Publications by authors named "Felipe Paiva Fonseca"

139 Publications

Late recurrence of Burkitt's lymphoma in the jaw: numb chin syndrome as the only symptom.

Autops Case Rep 2021 8;11:e2020218. Epub 2020 Dec 8.

Hospital Sírio-Libanês, Serviço de Medicina Bucal, São Paulo, SP, Brasil.

The Numb Chin Syndrome (NCS) is defined as facial and oral numbness restricted to the mental nerve's distribution involving the lower lip, skin of the chin, or gingiva of the lower anterior teeth. Hypoesthesia can occur unilaterally or bilaterally. Although this syndrome is rare, its importance is related to the fact that it represents the clinical manifestations of malignant diseases. Breast cancer and non-Hodgkin lymphoma are the most common cause of NCS. The patient, a 58-year-old woman, treated for a Burkitt Lymphoma (BL) nine years ago, described a two-week history of change in sensitivity and pain in the chin region, without relief with the use of analgesics. She had no headache, speech disturbance, dysphagia, visual disturbance, or other neurological symptoms. No surgical intervention has been performed recently. The intraoral examination revealed a healthy oral mucosa and a small area adjacent to the right mental nerve region that was uncomfortable to palpation. No changes were found in the bone trabeculae at cone-beam computed tomography. The contrasted magnetic resonance features made it possible to identify a change in the mandibular body extending to the entire right side, coinciding with the patient's complaint, indicating a probable mandibular medullary invasion. The patient was submitted to a biopsy to rule out a possible recurrence of BL. The microscopic findings were consistent with the diagnosis of BL. The present report described a very unusual presentation of late recurrent BL nine years after the first treatment, which manifested as an NCS.
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http://dx.doi.org/10.4322/acr.2020.218DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8101652PMC
December 2020

EDITORIAL.

J Oral Pathol Med 2021 Jul;50(6):529

Department of Oral and Maxillofacial Surgery, Queen Alexandra Hospital, Portsmouth, UK.

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http://dx.doi.org/10.1111/jop.13212DOI Listing
July 2021

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

Oral Dis 2021 Jul 15. Epub 2021 Jul 15.

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
July 2021

Emerging role of cellular senescence in the pathogenesis of oral submucous fibrosis and its malignant transformation.

Head Neck 2021 Jul 6. Epub 2021 Jul 6.

Department of Oral Pathology, Manipal College of Dental Sciences, Manipal, Manipal Academy of Higher Education, Manipal, India.

Senescence is a common denominator in wound healing, fibrosis, and cancer. Although, senescence is transiently antifibrotic, when prolonged, promotes fibrosis and malignant transformation. Eligible studies indexed in MEDLINE, Embase and Web of Science were searched to understand the role of cellular senescence in the pathogenesis of oral submucous fibrosis (OSF) and its malignant transformation. The senescence-associated secretory phenotype (SASP) components like IL-1, IL-6, and GRO-α induce double-strand DNA breaks in keratinocytes and drive genetic instability. SASP derived from myofibroblasts induces epithelial-mesenchymal transition in OSF and facilitates cancer progression. The use of senolytics has been shown to eliminate senescent cells from the areas of fibrosis, thereby preventing malignancy. Naturally occurring agents such as apigenin and kaempferol inhibit SASP. Mechanistic insight into the emerging role of senescence in the pathogenesis of OSF and modalities to inhibit senescence-associated antiapoptotic pathways as a supplementary therapy to prevent malignant transformation of OSF is underlined.
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http://dx.doi.org/10.1002/hed.26805DOI Listing
July 2021

Oral mucositis in paediatric cancer patients undergoing allogeneic hematopoietic stem cell transplantation preventively treated with professional dental care and photobiomodulation: Incidence and risk factors.

Int J Paediatr Dent 2021 Jun 11. Epub 2021 Jun 11.

Instituto de Ensino e Pesquisa, Hospital Sírio-Libanês, São Paulo, Brazil.

