Contribution of public oral pathology services to the diagnosis of oral and oropharyngeal cancer in Brazil

Abstract This study aimed to evaluate the contribution of oral and maxillofacial pathology laboratories (OMPLs) in Brazilian public universities to the diagnosis of lip, oral cavity, and oropharyngeal squamous cell carcinoma (SCC). A cross-sectional study was performed using biopsy records from a consortium of sixteen public OMPLs from all regions of Brazil (North, Northeast, Central-West, Southeast, and South). Clinical and demographic data of patients diagnosed with lip, oral cavity, and oropharyngeal SCC between 2010 and 2019 were collected from the patients' histopathological records. Of the 120,010 oral and maxillofacial biopsies (2010-2019), 6.9% (8,321 cases) were diagnosed as lip (0.8%, 951 cases), oral cavity (4.9%, 5,971 cases), and oropharyngeal (1.2%, 1,399 cases) SCCs. Most cases were from Brazil's Southeast (64.5%), where six of the OMPLs analyzed are located. The predominant profile of patients with lip and oral cavity SCC was Caucasian men, with a mean age over 60 years, low schooling level, and a previous history of heavy tobacco consumption. In the oropharyngeal group, the majority were non-Caucasian men, with a mean age under 60 years, had a low education level, and were former/current tobacco and alcohol users. According to data from the Brazilian National Cancer Institute, approximately 9.9% of the total lip, oral cavity, and oropharyngeal SCCs reported over the last decade in Brazil may have been diagnosed at the OMPLs included in the current study. Therefore, this data confirms the contribution of public OMPLs with respect to the important diagnostic support they provide to the oral healthcare services extended by the Brazilian Public Health System.

Estresse e periodontite: avaliação da inervação simpática no periodonto e da resposta adrenérgica após infecção por Porphyromonas gingivalis / Stress and periodontitis: evaluation of sympathetic innervation in the periodontium and the influence of adrenergic signaling on Porphyromonas gingivalis infection

O estresse agrava a doença periodontal por vários mecanismos, sendo a estimulação do sistema nervoso simpático (SNS) um deles. A literatura mostra que a estimulação de receptores ß-adrenérgicos (ß-AR) aumenta a angiogênese em ossos longos, e a expansão microvascular agrava a periodontite. Ainda, catecolaminas aumentam a virulência de periodontopatógenos e agem na resposta imune. Assim, o objetivo deste trabalho foi avaliar: (1) a inervação simpática no periodonto e a influência da ativação do SNS na vascularização periodontal em camundongos e (2) a influência do sistema adrenérgico nos fatores de virulência de Porphyromonas gingivalis (Pg) e na resposta imunológica a este patógeno in vivo (Galleria mellonella). Na primeira parte, camundongos receberam injeção intraperitoneal de solução salina (PBS) ou isoproterenol (ISO; agonista não seletivo ß adrenérgico) por 1 mês, para detecção in situ de tirosina hidroxilase, neuropeptídeo Y, transportador de norepinefrina (NET) e endomucina em mandíbulas. Expressão de mRNA de Vegf-a, Il-1ß, Il-6, Adrb2 e Rankl foi quantificada 2 h após administração de ISO/PBS em mandíbula e tíbias, que serviram como controle positivo. Diferentemente das tíbias, não houve alteração na expressão dos genes analisados em mandíbula. Por outro lado, NET foi mais expresso no osso alveolar do que na tíbia, sendo detectado nos osteoblastos, osteócitos e células do ligamento. Embora o padrão de inervação e a expressão de Adrb2 sejam semelhantes entre mandíbula e tíbia, o tratamento com ISO não influenciou no número e área de vasos positivos para endomucina. Na segunda parte, investigamos a influência adrenérgica na resposta imune de G. mellonella durante infecção por Pg utilizando norepinefrina (NE; agonista α e ß adrenérgico) e ISO. Pg também foi cultivada na presença de ISO (PgISO) ou NE para avaliação da ação direta dos compostos na bactéria. ISO sistêmico protegeu as larvas da infecção por Pg, aumentando o número de hemócitos e reduzindo a contagem de células de Pg na hemolinfa, exclusivamente pelo ß-AR. Diferentemente, NE aumentou mortalidade, diminuiu o número de hemócitos. Apenas PgISO aumentou a morte das larvas, apesar de ambos, NE e ISO, terem aumentado a expressão de fatores de virulência na bactéria in vitro. ISO circulante, concomitante com PgISO, reduziu parcialmente a mortalidade das larvas. A influência do estresse na doença periodontal envolve diversas vias que alteram os dois pilares da periodontite (microbiota e sistema imune). No entanto, a ação na resposta do hospedeiro parece ser superior, uma vez que a estimulação ß-AR em osso alveolar saudável não alterou a produção de citocinas pró-inflamatórias ou microvascularização e a modulação da resposta imune em G. mellonella por compostos adrenérgicos foi mais importante para o desfecho da infecção que sua ação direta sobre a bactéria.

