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This study aimed to map systemic alterations predisposing to oral squamous cell carcinoma (OSCC) onset. This review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Five databases were used to access (1) reports of OSCC co-occurring in patients with systemic conditions, (2) prevalence of OSCC among these patients, and (3) clinicopathological profiles. Data from more than 1 million patients worldwide showed that Fanconi's anemia, xeroderma pigmentosum, dyskeratosis congenital, chronic fatigue syndrome, and patients post bone marrow transplantation (BMT) present increased risk for OSCC development. The overall prevalence of OSCC in syndromic patients and post-BMT were 0.65% (95% CI = 0.13-3.11, p 0.01) and 5.83% (95% CI = 0.00-30.90, p 0.01), respectively. The certainty of the evidence was moderate. This study demonstrated that some systemic conditions predispose to OSCC. These results present an impact on the screening of OSCC in systemically compromised patients.

This systematic review aimed to identify the molecular alterations of head and neck rhabdomyosarcomas (HNRMS) and their prognostic values.An electronic search was performed using PubMed, Embase, Scopus, and Web of Science with a designed search strategy. Inclusion criteria comprised cases of primary HNRMS with an established histopathological diagnosis and molecular analysis. Forty-nine studies were included and were appraised for methodological quality using the Joanna Briggs Institute Critical Appraisal tools. Five studies were selected for meta-analysis.HNRMS predominantly affects pediatric patients (44.4%), and the parameningeal region (57.7%) is the most common location. The alveolar variant (43.2%) predominates over the embryonal and spindle cell/sclerosing types, followed by the epithelioid and pleomorphic variants. PAX-FOXO1 fusion was observed in 103 cases of alveolar RMS (79.8%). MYOD1 mutation was found in 39 cases of sclerosing/spindle cell RMS (53.4%). FUS/EWSR1-TFCP2 gene fusions were identified in 21 cases of RMS with epithelioid and spindle cell morphologies (95.5%). The 5-year overall survival rate of patients was 61.3%, and MYOD1 mutation correlated with significantly higher mortality.The genotypic profile of histologic variants of HNRMS is widely variable, and MYOD1 mutation could be a potential prognostic factor, but more studies are required to establish this.

Objective : The purpose of this multicenter retrospective study was to report the clinical and radiological features of 92 glandular odontogenic cysts (GOCs) diagnosed over a 20-year period. Study Design : Histologically confirmed cases of GOC were retrospectively reviewed from four Oral Pathology laboratories in South Africa and Brazil to categorize the clinical and radiological spectrum of GOCs. Results : The mean age of patients was 46 years (range 17-87) with a male-to-female ratio of 1.2:1. GOCs had a mandibular predilection (68%), with 42% of all cases located anteriorly. Additionally, 42% of cases crossed the midline. Radiologically, most lesions were unilocular (53%) and uniformly radiolucent (97%), with well-demarcated borders (93%). Cortical expansion (62%), loss of cortical integrity (71%), and maxillary sinus (67%) and nasal cavity encroachment (72%) were common findings. Significant differences in lesions between the two countries were discovered in sex predilection, clinical signs and symptoms, and lesion locations within the mandible and maxilla. Conclusion : GOCs present with a wide spectrum of clinical and radiological features, ranging from cysts with typical GOC-like presentations to more aggressive lesions. The need for advanced imaging in the surgical planning of GOCs exhibiting radiological signs of aggression is justified based on the high recurrence rate.

Objective The aim of the present study was to carry out a systematic review of available data regarding case reports and case series of oral and maxillofacial benign fibrous histiocytoma (BFH). Study Design A search strategy was performed using the PubMed, Web of Science, Scopus, and EMBASE electronic databases. Results Male individuals (56.89%) were more affected, with a mean age of 34.55 ± 20 years. The buccal mucosa (20.33%) represented the most common site, with the clinical presentation of a painless (86.95%) nodule (98.03%). The clinical hypothesis of a fibroma was reported in most cases (31.57%). Radiographic presentation of intraosseous lesions showed multilocular radiolucent images (55.55%). Regarding the histopathologic features, the biphasic population of fibroblastic and histiocytic cells was seen in 21 cases (39.62%), and a spindle-shaped fibroblastic cell population organized into a storiform pattern was observed in 25 cases (47.16%). CD68 (n = 26) and vimentin (n = 25) showed immunoreactivity in all BFH cases in which they were used. All cases were treated with a surgical resection, and 8.10% recurred. Conclusions The current systematic review demonstrated that BFH represents a rare lesion that mainly affects the buccal mucosa of male individuals, and the treatment is mainly surgical with a good prognosis.

The aim of the present study was to integrate the available data published in the literature on oral and maxillofacial neuroendocrine carcinomas concerning the demographic, clinical and histopathological features of this condition. An electronic search with no publication date restriction was undertaken in April 2021 in four databases. Eligibility criteria included reports published in English having enough data to confirm a definite diagnosis, always showing a neuroendocrine marker. Cases originating in the oropharynx, including base of the tongue and tonsils, were excluded. Outcomes were evaluated by the Kaplan–Meier method along with Cox regression. Twenty-five articles (29 cases) from nine different countries were detected. Mean patient age was 56.3 (± 17.5) years, with a slight male predilection. Symptomatology was present in 72.2% of informed cases. Regarding clinical presentation, a non-ulcerated nodule located in the gingiva with a mean size of 3.4 (± 2.0) cm was most frequently reported. Concomitant metastasis was identified in seven individuals. Histopathologically, most neoplasms were of the small cell type, and immunohistochemistry for both epithelial and neuroendocrine differentiation was used in 65.5% cases. Radical surgery was the treatment of choice in almost all cases, with or without adjuvant therapy. Mean follow-up was 20.5 (± 21.2) months, and only four patients developed recurrences. Eleven (44.0%) individuals died due to the disease. Ulcerated lesions were a prognostic factor. This study provides knowledge that can assist surgeons, oncologists, and oral and maxillofacial pathologists with the diagnosis and management of neuroendocrine carcinomas. Our findings demonstrated that the long-term prognosis of this lesion continues to be poor. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12105-021-01398-2.

Objective The aim of this study was to report the clinicopathologic features of 105 new cases of adenomatoid odontogenic tumor (AOT) from Brazil, Guatemala, Mexico, and South Africa. Study Design Clinical and radiographic data were collected from records of 5 oral pathology laboratories, and all cases were microscopically reviewed. Results This series of cases included 36 (34.2%) from South Africa; 33 (31.4%) from Brazil; 23 (21.9%) from Mexico; and 13 (12.3%) from Guatemala. Seventy-two patients (68.5%) were females and 33 patients (31.4%) were males, with an average age of 19.2 years. The tumors predominantly affected the anterior maxilla (48.5%), followed by the anterior mandible (29.5%); posterior mandible (15.2%); and posterior maxilla (6.6%). Sixty-three tumors (63.6%) were follicular, 34 (34.3%) were extrafollicular, and 2 (2%) were peripheral. In most cases, the tumors caused considerable cortical expansion (average size 3.4 cm). Microscopically, most cases showed rosette-like and duct-like structures. Conclusions This is one of the largest case series of AOTs reported in the literature and the first multicenter study involving populations from Latin America and South Africa. In a fifth of the present cases, the posterior regions of the gnathic bones were affected and the tumors demonstrated larger sizes compared with cases occurring in other populations.