Background: Oral mucositis (OM) is an important side effect related to allogeneic hematopoietic stem cell transplantation (allo-HSCT), and it has been associated with a significative reduction of quality of life. A negative impact of this toxicity in paediatric patients could result in increased use of parenteral feeding and opioids, longer periods of hospitalization, and a higher risk of systemic infection.

Aim: To investigate the clinical features and clinical outcomes associated with OM development and severity in hematological cancer paediatric patients undergoing allo-HSCT who underwent professional dental care (PDC) and photobiomodulation (PBM) as prophylactic treatment.

Design: Medical data and OM presentation were retrieved retrospectively from all patients younger than 18 years who were submitted to allo-HSCT between 2013 and 2016. The incidence of OM was assessed and graded by two oral medicine specialists following the WHO guidelines, and it was correlated with clinical parameters.

Results: Forty-nine consecutive paediatric patients were included. OM was diagnosed in 73.5% of patients, and in 36.1% of patients, OM was classified as severe. Acute lymphoblastic leukemia as a primary diagnosis and the use of a myeloablative regimen were associated with OM development. The primary diagnosis and use of total body irradiation (TBI) were associated with aggressive OM. Neither the incidence nor the severity of OM affected the overall survival, whereas only the use of a myeloablative regimen and a high body mass index (BMI) were determinants of lower OM-free survival rates.

Conclusions: A myeloablative conditioning and a high BMI were observed to be independent prognostic determinants of a lower OMFS rate. The cluster analysis allowed us to outline patient profiles with greater susceptibility to the development and severity of oral mucositis, which seems to be a useful tool to determine the risk of OM in paediatric patients.
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http://dx.doi.org/10.1111/ipd.12850DOI Listing
June 2021

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

Head Neck Pathol 2021 Jun 9. 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
June 2021

Leukaemic infiltration in the oral and maxillofacial region: An update.

J Oral Pathol Med 2021 Jul 28;50(6):558-564. Epub 2021 Jun 28.

¹Department of Oral Surgery and Pathology, School of Dentistry, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.

Background: The purpose of this study was to integrate the available data published on leukaemic infiltration in the oral and maxillofacial region into a comprehensive analysis of its clinical manifestations, imaginological characteristics, management and survival.

Materials And Methods: An electronic search with no publication date restriction was undertaken in October 2020 in the following databases: PubMed, Web of Science, Scopus and Embase. Overall survival was calculated by survival analysis with the Kaplan-Meier test. A critical appraisal of included articles was performed using the Joanna Briggs Institute tool.

Results: A total of 63 studies including 68 patients were selected for data extraction. The most common haematologic diagnosis was acute myeloid leukaemia (47%). The most affected individuals were 40 to 49 years old (20.9%). The male-to-female ratio was 1.2:1. The gingiva was the most affected site (37%). Swelling/mass/oedema (33.7%) and enlargement/hyperplasia/hypertrophy (25.5%) were the main clinical findings. Osteolytic lesions with bone destruction were the main imaginological characteristics among the reported cases. Follow-up was available for 36 patients. Overall, within the 21-month follow-up, the survival probability dropped to 14.3%.

Conclusion: A considerable number of studies reported oral manifestations mainly in individuals with the acute form of leukaemia. Children and adults were affected, but the fifth decade of life was the most common. Dentists should be vigilant since these manifestations may be important for a diagnosis and for the monitoring of the treatment response and recurrence of haematological neoplasia.
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http://dx.doi.org/10.1111/jop.13206DOI Listing
July 2021

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

Mantle cell lymphoma, malt lymphoma, small lymphocytic lymphoma, and follicular lymphoma of the oral cavity: An update.

J Oral Pathol Med 2021 Jul 1;50(6):622-630. Epub 2021 Jul 1.

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

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.
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http://dx.doi.org/10.1111/jop.13214DOI Listing
July 2021

Oral manifestations of Hydroa vacciniforme-like lymphoproliferative disorder: a clinicopathological study of a Peruvian population.

