Chronic Sclerosing Sialadenitis of the Submandibular Gland and its Histopathological Spectrum in the IgG4-Related Disease: a Series of 17 Cases.

PURPOSE: This study aimed to characterize the histopathological immunohistochemical features of chronic sclerosing sialadenitis, emphasizing the IgG4-related disease. METHODS: Seventeen cases of chronic sclerosing sialoadenitis were examined for histopathological aspects, (inflammation, fibrosis, glandular parenchyma, and lymphoid follicles) and immunohistochemistry (BCL2, CD3, CD20, CD34, CD163, p63, cyclin D1, mast cell, SMA, S100A4, IgG, and IgG4) which were scored. IgG4-related disease features were investigated. Demographic and clinical data were also collected. RESULTS: Males predominated (10:7), with an average lesion size of 3.9 cm. Common histopathological findings included reduced acinar parenchyma, lymphoid follicle formation, and ductular proliferation. CD3-positive T lymphocytes and CD34- and SMA-positive stromal fibroblasts were abundant. Nine cases (53%) showed sialoliths and three cases met the criteria for IgG4-related disease. CONCLUSION: CSS of the submandibular gland represents a reactive pattern rather than IgG4-RD as only 3 cases seemed to be related to IgG4-RD. The immunohistochemical profile revealed an abundant population of CD3-positive T lymphocytes, as opposed to regulatory proteins such as cyclin D1, demonstrating that populations of CD34- and SMA-positive stromal fibroblasts contribute to the fibrosis characteristic of CSS. In addition, our results provide a comprehensive insight into the study of CSS and its relationship with IgG4-RD.

Histopathologic findings in ointment pseudo-cheilitis: An alert to dermatopathologists.

Ointment pseudo-cheilitis is a recently recognized distinctive type of self-induced cheilitis. Lesions consist of a variable amount of crusts adhered to the vermilion. These crusts consist of dried saliva and dead cells mixed with applied medications attached to the lip surface. Patients are typically severely anxious or depressed; the condition impacts quality of life. Ointment pseudo-cheilitis is frequently misdiagnosed as exfoliative cheilitis or cheilitis glandularis. Biopsy reports are often non-revealing because there are no established histopathological criteria for this disease, and clinicians usually do not formulate the correct diagnostic hypothesis. Here, we present the histopathological findings of four cases of ointment pseudo-cheilitis. The most consistent finding was the presence of laminated parakeratotic material detached from the epithelium in biopsies that are devoid of other significant diagnostic changes. This material at the lip surface possibly represents physiologic labial desquamation mixed with dried saliva and applied medication. With this report, we intend to alert dermatopathologists to the diagnosis of ointment pseudo-cheilitis if they receive biopsies from patients who present clinically exuberant labial lesions that show only minimal histopathological changes.

Is the neutrophil-to-lymphocyte ratio a marker for differentiating between benign and malignant submandibular gland masses?

OBJECTIVE: This study aimed to evaluate the effect of the neutrophil-to-lymphocyte ratio on the differentiation of benign and malignant masses in the submandibular triangle. METHODS: We retrospectively evaluated 48 patients who underwent surgery for submandibular gland masses between January 2013 and February 2023. The patient's age, gender, preoperative complete blood count and imaging findings, postoperative histopathological diagnosis, and hemogram data were analysed. Patients were evaluated according to their postoperative histopathological diagnoses and categorised into four main groups: sialolithiasis, sialadenitis, benign tumours, and malignant tumours. Benign submandibular gland disease formations were evaluated under group B and malignant tumour formations under group M. RESULTS: A preoperative fine needle aspiration biopsy was performed on 19 patients due to sialadenitis, pleomorphic adenoma, and malignant diseases other than sialolithiasis. One patient died among the patients with malignant disease and the remaining 7 patients were compared with the benign group of 40 patients regarding preoperative and postoperative neutrophil-to-lymphocyte ratio. In the benign group, the neutrophil-to-lymphocyte ratio was 2.64 preoperatively and decreased to 2.34 in the first postoperative year. The preoperative neutrophil-to-lymphocyte ratio decreased from 4.79 to 1.77 postoperatively in the malignant group. A statistically significant difference was observed (p<0.05). CONCLUSION: This is the first study to demonstrate that the neutrophil-to-lymphocyte ratio can be used as a biomarker in submandibular gland masses and has prognostic significance in malignant masses. In addition to fine needle aspiration biopsy results, neutrophil-to-lymphocyte ratio can be used as a biomarker.

Escisión de Glándula Submandibular por Sialoadenitis Crónica Esclerosante Asociada a Sialolito en el Conducto Submandibular / Submandibular Gland Excision Due to Chronic Sclerosing Sialadenitis Associated With Sialolith in Submandibular Duct

La sialoadenitis crónica esclerosante puede extenderse desde una sialoadenitis focal hasta una cirrosis completa de la glándula. Aparece entre los 40 y 70 años de edad y afecta principalmente a la glándula submandibular. Se asocia con sialolitos y agentes infecciosos inespecíficos. La causa más frecuente de sialolitiasis es la formación de cálculos macroscópicamente visibles en una glándula salival o en su conducto excretor, de los cuales el 80 % al 90 % provienen de la glándula submandibular. Esta predilección probablemente se deba a que su conducto excretor es más largo, más ancho y tiene un ángulo casi vertical contra la gravedad, contribuyendo así a la estasis salival. Además, la secreción semimucosa de la misma es más viscosa. El sitio principal de ubicación de los litos en el conducto submandibular es la región hiliar con un 57 %. La sintomatología típica de la sialolitiasis es el cólico con tumefacción de la glándula y los dolores posprandiales. Reportamos el caso de un paciente masculino de 55 años, quien ingresa al servicio de Cirugía Oral y Maxilofacial del Hospital General Balbuena de la Ciudad de México por presentar un aumento de volumen en la región submandibular izquierda de consistencia dura y dolorosa a la palpación de 15 días de evolución, acompañada de aumento de temperatura en la zona compatible con un absceso. Los estudios de imagen reportan un sialolito en la región hiliar del conducto submandibular de 2,0 x 1,7 x 1,0 cm. Debido a su localización y tamaño, el tratamiento ideal en estos casos es la escisión de la glándula junto con el lito previo drenaje del absceso e inicio de terapia antibiótica doble.

