Epithelial salivary gland tumors in pediatric patients: An international collaborative study.

OBJECTIVE: Salivary gland tumors (SGT) are a diverse group of uncommon neoplasms that are rare in pediatric patients. This study aimed to characterize the clinicopathological profile of pediatric patients affected by SGT from a large case series derived from an international group of academic centers. STUDY DESIGN: A retrospective analysis of pediatric patients with SGT (0-19 years old) diagnosed between 2000 and 2021 from Brazil, South Africa, and the United Kingdom was performed. SPSS Statistics for Windows was used for a quantitative analysis of the data, with a descriptive analysis of the clinicopathological characteristics and the association between clinical variables and diagnoses. RESULTS: A total of 203 cases of epithelial SGT were included. Females were slightly more commonly (56.5%), with a mean age of 14.1 years. The palate was the most common site (43.5%), followed by the parotid gland (29%), lip (10%), and submandibular gland (7.5%). The predominant clinical presentation was a flesh-colored, smooth, and painless nodule. Pleomorphic adenoma (PA) was the most frequently diagnosed SGT (58.6%), followed by mucoepidermoid carcinoma (MEC) (26.6%). Surgery (90.8%) was the favored treatment option. CONCLUSIONS: Benign SGT in pediatric patients are more commonly benign than malignant tumors. Clinicians should keep PA and MEC in mind when assessing nodular lesions of possible salivary gland origin in pediatric patients.

Free three-dimensional image software in local extension assessment of oral squamous cell carcinoma: a pilot study

Abstract Objective: Oral Squamous Cell Carcinoma (OSCC) is conventionally treated by surgical resection, and positive surgical margins strongly increase local recurrence and decrease survival. This study aimed to evaluate whether a Three-Dimensional Segmentation (3DS) image of OSCC confers advantage over Multiplanar Reconstruction (MPR) of OSCC using images of computed tomography scan in surgical planning of tumor resection. Methods: Twenty-six patients with locally advanced OSCC had tumor morphology and dimensions evaluated by MPR images, 3DS images, and Surgical Pathology Specimen (SPS) analyses (gold standard). OSCC resection was performed with curative intent using only MPR images. Results: OSCC morphology was more accurately assessed by 3DS than by MPR images. Similar OSCC volumes and dimensions were obtained when MPR images, 3DS images and SPS measurements were considered. Nevertheless, there was a strong correlation between the OSCC longest axis measured by 3DS and SPS analyses (ICC = 0.82; 95% CI 0.59-0.92), whereas only a moderate correlation was observed between the longest axis of OSCC measured by MPR images and SPS analyses (ICC = 0.51; 95% CI 0.09-0.78). Taking only SPS with positive margins into account, MPR images and 3DS images underestimated the tumor's longest axis in eight out of 11 (72.7%) and 5 out of the 11 (45.5%) cases, respectively. Conclusion: Our data present preliminary evidence that 3DS model represents a useful tool for surgical planning of OSCC resection, but confirmation in a larger cohort of patients is required. Level of evidence: Laboratory study.

Free three-dimensional image software in local extension assessment of oral squamous cell carcinoma: a pilot study.

OBJECTIVE: Oral Squamous Cell Carcinoma (OSCC) is conventionally treated by surgical resection, and positive surgical margins strongly increase local recurrence and decrease survival. This study aimed to evaluate whether a Three-Dimensional Segmentation (3DS) image of OSCC confers advantage over Multiplanar Reconstruction (MPR) of OSCC using images of computed tomography scan in surgical planning of tumor resection. METHODS: Twenty-six patients with locally advanced OSCC had tumor morphology and dimensions evaluated by MPR images, 3DS images, and Surgical Pathology Specimen (SPS) analyses (gold standard). OSCC resection was performed with curative intent using only MPR images. RESULTS: OSCC morphology was more accurately assessed by 3DS than by MPR images. Similar OSCC volumes and dimensions were obtained when MPR images, 3DS images and SPS measurements were considered. Nevertheless, there was a strong correlation between the OSCC longest axis measured by 3DS and SPS analyses (ICC = 0.82; 95% CI 0.59‒0.92), whereas only a moderate correlation was observed between the longest axis of OSCC measured by MPR images and SPS analyses (ICC = 0.51; 95% CI 0.09‒0.78). Taking only SPS with positive margins into account, MPR images and 3DS images underestimated the tumor's longest axis in eight out of 11 (72.7%) and 5 out of the 11 (45.5%) cases, respectively. CONCLUSION: Our data present preliminary evidence that 3DS model represents a useful tool for surgical planning of OSCC resection, but confirmation in a larger cohort of patients is required. LEVEL OF EVIDENCE: Laboratory study.