J Oral Pathol Med 2021 Jul 29;50(6):530-539. Epub 2021 Jun 29.

Departamento de Patología, Medicina y Cirugía Oral, Facultad de Estomatología, Universidad Peruana Cayetano Heredia, Lima, Perú.

Background: Hydroa vacciniforme-like lymphoproliferative disorder (HVLPD) is a chronic Epstein-Barr virus (EBV)-positive lymphoproliferative disease which may either present as an indolent condition or progress to a systemic T-cell lymphoma.

Methods: All HVLPD diagnosed over a 10-year period were retrieved, and clinical data regarding sex, age, oral and systemic manifestations, and clinical follow-up were obtained. Immunohistochemistry was done in order to characterize the lymphoid cells, and in situ hybridization was used to demonstrate the presence of EBV.

Results: Eleven cases were included, with a male predominance and a mean age of 25.1 years. Buccal mucosa and the lips were the most affected oral sites, appearing as painful ulcers. All patients exhibited facial oedema, usually affecting the lips, nose and periorbital region. The clinical course was gradual but progressive, with four patients having fever and 3 showing lymphadenopathies. All cases showed a moderate to severe lymphocytic infiltrate with angiotropism, angiocentricity and epidermotropism. Two cases affecting the lip skin exhibited a periappendageal lymphocytic infiltrate. Few large pleomorphic cells were found, surrounded by smaller and medium-sized lymphoid cells, as well as reactive plasma cells, macrophages, neutrophils and eosinophils. All lesions exhibited a cytotoxic T-cell (CD8+) phenotype with a variable proliferative index. All cases were associated with EBV, and all patients died due to complications of the disease.

Conclusions: HVLPD is a rare disease that may show oral involvement with a cytotoxic T-cell phenotype, and is strongly associated with EBV. As shown in this series, HVLPD may show aggressive clinical behaviour.
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http://dx.doi.org/10.1111/jop.13203DOI Listing
July 2021

Benign lymphoproliferative disorders in the immunosuppressed patient: an update.

J Oral Pathol Med 2021 Jul 24;50(6):540-547. Epub 2021 Jun 24.

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

Immunosuppressed patients may be affected by a wide range of lymphoproliferative disorders (LPDs) ranging from self-limiting disorders to malignant lymphoid proliferations. These LPDs may be associated with systemic immune disorders, develop following organ transplantation or occur in the background of other forms of iatrogenic immunosuppression. Lymphotropic viruses, including Epstein-Barr virus (EBV) and human herpesvirus-8 (HHV8), have been associated with the pathogenesis of distinct LPDs. The resulting classification of this group of disorders is very complex and inconsistent, with several new and emerging entities. Consequently, the diagnosis of an LPD, especially in an immunosuppressed patient, and its subsequent clinical management usually represent an important pitfall in daily clinical and pathology work. Therefore, the aim of this review was to use the available literature to describe the clinicopathological features of the most important benign LPDs that may be diagnosed in the head and neck region of immunosuppressed patients. Original clinical and microscopic images were used to illustrate some of these entities.
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http://dx.doi.org/10.1111/jop.13204DOI Listing
July 2021

Burkitt lymphoma of the head and neck: An international collaborative study.

J Oral Pathol Med 2021 Jul 28;50(6):572-586. Epub 2021 Jun 28.

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

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 to 100%.

Conclusion: The clinicopathological and EBV profile of BLHN in South African, Guatemalan, and Brazilian patients is similar.
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http://dx.doi.org/10.1111/jop.13209DOI Listing
July 2021

Oral plasmablastic lymphoma: A clinicopathological study of 113 cases.

J Oral Pathol Med 2021 Jul 1;50(6):594-602. Epub 2021 Jul 1.

