Publications by authors named "Pablo Agustin Vargas"

215 Publications

Adenoid ameloblastoma harbors beta-catenin mutations.

Mod Pathol 2022 Jul 15. Epub 2022 Jul 15.

Department of Pathology, Biological Science Institute (ICB), Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, Brazil.

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.
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http://dx.doi.org/10.1038/s41379-022-01125-4DOI Listing
July 2022

Molecular profile of head and neck rhabdomyosarcomas: A systematic review and meta-analysis.

Oral Surg Oral Med Oral Pathol Oral Radiol 2021 Dec 25:4783. Epub 2021 Dec 25.

Unit of Oral & Maxillofacial Pathology, School of Clinical Dentistry, University of Sheffield, Sheffield, UK.

Objective: This systematic review aimed to identify the molecular alterations of head and neck rhabdomyosarcomas (HNRMS) and their prognostic values.

Study Design: 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.

Results: 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.

Conclusion: 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.
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http://dx.doi.org/10.1016/j.oooo.2021.12.128DOI Listing
December 2021

A rare case of squamous cell carcinoma of the gingiva: A diagnostic challenge.

Oral Oncol 2022 Sep 24;132:105995. Epub 2022 Jun 24.

Oral Semiology and Oral Pathology, Department of Oral Diagnosis, Piracicaba School of Dentistry, University of Campinas, Piracicaba, São Paulo, Brazil. Electronic address:

Background: Oral squamous cell carcinoma (OSCC) of the gingiva represents less than 6% of intraoral carcinomas.

Case Report: A 51-year-old male patient presented with a history of a symptomatic red spot with periods of remission and recurrence in the mandibular gingiva. On clinical examination red and white areas were observed in the gingiva, particularly around the left lower molars. Diagnosis of gingival lichen planus was suspected and topical corticosteroids was prescribed. A good clinical response was observed with reduction of symptom. The patient remained in regular follow-up and after 9 months, the lesion suddenly changed, became ulcerated and diagnosis of OSCC was established.

Conclusion: The clinical manifestation of OSCC can eventually mimic other even more common lesions of the oral mucosa, highlighting the importance of considering OSCC as differential diagnosis of any unexplained and persistent lesion in the oral cavity.
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http://dx.doi.org/10.1016/j.oraloncology.2022.105995DOI Listing
September 2022

State-of-the-science concepts of HPV-related oropharyngeal squamous cell carcinoma: a comprehensive review.

Oral Surg Oral Med Oral Pathol Oral Radiol 2022 08 8;134(2):190-205. Epub 2022 Apr 8.

Oral Diagnosis Department, Piracicaba Dental School, University of Campinas (UNICAMP), Piracicaba, Brazil. Electronic address:

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.
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http://dx.doi.org/10.1016/j.oooo.2022.03.016DOI Listing
August 2022

Distribution and Frequency of Salivary Gland Tumours: An International Multicenter Study.

Head Neck Pathol 2022 May 27. Epub 2022 May 27.

Unit of Oral and Maxillofacial Pathology, School of Clinical Dentistry, University of Sheffield, Sheffield, S10 2TA, UK.

Background: Salivary gland tumours (SGT) are a relatively rare group of neoplasms with a wide range of histopathological appearance and clinical features. To date, most of the epidemiological studies on salivary gland tumours are limited for a variety of reason including being out of date, extrapolated from either a single centre or country studies, or investigating either major or minor glands only.

Methods: This study aimed to mitigate these shortcomings by analysing epidemiological data including demographic, anatomical location and histological diagnoses of SGT from multiple centres across the world. The analysed data included age, gender, location and histological diagnosis from fifteen centres covering the majority of the world health organisation (WHO) geographical regions between 2006 and 2019.

