Intraoral Salivary Gland Cystadenomas: A Case Series Study and Literature Review.

BACKGROUND: Salivary gland cystadenoma (SGCA) is a rare benign tumor that predominantly occurs in the parotid gland. SGCAs affecting the minor salivary glands are uncommon and often resemble, clinically and histopathologically, other salivary gland lesions. METHODS: This study aimed to describe a series of four cases of SGCA affecting intraoral sites and performed a literature review of well-reported SGCA published in the English-language literature. RESULTS: SGCA cases included in this series were diagnosed in the buccal mucosa, lip, and hard palate of female patients aged between 19 and 78 years. All cases underwent excisional biopsy and were histologically characterized by a multicystic growth with variable degrees of capsule formation and were lined by several types of epithelium, including some cell types that are infrequently reported in SGCA. In some cases, a small collection of lymphocytes was observed adjacent to cystic formations. All SGCA were positive for periodic acid-Schiff, and immunohistochemical reactions were positive for CK7 and p63. The follow-up time ranged widely from 3 to 53 months, and to date, no recurrence has been observed. CONCLUSION: The literature review revealed a total of 33 published studies accounting for 55 SGCA cases.

Cell block preparation as an adjunctive tool after fine-needle aspiration cytology for screening oral and maxillofacial diseases.

OBJECTIVE: To describe the use of cell block (CB) preparation from fine-needle aspiration cytology for diagnosing oral and maxillofacial diseases. STUDY DESIGN: We performed a retrospective analysis of 568 samples collected by our laboratory for CB preparation from fine-needle aspiration cytology of the oral and maxillofacial region between January 2001 and October 2021. We performed cytologic diagnoses and compared them with the available histopathologic diagnoses to calculate the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of CB preparation for identifying malignant lesions. RESULTS: The most frequent diagnosis was pleomorphic adenoma (n = 44, 7.7%), followed by metastatic squamous-cell carcinoma (n = 28, 4.9%) and odontogenic keratocyst (n = 26, 4.6%). The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of CB preparation, which revealed detailed morphologic and architectural patterns, were 70.0%, 100.0%, 100.0%, 62.5%, and 80.0%, respectively. CONCLUSIONS: Cell block preparation from fine-needle aspiration cytology of the oral and maxillofacial region may be a useful adjunctive diagnostic tool for diagnosing oral and maxillofacial diseases because it reveals morphologic and architectural patterns similar to those shown on histopathologic slides, leading to the better categorization of diseases.

FGFR1 is an important prognostic factor in oral leukoplakia and tongue squamous cell carcinoma.

BACKGROUND: Fibroblast growth factor receptor 1 is a potential prognostic factor for tongue squamous cell carcinoma and is associated with oral epithelial dysplasia grade in oral leukoplakia. METHODS: Thirty cases of tongue squamous cell carcinoma and 30 cases of oral leukoplakia were analyzed. Fibroblast growth factor receptor 1 and phosphorylated Akt protein expression were analyzed by immunohistochemistry and quantified using a digital algorithm. Fibroblast growth factor receptor 1 gene amplification was analyzed by fluorescent in situ hybridization in the tongue squamous cell carcinoma cases. RESULTS: Clinical appearance and dysplasia grade were correlated with oral leukoplakia malignant transformation. Oral leukoplakia cases presenting high fibroblast growth factor receptor 1 expression showed a higher risk of malignant transformation (p = 0.016, HR: 7.3, 95% CI: 1.4-37.4). Phosphorylated Akt showed faint to no expression in oral leukoplakia, which did not correlate with dysplasia grade or malignant transformation. High expression of fibroblast growth factor receptor 1 and phosohorylated Akt were associated with poor overall survival and disease-free survival in tongue squamous cell carcinoma, although only fibroblast growth factor receptor 1 expression was significantly associated with poor overall survival (p = 0.024; HR: 4.9, 95% CI: 1.2-19.9). Cases presenting double fibroblast growth factor receptor 1/phosphorylated Akt overexpression (n = 8) showed markedly impaired overall survival (p = 0.020; HR: 6.4, 95% CI: 1.3-31.1) and disease-free survival (p = 0.001, HR: 13.0, 95% CI: 3.0-55.7). Fibroblast growth factor receptor 1 amplification was observed in 16.6% of tongue squamous cell carcinoma cases, being correlated with vascular and neural invasion (p = 0.001 and 0.017, respectively), but not with fibroblast growth factor receptor 1 protein expression, overall survival, or disease-free survival. CONCLUSION: Fibroblast growth factor receptor 1 protein expression is an important prognostic factor in oral leukoplakia and tongue squamous cell carcinoma.

