Single ulcers on the tongue dorsum: differential diagnosis between paracoccidioidomycosis and squamous cell carcinoma.

BACKGROUND: Paracoccidioidomycosis (PCM) is the leading cause of death among systemic mycoses in Brazil. On the other hand, oral squamous cell carcinoma (OSCC) is the most prevalent malignant neoplasm of the mouth. Both lesions rarely affect the tongue dorsum and may share similar clinical characteristics. This study aimed to retrieve cases of single oral ulcers diagnosed as PCM or OSCC. MATERIAL AND METHODS: A cross-sectional retrospective study was conducted. All patients who had a single ulcer on dorsum of the tongue and confirmed diagnosis of PCM or OSCC were evaluated. RESULTS: A total of 9 patients (5 women and 4 men) were evaluated, 5 patients had OSCCs (mean age = 69,8 years old), and 4 patients PCM (mean age = 51 years old). Most of the lesions were infiltrated and indurated in the palpation exam. Duration ranged from 1 to 12 months (mean time of 5.2 months and 4.7 months for OSCC and PCM, respectively). OSCC was the main clinical diagnosis hypothesis. CONCLUSIONS: Although uncommon, PCM and OSCC should be considered as a diferential diagnosis hypothesis in infiltrated ulcers on the tongue dorsum. Iincisional biopsy is mandatory to confirm the diagnosis and indicate the appropriate treatment.

Superficial mucoceles in cancer patients: a retrospective series from a Stomatology unit.

BACKGROUND: The aim of this study is to relate all the superficial mucoceles found in a cancer center, described the association with oncological conditions, and discuss its etiology and pathology that we found in the past few years. MATERIAL AND METHODS: Sixteen cases of superficial mucocele were retrieved from the patients' records of the Stomatology Department of the A. C. Camargo Cancer Center, São Paulo, Brazil, and demographic and clinical data were collected from electronic medical records. RESULTS: There were 16 patients, 8 patients were men and 8 women, with ages varying from 26 to 70 years old. Superficial mucoceles were observed in patients submitted to head and neck radiotherapy (n=6), graft versus host disease (n=4), one associated with oral mucositis related to allogenic bone marrow stem cells transplantation (n=1), systemic lupus (n=1), Sjögren's syndrome (n=1), oral lichenoid lesion associated with pembrolizumab (n=1) and no local or systemic inflammatory associated found (n=2). CONCLUSIONS: This study reports a series of superficial mucoceles from a single stomatology unit. Most patients had superficial mucoceles secondary to head and neck radiotherapy and graft versus host diseases. However, two patients (12.5%) had mucoceles related to systemic inflammatory conditions (Sjögren's Syndrome and Systemic Lupus).

Computed tomography bone density variations in oncological patients undergoing antiresorptive medication.

BACKGROUND: The purpose of this study was to compare jaw and cervical vertebrae bone density in computed tomography (CT) analyses of oncological patients undergoing antiresorptive medication with control patients, aiming to find information that may assist the radiologist and clinician in predicting risks and monitoring osteonecrosis in the jaw. MATERIAL AND METHODS: Thirty-one patients treated with zoledronic acid and 37 control were included in the study. Two areas in regions of interest were chosen and standardized, one in the lower portion of the mandible and another in the axial cervical vertebra (C2) of patients undergoing antiresorptive drug treatment (experimental group) and the control group. Density analysis was performed using Hounsfield scale grayscale values obtained from multislice CT exams. Interclass correlation coefficient test (ICC) was performed to assess reproducibility and repeatability. The test of normality of the samples was demonstrated using the Shapiro-Wilk test and the comparison performed using Mann-Whitney U non-parametric test. RESULTS: When compared to patients in the control group, patients undergoing antiresorptive medication depicted an increase in bone density in both jaw bone (p=0.021) and cervical vertebrae (p=0.002). The same pattern could be observed in patients who used the medication on a monthly basis for analysis of jaw bone (p=0.021), the cervical vertebrae (p=0.002), and the cervical vertebrae of the patients who used the medication on a quarterly basis (p=0.003). CONCLUSIONS: CT can be a potentially useful method for detecting alterations associated with antiresorptive therapy, serving as a possible tool in the prediction of the disease progression.

Periodontitis as a risk factor for head and neck cancer.