Results: A total of 5739 cases were analysed including 65% benign and 35% malignant tumours. A slight female predilection (54%) and peak incidence between the fourth and seventh decade for both benign and malignant tumours was observed. The majority (68%) of the SGT presented in major and 32% in the minor glands. The parotid gland was the most common location (70%) for benign and minor glands (47%) for malignant tumours. Pleomorphic adenoma (70%), and Warthin's tumour (17%), were the most common benign tumours whereas mucoepidermoid carcinoma (26%) and adenoid cystic carcinoma (17%) were the most frequent malignant tumours.

Conclusions: This multicentre investigation presents the largest cohort study to date analysing salivary gland tumour data from tertiary centres scattered across the globe. These findings should serve as a baseline for future studies evaluating the epidemiological landscape of these tumours.
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http://dx.doi.org/10.1007/s12105-022-01459-0DOI Listing
May 2022

Clinicoradiological spectrum of primary aneurysmal bone cysts of the maxillofacial region: A series of 31 cases.

Dentomaxillofac Radiol 2022 Jul 23;51(5):20220071. Epub 2022 May 23.

Department of Oral Pathology and Oral Biology, Faculty of Health Sciences, University of Pretoria, Pretoria, South Africa.

Objectives: The aim of the current study was to analyse the demographic, clinical and radiological features of primary aneurysmal bone cysts (ABCs) involving the maxillofacial region.

Methods: Histologically confirmed cases affecting the maxillofacial region were retrospectively reviewed over a 21-year period (2000-2021). Cases were collected from the archives of five Oral Pathology laboratories from three countries: South Africa, Guatemala and Brazil. The information was analysed, with emphasis on the clinical and radiological spectrum.

Results: Following the inclusion criteria, a total of 31 cases of primary ABCs were included in the study. A nearly equal male-to-female distribution was seen, with ABCs occurring in males at an earlier age compared to females. Localised swelling was the main clinical presentation. ABCs had a mandibular predominance, particularly in the posterior regions. All ABCs presented as blow-out expansile well-demarcated radiolucent lesions with the majority having a multilocular appearance. Cortical expansion was seen in 91% of cases with loss of cortical integrity being common (78%).

Conclusion: Primary ABCs involving the maxillofacial region are extremely rare with the majority of current published literature consisting of isolated case reports. The current study is the first large series detailing the radiological features.
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http://dx.doi.org/10.1259/dmfr.20220071DOI Listing
July 2022

Prognostic outcomes of oral squamous cell carcinoma derived from proliferative verrucous leukoplakia: A systematic review.

Oral Dis 2022 Feb 24. Epub 2022 Feb 24.

Department of Oral Diagnosis, Piracicaba Dental School, University of Campinas, Piracicaba, Brazil.

Objective: This study aimed to evaluate prognostic outcomes of PVL-derived oral squamous cell carcinomas (P-OSCC) based on recurrence, new primary tumour, metastasis and survival information.

Study Design: Five databases and grey literature were searched electronically with the following main keywords (proliferative verrucous leukoplakia, squamous cell carcinoma and malignant transformation) to answer the following review question: 'Are survival outcomes for P-OSCC worse?' based on the PECOS principle. The Joanna Briggs Institute Critical Appraisal tool was used to identify possible biases and assess the quality of each of the primary studies.

Results: A total of 21 articles met the inclusion criteria, and the results of this systematic review suggest that P-OSCC can recur and generate new primary tumours; however, metastases are rare. Thus, most patients remain alive for an average period of 5 years.

Conclusion: Apparently, P-OSCC has better clinical prognostic characteristics than conventional OSCC. There is a lack of information on the main prognostic outcomes of P-OSCC; therefore, specific studies must be performed to achieve a better comparison between P-OSCC and conventional OSCC progression.
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http://dx.doi.org/10.1111/odi.14171DOI Listing
February 2022

Adenocarcinoma not otherwise specified (NOS) arising in the sublingual gland: Rare case report and follow-up.

Oral Oncol 2022 03 2;126:105754. Epub 2022 Feb 2.