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

Background: Plasmablastic lymphoma (PBL) is an aggressive neoplasm that commonly develops in HIV-positive patients, usually affecting the oral cavity. EBV is present in the majority of cases, therefore, playing an important role in the pathogenesis of this neoplasm.

Methods: PBL diagnosed from 2000 to 2020 were retrieved from the archives of the Department of Oral Pathology and Oral Biology at the University of Pretoria, South Africa. The patients' clinical information including gender, age, tumour location and HIV status was obtained from the original histopathology request forms. A morphological description was assessed using H&E-stained slides, with diagnoses confirmed by immunohistochemistry, and EBV detection performed via in situ hybridisation.

Results: During the 20 years period investigated, 113 PBL were found. Males outnumbered females (M:F ratio of 3:1), with a median age of 41 years (range 8-62). The gingiva (50 cases or 44.2%) and the palate (23 cases or 20.4%) were the most affected sites. All cases with available information were HIV positive. The tumours were composed of a diffuse proliferation of immunoblasts or plasmablasts in all cases. A starry-sky pattern, tissue necrosis, cellular pleomorphism and mitotic figures were common microscopic findings. IHC for CD3 and CD20 were negative in all cases, while positivity for CD38, CD138 and MUM1 was observed in 70.2%, 79.2% and 98.9%, respectively. EBV was present in 100% of the cases.

Conclusion: PBL is a frequent diagnosis in South Africa, due to the country's HIV burden, where it usually affects the oral cavity and is always associated with EBV infection.
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http://dx.doi.org/10.1111/jop.13210DOI Listing
July 2021

Oral and oropharyngeal lymphomas: A multi-institutional collaborative study.

J Oral Pathol Med 2021 Jul 30;50(6):603-612. Epub 2021 Jun 30.

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

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.
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http://dx.doi.org/10.1111/jop.13211DOI Listing
July 2021

Mature T/NK-Cell lymphomas of the oral and maxillofacial region: A multi-institutional collaborative study.

J Oral Pathol Med 2021 Jul 29;50(6):548-557. Epub 2021 Jun 29.

Department of Oral Diagnosis and Pathology, School of Dentistry, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.

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 heterogeneous group of neoplasms has a very aggressive clinical behaviour.
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http://dx.doi.org/10.1111/jop.13205DOI Listing
July 2021

Plasmacytoma and plasma cell myeloma affecting the jaws: A multi-institutional collaborative study.

J Oral Pathol Med 2021 Jul 20;50(6):613-621. Epub 2021 Jun 20.

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

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, tumours 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 tumours 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.
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http://dx.doi.org/10.1111/jop.13213DOI Listing
July 2021

Role of Yes-associated protein and transcriptional coactivator with PDZ-binding motif in the malignant transformation of oral submucous fibrosis.

Arch Oral Biol 2021 Aug 23;128:105164. Epub 2021 May 23.

Department of Oral Pathology, Manipal College of Dental Sciences, Manipal Academy of Higher Education, Manipal, 576104, India. Electronic address:

Objective(s): The objective of the present manuscript is to elucidate the role of matrix stiffness in the malignant transformation of oral submucous fibrosis.

Design: The role of matrix stiffness in several cancers including oral cancer was reviewed with a tailored search strategy using relevant keywords as per the Medline format. The role of molecular mediators, Yes-associated protein 1 (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) was weighed in the context of OSF along two distinct pathways.

Results: Increased matrix stiffness activates the transcriptional coactivators, YAP and TAZ shuttling between the nucleus and cytoplasm. YAP and TAZ, serve as mechanical transducers in promoting cell migration, invasion and epithelial-mesenchymal transition (EMT). The hypoxic microenvironment in the advanced stage of OSF promotes the migratory phenotype through mechanical memory.

Conclusions: Reprogramming of a stiff matrix has the potential to restore the Hippo-YAP/TAZ tumor suppressor pathway and reverse fibrosis-associated tumor development.
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http://dx.doi.org/10.1016/j.archoralbio.2021.105164DOI Listing
August 2021

Xeroderma pigmentosum variant: squamous cell carcinoma of the lower lip harboring exon 11 mutation of POLH.

