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Background: Currently, the potential of FT-IR spectroscopy for rapid diagnosis of many pathologies has been demonstrated by numerous research studies including those targeting COVID-19 detection. However, the number of clinicians aware of this potential and who are willing to use spectroscopy in their clinics and hospitals is still negligible. In addition, lack of awareness creates a huge gap between clinicians and researchers involved in clinical translation of current FT-IR technology hence hindering initiatives to bring basic and applied research together for the direct benefit of patients., Methods: Knowledge and medical training on FT-IR on the side of clinicians should be one of the first steps to be able to integrate it into the list of complementary exams which may be requested by health professionals. Countless FT-IR applications could have a life-changing impact on patients' lives, especially screening and diagnostic tests involving biofluids such as blood, saliva and urine which are routinely non-invasively or minimally-invasively., Results: Blood may be the most difficult to obtain by the invasive method of collection, but much can be evaluated in its components, and areas such as hematology, infectiology, oncology and endocrinology can be directly benefited. Urine with a relatively simple collection method can provide pertinent information from the entire urinary system, including the actual condition of the kidneys. Saliva collection can be simpler for the patient and can provide information on diseases affecting the mouth and digestive system and can be used to diagnose diseases such as oral cancer in its early-stages. An unavoidable second step is the active involvement of industries to design robust and portable instruments for specific purposes, as the medical community requires user-friendly instruments of advanced computational algorithms. A third step resides in the legal situation involving the global use of the technique as a new diagnostic modality., Conclusions: It is important to note that decentralized funds for variety of technologies hinders the training of clinical and medical professionals for the use of newly arising technologies and affect the engagement of these professionals with technology developers. As a result of decentralized funding, research efforts are spread out over a range of technologies which take a long time to get validated and translated to the clinic. Partnership over similar groups of technologies and efforts to test the same technologies while overcoming barriers posed to technology validation in different areas around the globe may benefit the clinical/medical, research and industry community globally., Competing Interests: Declaration of Competing Interest There are no conflicts to declare., (Copyright © 2023. Published by Elsevier B.V.)

A proper antibody panel selection is one of the most important factors to reach an adequate diagnosis in challenging cases. This retrospective study was designed to determine the contribution of immunohistochemistry (IHC) in the primary diagnosis of oral diseases in one of the main services of oral pathology in the State of São Paulo, Brazil, and to identify the most common antibodies used, and recommend diagnostic algorithms based on our experience with challenging lesions. A total of 1698 IHC stains were performed in 401 cases from a total of 28,804 cases received from public dental clinics and private dental practitioners within a period of 13 years, representing a frequency of 1.4% of IHC solicitations. Among these, 112 (28%) were mandatory to reach a final diagnosis and 255 (63.6%) were confirmative. In 34 (8.4%) cases, it was not possible to reach a conclusive/final diagnosis, even with IHC. Regarding the nature of the lesions, 210 (52.3%) were benign, 163 (40.6%) were malignant tumors, 13 (3.2%) were reactive, 10 (2.5%) were premalignant, and 5 (1.2%) were lesions of uncertain malignancy. Small amount of tissue of some incisional biopsies, overlapping features of spindle cell lesions (epithelial, neural, melanocytic, smooth muscle, endothelial, and fibroblastic/myofibroblastic cell differentiation), and overlapping features of salivary gland lesions were the most frequent challenges in which IHC stains were requested. Spindle cell lesions were the most frequent (22%) among all cases that required IHC to reach a final diagnosis. The implementation of IHC for routine practice requires a wide range of markers, proper antibody selection, and knowledge to interpret the subjectivity of staining. The inherent limitation of incisional biopsies was pointed as a reason to inconclusive diagnosis, despite a wide range of antibodies that our laboratory displays., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Drug-induced sarcoidosis-like reaction (DISR) is a condition almost indistinguishable from sarcoidosis, both clinically and microscopically, consisting of granulomatous tissue reaction associated with a specific therapy. Commonly affected sites are the lungs, hilar lymph nodes, and skin. This report aimed to describe a very uncommon case of DISR with an unique involvement of the oral cavity. A 63-year-old female with a history of rheumatoid arthritis, who was treated with a TNF-α antagonist (adalimumab), presented multiple ulcerative nodules on the hard palate. Laboratory tests and imaging studies failed to show any other alterations. The biopsy specimen demonstrated multiple noncaseating granulomas. Histochemical reactions were negative for acid-fast bacilli and fungi, and immunohistochemical assessment highlighted the presence of normal lymphocytes and histiocytes. With the diagnosis of DISR, adalimumab was discontinued, and complete clinical resolution of the lesions was achieved after 14 months. Although uncommon, DISR should be considered in differential diagnoses of oral granulomatous reactions, especially in cases where the patient is being treated with TNF-α antagonists., (© 2021. International League of Associations for Rheumatology (ILAR).)

