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Although the mixed lineage leukemia 5 (MLL5) gene has prognostic implications in acute promyelocyte leukemia (APL), the underlying mechanism remains to be elucidated. Here, we demonstrate the critical role exerted by MLL5 in APL regarding cell proliferation and resistance to drug-induced apoptosis, through mtROS regulation. Additionally, MLL5 overexpression increased the responsiveness of APL leukemic cells to all-trans retinoic acid (ATRA)-induced differentiation, via regulation of the epigenetic modifiers SETD7 and LSD1. In silico analysis indicated that APL blasts with MLL5high transcript levels were associated with retinoic acid binding and downstream signaling, while MLL5low blasts displayed decreased expression of epigenetic modifiers (such as KMT2C, PHF8 and ARID4A). Finally, APL xenograft transplants demonstrated improved engraftment of MLL5-expressing cells and increased myeloid differentiation over time. Concordantly, evaluation of engrafted blasts revealed increased responsiveness of MLL5-expressing cells to ATRA-induced granulocytic differentiation. Together, we describe the epigenetic changes triggered by the interaction of MLL5 and ATRA resulting in enhanced granulocytic differentiation.

Made available in DSpace on 2022-04-29T08:30:47Z (GMT). No. of bitstreams: 0 Previous issue date: 2022-04-01 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. Oral Pathology Department of Stomatology Public Oral Health and Forensic Dentistry Ribeirão Preto Dental School (FORP/USP) University of São Paulo, São Paulo Oral Medicine Department of Diagnosis and Surgery Araraquara Dental School São Paulo State University (UNESP), São Paulo Centro Clínico de Cabeza y Cuello Department of Pathology and Forensic Medicine Ribeirão Preto Medical School (FMRP/USP) University of São Paulo, São Paulo Oral Medicine Department of Diagnosis and Surgery Araraquara Dental School São Paulo State University (UNESP), São Paulo

Made available in DSpace on 2020-12-12T01:47:05Z (GMT). No. of bitstreams: 0 Previous issue date: 2020-03-01 Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Background: SMARCB1 (INI-1)-deficient carcinomas and NUT carcinomas are aggressive neoplasms, often affecting the sinonasal region. Not uncommonly, their diagnoses are made retrospectively. Methods: Through SMARCB1 (INI-1) and NUT immunomarkers, 643 head and neck carcinomas were assessed retrospectively. Moreover, SMARCB1 (INI-1)-deficient and NUT carcinomas were additionally evaluated by immunohistochemistry, as well as in situ hybridization analysis for HPV and EBV. Results: Four SMARCB1 (INI-1)-deficient carcinomas (located in lower lip, soft palate, hypopharynx and vocal cord, this latter high-risk HPV positive) and three NUT carcinomas (all located in oropharynx) were detected, previously diagnosed as nonkeratinizing or moderately differentiated squamous cell carcinoma. All cases showed squamous differentiation. NUT carcinomas than SMARCB1 (INI-1)-deficient carcinomas showed low overall survival rate. Conclusion: The current cases expand the clinicopathological spectrum of SMARCB1 (INI-1)-deficient carcinomas and NUT carcinomas. Notably, the diagnosis of these cases is easily reached through immunohistochemistry, with impact on their accurate classification, treatment, and prognosis. Oral Pathology Department of Stomatology Public Oral Health and Forensic Dentistry Ribeirão Preto Dental School (FORP/USP) University of São Paulo Oral Medicine Department of Diagnosis and Surgery Araraquara Dental School São Paulo State University (UNESP) Department of Pathology and Forensic Medicine Ribeirão Preto Medical School (FMRP/USP) University of São Paulo Oral Medicine Department of Diagnosis and Surgery Araraquara Dental School São Paulo State University (UNESP) FAPESP: 2016/02713-2 FAPESP: 2016/11419-0 FAPESP: 2018/12734-2