A proper antibody panel selection is one of the most important factors to reach an adequate diagnosis in challenging cases. This retrospective study was designed to determine the contribution of immunohistochemistry (IHC) in the primary diagnosis of oral diseases in one of the main services of oral pathology in the State of São Paulo, Brazil, and to identify the most common antibodies used, and recommend diagnostic algorithms based on our experience with challenging lesions. A total of 1698 IHC stains were performed in 401 cases from a total of 28,804 cases received from public dental clinics and private dental practitioners within a period of 13 years, representing a frequency of 1.4% of IHC solicitations. Among these, 112 (28%) were mandatory to reach a final diagnosis and 255 (63.6%) were confirmative. In 34 (8.4%) cases, it was not possible to reach a conclusive/final diagnosis, even with IHC. Regarding the nature of the lesions, 210 (52.3%) were benign, 163 (40.6%) were malignant tumors, 13 (3.2%) were reactive, 10 (2.5%) were premalignant, and 5 (1.2%) were lesions of uncertain malignancy. Small amount of tissue of some incisional biopsies, overlapping features of spindle cell lesions (epithelial, neural, melanocytic, smooth muscle, endothelial, and fibroblastic/myofibroblastic cell differentiation), and overlapping features of salivary gland lesions were the most frequent challenges in which IHC stains were requested. Spindle cell lesions were the most frequent (22%) among all cases that required IHC to reach a final diagnosis. The implementation of IHC for routine practice requires a wide range of markers, proper antibody selection, and knowledge to interpret the subjectivity of staining. The inherent limitation of incisional biopsies was pointed as a reason to inconclusive diagnosis, despite a wide range of antibodies that our laboratory displays.

Background Lymphomas in the oral and oropharyngeal regions are relatively uncommon, and their diagnosis is challenging and complex due to the myriad histopathological subtypes. Herein, we report a large series of oral and oropharyngeal lymphomas and compare our data with the currently available literature. Methods All cases diagnosed as lymphomas affecting the oral and oropharyngeal regions were retrospectively retrieved from seven Brazilian institutions. Clinicodemographic data and histopathological features were evaluated and described, while a comprehensive literature review was undertaken in order to compare our findings. Results A total of 304 cases of oral and oropharyngeal lymphomas were obtained, mostly affecting individuals aged 60-69 years (n = 68) with a mean age at diagnosis of 54.2 ± 20.1 years. Males and females were equally affected. Mature B-cell neoplasms (87.2%) were the most common group, followed by mature T- and NK-cell neoplasms (11.2%) and precursor lymphoid neoplasms (1.6%). The most frequent subtypes in each group were diffuse large B-cell lymphomas, not otherwise specified (n = 99), extranodal NK/T-cell lymphomas, nasal type (n = 12), and B-lymphoblastic leukaemia/lymphomas, not otherwise specified (n = 4). The most commonly involved sites were the palate (26.3%), mandible (13%), and maxilla (10.5%). Conclusion Diffuse large B-cell lymphoma, not otherwise specified, remains the most common subtype of lymphomas in the oral and oropharyngeal region. Older patients are the most affected, with no gender predilection and the palate and jaw are usually affected.

Background Burkitt lymphoma (BL) is an aggressive B-cell lymphoma with three variants (endemic, sporadic, and immunodeficiency-associated), presenting with specific epidemiological and clinical features. Burkitt lymphoma affects the head and neck region (BLHN) in approximately 10% of cases. The aim of this study was to undertake a comparative analysis of the clinicopathologic and immunohistochemical (IHC) features of BLHN diagnosed in patients from Africa, Guatemala, and Brazil. Methods Cases diagnosed as BLHN were collected from the files of six oral pathology laboratory services (Brazil, South Africa, and Guatemala), and one Brazilian pediatric oncology hospital from 1986 to 2020. Clinicopathological and IHC data, and Epstein-Barr virus (EBV) status by in situ hybridization data for each case were reviewed and described. Results Of the 52 cases, BLHN was predominant in pediatric patients [43 (82.69%)] and males [43 (82.69%)], with a mean age of 11.26 ± 9.68 years (range, 1-39 years). Neck and cervical lymph nodes [14 (26.92%)], and involvement of both maxilla and mandible [8 (15.38%)], were the most common anatomical sites. Clinically, tumor/swelling [40 (31.25%)], cervical lymphadenopathy [14 (10.94%)], pain [12 (9.38%)], and bone destruction [12 (9.38%)] were frequent findings. All cases showed typical morphological characteristics of BL. IHC profiles included positivity for CD20 [52 (100%)], CD10 [38 (79.17%)], Bcl6 [29 (87.88%)], and c-Myc protein [18 (81.82%)]. EBV was positive in 18 cases (62.07%). The Ki-67 index ranged from 90-100%. Conclusion The clinicopathological and EBV profile of BLHN in South African, Guatemalan and Brazilian patients is similar.

Background CD30 is variably expressed in diffuse large B cell lymphoma (DLBCL), but its prognostic potential for the affected patients remains debatable and unclear. Therefore, we aimed to determine the frequency of CD30 expression in DLBCL and its potential for prognostic determination. Methods An electronic systematic review was performed using multiple databases, followed by a quantitative meta-analysis to assess the frequency of CD30 expression with a positivity cut-off values of > 0% and > 20%, and to determine its association with clinicopathological features and patients' survival. Results Using a cut-off value > 0%, we observed that 3.5% to 59.1% of the cases were considered positive for CD30. There was a significant association of the protein expression with a lower number of extra-nodal sites affected by the neoplasm, with Ann Arbor advanced stage, the absence of B-symptoms, the lack of MYC and BCL2 translocations, and a lower ECOG performance. Using a cut-off value > 20%, we observed that 2.5% to 36.7% of the cases were considered positive for CD30, being significantly associated with a lower number of extra-nodal sites affected by the neoplasm, Ann-Arbor stages III/IV, non-GCB tumors, the lack of MYC and BCL2 translocations, and a lower ECOG value. CD30 expression was significantly associated with a better survival rate, regardless of what cut-off parameter was used. Conclusion Despite variations in the cut-off values used to determine CD30 positivity in DLBCL, the expression of this protein seems to be associated with a higher survival rate and better prognosis.

Background Plasma cell neoplasms are characterized by the proliferation of a single clone of plasma cells with production of a monoclonal immunoglobulin. They can manifest as a single lesion (plasmacytoma) or as multiple lesions (multiple myeloma). Methods Paraffin-embedded tissue blocks of patients microscopically diagnosed with plasma cell neoplasms in the jaws were retrieved from five pathology files. Data including clinical, radiographic, microscopic and immunohistochemical findings, treatment employed, and follow-up status were retrieved from the pathology reports. Results Fifty-two cases were retrieved (mean age: 59.4 years) without sex predilection. The mandible was the most affected site (67.3%), usually associated with pain and/or paresthesia (53.8%). Lesions in other bones besides the jaws were reported for 24 patients (46.2%). Radiographically, tumors usually presented as poorly defined osteolytic lesions with unilocular or multilocular images, while microscopy revealed diffuse proliferation of neoplastic plasma cells with nuclear displacement and abundant eosinophilic cytoplasm. Two cases were classified as anaplastic, and amyloid deposits were found in two other cases. Immunohistochemistry was positive for plasma cell markers and negative for CD20 and CD3, and monoclonality for kappa light chain predominated. The overall survival rate after 5-years of follow-up was 26.6%. Conclusion Plasma cell neoplasms are aggressive tumors with a poor prognosis and involvement of the jaws may be the first complaint of the patient. Thus, oral pathologists, head and neck surgeons and dentists should be aware of their clinical, radiographic and microscopic manifestations.