BACKGROUND: Periodontitis may be associated with the development of head and neck cancer (HNC). A literature review was conducted to understand the possible association between them. MATERIAL AND METHODS: Articles published in the PubMed database from January 1999 and May 2020 were retrieved. Limitations of the studies and biological mechanisms were discussed. RESULTS: A total of 4,232 articles were found. Of these, 13 were analyzed according to inclusion criteria. Most papers found some association between periodontitis and HNC, although differences in periodontal evaluation, sample size, study design and tumor sites were observed. Porphyromonas gingivalis appears to increase the chance of both diseases, and it may be one of their main potential risk factors. Genetic predisposition is increased by exposure to environmental factors which can directly induce epigenetic changes that contribute to these diseases. CONCLUSIONS: Understanding the mechanisms related to periodontitis and HNC has increased, however, well-designed clinical studies are needed for better conclusions. Furthermore, the advent of multiple "omic" technologies will help comprehend their possible association.

Immunohistochemical evaluation of Sonic Hedgehog signaling pathway proteins (Shh, Ptch1, Ptch2, Smo, Gli1, Gli2, and Gli3) in sporadic and syndromic odontogenic keratocysts.

AIMS: The aim of this study was to compare the clinical and demographic features of 62 patients presenting sporadic odontogenic keratocysts (OKCs) or OKCs associated with nevoid basal cell carcinoma syndrome (NBCCS). In conjunction with this, we also evaluated the immunohistochemical expression of Shh, Ptch1, Ptch2, Smo, Gli1, Gli2 and Gli3 proteins in 86 OKCs. By doing this, we add to the understanding of the biology of this type of lesion, providing tools that will help facilitate the early diagnosis of NBCCS in those patients where the first manifestation is that of OKCs. METHODS: This is a retrospective study; patients were classified into two groups: group 1 which consisted of those who were not affected by NBCCS (49 patients and 57 OKCs) and group 2 which consisted of those who were diagnosed with NBCCS (13 patients and 29 OKCs). The clinical and demographic features were studied and the immunohistochemical expression of Sonic Hedgehog proteins (Shh, Ptch1, Ptch2, Smo, Gli1, Gli2, and Gli3) was analyzed in all samples. RESULTS: There was an increase in the expression of three proteins in the syndromic OKC, when compared to that of sporadic cysts. Shh and Gli1 showed higher cytoplasmic expression, while Smo revealed stronger nuclear and cytoplasmic expressions. CONCLUSION AND CLINICAL RELEVANCE: Our findings suggest that the expression patterns of important Shh pathway proteins can represent valuable markers for early diagnosis of NBCCS-associated OKCs, as the major criterion for the diagnosis of NBCCS is currently based on the late appearance of basal cellular carcinomas. Thus, standardizing a new diagnostic tool for diagnosis of NBCCS could be of great importance in the identification of therapeutic targets. We therefore suggest, as based on our findings, that OKCs showing high expression of Shh, Smo, and Gli1 are potentially associated with NBCCS.

Breast cancer patients have increased risk of developing mTOR inhibitor-associated stomatitis.

A total of 115 patients who used everolimus were evaluated. The mean age was 57 (±13.3) years old, and 87 patients were women (75.6%). mTOR inhibitor-associated stomatitis (mIAS) was observed in 36 patients (31.3%). The lesions ranged from 0.5 cm to 1.5 cm, and the tongue was the main site affected. In addition, 21 patients (58.3%) required a dose reduction of everolimus due to mIAS. Patients who had breast cancer presented 2.29-fold higher risk for developing mIAS when compared to patients with kidney or neuroendocrine tumors. This study emphasizes the high prevalence of mIAS in patients using everolimus, in particular, in patients with breast cancer.

Low efficacy of atopy patch test in predicting tolerance development in non-IgE-mediated cow's milk allergy.

BACKGROUND: The food atopy patch (APT) test has been used in previous studies to help the diagnosis of non-IgE mediated food allergies (FA). The aim of this study was to evaluate the efficacy of different cow's milk APT preparations to predict oral tolerance in children with previous non-IgE-mediated cow's milk allergy (CMA) diagnosis. METHODS: Thirty-two patients non-IgE-mediated CMA diagnosed by oral food challenge (OFC) were enrolled to perform APT with three different cow's milk preparations (fresh, 2% in saline solution, 2% in petrolatum) and comparing with a new OFC after at least three months of diet exclusion. RESULTS: Only six (18.7%) subjects presented positive OFC to cow's milk. No differences in gender, onset symptoms age, OFC age, Z-score, and exclusion period were found between positive and negative OFC patients. Preparations using fresh milk and powdered milk in petrolatum presented sensitivity equal to zero and specificity 92.3% and 96.1%. The preparation using powdered milk in saline solution showed sensitivity and specificity of 33.3% and 96.1%. Two patients presented typical IgE symptoms after OFC. CONCLUSION: Cow's milk APT presented a low efficacy to predict tolerance in patients with previous non-IgE-mediated CMA and should not be used in clinical routine. The presence of typical IgE reactions after OFC hallmark the necessity of previous IgE-mediated investigation for this patient group.