Oral Amelanotic Melanomas: Clinicopathologic Features of 8 Cases and Review of the Literature.

Mucosal melanomas are aggressive tumors, rarely observed in the oral cavity. The diagnosis is based on the clinical and microscopical features. Often these tumors had variable amounts of melanin pigmentation. However, when melanin is absent, the tumors are denominated amelanotic, presenting a tendency to misdiagnosis and delayed treatment. The aim of this study was to describe the clinicopathologic features of a series of oral amelanotic melanomas (OAM). Records of all cases of OAM were retrospectively retrieved from oral pathology services from January 2002 to January 2019. Data regarding the clinical features, morphological aspects, immunohistochemical reactions, treatment, and follow-up status were collected. Eight cases of OAM were included, 6 in men and 2 in women (ratio of 3:1) ranging in age from 33 to 77 years (mean 53.6 years). Clinically, the tumors presented as masses or ulcerated swellings. The most common intraoral locations of the tumors were gingiva and palate. Cervical lymph node metastasis was detected in 3 patients at the first examination. All but one patient died from complications of the tumors after a mean follow-up period of 8.5 months. In conclusion, OAM is a very aggressive malignant tumor, and when melanin is absent, an immunohistochemical panel comprising S100, melan A, HMB45, and SOX10 should be performed.

Expression of mitochondrial dynamics markers during melanoma progression: Comparative study of head and neck cutaneous and mucosal melanomas.

BACKGROUND: Head and neck mucosal melanomas (MMs) are rare tumors with adverse outcomes and poorer prognoses than their more common cutaneous counterparts (cutaneous melanomas-CMs). Few studies have compared the expression of mitochondrial dynamic markers in these tumors. This study aimed to assess the correlations of mitochondrial markers with melanoma progression and their potential as predictors of lymph node involvement and distant metastasis. METHODS: Immunohistochemistry against anti-mitochondrial (AMT), dynamin-related protein 1 (DRP1), mitochondrial fission protein 1 (FIS1), mitofusin-1 (MFN1), and mitofusin-2 (MFN2) antibodies was performed in 112 cases of head and neck CM and MM. A Cox regression multivariate model was used to assess the correlation of AMT, FIS1, and MFN2 expressions considering the risk for nodal and distant metastasis. RESULTS: All markers studied presented higher staining in tumor cells than normal adjacent tissues. Higher mitochondrial content was observed in MM than in CM, and it was significantly associated with nodal metastasis in oral melanomas. Both FIS1 and DRP1 expressions were related to advanced Clark's levels in CM, and they were overexpressed in oral melanomas. Moreover, increased immunoexpression of MFN2 was significantly associated with a higher risk of metastasis in CM, and it was also overexpressed in sinonasal melanomas. CONCLUSIONS: Our results suggest that mitochondrial fission and fusion processes can play an important role during multiple stages of tumorigenesis and the development of nodal and distant metastasis in cutaneous and mucosal melanomas.

Occupational Exposure to Potentially Infectious Biological Material Among Physicians, Dentists, and Nurses at a University.

OBJECTIVE: The objective of this study was to evaluate the prevalence and incidence of accidents with biological material, the level of knowledge, and compliance to standard precautions (SPs) among dentists, physicians, nurses, and dental and medical students. METHODS: A closed cohort study with a prospective and retrospective component was conducted between August 2014 and September 2015. The participants were contacted in two moments during the follow-up period, during which a structured questionnaire divided into six sections was used; the interviews were conducted during the follow-up period (Month 6) and at the end of the observation period (Month 12). RESULTS: The global prevalence of accidents in the previous 12 months was 10.2%, with a difference between professionals and students (13.0% vs. 5.1%, respectively; p < 0.003). The incidence rate was 6.49 per 100 person/year, with difference between the groups (6.09 per 100 person/year in professionals and 7.26 per 100 person/year in students), type of specialization (hazard ratio, 3.27), and hours worked per week (hazard ratio, 2.27). The mean of compliance to SP was 31.99 (±3.85) points, with a median of 33 (30, 35) points against the expected 27.75 points. Adherence to SP was associated with the accident report (p < 0.020). CONCLUSION: We conclude that the proportion/incidence rate of accidents with biological material was high in relation to that in the literature, being higher in professionals and especially among physicians. The levels of knowledge and adherence to SP were good, with the best found in dentists and dental students.

