Nerve growth factor receptor (p75 NTR) and pattern of invasion predict poor prognosis in oral squamous cell carcinoma.

AIMS: To evaluate the expression of p75 neurotrophin receptor (p75(NTR)) in oral squamous cell carcinoma (OSCC). The results were related to tumour node metastasis (TNM) stage, World Health Organization (WHO) grade, invasive front grading (IFG) and prognosis. METHODS AND RESULTS: Immunohistochemically, the expression of p75(NTR) was assessed in 53 T1-T2 OSCCs. Clinical data were recorded prospectively. The end-point was disease-free survival. All tumours expressed p75(NTR), and this expression, both in central/superficial tumour areas and at the invasive front, was associated with poor prognosis (P = 0.03 and P = 0.02) (log rank test). Tumours with marked cellular dissociation (IFG parameter) had more recurrences than tumours with collective tumour cell invasion (P = 0.03). In tumours showing both p75(NTR) at the invasive front and marked tumour cell dissociation, the average risk of recurrence was increased about 17 times (Cox regression analysis) compared with tumours with low p75(NTR) expression and collective invasion. Traditional prognostic systems were of no prognostic significance. CONCLUSION: p75(NTR) was expressed in all OSCCs. p75(NTR) expression and the pattern of invasion were significantly associated with a poor prognosis in OSCCs, and both were better prognostic factors than traditional prognostic parameters. The combination of p75(NTR) expression and the pattern of invasion strongly increased precision in the identification of tumours with poor disease-free survival.

DNA content as a prognostic marker in patients with oral leukoplakia.

BACKGROUND: Oral leukoplakia may develop into squamous-cell carcinoma, which has a poor prognosis. Risk factors for oral carcinoma have been identified, but there are no reliable predictors of the outcome in individual patients with oral leukoplakia. METHODS: We identified 150 patients with oral leukoplakia that was classified as epithelial dysplasia and measured the nuclear DNA content (ploidy) of the lesions to determine whether DNA ploidy could be used to predict the clinical outcome. Biopsy specimens obtained at annual follow-up visits were graded histologically and classified with respect to DNA content in a blinded fashion. Disease-free survival was assessed in relation to DNA ploidy and the histologic grade. The mean duration of follow-up was 103 months (range, 4 to 165). RESULTS: Among 150 patients with verified epithelial dysplasia, a carcinoma developed in 36 (24 percent). Of the 150 patients, 105 (70 percent) had diploid (normal) lesions, 20 (13 percent) had tetraploid (intermediate) lesions, and 25 (17 percent) had aneuploid (abnormal) lesions at the time of the initial diagnosis. A carcinoma developed in 3 of the 105 patients with diploid lesions (3 percent), as compared with 21 of the 25 patients with aneuploid lesions (84 percent), yielding a negative predictive value of 97 percent with respect to the diploid lesions and a positive predictive value of 84 percent with respect to the aneuploid lesions. Carcinoma developed in 12 of 20 patients with tetraploid lesions (60 percent). The mean time from the initial assessment of the DNA content to the development of a carcinoma was 35 months (range, 4 to 57) in the group with aneuploid lesions and 49 months (range, 8 to 78) in the group with tetraploid lesions (P=0.02). The cumulative disease-free survival rate was 97 percent among the group with diploid lesions, 40 percent among the group with tetraploid lesions, and 16 percent among the group with aneuploid lesions (P<0.001). CONCLUSIONS: The DNA content in cells of oral leukoplakia can be used to predict the risk of oral carcinoma.

[Crohn disease of the oral cavity, illustrated by some cases]. / Crohns sykdom i munnhulen, belyst med noen kasuistikker.

BACKGROUND: We have several times experienced that Crohn's disease has not been diagnosed until several years after the start of oral symptoms. This article presents some patients with oral manifestations of Crohn's disease, as a contribution to more awareness of this possibility. MATERIAL AND METHODS: Clinical and histological data from four patients are presented. RESULTS: All patients had granulomatous inflammation of the oral mucosa. In three patients, the disease started in the mouth. The diagnosis of intestinal Crohn's disease was made from some months up to seven years later. In one patient, no granuloma was found in the intestinal tract, but the patient had intestinal symptoms. Two patients experienced disappointments in their contacts with the local health care system, with considerable delay in diagnosis. INTERPRETATION: We interpret these cases as evidence that a greater awareness of the possibility of Crohn's disease in the oral cavity may lead to a quicker diagnosis, earlier correct treatment, and less patient worry caused by uncertainty.

Glandular odontogenic cyst (sialo-odontogenic cyst): report of two cases and literature review of 45 previously reported cases.

