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Gingival enlargement (GE) is an increase in the size of the gingiva. It may be due to inflammation caused by extensive plaque accumulation, intake of drugs, systemic conditions like pregnancy and puberty, systemic diseases such as leukemia or Wegener's granulomatosis, hereditary gingival fibromatosis, and neoplastic or false enlargement. Idiopathic GE is the massive increase in the size of the gingiva with an unknown etiology. It may have a hereditary basis, be linked to physical impairment, or begin with eruption of primary or permanent dentition. It is also referred as gingivomatosis, hereditary gingival fibromatosis, elephantiasis gingivae, gigantism of the gingiva, or congenital macrogingivae. The enlarged gingiva compromises oral hygiene maintenance, which secondarily adds to the inflammatory component of enlargement. Altogether, this exaggerates the existing condition. This type of extensively disfigured gingiva affects speech, mastication, and esthetics, causes halitosis, and disturbs the overall well-being of the individual. Surgical removal of the enlarged gingiva along with meticulous non-surgical means of plaque control is expected to provide a satisfactory functional and esthetic outcome. This case report presents a rare case of long-standing massive grade III GE extending up to the occlusal level in a 17-year-old systemically healthy, non-syndromic young female involving both arches, thereby posing a diagnostic dilemma. It was treated by gingivectomy using a conventional technique to facilitate precise incision, lower cost, and faster re-epithelialization. This was followed by gingivoplasty using electrocautery. The postoperative results of three months were satisfactory in terms of function and esthetics with uneventful healing. Further follow-up is ongoing for the same.
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Saw palmetto (SAW), the herbal drug used to treat prostatic hyperplasia, exerts its antiproliferative effects by blocking steroid 5 alpha-reductase (SRD5A1) activity, that has also been involved in gingival hyperplasia (GH) pathogenesis. Concurrently, folic acid (FA) could reduce GH prevalence via its antioxidant and anti-inflammatory effects. Thus, this study tended to assess the potential therapeutic efficacy of SAW, alone and along with FA, against amlodipine-induced gingival inflammation and overgrowth in rats. Rats were grouped into (CONT, AIGH, SAW, SAW-treated, FA-treated, and SAW + FA-treated). SAW and FA were administered once daily for 4 weeks. Gingival SRD5A1, CTGF, GSK-3ß, and NLRP3 expressions, as well as T, DHT, MDA, TAC, ET-1, and MMP2 levels were determined. In addition, histopathological and immunohistochemical analyses of TNF-α, IL-6, TGF-ß1, and α-SMA were documented. Results declared that SAW and FA administration markedly ameliorated amlodipine-associated GH and may be presenting a novel therapeutic avenue in the future.
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Anlodipino , Ácido Fólico , Hiperplasia Gengival , Metaloproteinase 2 da Matriz , Fator de Crescimento Transformador beta1 , Animais , Anlodipino/farmacologia , Masculino , Ácido Fólico/farmacologia , Ratos , Fator de Crescimento Transformador beta1/metabolismo , Hiperplasia Gengival/induzido quimicamente , Hiperplasia Gengival/metabolismo , Metaloproteinase 2 da Matriz/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Extratos Vegetais/farmacologia , Ratos Sprague-Dawley , Proteínas de Membrana/metabolismoRESUMO
This clinical case report details the comprehensive diagnosis and dental management of a seven-year-old female patient diagnosed with the rare genetic disorder, amelogenesis imperfecta and gingival fibromatosis syndrome (AIGFS). The case initially presented as congenital adrenal hyperplasia and amelogenesis imperfecta, but further genetic analysis revealed the involvement of AIGFS due to a mutation in the FAM20A gene. Diagnosis, confirmed through whole exome sequencing, clinical assessment, and laboratory tests, necessitated a multidisciplinary approach to address the treatment of such cases. The article underscores the critical importance of diagnosing and managing dental manifestations in pediatric patients with complex genetic conditions, highlighting the difficulties of treating AIGFS in mixed dentition. This case also highlights the indispensable role of pediatric dentists in diagnosing and treating these cases, ultimately improving the quality of life for individuals with AIGFS.