Oral Surg Oral Med Oral Pathol Oral Radiol 2021 Mar 28:4601. Epub 2021 Mar 28.

Department of Oral Surgery and Pathology, School of Dentistry, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil. Electronic address:

Xeroderma pigmentosum (XP) is a rare inherited disease caused by deficiencies in DNA damage repair, which mainly results from the failure of nucleotide excision repair or defects in translesion DNA synthesis. The development of multiple malignancies is one of the most prominent features of this condition, which is clinically characterized by the occurrence of hyperpigmentation and lesions associated with sunlight exposure. Lip squamous cell carcinoma in patients with XP has rarely been reported, and information regarding the genetic analysis of these patients is limited. In this report, a case of a 20-year-old patient who developed squamous cell carcinoma in the lower lip is described. Although the tumor was surgically excised, the patient presented with recurrence a few months later. Targeted sequencing using a customized panel of DNA repair genes revealed a mutation in POLH, the gene encoding DNA polymerase eta. Therefore, molecular characterization is important to further improve the understanding of possible phenotype-genotype correlations and mechanisms involved in the pathogenesis of XP.
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http://dx.doi.org/10.1016/j.oooo.2021.03.013DOI Listing
March 2021

DNA methylation status of MutS genes in ameloblastoma.

Oral Dis 2021 Apr 26. Epub 2021 Apr 26.

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

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.
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http://dx.doi.org/10.1111/odi.13887DOI Listing
April 2021

A bibliometric analysis of the top 100 most-cited articles in the Journal of Oral Pathology & Medicine (1972-2020).

J Oral Pathol Med 2021 Apr 2. Epub 2021 Apr 2.

Department of Oral & Maxillofacial Surgery, Queen Alexandra Hospital, Portsmouth, UK.

Objective: The steady and continued increase of the Journal of Oral Pathology & Medicine's (JOPM) popularity prompted a bibliometric analysis of the journal. The purpose was to assess the significance and effect of the published research articles in the Journal from 1972 and 2020, aiding the identification of landmark articles. We performed a bibliometric analysis using the top 100 cited papers in the Journal of Oral Pathology & Medicine.

Materials And Methods: An extensive review of the Web of Science was undertaken. Standard information such as author details, affiliated institutions, publication year and the country of origin was recorded.

Results: The top 100 cited articles in JOPM were assessed. The maximum and minimum number of citations in the top 100 articles was 1459 and 95, respectively. A total of 16 790 citations were recorded for these 100 articles. Authors were affiliated to 28 different countries, 17 research articles from the UK and 12 from the USA. Other countries furnished seven or fewer articles.

Conclusion: This bibliometric analysis provides a synopsis of research published in the journal over a 48-year period. Recent interest in the journal shows a healthy increase in submissions and profile.
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http://dx.doi.org/10.1111/jop.13181DOI Listing
April 2021

Oral lesions containing amyloid-like material.

Oral Surg Oral Med Oral Pathol Oral Radiol 2021 Aug 17;132(2):190-201. Epub 2021 Jan 17.

Department of Oral Surgery and Pathology, School of Dentistry, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil; Department of Oral Pathology and Oral Biology, School of Dentistry, University of Pretoria, Pretoria, South Africa. Electronic address:

During oral pathology daily practice, true amyloid may be identified in oral amyloidosis and several odontogenic tumors. However, histologic examination often reveals other oral and perioral diseases with similar eosinophilic, acellular, amorphous substances. These include extensive areas of collagenous sclerosis, fibrin deposition, elastic fiber degeneration, and dentinoid material, which may resemble amyloid under light microscopic examination. These materials are often termed "amyloid-like" due to their close histologic resemblance to true amyloid. The rarity of most of these conditions and their strong histologic similarity may hamper an accurate diagnosis. Definitive diagnosis of these lesions may require clinical correlation; laboratory evaluation; histochemical or immunohistochemical reactions; and, in some cases, genetic investigation. In this review, we describe the main clinicopathologic features of this group of diseases that may manifest in the oral and/or perioral regions and that have in common the presence of amyloid-like material deposition.
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http://dx.doi.org/10.1016/j.oooo.2021.01.016DOI Listing
August 2021

Fully digital pathology laboratory routine and remote reporting of oral and maxillofacial diagnosis during the COVID-19 pandemic: a validation study.

