Mateus José Dutra

Background/Objectives: Bullous pemphigoid (BP) in children is a rare autoimmune subepidermal blistering condition that shows significant clinical variability depending on age. This narrative review summarizes the available literature on the epidemiology, etiology, clinical manifestations, diagnosis, management, outcomes, and future perspectives of pediatric BP. Methods: A search of the PubMed/MEDLINE and Scopus databases from their inception to July 2026 was conducted for English-language articles on BP in patients younger than 18 years old. After record screening and full-text assessment, 55 publications were selected and narratively synthesized. Results: Infants with BP frequently present with acral and palmoplantar blistering, whereas older children and adolescents show more heterogeneous clinical manifestations. BP180 is the principal autoantigen, although antigenic heterogeneity has been reported. Diagnosis requires integration of clinical, histopathological, and immunopathological findings. Linear IgG and/or C3 deposition along the basement membrane zone on direct immunofluorescence (DIF) is an important but non-specific finding. Salt-split skin testing and antigen-specific serology may assist in distinguishing BP from other autoimmune subepidermal blistering diseases. Corticosteroids are the most frequently reported initial treatment, while dapsone and other steroid-sparing agents have been used in selected patients. Intravenous immunoglobulin (IVIG), immunosuppressants, and targeted therapies have primarily been reported in refractory cases, with evidence derived predominantly from case reports and small series. Conclusions: The prognosis reported in the pediatric literature is generally favorable, although there are some reports of resistant or recurrent cases. However, relapse rates in the long-term are not known. There is a need for multicenter prospective trials and standardization of outcomes.

Objective: To map the available evidence on direct oral healthcare costs associated with xerostomia and hyposalivation. Methods: A scoping review was conducted following PRISMA‐ScR guidelines. Searches were performed in PubMed, Scopus, Embase, and Web of Science, with additional screening of gray literature. Studies reporting direct oral healthcare costs associated with xerostomia or/and hyposalivation were eligible. Reported costs were standardized to a common currency and price year. Exploratory annual cost scenarios were generated by combining reported unit costs with reported guideline‐based or hypothetical frequencies. Results: Eight studies met the inclusion criteria. Six (75%) were conducted in the United States and two (25%) in the United Kingdom. Reported cost components included dental consultations, salivary stimulants and substitutes, restorative treatments, dental implants, fluoride applications, and management of oral infections. Evidence was heterogeneous in populations, etiologies, healthcare settings, cost components, and reporting methods. Illustrative base‐case scenarios ranged from USD 3296.08 to USD 10,414.51 per patient per year (USD 1791.23–5658.99 when hypothetical events and possible overlaps were excluded). Conclusion: The evidence base is limited and heterogeneous. The exploratory annual synthesis provides an initial framework for mapping reported cost components but does not represent a definitive estimate of economic burden.

Objective: Clinical signs observed during head and neck examination offer important diagnostic clues. This scoping review aimed to identify key clinical signs in this region associated with diseases and syndromes and to map them according to their location. Methods: An electronic literature search was performed in five databases (Embase, LILACS, PubMed, Scopus, and Web of Science) and in grey literature (Google Scholar and ProQuest). Studies were excluded if they did not involve humans, addressed non‐specific or non–head and neck signs, used auxiliary equipment during examination, were conducted outside clinical settings, lacked original data, or had no accessible full text. Clinical signs were categorized as ocular, cutaneous, intraoral, auricular, or other. Results: Overall, 54 studies met the criteria, identifying 43 distinct clinical signs. Intraoral signs were the most frequent ( n = 15), with “strawberry tongue” being the most common. Cutaneous signs (10) included café‐au‐lait lesions, facial trichilemmomas, and Pemberton's sign. Ocular manifestations appeared in nine cases, with Horner's syndrome being the most reported. Other signs accounted for six reports, and auricular signs (three) were the least frequent, with Frank's sign most cited. Conclusion: This review underscores the diagnostic relevance of head and neck clinical signs as indicators of systemic diseases, including intraoral ulcers, café‐au‐lait macules, Kayser‐Fleischer rings, Frank's sign, malar rash, and port‐wine stains.

This study aimed to characterize the tumor microenvironment (TME) in patient-derived xenograft (PDX) models of oral squamous cell carcinoma (OSCC) and compare histological findings with primary tumors of origin (PTT). OSCC samples from five donor patients were implanted into NOD/SCID mice (PDX0) and subsequently re-implanted into new animals (PDX1), yielding three groups for analysis: PTT, PDX0, and PDX1 ( n = 5 each). Histological slides with sections were stained with hematoxylin and eosin for grade analysis and subjected to immunohistochemical reactions with antibodies against SMA, CD4, CD8, CD31, CD34, Claudin-1, Vimentin, and Ki-67. Multiple comparisons were performed between samples (PTT, PDX0, and PDX1). The histological grade of PDX0 and PDX1 tumors showed instability across passages. The expression of SMA, claudin-1, vimentin, and Ki-67 was maintained, with no significant differences between PDX0 and PDX1 when compared with PTT. In contrast, the expression of CD4, CD8, CD31, and CD34 was significantly reduced in PDX0 and PDX1 tumors compared with PTT. OSCC PDX tumors may exhibit instability in the degree of differentiation compared with the donor tumors across passages, as well as alterations in certain components of the TME, including cancer-associated fibroblasts, epithelial–mesenchymal transition–related features, and cellular proliferation characteristics.

