Focal melanocytic lesions of the oral mucosa: An epidemiological and morphological study.

OBJECTIVE: This study aimed to analyse the clinical and histopathological characteristics of focal oral melanocytic lesions in a Brazilian reference service in Oral and Maxillofacial Pathology. MATERIALS AND METHODS: A cross-sectional study was conducted over an 18-year period. Demographic data and clinical features were collected from the archives, and all biopsy specimens diagnosed as oral melanocytic lesions were retrieved and reviewed. RESULTS: We identified 339 melanocytic lesions. Of these, 191 were melanotic macules, 112 melanocytic nevi, 14 mucosal lentigo simplex, 12 melanomas, 9 solar lentigos, and 1 melanoacanthoma. Lesions occurred mostly in white-skinned (74.2%) women (65.2%). The main reported clinical aspect was the macule (67.4%), and the most affected site was the lip vermilion (25.4%), followed by the palate (22.9%). Melanomas were larger in size and were observed in older patients with an overall shorter time of onset. The most frequent subtypes of melanocytic nevi were intramucosal (44.6%), compound (24.1%), and blue nevus (20.5%). They showed a heterogeneous architectural pattern with the presence of the three cell types. CONCLUSION: The most frequent lesions are melanotic macule and nevus, especially the intramucosal subtype. Patients are usually white-skinned women presenting a small, long-lasting, macular lesion on the lip vermilion or palate.

Usefulness of immunohistochemical staining in diagnosing a challenging case of oral primary syphilis.

Clinicians involved in the diagnosis of mucocutaneous diseases should be aware that syphilis is still prevalent among humans and its accurate diagnosis may require substantial clinical evaluation. Herein, we report a case of primary syphilis presenting as an isolated ulcer on the upper left labial oral mucosa. The lesion exhibited no specific features and could have been easily mishandled. An important clinical observation was the presence of a satellite-enlarged lymph node in the left submandibular area, which was highly indicative of primary syphilis. Histopathological examination of the specimen obtained by punch biopsy revealed features suggestive of syphilis and immunohistochemical staining with antitreponemal antibody confirmed its diagnosis with the detection of numerous Treponema pallidum in the specimen.

Histopathological features of photodamage and mast cell infiltrate in actinic cheilitis with different grades of epithelial dysplasia.

BACKGROUND: Actinic cheilitis is induced by chronic exposure to ultraviolet radiation and shows solar elastosis, a feature that has been associated with mast cell infiltrates. This study aimed to investigate the area of solar elastosis, collagen loss, and mast cell infiltrates in a series of actinic cheilitis. METHODS: We evaluated the epithelial dysplasia in 52 cases of actinic cheilitis and the solar elastosis with Weigert's resorcin-fuchsin. Collagen loss was evaluated with Picrosirius red, analyzed under polarized microscopy, and scored from 1 to 3. Elastosis proportionate area (EPA) was calculated with image software. Mast cells were highlighted with toluidine blue stain. RESULTS: EPA varied from 2% to 45%, with a mean of 17.1% in the cases, with no differences among epithelial dysplasia degrees. Most cases presented collagen loss scores of 2 or 3, and higher loss of type I collagen was associated with older age. Mast cell density was higher in severe epithelial dysplasia (P = 0.002) and in high-risk cases (P = 0.01). CONCLUSION: Actinic cheilitis presented variable EPA and marked loss of type I collagen; however, these features were not associated with the degrees of epithelial dysplasia. Besides, mast cell density increased with epithelial dysplasia worsening and this was not associated with elastosis area or collagen loss.

Oral granular cell tumour: A multicentric study of 56 cases and a systematic review.