Oral Semiology and Oral Pathology, Department of Oral Diagnosis, Piracicaba Dental School, University of Campinas, Piracicaba, São Paulo, Brazil. Electronic address:

Background: Adenocarcinoma not otherwise specified (AdCaNOS) is a rare malignant salivary gland tumor that occurs with higher frequency in the parotid gland of male patients. In this study, we described a second case of AdCaNOS arising in the sublingual gland, in a female patient with 39 years of age, highlighting the clinical, radiographic, microscopic, treatment features and follow-up.

Case Report: A 39-year-old female patient presented a fibroelastic nodule with a yellowish coloration, in the left region of the floor of mouth, measuring about 4.0 cm in its largest diameter. An incisional biopsy was performed and the main microscopic features revealed an infiltrative lesion with glandular differentiation organized in cystic spaces, where neoplastic cells secreting eosinophilic material were observed. The tumor showed immunopositivity for pancytokeratin (AE1/AE3), keratins 7 (CK7) and 14 (CK14), and negativity for p63. The proliferation level measured by Ki-67 marker was considered higher. The patient underwent radical surgical resection, but unfortunately, she developed local recurrence, lymph node mestastasis and died 1.5 year after diagnosis.

Conclusion: Although rare in the sublingual gland, particularly at this age, AdCaNOS can occur and early diagnosis and early treatment are essential for a better prognosis and survival rates of the patients.
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http://dx.doi.org/10.1016/j.oraloncology.2022.105754DOI Listing
March 2022

Preservation of immunoexpression of type I collagen, BSP and BMP4 in the dentin-pulp complex of head and neck cancer patients after radiotherapy.

Braz Oral Res 2022 14;36:e012. Epub 2022 Jan 14.

Universidade Estadual de Campinas - Unicamp, Piracicaba Dental School, Oral Diagnosis Department, Semiology and Oral Pathology Areas, Piracicaba, SP, Brazil.

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.
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http://dx.doi.org/10.1590/1807-3107bor-2022.vol36.0012DOI Listing
January 2022

The need for communication between clinicians and pathologists in the context of oral and maxillofacial diseases.

Braz Oral Res 2022 14;36:e008. Epub 2022 Jan 14.

Universidade Estadual de Campinas - Unicamp, Piracicaba Dental School, Department of Oral Diagnosis, Oral Pathology and Semiology Areas, Piracicaba, SP, Brazil.

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.
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http://dx.doi.org/10.1590/1807-3107bor-2022.vol36.0008DOI Listing
January 2022

Impact of the COVID-19 pandemic on public University laboratories of oral and maxillofacial pathology: A Brazilian multicenter study.

Oral Dis 2022 Jan 26. Epub 2022 Jan 26.

Diagnostic Center for Oral Diseases, School of Dentistry, Federal University of Pelotas, Pelotas, Rio Grande do Sul, Brazil.

Objective: 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.

Material And Methods: 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.

Results: 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.

Conclusion: 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.
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http://dx.doi.org/10.1111/odi.14136DOI Listing
January 2022

Clinical and radiologic spectrum of glandular odontogenic cysts: A multicenter study of 92 cases.

Oral Surg Oral Med Oral Pathol Oral Radiol 2022 05 27;133(5):593-603. Epub 2021 Nov 27.

Department of Oral Pathology and Oral Biology, Faculty of Health Sciences, University of Pretoria, Pretoria, South Africa. Electronic address:

Objective: The purpose of this multicenter retrospective study was to report the clinical and radiologic features of 92 glandular odontogenic cysts (GOCs) diagnosed over a 20-year period.

Study Design: Histologically confirmed cases of GOC were retrospectively reviewed from 4 oral pathology laboratories in South Africa and Brazil to categorize the clinical and radiologic 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 2 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 radiologic 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 radiologic signs of aggression is justified based on the high recurrence rate.
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http://dx.doi.org/10.1016/j.oooo.2021.11.008DOI Listing
May 2022

Expression of DNMTs and H3K9ac in Ameloblastoma and Ameloblastic Carcinoma.