FAS and FASL variations in outcomes of tobacco- and alcohol-related head and neck squamous cell carcinoma patients.

Radiotherapy and cisplatin lead to cell killing in head and neck squamous cell carcinoma patients, but adverse events and response to treatment are not the same in patients with similar clinicopathological aspects. The aim of this prospective study was to evaluate the roles of TP53 c.215G > C, FAS c.-671A > G, FAS c.-1378G > A, FASL c.-844 C > T, CASP3 c.-1191A > G, and CASP3 c.-182-247G > T single nucleotide variants in toxicity, response rate, and survival of cisplatin chemoradiation-treated head and neck squamous cell carcinoma patients. Genomic DNA was analyzed by polymerase chain reaction for genotyping. Differences between groups of patients were analyzed by chi-square test or Fisher's exact test, multiple logistic regression analysis, and Cox hazards model. One hundred nine patients with head and neck squamous cell carcinoma were enrolled in study. All patients were smokers and/or alcoholics. Patients with FAS c.-671GG genotype, FAS c.-671AG or GG genotype, and FASL c.-844CC genotype had 5.52 (95% confidence interval (CI): 1.42-21.43), 4.03 (95% CI: 1.51-10.79), and 5.77 (95% CI: 1.23-27.04) more chances of presenting chemoradiation-related anemia of grades 2-4, lymphopenia of grade 3 or 4, and ototoxicity of all grades, respectively, than those with the remaining genotypes. FAS c.-671GG genotype was also seen as an independent predictor of shorter event-free survival (hazard ratio (HR): 2.05; P = 0.007) and overall survival (HR: 1.83; P = 0.02) in our head and neck squamous cell carcinoma patients. These findings present, for the first time, preliminary evidence that inherited abnormalities in apoptosis pathway, related to FAS c.-671A > G and FASL c.-844 C > T single nucleotide variants, can alter toxicity and survival of tobacco- and alcohol-related head and neck squamous cell carcinoma patients homogeneously treated with cisplatin chemoradiation.

Gene and immunohistochemical expression of HIF-1α, GLUT-1, FASN, and adipophilin in carcinoma ex pleomorphic adenoma development.

OBJECTIVE: To analyze the gene and immunohistochemical expression of HIF-1α, GLUT-1, FASN, and adipophilin in normal salivary gland (NSG), pleomorphic adenoma (PA), and carcinoma ex pleomorphic adenoma (CXPA) samples. MATERIAL AND METHODS: The gene expression was investigated by the real-time PCR (qRT-PCR) method in 9 samples of frozen tissues of normal salivary gland, 13 PA, and 10 CXPA. We validated the reactions by immunohistochemistry on 20 samples from NSG, 85 PA, and 44 CXPA. RESULTS: Our results showed that there was no statistically significant difference in HIF-1α gene and immunohistochemistry expression among the tissues studied while FASN gene and immunohistochemistry expression increased along the carcinogenesis of the PA. GLUT-1 was significantly more expressed in tumor tissues (PA and CXPA), although protein is mainly expressed in transformed cells than in PA and NSG. In contrast, adipophilin was significantly more expressed in NSG while the expression of the protein increased in PA and CXPA. CONCLUSIONS: In summary, the data presented here suggest that neoplastic cells reprogram the expression of GLUT-1 and adipophilin to adapt to the tumor microenvironment and reinforce, through immunohistochemical results, a possible transcriptional and post-translational regulatory mechanisms that act on the expression of these genes.