Made available in DSpace on 2022-04-28T19:42:31Z (GMT). No. of bitstreams: 0 Previous issue date: 2019-10-20 Carcinoma cuniculatum (CC), a rare variant of oral squamous cell carcinoma, presents well-differentiated neoplastic epithelial cells infiltrating the underlying submucosal or bone tissues, forming the so-called rabbit burrows filled with keratin. A 67-year-old female patient was referred complaining of a painless tumoral mass in the left mandibular body, with several months of evolution. Previous history indicated extraction of the teeth #37 and #38 and diagnosis of chronic suppurative osteomyelitis. A deep incisional biopsy revealed CC. Due to its microscopic features, suggesting an inflammatory or reactive process, strict clinicopathological correlation is necessary for the correct diagnosis of CC. Universidade de São Paulo (USP), São Paulo Universidade do Estado de São Paulo (UNESP), São Paulo Universidade do Estado de São Paulo (UNESP), São Paulo

To perform a systematic review focusing on the prognosis of oral cavity squamous cell carcinoma (OSCC) in young patients (≤40 years old) compared to older (>40 years old). Four databases were used in our search strategy. First, all titles were systematically organized using the Covidence platform online. In the second phase, 118 full texts of potentially eligible studies were analyzed by reviewers independently and in pairs. Twelve studies were considered eligible for data extraction. The relapse was higher in the young than in controls (pooled relative risk (RR) = 1.31; 95% CI [1.10-1.56]). The 5-year disease-free survival (DFS) was worse in young group (pooled hazard ratio (HR) = 0.73; 95% CI [0.63-0.85]) but the 5-year overall survival (OS) estimate was similar between the groups (pooled HR = 0.84; 95% CI [0.70-1.00]). While the 5-year OS was similar between groups, the number of relapses and 5-year DFS were worse in patients with OSCC ≤40 years old.

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.

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 analysed 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.

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, CK34βE12, 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.

Made available in DSpace on 2021-06-25T10:34:21Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-05-01 Oral Medicine Department of Diagnosis and Surgery Araraquara Dental School São Paulo State University (UNESP) Department of Pathology and Forensic Medicine Ribeirão Preto Medical School (FMRP/USP) University of São Paulo Oral Pathology Department of Stomatology Public Oral Health and Forensic Dentistry Ribeirão Preto Dental School (FORP/USP) University of São Paulo Oral Medicine Department of Diagnosis and Surgery Araraquara Dental School São Paulo State University (UNESP)

Oral Medicine Department of Diagnosis and Surgery Araraquara Dental School Universidade Estadual Paulista (UNESP)

Myoepithelial carcinomas of the head and neck are often located in the major salivary glands, notably in the parotid glands, being less frequent in the minor salivary glands. Noteworthy, myoepithelial carcinoma in the maxillary sinus is extremely rare. In fact, only five cases have been previously published to date. Here, we present, for the first time, a detailed immunohistochemical and in situ hybridization analysis of a SMARCB1 (INI-1)-intact myoepithelial carcinoma with rhabdoid features, expanding the histopathological spectrum of high-grade sinonasal carcinomas.

Made available in DSpace on 2022-04-29T08:30:52Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-01-01 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. Oral Medicine Department of Diagnosis and Surgery Araraquara Dental School Sao Paulo State University (UNESP) Oral Pathology Department of Stomatology Public Oral Health and Forensic Dentistry School of Dentistry of Ribeirão Preto University of São Paulo (FORP/USP) Oral Pathology Department of Oral Diagnosis and Pathology School of Dentistry Federal University of Rio de Janeiro (UFRJ) Department of Pathology and Forensic Medicine Ribeirão Preto Medical School (FMRP/USP) University of São Paulo Department of Ophthalmology Otorhinolaryngology and Head and Neck Surgery Ribeirão Preto Medical School University of São Paulo Departament of Pathology Hospital Herrera-Llerandi/AMEDESGUA Oral Medicine Department of Diagnosis and Surgery Araraquara Dental School Sao Paulo State University (UNESP)

