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Chlorhexidine (CHX) is a prime choice to control the oral microbiota. However, it's a chemical agent leading to side effects such as teeth strains, taste disturbance, and desquamation of oral mucosa. Alternatively, the lactoferrin and oxygen-based Blue®M has been introduced as an alternative to the CHX, not disturbing tissue repair. Therefore, the study aimed to evaluate the effects of Blue®M and CHX on oral human fibroblasts (HGF-1) and keratinocytes (NOK-SI). Cell cultures using HGF-1 and NOK-SI evaluated cell proliferation, cell cycle, apoptosis and necrosis, and migration. In the dose-effect test, Blue®M reduced the HGF-1 sample in a 4-fold concentration than CHX (CHX: 173.07 ±10.27; Blue®M: 43.86 ±3.04). The proliferation test revealed an eightfold reduction of the sample for CHX, while for Blue®M, the proliferation rate was eighteen times lower. The apoptosis and necrosis rates increased by 25% (p<0.0001) for HGF-1 for both substances. In NOK-SI, the apoptosis rates increased by 10% (p=0.02) and 15% (p=0.001) for CHX and Blue®M, respectively. Furthermore, the fibroblast had a lower capacity for wound closure in the Scratch Assay (monolayer cell migration) for Blue®M. Despite the limitations of this in vitro study, the results of the lactoferrin and oxygen-based Blue®M demonstrated cytotoxicity in doses over the Minimum inhibitory concentration and Minimum bactericidal concentration for Oral fibroblasts (HGF- 1) and Keratinocytes (NOK-SI).
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Oral potentially malignant disorders (OPMD) are clinical presentations that carry an increased risk of cancer development. Currently, epithelial dysplasia grade is based on architectural and cytological epithelial changes and is used to predict the malignant transformation of these lesions. However, predicting which OPMD will progress to a malignant tumor is very challenging. Inflammatory infiltrates can favor cancer development, and recent studies suggest that this association with OPMD lesions may be related to the etiology and/or aggressive clinical behavior of these lesions. Epigenetic changes such as histone modifications may mediate chronic inflammation and also favor tumor cells in immune resistance and evasion. This study aimed to evaluate the relationship between histone acetylation (H3K9ac) and DNA damage in the context of dysplastic lesions with prominent chronic inflammation. Immunofluorescence of "low-risk" and "high-risk" OPMD lesions (n = 24) and inflammatory fibrous hyperplasia (n = 10) as the control group was performed to assess histone acetylation levels and DNA damage through the phosphorylation of H2AX (γH2AX). Cell co-culture assays with PBMCs and oral keratinocyte cell lines (NOK-SI, DOK, and SCC-25) were performed to assess proliferation, adhesion, migration, and epithelial-mesenchymal transition (EMT). Oral dysplastic lesions showed a hypoacetylation of H3K9 and low levels of γH2AX compared to control. The contact of dysplastic oral keratinocytes with PBMCs favored EMT and the loss of cell-cell adhesion. On the other hand, p27 levels increased and cyclin E decreased in DOK, indicating cell cycle arrest. We conclude that the presence of chronic inflammation associated to dysplastic lesions is capable of promoting epigenetic alterations, which in turn can favor the process of malignant transformation.
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Lipomas are mesenchymal neoplasms relatively uncommon in the oral cavity. Lipomas can exhibit histopathological features mimicking atypical lipomatous tumors (ALT) or dysplastic lipoma (DL) in the presence of degenerative changes. Relevantly, immunohistochemistry assists in the correct diagnosis. Herein, we present the case of a 54-year-old male with a sessile nodule located on the dorsum of the tongue. The histopathological analysis showed a diffuse, non-circumscribed adipocytic proliferation constituted by cells of variable size containing cytoplasmic vacuoles and displaced nuclei, some resembling lipoblasts supported by fibrous connective tissue stroma. By immunohistochemistry, tumor cells were positive for vimentin, S100, FASN, CD10, and p16. Rb expression was intact. Moreover, CD34, p53, MDM2, and CDK4 were negative. After 2-year of follow-up, no alteration or recurrence was observed. In conclusion, MDM2, CDK4, p53, and Rb immunomarkers can be used reliably to differentiate benign lipoma with degenerative changes from ALT and DL.