Objective This systematic review aimed to evaluate the epidemiologic profile, screen for possible risk factors, and evaluate the spectrum of clinical characteristics of oral squamous cell carcinoma (OSCC) around dental implants (DIs). Methods The systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta‐ Analyses statement. Results Thirty-three articles met the eligibility criteria. In total, the sample consisted of 63 patients, and women comprised the majority (55.5%). The mean age of patients was 66.7 years. Oral potentially malignant disorders were reported in 46% of patients, of which 65.5% occurred in women. The most common lesion found in women was oral lichen planus (52.6%). In 88.8% of patients OSCC around DIs occurred in the mandible, and the most common clinical appearance of the lesions was an exophytic mass (46%). Most of these lesions were initially treated as peri-implantitis. Conclusions Most patients with OSCC around DIs were women without known risk factors. It is important to emphasize that these lesions may present clinical and radiographic features that could resemble peri-implantitis, which can lead to delay in the diagnosis and subsequent treatment.

Objective The aim of this study was to report the clinicopathologic features of 62 cases of central odontogenic fibroma (COdF). Study Design Clinical and radiographic data were collected from the records of 13 oral pathology laboratories. All cases were microscopically reviewed, considering the current World Health Organization classification of tumors and were classified according to histopathologic features. Results There were 43 females and 19 males (average age 33.9 years; range 8–63 years). Clinically, COdF lesions appeared as asymptomatic swellings, occurring similarly in the maxilla (n = 33) and the mandible (n = 29); 9 cases exhibited palatal depression. Imaging revealed well-defined, interradicular unilocular (n = 27), and multilocular (n = 12) radiolucencies, with displacement of contiguous teeth (55%) and root resorption (46.4%). Microscopically, classic features of epithelial-rich (n = 33), amyloid (n = 10), associated giant cell lesion (n = 7), ossifying (n = 6), epithelial-poor (n = 3), and granular cell (n = 3) variants were seen. Langerhans cells were highlighted by CD1a staining in 17 cases. Most patients underwent conservative surgical treatments, with 1 patient experiencing recurrence. Conclusions To the best of our knowledge, this study represents the largest clinicopathologic study of COdF. Most cases appeared as locally aggressive lesions located in tooth-bearing areas in middle-aged women. Inactive-appearing odontogenic epithelium is usually observed within a fibrous/fibromyxoid stroma, occasionally exhibiting amyloid deposits, multinucleated giant cells, or granular cells.

Objective The aim of this study was to evaluate the expression of BPIFA proteins in the saliva and salivary glands of hematopoietic cell transplant (HCT) patients. Material and Methods This longitudinal study included patients who had undergone autologous HCT (auto‐HCT) and allogeneic HCT (allo‐HCT) and unstimulated saliva were collected at three timepoints, with a fourth collection at oral chronic graft versus host disease (cGVHD) onset. BPIFA expression was analysed by Western blotting in saliva and immunostaining in the minor salivary glands of cGVHD patients. Results Auto‐HCT patients showed increased levels of BPIFA1 (P = 0.021) and BPIFA2 at D+7 (P = 0.040), whereas allo‐HCT group demonstrated decreased expression of BPIFA2 at D+8 (P = 0.002) and at D+80 (P = 0.001) and a significant association between BPIFA2 low levels and hyposalivation was observed (P = 0.02). BPIFA2 was significantly lower in the cGVHD patients when compared to baseline (P = 0.04). Conclusions The results of this study show distinct pattern of expression of BPIF proteins in both auto‐HCT and allo‐HCT recipients with decreased levels of BPIFA2 during hyposalivation and cGVHD. Further studies are necessary to elucidate these proteins mechanisms and their clinical implications in these groups of patients.

The role of digital pathology in remote reporting has seen an increase during the COVID-19 pandemic. Recently, recommendations had been made regarding the urgent need of reorganizing head and neck cancer diagnostic services to provide a safe work environment for the staff. A total of 162 glass slides from 109 patients over a period of 5 weeks were included in this validation and were assessed by all pathologists in both analyses (digital and conventional) to allow intraobserver comparison. The intraobserver agreement between the digital method (DM) and conventional method (CM) was considered almost perfect (κ ranged from 0.85 to 0.98, with 95% CI, ranging from 0.81 to 1). The most significant and frequent disagreements within trainees encompassed epithelial dysplasia grading and differentiation among severe dysplasia (carcinoma in situ) and oral squamous cell carcinoma. The most frequent pitfall from DM was lag in screen mirroring. The lack of details of inflammatory cells and the need for a higher magnification to assess dysplasia were pointed in one case each. The COVID-19 crisis has accelerated and consolidated the use of online meeting tools, which would be a valuable resource even in the post-pandemic scenario. Adaptation in laboratory workflow, the advent of digital pathology and remote reporting can mitigate the impact of similar future disruptions to the oral and maxillofacial pathology laboratory workflow avoiding delays in diagnosis and report, to facilitate timely management of head and neck cancer patients. Graphical abstract.

Neuroblastoma is the most common extracranial solid cancer of infancy, occurring mainly in the adrenal gland, with high metastatic potential. However, involvement of the head and neck region is rare. Here, we present two cases of metastatic neuroblastoma of childhood, in which a mandibular swelling was the first sign of disseminated disease. Case 1 describes a 4-year-old boy with a 2-week history of painful swelling in the left mandibular region, body soreness and weakness. Panoramic radiography and computed tomography showed a destructive lesion in the left mandibular ramus. Case 2 describes a 3-year-old boy with a 1-month history of swelling in the right mandibular area. Panoramic radiograph and cone-beam computed tomography showed a destructive lesion in the right body and ramus of the mandible, displacing tooth germs, with the destruction of vestibular and lingual bone cortices. In both cases, microscopic analyses revealed a diffuse proliferation of small, round, and blue cells with hyperchromatic nuclei and scant cytoplasm. While Case 1 was more undifferentiated, Case 2 presented eosinophilic areas suggestive of neuropil. A large immunohistochemical panel was performed, showing expression of neural markers such as CD56, neuron-specific enolase (in Case 2), chromogranin, and synaptophysin. Both lesions presented a high proliferation index (Ki67 > 70% and 80%, respectively). Positron emission tomography-computed tomography revealed ipsilateral adrenal primary lesions in both cases, with multiple bone metastatic lesions. Besides the mandible, multiple sites of the axial and appendicular skeleton were affected. Treatment consisted of induction chemotherapy, adrenalectomy, consolidation chemoradiotherapy, and post-consolidation therapy.