Implant osseointegration in irradiated bone: an experimental study.

BACKGROUND AND OBJECTIVES: The aim of this study was to evaluate the effect of radiotherapy on the osseointegration of dental implants in the tibia and the action of platelet-rich plasma (PRP) as an adjuvant therapy. MATERIAL AND METHODS: A total of 18 rabbits received two implants in each tibial epiphysis, totalizing 72 implants. The control group (group I) was composed by six rabbits and did not receive radiotherapy. The test groups (II and III) received a single dose of 1727 cGy. Group II was composed by six irradiated animals and group III by six animals that received irradiation and PRP during implant placement. The implant success rate, the bone-implant contact (BIC), and the bone volume were analyzed. RESULTS: There was no osseointegration in four of the implants, three in group II and one in group III. Total BIC was significantly higher in group I, when compared to the other groups. There was a significant difference of osteoid BIC only between irradiated animals (group II, 8.5%; group III, 4.7%; p = 0.001). On the other hand, the mineralized BIC was significantly higher in group I. Furthermore, group II had a lower mineralized BIC than group III (p = 0.002). Bone volume was higher in the control group (41.3%), followed by group III (33.4%) and II (25.1%), with differences between groups I and II (p = 0.001) and groups II and III (p = 0.022). CONCLUSIONS: The present study showed that both the bone volume and BIC were higher in the control group. However, the failure rates of the implants were low in both irradiated groups. The PRP was a positive adjuvant in the osseointegration process.

Oral granulomatosis-like lesions in liver-transplanted pediatric patients.

OBJECTIVE: This study evaluated oral mucosal lesions in liver-transplanted children. METHODS: A retrospective study was performed on pediatric patients who underwent liver transplantation between 2002 and 2009, at A.C. Camargo Hospital, Sao Paulo-SP. Alterations, such as polypoid lesions over the dorsum of the tongue, lip swelling, angular cheilitis, fissures of the lips, mucosal tags, cobblestone appearance, and fissures of the tongue, were considered as orofacial granulomatosis (OFG)-like lesions. All clinical data were collected from medical records. Descriptive analyses and logistic regression were used to characterize and identify OFG-like lesion predictors. RESULTS: Of the 265 transplanted children, 56.6% were female, and 64.1% had biliary atresia. Fourteen patients died as a consequence of the transplantation surgery and were therefore excluded from the analysis related to oral lesions. Hence, among 251 patients, 64 showed OFG-like lesions. The lesions occurred around 26 months after transplantation, and the only therapy that all the patients were receiving in common was tacrolimus. Furthermore, patients aged 12 months old or less at transplantation presented higher risk to present oral lesions. CONCLUSIONS: This study described specific oral mucosal lesions in liver-transplanted children. Such lesions have recently been described as a novel entity. Although young age at transplantation has been associated to its development, the etiology of this condition is uncertain.

Evaluation of low-level laser therapy in the prevention and treatment of radiation-induced mucositis: a double-blind randomized study in head and neck cancer patients.

The purpose of this prospective study was to determine the effect of the low-level laser in the prevention and treatment of mucositis in head and neck cancer patients. A total of 70 patients with malignant neoplasms in the oral cavity or oropharynx were evaluated. The patients were randomized into two low-level laser therapy groups: Group 1 (660nm/15mW/3.8J/cm(2)/spot size 4mm(2)) or Group 2 (660nm/5mW/1.3J/cm(2)/spot size 4mm(2)) starting on the first day of radiotherapy. Oral mucositis was assessed daily and weekly using the NCI and WHO scales. Oral pain was scored daily with a visual analogue scale before laser application. The patients in Group 1 had a mean time of 13.5days (range 6-26days) to present mucositis grade II, while the patients in Group 2 had a mean time of 9.8days (range 4-14days) (both WHO and NCI p=0.005). In addition, Group 2 also presented a higher mucositis grade than Group 1 with significant differences found in weeks 2 (p=0.019), 3 (p=0.005) and 4 (p=0.003) for WHO scale and weeks 2 (p=0.009) and 4 (p=0.013) for NCI scale. The patients in Group 1 reported lower pain levels (p=0.004). Low-level laser therapy during radiotherapy was found to be effective in controlling the intensity of mucositis and pain.