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Oral leukoplakia (OL) and proliferative verrucous leukoplakia (PVL) are oral potentially malignant disorders (OPMDs) that microscopically show no or varying degrees of dysplasia. Even sharing clinical and microscopic aspects, PVL shows a more aggressive clinical behaviour, with a malignant transformation rate greater than 40%. Inflammatory infiltrate associated with dysplastic lesions may favour malignant transformation of OPMDs. This study aimed to evaluate the density of T cells and cytokines in dysplastic lesions from OL and PVL patients. Additionally, we evaluated whether soluble products produced in vitro by dysplastic keratinocytes are capable of modulating apoptosis rates and Th phenotype (Th1, Th2, Th17 and Treg) of peripheral blood mononuclear cells. The density of CD3, CD4 and CD8 T cells was assessed by immunohistochemistry. Cytokines and chemokines profile from frozen tissue samples were analysed using the LUMINEX system. Apoptosis rates and Th phenotype modulation were evaluated by flow cytometry. Our results showed an increase in the number of CD8 T cell in the subepithelial region from PVL dysplastic lesions in relation to OL samples. PVL showed increased levels of IL-5 and a decrease in IL-1ß and IFN-γ levels compared to OL. Soluble products of PVL and oral carcinoma cell cultures were able to reduce apoptosis rate and promote an imbalance of Th1/Th2 and Th17/Treg. The high-subepithelial density of CD8 T cells and immune imbalance of T lymphocytes subsets probably play an important role in the pathogenesis of PVL and may explain its more aggressive behaviour in relation to OL.
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Neoplasias Bucais , Lesões Pré-Cancerosas , Humanos , Leucócitos Mononucleares/patologia , Leucoplasia Oral/patologia , Neoplasias Bucais/patologia , Lesões Pré-Cancerosas/patologia , Linfócitos T CD8-Positivos/patologia , Citocinas , Transformação Celular NeoplásicaRESUMO
OBJECTIVES: To investigate the potential effect of fatty acid synthase (FASN) inhibitor orlistat to enhance the effectiveness of chemotherapy drugs widely used to treat oral squamous cell carcinomas (OSCC), such as 5-fluorouracil, cisplatin, and paclitaxel. METHODS: The OSCC SCC-9 LN-1 metastatic cell line, which expresses high levels of FASN, was used for drug combination experiments. Cell viability was analyzed by crystal violet staining and automatic cell counting. Apoptosis and cell cycle were analyzed by flow cytometry with Annexin-V/7-AAD and propidium iodide staining, respectively. Cyclin B1, Cdc25C, Cdk1, FASN, and ERBB2 levels were assessed by Western blotting. Finally, cell scratch and transwell assays were performed to assess cell migration and invasion. RESULTS: Inhibition of FASN with orlistat sensitized SCC-9 LN-1 cells to the cytotoxic effects of paclitaxel and cisplatin, but not 5-fluorouracil, which was accompanied by a significant reduction in cyclin B1. The suppression of proliferation, migration, and invasion of SCC-9 LN-1 cells induced by orlistat plus cisplatin or paclitaxel was not superior to the effects of chemotherapy drugs alone. CONCLUSION: Our results suggest that orlistat enhances the chemosensitivity of SCC-9 LN-1 cells to cisplatin and paclitaxel by downregulating cyclin B1.
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Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Bucais , Humanos , Cisplatino/farmacologia , Paclitaxel/farmacologia , Paclitaxel/uso terapêutico , Orlistate/farmacologia , Orlistate/uso terapêutico , Carcinoma de Células Escamosas de Cabeça e Pescoço , Ciclina B1/farmacologia , Ácido Graxo Sintases/metabolismo , Ácido Graxo Sintases/farmacologia , Neoplasias Bucais/tratamento farmacológico , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/patologia , Fluoruracila/farmacologia , Linhagem Celular Tumoral , Apoptose , Proliferação de Células , Ácido Graxo Sintase Tipo IRESUMO
ABSTRACT Lipomas are mesenchymal neoplasms relatively uncommon in the oral cavity. Lipomas can exhibit histopathological features mimicking atypical lipomatous tumors (ALT) or dysplastic lipoma (DL) in the presence of degenerative changes. Relevantly, immunohistochemistry assists in the correct diagnosis. Herein, we present the case of a 54-year-old male with a sessile nodule located on the dorsum of the tongue. The histopathological analysis showed a diffuse, non-circumscribed adipocytic proliferation constituted by cells of variable size containing cytoplasmic vacuoles and displaced nuclei, some resembling lipoblasts supported by fibrous connective tissue stroma. By immunohistochemistry, tumor cells were positive for vimentin, S100, FASN, CD10, and p16. Rb expression was intact. Moreover, CD34, p53, MDM2, and CDK4 were negative. After 2-year of follow-up, no alteration or recurrence was observed. In conclusion, MDM2, CDK4, p53, and Rb immunomarkers can be used reliably to differentiate benign lipoma with degenerative changes from ALT and DL.