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AIM: Loss-of-function mutations in FAM20A result in amelogenesis imperfecta IG (AI1G) or enamel-renal syndrome, characterized by hypoplastic enamel, ectopic calcification, and gingival hyperplasia, with some cases reporting spontaneous tooth infection. Despite previous reports on the consequence of FAM20A reduction in gingival fibroblasts and transcriptome analyses of AI1G pulp tissues, suggesting its involvement in mineralization and infection, its role in deciduous dental pulp cells (DDP) remains unreported. The aim of this study was to evaluate the properties of DDP obtained from an AI1G patient, providing additional insights into the effects of FAM20A on the mineralization of DDP. METHODOLOGY: DDP were obtained from a FAM20A-AI1G patient (mutant cells) and three healthy individuals. Cellular behaviours were examined using flow cytometry, MTT, attachment and spreading, colony formation, and wound healing assays. Osteogenic induction was applied to DDP, followed by alizarin red S staining to assess their osteogenic differentiation. The expression of FAM20A-related genes, osteogenic genes, and inflammatory genes was analysed using real-time PCR, Western blot, and/or immunolocalization. Additionally, STRING analysis was performed to predict potential protein-protein interaction networks. RESULTS: The mutant cells exhibited a significant reduction in FAM20A mRNA and protein levels, as well as proliferation, migration, attachment, and colony formation. However, normal FAM20A subcellular localization was maintained. Additionally, osteogenic/odontogenic genes, OSX, OPN, RUNX2, BSP, and DSPP, were downregulated, along with upregulated ALP. STRING analysis suggested a potential correlation between FAM20A and these osteogenic genes. After osteogenic induction, the mutant cells demonstrated reduced mineral deposition and dysregulated expression of osteogenic genes. Remarkably, FAM20A, FAM20C, RUNX2, OPN, and OSX were significantly upregulated in the mutant cells, whilst ALP, and OCN was downregulated. Furthermore, the mutant cells exhibited a significant increase in inflammatory gene expression, that is, IL-1ß and TGF-ß1, whereas IL-6 and NFκB1 expression was significantly reduced. CONCLUSION: The reduction of FAM20A in mutant DDP is associated with various cellular deficiencies, including delayed proliferation, attachment, spreading, and migration as well as altered osteogenic and inflammatory responses. These findings provide novel insights into the biology of FAM20A in dental pulp cells and shed light on the molecular mechanisms underlying AI1G pathology.
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Amelogênese Imperfeita , Diferenciação Celular , Proteínas do Esmalte Dentário , Polpa Dentária , Nefrocalcinose , Osteogênese , Dente Decíduo , Humanos , Células Cultivadas , Proteínas do Esmalte Dentário/genética , Proteínas do Esmalte Dentário/metabolismo , Polpa Dentária/citologia , Polpa Dentária/metabolismo , Expressão Gênica , Mutação , Osteogênese/genéticaRESUMO
BACKGROUND: Plasminogen serves as the precursor to plasmin, an essential element in the fibrinolytic process, and is synthesized primarily in the liver. Plasminogen activation occurs through the action of plasminogen activator, converting it into plasmin. This conversion greatly enhances the fibrinolytic system within tissues and blood vessels, facilitating the dissolution of fibrin clots. Consequently, congenital deficiency of plasminogen results in impaired fibrin degradation. Patients with plasminogen deficiency typically exhibit fibrin deposits in various mucosal sites throughout the body, including the oral cavity, eyes, vagina, and digestive organs. Behcet's disease is a chronic recurrent systemic inflammatory disease with four main symptoms: aphthous ulcers of the oral mucosa, vulvar ulcers, skin symptoms, and eye symptoms, and has been reported worldwide. This disease is highly prevalent around the Silk Road from the Mediterranean to East Asia. We report a case of periodontitis in a patient with these two rare diseases that worsened quickly, leading to alveolar bone destruction. Genetic testing revealed a novel variant characterized by a stop-gain mutation, which may be a previously unidentified etiologic gene associated with decreased plasminogen activity. CASE PRESENTATION: This case report depicts a patient diagnosed with ligneous gingivitis during childhood, originating from plasminogen deficiency and progressing to periodontitis. Genetic testing revealed a suspected association with the PLG c.1468C > T (p.Arg490*) stop-gain mutation. The patient's periodontal condition remained stable with brief intervals of supportive periodontal therapy. However, the emergence of Behçet's disease induced acute systemic inflammation, necessitating hospitalization and treatment with steroids. During hospitalization, the dental approach focused on maintaining oral hygiene and alleviating contact-related pain. The patient's overall health improved with inpatient care and the periodontal tissues deteriorated. CONCLUSIONS: Collaborative efforts between medical and dental professionals are paramount in comprehensively evaluating and treating patients with intricate complications from rare diseases. Furthermore, the PLG c.1468C > T (p.Arg490*) stop-gain mutation could contribute to the association between plasminogen deficiency and related conditions.