Front Oral Health 2021 26;2:751162. Epub 2021 Oct 26.

Department of Oral Diagnosis, Piracicaba Dental School, University of Campinas, Piracicaba, Brazil.

DNA methyltransferases (DNMTs) and the histone modification H3K9ac are epigenetic markers. This study aimed to describe the immunohistochemical expression of DNMT1, DNMT3A, DNMT3B, and H3K9ac in the dental follicle (DF), ameloblastoma (AME), and ameloblastic carcinoma (AC), correlating these expressions with the recurrence and aggressive behavior in ameloblastoma. Immunohistochemical reactions were performed in 10 human DFs, 38 ameloblastomas, and 6 AC samples. Another 59 ameloblastomas assembled in a tissue microarray were used to compare the immunoexpression with the clinical, radiographic, and histopathological characteristics and the presence of BRAFv600e mutation. Each slide was digitized as a high-resolution image and quantified by Aperio ScanScope Nuclear V9 software. All statistical analyzes were performed using GraphPad Prism statistical software. DNMT3B expression was higher in ameloblastomas than in the DFs, while the AC overexpressed all proteins. The ameloblastomas with BRAFv600e mutation, vestibular/lingual, or vestibular/palatine bone cortical disruption and maxilla involvement showed DNMT1 overexpression, while recurrent cases had high DNMT3B levels. DNA methylation and histone modification might play a role in the development, clinical aggressiveness, and recurrence rates of ameloblastoma, such as the progression to AC. Further investigation about gene methylations in ameloblastomas is needed to better understand its relationship with aggressiveness and recurrence.
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http://dx.doi.org/10.3389/froh.2021.751162DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8757744PMC
October 2021

Head and neck radiotherapy leading to extensive late oral soft-tissue necrosis.

Oral Oncol 2022 02 12;125:105710. Epub 2022 Jan 12.

Department of Oral Diagnosis, Piracicaba Dental School, University of Campinas, Piracicaba, Brazil. Electronic address:

Radiotherapy is generally used as an adjuvant treatment in malignant head and neck tumors, which can cause a series of toxicities to tissues involved in the radiation field. Hard tissue necrosis surrounding the tumor is widely debated and recognized; however, oral mucosa necrosis as a late effect of head and neck radiotherapy is a toxicity that has been little explored and understood in the literature. The present report describes a 53-year-old Caucasian, diabetic man with a painful yellowish mass in the buccal mucosa, remaining oral mucositis with history of radiotherapy completed 90 days ago as adjuvant treatment for a polymorphic adenocarcinoma in the palate. Photobiomodulation was used as therapy for tissue necrosis with good therapeutic response despite discontinuation of treatment by the patient. Since there are few descriptions and illustrations of radiotherapy-related soft tissue necrosis, the current case may bring some new experience with this important topic, which directly impacts on the patient's quality of life.
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http://dx.doi.org/10.1016/j.oraloncology.2021.105710DOI Listing
February 2022

Oral and Maxillofacial Neuroendocrine Carcinoma: A Systematic Review.

Head Neck Pathol 2022 Jun 6;16(2):525-537. Epub 2021 Dec 6.

Department of Oral Pathology, Faculdade de Odontologia, School of Dentistry, Universidade Federal do Rio Grande do Sul, R. Ramiro Barcelos, 2492, room 503, Porto Alegre, Rio Grande do Sul, CEP: 90035-003, Brazil.

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.
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http://dx.doi.org/10.1007/s12105-021-01398-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9187797PMC
June 2022

Intraoral mass, extraoral suppuration, and jaw lesions.

Oral Surg Oral Med Oral Pathol Oral Radiol 2022 07 26;134(1):10-14. Epub 2021 Sep 26.

Department of Oral Diagnosis, Piracicaba Dental School, University of Campinas, Piracicaba, Brazil. Electronic address:

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http://dx.doi.org/10.1016/j.oooo.2021.09.010DOI Listing
July 2022

Oral leukoplakia in adolescents: Report of a rare case and review of the literature.