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BACKGROUND: Colorectal cancer (CRC) has a high mortality rate and can develop in either colitis-dependent (colitis-associated (CA)-CRC) or colitis-independent (sporadic (s)CRC) manner. There has been a significant debate about whether mast cells (MCs) promote or inhibit the development of CRC. Herein we investigated MC activity throughout the multistepped development of CRC in both human patients and animal models. METHODS: We analyzed human patient matched samples of healthy colon vs CRC tissue alongside conducting a The Cancer Genome Atlas-based immunogenomic analysis and multiple experiments employing genetically engineered mouse (GEM) models. RESULTS: Analyzing human CRC samples revealed that MCs can be active or inactive in this disease. An activated MC population decreased the number of tumor-residing CD8 T cells. In mice, MC deficiency decreased the development of CA-CRC lesions, while it increased the density of tumor-based CD8 infiltration. Furthermore, co-culture experiments revealed that tumor-primed MCs promote apoptosis in CRC cells. In MC-deficient mice, we found that MCs inhibited the development of sCRC lesions. Further exploration of this with several GEM models confirmed that different immune responses alter and are altered by MC activity, which directly alters colon tumorigenesis. Since rescuing MC activity with bone marrow transplantation in MC-deficient mice or pharmacologically inhibiting MC effects impacts the development of sCRC lesions, we explored its therapeutic potential against CRC. MC activity promoted CRC cell engraftment by inhibiting CD8+ cell infiltration in tumors, pharmacologically blocking it inhibits the ability of allograft tumors to develop. This therapeutic strategy potentiated the cytotoxic activity of fluorouracil chemotherapy. CONCLUSION: Therefore, we suggest that MCs have a dual role throughout CRC development and are potential druggable targets against this disease.
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Colite , Neoplasias Colorretais , Animais , Fluoruracila , Humanos , Mastócitos , CamundongosRESUMO
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.
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Sialadenite , Síndrome de Sjogren , Biópsia , Centro Germinativo , Humanos , Linfócitos/metabolismo , Sialadenite/complicações , Sialadenite/patologia , Síndrome de Sjogren/complicaçõesRESUMO
The localized juvenile spongiotic gingival hyperplasia (LJSGH) mainly affects the maxillary vestibular attached gingiva of juvenile patients, without sex predilection. Similar lesions involving extragingival sites have not been reported to date. Here, we report 2 cases of extragingival soft tissue lesions with similar clinicopathological features to those reported in LJSGH and 12 cases of intraoral reactive soft tissue lesions microscopically showing LJSGH-like focal areas. The 2 cases were adult patients, affecting the maxillary alveolar ridge (55-year-old female) and hard palate (78-year-old male), which were diagnosed as "spongiotic hyperplasia of the oral mucosa." The 12 intraoral reactive soft tissue lesions (6 men and 6 women; mean age, 49.5 years) were diagnosed as inflammatory fibrous hyperplasia (n = 6), peripheral ossifying fibroma (n = 3), and pyogenic granuloma (n = 3), each of them presenting LJSGH-like focal areas. By immunohistochemistry, the spongiotic hyperplasia areas showed positivity for CK19, CK14, CK34ßE12, and CAM5.2 (weak/focal), while CK4 was negative. Considering the anatomical locations (extragingival) of these 2 cases, the term "spongiotic hyperplasia of the oral mucosa" is suggested. Moreover, LJSGH-like focal areas can be detected when microscopically assessing common intraoral reactive soft tissue lesions.