Chronic sclerosing sialadenitis can range from focal sialadenitis to complete cirrhosis of the gland. It appears between 40 and 70 years of age and mainly affects the submandibular gland. It is associated with sialoliths and nonspecific infectious agents. The most common cause of sialolithiasis is the formation of macroscopically visible stones in a salivary gland or its excretory duct, of which 80 % to 90 % come from the submandibular gland. This predilection isprobably due to the fact that their excretory duct is longer, wider and has an almost vertical angle against gravity, thus contributing to salivary stasis. In addition, the semimucous secretion of it is more viscous. The main location of the stones in the submandibular duct is the hilar region with 57 %. The typical symptomatology of sialolithiasis is colic with swelling of the gland and postprandial pain. We report the case of a 55-year-old male patient, who was admitted to the Oral and Maxillofacial Surgery Service of the Hospital General Balbuena in Mexico City due to an increase in volumen in the left submandibular region that was hard and painful on palpation of 15 days of evolution, accompanied by increased temperature in the area compatible with an abscess. Imaging studies report a 2.0 x 1.7 x 1.0 cm sialolith in the submandibular duct hilar region. Due to its location and size, the ideal treatment in these cases is excision of the gland together with the stone previous drainage of the abscess and initiation of dual antibiotic therapy.

Prevalence of Sjögren's syndrome according to 2016 ACR-EULAR classification criteria in patients with systemic lupus erythematosus.

BACKGROUND: Diagnosis of SS is a complex task, as no symptom or test is unique to this syndrome. The American-European Consensus Group (AECG 2002) and the American-European classification criteria of 2016 (ACR/EULAR 2016) emerged through a search for consensus. This study aims to assess the prevalence of Sjögren's Syndrome (SS) in patients with Systemic Lupus Erythematosus (SLE), according to AECG 2002 and ACR-EULAR 2016 classifications, as well as clinical and histopathological features in this overlap. To date, there is no study that has evaluated SS in SLE, using the two current criteria. METHODS: This cross-sectional study evaluated 237 SLE patients at the outpatient rheumatology clinic between 2016 and 2018. Patients were submitted to a dryness questionnaire, whole unstimulated salivary flow (WUSF), "Ocular Staining Score" (OSS), Schirmer's test I (ST-I), and labial salivary gland biopsy (LSGB). RESULTS: After verifying inclusion and exclusion criteria, a total of 117 patients were evaluated, with predominance of females (94%) and mixed ethnicity (49.6%). The prevalence of SS was 23% according to AECG 2002 and 35% to ACR-EULAR 2016. Kappa agreement between AECG 2002 and ACR-EULAR 2016 were 0.7 (p < 0.0001). After logistic regression, predictors for SS were: anti/Ro (OR = 17.86, p < 0.05), focal lymphocytic sialadenitis (OR = 3.69, p < 0.05), OSS ≥ 5 (OR = 7.50, p < 0.05), ST I positive (OR = 2.67, p < 0.05), and WUSF ≤ 0.1 mL/min (OR = 4.13, p < 0.05). CONCLUSION: The prevalence of SS in SLE was 23% (AECG 2002) and 35% (ACR-EULAR 2016). The presence of glandular dysfunction, focal lymphocytic sialadenitis, and anti/Ro were predictors of SS in SLE. The greatest advantage of the new ACR-EULAR 2016 criteria is to enable an early diagnosis and identify the overlapping of these two diseases. ACR-EULAR 2016 criteria is not yet validated for secondary SS and this study is a pioneer in investigating prevalence based on the new criteria.

Cheilitis glandularis: case report and systematic literature review.

Cheilitis glandularis (CG) is a rare inflammatory disease of unknown etiology that affects the minor salivary glands predominantly in the lower lip. In this article, we report the case of an 18-year-old black woman who presented with a deep suppurative type of CG in both lips. In addition, we performed a systematic literature review in five databases (PubMed, Scopus, Web of Science, Ovid, and Embase) to identify CG case reports or case series. A total of 360 references were retrieved in the electronic databases. Thirty-four articles met the inclusion criteria, and six were retrieved through manual search, totaling 40 articles included in the systematic review. Thirty-nine (68.4%) cases occurred in male individuals and 18 (31.6%) in female individuals. The mean age of affected individuals was 40.9 years. Different clinical manifestations ranging from no symptoms to discomfort, pain, swelling, erythema, eversion of the lip, dilated ductal openings, ulcers, and crust have been reported. Among the included CG cases, 41 affected exclusively the lower lip (71.9%). In four cases, the CG only affected the upper lip (7.0%). In 12 cases, the lesion affected both the lower and upper lips (21.1%). Different treatment modalities were adopted in the management of CG. Although the surgical treatment was indicated (42.1%), the conservative treatment with topical medications, as in the present case, resulted in resolution in 21.0% of cases.