Made available in DSpace on 2022-04-29T08:31:59Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-01-01 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, CK34βE12, 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. Department of Diagnosis and Surgery Araraquara Dental School São Paulo State University (UNESP) Oral Pathology Department of Stomatology Public Oral Health and Forensic Dentistry Ribeirão Preto Dental School (FORP/USP) University of São Paulo School of Dentistry National Autonomous University of Mexico Universidade Vale Do Rio Verde (UninCor) Department of Pathology and Forensic Medicine Ribeirão Preto Medical School (FMRP/USP) University of São Paulo Department of Diagnosis and Surgery Univ Estadual Paulista (UNESP), Rua Humaitá, 1680 Department of Diagnosis and Surgery Araraquara Dental School São Paulo State University (UNESP) Department of Diagnosis and Surgery Univ Estadual Paulista (UNESP), Rua Humaitá, 1680

Made available in DSpace on 2021-06-25T11:12:50Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-05-01 Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) 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. Oral Medicine Department of Diagnosis and Surgery São Paulo State University (UNESP) School of Dentistry Department of Orthodontics and Pediatric Dentistry São Paulo State University (UNESP) School of Dentistry Department of Pathology and Forensic Medicine Ribeirão Preto Medical Scholl (FMRP/USP) University of São Paulo Oral Pathology Department of Stomatology Public Oral Health and Forensic Dentistry Ribeirão Preto Dental School (FORP/USP) University of São Paulo, Avenida do Café, S/N Oral Medicine Department of Diagnosis and Surgery São Paulo State University (UNESP) School of Dentistry Department of Orthodontics and Pediatric Dentistry São Paulo State University (UNESP) School of Dentistry FAPESP: 2016/11419-0 FAPESP: 2017/01438-0 FAPESP: 2018/18440-0 FAPESP: 2020/07110-0 CNPq: 423945/2016-5

Background Differentiation syndrome (DS) is the main life-threatening adverse event that occurs in acute promyelocytic leukemia (APL) patients treated with all-trans retinoic acid (ATRA). Cytokine imbalances have been reported to play role during the developing of acute promyelocytic leukemia differentiation syndrome (APL-DS). However, the relationship between the plasma cytokine levels and their prognostic value for the prediction of DS developing in patients with APL during the treatment with ATRA and anthracyclines has not been previously reported. Methods In this study, we followed an APL cohort (n = 17) over 7 days of ATRA therapy in DS (n = 6) and non-DS groups (n = 11). Interleukin (IL)-1β, IL-6, IL-8, IL-10, IL-12p70 and TNF-α were measured in the peripheral blood plasma from 17 patients with APL and 11 healthy adult controls by using the cytometric bead array method. Results In non-DS patients, IL-8 plasma levels were significantly reduced in the seventh day of ATRA treatment (34.16; 6.99 to 147.11 pg mL− 1 in D0 vs. 10.9; 0 to 26.81 pg mL− 1 in D7; p = 0.02) whereas their levels did not discriminate between DS and non-DS development during the entire induction period (all p > 0.05 in D0, D3, and D7). No significant differences were found in IL-6 levels between groups (p > 0.05 in D0-D7). Other cytokines tested were all undetectable in patients with APL or healthy controls. Conclusions We demonstrated that the modulation of IL-8 following ATRA treatment may occur regardless of the development of DS and, therefore, does not appear to be a predictive biomarker to monitor the APL-DS.

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.

Made available in DSpace on 2021-06-25T10:48:29Z (GMT). No. of bitstreams: 0 Previous issue date: 2020-11-01 Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) We report a 7-year-old boy who presented with a nodule on the upper lip. A previous clinical history of mechanical trauma in the lesional area had been noted. After surgical excision, microscopy revealed fibrocollagenous fascicles associated with neurovascular bundles and skeletal striated muscle fibers in diffuse subepithelial distribution, suggesting rhabdomyomatous mesenchymal hamartoma. However, strict clinicopathological correlation favored a healing process with trapped striated skeletal muscle tissue. After three years of follow-up, an improvement in the aesthetic appearance of the upper lip was observed. To the best of our knowledge, a case of pseudo-rhabdomyomatous mesenchymal hamartoma has not been reported to date. Department of Pediatric Dentistry School of Dentistry of Ribeirão Preto FORP/USP University of Sao Paulo Oral Medicine Department of Diagnosis and Surgery Araraquara Dental School Universidade Estadual Paulista (UNESP) Oral Pathology Department of Stomatology Public Oral Health and Forensic Dentistry School of Dentistry of Ribeirão Preto FORP/USP University of São Paulo Oral Medicine Department of Diagnosis and Surgery Araraquara Dental School Universidade Estadual Paulista (UNESP) FAPESP: 2016/02713-2