Stress aggravates periodontitis, and one possible mechanism is the activation of sympathetic nervous system (SNS). The literature shows that stimulation of ß-adrenergic receptors (ß-AR) induces angiogenesis in long bones, and microvasculature amplification was linked to periodontitis severity. Moreover, catecholamines increase the virulence of some periodontopathogenic bacteria in vitro and influences the innate immunity. Thus, the aim of this study was (1) evaluate the presence and influence of the SNS in the stimulation of periodontal vasculature, and (2) the influence of the adrenergic system on Porphyromonas gingivalis (Pg) virulence and on the immunological response to this pathogen in vivo (Galleria mellonella larvae). For the first part, mice received isoproterenol (ISO, a non-selective ß-AR agonist) or saline (PBS) for 1 month, for in situ analysis of tyrosine hydroxylase, neuropeptide Y, norepinephrine transporter (NET) and endomucin in the mandibles. Vegfa, Il-1ß, Il-6, Adrb2 and Rankl mRNA expression was assessed 2 hours after PBS/ISO treatment for mandibles and tibia, that served as positive control. We observed that, differently from the tibia, the expression of these genes did not alter on the mandible. However, NET expression was detected in osteoblasts, osteocytes, and periodontal ligament fibroblasts, and were higher expressed when compared to the tibias from the same animals. Although the pattern of sympathetic innervation and Adrb2 expression were similar between tissues, ISO treatment did not increase the area or number of endomucin+ vessels. For the second part, we addressed the adrenergic signaling influence on G. mellonella immune system during Pg infection using norepinephrine (NE, α- and ß-AR agonist), ISO and octopamine (insect's endogenous hormone). Pg was also cultivated in the presence of ISO (PgISO) or NE to investigate the direct action of the ligands on bacterial virulence. Systemic administration of ISO protected the larvae from Pg infection by increasing hemocyte density accompanied by reduction of Pg load in hemolymph, in a ß-AR manner. In contrast, NE increased mortality, with decreased hemocyte count and no influence on the other parameters. Only PgISO increased larvae death, despite of ISO and NE increased virulence in vitro. The concomitant injection of systemic ISO partially reversed the toxicity of the PgISO. The influence of stress on periodontitis involves different pathways, that alter the two pillars of disease's pathogenesis (microbiota and immune system). However, the influence on the host's inflammatory response seems to overcome the other players, since ß-AR activation on healthy alveolar bone didn't alter cytokines production or microvasculature. Besides, the modulation of innate immunity by adrenergic signaling in G. mellonella was more important for the disease's outcome than it's direct action on the bacteria.

Oral ulcerative lesions in a post-liver-transplantation patient

Oral involvement is rarely found in histoplasmosis, except in its disseminated form, which is mostly observed in the severely immunocompromised host. Herein, we presented the case of a 36-year-old female with a previous history of liver transplant, who was hospitalized due to fever, chills, night sweats, diarrhea, and painful oral lesions over the last 3 days. The oral examination revealed the presence of painful shallow ulcers lined by a pseudomembrane in the gingiva and the soft and hard palate. The initial working diagnosis comprised cytomegalovirus reactivation or herpes simplex virus infection. The diagnostic work-up included incisional biopsies of the gingiva and the sigmoid colon. Both biopsies confirmed the diagnosis of histoplasmosis. Intravenous itraconazole was administered with significant improvement after 7 days. Although oral involvement is rare, histoplasmosis should be included in the differential diagnosis of oral lesions, particularly when the patient is immunosuppressed. This study reports a rare presentation of histoplasmosis involving the mucosa of the oral cavity and the colon.

Agreement, correlation, and kinetics of the alveolar bone-loss measurement methodologies in a ligature-induced periodontitis animal model

Abstract Periodontal research involves the use of animal models to better understand the biological processes of periodontal diseases and the potential of new or existing therapies. Currently, ligature-induced periodontitis in rats is the main model used in periodontal research, in this model, alveolar bone loss (ABL) is the main parameter evaluated by radiographic, morphometric, and histological techniques. Interestingly, although these methodologies are widely used, it is not totally clarified neither the kinetics of ABL over the induction time nor the agreement degree (repeatability and reproducibility) of these techniques. Objective: To characterize ABL kinetics at 0, 3, 7, 15, 30, and 60 days after ABL induction by ligature and to evaluate the intra- (repeatability) and inter-examiner (reproducibility) agreement and the correlation among the radiographic, morphometric, and histological methodologies. Material and Methods: 60 male Wistar rats with induced ABL were randomly divided into 6 experimental groups (n = 10 animals/group). After 0, 3, 7, 15, 30, and 60 days, the animals were euthanized and their hemimandibles were removed for ABL determination using radiographic, morphometric and histological techniques. Results: Radiographic and morphometric/linear techniques allowed the detection of statistically significant ABL on the third day, while histological and morphometric/area techniques could only detect ABL after the seventh day (ANOVA/Tukey, p<0.05). After the fifteenth day, except for histological analysis, the ABL was stabilized. Concerning the agreement of the methodologies, Bland Altman's test (intra and inter-examiner evaluations) showed no difference among the measurements (p>0.05). In addition, high correlations (Pearson's test, r2>0.9, p<0.05) were observed. Conclusion: The results indicated that the minimum time for ABL induction could vary from 3 to 7 days, according to the chosen analysis methodology. Agreement and correlation data support the comparison of results between studies with same induction time.

Mandible metastasis of small cell lung cancer mimicking a residual cyst

Small cell lung carcinoma (SCLC) is an uncommon tumor characterized by an aggressive behavior with early metastasis, usually to the contralateral lung, liver, brain, and bones. There are only five cases of this particular tumor metastasizing to the oral cavity described in the English literature. We present the case of metastatic SCLC in the mandible with radiographic findings resembling a residual cyst. A 66-year-old man with previous diagnosis and treatment for a SCLC was referred to the Stomatology Department with a history of persistent pain in the mandible 1 year after the inferior right pre-molar tooth extraction. The radiographic exam showed a well-delimited radiolucent area on that extracted tooth's region resembling a residual cyst. Biopsy was performed yielding the diagnosis of metastatic SCLC. The patient was referred to the clinical oncologist for chemotherapy. Although uncommon, this tumor should be included in the differential diagnosis of jawbone lesions, particularly when the patient presents a previous diagnosis of SCLC.