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Hiperplasia Gengival , Mucosa Bucal , Adulto , Idoso , Edema , Feminino , Gengiva , Hiperplasia Gengival/diagnóstico , Hiperplasia Gengival/patologia , Humanos , Hiperplasia/patologia , Masculino , Maxila/patologia , Pessoa de Meia-Idade , Mucosa Bucal/patologiaRESUMO
OBJECTIVES: While unknown for oropharyngeal squamous cell carcinoma (OPSCC) and oral squamous cell carcinoma (OSCC), some studies assessing cervical carcinoma have shown that human papillomavirus (HPV) co-infection can be associated with its prognosis. METHODS: Through in situ hybridization (HPV and Epstein-Barr virus [EBV] probes) and immunohistochemistry (p16INK4a, cyclin D1, p53, and Ki-67 antibodies), 126 OPSCC and 109 OSCC samples were assessed. RESULTS: All patients were EBV-negative. OPSCC (25%) showed a significant association with HPV compared to OSCC (11%). Almost all HPV-associated cases were p16INK4a-positive. Regarding OPSCC and OSCC, 23 and 7 cases were positive for high-risk HPV (HRHPV) only, 6 and 3 cases for low-risk HPV (LRHPV) only, and 3 and 2 cases for HRHPV/LRHPV, respectively. HPV-associated carcinomas showed a significantly higher proliferative index than HPV-unassociated carcinomas. Both carcinomas showed a similar overall survival rate, which was not affected by the HPV status. However, when comparing HPV-associated subgroups, patients with HRHPV/LRHPV-associated carcinomas showed worse survival. CONCLUSION: LRHPV-associated and HRHPV/LRHPV-associated cases can also be detected when assessing OSCC and OPSCC. Further studies, especially in populations with a high prevalence of HPV-associated OPSCC, are necessary to understand the clinicopathological behavior of these neoplasm subgroups.
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Alphapapillomavirus , Carcinoma de Células Escamosas , Coinfecção , Infecções por Vírus Epstein-Barr , Neoplasias de Cabeça e Pescoço , Neoplasias Bucais , Neoplasias Orofaríngeas , Infecções por Papillomavirus , Carcinoma de Células Escamosas/patologia , Coinfecção/complicações , Coinfecção/epidemiologia , Infecções por Vírus Epstein-Barr/complicações , Neoplasias de Cabeça e Pescoço/complicações , Herpesvirus Humano 4 , Humanos , Neoplasias Bucais/epidemiologia , Neoplasias Orofaríngeas/patologia , Papillomaviridae , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/epidemiologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/complicaçõesRESUMO
BACKGROUND/AIM: Antimony is a chemical element used in the therapy of parasitic diseases with a promising anticancer potential. The aim of this study was to evaluate in vitro activity of free or liposomal vesicle-packed antimony trioxide (AT or LAT) in the t(15;17)(q22;q21) translocation-positive acute promyelocytic leukemia (APL) cell line NB4. MATERIALS AND METHODS: Cytotoxicity was analysed with trypan blue exclusion, the MTT assay and neutral red exclusion assay; cell proliferation with PicoGreen®; and reactive oxygen species (ROS) production with DCFDA. RESULTS: Liposomal particles did not change the pH of the cell culture medium and entered the cells. Both formulations resulted in a time- and concentration-dependent cytotoxicity and production of ROS. LAT showed higher toxicity at lower concentrations compared to AT. CONCLUSION: LAT may be used to decrease drug dosage and maintain high anti-tumoral effects on APL cells.
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Antimônio/administração & dosagem , Antimônio/farmacologia , Lipossomos , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Portadores de Fármacos , Humanos , Leucemia Promielocítica Aguda , Sistemas de Liberação de Fármacos por Nanopartículas , Espécies Reativas de Oxigênio/metabolismoRESUMO
In approximately 15% of patients with acute myeloid leukemia (AML), total and phosphorylated EGFR proteins have been reported to be increased compared to healthy CD34+ samples. However, it is unclear if this subset of patients would benefit from EGFR signaling pharmacological inhibition. Pre-clinical studies on AML cells provided evidence on the pro-differentiation benefits of EGFR inhibitors when combined with ATRA or ATO in vitro. Despite the success of ATRA and ATO in the treatment of patients with acute promyelocytic leukemia (APL), therapy-associated resistance is observed in 5-10% of the cases, pointing to a clear need for new therapeutic strategies for those patients. In this context, the functional role of EGFR tyrosine-kinase inhibitors has never been evaluated in APL. Here, we investigated the EGFR pathway in primary samples along with functional in vitro and in vivo studies using several APL models. We observed that total and phosphorylated EGFR (Tyr992) was expressed in 28% and 19% of blast cells from APL patients, respectively, but not in healthy CD34+ samples. Interestingly, the expression of the EGF was lower in APL plasma samples than in healthy controls. The EGFR ligand AREG was detected in 29% of APL patients at diagnosis, but not in control samples. In vitro, treatment with the EGFR inhibitor gefitinib (ZD1839) reduced cell proliferation and survival of NB4 (ATRA-sensitive) and NB4-R2 (ATRA-resistant) cells. Moreover, the combination of gefitinib with ATRA and ATO promoted myeloid cell differentiation in ATRA- and ATO-resistant APL cells. In vivo, the combination of gefitinib and ATRA prolonged survival compared to gefitinib- or vehicle-treated leukemic mice in a syngeneic transplantation model, while the gain in survival did not reach statistical difference compared to treatment with ATRA alone. Our results suggest that gefitinib is a potential adjuvant agent that can mitigate ATRA and ATO resistance in APL cells. Therefore, our data indicate that repurposing FDA-approved tyrosine-kinase inhibitors could provide new perspectives into combination therapy to overcome drug resistance in APL patients.