Sialolitiasis, sialoadenitis y sialoadenosis. Revisión de literatura y reporte de un caso clínico / Sialolithiasis, sialadenitis and sialadenosis. Review of literature and report of a clinical case

Introducción: la formación de sialolitos se considera la alteración más común en las glándulas salivales. Su origen aún no es claro en cuanto a qué provoca la obstrucción parcial o total del sistema de conductos salivales, con una predilección significativa en las glán - dulas submandibulares, lo que permite un desplazamiento retrógrado de bacterias a través del conducto salival hacia la glándula afectada, el cual se traducirá clínicamente como inflamación unilateral o bila - teral. El tratamiento para la sialolitiasis y sialoadenitis puede variar desde un manejo conservador hasta tratamientos que implican la remoción de la glándula salival afectada. La sialoadenosis difiere de las anteriores en su origen, ya que ésta no se considera inflamatoria ni neoplásica y no afecta la función glandular de excretar saliva. Presentación de caso clínico: se trata de paciente masculino con diagnósticos presuntivos de sialoadenitis y sialolitiasis, al cual se le realizó biopsia escisional de la glándula afectada, su estudio histo- patológico corroboró los diagnósticos mencionados anteriormente que además confirmó un diagnóstico de sialoadenosis. Conclusio- nes: la escisión de la glándula salival involucrada se realizará en casos diagnosticados de sialoadenitis y sialolitiasis con sialolitos de gran tamaño y procesos supurativos crónicos que no resuelven con antibioticoterapia (AU)

Sialoendoscopia y abordaje mixto para el manejo dela patología obstructiva de las glándulas salivales / Sialoendoscopy and mixed approach for the management of obstructive pathology of the salivary glands

Introducción. La sialoendoscopia es un procedimiento cuya finalidad es visualizar los conductos salivales. Se utiliza como método diagnóstico y terapéutico de procesos inflamatorios, estenosis de los conductos y procesos obstructivos. Métodos. Describir los procedimientos realizados para el tratamiento de pacientes con patología inflamatoria y obstructiva de las glándulas salivales, de forma única con sialoendoscopia o con abordajes mixtos. Resultados. Un total de 24 pacientes fueron incluidos en el estudio, con edad promedio de 42 años, en su mayoría mujeres y compromiso submaxilar en 58,3 % y de parótida en 41,7 %. Respecto a la intervención, al 29,2 % de los sujetos se le realizó extracción de cálculos, al 29,2 % sialoplastia, al 25 % dilatación de conductos y al 37,5 % lavado de conductos en el mismo momento quirúrgico. Conclusión. La sialoendoscopia y el abordaje mixto es un procedimiento que puede garantizar el manejo de patologías obstructivas y estenosis de los conductos salivales, con buen pronóstico y resultados, preservando la glándula y evitando las complicaciones de la cirugía.

Introduction. Sialoendoscopy is a procedure which purpose is to visualise the salivary ducts. It is used as a diagnostic and therapeutic method for inflammatory and obstructive processes and duct stenosis. Methods. To describe the procedures performed for the management of patients with inflammatory and obstructive pathology of the salivary glands, only with sialoendoscopy or with mixed approaches. Results. A total of 24 patients were included in the study, with mean age of 42 years, mostly female, and 58.3% submaxillary involvement 41.7% parotid involvement. Regarding the intervention, 29.2% of the subjects underwent stone extraction, 29.2%, sialoplasty, 25% duct dilatation, and 37.5% duct lavage at the same surgical time. Conclusions. Sialoendoscopy and the mixed approach is a procedure that can guarantee the management of obstructive pathologies and stenosis of the salivary ducts with good prognosis and results, preserving the gland and avoiding the complications of surgery.

Sialoadenitis esclerosante asociada a enfermedad por IgG4: reporte de un caso / Sclerosing sialadenitis associated with IgG4 disease: case report

Las enfermedades relacionadas con IgG4 (ER-IgG4) son entidades fibroinflamatorias e inmunomediadas, caracterizadas por la afección multiorgánica, con la formación de pseudotumores que provocan lesión tisular y daño orgánico subsecuente. Se describe el caso de un paciente de 43 años que presentó sialoadenitis esclerosante y cumplió todos los criterios diagnósticos de enfermedad relacionada con IgG4.

IgG4-related diseases (IgG4-RD) are fibroinflammatory immune-mediated entities characterized by multiorgan involvement with the development of pseudotumors that cause tissue injury and subsequent organ damage. We describe the case of a 43-year-old man who presented sclerosing sialadenitis and fulfilled the diagnostic criteria for IgG4-related disease.

Sialoendoscopía en patología obstructiva de glándulas salivales / Sialendoscopy for Obstructive Salivary Gland Disease