Objective: In the present study, we aimed to investigate the prognostic value of RUNX1 expression in 76 patients with adenoid cystic carcinoma (ACC)., Materials and Methods: All cases were arranged in tissue microarray blocks and submitted to immunohistochemistry against RUNX1. These results were statistically correlated with clinicopathologic features, including age, gender, tumour site, tumour size, lymph node status, AJCC clinical stage, distant metastasis, treatment, recurrences, follow-up, histologic pattern, vascular and neural invasion, all of which obtained from patient's medical records., Results: RUNX1 was expressed in the nuclei of tumour cells, with a mean of 18.1% of positivity. Nuclear RUNX1 expression was significantly associated with AJCC clinical stage (p < .0001), solid histologic pattern (p < .0001), vascular invasion (p < .0001) and presence of local recurrence (p < .0001). Using univariate and multivariate analyses, RUNX1 nuclear expression was significantly associated with a lower disease-free survival (p < .0001 and p = .028, respectively) and disease-specific survival (p < .0001 and p = .018, respectively) rates., Conclusion: In summary, RUNX1 nuclear expression may represent an indicator of unfavourable outcome for patients affected by head and neck ACC., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. All rights reserved.)

Background: Oral focal mucinosis (OFM) is a rare benign condition of unknown etiology, considered the oral counterpart of cutaneous focal mucinosis. We report the clinicopathologic features of 21 cases of OFM in conjunction with a review of the literature., Methods: Clinical data were collected from the records of five oral and maxillofacial pathology services. All cases were evaluated by hematoxylin and eosin staining, histochemistry, and immunohistochemistry (vimentin, S-100, α-SMA, CD34, and mast cell)., Results: The series comprised 14 females (66.7%) and seven males (33.3%), with a mean age of 48.2 ± 20.7 years (range: 8-77 years) and a 2:1 female-to-male ratio. Most of the lesions affected the gingiva (n = 6, 28.6%) and presented clinically as asymptomatic sessile or pedunculated nodules with fibrous or hyperplasic appearance. All cases were negative for S-100 protein, CD34, and α-SMA and positive for Alcian blue staining. Conservative surgical excision was the treatment in all cases, and there was only one recurrence., Conclusion: OFM is a rare benign disorder that is often clinically misdiagnosed as reactive lesions or benign proliferative processes. Dermatologists and pathologists should consider OFM in the differential diagnosis of soft tissue lesions in the oral cavity, mainly located in the gingiva., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Aims: The hallmarks of type 2 diabetes (T2D) are hyperglycaemia and insulin resistance. These factors, at the cellular level, are associated with mitochondrial dysfunction and increased glucose uptake. Such events are poorly explored in the context of the salivary glands. In this study, we present a series of eight cases of a distinct salivary gland lesion characterised by multiple oncocytic cysts, and we provide new pathological insights regarding its pathogenesis., Methods and Results: Seven patients (87.5%) had confirmed T2D, and obesity was identified in five (62.5%) patients. Clinically, the patients showed bilateral parotid gland swelling with recurrent episodes of pain and enlargement. Imaging examination revealed multiple cystic lesions in both parotid glands. Microscopically, the parotid glands showed multiple cysts of different sizes, lined by oncocytic epithelial cells. Intraluminally, strongly eosinophilic glass-like crystalloid material was observed. Immunohistochemical studies were performed, and the most notable finding was glucose transporter 1 (GLUT1) overexpression in the oncocytic cysts which is not observed in any other oncocytic lesion of patients without T2D. In addition, high expressions of mitochondrial antigen, fission 1 protein and mitofusin-2 were observed in the oncocytic epithelium of the cysts. Furthermore, most of the oncocytic cysts showed a pattern of cytokeratin expression consistent with striated ducts., Conclusions: These results strongly suggest that T2D is associated with alterations in GLUT1 expression in the cells of striated ducts with mitochondrial dysfunction, causing a hyperplastic process characterised by multiple oncocytic cysts. For this lesion, the designation of 'diabetes-associated-bilateral multiple oncocytic cysts of the parotid gland' is proposed., (© 2019 John Wiley & Sons Ltd.)