Virchows Arch 2021 Mar 13. Epub 2021 Mar 13.

Oral Diagnosis Department, Semiology and Oral Pathology Areas, Piracicaba Dental School, University of Campinas (UNICAMP), Av. Limeira, 901, Bairro Areião, Piracicaba, SP, 13414-903, Brazil.

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.
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http://dx.doi.org/10.1007/s00428-021-03075-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7955219PMC
March 2021

Epigenetic alterations in ameloblastomas: A literature review.

J Clin Exp Dent 2021 Mar 1;13(3):e295-e302. Epub 2021 Mar 1.

Brazilian Biosciences National Laboratory, The Brazilian Center for Research in Energy and Materials, Campinas, Brazil.

Background: Ameloblastoma is a locally aggressive tumor, originated from odontogenic epithelium, and affects the jawbones with an elevated recurrence rate. The molecular mechanisms involved with the pathogenesis of this tumor remain undetermined. This review aimed to describe the current data regarding epigenetic alterations in ameloblastoma.

Material And Methods: A systematized electronic search was performed in the English-language literature in three databases, combining the following keywords: ameloblastoma, epigenetic, methylation, noncoding RNA, histone acetylation.

Results: According to the gathered results of 11 studies in this review, epigenetic alterations could induce the development and progression of ameloblastoma. DNA methylation has been the most assessed mechanism in ameloblastomas.

Conclusions: Current literature data indicate that epigenetic events can be involved in the etiopathogenesis of ameloblastomas. Ameloblastoma, epigenetic, methylation, noncoding RNA, histone acetylation.
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http://dx.doi.org/10.4317/jced.56191DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7920560PMC
March 2021

Oral and oropharyngeal diffuse large B-cell lymphoma and high-grade B-cell lymphoma: A clinicopathologic and prognostic study of 69 cases.

Oral Surg Oral Med Oral Pathol Oral Radiol 2021 Apr 20;131(4):452-462.e4. Epub 2020 Nov 20.

Private Pathology Service, Natal, Rio Grande do Norte, Brazil.

Objective: The objective of this study was to describe the clinicopathological, molecular, and prognostic features of oral/oropharyngeal diffuse large B-cell lymphoma (DLBCL) and high-grade B-cell lymphoma.

Study Design: All cases were retrieved from 7 Brazilian institutions. Immunohistochemical reactions were performed to confirm the diagnoses and to categorize the tumors. In situ hybridization was used to detect Epstein-Barr virus (EBV) and fluorescence in situ hybridization was used to identify gene rearrangements.

Results: Most cases involved the oral cavity (76.8%). Males and females, with a mean age of 60 years, were evenly affected. Tumors mostly presented as painful swellings. Forty cases represented germinal center B-cell type (58%). Five cases presented double-hit translocation and 3 harbored rearrangement for MYC/BCL2/BCL6. EBV was detected in 3 cases (4.3%). The 5-year overall survival was 44.4%. Female sex, presence of pain and ulcer, microscopic "starry sky pattern" and necrosis, co-expression of c-Myc/Bcl2, and translocation of MYC were associated with a lower survival in univariate analysis (P = .05, P = .01, P = .01, P = .03, P = .05, P = .006, P = .05, respectively).