Prognostic importance of mitochondrial markers in mucosal and cutaneous head and neck melanomas.

Mitochondrial dysfunction is caused by an imbalance in the fission and fusion processes, and it has been implicated in the pathogenesis of several human cancers. However, the role of mitochondrial markers in melanomas still remains poorly understood. In this study, the authors assessed the expression of 3 mitochondrial markers (antimitochondrial, fission protein 1 [FIS1], and mitofusin 2 [MFN2]) in a series of head and neck mucosal and cutaneous melanomas. Patients with cutaneous (n = 56) and mucosal (oral, n = 30, sinonasal, n = 26) melanomas of the head and neck region were enrolled in this study. Clinical and follow-up data were retrieved from medical records. The expression of 3 mitochondrial markers was assessed by the immunohistochemistry, and then digitally quantified and correlated with clinicopathological data and outcome information. In the multivariate model, high mitochondrial content was identified as an independent prognostic value for disease-free survival (DFS) in cutaneous melanomas and overall survival in oral melanomas. FIS1 expression was significantly associated with lower overall survival rates in patients with oral melanomas and strictly correlated with vascular invasion in mucosal melanomas. MFN2 was associated with high risk of distant metastasis in patients with cutaneous melanomas. In summary, the authors demonstrated that mitochondrial content, along with FIS1 and MFN2 expressions, is correlated with important clinicopathological characteristics in patients with cutaneous and mucosal head and neck melanomas.

Expression of FGF-2/FGFR-1 in normal mucosa, salivary gland, preneoplastic, and neoplastic lesions of the oral cavity.

Fibroblast growth factor 2 (FGF-2) is a multifunctional cytokine expressed in several tissues and involved in a wide variety of biologic activities, with one low molecular weight (LMW) protein present in the cytosol, which is secreted, acting via its receptors (FGFRs), and four high molecular weight (HMW) proteins located in the nucleus. Fibroblast growth factor receptor (FGFR) family has four (FGFR1-4) transmembrane tyrosine kinase receptors expressed on several cell types, and FGFR-1 has been indicated as a potential molecular target in several types of cancer, including oral squamous cell carcinoma (OSCC). The FGF-2/FGFR-1 expression has been studied in the oral cavity, and it was associated with the wound repair process, the development of benign and malignant salivary gland tumors, besides being related to oral potentially malignant disorders (OPMDs) and OSCC. Hence, we critically review the currently available data on FGF-2/FGFR-1 expression in the normal mucosa and lesions of the oral cavity.

Sebaceous adenocarcinomas of the major salivary glands: a clinicopathological analysis of 10 cases.

AIMS: Sebaceous carcinomas are uncommon malignant cutaneous tumours originating from the pilosebaceous unit. Although its occurrence is mostly common in peri-ocular glands, other anatomical regions of the head and neck may be affected, including major and minor salivary glands. METHODS AND RESULTS: We describe a series of sebaceous adenocarcinomas of the parotid and submandibular glands. The mean age was 62.1 (range = 31-90) years. Two patients (20%) presented regional or distant metastasis to mandible and lungs. All cases were positive for cytokeratins (AE1AE3 and CK-5), epithelial membrane antigen and adipophilin and negative for androgen receptor, Factor XIIIa, S-100, vimentin and perforin. MLH1 and MSH2 were expressed in the nuclei of most tumour cells, and one case showed loss of MSH2 expression. Proliferative index (assessed by Ki-67 expression) and microvessel density (CD34-positive vessels) were higher in metastasis-associated cases. P63 expression was noted in the periphery of the tumour nests, in the basaloid cells, with a mean of 69.2% nuclear positivity. CONCLUSIONS: The sebaceous adenocarcinoma of salivary glands is rare and may show an unfavourable outcome; therefore, its correct diagnosis may be challenging. For this reason, immunohistochemical studies, including adipophilin in particular, constitute an important diagnostic tool.