Smooth muscle tumors associated with Epstein-Barr virus infections (EBV-SMT) of laryngeal origin are exceedingly rare and have been reported in few adult patients, but not in children. This reported case describes a lesion found in the larynx of an 8-year-old Guatemalan undernourished girl. Microscopically, the lesion showed a highly cellular mesenchymal spindle cell tumor, containing frequent lymphocytes. The immunohistochemical analysis revealed positivity for α-smooth muscle actin and h-caldesmon. In addition, most of the tumor cells were positive for EBV by in situ hybridization. To the best of the author's knowledge, this is the first literature-reported case of laryngeal EBV-SMT occurring in an undernourished child.

Mammaglobin is expressed in breast and salivary gland secretory carcinomas; however, its expression in salivary duct carcinomas (SDCs) still not well established. Therefore, the aim of this study was to investigate the presence and distribution of mammaglobin immunoexpression in SDC ex-PA in different phases of the adenoma to carcinoma sequence evaluating its possible involvement in carcinogenesis and tumor progression, as well as to determine its expression in SDC de novo. Mammaglobin immunohistochemistry was performed in 84 SG tumors, including 41 pleomorphic adenomas (PA) without malignant transformation, 13 intracapsular SDC ex-PA, 5 frankly invasive SDC ex-PA, 25 SDC de novo and 10 secretory carcinomas. The reactions were qualitatively analyzed and digitally scored. Positive immunostaining for mammaglobin was observed in 37 out of 84 SG tumors evaluated (44.1%), but strong staining was consistently seen only in secretory carcinomas, SDC de novo and frankly invasive SDC ex-PA, while it was weaker in intracapsular SDC ex-PA and PA. In PA, mammaglobin expression was significantly associated with recurrence. This study has confirmed that the mammaglobin is commonly expressed in SDC de novo and secretory carcinomas. Its expression was higher in SDC ex-PA than in PA, suggesting that mammaglobin may play a role in its malignant transformation., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Head and neck mucosal melanomas (MMs) are rare tumors with adverse outcomes and poorer prognoses than their more common cutaneous counterparts (cutaneous melanomas-CMs). Few studies have compared the expression of mitochondrial dynamic markers in these tumors. This study aimed to assess the correlations of mitochondrial markers with melanoma progression and their potential as predictors of lymph node involvement and distant metastasis., Methods: Immunohistochemistry against anti-mitochondrial (AMT), dynamin-related protein 1 (DRP1), mitochondrial fission protein 1 (FIS1), mitofusin-1 (MFN1), and mitofusin-2 (MFN2) antibodies was performed in 112 cases of head and neck CM and MM. A Cox regression multivariate model was used to assess the correlation of AMT, FIS1, and MFN2 expressions considering the risk for nodal and distant metastasis., Results: All markers studied presented higher staining in tumor cells than normal adjacent tissues. Higher mitochondrial content was observed in MM than in CM, and it was significantly associated with nodal metastasis in oral melanomas. Both FIS1 and DRP1 expressions were related to advanced Clark's levels in CM, and they were overexpressed in oral melanomas. Moreover, increased immunoexpression of MFN2 was significantly associated with a higher risk of metastasis in CM, and it was also overexpressed in sinonasal melanomas., Conclusions: Our results suggest that mitochondrial fission and fusion processes can play an important role during multiple stages of tumorigenesis and the development of nodal and distant metastasis in cutaneous and mucosal melanomas., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Extracorporeal shock wave therapy (ESWT) has been extensively studied for its multiple biological properties, and although it is widely applied in esthetical procedures, little is known about its effects on the epidermis and dermis. In this study, a histological and immunohistochemical study of the effects of ESWT was performed