CONTEXTO CLÍNICO: La obstrucción de las glándulassalivales(sialoadenitis obstructiva) es una patología que se caracteriza por la presencia de dolor recurrente e inflamación de la glándula afectada.1 Actualmente representa alrededor del 50% de las patologías benignas de las glándulas salivales. La etiología más frecuente es la litiasis (sialolitiasis), seguida de estenosis ductal, aunque puede observarse también asociada a enfermedades autoinmunes o como complicación de tratamiento con iodo radioactivo. La sialolitiasis consiste en la presencia de litos que producen obstrucción mecánica de la glándula, o su conducto excretor, produciendo inflamación y dolor usualmente durante la masticación. Se calcula una incidencia del 1,2% en la población general y representa el 66% de las patologías obstructivas. Es más frecuente en hombres entre los 30 y 60 años. La glándula afectada principalmente es la submaxilar (80-90%) dado que su conducto es largo, el flujo de saliva es lento y en contra de la gravedad, al mismo tiempo que la saliva en este sector es más alcalina con una mayor concentración de mucina y calcio, en comparación con las otras glándulas. 2,5 Al momento se considera que la elevada concentración de calcio en la saliva, asociada a una disminución del flujo salival, serían los principales factores etiopatogénicos en la producción de litos. Los litos suelen estar formados por carbonato de calcio y fosfato de calcio, y en menor concentración con magnesio, potasio y amonio. La estenosis ductal es la segunda causa más frecuente de sialoadenitis obstructiva observándose principalmente en el conducto de Stenon de la parótida y en mujeres.5,6 La misma puede observarse en la parotiditis juvenil recurrente, síndrome de Sjögren, así como consecuencia de infecciones o traumatismos recurrentes, o secundaria al uso de radiación (Iodo 131 o radioterapia externa). Los estudios por imágenes pueden brindar información sobre la etiología y localización en caso de ser secundaria a un lito. TECNOLOGÍA: La sialoendoscopía es un procedimiento mini invasivo que permite la directa visualización del conducto salival mediante un endoscopio de pequeño calibre que se introduce en la glándula. Em general permite al mismo tiempo el tratamiento de patologías obstructivas no tumorales. La sialoendoscopía diagnóstica se realiza habitualmente de manera ambulatoria con anestesia local y el procedimiento tiene una duración menor a los 30 minutos. Cuando se utiliza con fin terapêutico requiere anestesia local o general y tiene una duración de aproximadamente 60 minutos al realizarse por un operador experimentado.1 En caso de litos menores a los cuatro milímetros (glândula submaxilar) y tres milímetros (glándula parótida), los mismos se pueden extraer con canastillas de alambre o fórceps.9,10 En litos más grandes (hasta seis milímetros) puede ser necesaria la fragmentación previa con litotricia con láser y luego ser retirados con canastillas de alambre. Actualmente también se propone la utilización de sialoendoscopía asociado a un abordaje quirúrgico externo con el fin de evitar la sialoadenectomía.9,11 En situaciones de estenosis o cicatrices de los conductos por patologías como parotiditis juvenil recurrente, síndrome de Sjögren, etc.; la sialoendoscopía permite la irrigación de solución salina y/o corticoesteroides al mismo tiempo que realiza la dilatación mediante el uso de balón. OBJETIVO: El objetivo del presente informe es evaluar la evidencia disponible acerca del desempeño diagnóstico, la eficacia, seguridad y aspectos relacionados a las políticas de cobertura del uso de la sialoendoscopía para patología obstructiva de glándulas salivales. MÉTODOS: Se realizó una búsqueda en las principales bases de datos bibliográficas, en buscadores genéricos de internet, y financiadores de salud. Se priorizó la inclusión de revisiones sistemáticas (RS), ensayos clínicos controlados aleatorizados (ECAs), evaluaciones de tecnologías sanitarias (ETS), evaluaciones económicas, guías de práctica clínica (GPC) y políticas de cobertura de diferentes sistemas de salud. RESULTADOS: Se incluyó una RS, dos GPC, dos evaluaciones de tecnologías sanitarias, y ocho informes de políticas de cobertura para sialoendoscopía diagnóstica y/o terapéutica en patología obstructiva de glândulas salivales. No se encontraron estudios que comparen el desempeño diagnóstico de la sialoendoscopía con otros métodos de diagnóstico como ecografía y/o tomografía. CONCLUSIONES: Evidencia de baja calidad sugiere que la sialoadenectomía terapéutica para patología obstructiva glandular no neoplásica puede producir un beneficio neto considerable dada la baja incidencia de eventos adversos serios y la baja incidencia de requerimiento de sialoadenectomías ulteriores. No se encontraron estudios que comparen el desempeño diagnóstico de la sialoendoscopía respecto a otros métodos de diagnóstico, en el estudio de la patología obstructiva glandular no neoplásica. Evaluaciones de tecnologías sanitarias de Francia y España concluyen que la sialoendoscopía se debe tener en cuenta en la práctica, dada la ventaja que ofrece al permitir realizar diagnóstico y tratamiento en simultáneo, disminuyendo el requerimiento de sialoadenectomías. Un consenso de expertos de Polonia refiere que la sialoendoscopía terapéutica es el procedimiento de elección para el abordaje inicial de sialolitiasis submaxilar. No se encontraron evaluaciones económicas locales ni internacionales acerca de la costo-efectividad de la sialoendoscopía diagnostica y/o terapéutica en esta indicación.

Quality of life after sialendoscopy: prospective non-randomized study.

BACKGROUND: The symptomatic (swelling and pain) salivary gland obstructions are caused by sialolithiasis and salivary duct stenosis, negatively affecting quality of life (QOL), with almost all candidates for clinical measures and minimally invasive sialendoscopy. The impact of sialendoscopy treatment on the QOL has been little addressed nowadays. The objective is to prospectively evaluate the impact of sialendoscopy on the quality of life of patients undergoing sialendoscopy due to benign salivary obstructive diseases, measured through QOL questionnaires of xerostomia degree, the oral health impact profile and post sialendoscopy satisfaction questionnaires. RESULT: 37 sialendoscopies were included, most young female; there were 64.5% sialolithiasis and 35.4% post-radioiodine; with 4.5 times/week painful swelling symptoms and 23.5 months symptom duration. The pre- and post-sialendoscopy VAS values were: 7.42 to 1.29 (p < 0.001); 86.5% and 89.2% were subjected to sialendoscopy alone and endoscopic dilatation respectively; 80.6% reported improved symptoms after sialendoscopy in the sialolithiasis clinic (p < 0.001). The physical pain and psychological discomfort domain scores were mostly impacted where sialendoscopy provided relief and improvement (p < 0.001). We found a positive correlation between sialendoscopy and obstructive stone disease (p < 0.001) and no correlation in sialendoscopy satisfaction in xerostomia patients (p = 0.009). CONCLUSIONS: We found improved symptoms with overall good satisfaction after sialendoscopy correlated with stones; and a negative correlation between xerostomia. Our findings support the evident indication of sialendoscopy for obstructive sialolithiasis with a positive impact on QOL and probably a relative time-dependent indication for stenosis/other xerostomia causes that little improved QOL satisfaction. LEVEL OF EVIDENCE: 2b-Prospective non-randomized study. TRIAL REGISTRATION: WHO Universal Trial Number (UTN): U1111-1247-7028; Brazilian Clinical Trials Registry (ReBeC): RBR-6p8zfs.

The applicability of ultrasound in the diagnosis of inflammatory and obstructive diseases of the major salivary glands: a scoping review.