DNA sequencing of 13 cytokine gene fragments of Aotus infulatus and Saimiri sciureus, two non-human primate models for malaria.

Aotus and Saimiri are non-human primate models recommended by the World Health Organization for experimental studies in malaria, especially for vaccine pre-clinical trials. However, research using these primates is hindered by the lack of specific reagents to evaluate immune responses to infection or vaccination. As a step toward developing molecular tools for cytokine expression studies in these species, primer pairs for 18 cytokine gene fragments were designed based on human DNA sequences and used to amplify the corresponding genes in Aotus infulatus and Saimiri sciureus genomic DNA samples. IFNγ, TNFα, LTA, IL2, IL3, IL4, IL5, IL6, IL10, IL12, IL13, CSF2 and TGFß2 gene fragments were amplified and sequenced. Primer pairs for IL8, IL17, IL18, IL27 and MIF failed to generate amplification products. When compared to the available corresponding human and non-human primate sequences, most--except IL3 and IL4--showed identity degrees above 90%. Small variations in sequence can help to explain the failure to amplify certain genes or the amplification only at lower annealing temperatures as compared to human DNA samples for several primer pairs. The sequences made available provide the basis for designing molecular tools such as primers for real time PCR specific for A. infulatus and/or S. sciureus. The nucleotide sequences reported in this paper have been submitted to the GenBank nucleotide sequence database and have been assigned accession numbers DQ985386 to DQ985389, DQ989356 to DQ989369, FJ89020 to FJ89024, and FJ89029.

Impact of submandibular gland excision on salivary gland function in head and neck cancer patients.

Head and neck cancer surgery is often associated with neck dissection and usually includes the submandibular glands. Literature data related to remaining salivary gland function after surgery is scarce and controversial. A reduction in salivary output and increase in complaints of xerostomia have been suggested. However, a compensatory salivary mechanism has also been reported. The aim of this prospective study was to evaluate the effect of neck dissection (with submandibular excision) on salivary gland function measured by salivary flow rate and salivary gland scintigraphy. A total of 80 patients with head and neck tumors were evaluated. The surgery group was composed of 37 patients, who underwent submandibular gland resection, and the non-surgery group of 43 patients evaluated prior to radiation and/or chemotherapy treatment. Whole unstimulated and stimulated saliva collection and salivary gland scintigraphy were performed in all patients. Twenty-one percent of patients in the surgery group reported xerostomia, whereas 7% in the non-surgery group. The mean unstimulated salivary flow was 0.60 and 0.94 m/min for the surgery and non-surgery groups, respectively (p=0.008). Nevertheless, no statistical difference in the stimulated salivary flow was observed between the groups (p=0.26). In addition, the mean uptake and excretion rates for parotid and remaining submandibular glands also showed no statistical difference. The data of the present study support the contention that submandibular gland resection causes a decrease in unstimulated salivary volume. However, the residual submandibular glands in the surgery group showed similar function to that of submandibular glands in the non-surgery group. Consequently, the compensatory salivary mechanism seems not to be a possibility.

Patterns of demineralization and dentin reactions in radiation-related caries.

Radiation-related caries is a unique form of rampant decay and is a complication of head and neck radiotherapy that frequently causes generalized dental destruction and impairs quality of life in cancer patients. The aim of this study was to investigate the patterns of demineralization of caries in irradiated patients and to establish whether direct radiogenic damage to the dentition might be important in the progression of radiation-related caries. Teeth from patients who had concluded radiotherapy were examined histologically by polarized light microscopy, and the ultrastructure was examined by scanning backscattered electron microscopy. Cervical caries and incisal caries, a very unusual sort of lesion, were widely detected. Additionally, diffuse brown discoloration of the smooth surface of enamel was frequently observed. Polarized light microscopy suggested that these areas were incipient caries. Evidence of normal odontoblast function was observed in the detection of reactionary dentin and intratubular dentin deposition. In conclusion, radiation-related caries seems to have the same morphological and demineralization pattern as ordinary caries, with the presence of demineralized dentin, a translucent zone, dentin dead tracts, reactionary dentin and intratubular dentin deposition. Based on these findings, direct radiogenic destruction of the teeth seems to be not essential to the microscopic progression of radiation-related caries.