Objectives: Tobacco has been associated with the development of oral leukoplakia (OL) and oral squamous cell carcinoma (OSCC). This study aimed to evaluate the in vitro and in vivo changes caused by carcinogen 4-nitroquinoline 1-oxide (4NQO), simulating smoking conditions. Materials and Methods: In the in vitro study, normal keratinocytes were exposed to 1.3 µM and 2.6 µM concentrations of 4NQO to induce dysplastic transformation (H-DISP) and malignant transformation (H-SCC), respectively. The cells were collected and subjected to hematoxylin and eosin (H&E) staining and immunocytochemistry with Ki-67. For the in vivo study, female C57BL/6J mice were divided into a pure control (PC) group and experimental groups exposed to 50 µg/mL (NQ) and 100 µg/mL (CM) of 4NQO in autoclaved drinking water. Each group was euthanized after 8, 12, 16, and 20 weeks of exposure. The tongues were collected, processed, stained with H&E, and analyzed using conventional light microscopy. Results: In vitro, significant morphological changes were observed in the H-DISP and H-SCC groups, with a cell proliferation index exceeding 30% in the H-DISP group. In vivo, the CM group showed greater progression to severe dysplasia/carcinoma within a shorter treatment period compared to the NQ group. Conclusions: We established critical doses and exposure durations for 4NQO, both in vitro and in vivo, to induce cellular changes and the formation of OL and OSCC, providing a standardized model for studies related to oral carcinogenesis.

There has been a significant increase in cases of oral squamous cell carcinoma (OSCC) in young adults, unrelated to smoking, alcohol consumption, or high-risk human papilloma virus (HPV). This article presents the case of a 39-year-old woman who denied habits such as smoking and alcohol consumption. She presented with a red plaque with ulcerated areas, located on the left border of the tongue, measuring 3 cm at its largest diameter, with an 8-year evolution characterized by periods of exacerbation and remission, accompanied by a burning sensation in the area. Under the hypothesis of oral erythroplakia (OE), an incisional biopsy was performed, and histopathological analysis revealed severe epithelial dysplasia, disruption of the basement membrane, and discrete epithelial islands on the surface of the adjacent connective tissue, which tested positive for pancytokeratin in immunohistochemical analysis. The diagnosis was microinvasive OSCC, and the patient underwent surgical treatment, with the diagnosis confirmed in the surgical specimen, and is currently disease-free. The importance of early diagnosis and histopathological examination in OE is highlighted to prevent progression to OSCC, an entity increasingly present in young adults without associated risk factors. We reiterate that further studies, including genetic studies, may clarify and explain cases of OSCC and potentially malignant lesions in young adults, such as the one reported here.

Objective: Integrate studies on germline variations (GV) in patients with oral squamous cell carcinoma (OSCC), aiming to assess the highest frequencies of which genes were altered in patients with this diagnosis. Methods: An electronic search was conducted in four databases and in the gray literature, following the PRISMA 2020 recommendations. Case reports, case series, case–control studies, cross‐sectional studies, prospective cohort studies, and retrospective cohort studies reporting GV in patients with OSCC were included for data extraction. Results: Twenty articles were included, covering 146 cases of OSCC. Patients had a mean age of 47.5 years; the majority were male, non‐drinkers, and non‐smokers. For most cases, p16 staining and human papilloma virus (HPV) status were not investigated/reported. A total of 231 different GV genes were identified in the 146 patients, with the most frequently altered being ND5 (6.1%), CYTB (4.8%), COX1 (4.6%), PDE4DIP (4.1%), ND1 (3.9%), ND4 (3.2%), ND2 (2.7%), ATP6 (2.7%), CDKN2A (2.6%), COX2 (2.4%), COX3 (2.2%), and ND3 and ND6 , both accounting for 2% each. Conclusion: This review compiles important data on the most frequent GV in patients with OSCC, enabling new understandings of oral carcinogenesis, as well as future directions for prognosis and treatment.

Resumen Presentamos el caso de un hombre de 45 años con úlcera en paladar de 10 días de evolución. El paciente era consumidor de alcohol y tenía antecedentes de consumo de cocaína desde hacía 17 años, discontinuada durante los últimos 7 años. Se realizó biopsia incisional y los cortes histológicos revelaron una extensa área ulcerada recubierta por una membrana fibrinopurulenta, con pequeños nidos de células escamosas que presentaban citoplasma eosinófilo, nucleolos evidentes y en ocasiones múltiples, leve atipia celular y varias figuras mitóticas. Las características clínicas e histológicas indicaron el diagnostico de Sialometaplasia Necrotizante y el paciente fue sometido a seguimiento clínico. En la tercera semana de seguimiento se hizo evidente la remisión de la lesión. Destacamos la importancia del examen histopatológico e inmunohistoquímico en el correcto diagnóstico.