OBJECTIVE: Granular cell tumour (GCT) is a benign neoplasm that originates from Schwann cells. Within the oral cavity, it usually appears as a lingual nodule and especially amongst female adults. Histologically, GCT shows a proliferation of polygonal cells with eosinophilic granular cytoplasm, which can be associated with a pseudoepitheliomatous hyperplasia (PEH). In this study, we analyse the main clinicopathological data of intraoral GCT and we compare our results with previous studies. MATERIAL AND METHODS: We have studied a series of 56 cases of oral GCT in Spain and Brazil, and we have conducted a systematic review in PubMed, Web of Knowledge and Scopus databases, using the keywords: "granular cell tumour" and oral. RESULTS: In our series, GCT appeared as an asymptomatic benign tumour that is more frequent in women and in the tongue. PEH was observed in 32% of the lesions. In the review, we collected 282 cases of oral GCT with a similar clinical profile; seven patients had multiple lesions, and 33% of the cases presented PEH. No cases of malignant oral GCT have been described to date. GCT is an uncommon oral benign neoplasm, mainly unique and asymptomatic, derived from Schwann cells. CONCLUSIONS: Although the etiopathogenesis of this oral tumour is unknown, its characteristics suggest that it could have a reactive nature. Conducting a complete clinicopathological study in all intraoral GCT is fundamental in order to dismiss other entities, including oral carcinoma.

Subset of CD8+ and FOXP3 + T cells in lichen planus associated with chronic hepatitis C infection.

OBJECTIVE: To verify whether there are differences between populations of CD8 + and FoxP3 + T cells in lesions of oral lichen planus associated with hepatitis C virus chronic infection (OLP-HCV) and lesions of idiopathic oral lichen planus (OLP-I). MATERIALS AND METHODS: A case-control study was performed using a convenience sample of 11 paraffin-embedded tissue blocks of OLP-HCV and 19 of OLP-I. Histological sections stained with haematoxylin and eosin were used to classify the intensity of inflammatory infiltrate. Immunohistochemistry was used to identify CD8 + and FoxP3 + T cells. The count of positive cells was compared between the two groups and correlated to clinical and demographic data (p < 0.05). RESULTS: There were no statistically significant differences in the distribution of CD8 + and FoxP3 + T cells regarding the inflammatory infiltrate in lesions of OLP-HCV and OLP-I. Atrophic/erosive lesions showed a higher relationship between counts of CD8/FoxP3 T cells per mm2 (p = 0.018) and counts of CD8 + T cells per mm2 (p = 0.034) in OLP-HCV group compared to OLP-I group. CONCLUSION: Overall, no difference was found between cell populations in the lesions of OLP-HCV and OLP-I. However, atrophic/erosive lesions of OLP-HCV had a higher amount of CD8 + T cells and lower FoxP3 expression.

Morphological alterations in minor salivary glands of HTLV1+ patients: A pilot study.

BACKGROUND: Among the complex of HTLV-associated diseases, Sjögren's syndrome (SS) is one of the most controversial. This work aims to detect morphological and inflammatory alterations, including clues of the presence of HTLV-1, in minor salivary glands of patients with dryness symptoms. METHODS: We have assessed HTLV-1-seropositive patients (HTLV-1 group) and patients with SS (SS group). We used formalin-fixed, paraffin-embedded minor salivary gland tissue to evaluate the morphological aspects and, by means of immunohistochemistry, the presence of Tax protein, CD4, CD8 and CD20 cells. Additionally, viral particles and proviral load were analysed by PCR. RESULTS: The HTLV-1 group had the highest prevalence of non-specific chronic sialadenitis (85.71%; P = 0.017) and greater amount of T CD8+ cells. In the SS group, focal lymphocytic sialadenitis (80%; P = 0.017) prevailed, with a greater amount of B CD20+ . Both immunohistochemistry and PCR identified the Tax protein and its gene in the salivary glands of both groups and in similar proportions. CONCLUSION: The results indicate that HTLV-1-seropositive patients have different patterns of morphological/inflammatory alterations, suggesting a likely difference in the process of immune activation.

Evaluation of epithelial dysplasia adjacent to lip squamous cell carcinoma indicates that the degree of dysplasia is not associated with the occurrence of invasive carcinoma in this site.