Fatty acid synthase expression in squamous cell carcinoma of the tongue: clinicopathological findings.

BACKGROUND: Overexpression of fatty acid synthase (FAS), the cytosolic enzyme responsible for the conversion of dietary carbohydrates to fatty acids, has been reported in several human malignancies and pointed as a potential prognostic marker for some tumors. This study investigated whether FAS immunohistochemical expression is correlated with the clinicopathological characteristics of oral squamous cell carcinoma (OSCC). MATERIALS AND METHODS: The clinical features of 102 patients with OSCC of the tongue treated in a single institution were obtained from the medical records and all histopathological diagnoses were reviewed. The expression of FAS was determined by the standard immunoperoxidase technique in formalin-fixed and paraffin-embedded specimens and correlated with the clinicopathological characteristics of the tumors. RESULTS: Eighty-one cases (79.41%) were positive for FAS. Microscopic characteristics such as histological grade (P < 0.05), lymphatic permeation (P < 0.001), perineural infiltration (P < 0.05), and nodal metastasis (P < 0.02) were associated with FAS status. A significantly lower survival probability for patients with advanced clinical stage (log-rank test, P < 0.001), lymph nodes metastasis (log-rank test, P < 0.001), presence of vascular permeation (log-rank test, P = 0.05), and perineural invasion (log-rank test, P = 0.01) was observed in the studied samples. CONCLUSION: The expression of FAS in OSCC of the tongue is associated with the microscopic characteristics that determine disease progression and prognosis.

Dental extractions and radiotherapy in head and neck oncology: review of the literature.

Management of irradiated patients with cancer in the head and neck region represents a challenge for multidisciplinary teams. Radiotherapy promotes cellular and vascular decrease that results in a low response rate in the healing. Consequently, surgical procedures in irradiated tissues present high rates of complication. Osteoradionecrosis (ORN) is the most severe sequelae caused by radiotherapy. It is associated with previous extractions especially those carried out post-irradiation. The management of this side effect is difficult and can result in bone or soft tissue loss, affecting the quality of life. The literature regarding dental extractions performed before and after head and neck radiotherapy was evaluated, focusing on indications, criteria, surgical techniques and adjunctive therapies such as antibiotics and hyperbaric oxygen. Osteoradionecrosis can be minimized by oral evaluation and care prior to irradiation and healing time which allows tissue repair until the commencement of radiotherapy. In dental extractions realized after irradiation, minimal trauma, alveolectomy, primary alveolar closure and adjunctive therapies are recommended. Patients must be evaluated before radiation therapy and at that time all unrestorable teeth and/or teeth with periodontal problems must be extracted to reduce the post-radiotherapy exodontias that contribute to ORN. Once dental extractions become unavoidable after irradiation, additional care is needed.

Low-energy laser therapy for prevention of oral mucositis in hematopoietic stem cell transplantation.

AIM: To evaluate the clinical effects of laser therapy on the prevention and reduction of oral mucositis in patients who underwent hematopoietic stem cell transplantation (HSCT). PATIENTS AND METHODS: From January 2003 to September 2004, 24 patients received prophylactic laser therapy (L+ group). The applications started from the beginning of the conditioning regimen up to day +2. The oral assessment was performed daily until day +30. This group was compared with historical controls, namely 25 patients, who did not receive laser therapy (L- group). RESULTS: All patients developed some grade of mucositis. However, the L- group presented initial mucositis by 4.36 days, whereas the L+ group presented it in 6.12 days (P = 0.01). The maximum mucositis occurred between day +2 and day +6 with healing by day +25 in the L- group and between day +2 and day +7 with healing by day +14 for the L+ group (P = 0.84). Laser therapy also reduced the time of oral pain from 5.64 to 2.45 days (P = 0.04), and decreased the consumption of morphine (P = 0.07). CONCLUSION: This study suggests that laser therapy can be useful in oral mucositis to HSCT patients and improve the patient's quality of life. However, controlled randomized trials should be performed to confirm the real efficacy of laser therapy.

