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A hamartoma is a benign proliferation of typical mature cells specific to a particular anatomical site. In the oral cavity, they may occur as isolated cases or be associated with genetic syndromes. Oral-facial-digital syndrome type VI is a rare genetic disorder with an estimated incidence of one in 50,000-250,000 newborns. Here, we report a case of a 2-year-old boy diagnosed with oral-facial-digital syndrome type VI who was referred for evaluation of a bilateral and normochromic to slightly pinkish nodule on the lateral surface of the tongue. Clinically, the child presented hypotonia, low visual acuity, absence of oculocephalic reflex, delay in neuropsychomotor development, and polydactyly in the feet. Excisional biopsies of both sides of the tongue were performed using a 1.5 W high-power diode laser (wavelength of 980 nm), and histopathological analysis revealed abundant mature adipocytes predominantly arranged in lobules that mainly surrounded the minor salivary gland parenchyma. The surgical sites healed with no complications and the patient remains under follow-up for 10 months. Due to the limited literature on this syndrome and the frequent presence of tongue hamartomas in children, dentists need to be familiar with them.

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BACKGROUND: The present study aimed to analyze the histopathologic aspects of cases diagnosed as chronic hyperplastic candidiasis (CHC) in an oral pathology service, pointing out the most important features found. METHODS: All cases histopathologically diagnosed as CHC between 2002 and 2018 were retrieved from the files of the service. Data of the patients and the lesions were collected. Histopathological analysis was performed to evaluate the microscopic characteristics and the amount of Candida present. RESULTS: Thirty-six cases of CHC were retrieved. Women were more affected and there was a predilection for Whites. Most lesions appeared as a nodule or a white plaque, asymptomatic, on the tongue or buccal mucosa. Histopathologically, statistical significance was noted for the presence of epithelial hyperplasia, exocytosis, and mononuclear inflammatory infiltrate. Interestingly, only the association between dysplasia and the amount of fungus was noted. CONCLUSIONS: CHC appears to be a distinct entity presenting typical histopathologic aspects. CHC might even show epithelial dysplasia. In those cases, the presence of a large amount of Candida together with other histopathological features should lead to the diagnosis of CHC and subsequent treatment. However, close follow up is important.

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Hyaline ring granuloma (HRG) is a rare and atypical foreign-body granulomatous chronic inflammatory condition. Our aim was to make a critical review of the literature cases and also to illustrate histochemical and immunohistochemical findings of a new case. A modified PICO strategy was used. Inclusion criteria were met by case reports and case series with a histologically confirmed diagnosis of HRG, necessarily in mouth or maxillary bones. Exclusion criteria were no access to the full-text paper. The search was done up to 2019, totalizing 231 selected cases in 54 papers. The new case was analyzed through PAS, Azan-Mallory's trichrome, and CD34 and CD68 reactions. HRG is found mainly in the mandible of men, edentulous and prosthesis users, between 51 and 60 years of age, with 0.5-120 months of duration, usually causing edema and pain or discomfort. Endogenous and exogenous theories may be complementary in HRG. Eosinophilic areas could represent particles of vegetal origin, while the hyaline material could be the result of collagen degradation. Considering the material is not always present or even is ring-shaped, we suggest the change from "hyaline ring granuloma" to "granuloma induced by vegetal inoculation."

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PURPOSE: To investigate the expression of upstream and downstream targets of mTOR signalling pathway in the secretory carcinoma of salivary gland origin (SCsg). METHODS: Seven cases of secretory carcinoma diagnosed by a combination of immunohistochemistry and/or molecular testing were retrieved from our pathology files. For comparison purposes, 27 other salivary carcinomas were selected. Immunohistochemical staining was performed against phospho-Akt, PTEN, phospho-mTOR, phospho-4E-BP, eIF4E and phospho-S6 ribosomal protein. RESULTS: With the exception of Akt, all the other proteins were present at some level in the SCsg and in other salivary carcinomas. PTEN was diffusely expressed in 57.1% of SCsg, but only in 14.8% of other salivary carcinomas. mTOR is expressed in more than half of the cases both for SCsg and other salivary tumour types. Most cases of SCsg showed negative expression for S6 ribosomal protein (71.4%) and 4E-BP1 (57.1%). For both groups evaluated, eIF4E was the most expressed protein. CONCLUSION: SCsg shows different expression patterns for the mTOR signalling molecules, but only eIF4E was highly expressed. This may suggest alternative signalling pathways other than Akt and mTOR in this group of tumours.