on rat skin. Forty-five female rats were treated with one or two sessions of ESWT and sacrificed on days 1, 7, 14, and 21 after treatment. The samples were histologically processed and then morphometric analyses were performed to assess the epidermis, dermis, and subcutaneous fat tissue thickness. Immunohistochemical reactions were also performed against the antibodies: basic fibroblastic growth factor (FGF2), its receptor (FGFR1), and α-smooth muscle actin. Slides were scanned and digitally assessed, to determine the microvessel density (MVD) and digital scoring of the immunohistochemical staining. The results showed that ESWT produced a significantly higher collagen content, MVD, and epidermis and dermis thickness than the control, non-treated group. Both in epidermis and dermis, FGF2 was overexpressed in the ESWT-treated groups, whereas FGFR1 was increased only in the group treated with two ESWT sessions at 21-days post-treatment. The ESWT-treated groups have also shown diminished thickness of subcutaneous fat tissue. In conclusion, ESWT induces neocollagenesis and neoangiogenesis, and upregulates the FGF2 expression, particularly in the groups treated with two sessions. Furthermore, it was demonstrated that overexpression of FGF2 on skins treated with ESWT seems to be a key role on its mechanism of action.

Dentinogenic ghost cell tumor (DGCT), a rare, benign odontogenic tumor with aggressive behavior, causes bone destruction and cortical expansion. We report here a case of DGCT in a 38-year-old male, presenting with enormous extraoral protrusion, which radiographically was predominantly radiolucent with radiopaque areas. Microscopically, it was observed to be a solid ameloblastomatous proliferation with pseudoglandular structures associated with clusters of ghost cells. Abundant dentinoid material adjacent to the epithelial sheets containing entrapped epithelial tumor cells was also evident. Immunohistochemistry revealed positivity for pan-cytokeratin (CK), CK-14, CK-7, and CK-19; CD138; and β-catenin. The Ki-67 proliferative index was very low (<1%). The clinical, histopathologic, and immunohistochemical features led to the diagnosis of DGCT. The patient underwent partial mandibulectomy, and no recurrences have occurred. To our knowledge, this is the largest DGCT described in the English language literature., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Fibroblast growth factor 2 (FGF2) and FGF receptor 1 (FGFR1) have been investigated in different human neoplasms and were shown to play important roles in the pathogenesis of these diseases; however, very few are known regarding their prognostic importance in the context of ameloblastoma. Therefore, the aim of this study was to investigate whether the expression of FGF2 and FGFR1 is associated with ameloblastoma clinical behavior., Methods: Fifty-eight cases of ameloblastoma arranged in tissue microarray were submitted to immunohistochemistry against FGF2 and FGFR1. Clinicopathological parameters regarding sex, age, tumor size, duration and location, treatment, recurrences, radiographic features, cortical disruptions, and follow-up data were obtained from patients' medical records and correlated with the molecules expression. Univariate and multivariate Cox regression analyses were used to investigate the prognostic potential of the biomarkers., Results: Forty-four cases (75.9%) exhibited cytoplasmic positivity for FGF2 in central and peripheral epithelial cells, 46 of 58 (79.3%) showed FGFR1 cytoplasmic positivity predominantly in the columnar peripheral cells, and 43 cases (74.1%) were positive for both. Expression of FGF2 and FGF2 + FGFR1 was associated with tumor recurrences (P = .05). However, univariate and multivariate analyses did not demonstrate a significant influence of FGF2, FGFR1, or FGF2 + FGFR1 in the 5-year disease-free survival (DFS) rate (P = .27, P = .33, and P = .25, respectively)., Conclusion: Cytoplasmic expression of FGF2 and FGF2 + FGFR1 is associated with ameloblastoma recurrence, but FGF2 and FGFR1 are not determinants of a lower DFS., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)