BACKGROUND: We analyzed the different grades of dysplasia in the epithelium adjacent to lip squamous cell carcinoma (LSCC), as a parallel to actinic cheilitis (AC) that suffered malignant transformation. METHODS: Forty samples of epithelium adjacent to LSCC were histologically graded according to the World Health Organization (WHO) and the binary systems. The expression of mutated p53 was evaluated through immunohistochemistry. RESULTS: According to WHO system, 37.5% of the cases were graded as mild, 45% as moderate and 17.5% as severe dysplasia (P = 0.09). Considering the binary system, 90% of the cases were classified as low-risk and 10% as high-risk lesions. Mutated p53 was present in 73.3% of mild, 88.8% of moderate and 71.4% of severe dysplasia cases. Considering the binary system, 80.5% of the low-risk and 75% of high-risk lesions were immunopositive; 62.5% expressed the protein in both tumor cells and adjacent epithelium; 17.5% in adjacent epithelium only, and 7.5% in LSCC islands only (P = 0.03). CONCLUSIONS: We observed heterogeneous grades of epithelial dysplasia in the epithelium adjacent to LSCC, which indicates that the analysis of AC morphological features is insufficient to predict patient's prognosis and to determine a treatment decision. Positive expression of mutant p53 in mild dysplasia reinforces this idea.

Expression of cancer stem cell markers CD44, ALDH1 and p75NTR in actinic cheilitis and lip cancer.

PURPOSE: The aim of this work was to evaluate the expression of the cancer stem cell (CSC) markers CD44, ALDH1 and p75NTR in the ultraviolet-induced lesions actinic cheilitis (AC) and lip squamous cell carcinoma (LSCC), and to correlate it with p53 expression. METHODS: Immunohistochemistry was performed in 4 cases of normal lip (NL), 43 of AC and 20 of LSCC. RESULTS: All cases were positive for CD44, showing a membranous staining without differences between the groups. ALDH1 showed cytoplasmic staining and it was invariable amongst the grades of epithelial dysplasia and between AC and LSCC. p75NTR presented membranous/cytoplasmic staining in the basal and parabasal layer of NL and AC, while LSCC presented cytoplasmic staining in the peripheral layers of the tumor islands. p75NTR showed different expression amongst the dysplasia grades (p < 0.001) but no differences between AC and LSCC. p53 expression was similar amongst the dysplasia grades and between AC and LSCC. CD44, ALDH1 and p75NTR were unrelated amongst themselves and to p53 expression. CONCLUSIONS: CSC markers are expressed in potentially malignant and malignant lesions of the lip. Their expressions were invariable between AC and LSCC and unrelated to p53. p75NTR expression increased with the worsening of epithelial dysplasia grade.

Glypican-3 distinguishes aggressive from non-aggressive odontogenic tumors: a preliminary study.

BACKGROUND: Glypican-3 is a cell surface proteoglycan that is found in embrionary tissues, and there are no studies investigating this protein in odontogenic tumor. Thus, the aim of this study was to investigate glypican-3 in a series of aggressive and non-aggressive odontogenic tumors. METHODS: Fifty-nine cases of tumors were divided into aggressive odontogenic tumors (20 solid ameloblastomas, four unicystic ameloblastoma, 28 KOTs including five associated with Gorlin-Goltz syndrome) and non-aggressive odontogenic tumors (five adenomatoid odontogenic tumors and two calcifying cystic odontogenic tumors) and analyzed for glypican-3 using immunohistochemistry. RESULTS: Glypican-3 was observed in seven solid ameloblastoma and eighteen keratocystic odontogenic tumors including three of the five syndromic cases, but there was no significant difference between syndromic and sporadic cases (P > 0.05; Fisher's exact Test). All cases of unicystic ameloblastoma (n = 4), adenomatoid odontogenic tumor (n = 5), and calcifying cystic odontogenic tumor (n = 2) were negative. CONCLUSIONS: This provided insights into the presence of glypican-3 in odontogenic tumors. This protein distinguished aggressive from non-aggressive odontogenic tumors.