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Squamous odontogenic tumor (SOT) is a rare benign neoplasm of the jaw that likely arises from remnants of the dental lamina. It is a slow-growing lesion, with a radiolucent appearance in the central variant. Microscopically, SOT shows islands of squamous epithelium supported by fibrous stroma. In rare cases, squamous odontogenic tumor-like proliferation (SOT-LP) can be observed arising from odontogenic cysts (SOT-LPOC). Herein, we describe the case of a 42-year-old man who presented with discreet bleeding in the maxillary gingiva. Imaging revealed a well-defined, ovoid-shaped lesion with sclerotic margins involving tooth #18 in the intraosseous location. Fine needle aspiration supported the cystic nature of the lesion. After surgery, microscopy revealed a dentigerous cyst showing SOT-LP features. There was no recurrence after a 3-year follow-up. To the best of our knowledge, this is the first report of a dentigerous cyst showing SOT-LP features in the maxilla. Such cysts should be identified to avoid misdiagnosis, with the finding having therapeutic and prognostic implications.
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Spindle cell squamous cell carcinoma (SpSCC) is a rare biphasic malignant neoplasm, uncommonly affecting the oral cavity. The SpSCC diagnosis is difficult, especially when it exhibits inconspicuous morphology, inadequate tissue sampling, or association with an exuberant inflammatory reaction. Post-radiotherapy recurrent SpSCC occurring at the same site of conventional SCC is a rare phenomenon. A 59-year-old man was complained of "painful injury on the tongue" with 20 days of duration. He reported smoking and alcohol consumption. Medical history revealed conventional SCC on the tongue treated with surgery and radiotherapy 10 years ago. Intraoral examination showed a polypoid lesion with ulcerated areas, measuring 3 cm in diameter, on the tongue and floor of the mouth, at the same site of previous conventional SCC. The microscopical analysis showed small foci of carcinomatous component admixed with an exuberant inflammatory reaction. Immunohistochemistry highlighted the sarcomatoid component. Both malignant components were positive for EMA, CD138, p40 (deltaNp63), p63, and p53. Moreover, CK AE1/AE3 evidenced the carcinomatous component, whereas vimentin stained the sarcomatoid component. The Ki-67 was >10%. The current case emphasizes the importance of immunohistochemistry in the differential diagnosis of SpSCC from mimics and documents a rare complication of Ionizing Radiation.
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Macrophages are phagocytic cells with essential participation in immunological events of the oral cavity. However, the role of these cells in oral lichen planus (OLP) and oral lichenoid lesions (OLL) remains unclear. The present study aimed to evaluate the density of macrophages in OLP and OLL, and to compare it with that of oral inflammatory fibrous hyperplasia (OIFH) (control group). 14 cases of OLP, 14 cases of OLL and 14 cases of OIFH were selected for immunohistochemical analysis of CD68+ (M1) and CD163+ (M2) macrophage expression. CD68+ and CD163+ macrophages densities were measured in the intraepithelial and subepithelial areas. The statistical tests used were multivariate analysis of variance, as well as a correlation and linear regression. OLP has more CD68+ macrophages when comparing with OLL (p = 0.001) and OIFH (p = 0.045). There is a very strong relationship between the macrophages types (p < 0.0001) in OLP and OLL. The linear regression showed that to OLL development (p < 0.0001/R2' = 0.9584), the presence of different types of macrophages are more essential than to OLP (p < 0.0001/R2' = 0.8983). However, in the OLP these dependencies are also largely. CD68+ macrophages may be associated with immunopathogenesis of OLP, indicating a pro-inflammatory activity and regulatory role in the type of T-cell response. Besides, CD68+ macrophages can cooperate in the diagnosis of OLP. These results are essential to future studies that seek a therapeutic target for OLP and OLL.