Polymorphisms in DNA mismatch repair pathway genes predict toxicity and response to cisplatin chemoradiation in head and neck squamous cell carcinoma patients.

Head and neck squamous cell carcinoma (HNSCC) is treated with cisplatin (CDDP) and radiotherapy (RT), and distinct results are observed among patients with similar clinicopathological aspects. This prospective study aimed to investigate whether MLH1 c.-93G>A (rs1800734), MSH2 c.211+9C>G (rs2303426), MSH3 c.3133G>A (rs26279), EXO1 c.1765G>A (rs1047840), and EXO1 c.2270C>T (rs9350) single nucleotide polymorphisms (SNPs) of the mismatch repair (MMR) pathway change side effects and response rate of 90 HNSCC patients treated with CDDP and RT. DNA from peripheral blood was analyzed by PCR-based methods to obtain genotypes. It was observed 4.27-fold and 4.69-fold increased risks of presenting pronounced nephrotoxicity with treatment in patients with MSH3 GG and EXO1 rs9350 CC genotypes compared with patients with GA or AA and CT or TT genotypes, respectively. MSH3 GG or GA and GT haplotype of EXO1 rs1047840 and rs9350 SNPs conferred to patients 10.29 and 4.00 more chances of presenting pronounced ototoxicity after treatment than MSH3 AA genotype and other EXO1 haplotypes, respectively. Patients with EXO1 rs1047840 GA or AA genotype and AC haplotype of EXO1 rs1047840 and rs9350 SNPs had both 9.55-fold increased risks of achieving partial response or stable disease instead of complete remission after treatment than patients with EXO1 GG genotype and other EXO1 haplotypes, respectively. For the first time, our data show preliminary indication that inherited alterations of DNA MMR pathway, related to MSH3 rs26279, EXO1 rs1047840 and EXO1 rs9350 SNPs, modify toxicity and response to chemoradiation in HNSCC, and may contribute to future personalized treatment of patients.

Metastasis to Paranasal Sinuses from Carcinoma of Prostate: Report of a Case and Review of the Literature.

Metastasis from distant primary tumors is extremely rare in the paranasal sinuses with few hundred cases in the literature. Metastatic carcinoma of the prostate is even rarer, despite being one of the most common tumors, with only 24 cases published. In this article, we report a case of a 58-year-old male presenting with epistaxis and nasal obstruction as initial symptoms of a metastatic prostate carcinoma in the ethmoid cells and maxillary sinus.

Three-dimensional volumetric analysis of ghost cell odontogenic carcinoma using 3-D reconstruction software: a case report.

OBJECTIVE: Ghost cell odontogenic carcinoma is a very rare malignant neoplasm. Tumor volume may be a more precise alternative for determining size, which is usually measured by maximum linear dimension. The purpose of this case report is to highlight the importance of obtaining 3-dimensional (3-D) images of the tumor for volumetric analysis to improve the chances of surgical success. This report presents a case of ghost cell odontogenic carcinoma infiltrating the maxillary sinus through the palate. The lesion was surgically treated and subsequently selected for volumetric reconstruction and analysis of the tumor by using InVesalius software. In this case report, we describe the use of a pictorial technique in which the tumor volume was calculated to help predict the surgical results. RESULTS: The tumor could be visualized in 3-D, with color improving the image of the segmented volume and thus increasing the perception of boundaries and depth. CONCLUSIONS: Recognition of the lesion shape by volumetric analysis can provide the surgical team with clearer information, thereby helping in surgical planning and consequently increasing the chances of surgical success.

Histologic correlation of expression of Ki-67 in squamous cell carcinoma of the glottis according to the degree of cell differentiation.