Mucocutaneous histoplasmosis as the first manifestation of AIDS.

Immunosuppressed patients can present with opportunistic infections resulting from an intrinsic systemic disease, which easily evolves into more aggressive and less common conditions. This work reports a clinical case of a female patient with histoplasmosis lesions in the nasal and oral mucosa, including pulmonary, hematological, and hepatic impairment, which led to the diagnosis of HIV seropositivity. In the presence of severe immunosuppression, morbidity is increased due to deep fungal infections and their unusual clinical characteristics can make diagnosis difficult. Therefore, it can be very helpful to recognize these clinical characteristics in order to determine early diagnostic interventions. It is important to recognize mucocutaneous manifestations of histoplasmosis because the biopsy of these lesions, and subsequent histopathological analysis, is one of the quickest, safest, and cheapest methods of diagnosis.

Bilateral intraosseous lipoma of the maxillary tuberosity: A challenging entity.

Lipomas can occur anywhere in the body where fat cells are present; however, intraosseous lipomas are rare. Although solitary lesions have already been reported in the gnathic bones, to the best of our knowledge, this is the first case of bilateral intraosseous lipoma. A 62-year-old woman was referred for evaluation of a swelling on both maxillary tuberosities. The radiographic examination showed a mixed radiolucent-radiopaque image with ill-defined borders on the right side of the maxilla, and an ill-defined radiolucency on the left side. Histologically, both sides revealed numerous mature adipocytes surrounded by immature bone and dystrophic calcification. The patient remains under follow-up and free of disease for 8 months. Due to the rarity of the intraosseous lipomas in the jaws, a literature review of the published cases was performed jointly with this unique case report.

Glandular Odontogenic Cyst in the Anterior Mandible: A Case Report of a Conservative Approach and a Recurrence Detection.

PURPOSE: The glandular odontogenic cyst (GOC) is considered a rare developmental cyst, with an odontogenic origin and both epithelial and glandular characteristics, with less than 200 reported cases in the literature. METHODS: In the present case, a 29-year-old man was referred for evaluation of an asymptomatic slow-growing swelling in the anterior region of the mandible, with one-year history. The patient's medical history did not reveal any systemic alteration. The extraoral examination did not show enlargement of the facial contour and the intraoral examination showed vestibular and lingual swelling. Panoramic radiography and CT scan revealed a well-defined unilocular radiolucent lesion involving the inferior incisors and canines bilaterally. RESULTS: Histopathological analysis revealed multiple cysts lined by stratified epithelium with varying thickness and characteristics, in addition to duct-like structures filled with PAS-positive amorphous material, suggestive of GOC. Conservative treatment was performed through surgical curettage, peripheral ostectomy of the surgical site and apicectomy of the teeth involved in the lesion. There was one recurrence, which was detected in postoperative follow-up, leading to a new surgical approach. CONCLUSIONS: Fifteen months after the second procedure, no signs of recurrence were identified, and bone neoformation within the surgical site occurred, supporting that a conservative approach for the treatment of GOC is viable.

Periodontal ligament cells mobilized by transforming growth factor-beta 1 and migrated without stimuli showed enhanced osteogenic differentiation.