The clinical, radiological, histopathological and immunohistochemical (cytokeratin) features of two cases of glandular odontogenic cyst (GOC) are presented and discussed in a review of 45 cases of GOC hitherto reported. Of cases with available information, 34 occurred in the mandible and 6 in the maxilla; the male:female ratio was 19:28, and the mean age was 46.7 years in males and 50.0 years in females. Six cysts recurred once after 2-8 years (mean 2 years 8 months) and 2 (5.3%) recurred twice after 2 and 5 years and after 3 and 5 years, respectively, giving a rate of recurrence of 21%. The identification of osteodentin in one of the present cases and the co-expression of cytokeratins (CK) 13, 19 and 8 strongly support the concept of odontogenic differentiation in the GOC. Careful surgical removal of the lesion succeeded by a 5-year follow-up period is recommended.

Is the carbohydrate sialosyl-Tn a marker for altered, non-malignant activity in squamous epithelium in the head and neck region?

Cell surface carbohydrates are involved in many cell functions such as cellular differentiation, adhesion, and invasion. A carbohydrate, sialosyl-Tn (STn), is expressed in many human carcinomas but generally not in normal epithelia. In the oral mucosa, however, STn has recently been observed on basal cells in some lesions with epithelial hyperplasia and dysplasia. The aim of this study was to carry out a systematic investigation of STn expression on epithelial basal cells in hyperplastic, 'borderline' malignant, and malignant head and neck lesions, to see if the expression of STn is associated specifically with hyperplastic conditions. Using the primary monoclonal antibody TKH2, normal controls did not reveal STn. STn was detected on probably post-mitotic basal cells in hyperplastic head and neck lesions and on basal cells adjacent to cancers, but not within the carcinomas. A Ki67 antibody reacted with basal cells in other locations. The most highly differentiated lesions, such as focal epithelial hyperplasia and verrucous hyperplasia, revealed a high percentage (86 per cent in both cases) of STn reactivity. The least-differentiated verrucous carcinomas (VCs) and keratoacanthomas (KAs) did not express STn, in contrast to the highly differentiated VCs and KAs. These findings indicate that STn-negative cases may have a greater malignant potential that the STn-positive cases. In conclusion, STn expressed on basal cells is possibly a marker for non-malignant conditions with altered basal cell activity and for highly differentiated verrucous carcinomas.

Relationship between age and deposit of peritubular dentine.

Peritubular dentine is a mineralised deposit formed centripetally in the dentine tubules with advancing age, so that the tubular diameter is smaller in teeth from older persons. The aim of the present study was to investigate the relationship between age in humans and the amount of peritubular dentine and the extent of the consequent obliteration of the tubules, and to find out whether this relationship was strong enough to be used as a parameter for age estimation. Fifty mandibular central and lateral human incisors were ground on the lingual aspect of the root and examined in a scanning electron microscope (SEM). The number of open tubules was counted and the diameter of the tubules measured both before and after etching with 35% orthophosphoric acid. The difference in the number of tubules in unetched and etched specimens was taken to be the number of occluded tubules, and the difference in radii before and after etching to be the thickness of peritubular dentine. The results did not demonstrate a significant relationship between age and the reduction in the number of tubules. One explanation might be that a certain age has to be reached before obliterated dentine tubules can be observed. The correlation between age and the thickness of peritubular dentine was not significant in teeth extracted because of periodontal disease, so these teeth were excluded from the regression analysis with age as the dependent variable.(ABSTRACT TRUNCATED AT 250 WORDS)

Mineralized deposits in pulps of incompletely developed permanent monkey incisors after pulpotomy with tungsten carbide fissure burs.

The exposed pulp of incompletely developed permanent incisors of nine monkeys were treated with partial pulpotomy with tungsten carbide fissure burs on an air turbine equipment. The pulps were capped with calcium hydroxide (Dycal) followed by insertion of conventional amalgam. The results were studied by conventional light microscopy after 1 and 6 months. Rod-like mineralized pulpal deposits were seen in five of the nine animals, in 9 out of 67 teeth, evenly distributed at the two observation times. Also the lengths of the deposits appeared similar, while the thickness had increased markedly after 6 months. After 1 month the presence of a central vessel lumen was observed in the deposits. The results seemed to indicate that the mechanism of formation was an initial pathologic mineralization of the vessel wall, and a growth of the deposits by the elaboration of fibrous, atubular dentin on to the outside of this wall.

Assessment in rats of a new bioerodible bone-wax-like polymer.

Holes drilled in rats' skull, iliac crest, and tibia were filled with beeswax or with a new, wax-like, bioerodible polyorthoester (Alzamer). Empty drill-holes served as controls. In addition, beeswax and polyorthoester were deposited between the left and the right oblique abdominal muscles, respectively. In muscle, both the beeswax and polyorthoester elicited a transient foreign body reaction. The beeswax was not resorbed in bone or muscle, whereas the polyorthoester was. Bone healing was inhibited in the iliac crest and the tibiae filled with beeswax, whereas holes filled with polyorthoester healed readily.