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We present the frequency of cases of isolated odontogenic keratocysts submitted to microscopic examination at 10 Brazilian referral centres in Oral and Maxillofacial Pathology. In a retrospective (1953-2017) analysis, data on clinicoradiographic features and treatment of these lesions were collected and analysed descriptively. Among the 258,867 cases retrieved, 2,497 (0.96%) were isolated odontogenic keratocysts. In summary, an overview of individuals affected with isolated odontogenic keratocysts is reported herein. This lesion showed predilection for the posterior mandible of young adult men.

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Differential diagnosis among fibrous dysplasias, cemento-ossifying fibromas and cemento-osseous dysplasias is difficult, since there is considerable overlap of histologic features, but also extremely important, since they differ greatly in etiology, clinical behaviour, prognosis and terapeuthic approach. There is no data about the use of immunohistochemistry, a viable and accessible technique, for this purpose. The objective of this study was to investigate, comparatively, the immunohistochemical expression of major non-collagenous proteins (osteonectin [ON], osteopontin [OP], bone sialoprotein [BSP] and osteocalcin [OC]) of mineralized tissue extracellular matrix in 22 cases of fibrous dysplasias, 16 of cemento-ossifying fibromas and 16 of cemento-osseous dysplasias. ON maintained the same expression profile in all cases; the staining for OP was negative in fusiform cells producing cementoid globules and weak, as well as heterogeneous, in high mineralized matrixes; there was negativity for BSP in cementoid globules and in the fusiform cells that produce them, differently from the strong positive expression found in the majority of bone trabeculae and their peripheral cuboidal osteoblasts; and finally, the immuno-reactivity for OC was weak, except in cuboidal osteoblasts and osteocytes. We can conclude that the nature of mineralized structure and the cellular phenotype are much more responsible for variability in immunohistochemical profile than the type of lesion (fibrous dysplasias, cemento-ossifying fibromas and cemento-osseous dysplasias) which makes difficult, at least for a while, the use of these proteins with diagnosis purpose.

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Gingival cyst of the adult (GCA) is a rare entity and comprises around 0.3% of all odontogenic cysts. Due to its rarity, there are a few retrospective studies on it. Therefore, the aim of this study was to present casuistic data of a 20-year retrospective study performed in a Brazilian oral pathology reference center. All cases diagnosed as gingival cyst of the adult in the last 20 years were retrieved from the files of the Oral Pathology Service. Data from the lesions and patients were tabulated and presented descriptively. From a total of 68,229 oral biopsies, 7,023 were odontogenic cysts, and among these only 20 cases were diagnosed as gingival cyst of the adult, resulting in the largest series of gingival cyst of the adult, from a single center, in the last 15 years. Most cases occurred in women, and although 53% affected the anterior mandible, 40% occurred in the anterior maxilla, which contrasts with the previous literature. Despite being a rare lesion GCA should be considered in the clinical differential diagnosis of gingival lesions presenting either in the maxilla or mandible.