Adenoid cystic carcinoma (ACC) is a biphasic malignant lesion that can develop at various anatomical sites. Salivary and lacrimal ACC lesions have a high risk of local invasion, metastasis, and poor prognosis. In more distant organs, such as the breast, ACC is a rarer and less aggressive lesion. One of the major predictors of mortality of ACC is perineural invasion, which can be seen in 30 % of breast lesions, 85% of salivary lesions, and almost 100 % of lacrimal gland tumors. The biological differences between these three ACC tumors are still poorly understood. We focused on the current understanding of the genetic variations observed on ACC tumors and prognostic differences associated with distinct anatomical sites. A special effort was made to present the currently available therapies alongside the emerging strategies under development.

Electronic cigarette (e-cigarette) use is growing significantly worldwide, especially among young people. This product has been associated with renormalizing smoking and hindering quit attempts in smokers. Moreover, among nonsmokers, it can lead to subsequent cigarette smoking and nicotine dependence. The present study aimed to assess the epidemiological profile of e-cigarette users worldwide.A systematic review was performed using 3 main electronic databases (Medline/PubMed, SCOPUS, and EMBASE). Studies were independently assessed by 2 reviewers based on established eligibility criteria. The risk of bias was assessed using the MAStARI critical appraisal instrument.From 4,496 records, 43 were included. Among the 1,238,392 participants, 132,786 (10.72%) were e-cigarette users. The age range with the highest percentage of e-cigarette users was 18-24 years old, with 40,989 (30.86%) males, 34,875 (26.26%) females, and 33.6% being current cigarette smokers. The highest prevalence of users was 52.88% in Croatia and 49.62% in New Zealand. Other possible correlations were observed with e-cigarette use, such as a high level of education.Overall, e-cigarette users tended to be male young adults with a higher level of education. The highest prevalence of use was found in Croatia. This systematic review provides valuable information to improve the development of appropriate intervention strategies targeting e-cigarette users for more accurate anti-smoking actions.

Objectives Describe the epidemiological profile of patients with oral squamous cell carcinoma (OSCC) around dental implants (DI), investigate the spectrum of clinical and pathological characteristics, and discuss the implications of diagnosis delay of these lesions. Methods Retrospective analysis of patients treated of OSCC adjacent to DI at A.C. Camargo Cancer Center between 2009 and 2020. Results Thirty one patients were identified, being women the majority (58.1%). The mean age of the patients was 68.8 years. Never smoker corresponds to 46.9% and never alcohol consumer to 54.9% of the sample. OPMD was reported in 45.2% of patients, affecting mainly women (78.5%). Leukoplakia (63.7%) followed by oral lichen planus (36.3%) was the most common OPMD found in women. OSCC adjacent to DI occurred in the inferior gingiva/alveolar mucosa in 48.3% of cases, and ulceration was the most common clinical appearance (87%). Peri-implantitis (PI) was initial clinical diagnosis in 16.1% of cases. Conclusions Oral squamous cell carcinoma adjacent to DI was more common in women over 70 years old, non-smokers and non-drinker, and the majority had oral leukoplakia before the diagnosis of OSCC. OSCC may present clinical and radiographic features that resemble PI which can delay the diagnosis and impair the prognosis.

Eruption sequestrum (ES) is a single or even multiple, small whitish calcified masses found within the soft tissue of the opercula overlying the crown of erupting permanent molars of children. We herein report a well-documented case of ES, offering a review of published cases in the English literature. An otherwise healthy 6-year-old girl was seen for routine dental examination. A fragment of hard whitish tissue was observed in the gingiva overlying the erupting lower first permanent molar, which showed radiographic appearance of a faint round radiopacity above and separated from the occlusal surface of the related tooth. The patient was submitted to an excisional biopsy, and gross examination showed a hardened whitish fragment surrounded by gingival mucosa. Microscopic examination revealed odontogenic epithelium in association with chronic inflammatory infiltrate and small blood vessels in the connective tissue. Small concentric basophilic calcifications, round osteodentin, and pulp-like structures were also observed. The microscopic evaluation of additional cases of ES may improve the understanding of this uncommon inflamed odontogenic hamartoma.

Myofibroma (MF) is a benign mesenchymal myofibroblast-derived tumor, which occurs most frequently in children, and rarely affects the maxilla. We reported a case of an aggressive intraosseous lesion found in the maxilla of a 9-year-old female child. Intraorally, the swelling extended from tooth 12 to 16, causing displacement of teeth 13, 14, and 15. Computed tomography revealed a large osteolytic lesion causing thinning and cortical erosion. Microscopically, the lesion showed a proliferation of spindle-shaped cells, with elongated nuclei and eosinophilic cytoplasm, arranged in interlaced fascicles. The immunohistochemical analysis revealed cytoplasmic positivity for α-SMA and HHF-35, and negativity for desmin, laminin, S-100, β-catenin, and CD34. Ki-67 was positive in 8% of tumor cells. The diagnosis was MF. Herein, we describe an additional case of central MF arising in the maxilla, including clinical, imaging, microscopical, and immunohistochemical features, as well as a review of the literature.

Adenoid ameloblastoma is a very rare benign epithelial odontogenic tumor characterized microscopically by epithelium resembling conventional ameloblastoma, with additional duct-like structures, epithelial whorls, and cribriform architecture. Dentinoid deposits, clusters of clear cells, and ghost-cell keratinization may also be present. These tumors do not harbor BRAF or KRAS mutations and their molecular basis appears distinct from conventional ameloblastoma but remains unknown. We assessed CTNNB1 (beta-catenin) exon 3 mutations in a cohort of 11 samples of adenoid ameloblastomas from 9 patients. Two of the 9 patients were female and 7 male and in 7/9 patients the tumors occurred in the maxilla. Tumors of 4 of these 9 patients harbored CTNNB1 mutations, specifically p.Ser33Cys, p.Gly34Arg, and p.Ser37Phe. Notably, for one patient 3 samples were analyzed including the primary tumour and two consecutive recurrences, and results were positive for the mutation in all three tumors. Therefore, 6/11 samples tested positive for the mutation. In the 6 mutation-positive samples, ghost cells were present in only 2/6, indicating beta-catenin mutations are not always revealed by ghost cell formation. Dentinoid matrix deposition was observed in 5/6 mutation-positive samples and clear cells in all 6 cases. None of the cases harbored either BRAF or KRAS mutations. Beta-catenin immunoexpression was assessed in the samples of 8 patients. Except for one wild-type case, all cases showed focal nuclear expression irrespective of the mutational status. Together with the absence of BRAF mutation, the detection of beta-catenin mutation in adenoid ameloblastomas supports its classification as a separate entity, and not as a subtype of ameloblastoma. The presence of this mutation may help in the diagnosis of challenging cases.

Good communication between clinicians and pathologists is a vital element in the diagnostic process, and poor communication can adversely affect patient care. There is a lack of research about communication in diagnostic oral and maxillofacial pathology. This narrative review explores different aspects of the quality of communication between clinicians and oral pathologists, with a focus on the diagnosis of oral and maxillofacial diseases. An electronic search was carried out in MEDLINE through the PubMed, Scopus, and Embase databases up to April 2021. No studies reporting communication, its adequacy or the required skills between clinicians and pathologists in oral diagnosis were found. According to studies published in medicine, strategies for improving communication skills include clinician-pathologist collaboration; a well-formatted, clear and thorough report; training in communication skills; and patient-centered care. Further studies evaluating the current practices and quality in oral and maxillofacial pathology are required to identify barriers and encourage optimal communication to facilitate diagnosis, as well as patient safety.