Conclusion: Patients affected by oral/oropharyngeal DLBCL have a low survival rate. High-grade B-cell lymphoma (17.7%) and EBV-positive DLBCL, not otherwise specified (4.3%) account for a small number of cases.
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http://dx.doi.org/10.1016/j.oooo.2020.11.005DOI Listing
April 2021

Clinicopathological analysis of oral and maxillofacial acinic cell carcinoma: A systematic review.

J Oral Pathol Med 2021 Jan 17. Epub 2021 Jan 17.

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

Background: The aim of the present systematic review was to analyze the available data regarding acinic cell carcinoma of the oral and maxillofacial region.

Methods: A search strategy was performed using PubMed, Web of Science, Scopus, and Embase electronic databases.

Results: Available data revealed a slight female preference (54.73%) and a mean age at diagnosis of 47.51 ± 19.85 years. The parotid glands (67.72%) were most frequently affected, and most cases were asymptomatic (69.54%). A microcystic histopathological pattern was reported in 21.56% of the cases, and the Periodic acid-Schiff was the staining method most frequently used, after the hematoxylin and eosin staining, in the tumors analyzed. The lesions were mainly treated by surgical removal (72.32%). Recurrence was reported in 81 cases (27.83%) and metastasis in 100 (42.91%). Statistical data analysis revealed that tumors located in major salivary glands and exhibiting high-grade histology were associated with local recurrence (P = .01). In addition, the patients older than 57 years, lesions with bone involvement, the high-grade tumors and the cases with a history of recurrence and metastasis were associated with a lower overall survival (P < .05).

Conclusion: By assembling all eligible cases in the literature, the present systematic review determined the most common clinicopathological profile of acinic cell carcinoma and the most relevant prognostic factors in a distinctly representative sample. The survey demonstrated the importance of considering the histopathological grading in order to better define the treatment for each case.
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http://dx.doi.org/10.1111/jop.13159DOI Listing
January 2021

BRAF p.V600E status in epithelial areas of ameloblastoma with different histological aspects: Implications to the clinical practice.

J Oral Pathol Med 2021 May 18;50(5):478-484. Epub 2021 Jan 18.

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

Background: BRAF p.V600E is reported in up to 80% of ameloblastomas. Despite the high frequency, the presence of this mutation in different histopathological areas of the tumour has not been investigated. This information has an important role in the use of BRAF p.V600E assessment as an auxiliary tool in the differential diagnosis between unicystic ameloblastoma and other odontogenic cystic lesions, especially when only incisional biopsies are available. Therefore, the purpose of the present study was to investigate BRAF p.V600E heterogeneity in unicystic ameloblastoma.

Methods: Five cases of ameloblastoma and two dentigerous cysts were analysed. The regions exhibiting different microscopic characteristics were selected from each ameloblastoma case and manually dissected. TaqMan allele-specific qPCR or Sanger sequencing was performed to determine BRAF p.V600E status.

Results: We screened the mutation in a small cohort of UA and no molecular heterogeneity was found. Four cases of ameloblastoma (80%) exhibited BRAF p.V600E in all different areas evaluated. One case did not harbour the mutation in any microscopic region analysed. The BRAF mutation was absent in the dentigerous cysts.

Conclusion: Ameloblastomas appear to exhibit a homogeneous profile regarding the BRAF p.V600E no matter what histological feature is observed under light microscopy, suggesting that this molecular test may contribute to establish the correct diagnosis in cases microscopically resembling other odontogenic lesions.
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http://dx.doi.org/10.1111/jop.13155DOI Listing
May 2021

Myeloid sarcoma in the tongue.

Autops Case Rep 2020 May 6;10(2):e2020160. Epub 2020 May 6.

Hospital Sírio-Libanês, Oral Medicine Department. São Paulo, SP, Brazil.