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Síndrome de Behçet , Periodontite , Feminino , Humanos , Fibrinolisina , Síndrome de Behçet/complicações , Síndrome de Behçet/genética , Doenças Raras/complicações , Periodontite/complicações , Periodontite/genética , Plasminogênio/genética , FibrinaRESUMO
Background: Asperger syndrome is a type of autism spectrum disorder that may affect oral health and dental management. Spongiotic gingival hyperplasia is a rare lesion with unique clinicopathological features and unknown pathogenesis that has not been previously reported in a patient with autism spectrum disorder. The purpose of this case report is to present the first case of spongiotic gingival hyperplasia in a child with Asperger syndrome. Methods: A 14-year-old boy with Asperger syndrome was referred for diagnosis and management of bright red granular overgrowths of the marginal gingiva and interdental papilla of the mandibular right incisors and marginal gingiva of the mandibular left incisor. A biopsy was performed on the interdental papilla between the mandibular right incisors. Results: Microscopic examination and cytokeratin 19 immunopositivity confirmed the diagnosis of spongiotic gingival hyperplasia. The parents of the patient declined any further intervention, and four months later the gingival lesions, including the biopsied area, did not show any significant difference from the initial examination. Conclusions: Patients with autism spectrum diseases, such as Asperger syndrome, cannot achieve a good level of oral hygiene. Thus, it is expected that the incidence of spongiotic gingival hyperplasia should be higher in this group of patients, in case oral microbiome participates in its pathogenesis. Management of such lesions is challenging, as such patients do not comply with a proper oral hygiene program and do not cooperate with surgical excision.
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Objective: The purpose of this research was to examine patients' periodontal health before, during, and after treatment using a fixed orthodontic device. Methods: Forty normal teenagers with full sets of permanent teeth and a clinical need for fixed orthodontics participated. Individuals were chosen from the Class I population who would benefit from utilizing traditional orthodontic braces and techniques that did not need extractions. Respondents were sent to the periodontist for required checkups after the placement of a fixed orthodontic device at 3-, 6-, 12-, and 24-month intervals, respectively, till the conclusion of orthodontic treatment. Results: After having a fixed orthodontic device put in place, patients had a rise in the average values of the Plaque Index and Sulcus Bleeding Index at each checkup. Keeping an eye on the progression three months, six months, a year, and two years after the initiation of orthodontic treatment reveals a statistically significant difference in the presence of gingival hyperplasia. Conclusion: Patients' periodontal health before, during, and after fixed orthodontic treatment shows the need for close collaboration between the orthodontist and the periodontist.
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Background and objective: Some studies support the superiority of diode laser gingivectomy to scalpel surgery and nonsurgical treatments. However, a systematic review on this topic is lacking. This study aimed to compare gingivectomy with diode laser versus the conventional scalpel surgery and nonsurgical periodontal therapy (NSPT) in the treatment of orthodontic treatment-induced gingival enlargement (GE). Materials and methods: In this systematic review, an electronic search of the relevant literature was conducted in Web of Science, Medline/PubMed, Scopus, Cochrane Central Register of Controlled Trials, and ProQuest with no language restriction. Randomized clinical trials published between 1985 and 2020 on comparative treatment of orthodontic treatment-induced GE by diode laser gingivectomy and scalpel surgery or NSPT regarding intraoperative and postoperative bleeding and/or pain were included. Risk of bias was assessed by the Cochrane 1 tool. Results: Of the initially retrieved 288 articles, 40 were duplicates and excluded; 236 articles were excluded following title and abstract screening, and 5 others were excluded following full-text assessment. Finally, 7 studies underwent systematic review. In the risk-of-bias assessment, 5 studies scored 2, and 2 studies scored 3 out of 6. Intraoperative and postoperative bleeding and pain were found to be significantly lower in the laser group. Conclusions: Within the limitations of this systematic review and with respect to the quality of evidence, the present results revealed lower level of pain and bleeding in diode laser gingivectomy compared with the conventional scalpel surgery and NSPT for treatment of orthodontic treatment-induced GE.