OBJECTIVES: The purpose of the present scoping review was to determine the contribution of ultrasound images in the diagnosis of inflammatory and obstructive diseases of the major salivary glands (MSGs). METHODS: A search of studies of ultrasonographic assessments of human samples was performed in several electronic databases and grey literature up to July 2021. The extracted data were the examined MSG; the diagnostic value of ultrasound (sensibility, specificity, positive- and negative predictive value, accuracy); features of lesions, including number, echogenicity, echotexture, form, margins, size, posterior acoustic aspect, and location; and related clinical information, such as swelling, palpation, sensible to pain, salivation, lymph nodes, recurrence, duration, and causes. RESULTS: After verifying the eligibility criteria, 90 articles focused on detecting inflammatory, and obstructive diseases of the MSG were gathered, with variable study designs and size samples. A wide variety of pathologies were assessed, including sialolitiasis (n = 45), acute sialadenitis (n = 30), chronic sialadenitis (n = 25), granulamatous diseases (n = 15), Kuttner's tumor (n = 11), juvenile recurrent parotitis (n = 9), abscess (n = 7), post-radiotherapy sialadenitis (n = 6), sialadenosis (n = 9), abscess (n = 7), IgG4-related disease sialadenitis (n = 5), HIV-sialadenitis (n = 4), obstructive sialadenitis (n = 3), iodinated contrast-induced sialadenitis (n = 2), and pneumoparotitis (n = 1). Most studies were case reports or series of cases. Few studies exhibited data about the accuracy of ultrasound in detecting MSG diseases. CONCLUSIONS: The present scoping review concluded that ultrasound aspects of different MSG pathologies are similar but contribute to their differential diagnosis and can be considered as a valuable initial method for assessing the MSG of adults and children.

Focal lymphocytic sialadenitis and ectopic germinal centers in oral reactive lesions and primary Sjögren's syndrome: a comparative study.

Focal lymphocytic sialadenitis (FLS), an important diagnostic criterion for Sjögren's syndrome (SS) diagnosis, can also be observed when assessing minor salivary gland (mSG) biopsies from healthy asymptomatic individuals (non-SS patients). Fifty cases of primary SS (pSS group) and 31 cases of oral reactive lesions (non-SS non-sicca group) containing also typical FLS features, were assessed by morphological and immunohistochemical (CD10, CD23 and Bcl-6) analysis, aiming at the detection of GCs. All pSS cases showed FLS with focus score (FS) ≥ 1. In the non-SS non-sicca group, 12, 10 and 9 cases showed FLS with FS ≥ 1, FLS with FS < 1 and FLS associated with chronic sclerosing sialadenitis with FS < 1, respectively. The morphological analysis revealed similar frequency of GCs in pSS (20%) and non-SS non-sicca group (19%). The area (p = 0.052) and largest diameter (p = 0.245) of GCs were higher in pSS than non-SS non-sicca group. The FS and number of foci were significantly higher in pSS than non-SS non-sicca group with FS < 1. Immunohistochemistry confirmed all morphological findings (GCs showing CD23 and Bcl-6 positivity, with variable CD10 expression) and additionally in 3 and 1 cases of the pSS and non-SS non-sicca group, respectively. Moreover, another 6 and 2 cases of the pSS and non-SS non-sicca group with FS ≥ 1, respectively, showed positivity only for CD23. FLS can also be observed when assessing oral reactive lesions, which showed similar frequency of GCs with those found in pSS patients. Further studies, including functional analysis of lymphocytic populations and GCs in FLS, are encouraged.

Acurácia diagnóstica da ultrassonografia na avaliação de doenças inflamatórias e obstrutivas das glândulas salivares maiores: uma revisão sistemática e meta-análise / Diagnostic accuracy of ultrasonography in the assessment of inflammatory and obstructive diseases of the major salivary glands - a systematic review and meta-analysis

Os distúrbios inflamatórios e obstrutivos das glândulas salivares maiores são muito comuns e podem estar inter-relacionados. A sialadenite é um termo genérico que se refere às alterações inflamatórias e pode ter causa infecciosa, de origem bacteriana ou viral, não infecciosa ou, ainda, por obstrução. A sialolitíase, uma das causas de distúrbios obstrutivos, se dá pela formação de estruturas calcificadas no interior dos parênquimas ou ductos, em decorrência da deposição de sais de cálcio ao redor de debris, notadamente na luz dos ductos. Como ferramenta para o diagnóstico dessas alterações, pode-se lançar mão da ultrassonografia, método seguro, sem efeito deletério conhecido, de custo reduzido, fácil execução e que permite a aquisição de imagens em tempo real, comboa resolução. A presente revisão sistemática e meta-análise teve como objetivo analisar estudos que realizaram avaliação comparativa da acurácia diagnóstica da ultrassonografia para o diagnóstico de sialadenites e sialolitíase, comparativamente a outros métodos de diagnóstico por imagem. Foi realizada busca nas bases de dados eletrônicas PubMed (National Library of Medicine), Web of Science (Thomson Reuters), EMBASE (Elsevier) e SCOPUS (Elsevier), que resultaram na seleção de 1.205 referências. A amostra final foi composta por 10 artigos que contemplaram os critérios de elegibilidade. Foram coletados dados sobre os autores, data de publicação, tipo de estudo, alteração ou patologia avaliada, glândula avaliada e valor diagnóstico da US (ultrassonografia), considerando sua acurácia, sensibilidade,especificidade, valor preditivo positivo, valor preditivo negativo, razão de verossimilhança positiva e razão de verossimilhança negativa. A ultrassonografia apresentou resultados satisfatórios para o diagnóstico das alterações inflamatórias e obstrutivas das glândulas salivares maiores que, comparativamente a outros exames diagnósticos por imagem, a habilitam como um método de escolha para este propósito.