Distribution of blood-group-related carbohydrate antigens on oral endothelial cells.

Recent studies indicate that carbohydrate structures are involved in various endothelial functions such as inflammatory processes, adhesion of metastatic cells to endothelium and endothelial differentiation. In this paper we report the endothelial expression of various blood-group-related carbohydrate structures in normal oral mucosa using 15 different monoclonal antibodies reacting with type 1, 2 or 3 carbohydrate chains. Twenty biopsies, including normal oral mucosa, from secretor individuals comprised nine blood group O, nine A, one B and one AB. Endothelial staining was compared with epithelial staining in the same biopsies. Five blood-group-related carbohydrate antigens were detected on endothelial cells. The H type 2 antigen, which is the precursor of A, B and AB antigens, has previously been believed to be a universal marker for endothelial cells. All blood group O individuals (n = 9) showed strong H antigen staining in the endothelium of most vessels. However, of blood group A, B and AB individuals (n = 11), four showed heterogenous H antigen staining. In addition, we found that six out of ten blood group A or AB individuals, who expressed A or A and B antigens on spinous squamous cells and glandular epithelium, showed either heterogenous or no staining for these structures on their endothelial cells. It is concluded that there are differences between the biosynthesis of blood-group-related carbohydrate antigens in oral endothelium and epithelium.

Identification of common foreign material in postendodontic granulomas and cysts.

The present investigation was undertaken to identify commonly occurring foreign material in postendodontic periapical granulomas and cysts. 29 biopsies from such lesions with observed foreign material were routinely processed, stained with H&E, von Kossa and Calcofluor White and investigated by light, polarization and fluorescence microscopy. Applying back-scattered SEM images, the foreign material was subjected to energy dispersive X-ray analysis. 4 groups of foreign material were observed: 1. Black/brownish fragments and yellow/brown granules containing Au, Ag, Cu, Hg, Sn and Zn compatible with amalgam. 2. Fine black/brown/yellow granules compatible with endodontic sealer components revealing Ag, Ba, Bi, Cu, S, Ti and Zn. 3. Basophilic fragments compatible with Ca salts from Ca(OH), extruded periapically and containing Ca and P. 4. Elongated/rounded/oval/kidney-shaped, colourless to slightly basophilic, birefringent structures revealing C and O and with a slit-like central canal and a bright, pale-blue fluorescence specific for cellulose.

Malignancy grading of the deep invasive margins of oral squamous cell carcinomas has high prognostic value.

Several recent studies have indicated that cells at the invasive tumour margins often are different from cells within other parts of various human cancers. In this work, we have studied all squamous cell carcinomas of the floor of the mouth registered in Norway during the years 1963-1972 (N = 96). Borderline cases and cases given no treatment were excluded. Of the remaining 79 cases, biopsy specimens acceptable for histological grading were obtained from 61 patients. Only the most invasive margins of the tumours were histologically graded independently by two pathologists according to a multifactorial grading system. The results confirmed our previous findings that grading of invasive tumour margins is an independent prognostic factor in Cox's multivariate survival analysis (P less than 0.01). Inter-observer agreement was calculated by kappa statistics, and good agreement was obtained (kappa = 0.63). Neither agreement nor prognostic value was improved after calibration of the pathologists. Conventional Borders' grading of the whole biopsy had no prognostic value (P less than 0.38). We conclude that invasive cell grading may be of value for treatment planning of oral cancers, and that further studies of the deep, invasive parts of oral and other cancers are needed in order to obtain a better understanding of tumour cell invasion and metastasis.

Cytokeratins as epithelial differentiation markers in premalignant and malignant oral lesions.

The keratin expression pattern in oral stratified epithelium is related to the cellular differentiation level. The normal pattern shows the keratin pair K5 and K14 in the stratum basale whereas K1 and K10, or K4 and K13, are the two pairs associated with differentiating suprabasal cells. Monoclonal and polyclonal antibodies to individual keratins (K10, K13 and K14) were used in a two-color immunofluorescence staining method to study their coexpression in single cells. Altered keratin expression in premalignant and malignant lesions indicated abnormal differentiation. Monospecific keratin antibodies were suggested to be useful for evaluation of epithelial differentiation changes in oral dysplasias and oral squamous cell carcinomas.

Reproducibility of two malignancy grading systems with reportedly prognostic value for oral cancer patients.