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Hiperplasia Gengival , Crescimento Excessivo da Gengiva , Humanos , Lasers Semicondutores/uso terapêutico , Gengivectomia , DorRESUMO
Hypertension rightfully termed as "Silent killer" is associated with increase in morbidity and mortality when left untreated. Calcium channel blockers are the most commonly prescribed first-line anti-hypertensive drugs in India. Calcium channel blockers are known to cause gingival hyperplasia but with lower incidence rates compared to the other two groups causing iatrogenic gingival overgrowth, immunosuppressants, and anticonvulsants. Nifedipine administration, among the calcium channel blockers, has been frequently associated with iatrogenic gingival hyperplasia. Incidence of amlodipine-induced gingival hyperplasia which has similar pharmacodynamic action like nifedipine, had been reported rarely. Here, we present a case series of drug induced gingival overgrowth caused by calcium channel blockers used for the management of hypertension. All the patient's condition improved after withdrawal of the offending drug, oral prophylaxis and intervention, and alternate drug from other first-line drugs were started for managing hypertension.
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Various systemic diseases can manifest oral signs and symptoms early, which may be crucial for diagnosis and outlining the treatment plan. This case report highlights the presentation of acute leukemia (a malignancy of white blood cells) in a young female. An 11-year-old girl presented with gingival overgrowth and bleeding from the gingiva, weakness, and recent history of weight loss. A detailed workup consisting of complete blood count, bone marrow examination, flow cytometric immunophenotyping, cytogenetics, and molecular studies were carried out. The investigations confirmed the infiltration of blast cells of myelomonocytic origin, and a confirmatory diagnosis of acute myeloid leukemia (French-American-British classification M5) was made. The patient was put on induction chemotherapy and responded well. She developed febrile neutropenia following chemotherapy, which was managed conservatively. Gingival overgrowth subsided after the chemotherapy, and at the time of discharge, she was asymptomatic and hemodynamically stable. The oral health-care professionals must recognize that gingival overgrowth/enlargement may represent an initial manifestation of an underlying systematic disease.
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INTRODUCTION: This article describes the management of two patients who presented with localized juvenile spongiotic gingival hyperplasia. This disease entity is poorly understood, and literature regarding successful treatment is scant. However, there are common themes to management including proper diagnosis and treatment via removal of the affected tissue. The biopsy demonstrates intercellular edema and neutrophil infiltrate with epithelial and connective tissue disease components, so surgical deepithelialization may not be adequate to definitively treat the disease. METHODS AND RESULTS: This article presents two cases of the disease and suggests the use of the Nd:YAG laser as an alternative management modality. CONCLUSION: To our knowledge, we present the first cases of localized juvenile spongiotic gingival hyperplasia treated with the Nd:YAG laser. KEY POINTS: Why are these cases new information? To our knowledge, this case series illustrates the first use of an Nd:YAG laser to treat the rare pathology localized juvenile spongiotic gingival hyperplasia. What are the keys to successful management of these cases? To properly manage this rare presentation, proper diagnosis is paramount. Following diagnosis with microscopic evaluation, deepithelialization and treatment of underlying connective tissue infiltrate via the Nd:YAG laser offers an elegant option to treat the pathology and maintain esthetic outcomes. What are the primary limitations to success in these cases? The primary limitations of these cases include the small sample size, which is attributable to the rarity of the disease.