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Suscetibilidade a Doenças , Líquen Plano Bucal/etiologia , Líquen Plano Bucal/metabolismo , Macrófagos/imunologia , Macrófagos/metabolismo , Adulto , Idoso , Antígenos CD/metabolismo , Antígenos de Diferenciação Mielomonocítica/metabolismo , Biomarcadores , Plasticidade Celular/imunologia , Feminino , Humanos , Imuno-Histoquímica , Imunofenotipagem , Líquen Plano Bucal/diagnóstico , Masculino , Pessoa de Meia-Idade , Receptores de Superfície Celular/metabolismo , Fatores de RiscoRESUMO
OBJECTIVE: the aim of this study was to evaluate the density of Langerhans cells in oral lichen planus (OLP) and oral lichenoid lesions (OLL). DESIGN: 14 cases of OLP, 15 cases of OLL and 14 cases of oral inflammatory fibrous hyperplasia (OIFH), were selected for immunohistochemical analysis of CD1a, CD207 and S100 expression. The OIFH group was subdivided according to the presence (OIFHL nâ¯=â¯14) or absence (OIFHNL nâ¯=â¯14) of lichenoid inflammatory infiltrate. Positive cells were counted in intraepithelial and subepithelial areas. Results were analyzed by multivariate comparative analysis, correlation analysis, linear regression models and Student's T-test. RESULTS: A significantly higher amount of CD207+ cells in OLL vs OLP was observed (pâ¯=â¯0.015). The prevailing reticular pattern observed was CD207high for OLP (pâ¯=â¯0.0329). A statistically significant difference in the expression of CD1a and CD207 was observed for intraepithelial vs subepithelial areas (pâ¯=â¯0.024 and p=0.015, for CD1a and CD207, respectively). Significant correlations were also observed between the expression of CD1aâ¯+â¯and CD207+ cells in the pathogenesis of OLP and OLL. CONCLUSION: High levels of CD207+cells in OLP compared with OLL may help explain the differences in the immunopathogenesis of both diseases. Additionally, CD1aâ¯+â¯and CD207+ cells appear to be more essential to immunopathogenesis of OLL than to the pathogenesis of OLP.
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Líquen Plano Bucal , Erupções Liquenoides , Humanos , Células de LangerhansRESUMO
Spindle cell squamous cell carcinoma (SpSCC) is a rare biphasic malignant neoplasm, uncommonly affecting the oral cavity. The SpSCC diagnosis is difficult, especially when it exhibits inconspicuous morphology, inadequate tissue sampling, or association with an exuberant inflammatory reaction. Post-radiotherapy recurrent SpSCC occurring at the same site of conventional SCC is a rare phenomenon. A 59-year-old man was complained of "painful injury on the tongue" with 20 days of duration. He reported smoking and alcohol consumption. Medical history revealed conventional SCC on the tongue treated with surgery and radiotherapy 10 years ago. Intraoral examination showed a polypoid lesion with ulcerated areas, measuring 3 cm in diameter, on the tongue and floor of the mouth, at the same site of previous conventional SCC. The microscopical analysis showed small foci of carcinomatous component admixed with an exuberant inflammatory reaction. Immunohistochemistry highlighted the sarcomatoid component. Both malignant components were positive for EMA, CD138, p40 (deltaNp63), p63, and p53. Moreover, CK AE1/AE3 evidenced the carcinomatous component, whereas vimentin stained the sarcomatoid component. The Ki-67 was >10%. The current case emphasizes the importance of immunohistochemistry in the differential diagnosis of SpSCC from mimics and documents a rare complication of Ionizing Radiation.