This study tested the hypothesis that head and neck radiotherapy (HNRT) impacts the immunoexpression of type I collagen, bone sialoprotein (BSP) and bone morphogenetic protein 4 (BMP4), thereby leading to micromorphological changes in the dentin-pulp complex (DPC), and promoting the onset and progression of radiation caries (RC). Twenty-two demineralized sections of carious teeth (a group of 11 irradiated teeth and a control group of 11 non-irradiated teeth) extracted from 19 head and neck cancer patients were analyzed by conventional optical microscopy and immunohistochemistry to investigate the micromorphology (cellular layer hierarchy, blood vessels, odontoblasts, fibroblasts, extracellular matrix, calcification, necrosis, reactionary dentin formation, and chronic inflammation), and the patterns of staining/immunolocalization of type I collagen, BSP and BMP4 in the dental pulp of irradiated and control samples. No significant differences attributable to the direct impact of radiotherapy were detected in DPC micromorphology between the groups. In addition, the patterns of immunohistochemical staining and immunolocalization of the proteins studied did not differ between the irradiated and the control samples for type I collagen, BSP or BMP4. This study rejected the hypothesis that HNRT directly damages dentition by changing the organic components and the microstructure of the DPC, ultimately leading to RC.

High-risk (HR) human papillomavirus (HPV) infection is recognized as a primary etiologic factor of anogenital cancers and more recently of a subgroup of oropharyngeal squamous cell carcinomas (OPSCC). The incidence of HPV-related OPSCC has increased dramatically in several developed countries in the past 3 decades and is currently the most common cancer caused by HR-HPV in the United States and Germany, surpassing cervical cancer. Consequently, the patient's demographic and clinicopathologic profile has shifted to nonsmoking and nondrinking younger men with higher schooling level and with a history of multiple oral sex partners. Patients with HPV-related OPSCC often show better treatment outcomes and higher survival rates than their HPV-unrelated counterparts, which has led to a change in tumor staging for HPV-related cases. HPV vaccination is emerging as an effective primary prevention strategy, and systematic screening of HPV DNA in blood and salivary oral rinse samples of HR patients is being examined to determine if it may provide a surveillance method and support early diagnosis of HPV-related OPSCC. In this context, a narrative review was conducted to provide an overview of the state-of-the-art of HPV-related OPSCC, including epidemiology, risk factors, clinicopathologic and molecular features, screening, prevention, management, and prognosis.

This study reports 9 additional tongue hamartomas in children paired with a literature review. A retrospective analysis was performed from 3 Oral Pathology laboratories. Additionally, a literature review was conducted through 5 electronic databases and gray literature. A total of 9 cases were identified in the retrospective analysis. Females outnumbered males with a ratio of 1.25:1. The age of presentation ranged from 2 weeks to 7 years. The posterior dorsum tongue was the most affected subsite (n = 4). One case was seen in a patient with oro-facial-digital syndrome, 2 cases in patients with cleft palates, and one case with an encephalocele. The most common predominant component was salivary gland tissue (n = 4). A literature search included 79 pediatric patients presenting with 95 tongue hamartomas. A slight female (n = 47) predilection was observed, with ages varying from 15 hours to 19 years. The posterior tongue dorsum (n = 31) was the most affected site. Seven cases were seen in association with syndromes. The most common predominant component was smooth muscle (n = 35). Although hamartomas are rare in the oral cavity, they should be considered in the differential diagnosis of masses involving the posterior tongue dorsum in children.

Diffuse large B cell lymphoma, not otherwise specified (DLBCL, NOS) is the most frequent non-Hodgkin lymphoma subtype. This aggressive neoplasm may variably express the CD30 protein, which may be used as a therapeutic target for this tumor. However, CD30 expression in DLBCL NOS arising from the oral cavity and the oropharynx has not been investigated. Therefore, this study aims to determine the frequency of CD30 expression and its prognostic significance for patients affected by oral/oropharyngeal DLBCL NOS. Fifty cases were retrieved from pathology files and submitted to immunohistochemistry against CD30. Reactivity was accessed by two oral pathologists using two cut-off values (> 0% and > 20% of tumor cells) to determine positivity in each case. Clinical data were obtained from the patients' medical files to investigate the prognostic potential of the protein. Seven high-grade B cell lymphomas and two EBV-positive DLBCL NOS were identified. We found one CD30-positive case in each of these two groups of lymphomas. Among the remaining 41 DLBCL NOS, other four cases (three in the oral cavity and one in the oropharynx) were positive for CD30, but only two expressed the protein in > 20% of tumor cells, both in the oral cavity. Survival analysis demonstrated that CD30-positive cases had a higher five-year overall survival rate (75%) than CD30-negative cases (32.3%), although a statistically significant result was not achieved (p = 0.19). Only a minor subset of oral and oropharyngeal DLBCL NOS express CD30 and these patients seems to have a higher survival rate.

To evaluate the impact of the COVID-19 pandemic on the number of diagnoses of oral and maxillofacial lesions in public laboratories after one year of COVID-19 outbreak in Brazil.This is a cross-sectional study. Biopsies submitted to histopathologic examination from March 2019 to February 2020 (pre-pandemic period) and from April 2020 to March 2021 (pandemic period) in nine Brazilian public oral pathology laboratories were retrieved and the number of diagnoses, types of lesion, and percentage changes during both periods were analyzed.There were 7389 diagnoses in the pre-pandemic period and 2728 in the pandemic era, indicating a reduction of 63.08%. The reduction was 64.23% for benign lesions and 49.48% for malignant lesions, with a 50.64% reduction in squamous cell carcinoma. The largest decreases were observed in April 2020 and January 2021.An important reduction in the diagnoses of benign and malignant lesions was noted in the Brazilian public oral pathology laboratories during the first year of the COVID-19 pandemic.

AIM: To Evaluate the potential use of Cephaeline as a therapeutic strategy to manage mucoepidermoid carcinomas of the salivary glands. MATERIAL AND METHODS: Mucoepidermoid carcinoma cell lines UM-HMC-1, UM-HMC-2, and UM-HMC-3A MEC were used to establish the effects of cephaeline over tumor viability determined by MTT assay. In vitro wound healing scratch assays were performed to address cellular migration while immunofluorescence staining for histone H3 lysine 9 (H3k9ac) was used to identify the acetylation status of tumor cells upon cephaeline administration. The presence of CSC was evaluated by the identification of ALDH enzymatic activity by flow cytometry and through functional assays using in vitro tumorsphere formation. RESULTS: A single administration of Cephaeline resulted in reduced viability of MEC cells along with the halt on tumor growth and cellular migration potential. Administration of Cephaeline resulted in chromatin histone acetylation as judged by increased levels of H3K9ac and disruption of tumorspheres formation. Interestingly, ALDH levels were increased in UM-HMC-1 and UM-HMC-3A cell lines, while UM-HMC-2 shown a reduced enzimatic activity. CONCLUSION: Cephaeline has shown anti-cancer properties in all MEC cell lines tested by regulating tumor cells viablity, migration, proliferation, and by disrupting the ability of cancer cells in generate tumorspheres.