Leukemic cells are rarely present in the oral cavity, and there are very few reports regarding such cases. However, we identified some reports of leukemic cells infiltrating tissues in the oral cavity, including gingival involvement. Recurrent painful oral ulcerations and prominent generalized periodontal destruction are the most common oral features of neutrophil disorders, and they may even be the initial symptoms of the disease. The ulcers may affect any part of the oral mucosa, including the tongue and palate. The objective of this report is to describe and discuss a case of myeloid sarcoma in the oral cavity of a 48-year-old male patient.
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http://dx.doi.org/10.4322/acr.2020.160DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7703000PMC
May 2020

Immunoexpression of BDNF, TrkB, and p75NTR receptors in peripheral neural lesions of the head and neck.

J Oral Pathol Med 2021 May 30;50(5):492-501. Epub 2020 Dec 30.

Department of Oral Pathology, School of Dentistry, Federal University of Rio Grande do Sul, Porto Alegre, Brazil.

Background: Brain-derived neurotrophic factor (BDNF) and neurotrophin receptors have been recognized as fundamental regulators of normal brain development, homeostasis, and plasticity. They have also been studied in the behavior of central nervous system tumors. Here, we studied the pattern of BDNF, TrkB and p75NTR immunoexpression in peripheral benign and malignant neural lesions in head and neck.

Methods: This cross-sectional analytical study included 79 cases of head and neck neural lesions. Nineteen cases of traumatic neuromas (TN), 20 cases of granular cell tumors (GCT), 16 cases of neurofibromas (NF), 20 cases of schwannomas (SC), and 4 malignant peripheral nerve sheath tumor (MPNST) were submitted to immunohistochemistry with BDNF, TrkB, and p75NTR antibodies. A semi-quantitative analysis was performed.

Results: The analysis of BDNF demonstrated a high percentage of positive cells in TN, GCT and SC with a decrease in cases of NF and MPNST. TrkB presented a lower significant immunoexpression in GCT in relation to the TN, NF, SC, and MPNST (P < .0001); and TN showed less percentage of positive cell compared to SC (P = .0017). Regarding p75NTR, the percentage of positive cell was significantly reduced in MPNST compared GCT (P = .009), NF (P = .0138) and SC (P = .0069). Also, a decrease in TN compared to GCT (P = .007) was observed.

Conclusions: Our results showed the immunoreactivity of BDNF, TrkB, and p75NTR in head and neck peripheral neural lesions. Reduction of BDNF and p75NTR in MPNST might suggest down-regulation during the acquisition of malignant phenotype.
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http://dx.doi.org/10.1111/jop.13145DOI Listing
May 2021

Metabolic landscape of oral squamous cell carcinoma.

Metabolomics 2020 09 30;16(10):105. Epub 2020 Sep 30.

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

Background: Head and neck cancers are the seventh most common type of cancer worldwide, with almost half of the cases affecting the oral cavity. Oral squamous cell carcinoma (OSCC) is the most common form of oral cancer, showing poor prognosis and high mortality. OSCC molecular pathogenesis is complex, resulting from a wide range of events that involve the interplay between genetic mutations and altered levels of transcripts, proteins, and metabolites. Metabolomics is a recently developed sub-area of omics sciences focused on the comprehensive analysis of small molecules involved in several biological pathways by high throughput technologies.

Aim Of Review: This review summarizes and evaluates studies focused on the metabolomics analysis of OSCC and oral premalignant disorders to better interpret the complex process of oral carcinogenesis. Additionally, the metabolic biomarkers signatures identified so far are also included. Moreover, we discuss the limitations of these studies and make suggestions for future investigations.

Key Scientific Concepts: Although many questions about the metabolic features of OSCC have already been answered in metabolomic studies, further validation and optimization are still required to translate these findings into clinical applications.
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http://dx.doi.org/10.1007/s11306-020-01727-6DOI Listing
September 2020

Central odontogenic fibroma: an international multicentric study of 62 cases.

Oral Surg Oral Med Oral Pathol Oral Radiol 2021 May 27;131(5):549-557. Epub 2020 Aug 27.

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

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.
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http://dx.doi.org/10.1016/j.oooo.2020.08.022DOI Listing
May 2021
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