OBJECTIVE: This study aimed to analyze the ability of G-CSF and TGF-ß1 to mobilize periodontal ligament stem cells to obtain populations with better potential for proliferation and osteogenic differentiation. DESIGN: Primary cultures were established from the periodontal ligament of Wistar rats. After a cell migration assay, four experimental groups were obtained: PDLSC, composed of the primary culture, non-mobilized cells; MPDLSC, the spontaneously migrated cells; MPDLSC-GCSF, the cells mobilized with G-CSF; and MPDLSC-TGF-ß1, the cells mobilized with TGF-ß1. The expression of mesenchymal stem cell markers was assessed by flow cytometry. Clonogenicity, viability, proliferative potential, and osteogenic differentiation capacity were also analyzed. RESULTS: All the study groups expressed well-known mesenchymal stem cell markers and exhibited clonogenic capacity. The higher proliferation potential was seen in the PDLSC and MPDLSC groups, while the MPDLSC and MPDLSC-TGFß1 groups showed a higher number of mineralized deposits in vitro and higher ALP activity after osteogenic differentiation induction. Cells of all the groups also expressed mRNA of genes associated with osteogenic differentiation without previous induction. CONCLUSIONS: Both agents were able to mobilize stem cells from the periodontal ligament, but G-CSF did not show an advantage, whereas TGF-ß1 appears to direct the cells towards a state of increased osteogenic differentiation. Furthermore, spontaneous cell migration through a membrane was sufficient to enrich the cell population.

Temporo-spatial distribution of stem cell markers CD146 and p75NTR during odontogenesis in mice.

Mesenchymal and epithelial stem cells were identified in dental tissues; however, knowledge about the odontogenic stem cells is limited, and there are some questions regarding their temporo-spatial dynamics in tooth development. OBJECTIVE: Our study aimed to analyze the expression of the stem cell markers CD146 and p75NTR during the different stages of odontogenesis. METHODOLOGY: The groups consisted of 13.5, 15.5, 17.5 days old embryos, and 14 days postnatal BALB/c mice. The expression of CD146 and p75NTR was evaluated by immunohistochemistry. RESULTS: Our results showed that positive cells for both markers were present in all stages of tooth development, and the number of positive cells increased with the progression of this process. Cells of epithelial and ectomesenchymal origin were positive for CD146, and the expression of p75NTR was mainly detected in the dental papilla and dental follicle. In the postnatal group, dental pulp cells were positive for CD146, and the reduced enamel epithelium and the oral mucosa epithelium showed immunostaining for p75NTR. CONCLUSIONS: These results suggest that the staining pattern of CD146 and p75NTR underwent temporal and spatial changes during odontogenesis and both markers were expressed by epithelial and mesenchymal cell types, which is relevant due to the significance of the epithelial-ectomesenchymal interactions in tooth development.

Effects of serum-free culture media on human apical papilla cells properties.

OBJECTIVE: Aiming at more effective and safer cell therapies, the objective of this study was to evaluate the biological properties of human apical papilla cells cultured in the absence of serum supplementation in comparison to cells cultured with fetal bovine serum (FBS). DESIGN: Two apical papilla cell populations were isolated from third molars with incomplete rhizogenesis, and cultured in four different media: minimum essential Eagle medium - alpha modification (alpha-MEM); alpha-MEM supplemented with FBS (alpha-MEM + FBS); Dulbecco's modified Eagle medium/nutrient mixture F-12 (DMEM/F12); and DMEM/F12 supplemented with FBS (DMEM/F12 + FBS). We evaluated their proliferation, clonogenicity, and in vitro osteogenic and chondrogenic differentiation potential. RESULTS: Apical papilla cells cultured in DMEM/F12 + FBS and alpha-MEM + FBS were more proliferative than those grown in serum-free media, and also exhibited greater efficiency in colony cell formation. Despite this, all study groups showed immunostaining for the marker of mitosis anti-PHH3. Also, alpha-MEM + FBS, alpha-MEM, and DMEM/F12 + FBS exhibited higher amount of mineralized deposits in vitro than DMEM/F12, while only cells cultured with FBS were able to form spheres in chondrogenic differentiation assay. CONCLUSIONS: Our results showed that, although the cultivation of apical papilla cells in a serum-free medium has reduced the properties of cell proliferation and differentiation, these cells are still capable of maintaining their desirable characteristics.

Therapeutic potential of periodontal ligament stem cells.