A challenging diagnosis: Case report of oral metastasis from gastric adenocarcinoma mimicking pyogenic granuloma.

RATIONALE: Oral metastases occur more commonly in bone, but can also manifest in soft tissues and eventually resemble a reactive lesion. Few cases of oral metastases mimicking reactive lesions in soft tissues have been reported to date. PATIENT CONCERNS: We report a metastasis of gastric carcinoma (GC) to the oral mucosa without bone involvement in a 43 yom clinically and microscopically mimicking a reactive lesion. The patient related that the lesion had 1 month of evolution, and the ulcerated area suggested the lesion was related to trauma. DIAGNOSES: The histopathological examination of the lesion revealed an exuberant granulation tissue with few neoplastic cells, and the initial diagnosis of pyogenic granuloma was considered. In a second analysis, clusters of clear cells morphologically similar to degenerating mucous cells or macrophages, positive for Cytokeratin (CK)-20, and CDX2 were found. At the moment, it was confirmed the presence of a primary GC in the patient. INTERVENTIONS: A palliative radiotherapy/chemotherapy was started. OUTCOMES: However, the patient died 3 months after the diagnosis of oral metastasis. LESSONS: This report highlights the importance of careful clinical and microscopic examinations in cases of oral metastasis that may mimic a reactive lesion.

Oral and maxillofacial manifestations of chronic kidney disease-mineral and bone disorder: a multicenter retrospective study.

OBJECTIVE: To describe the oral and maxillofacial manifestations of patients diagnosed with chronic kidney disease-mineral and bone disorders. STUDY DESIGN: Over a 13-year period, clinicopathologic data of patients diagnosed with CKD-MBD who had oral and maxillofacial alterations were retrieved from the files of 4 Brazilian institutions. Data included clinical, radiographic, microscopic, and biochemical findings; treatment employed; and follow-up status. RESULTS: Twenty-one cases were identified, with 13 patients diagnosed as brown tumor of hyperparathyroidism (BTH) and 8 as osteitis fibrosa/renal osteodystrophy (OF/RO) (4 of them clinically consistent with Sagliker syndrome). The mean age was 32.7 years, and the mandible was the most affected site (42.8%). OF/RO had an ill-defined "ground glass" radiographic appearance, and BTH produced well-defined radiolucent images. Biochemically the following mean values were obtained: parathormone 1511.07 pg/mL, calcium 9.25 mg/dL, phosphorus 5.19 mg/dL, alkaline phosphatase 941.55 U/L, urea 125.42 mg/dL, and creatinine 7.14 mg/dL. Treatment comprised vitamin D and calcium intake, parathyroidectomy, hemodialysis, renal transplantation, and local surgery. During follow-up, 5 patients with BTH were free of lesions, whereas 2 affected by OF/RO/Sagliker syndrome died. CONCLUSIONS: Oral and maxillofacial manifestations of BTH and OF/RO are uncommon, but they can be associated with an important life-threatening scenario.

Phosphorylated Akt1 expression is associated with poor prognosis in cutaneous, oral and sinonasal melanomas.

Melanomas are highly aggressive tumours derived from melanocytes, which occur most commonly in the skin. Occasionally, these tumours may appear in oral and sinonasal mucous membranes. In this study, we performed a comparative analysis of the Phosphorylated Akt1 (p-Akt1) expression in 144 patients affected by cutaneous (CM), 34 oral cavity (OM), and 31 sinonasal melanomas (SNM). Similar to the metastatic cutaneous melanomas, p-Akt1 was overexpressed in 17/34 of the oral cavity and 20/31 of the sinonasal melanomas. In addition, the p-Akt1-nuclear expression was associated with poorer cancer-specific survival in cutaneous (P < .0001), oral (P < .0001), and sinonasal (P = .001) melanomas. Multivariate analysis showed p-Akt1 to be an independent prognostic marker in oral (P = .041) and sinonasal (P < .0001) melanomas patients. In conclusion, p-Akt1 overexpression is an independent prognostic marker in mucosal melanomas and is significantly up-regulated in sinonasal melanomas. As both mucosal and metastatic cutaneous melanomas showed high frequency of p-Akt1 expression, these findings suggest that mucosal melanomas have a biological behaviour, similar to the aggressive cutaneous melanomas.