Oral Oncol 2021 11 18;122:105565. Epub 2021 Oct 18.

Department of Oral Diagnosis, Semiology and Pathology Areas, Piracicaba Dental School, University of Campinas, Piracicaba, São Paulo, Brazil.

The aim of this report was to describe a rare case of leukoplakia in a young patient without any risk factors for squamous cell carcinoma. An 18-year-old male patient presented with an asymptomatic white lesion on the right lateral border of the tongue. Microscopic examination of the excisional biopsy specimen displayed hyperkeratosis and acanthosis without epithelial dysplasia, which were consistent with the clinical diagnosis of oral leukoplakia. The patient is undergoing systematic and regular evaluation, and after 28 months of follow-up, no recurrence has been observed. This report showed that, although uncommon, adolescents and/or young adults can also be affected by oral potentially malignant disorders. Therefore, dentists should be aware of this condition to establish the proper diagnosis and management.
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http://dx.doi.org/10.1016/j.oraloncology.2021.105565DOI Listing
November 2021

Cephaeline is an inductor of histone H3 acetylation and inhibitor of mucoepidermoid carcinoma cancer stem cells.

J Oral Pathol Med 2022 Jul 27;51(6):553-562. Epub 2021 Oct 27.

Department of Oral Diagnosis, Piracicaba Dental School, University of Campinas, São Paulo, Brazil.

Aim: To evaluate the potential use of Cephaeline as a therapeutic strategy to manage mucoepidermoid carcinomas (MEC) of the salivary glands.

Material And Methods: UM-HMC-1, UM-HMC-2, and UM-HMC-3A MEC cell lines 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 cancer stem cells 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 the 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 showed a reduced enzymatic activity.

Conclusion: Cephaeline has shown anti-cancer properties in all MEC cell lines tested by regulating tumor cells' viability, migration, proliferation, and disrupting the ability of cancer cells to generate tumorspheres.
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http://dx.doi.org/10.1111/jop.13252DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9013730PMC
July 2022

CD30 Expression in Oral and Oropharyngeal Diffuse Large B Cell Lymphoma, not Otherwise Specified.

Head Neck Pathol 2022 Jun 16;16(2):476-485. Epub 2021 Oct 16.

Department of Oral Surgery and Pathology, School of Dentistry, Universidade Federal de Minas Gerais, Av. Antônio Carlos, 6627, 31270-901, Pampulha, Belo Horizonte, Brazil.

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.
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http://dx.doi.org/10.1007/s12105-021-01387-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9187795PMC
June 2022

Adenoid ameloblastoma with dentinoid is molecularly different from ameloblastomas and adenomatoid odontogenic tumors.

J Oral Pathol Med 2021 Nov 29;50(10):1067-1071. Epub 2021 Sep 29.

Department of Pathology, Biological Sciences Institute, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, Brazil.

Background: Adenoid ameloblastoma is a rare epithelial neoplasm, histologically characterized by the presence of ameloblastoma-like features, duct-like structures, epithelial whorls, and cribriform architecture. Dentinoid material is usually present. Some advocate adenoid ameloblastoma is an ameloblastoma variant. However, there are overlapping features not only with ameloblastoma, but also with adenomatoid odontogenic tumor. Most ameloblastomas are characterized by the presence of BRAF p.V600E mutations and adenomatoid odontogenic tumors harbor signature KRAS mutations. The molecular features of adenoid ameloblastoma remain unknown.

Methods: Nine adenoid ameloblastoma cases were screened by TaqMan allele-specific qPCR to assess BRAF p.V600E, ameloblastoma signature mutation, and KRAS p.G12V and p.G12R, adenomatoid odontogenic tumor signature mutations.

Results: BRAF and KRAS mutations were not detected in any of the adenoid ameloblastoma cases.