INTRODUCTION: Squamous cell carcinoma is the most common neoplasm of the larynx and glottis, and its prognosis depends on the size of the lesion, level of local invasion, cervical lymphatic spread, and presence of distant metastases. Ki-67 (MKI67) is a protein present in the core, whose function is related to cell proliferation. AIM: To evaluate the expression of marker Ki-67 in squamous cell carcinoma of the larynx and glottis and its correlation to pathological findings. METHODS: Experimental study with immunohistochemistry analysis of Ki-67, calculating the percentage of the cell proliferation index in glottic squamous cell carcinomas. RESULTS: Sixteen cases were analyzed, with six well-differentiated and 10 poorly/moderately differentiated tumors. There was a correlation between cell proliferation index and degree of cell differentiation, with higher proliferation in poorly/moderately differentiated tumors. CONCLUSION: The cell proliferation index, as measured by Ki-67, may be useful in the characterization of histological degree in glottic squamous cell tumors.

Histologic correlation of expression of Ki-67 in squamous cell carcinoma of the glottis according to the degree of cell differentiation / Correlação histológica da expressão do Ki-67 no Carcinoma Epidermoide Glótico de acordo com grau de diferenciação celular

INTRODUCTION: Squamous cell carcinoma is the most common neoplasm of the larynx and glottis, and its prognosis depends on the size of the lesion, level of local invasion, cervical lymphatic spread, and presence of distant metastases. Ki-67 (MKI67) is a protein present in the core, whose function is related to cell proliferation. AIM: To evaluate the expression of marker Ki-67 in squamous cell carcinoma of the larynx and glottis and its correlation to pathological findings. METHODS: Experimental study with immunohistochemistry analysis of Ki-67, calculating the percentage of the cell proliferation index in glottic squamous cell carcinomas. RESULTS: Sixteen cases were analyzed, with six well-differentiated and 10 poorly/moderately differentiated tumors. There was a correlation between cell proliferation index and degree of cell differentiation, with higher proliferation in poorly/moderately differentiated tumors. CONCLUSION: The cell proliferation index, as measured by Ki-67, may be useful in the characterization of histological degree in glottic squamous cell tumors. .

INTRODUÇÃO: O carcinoma de células escamosas é a neoplasia mais frequente da laringe e da região glótica, seu prognóstico depende do tamanho da lesão, do nível de invasão local, disseminação cervical linfática e da existência de metástases à distância. Ki-67 (MKI67) é uma proteína presente no núcleo, cuja função está relacionada com a proliferação celular. OBJETIVOS: Avaliar a expressão do marcador Ki-67 em carcinoma de células escamosas da laringe glóticos e correlacionar sua expressão com os achados anatomopatológicos. MÉTODO: Trabalho experimental de análise imunohistoquímica do Ki 67 através do cálculo percentual do índice de proliferação celular em produtos de carcinomas epidermóides glóticos. RESULTADOS: Dezesseis casos foram analisados, sendo seis bem diferenciados e dez pouco/moderadamente diferenciados. Houve correlação entre o índice de proliferação celular e o grau de diferenciação celular, sendo a proliferação maior nos pouco/moderadamente diferenciados. CONCLUSÃO: O índice de proliferação celular, medido pelo Ki-67 pode ser útil na caracterização do grau histológico em tumores glóticos de células escamosas. .

Efeitos do uso tópico de Ciprofloxacina na cicatrizaçäo de defeito epitelial corneano / Effect of topical ciprofloxacin on corneal ephithelial wound healing