Inflammatory periodontal disease known as periodontitis is one of the most common conditions that affect human teeth and often leads to tooth loss. Due to the complexity of the periodontium, which is composed of several tissues, its regeneration and subsequent return to a homeostatic state is challenging with the therapies currently available. Cellular therapy is increasingly becoming an alternative in regenerative medicine/dentistry, especially therapies using mesenchymal stem cells, as they can be isolated from a myriad of tissues. Periodontal ligament stem cells (PDLSCs) are probably the most adequate to be used as a cell source with the aim of regenerating the periodontium. Biological insights have also highlighted PDLSCs as promising immunomodulator agents. In this review, we explore the state of knowledge regarding the properties of PDLSCs, as well as their therapeutic potential, describing current and future clinical applications based on tissue engineering techniques.

Clear Cell Odontogenic Carcinoma Harboring the EWSR1-ATF1 Fusion Gene: Report of a Rare Case.

Clear cell odontogenic carcinoma (CCOC) is a rare and aggressive malignant epithelial neoplasm, which occurs most frequently in the mandible of elderly patients. Morphologically, CCOC shares similar characteristics with other clear cell tumors, especially hyalinizing clear cell carcinoma of the salivary glands (HCCC). Both CCOC and HCCC are known to harbor EWSR1 rearrangements, especially the EWSR1-ATF1 gene fusion, which indicates a possible link between the two lesions. So far, this fusion has been demonstrated in five cases of CCOC in the literature. Herein, we add another CCOC case to the literature, which arose in the mandible of an 82-year-old female patient and was proven to harbor the EWSR1-ATF1 gene fusion. Immunohistochemically, this case was focally positive for CK7, CK14, CK19 and p63. The patient was referred to surgical treatment; however, she died of disease 2 months after the diagnosis, thereby demonstrating the aggressive nature of this tumor.

Oral leishmaniasis: Report of two cases.

Leishmaniasis is a chronic inflammatory disease caused by several species of the parasite Leishmania that is transmitted by insects of the genus Phlebotomus spp. or Lutzomyia spp. This disease can affect skin, mucous membranes and viscera being classified as cutaneous, mucocutaneous and visceral leishmaniasis, depending on the spectrum of clinical manifestations. Diagnosis can be achieved through biopsy, microscopical analysis, Montenegro intradermoreaction and/or ELISA. The dentist plays an important role in the diagnosis of this disease due to frequent involvement of oral mucosa. This article reports two clinical cases of leishmaniasis with oral mucosa involvement, their diagnosis workup and treatment.

Demographic and Clinicopathologic Features of Actinic Cheilitis and Lip Squamous Cell Carcinoma: a Brazilian Multicentre Study.

Data on the occurrence and clinicopathological characteristics of actinic cheilitis (AC) and lip squamous cell carcinoma (LSCC) are well studied; however, they are based on studies limited to a single centre. Herein, we described the frequency of AC and LSCC submitted to microscopic examination from representative geographic regions of Brazil. A retrospective multicentre study was performed on biopsies obtained from 1953 to 2018 at 10 Brazilian oral and maxillofacial pathology centres. A total of 198,709 biopsy specimens were surveyed. Sociodemographic data and clinicopathologic characteristics were analysed. A total of 2017 cases of ACs (1.0%) and 850 cases of LSCCs (0.4%) were recorded. A strong fair-skinned (> 87%) male (> 70%) predilection was observed in both conditions. The mean age was 54.8 ± 18.7 for individuals with AC and 57.8 ± 19.0 for individuals with LSCC. The most commonly affected site was the lower lip (> 90%). This is a large multicentre study of AC and LSCC from Brazil. The frequency and clinicopathological features of AC and LSCC were similar to those described worldwide. This study provides robust and representative epidemiological data of these conditions for the scientific community.

Gingival complex odontoma: a rare case report with a review of the literature.

Odontomas are odontogenic tumors composed of a mixture of dental tissues. They are very common hamartomas of the jaws. However, their peripheral or gingival counterparts are extremely uncommon. The objective of this article is to report a rare case of gingival complex odontoma in an 11-year-old patient, and also to review all published cases of this type of lesion.