range, 37 to 70 years), and all patients were men. The histologic types were lymphocyte predominance (one case), nodular-sclerosis (one case), and mixed cellularity (two cases). The patients were respectively staged as IAa, IIAa, and IIIA. They were treated with radiation, chemotherapy, or both. All four patients are now free of tumor and have been followed from 18 months to more than 6 years after definitive diagnosis and appropriate therapy. Immunohistochemistry significantly contributes to the differential diagnosis of atypical Hodgkin's disease from non-Hodgkin's lymphomas, especially in extranodal sites. Dako-EMA and Leu-M1 monoclonal antibodies are reactive, respectively, with L and H variants (Dako-EMA+, Leu-M1-) in the lymphocyte predominance type (Type 1) and with Reed-Sternberg cells (Dako-EMA-, Leu-M1+) in the nodular-sclerosis (Type 2), mixed cellularity (Type 3), and lymphocyte depletion (Type 4) types.

Periapical cemental dysplasia and periodontal disease. A case report with review of the literature.

The patient reported here was seen with periapical cemental dysplasia (PCD) superimposed on chronic inflammatory periodontal disease. Various aspects of the diseases and their relationships are reviewed, including the diagnosis of PCD, its significance, and suggestions for therapy.

Prevention of cancer of the oral cavity and pharynx.

Multiple environmental factors and a multistage pathogenic mechanism appear to be involved in oropharyngeal carcinogenesis. Tobacco and alcohol are the most important risk factors, but other agents may also contribute to malignant transformation. Individual susceptibility to environmental carcinogens, although significant, is still incompletely understood. Based on our present-day knowledge of risk factors, prevention should be possible in about two thirds of all oropharyngeal cancers. It cannot be achieved, however, without both public and professional education. A rational approach to prevention of oropharyngeal cancer should start in school before habits are formed, continued throughout adolescence, and reinforced in adults. Reduction or elimination of risk factors is of prime importance. For those who cannot quit tobacco, a reduction of tar content in cigarettes, cigars, pipes, and chewing tobacco, and elimination of nitrosamines, especially from smokeless tobacco, might also help to reduce risks. Control of chronic alcoholism is more difficult, but diet supplementation, especially with proteins, vitamins, and trace metals, would decrease the promoter effect of alcohol. Control of occupational risks is of less significance. The clinician must have a state-of-the-art understanding of all known risk factors for the prevention, early detection, and control of oropharyngeal cancer. The history should review in detail exposure to tobacco, alcohol, actinic radiation, and other agents. Age of first exposure or onset of habit; duration (years); quantity of tobacco smoked, chewed, or snuffed; and its relationship with the anatomic site at risk should all be precisely recorded. Exposure to alcohol or any other risk factor should be evaluated in the same way. This review has emphasized the relationship between the various risk factors and the site prevalence of malignant lesions. Habits, customs, and cultures, as well as anatomic physiologic factors, all have a bearing on the actual target sites at which the carcinogen(s) and promotor(s) are brought in contact with the oral mucosa. Habits and customs vary widely, both geographically and among individuals. Dentists and physicians should be aware of these individual factors as they examine their patients.

Experimental lathyrism: exostoses and aneurysmal-like bone cysts of the mandible in the rat.

The effect of chronic lathyrism on the mandible of the rat was studied. Exostoses, thinning and discoloration of the cortical plates, intraosseous bleeding and hemorrhagic cyst were observed after six weeks of administration of beta-aminoproprionitrile fumarate. The exostoses consisted of homogeneous cellular fibrous tissue containing osteoid, hyalin-like material and abundant ground substance. The cysts were filled with erythrocytes and lined by spindle-shaped fibroblasts, collagen fibers or osteoblast-like cells. Between the cysts, bands and sheets of dense and cellular connective tissue presenting foci of hemorrhage, osteoid and metaplastic cartilage were found. Numerous mast cells were demonstrated with alcian and toluidine blue in the hematopoietic bone marrow, cancellous bone and around the capillary network surrounding the exostoses and cysts. Exostoses have already been studied and explained by the action of BAPN (lysyl oxidase). Hemorrhagic cysts could be explained by histamine release from the mast cells (hypervascularity, hyperemia, increased permeability, rupture and progressive confluence of these small hemorrhagic cysts). Histopathology of the experimental cysts had some points in common with the human aneurysmal bone cyst. Could the pathogenic mechanisms be similar for both lesions?

Gingival salivary gland choristoma. Report of a case.

A unique example of a gingival salivary gland choristoma together with a gingival cyst is described in a human autopsy specimen of periodontal tissues. A choristoma is a tumor-like growth which is derived from primordial cells which have been displaced from their original tissue or organ. Only 6 other examples of the gingival salivary gland choristoma have been described in the world literature.

Odontogenic fibroma of the complex (WHO) type: report of six cases.

Six cases of the complex (World Health Organization) type of odontogenic fibroma are described. The relationships of these lesions to the simple type of odontogenic fibroma, desmoplastic fibroma, and to certain reactive lesions are discussed.