Soroprevalência e fatores de risco para a leptospirose em cães de Campina Grande, Paraíba / Soroprevalence and risk factors for leptospirosis in dogs from Campina Grande, State of Paraíba, Brazil

Investigou-se a prevalência de leptospirose em cães da cidade de Campina Grande, PB, e realizou-se um estudo de fatores de risco para a infecção. Foram examinadas 285 amostras de soro sangüíneo de cães colhidas durante a campanha de vacinação anti-rábica animal, conduzida em setembro de 2003. O diagnóstico da leptospirose foi realizado pela técnica de soroaglutinação microscópica, utilizando-se uma coleção de 22 sorovares. Para a caracterização do sorovar mais provável, levou-se em conta a titulação e a freqüência. A prevalência encontrada foi de 21,4% (IC 95% = 16,8%-26,6%), com maior freqüência dos sorovares autumnalis (7,4%), copenhageni (6%) e canicola (2,1%). A análise de regressão logística multivariada mostrou que os fatores de risco para a leptospirose foram: idade superior a um ano (odds ratio = 3,00; P = 0,006), raça não definida (odds ratio = 4,02; P = 0,011) e ocorrência de enchentes (odds ratio = 2,32; P = 0,039).

The prevalence of leptospirosis was investigated in dogs from Campina Grande city, State of Paraíba, Brazil, and the risk factors for infection were analyzed. Two hundred and eighty five blood samples were collected from dogs during the rabies vaccination campaign, in September 2003. The diagnostic method run for leptospirosis was the microscopic agglutination test, using a batch of 22 leptospiral serovars. The most prevalent serovar was found crossing the results of frequency and titer of agglutinins. The prevalence was 21.4% (95% CI = 16.8%-26.6%) and most frequent reactant serovars were autumnalis (7.4%), copenhageni (6%) and canicola (2.1%). The multivariate logistic regression analysis showed that the risk factors for leptospirosis were: age older than one year (odds ratio = 3.00; P = 0.006), mixed breed (odds ratio = 4.02; P = 0.011) and occurrence of floods in the area (odds ratio = 2.32; P = 0.039).

Soroprevalência e fatores de risco para a leptospirose em cães de Campina Grande, Paraíba / Soroprevalence and risk factors for leptospirosis in dogs from Campina Grande, State of Paraíba, Brazil

Investigou-se a prevalência de leptospirose em cães da cidade de Campina Grande, PB, e realizou-se um estudo de fatores de risco para a infecção. Foram examinadas 285 amostras de soro sangüíneo de cães colhidas durante a campanha de vacinação anti-rábica animal, conduzida em setembro de 2003. O diagnóstico da leptospirose foi realizado pela técnica de soroaglutinação microscópica, utilizando-se uma coleção de 22 sorovares. Para a caracterização do sorovar mais provável, levou-se em conta a titulação e a freqüência. A prevalência encontrada foi de 21,4 (IC 95 = 16,8-26,6), com maior freqüência dos sorovares autumnalis (7,4), copenhageni (6) e canicola (2,1). A análise de regressão logística multivariada mostrou que os fatores de risco para a leptospirose foram: idade superior a um ano (odds ratio = 3,00; P = 0,006), raça não definida (odds ratio = 4,02; P = 0,011) e ocorrência de enchentes (odds ratio = 2,32; P = 0,039).

PCNA, Ki-67 and p53 expressions in submandibular salivary gland tumours.

Salivary gland tumours are uncommon with a broad heterogeneity. The most common benign tumour is the pleomorphic adenoma, whereas mucoepidermoid carcinoma and adenoid cystic carcinoma predominate among the malignancies. Most salivary gland tumours occur in the parotid, and consequently clinical and biological data are normally derived from this site. This work describes the expressions of PCNA, Ki-67 and p53 in 15 pleomorphic adenomas, 15 mucoepidermoid carcinomas and 15 adenoid cystic carcinomas of the submandibular gland. Our results showed that all pleomorphic adenomas were negative for p53 and Ki-67 with 66.6% being positive for PCNA. Conversely, p53 was positive in 53% of the mucoepidermoid carcinomas and in 20% of the adenoid cystic carcinomas. Ki-67 was expressed in 47.7% of the mucoepidermoid carcinomas and 40% of the adenoid cystic carcinomas. All malignant tumours were positive for PCNA. These results indicate that the proliferative rate analysed with PCNA and Ki-67 and the expression of p53 in pleomorphic adenoma and adenoid cystic carcinoma of the submandibular gland were similar to those described in the parotid and minor salivary glands. However, mucoepidermoid carcinomas showed higher expression of these markers than those of other salivary glands. This work is the first describing the expression of these immunohistochemical markers exclusively in submandibular salivary gland tumours.