Prognostic significance of cyclooxygenase 2 and phosphorylated Akt1 overexpression in primary nonmetastatic and metastatic cutaneous melanomas.

Cyclooxygenase 2 (COX-2) and phosphorylated Akt1 (p-Akt1) are associated with tumor spreading, cell proliferation, high metabolism, and angiogenesis in solid tumors. This study aimed to investigate COX-2 and p-Akt1 expression in primary and metastatic melanomas by correlating with the cellular proliferation index (as revealed by minichromosome maintenance 2 expression) and the outcome of patients with malignant melanomas. Seventy-seven biopsies of malignant melanomas, including 42 primary nonmetastatic melanomas (PNMMs), 12 primary metastatic melanomas (PMMs), and 23 metastatic melanomas (MMs), were retrospectively selected. Tissue microarrays were developed and submitted for immunohistochemical staining for COX-2, p-Akt1, and minichromosome maintenance 2. Increased COX-2 cytoplasmic staining patterns were observed in PMM and MM when compared with PNMM (P=0.0011). Higher nuclear and cytoplasmic expression of p-Akt1 was more closely associated with PMM than with MM and PNMM (P<0.00001). Coexpression of these biomarkers was closely correlated with lower overall survival rates in melanomas. Furthermore, we observed a statistically significant positive correlation between the mitosis index and increased COX-2 expression (P=0.0135) and between p-Akt1 (P=0.0038) and the cellular proliferation index (P=0.0060). Taken together, our findings demonstrate that COX-2 and p-Akt1 play an important combined role during melanoma progression and are associated with highly metastatic tumors and survival rates in patients with MM. In addition, these biomarkers can be used to predict melanoma prognosis independently of metastatic status. However, further studies are required to elucidate the biological role of these biomarkers during the progression of MM events.

Cementoblastoma: oito novos casos, revisão da literatura e considerações sobre melhor manejo clínico / Cementoblastoma: report of eight cases, literature review and considerations of best approach

Cementoblastoma é um tumor odontogênico benigno incomum de origem mesenquimalque usualmente afeta ossos gnáticos de indivíduos jovens, produzindo dor ou desconforto. Pode ser erroneamente diagnosticado como outras lesões, devido sua variada apresentação clínica era diográfica. Frequentemente o tratamento sugerido é a ressecção tumoral em conjunto como dente associado. Entretanto, abordagem mais conservadora pode ser uma opção em alguns casos assintomáticos e estáveis, como observado neste estudo. Apresentamos oito novos casos e uma breve revisão da literatura a fim de melhor caracterizar o comportamento biológico desta relativamente rara lesão.

Cementoblastoma is an uncommon benign odontogenic tumour of mesenchymal originthat affects the jaws of generally young persons, producing pain or discomfort. It may be mistakenfor several other lesions, due to its varied clinical and radiographic features. The suggestedtreatment is often tumour resection in conjunction with the associated tooth. However, a moreconservative approach could be an option in asymptomatic and stable lesions as seen in thepresent study. Eight new cases and a brief review of the literature are presented here to bettercharacterize the biological behavior of this relatively rare lesion.

Tongue squamous cell carcinoma in young nonsmoking and nondrinking patients: 3 clinical cases of orthodontic interest.

Oral squamous cell carcinoma traditionally affects older men who smoke and drink. A change in this profile has been reported because of an increased incidence in young nonsmoking and nondrinking patients. The purpose of this article was to describe a series of young nonsmoking and nondrinking patients diagnosed with tongue squamous cell carcinoma who had recently received orthodontic treatment or evaluation. Details regarding diagnosis, treatment, follow-up, and disease evolution are presented, with a review of the pertinent literature. Orthodontists often treat young adults, who have frequent dental appointments and long-term follow-ups. Thus, practitioners should pay special attention to young patients during dental consultations, since the incidence of malignant oral lesions in this segment of the population seems to be increasing.

Oral carcinoma cuniculatum: two cases illustrative of a diagnostic challenge.