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Humanos , Masculino , Pessoa de Meia-Idade , Imuno-Histoquímica , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Radioterapia , Diagnóstico DiferencialRESUMO
Background: Oral squamous cell carcinoma (OSCC) is the most frequently occurring malignant tumor of the head and neck region. Chk2 (Checkpoint kinase 2) is considered a tumor suppressor gene that acts on the cellular response to DNA damage. However, the role of Chk2 in OSCC prognosis is not yet fully understood. The objective of this study was to evaluate Chk2 immunoexpression in OSCC and to elucidate the association between its expression and clinicopathological parameters of prognostic importance, including overall survival, disease-free survival, and metastasis-free survival. Methods: Chk2 expression was analyzed in 101 samples from patients with OSCC using immunohistochemistry. We stratified the patients into high expression (> 66% of cells positive for Chk2) and low expression (< 66%) groups. Results: Chk2 showed high expression in 57.43% of OSCC. In our study, the expression of Chk2 did not correlate with any of the prognostic parameters evaluated. There was no difference between overall survival, metastasis-free survival, and disease-free survival according to Chk2 expression. Conclusion: Despite the great importance of Chk2 in the development of different types of cancer, our findings do not favor Chk2 as a prognostic marker in oral squamous cell carcinoma.
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Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Neoplasias Bucais/metabolismo , Imuno-Histoquímica , Carcinoma de Células Escamosas/metabolismo , Quinase do Ponto de Checagem 2/metabolismo , Prognóstico , Análise de SobrevidaRESUMO
Langerhans cell histiocytosis (LCH) is an inflammatory myeloid neoplasia commonly affecting children with frequent somatic mutations in MAPK pathway genes including BRAFV600E and MAP2K1. Some studies suggest that LCH cells can recruit and modulate inflammatory cells, which could provide reciprocal survival signals. To characterize the immune profile of infiltrating inflammatory cells, and to clarify their participation in LCH pathogenesis, a detailed immunohistochemical analysis was performed. Fifteen (10 children, 5 adults) LCH cases were assessed through macrophage (CD68 and CD163), mature dendritic cell (mDC; CD83 and CD208), regulatory T cell (Treg; CD4, CD25 and FOXP3) and cytotoxic lymphocyte (CL; CD56, CD57, perforin and granzyme B) immunomarkers. Moreover, lymphocytic and LCH markers were also analysed. All cases were S100, CD1a, CD207 and CD4-positive. Bcl-2 and cyclin D1 expression was observed in 13 of 15 cases. In the immune microenvironment, M2-polarized macrophages and Tregs were the predominant cell populations, followed by significantly (P < .005) smaller levels of mDCs and CLs. Additionally, the number of CD3 + cells was significantly higher than that of CD20 + cells. In the CD3 + cell population, there were a significantly higher number of CD4 + cells than CD8 + cells. While there were no differences when comparing the paediatric and adult populations, FOXP3 + cells were significantly higher in patients with multisystem involvement and treated with chemotherapy, than single-site cases and those without chemotherapy. Our results suggest that M2-polarized macrophages and Treg infiltration can promote LCH development and survival, probably through pro-tumoral, immunosuppressive and/or cytokine-mediated mechanisms. This work highlights the need for further exploration of immune-targeted therapy for LCH.
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Histiocitose de Células de Langerhans/metabolismo , Células de Langerhans/fisiologia , Macrófagos/metabolismo , Linfócitos T Reguladores/metabolismo , Adulto , Antígenos CD/metabolismo , Diferenciação Celular , Microambiente Celular , Criança , Pré-Escolar , Citocinas/metabolismo , Células Dendríticas/metabolismo , Feminino , Fatores de Transcrição Forkhead/metabolismo , Humanos , Imuno-Histoquímica/métodos , Lactente , Macrófagos/imunologia , Masculino , Linfócitos T Citotóxicos/metabolismo , Linfócitos T Reguladores/imunologia , Células Th2/imunologiaRESUMO
Besides the Waldeyer's ring, other lymphoid aggregates can also be detected in the soft palate, floor of the mouth and ventral tongue. The lingual tonsil is located at the base of the tongue and related to circumvallate papillae, whereas subepithelial lymphoid tissue at the posterior lateral portion of the tongue and related to foliate papillae constitutes the lateral lingual tonsil. Unilateral tonsillar enlargement is critical, because it can suggest malignancy, notably non-Hodgkin lymphoma or squamous cell carcinoma. Herein, we report an unusual presentation of unilateral enlargement of the lateral lingual tonsil, diagnosed as follicular lymphoid hyperplasia.