Inflammatory and obstructive disorders of the major salivary glands are very common and may be interrelated. Sialadenitis is a generic term that refers to inflammatory changes in these glands and may have an infectious, bacterial or viral origin, non- infectious or even obstruction. Sialolithiasis, one of the causes of obstructive disorders, is caused by the formation of calcified structures within the parenchyma or ducts of the salivary glands, as a result of the deposition of calcium salts around debris, notably in the lumen of the ducts. As a tool for the diagnosis of these alterations, ultrasound can be used, a safe method, which does not emit ionizing radiation, has no known deleterious effect, is inexpensive, easy to perform and which allows the acquisition of images in real time, with good resolution. Given these assumptions, the present systematic review and meta- analysis aimed to analyze studies that performed a comparative evaluation of the diagnostic accuracy of ultrasound for the diagnosis of sialadenitis and sialolithiasis, compared to other diagnostic imaging methods. A search was performed in the electronicdatabases PubMed (National Library of Medicine), Web of Science (Thomson Reuters),EMBASE (Elsevier) and SCOPUS (Elsevier), which resulted in the selection of 1,205 references. After reading titles and abstracts, 205 studies remained. These, read in full, led to 10 articles that met the eligibility criteria. Data on authors, date of publication, type of study, alteration or pathology evaluated, gland evaluated and diagnostic value of US (ultrasonography), considering its accuracy, sensitivity, specificity, positive predictive value, negative predictive value, positivelikelihood ratio and of negative likelihood. Ultrasonography showed satisfactory results for the diagnosis of inflammatory and obstructive changes in the major salivary glands, which, compared to other diagnostic imaging tests, make it a method of choice for this purpose.

Potencial Afectación de las Glándulas Salivales en la Infección por SARS-CoV-2 (COVID-19) / Potential Affection of the Salivary Glands in Infection By SARS-CoV-2 (COVID-19)

La nueva enfermedad por coronavirus 2019 (COVID-19) es la última patología de preocupación internacional. Originada en Wuhan, China, se extendió rápidamente a nivel mundial, razón por la cual fue declarada una emergencia de salud pública. Producida por SARS-CoV-2 pertenece al género de los betacoronavirus junto con SARS-CoV y MERS- CoV. Se ha demostrado que SARS-CoV-2 utiliza la enzima convertidora de la angiotensina 2 (ACE2) como receptor para el ingreso en una célula huésped. Diversos estudios han demostrado la expresión de este receptor en diversos órganos y tejidos, dentro de los cuales se han reportado la cavidad oral y las glándulas salivales, los cuales han recibido vital importancia en el último tiempo dada su importancia como potencial reservorio de este virus. El objetivo de esta revisión es conocer el rol de las glándulas salivales como potencial reservorio de SARS-COV-2 y sus manifestaciones asociadas.

The new coronavirus disease 2019 (COVID-19) is the latest pathology of international concern. Originating in Wuhan, China, it spread rapidly globally, which is why it was declared a public health emergency. Produced by SARS-CoV-2 it belongs to the genus of betacoronaviruses together with SARS-CoV and MERS-CoV. SARS-CoV-2 has been shown to use angiotensin converting enzyme 2 (ACE2) as a receptor for entry into a host cell. Various studies have demonstrated the expression of this receptor in various organs and tissues, within which the oral cavity and salivary glands have been reported, which have received vital importance in recent times due to their importance as a potential reservoir for this virus. The objective of this review is to understand the role of the salivary glands as a potential reservoir for SARS-CoV-2 and its associated manifestations.

Covid-19 and oral diseases: Crosstalk, synergy or association?

The coronavirus disease 2019 (Covid-19) is a viral infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that clinically affects multiple organs of the human body. Cells in the oral cavity express viral entry receptor angiotensin-converting enzyme 2 that allows viral replication and may cause tissue inflammation and destruction. Recent studies have reported that Covid-19 patients present oral manifestations with multiple clinical aspects. In this review, we aim to summarise main signs and symptoms of Covid-19 in the oral cavity, its possible association with oral diseases, and the plausible underlying mechanisms of hyperinflammation reflecting crosstalk between Covid-19 and oral diseases. Ulcers, blisters, necrotising gingivitis, opportunistic coinfections, salivary gland alterations, white and erythematous plaques and gustatory dysfunction were the most reported clinical oral manifestations in patients with Covid-19. In general, the lesions appear concomitant with the loss of smell and taste. Multiple reports show evidences of necrotic/ulcerative gingiva, oral blisters and hypergrowth of opportunistic oral pathogens. SARS-CoV-2 exhibits tropism for endothelial cells and Covid-19-mediated endotheliitis can not only promote inflammation in oral tissues but can also facilitate virus spread. In addition, elevated levels of proinflammatory mediators in patients with Covid-19 and oral infectious disease can impair tissue homeostasis and cause delayed disease resolution. This suggests potential crosstalk of immune-mediated pathways underlying pathogenesis. Interestingly, few reports suggest recurrent herpetic lesions and higher bacterial growth in Covid-19 subjects, indicating SARS-CoV-2 and oral virus/bacteria interaction. Larger cohort studies comparing SARS-CoV-2 negative and positive subjects will reveal oral manifestation of the virus on oral health and its role in exacerbating oral infection.

Co-existence of cheilitis glandularis and actinic cheilitis-an update.

Cheilitis Glandularis (CG) is a chronic inflammatory disorder with no specific etiology that affects the minor salivary glands of the lips. The main characteristic of this condition consists of the exit of thick saliva or mucopurulent secretion through the dilated ducts present in the vermilion border of the lip, associated to varying degrees of macrocheilia. In this article we report the case of a male patient, leucoderma, 48 years old, that exhibited actinic cheilitis and glandular cheilitis. We emphasized the clinical management, diagnosis criteria and treatment, taking into consideration that GC is a rare condition and makes a differential diagnosis with other entities that may occur on lips. Although a diagnosis of CG is not difficult, its treatment is a challenge, considering the unknown etiology that hinders the development of more specific and effective treatments.