Supplementary prognostic factors should be added to the TNM classification for oral squamous cell carcinomas in order to optimize its clinical value. We have recently published two prognostically valuable malignancy grading systems based on histopathology and immunohistology of the most invasive cells in oral squamous cell carcinomas (OSCCs). However, a major problem with classifications based on histologic features is frequent lack of interobserver agreement which limits the clinical value of subjective histologic classifications. Thirty-eight file cases of OSCCs were therefore graded by three pathologists according to criteria of the histologic malignancy grading system which includes 5 morphologic features, each graded from 1 to 4. Agreement was calculated by kappa statistics, which showed that interobserver agreement was not optimal, but significantly better than by chance alone. We also studied the reproducibility of grading of immunohistologic membrane expression of a tumor-associated marker (blood group antigen H), and found a similar level of agreement. We conclude that the clinical value of our grading systems will increase by improving reproducibility.

Aureobasidium infection of the jaw.

A 32-yr-old white North American male resident of Norway presented with an asymptomatic radiolucency first identified 3 yr after the removal of an impacted mandibular right third molar in Southern California 16 yr previously. Surgical exploration revealed an intraosseous cavity filled with a black, homogeneous, gelatinous substance thought to be foreign material, but which was diagnosed histologically as containing black yeasts. Cultivation of a microbiologic sample for 6 wk grew black yeast-like colonies. The yeast isolate was identified as an Aureobasidium species different from the typical A. pullulans. A blood sample was negative with regard to antibodies both with double diffusion technique and ELISA. Also, examination with respect to dermatologic manifestations gave negative results. Flucytocin 10 g/d was administered systemically for 30 d. Six months postoperatively bone regeneration was satisfactory radiologically.

Grading of nuclear pleomorphism in oral carcinomas. Higher prognostic value than stereological assessment of nuclear volume.

A more objective and reproducible grading system is needed in order to give better prognostic indicators and thereby offer improved treatment to oral cancer patients. Recently, simple objective stereological techniques for cellular estimates have emerged, of which the estimate of mean nuclear volume has shown a correlation with prognosis for various cancers. We have therefore measured the mean nuclear volume in 44 invasive buccal mucosal squamous cell carcinomas and related it to the survival of patients. The mean nuclear volume did not correlate with prognosis for these patients (p = 0.25). However, the nuclear polymorphism, which is subjective even though it is based on well-described criteria in a histopathological grading system, correlated significantly with prognosis (p = 0.03). These findings indicate that the traditional histopathological evaluation of nuclear polymorphism includes valuable prognostic information.

New malignancy grading is a better prognostic indicator than Broders' grading in oral squamous cell carcinomas.

The prognostic value of histopathologic grading of oral squamous cell carcinomas (SCC) has varied from not any to highly significant. We have retrospectively studied all (130) SCCs registered in Norway 1963-72 in the buccal and maxillary alveolar mucosa. From 68 of these cases biopsy specimens of acceptable quality were obtained. Broders' method of grading was compared with a modification of a recent malignancy grading system recommended by Anneroth et al. which was performed only within the histologically most invasive areas of the tumors. Cox's multivariate survival analyses showed that this grading in the invasive sites had highly significant prognostic value. Broders grade had no prognostic value. The stage of tumor had also prognostic value. These highly significant results indicate that the histologically invasive areas may be primarily responsible for the clinical behavior of the tumor, and this may be of importance for the choice of therapy for oral SCC.

In situ detection of human papillomavirus types 13 and 32 in focal epithelial hyperplasia of the oral mucosa.

17 cases of focal epithelial hyperplasia of the oral mucosa (FEH, Heck's disease) were investigated for the presence of human papillomavirus (HPV) nucleic acid sequences by means of in situ DNA hybridization using biotinylated DNA probes of HPV types 1, 6, 11, 13, 16, 18, and 32. Ten of 17 cases were positive for HPV 13 DNA in contrast to 6 of 17 positive cases obtained after application of the HPV 32 probe, with a double infection in one case. The results of our study suggest, that HPV 13 and HPV 32 are very specifically found in lesions of FEH and can be detected in a high percentage of cases using in situ hybridization.

Cellulose fibers from endodontic paper points as an etiological factor in postendodontic periapical granulomas and cysts.

Histological sections of eight periapical granulomas and cysts developing after conventional endodontic therapy and displaying faintly hematoxylinophilic, birefringent foreign bodies were investigated by light and polarization microscopy, scanning electron microscopy, energy-dispersive X-ray, and chemical analysis. In addition to a variably dense mononuclear infiltrate, the granulomas and cysts revealed varying amounts of giant cells associated with the birefringent foreign bodies. These structures were identified as cellulose fibers, most probably originating from endodontic paper points, which in our opinion can be held responsible for the initiation and perpetuation of chronic postendodontic periapical lesions.