Conclusion: The molecular results support adenoid ameloblastoma as an entity distinct from adenomatoid odontogenic tumor and ameloblastoma.
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http://dx.doi.org/10.1111/jop.13243DOI Listing
November 2021

Benign fibrous histiocytoma of the oral and maxillofacial region: A systematic review.

Oral Surg Oral Med Oral Pathol Oral Radiol 2022 02 15;133(2):e43-e56. Epub 2021 Jul 15.

Oral Diagnosis Department, Piracicaba Dental School, Universidade Estadual de Campinas, Piracicaba, São Paulo, Brazil; Department of Oral Pathology, Dental School, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil; Department of Oral Medicine, Hospital de Clínicas de Porto Alegre (HCPA/UFRGS), Porto Alegre, Rio Grande do Sul, Brazil. Electronic address:

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.
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http://dx.doi.org/10.1016/j.oooo.2021.07.003DOI Listing
February 2022

An ulcerated nodule on the tip of the tongue of a patient with skin lesions.

Oral Surg Oral Med Oral Pathol Oral Radiol 2022 04 8;133(4):363-368. Epub 2021 Aug 8.

Oral Diagnosis Department, Piracicaba Dental School, University of Campinas (Unicamp), Piracicaba, São Paulo, Brazil.

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http://dx.doi.org/10.1016/j.oooo.2021.08.001DOI Listing
April 2022

Malignant peripheral nerve sheath tumour of the oral and maxillofacial region-A systematic review.

Oral Dis 2021 Aug 1. Epub 2021 Aug 1.

Department of Oral Diagnosis, Piracicaba Dental School, Universidade Estadual de Campinas, Piracicaba, Brazil.

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.
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http://dx.doi.org/10.1111/odi.13982DOI Listing
August 2021

Ossifying fibromyxoid tumor of the oral cavity: rare case report and long-term follow-up.

Autops Case Rep 2021 8;11:e2020216. Epub 2020 Dec 8.

Universidade Estadual de Campinas (UNICAMP), Faculdade de Odontologia de Piracicaba, Departamento de Diagnóstico Oral, Área de Semiologia e Patologia Oral, Piracicaba, SP, Brasil.

Ossifying fibromyxoid tumor (OFMT) is a rare mesenchymal soft tissue benign neoplasm with an uncertain line of differentiation, which arises most frequently in extremities. The head and neck region involvement is uncommon, with only ten intraoral cases published in the English-language literature. One additional case of OFMT is reported here, including a literature review of intraoral reported cases. A 45-year-old female patient presented a painless nodule involving the buccal mucosa of approximately two years duration, measuring nearly 1.3 cm in maximum diameter. The main histopathological features include ovoid to round cells embedded in a fibromyxoid matrix with a perpheral shell of lamellar bone. Immunohistochemically, the tumor showed immunoreactivity for vimentin and S100. No recurrence has been detected after 7 years of follow-up.
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http://dx.doi.org/10.4322/acr.2020.216DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8101660PMC
December 2020

Acquired oral syphilis: A multicenter study of 339 patients from South America.

Oral Dis 2022 Sep 1;28(6):1561-1572. Epub 2021 Aug 1.

Molecular Pathology Area, Faculty of Dentistry, Universidad de la República, Montevidéu, Uruguay.

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.
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http://dx.doi.org/10.1111/odi.13963DOI Listing
September 2022

Oral Lymphoepithelial Cyst: A Collaborative Clinicopathologic Study of 132 Cases from Brazil.

Head Neck Pathol 2022 Mar 29;16(1):268-277. Epub 2021 Jun 29.

Department of Oral Diagnosis, Piracicaba Dental School, University of Campinas (UNICAMP), Piracicaba, Brazil.