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PURPOSE: Neoplasms of the salivary glands comprise more than thirty subtypes of lesions with various clinical behaviors. The present study aimed to describe the incidence and main features of salivary gland tumors in Brazil. MATERIAL AND METHODS: A retrospective descriptive cross-sectional study was performed (1997-2017). A total of 88,430 biopsy records of oral and maxillofacial lesions from 5 pathology referral centers were analyzed. All cases of salivary gland tumors were reviewed and data such as gender, age, skin color, anatomical location, symptomatology, tumor size and histopathological diagnosis were collected. RESULTS: Among all lesions, there were 2,292 (2.6%) cases of salivary gland tumors. The most frequent benign and malignant neoplasm was pleomorphic adenoma (n = 1,086; 47.4%) and mucoepidermoid carcinoma (n = 322; 14.0%), respectively. The majority of the patients were white (n = 757; 33%) and female (n = 1,391; 60.7%), and most cases involved the parotid gland (n = 933; 40.7%; p < 0.001). Age ranged from 1 to 101 years, occurring more in the fourth decade of life. Tumor size varied from 0.3 to 15 cm and the presence of symptomatology (pain/swelling) occurred more in patients with malignant tumors (p < 0.001). CONCLUSION: The incidence profile and clinical findings of salivary gland tumors were similar to those described worldwide; nevertheless, multicenter studies are valuable to better characterize these neoplasms.

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INTRODUCTION: Cripto-1 is a member of the epidermal growth factor-Cripto-1/FRL-1/Cryptic family. Besides being critical for early embryonic development, Cripto-1 is also associated with the development and behavior of several cancers. OBJECTIVE: We analyzed the immunoexpression of Cripto-1 in normal salivary glands (NSGs), pleomorphic adenomas (PAs), and carcinoma ex pleomorphic adenomas (CaExPAs) of salivary glands. METHODS: A total of 12 NSGs, 16 PAs and 12 CaExPAs underwent immunohistochemical study by the polymeric biotin-free technique. Immunopositive cells were evaluated semiquantitatively (scores 0-3). For statistical analysis, Mann-Whitney and Kruskal-Wallis tests were performed and a significance level of p ≤ 0.05 was established. RESULTS: Most CaExPAs (n = 10) were strong positive (score 3) for Cripto-1, and only three cases of PAs and two specimens of NSGs exhibited some expression (score 1), being statistically significant these findings (p < 0.001). No difference between the expression of this protein in tumors of major and minor salivary glands was observed. Overexpression was found mainly in cases of CaExPAs with invasive growth (n = 8) when compared to those without capsular invasion (intracapsular pattern) (p = 0.036). Patients with or without lymph node metastasis showed no difference (p = 0.294). CONCLUSION: The results revealed a significantly higher expression of Cripto-1 in CaExPA compared to PA and NSG, suggesting this protein is possibly deregulated in PA malignant transformation. Furthermore, the increased expression of this protein is associated with a more aggressive behavior (invasive growth) in salivary gland tumors.

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Toll-like receptors (TLRs) have been widely investigated due to their importance in the inflammatory response and possible links to tumor promotion/regression and prognosis. In cancers with an infective etiology, such as human papillomavirus (HPV)-associated Oropharyngeal Squamous Cell Carcinoma (OPSCC), TLR responses may be activated and play a role in tumorigenesis. Our aim was to assess the expression of all TLRs in OPSCC cell lines (both HPV+ and HPV-) by qPCR, Western Blot and flow cytometry and assess their response to TLR ligands lipopolysaccharide (LPS), LPS ultra-pure (LPS-UP) and peptidoglycan (PGN) by analyzing IL-8 and IL-6 production. We also immunostained 61 OPSCC tissue samples with anti-TLR4. Results showed lower TLR1 and TLR6 mRNA expression and higher TLR9 protein expression in HPV+ when compared to HPV-OPSCC cells. TLR4 expression did not vary by HPV status in OPSCC cells, but TLR4 expression was significantly lower in HPV+OPSCC tissues. After stimulation with PGN, only one cell line (HPV+) did not secrete IL-6 or IL-8. Furthermore, HPV+OPSCC lines showed no IL-6 or IL-8 production on treatment with LPS/LPS-UP. The data suggest changes in TLR4 signaling in HPV+OPSCC, since we have shown lower tissue expression of TLR4 and no pro-inflammatory response after stimulation with LPS and LPS-UP. Also, it suggests that OPSCC may respond to HPV infection by increased expression of TLR9. This study demonstrates differences in expression and function of TLRs in OPSCC, which are dependent on HPV status, and may indicate subversion of the innate immune response by HPV infection.