To integrate the available data published on malignant peripheral nerve sheath tumours (MPNST) of the oral and maxillofacial region. Searches in Embase, PubMed, Web of Science and Scopus were conducted for the identification of case reports/case series in English language. The risk of bias was assessed using the Joanna Briggs Institute tool. Outcomes were evaluated by Cox regression and Kaplan-Meier methods. A total of 306 articles were retrieved, 50 of which reporting 57 MPNST were included. The lesion showed a predilection for the mandible (n = 18/31.57%) of middle-aged adults (~40.5 years) with a male/female ratio of 1.1:1. The individuals were mostly symptomatic with a mean evolution time of 9.6 months. Surgical removal plus adjuvant therapy (especially radiotherapy) was the main approach (51.86%). Recurrence was reported in 39.62% of cases. Nodal and distant metastases were identified in 28.26% and 26.66% of cases, respectively. The 2-year cumulative survival rate was 55%. Independent predictors of poor survival were the presence of neurofibromatosis type 1 (p = 0.04) and distant metastases (p = 0.004). The diagnosis of MPNST is challenging due to the variety of its clinical and histopathological presentations. Local aggressiveness and the potential for metastases are common outcomes of this neoplasm.

Background Although uncommon, mature small B-cell lymphomas may arise in the oral/maxillofacial area and oral pathologists must be aware of the key characteristics of these neoplasms to perform an accurate diagnosis. In this manuscript, we attempted to integrate the currently available data on the clinicopathological features of follicular lymphoma (FL), mantle cell lymphoma (MCL), extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT-L), and chronic lymphocytic leukemia/ small lymphocytic lymphoma (CLL/SLL) affecting these anatomical regions. Methods An updated descriptive literature review was carried out and a detailed electronic search was done in multiple databases to gather all cases affecting the oral/maxillofacial region and palatine tonsils. Results We observed that MALT-L was the most frequently reported subtype, followed by FL, MCL, and CLL/SLL. The palate was affected in a high proportion of cases and the most usual clinical presentation was an asymptomatic swelling. MALT-L and CLL/SLL neoplastic cells were strongly associated with small salivary glands. FL showed no gender preference, while MCL and CLL/SLL were more prevalent in males and MALT-L in females. Overall, cases were more common in elderly individuals. Patients' treatment and outcome varied, with MCL being the most aggressive neoplasm with a dismal prognosis in comparison to FL and MALT-L. Conclusion Despite the poor documentation in many of the cases available, especially regarding the microscopic and molecular features of tumors, this review demonstrated that the oral mature small B-cell lymphomas investigated share similar clinical presentation, but carry different prognostic significance, demanding an accurate diagnosis. The authors are grateful to the SAo Paulo State Research Foundation (FAPESP 2016/21785-4) for the student scholarship. Felipe Paiva Fonseca, Jean Nunes dos Santos, Pablo Agustin Vargas, and Manoela Domingues Martins are research fellows of the Brazilian National Council for Scientific and Technological Development (CNPq)

Background The objective of this study investigated the distribution of immature dendritic cells (DCs), Langerhans cells and plasmacytoid DCs in oral submucous fibrosis (OSMF), OSMF associated with oral squamous cell carcinoma (OSMF-OSCC), oral leukoplakia (OL), and oral squamous cell carcinoma (OSCC). Material and Methods Fourteen cases of OSMF, 9 of OSMF-OSCC, 8 of OL¸ 45 of OSCC and 8 of normal epithelium were retrospectively retrieved and their diagnoses confirmed. Immunoreactions against CD1a, CD207 e CD303 were performed and the number of positive cells quantified. Results A significant decrease of CD1a+ was found in OSMF (p≤0.05), OSMF-OSCC (p ≤ 0.01), and OSCC (p ≤ 0.001) when compared to normal epithelium. For CD207+ the significance decrease was observed in OSMF-OSCC (p ≤ 0.05), and OSCC (p ≤ 0.01) when compared with normal epithelium, and in OSMF when compared with OL (p ≤ 0.05). There was no significant difference for CD303, but increased in CD303+ was observed in OSCC when compared with normal epithelium. Conclusions The decrease in the number of CD1a+ and CD207+ cells may be associate to the development of oral OSCC, and in OPMDs they might be indicators of malignant transformation. Key words:Premalignant lesions, oral submucous fibrosis, oral squamous cell carcinoma, immune response.

Objective The aim of this study was to determine the proteome of adenoid cystic carcinoma (AdCC) and polymorphous adenocarcinoma (PAc) and to identify a protein signature useful in distinguishing these two neoplasms. Study Design Ten cases of AdCC and 10 cases of PAc were microdissected for enrichment of neoplastic tissue. The samples were submitted to liquid chromatography–tandem mass spectrometry (LC-MS/MS), and the proteomics data were analyzed by using the MaxQuant software. LC-MS/MS spectra were searched against the Human UniProt database, and statistical analyses were performed with Perseus software. Bioinformatic analyses were performed by using discovery-based proteomic data on both tumors. Results LC-MS/MS analysis identified 1957 proteins. The tumors shared 1590 proteins, and 261 were exclusively identified in AdCC and 106 in PAc. Clustering analysis of the statistically significant proteins clearly separated AdCC from PAc. Protein expression 10 times higher in one group than in the other led to a signature of 16 proteins—6 upregulated in AdCC and 10 in PAc. A new clustering analysis showed reverse regulation and also differentiated both tumors. Conclusions Global proteomics may be useful in discriminating these two malignant salivary neoplasms that frequently show clinical and microscopic overlaps, but additional validation studies are still necessary to determine the diagnostic potential of the protein signature obtained.

OBJECTIVES The aim of this study was to investigate the prevalence of oral sarcomas from geographic regions of Brazil. MATERIALS AND METHODS A cross-sectional study was conducted on biopsies obtained from January 2007 to December 2016 at twelve Brazilian oral and maxillofacial pathology centres. Gender, age, evolution time, clinical aspects, tumour location, tumour size at diagnosis, radiographic aspects and histopathological diagnosis were evaluated. Data were analysed using descriptive statistical methods. RESULTS From 176,537, a total of 200 (0.11%) oral sarcomas were reported, and the most prevalent were osteosarcomas (74 cases; 37%) and Kaposi's sarcomas (52 cases; 26%). Males were more affected than females at a mean age of 32.2 years old (range of 3-87 years). The most common symptoms were swelling¸ localised pain and bleeding at a mean evolution time of 5.14 months (range

Objectives To evaluate the expression of brain-derived neurotrophic factor (BDNF), its tyrosine kinase receptor B (TrkB), and two downstream targets of this pathway, Akt and ribosomal protein S6 (RPS6), in normal oral mucosa (NOM), oral leukoplakia (OL), and oral squamous cell carcinoma (OSCC) and correlate this expression with OSCC patients' outcomes, cell senescence, and "stemness" profile. Materials and methods Ten cases of NOM, 32 OL, and 72 primary OSCC were included. Immunohistochemical analysis for BDNF, TrkB, p-TrkB, p-Akt, and p-RPS6 was performed. Cell senescence and stemness profile of OSCC were evaluated through p16 and BMI-1 immunohistochemical expression, respectively. The slides were scanned into high-resolution images and quantified through digital analysis. Results Oral squamous cell carcinoma presented increased expression of BDNF/TrkB/Akt pathway compared to NOM and OL. OSCC diagnosed in advanced clinical stages presented an upregulation of BDNF and p-TrkB. BDNF and p-Akt were identified as predictors of poor disease-specific survival. The increase in stemness profile was correlated with a decrease in p-TrkB and p-Akt expression. Conclusions BDNF/TrkB/Akt pathway is significantly increased in malignant cells from OSCC. Moreover, BDNF and Akt represent biomarkers capable to predict a poor prognosis of OSCC patients.