Aplicabilidade da ultrassonografia no diagnóstico de doenças inflamatórias e obstrutivas das glândulas salivares maiores: revisão de escopo / Applicability of ultrasonography in the diagnosis of inflammatory and obstructive diseases of the major salivary glands: scoping review

Alterações em glândulas salivares maiores (GSM) ocorrem em adultos ou crianças. Sialoadenites agudas ou crônicas são alterações inflamatórias que podem estar ou não associadas à infecção. Sialolitíases se caracterizam pela presença de calcificações (sialolitos) nos ductos ou parênquima glandular. Radiografia e tomografia computadorizada (TC) podem detectar sialolitos, mas possuem limitações relacionadas ao grau de mineralização ou para a caracterização de algumas alterações em tecidos moles. A ressonância magnética (RM) detecta alterações em GSM e sialolitos mineralizados ou não, porém possui alto custo e baixa disponibilidade que inviabilizam seu uso na rotina de atendimento. Ultrassonografia (US) é uma alternativa viável de exame para avaliação das GSMs, devido ao baixo custo, facilidade de aquisição de imagem em tempo real, boa resolução, e não utilização de radiação ionizante. O objetivo da presente revisão de escopo foi verificar a aplicabilidade da US na detecção de alterações em GSMs acometidas por sialoadenites ou sialolitíase. Foi realizada busca nas bases de dados eletrônicas PubMed, Web of Science, EMBASE e SCOPUS, que resultaram na seleção de 2277 referências. Após a leitura de títulos e resumos, 92 artigos contemplaram os critérios de elegibilidade desta revisão. Foram coletados dados sobre os autores, data de publicação, tipo de estudo, condição/alteração/patologia avaliada, GSM, valor diagnóstico da US, características ultrassonográficas das lesões, dados clínicos e informações adicionais. US pôde detectar alterações em GSM, com exceção do lobo profundo das parótidas. O Doppler colorido permitiu avaliar o padrão de vascularização dos tecidos alterados, auxiliando no estabelecimento de diagnósticos diferenciais. Sialolitos, únicos ou múltiplos, maiores que 2 mm foram bem detectados, inclusive tampões mucosos não mineralizados. Sialolitos menores que 1 mm foram melhor visualizados utilizando a técnica de sonopalpação e administração de ácido ascórbico ou suco de limão. Alterações glandulares causadas por sialoadenites agudas ou crônicas foram visualizadas através da US. A associação entre características ultrassonográficas e dados clínicos foi útil no estabelecimento de diagnósticos diferenciais. A ultrassonografia foi considerada como o método de escolha para avaliação inicial de alterações em GSM, tanto em adultos como crianças.

Alterations in major salivary glands (GSM) occur in adults or children. Acute or chronic sialoadenitis are inflammatory alterations associated or not with infections. Sialolithiasis is characterized by the presence of calcifications (sialoliths) in the ducts or glandular parenchyma. Radiography and computed tomography (CT) can detect sialoliths, but they have limitations related to the grade of mineralization or for the characterization of some alterations in soft tissue. Magnetic resonance imaging (MRI) detects alterations in GSM and mineralized or not mineralized sialoliths, but it has a high cost and low availability that make its use in routine care unfeasible. Ultrasonography (US) is a viable alternative exam for evaluating GSMs, due to its low cost, easy real-time image acquisition, good resolution, and no use of ionizing radiation. The objective of this scope review was to verify the applicability of US in detecting alterations in GSMs affected by sialoadenitis or sialolithiasis. A search was performed in the electronic databases PubMed, Web of Science, EMBASE and SCOPUS, which resulted in the selection of 2277 references. After reading the titles and abstracts, 92 articles met the eligibility criteria for this review. Data on authors, publication date, type of study, condition/alteration/pathology evaluated, GSM, diagnostic value of US, ultrasound characteristics of the lesions, clinical data and additional information were collected. US could detect alterations in GSM, with the exception of the deep parotid lobe. Color Doppler allowed us to assess the vascularization pattern of altered tissues, helping to establish differential diagnoses. Single or multiple sialoliths larger than 2 mm were well detected, including non-mineralized mucus plugs. Sialoliths smaller than 1 mm were better visualized using the sonopalpation technique and administration of ascorbic acid or lemon juice. Glandular alterations caused by acute or chronic sialoadenitis were visualized through US. The association between ultrasound characteristics and clinical data was useful in establishing differential diagnoses. Ultrasonography was considered the method of choice for the initial assessment of alterations in GSM, both in adults and children.

Aplicabilidade da ultrassonografia no diagnóstico de doenças inflamatórias e obstrutivas das glândulas salivares maiores: revisão de escopo / Applicability of ultrasonography in the diagnosis of inflammatory and obstructive diseases of the major salivary glands: scoping review

Alterações em glândulas salivares maiores (GSM) ocorrem em adultos ou crianças. Sialoadenites agudas ou crônicas são alterações inflamatórias que podem estar ou não associadas à infecção. Sialolitíases se caracterizam pela presença de calcificações (sialolitos) nos ductos ou parênquima glandular. Radiografia e tomografia computadorizada (TC) podem detectar sialolitos, mas possuem limitações relacionadas ao grau de mineralização ou para a caracterização de algumas alterações em tecidos moles. A ressonância magnética (RM) detecta alterações em GSM e sialolitos mineralizados ou não, porém possui alto custo e baixa disponibilidade que inviabilizam seu uso na rotina de atendimento. Ultrassonografia (US) é uma alternativa viável de exame para avaliação das GSMs, devido ao baixo custo, facilidade de aquisição de imagem em tempo real, boa resolução, e não utilização de radiação ionizante. O objetivo da presente revisão de escopo foi verificar a aplicabilidade da US na detecção de alterações em GSMs acometidas por sialoadenites ou sialolitíase. Foi realizada busca nas bases de dados eletrônicas PubMed, Web of Science, EMBASE e SCOPUS, que resultaram na seleção de 2277 referências. Após a leitura de títulos e resumos, 92 artigos contemplaram os critérios de elegibilidade desta revisão. Foram coletados dados sobre os autores, data de publicação, tipo de estudo, condição/alteração/patologia avaliada, GSM, valor diagnóstico da US, características ultrassonográficas das lesões, dados clínicos e informações adicionais. US pôde detectar alterações em GSM, com exceção do lobo profundo das parótidas. O Doppler colorido permitiu avaliar o padrão de vascularização dos tecidos alterados, auxiliando no estabelecimento de diagnósticos diferenciais. Sialolitos, únicos ou múltiplos, maiores que 2 mm foram bem detectados, inclusive tampões mucosos não mineralizados. Sialolitos menores que 1 mm foram melhor visualizados utilizando a técnica de sonopalpação e administração de ácido ascórbico ou suco de limão. Alterações glandulares causadas por sialoadenites agudas ou crônicas foram visualizadas através da US. A associação entre características ultrassonográficas e dados clínicos foi útil no estabelecimento de diagnósticos diferenciais. A ultrassonografia foi considerada como o método de escolha para avaliação inicial de alterações em GSM, tanto em adultos como crianças.