Carcinoma cuniculatum is a rare variant of squamous cell carcinoma originally described on the sole of the foot and for a long time believed to be restricted to the skin. However, since its first description in 1954, several cases have been reported at other sites. Carcinoma cuniculatum characteristically invades the underlying subcutaneous, submucosal, or bone tissues, forming so-called "rabbit burrows," with crypts filled with keratin that are of utmost importance for distinguishing this neoplasm from other variants of squamous cell carcinoma. Oral carcinoma cuniculatum is an even rarer entity that is frequently misdiagnosed initially, a phenomenon described in about one-third of previously reported cases. The aim of this report is: (1) to describe the clinicopathologic features of 2 new cases of oral carcinoma cuniculatum, initially misdiagnosed as infected orthokeratinized cyst and abscess, respectively; and (2) to review the related English language literature.

Hard palate hyperpigmentation secondary to chronic chloroquine therapy: report of five cases.

Antimalarials are commonly prescribed in medical practice for conditions such as rheumatoid arthritis, lupus erythematosus, as well as malaria. They are generally well-tolerated, but side effects, although infrequent, are well known. The antimalarial chloroquine diphosphate may be associated with a bluish-gray to black hyperpigmentation of the oral mucosa, mainly on the hard palate. In this report we described five additional cases of palate hyperpigmentation related to the chronic use of chloroquine diphosphate. Professionals must be aware of the adverse effects of antimalarials as chloroquine diphosphate in order to make the correct diagnosis and appropriate management of the patient. Early diagnosis of oral pigmentation by antimalarials may be of great relevance, because it might be an early sign of ocular involvement, and therefore it may be helpful to prevent further complications of antimalarial therapy for the patient.

Oral vascular malformation in a patient with hereditary hemorrhagic telangiectasia: a case report.

Hereditary hemorrhagic telangiectasia (HHT) is an inherited mucocutaneous disease characterized by recurrent epistaxis, lesions on skin and oral mucosa, and arteriovenous malformations of the soft tissues. This article describes the treatment of a 64-year-old woman with a bleeding nodule, which was diagnosed as an arteriovenous malformation of the gingival mucosa. She was treated using sclerotherapy. Patients with HHT can be treated in the dental office and vascular malformations of these patients can be successfully managed with sclerotherapy, which eliminates the need for invasive surgical procedures and the possibility of postsurgical complications.

Digit ratio (2D:4D) is associated with gastric cancer.

BACKGROUND: Sex steroid exposure during early human development may influence disease susceptibility. Digit ratio (2D:4D) is a putative marker for prenatal hormone exposure and sensitivity, as well as the action of genes closely related to carcinogenesis. Digit ratio could act as a possible marker for cancer predisposition. AIMS: The aim of this study is to investigate the possible correlations between right hand, left hand and right minus left (R-L) 2D:4D and gastric cancer (GCA) in men and women and assess the correlations with tumor staging and histological diagnosis. METHODS: Digital images of the right and left hand palms of patients diagnosed with GCA (n=57, 42 males, 15 females) and age and sex-matched controls (n=59, 41 males, 18 females) were obtained. Means for 2D:4D were compared. Data were analyzed by repeated-measures one-way ANOVA and Student's t-test for finger measurements and group comparisons and Pearson's and Spearman's tests for correlations with tumor staging (α=0.05). RESULTS: GCA group presented significantly higher left 2D:4D, but significantly lower R-L in comparison to healthy controls, particularly so for males. Digit ratio did not correlate to clinical staging or TNM staging. However, low R-L was significantly related to adenocarcinomas. CONCLUSIONS: Early developmental conditions, including prenatal testosterone seem to play a role on the malignant transformation of gastric lesions. The 2D:4D pattern found for gastric cancer parallels that earlier described for breast cancer. The findings suggest that 2D:4D could add to the list of etiological factors and be a putative marker for the screening of patients' susceptibility to develop gastric cancer.

Atypical presentations of simple bone cysts of the mandible: a case series and review of literature.

Simple bone cysts are well-defined intraosseous radiolucencies that often extend between the roots and appear clinically like empty cavities. This article aims to provide more information about this lesion with limited prominence in academic literature, to illustrate atypical cases, and to provide a review of the current literature. A series of six atypical cases of simple bone cysts is presented and their clinical, radiographic and microscopic characteristics, differential diagnosis, treatment and follow-up are discussed. Correct diagnosis of this entity is of key importance, since it presents with clinical & radiographic similarities to other bone lesions, some exhibiting more aggressive behaviour.