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Hiperplasia Gengival , Lasers de Estado Sólido , Humanos , Hiperplasia Gengival/diagnóstico , Hiperplasia Gengival/cirurgia , Lasers de Estado Sólido/uso terapêutico , Estética Dentária , Biópsia , EdemaRESUMO
INTRODUCTION: Granulomatosis with polyangiitis (GPA), is a rare systemic disease that if left untreated, it may lead to death within 6-12 months. This case report describes a 15-year-old female with a 14-month history of epiphora, nasal breathing difficulties, headaches, and jaw pain. The patient reported having various medical procedures attempted to address her symptoms. The classical presentation of strawberry gingivitis led to the diagnosis of GPA. Based on a multi-language search, this is the first reported case, that GPA is mistaken as Temporomandibular Joint Disorders (TMD). CASE PRESENTATION: A 15-year-old female with nearly 14 months of numerous complaints, including headaches and jaw pain, was referred for an orofacial pain (OFP) consultation. The patient had completed a dental examination and was prescribed chlorhexidine for gingivitis control. The OFP examination was not consistent with signs and symptoms of TMD. However, the gingival appearance of strawberry gingivitis was suggestive of GPA. A rheumatologist confirmed the diagnosis of GPA based on the clinical interview, serology testing, and dental findings. A course of rituximab and corticosteroids, and regular dental cleanings were recommended. A 4-month follow-up visit demonstrated complete resolution of her jaw pain and headaches. Gingival tissue appeared normal. CONCLUSION: This case emphasizes the need for familiarity with systemic diseases that can present oral manifestations. It also stresses the importance for dental professionals to be knowledgeable of differential diagnoses for TMD, headaches, and autoimmune disorders. Why is this case new information? This is believed to be the first published case mistaking GPA as TMD. This is a case in which a multidisciplinary approach and management were keys for a successful treatment outcome. What are the keys to successful management of this case? Obtain a thorough clinical history. Know the oral manifestation of systemic diseases. Know differential diagnosis of TMD and headaches. What are the primary limitations to success in this case? Having no access to the medical records during the OFP consultation. Having no awareness of differential diagnosis for gingivitis: strawberry, plaque-induced.
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Gengivite , Granulomatose com Poliangiite , Transtornos da Articulação Temporomandibular , Humanos , Feminino , Adolescente , Granulomatose com Poliangiite/diagnóstico , Granulomatose com Poliangiite/complicações , Transtornos da Articulação Temporomandibular/diagnóstico , Transtornos da Articulação Temporomandibular/complicações , Dor Facial/complicações , Cefaleia/etiologia , Cefaleia/complicaçõesRESUMO
Localized juvenile spongiotic gingival hyperplasia (LJSGH) is a poorly understood entity and is probably a misnomer too. Although this lesion is thought to be predominantly found in young children, a significant number of cases have also been reported in adults. A 41-year-old female patient presented with an erythematous, velvety-appearing gingival mass in the mandibular anterior region. The lesion was recurrent in nature, although it was asymptomatic. A diagnosis of LJSGH was made after correlating the clinical and histopathological features. A literature search revealed that a large number of cases have been reported in adults, some as old as 87 years old. There seems to be no gender predilection, and the lesion is frequently noticed in relation to maxillary anterior gingiva. Recurrence is a characteristic feature of this lesion, although its etiology and pathogenesis are poorly understood till date. Since it has a unique behavior in terms of high recurrences, dentists and periodontists need to be made aware about spongiotic gingival hyperplasia since the lesion may be mistaken for common reactive lesions.
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In Hungary, there are around 3500 people living with a transplanted organ, there are around 400 total donations, including between 250 and 300 kidney transplants per year. Due to the development of immunosuppression and surgical techniques, the survival rate of patients has improved, and therefore dentists are increasingly confronted with gingival hyperplasia due to immunosuppressive therapy in addition to oro-dental lesions resulting from renal failure. The prevalence of gingival hyperplasia with cyclosporin A can be as high as 90%. The aim of our study is to raise awareness of the importance of dental plaque in the development of cyclosporin A induced gingival hyperplasia and to emphasize that gingival hyperplasia and the risk of organ rejection can be prevented or greatly reduced by the development of appropriate individual oral hygiene and successful periodontal outpatient therapy. Particular mention should be paid to the importance of interdisciplinary cooperation and regular patient care. Our examinations and treatments were carried out at the Division of Periodontology at the Department of Dentistry and Oral Surgery of the University of Pecs, Hungary.