The oral lymphoepithelial cyst (OLC) is an uncommon lesion whose pathogenesis remains poorly understood. The aim of this study was to report the clinicopathologic features of the OLCs and to verify a possible association between OLCs and subgemmal neurogenous plaque (SNP) in the posterior lateral region of the tongue. A retrospective descriptive cross-sectional study was carried out. A total of 106,282 biopsy records of oral and maxillofacial lesions from six oral pathology services in Brazil were analyzed. All cases of OLCs were reviewed, and clinical and histopathological data were collected. Immunohistochemical reactions for S-100 protein were performed to confirm the diagnosis of SNP. Among all lesions, there were 132 (0.11%) cases of OLCs. The series comprised 83 females (62.9%) and 49 males (37.1%), with a 1.7:1 female-to-male ratio and a mean age of 45.8 ± 17.7 years. Most cases involved the tongue (n = 80; 62.0%) and presented clinically as asymptomatic papules or nodules with a yellow or whitish color. Microscopically, most of the cysts were entirely lined by parakeratinized stratified epithelium (n = 89; 67.4%) and filled with desquamated cells, keratin debris, amorphous eosinophilic material, and inflammatory cells in varying amounts. Connection with the epithelium of oral mucosa was observed in 18 cases (13.6%). SNP was found in 9/80 (11.2%) cases involving the tongue. The clinical and demographic features of OLCs were similar to those described in previous studies. Overall, this lesion has a predilection for the posterior region of the tongue of female adults. Clinicians must include the OLC in the differential diagnosis of yellow/white papules and nodules of the oral cavity.
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http://dx.doi.org/10.1007/s12105-021-01352-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9018938PMC
March 2022

Leiomyoma and Leiomyosarcoma (Primary and Metastatic) of the Oral and Maxillofacial Region: A Clinicopathological and Immunohistochemical Study of 27 Cases.

Head Neck Pathol 2022 Mar 9;16(1):294-303. Epub 2021 Jun 9.

Department of Oral Surgery and Pathology, School of Dentistry, Federal University of Minas Gerais, Belo Horizonte, Brazil.

Smooth muscle neoplasms represent an important group of lesions which is rare in the oral cavity. Leiomyoma (LM) is benign smooth muscle/pericytic tumor usually presenting as non-aggressive neoplasm, while leiomyosarcoma (LMS) represents its malignant counterpart. The rarity of these lesions, together with its unspecific clinical presentation and a variable histopathological appearance, lead to a broad list of differential diagnoses, hampering their diagnoses. Therefore, in this study we describe the clinical and microscopic features of a series of oral and maxillofacial LMs and LMSs. A retrospective search from 2000 to 2019 was performed and all cases diagnosed as LM and LMS affecting the oral cavity and gnathic bones were retrieved. Clinical and demographic data were obtained from the patients' pathology records, while microscopic features and immunohistochemistry were reviewed and completed when necessary to confirm the diagnoses. Twenty-two LMs and five LMSs were obtained. In the LM group, males predominated, with a mean age of 45.7 years. The upper lip was the most affected site, and 18 cases were classified as angioleiomyomas and four as solid LM. In the LMS group, females predominated, with a mean age of 47.6 years. The mandible was the most affected site. Diffuse proliferation of spindle cells, with necrosis and mitotic figures, were frequent microscopic findings. LMs and LMSs were positive for α-smooth muscle actin, HHF-35 and h-caldesmon. In conclusion, oral LM/LMS are uncommon neoplasms with the latter usually presenting as metastatic disease. H&E evaluation may be very suggestive of oral LMs, but h-caldesmon staining is strongly recommended to confirm LMS diagnosis.
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http://dx.doi.org/10.1007/s12105-021-01336-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9018928PMC
March 2022

Prognostic significance of CD30 expression in diffuse large B-cell lymphoma: A systematic review with meta-analysis.

J Oral Pathol Med 2021 Jul 28;50(6):587-593. Epub 2021 Jun 28.

Department of Oral Diagnosis, Piracicaba Dental School, University of Campinas, Piracicaba, Brazil.

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 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%-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%-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 tumours, 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.
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http://dx.doi.org/10.1111/jop.13208DOI Listing
July 2021
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