Head and neck cancer (HNSCC) are one of the most common solid malignancies of the world, being responsible for over 350,000 deaths every year. Much of the complications in managing and treating HNSCC advent from the complex genetic and epigenetic landscape of the disease. Emerging information has shown promising results in targeting BRD4, an epigenetic regulator bromodomain that functions as a scaffold for transcription factors at promoters and super-enhancers. Here we show that by disrupting the interaction between BRD4 and histones using the bromodomain inhibitor JQ1, HNSCC cells undergo cell growth arrest followed by cellular senescence. Mechanistically, JQ1 negatively impacted the phosphorylation levels of SIRT1 along with the acetylation levels of mutant p53 (active). In vivo administration of JQ1 resulted in disruption of HNSCC growth along with the activation of cellular senescence, observed by the accumulation of DNA double-strand breaks, p16(ink4), accumulation of senescence-associated beta-galactosidase, and loss of phosphorylated Sirt1(ser47). Furthermore, we also demonstrate that JQ1 was efficient in reducing the population of cancer stem cells from HNSCC xenografts.

The presence of lymphovascular invasion is considered a prognostic determinant for different human neoplasms and is frequently taken into account by surgeons and oncologists to determine patients’ treatment. However, the exact frequency of this microscopic event and its prognostic impact for patients affected by adenoid cystic carcinoma (AdCC) remains unclear. Therefore, the aim of this study was to carry out a systematic review and meta-analysis to address the prevalence and the prognostic potential of lymphovascular invasion in head and neck AdCC. A literature search on PubMed, Scopus, ClinicalTrials.gov , Web of Science and ProQuest databases was undertaken in January 2019. The primary outcomes of interest were overall survival (OS) and disease-free survival (DFS). The relative frequency of lymphovascular invasion and its possible association with other clinicopathological parameters were addressed. A total of 22 studies and 2117 patients were included in this study. The frequency of lymphovascular invasion ranged from 5.2% to 72.5%. Lymphovascular invasion was associated with an increased likelihood of lymph node metastasis (OR = 2.58; 95% CI 1.61–4.12; p = 0.0001) and death (OR = 3.09; 95% CI 1.82–5.26; p = 0.0001), solid/higher-grade AdCC were more likely to present lymphovascular invasion (OR = 5.51; 95% CI 1.87–16-21; p = 0.002) and patients with this microscopic finding had a significantly lower OS (HR = 8.30; 95% CI 1.68–40.91; p = 0.009) and DFS (HR = 3.76; 95% CI 1.13–12.53; p = 0.03). In conclusion, lymphovascular invasion seems to be a significant predictor of poor prognosis for head and neck AdCC patients.

The purpose of this study was to perform a systematic review of the literature concerning all documented cases of malignant transformation of craniomaxillofacial fibro-osseous lesions (FOLs). Three electronic databases were searched. Data were evaluated descriptively. Kaplan-Meier survival curves were constructed and compared using the log-rank test. A critical appraisal of included articles was performed through the Joanna Briggs Institute tool. A total of 19 studies including 27 patients were selected for data extraction. Twenty-six cases were initially diagnosed as fibrous dysplasia and one as ossifying fibroma. The mean age at the time of malignant transformation was 38.11 years, and the average time from initial diagnosis to malignant transformation was 18.2 years. The male:female ratio was 1:1.2, and the maxilla:mandible ratio was 1.5:1. The histological type of the malignant tumor was predominantly osteosarcoma. Follow-up was available for 21 patients. The 3-year overall survival rate was 51%. Mandible tumors and diagnoses other than osteosarcoma tended to have poor survival rates, but no significant difference was identified. We concluded that between all FOLs, only fibrous dysplasia seems to have a considerable increased risk of malignant transformation. Thus, a regular and long follow-up period is advised.

Validation studies of whole slide imaging (WSI) systems produce evidence regarding digital microscopy (DM). This systematic review aimed to provide information about the performance of WSI devices by evaluating intraobserver agreement reported in previously published studies as the best evidence to elucidate whether DM is reliable for primary diagnostic purposes. In addition, this review delineates the reasons for the occurrence of discordant diagnoses. Scopus, MEDLINE/PubMed, and Embase were searched electronically. A total of 13 articles were included. The total sample of 2145 had a majority of 695 (32.4%) cases from dermatopathology, followed by 200 (9.3%) cases from gastrointestinal pathology. Intraobserver agreements showed an excellent concordance, with values ranging from 87% to 98.3% (κ coefficient range 0.8-0.98). Ten studies (77%) reported a total of 128 disagreements. The remaining three studies (23%) did not report the exact number and nature of disagreements. Borderline/challenging cases were the most frequently reported reason for disagreements (53.8%). Six authors reported limitations of the equipment and/or limited image resolution as reasons for the discordant diagnoses. Within these articles, the reported pitfalls were as follows: difficulties in the identification of eosinophilic granular bodies in brain biopsies; eosinophils and nucleated red blood cells; and mitotic figures, nuclear details, and chromatin patterns in neuropathology specimens. The lack of image clarity was reported to be associated with difficulties in the identification of microorganisms (e.g., Candida albicans, Helicobacter pylori, and Giardia lamblia). However, authors stated that the intraobserver variances do not derive from technical limitations of WSI. A lack of clinical information was reported by four authors as a source for disagreements. Two studies (15.4%) reported poor quality of the biopsies, specifically small size of the biopsy material or inadequate routine laboratory processes as reasons for disagreements. One author (7.7%) indicated the lack of immunohistochemistry and special stains as a source for discordance. Furthermore, nine studies (69.2%) did not consider the performance of the digital method-limitations of the equipment, insufficient magnification/limited image resolution-as reasons for disagreements. To summarize the pitfalls of digital pathology practice and better address the root cause of the diagnostic discordance, we suggest a Categorization for Digital Pathology Discrepancies to be used in further validations studies. Among 99 discordances, only 37 (37.3%) had preferred diagnosis rendered by means of WSI. The risk of bias and applicability concerns were judged with the QUADAS-2. Two studies (15.4%) presented an unclear risk of bias in the sample selection domain and 2 (15.4%) presented a high risk of bias in the index test domain. Regarding applicability, all studies included were classified as a low concern in all domains. The included studies were optimally designed to validate WSI for general clinical use, providing evidence with confidence. In general, this systematic review showed a high concordance between diagnoses achieved by using WSI and conventional light microscope (CLM), summarizes difficulties related to specific findings of certain areas of pathology-including dermatopathology, pediatric pathology, neuropathology, and gastrointestinal pathology-and demonstrated that WSI can be used to render primary diagnoses in several subspecialties of human pathology.