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Hiperplasia Gengival , Transplante de Rim , Ciclosporina/efeitos adversos , Hiperplasia Gengival/patologia , Humanos , Hiperplasia , PrevalênciaRESUMO
Background: Periodontal complications are one of the common side effects associated with orthodontic therapy. Objective: This study aimed to evaluate the periodontal changes in patients before, during, and after the therapy with a fixed orthodontic appliance. Methods: Out of 38 healthy adolescents with permanent dentition who were indicated for fixed orthodontic therapy were included in this study. Patients were selected from Class I, treated by non-extraction methods, by using conventional orthodontic braces. After their examination and treatment by an orthodontist, the patients were referred to the periodontist before the placement of a fixed orthodontic appliance. The patients underwent the application of a periodontal anamnestic-diagnostic protocol, and the clinical-radiological evaluation. After a fixed orthodontic appliance was placed, the respondents were referred to the periodontist for regular mandatory check-ups, initially, after three months, and later on-after 6 months, after 1 year and after 2 years until the end of orthodontic therapy. Results: An increase in the mean value of the Plaque Index and Sulcus Bleeding Index was found at each check-up after the placement of a fixed orthodontic appliance. There is a statistically significant difference in the presence of gingival hyperplasia found by monitoring the changes after three and six months, and after one and two years following the start of orthodontic therapy. Conclusion: The assessment of periodontal changes in patients before, during and after the completion of fixed orthodontic therapy revealed that there is a strong need for mutual and close cooperation between orthodontist and periodontist during orthodontic therapy.
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Levetiracetam is a new generation antiseizure medication which binds to synaptic vesicle protein SV2A and inhibits the release of neurotransmitters. Gingival hyperplasia is a common side effect of conventional antiseizure medications like phenytoin, but very rare with the newer ones. A 14-year-old boy was started on levetiracetam 250 mg twice daily after a generalized seizure. Five days later he presented with gingival swelling and painful oral aphthae, without lymphadenopathy or systemic symptoms. Blood investigations were normal. After one-month of stopping the drug, the lesions cleared. This case highlights the importance of maintaining good oral hygiene and periodic dental review in patients on antiseizure medications.
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Hiperplasia Gengival , Adolescente , Anticonvulsivantes , Humanos , Levetiracetam , Masculino , Fenitoína , ConvulsõesRESUMO
Gingival enlargement may manifest as a side effect of medications (calcium channel blockers, anticonvulsants, or immunosuppressants) and may be associated with inflammation, malignancy, or genetic inheritance. This condition has a significant impact on a patient's quality of life and affects their oral health status. This case report describes the management of a 68-year-old gentleman who presented with generalized gingival enlargement and chronic periapical abscess originating from tooth 34, which served as an abutment for a fixed partial prosthesis. The patient's medical history revealed that felodipine, an antihypertensive medication, was prescribed to him. A comprehensive treatment plan was developed to improve the patient's quality of life.
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Peripheral ossifying fibroma (POF) is a localized reactive enlargement of the gingiva often associated with the papilla and originate from underneath the periodontium. POF occurs predominantly in females, especially in the anterior maxillary region of young adults. The histopathological examination provides a confirmatory diagnosis of such lesions due to their heterogeneous clinical and radiographic characteristics. This case report describes an atypical presentation of POF in the anterior mandible in an adult male patient. Treatment consisted of complete surgical excision and gingival curettage resulting in uneventful healing during the postoperative follow-up period.
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Oral lesions may be the initial or only manifestation of leukemia and can be the key to early diagnosis. The varied nature of presenting signs and dentists' general lack of familiarity with oral presentations makes diagnosis challenging. This retrospective review reports a series of cases of leukemia to familiarize dentists with the oral manifestations and facilitate earlier diagnosis or recognition of relapse of this life-threatening disease. Following institutional review board approval, the University of Florida Oral Pathology Biopsy Service archive from 1994 to 2018 was queried for all oral biopsies resulting in a diagnosis of leukemia. Cases with insufficient diagnostic information or extraoral manifestations were excluded. Demographic, clinical, and histologic findings were tabulated. Ten cases with 12 biopsy sites were identified. Men (n = 6) were affected more commonly. The mean age of the patients was 58.4 years (range of 17 to 88 years). The gingiva was the most frequently biopsied site (n = 6; 50%). Importantly, 40% of the patients (n = 4) had no prior diagnosis of leukemia. A wide spectrum of clinical impressions was rendered, pyogenic granuloma being the most common, and the reported duration of lesions ranged from several weeks to 6 months. The rarity of patients presenting with leukemia may lead to low levels of clinical suspicion, misdiagnosis, and delays in treatment. However, oral lesions may be the first and only manifestation of leukemia, and clinicians should be aware of the clinical characteristics of these oral presentations to ensure early diagnosis and treatment, thereby helping to reduce disease-related morbidity and mortality.