O trabalho foi realizado para avaliar a influência do uso tópico de Ciprofloxacina, nas concentraçöes de 0,30 por cento, 0,75 por cento, 1,20 por cento com controles, na reparaçäo de defeito epitelial corneano central de 7,75 mm de diâmetro, em coelhas. A avaliaçäo da regeneraçäo epitelial foi feita com fotografias seriadas da área sem epitélio, corada com fluoresceína e medida com u auxílio de um analisador de imagem computadorizado, com exames biomicroscópicos diários e análise histológica. Presença de precipitado branco, na área sem epitélio foi observada em 35,71 por cento dos olhos tratados com Ciprofloxacina a 0,30 por cento e em 100 por cento dos olhos medicados com Ciprofloxacina a 0,75 por cento e a 1,20 por cento. A Ciprofloxacina a 0,30 por cento näo interferiu na regeneraçäo epitelial e näo induziu alteraçöes histopatológicas. Nas concentraçöes a 0,75 por cento e 1,20 por cento provocou retardo de cicatrizaçäo epitelial (p<0,001) e alteraçöes histopatológicas caracterizadas por aumento da celularidade no estroma subjacente, desorganizaçäo de lamelas do colágeno, espessamento da membrana basal e desprendimento do epitélio regenerado nos cortes histológicos.

Nucleolar organizer region (NORs) in pseudocarcinomatous hyperplasia and squamous cell carcinoma of the oral mucosa

Introduçäo e Objetivos: Regiöes organizadoras do nucléolo podem ser detectadas através do nitrato de prata em secçöes de parafina. A contagem de AgNORs tem sido utilizada para distinguir entre lesöes benignas e malignas. Material e Métodos: AgNORs foram contados em 24 biopsias da cavidade oral (5 casos de mucosa oral normal, 5 de hiperplasia pseudocarcinomatosa e 14 de carcinoma epidermóide, subdivididos segundo o grau de diferenciaçäo: 5 grau 1; 5 grau 2 e 4 grau 3) para verificar sua utilidade no diagnóstico diferencial entre hiperplasia pseudocarcinomatosa, secundária a infecçöes parasitárias crônicas, e carcinoma epidermóide. Foram usados dois métodos de contagem de AgNORs: um mais simples(A), que conta os agregados nucleolares (AgNU) e AgNOR satélites e o outro (B) que conta todos os AgNORs, inclusive aqueles dentro do AgNUs. Resultados e Conclusäo: Em ambos os métodos as médias mais baixas foram do carcinoma grau 3 e as mais altas do carcinoma grau 2. O método mais simples (A) foi o mais útil, pois a contagem de AgNU mostrou valores significantemente diferentes quando comparou-se hiperplasia pseudocarcinomatosa e carcinomas graus 1 e 2, que säo os mais difíceis de distinguir da hiperplasia. Entretanto, devido à sobreposiçäo de valores a técnica foi de utiliddade limitada em casos individuais

Nucleolar organizer regions (NORs)

Regiöes organizadoras do nucléolo podem ser detectadas através do nitrato de prata em seçöoes de parafina. A contagem de AgNORs tem sido utilizada para distinguir entre lesöes benignas e malignas. AgNORs foram contados em 24 biópsias da cavidade oral (5 casos de mucosa oral normal, 5 de hiperplasia pseudocarcinomatosa e 14 de carcinoma epidermóide, subdivididos segundo o grau de diferenciaçäo: 5 - grau 1,5 grau 2 e 4 grau 3) para verificar sua utilidade no diagnóstico diferencial entre hiperplasia pseudocarcinomatosa, secundária à infecçöes parasitárias crônicas, e carcinoma epidermóide. Foram usados dois métodos de contagem de AgNORs: um mais simples(A), que conta os agregados nucleolares (AgNU) e AgNOR satélites e o outro (B) que conta todos os AgNORs, inclusive aqueles dentro do AgNUs. Em ambos os métodos as médias mais baixas foram do carcinoma grau 3 e as mais altas do carcinoma grau 2. O método mais simples (A) foi o mais útil, pois a contagem de AgNU mostrou valores significantemente diferentes quando comparou-se hiperplasia psudocarcinomatosa e carcinomas graus 1 e 2, que säo os mais difíceis de distingüir da hiperplasia. Entretanto, devido à sobreposiçäo de valores a técnica foi de utilidade limitada em casos individuais