Alterations in major salivary glands (GSM) occur in adults or children. Acute or chronic sialoadenitis are inflammatory alterations associated or not with infections. Sialolithiasis is characterized by the presence of calcifications (sialoliths) in the ducts or glandular parenchyma. Radiography and computed tomography (CT) can detect sialoliths, but they have limitations related to the grade of mineralization or for the characterization of some alterations in soft tissue. Magnetic resonance imaging (MRI) detects alterations in GSM and mineralized or not mineralized sialoliths, but it has a high cost and low availability that make its use in routine care unfeasible. Ultrasonography (US) is a viable alternative exam for evaluating GSMs, due to its low cost, easy real-time image acquisition, good resolution, and no use of ionizing radiation. The objective of this scope review was to verify the applicability of US in detecting alterations in GSMs affected by sialoadenitis or sialolithiasis. A search was performed in the electronic databases PubMed, Web of Science, EMBASE and SCOPUS, which resulted in the selection of 2277 references. After reading the titles and abstracts, 92 articles met the eligibility criteria for this review. Data on authors, publication date, type of study, condition/alteration/pathology evaluated, GSM, diagnostic value of US, ultrasound characteristics of the lesions, clinical data and additional information were collected. US could detect alterations in GSM, with the exception of the deep parotid lobe. Color Doppler allowed us to assess the vascularization pattern of altered tissues, helping to establish differential diagnoses. Single or multiple sialoliths larger than 2 mm were well detected, including non- mineralized mucus plugs. Sialoliths smaller than 1 mm were better visualized using the sonopalpation technique and administration of ascorbic acid or lemon juice. Glandular alterations caused by acute or chronic sialoadenitis were visualized through US. The association between ultrasound characteristics and clinical data was useful in establishing differential diagnoses. Ultrasonography was considered the method of choice for the initial assessment of alterations in GSM, both in adults and children.

Concordancia diagnóstica del sistema de graduación Chisholm Mason y Focus Score en la sialoadenitis linfocítica focal como aproximación al síndrome de Sjögren / Diagnostic agreement of the Chisholm Mason and Focus Score grading system in focal lymphocytic sialadenitis in patients with dry symptoms

RESUMEN Introducción: Existen diferentes sistemas de graduación para interpretar la biopsia de glándula salival menor (BGSM) en pacientes con síntomas secos. En la actualidad la metodología recomendada (Focus Score [FS]), aunque no se emplea de forma rutinaria, conlleva discrepancias diagnósticas. Objetivo: Determinar la concordancia de la lectura histopatológica de BGSM entre las técnicas FS y Chisholm Mason (CM) para el diagnóstico de sialoadenitis linfocítica focal en el hospital de San José, entre enero de 2017 y junio de 2018. Métodos: Estudio de concordancia. Se incluyeron BGSM de pacientes con síntomas secos. Se excluyó material no apto para el estudio, o con menos de 4 lóbulos o menos de 8 mm de área. Se clasificaron utilizando las técnicas FS y CM por 2 evaluadores independientes. Se evaluó el acuerdo interobservador, intraobsevador y global entre las pruebas mediante el coeficiente de Kappa de Cohen. Resultados: Se evaluaron 130 biopsias. Los valores K intraobservador entre FS y CM fueron 0,42 para el observador 1 y 0,23 para el observador 2. Los valores K del acuerdo interobservador fueron 0,47 para FS y 0,65 para CM. La concordancia entre los 2 sistemas de puntuación fue K de 0,13. Conclusiones: Se evidencia una probable sobreestimación de focos con CM, que resalta sus debilidades, y mayor precisión con FS. Por ende, la concordancia entre las 2 pruebas es débil. Es necesario un mayor esfuerzo para el uso del método estandarizado de lectura de BGSM con el FS para una correcta interpretación y beneficio en la clasificación de pacientes con síndrome seco.

ABSTRACT Introduction: There are different grading systems for interpreting the minor salivary gland biopsy (MSGB) in patients with dry symptoms (Sicca). The recommended methodology is currently the Focus Score (FS), which, although not performed routinely, results in diagnostic discrepancies. Objective: To determine the concordance of the histopathological reading of MSGB between the FS and Chisholm Mason (CM) techniques for diagnosis of focal lymphocytic sialadenitis at the San José Hospital between January 2017 and June 2018. Methods: Concordance study. MSGB of patients with sicca symptoms were included. Material not suitable for study and / or with less than 4 lobules and / or less than 8 mm of surface area was excluded. They were classified, using the FS and CM techniques, by two independent evaluators. The inter-observer, intra-observer, and overall agreement between the tests were evaluated using Cohen's Kappa coefficient. Results: A total of 130 biopsies were evaluated. The intra-observer K values between FS and CM were 0.42 for observer 1, and 0.23 for observer 2. The K values of the inter-observer agreement were 0.47 for FS, and 0.65 for CM. The concordance between the two scoring systems was K = 0.13. Conclusions: There is evidence of a probable over-estimation of foci with CM, highlighting its weaknesses and greater precision with FS technique, resulting in the weak concordance between the two tests. A greater effort is necessary for the use of the standardised MSGB FS reading method for a correct interpretation and benefit in the classification of patients with dry syndrome.