BACKGROUND Fatty acid synthase (FASN) is the key molecule for catalyzing fatty acid synthesis and have been associated with several malignant tumors. METHODS We analyzed the expression of FASN and Ki-67, by immunohistochemistry on 29 carcinomas ex-pleomorphic adenoma (CXPAs) and 25 pleomorphic adenomas (PAs). RESULTS Ki-67 proliferation index and FASN expression were significantly higher in patients with CXPA than patients with PA (P

Background The diagnosis of oral and maxillofacial mature T/NK-cell neoplasms is challenging because of their rarity, morphological heterogeneity and complex immunophenotype, with scarce available data describing their clinical and microscopic aspects. Therefore, in this study we investigated a series of mature T/NK-cell neoplasms affecting this anatomical region and provided an updated literature review. Methods Cases diagnosed as mature T/NK cell lymphomas affecting the oral and maxillofacial region were retrospectively retrieved from six pathology files and their diagnoses were confirmed using haematoxylin and eosin-stained slides, immunohistochemical reactions and in situ hybridization for Epstein-Barr virus (EBV) detection. Patients' clinical data were collected from their pathology forms. Results A total of 22 cases were included in this study. Eleven (50%) consisted of extranodal NK/T-cell lymphomas, nasal type; eight (36.4%) were peripheral T-cell lymphomas, NOS; two (9.1%) were adult T-cell leukaemia/lymphomas, and one (4.5%) was an ALK-positive anaplastic large cell lymphoma. Overall, males predominated, with a mean age of 55.7 years. The palate was the most affected site (50%), and tumours usually presented as destructive and painful ulcers. EBV was present in all cases of extranodal NK/T cell lymphoma nasal type, but was absent in the other subtypes. Conclusion Among mature T/NK-cell lymphomas of the oral and maxillofacial region, extranodal NK/T cell lymphoma, nasal type and peripheral T-cell lymphoma, NOS predominated. Older men were the most affected patients, and this heterogenous group of neoplasms has a very aggressive clinical behaviour.

Background Langerhans cell histiocytosis (LCH) is a rare disorder characterized by abnormal proliferation and infiltration of histiocytic cells. Methods This review focused on the main aspects associated with LCH. Results LCH can involve single or multiple organs and systems, with bone and skin being the most commonly affected sites. Regarding skeletal manifestations, the jawbones are involved in about 20%-30% of all cases. Such lesions may present as unilocular or multilocular images mainly affecting the posterior mandible. Oral soft tissue lesions may also occur, with the gingiva and hard palate being the most frequently affected sites. Conclusion The diagnosis and management of LCH are challenging, requiring a multidisciplinary approach, with dentists playing a central role since oral manifestations can be the first sign of the condition.

Optimizing the quality of referral letters could be the first step to a correct clinical approach for patients. Referral letters should be legible and contain the necessary information to avoid delaying the patient's diagnosis and treatment. However, to date, few studies have been conducted on how referrals are performed in Brazil. Knowledge regarding the quality of referral letters can provide information to better guide health care professionals. This study was aimed at analyzing all referrals received by a single oral medicine service in Brazil. Referral letters were classified into poor, regular, good, and excellent based on key items concerning the primary morphology of the lesion, location, diagnostic hypothesis, symptomatology, time of evolution, consistency, size, and limits. A total of 500 referral letters were evaluated, including 271 (54.2%) from a private service and 229 (45.8%) from a public service. Dentists and physicians had written 475 (95%) and 25 (5%) referral letters, respectively. Among the 500 referrals analyzed in this study, the number of regular, poor, good, and excellent referrals was 236 (47.2%), 203 (40.6%), 58 (11.6%), and one (0.6%), respectively, showing a lack of important clinical information in referrals.

Objectives Ameloblastoma is an odontogenic epithelial tumour with a low expression of mismatch repair system components. We aimed to investigate the methylation status of the genes MSH2, MSH3 and MSH6 (MutS group) in conventional ameloblastomas. Materials and methods The ameloblastoma and dental follicle samples (n = 10 each) were collected from 20 different patients. Each ameloblastoma sample was sectioned into two fragments: one was paraffin-embedded while the other one, likewise the dental follicle samples, was fixed in RNAlater and frozen at -196°C. All frozen samples were investigated for the MutS genes methylation levels, using the enzymatic restriction digestion and quantitative real-time PCR (qPCR) assay. The ameloblastoma paraffin-embedded samples were submitted to immunohistochemical reactions for MutS proteins detection and digitally quantification. Correlation analyses were performed between the immunohistochemical results and the respective gene methylation percentage. Results There are no significant differences between the MutS genes methylation levels in the ameloblastoma and the dental follicle. However, a strong negative correlation was found between MSH2 and MSH6 gene methylation status and their respective proteins expressions evaluated by immunohistochemistry. Conclusion Our results show that the genes methylations is in part responsible for decreasing the expression of MSH2 and MSH6 genes in ameloblastoma.

We present a challenging case of HIV-related lymphangioma-like Kaposi sarcoma (LLKS) affecting the oral cavity. A 54-year-old Brazilian male patient was referred to our center complaining of bleeding lesions affecting the oral cavity for 2 months. Interestingly, these oral lesions were the first clinical manifestation of HIV infection. Clinically, multiple erythematous nodular and patch lesions were observed. An incisional biopsy was performed, revealing numerous microscopic angled and irregular vascular channels lined with flattened endothelial cells. More cellularized and solid areas consisting of more fusiform cells with little pleomorphism and with slit-like vascular channels were noted. Based on immunoreactivity for CD31, CD34, D2-40, and HHV-8, the final diagnosis was oral LLKS. Highly active antiretroviral therapy (HAART) was initiated with dolutegravir, tenofovir, and lamivudine. During follow-up, the patient showed KS metastases to other sites and a chemotherapeutic protocol was initiated. Regression of the oral lesion was clearly noted by the clinicians 1 year after the KS diagnosis. Dentists should be able to recognize systemic diseases that affect the oral cavity such as KS in order to make an early diagnosis of its oral manifestations and to implement effective therapeutic measures to ensure a better prognosis.

OBJECTIVE: To report the clinicopathologic features of acquired oral syphilis cases in South American countries. MATERIALS AND METHODS: Clinical data were retrospectively collected from the records of 18 oral diagnostic services in Argentina, Brazil, Chile, Colombia, Venezuela, Uruguay, and Peru. Serologies of nontreponemal and treponemal tests were used for diagnosis. RESULTS: The series comprised 339 cases of acquired oral syphilis. Secondary syphilis ranked as the most common stage (86.7%). Lesions were more frequent among males (58.0%) and young adults with a mean age of 33.3 years. Individuals aged 20-29 years were most affected (35.3%). The most commonly involved sites were the tongue (31.6%), lip/labial commissure (25.1%), and hard/soft palate (20.4%). Clinically, acquired oral syphilis usually presented as mucous patches (28.4%), papules (25.7%), and ulcers (18.1%). Skin manifestations occurred in 67.7% of individuals, while lymphadenopathy and fever were observed in 61.3% and 11.6% of all subjects, respectively. Most patients were treated with the benzathine penicillin G antibiotic. CONCLUSION: This report validates the spread of acquired oral syphilis infection among young adults in South America. Our directives include accessible diagnostic tools for proper disease screening, surveillance, and counselling of affected individuals, especially in low- and middle-income countries