Stafne’s bone cavity (SBC) is an asymptomatic lingual bone cavity situated near the angle of the mandible. The anterior variant of SBC, which shows a radiolucent unilateral ovoid lingual bone concavity in the canine-premolar mandibular region, is uncommon. A 73-year-old man was referred for assessment of loss of mandibular bone. Panoramic radiographs and computerized tomography scans showed a well-defined lingual bony defect in the anterior mandible. Analysis of imaginological documentation, made 14 years ago, revealed a progressive increase in mesiodistal diameter and intraosseous bony defect. The soft tissue obtained within the bony defect, microscopically revealed fibrous stroma containing blood vessels of varied caliber. The current anterior lingual mandibular bone defect case is probably caused by the salivary gland entrapped or pressure resorption, which can explain the SBC pathogenesis.KEYWORDSBone defect; Mandible; Cone beam computed tomography; Diagnosis; Case report.

Made available in DSpace on 2020-12-12T01:53:54Z (GMT). No. of bitstreams: 0 Previous issue date: 2020-03-01 Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Oral Medicine Department of Diagnosis and Surgery Araraquara Dental School Universidade Estadual Paulista (UNESP) Department of Dentistry Clinical Stomatology Federal University of the Jequitinhonha and Mucuri Valleys Department of Pathology and Forensic Medicine Ribeirão Preto Medical School (FMRP/USP) University of São Paulo Oral Pathology Department of Stomatology Public Oral Health and Forensic Dentistry Ribeirão Preto Dental School (FORP/USP) University of São Paulo Oral Medicine Department of Diagnosis and Surgery Araraquara Dental School Universidade Estadual Paulista (UNESP) FAPESP: 2016/02713-2 FAPESP: 2016/11419-0 FAPESP: 2018/12734-2

Background and objective Some studies suggest that regulatory T cells (Tregs) have suppressive effects on inflammatory osteolysis. The aim of this study was to evaluate Treg immunomarkers in periodontitis-affected tissues from patients with periodontitis and clinically healthy gingiva (control). Material and methods The presence and distribution of positive cells for CD4, CD25 and FOXP3 (Treg immunomarkers) in periodontitis-affected tissues (epithelium and lamina propria) of 30 patients (ten per group) with a diagnosis of stage IV, grade C periodontitis (IV-C), stage III, grade B periodontitis (III-B) and the control were evaluated. A two-way ANOVA followed by Fisher's LSD test was used to demonstrate differences between the groups and immunomarkers; Student's t test was used to demonstrate differences between the epithelium and the lamina propria. Results Both IV-C and III-B periodontitis presented a significantly high proportion of immune-stained cells for all immunomarkers when compared to the control group. Notably, CD25+ and FOXP3+ cells were detected in a significantly higher number in III-B than IV-C periodontitis (P Conclusion Our results suggest the participation of Tregs on the osteoimmunological mechanisms in IV-C and III-B periodontitis patients, notably contributing to strategies for alveolar bone regeneration in clinical treatment decisions.

Made available in DSpace on 2021-06-25T10:58:50Z (GMT). No. of bitstreams: 0 Previous issue date: 2020-01-01 Lymphoepithelial-like carcinoma (LEC) is a rare malignant neoplasm, which can be associated with Epstein-Barr virus (EBV) infection. Histologically, LEC is an undifferentiated carcinoma with an intermixed reactive lymphoplasmacytic infiltrate. LEC appears to be an uncommon tumor type of lip carcinoma. An 82-year-old white woman presented a lesion on her lower lip that developed over the last year. The lesion was characterized by ulceration with flat edges, hardened base, painful, and absence of regional lymphadenopathy. Microscopical analysis evidenced an intense inflammatory infiltrate, composed of lymphoplasmacytic cells, associated with scarce pleomorphic epithelial cells. Immunohistochemistry highlighted the LEC cells with strong expression of pan-CK AE1/AE3, EMA, p63, and p53. CD138 was also faintly positive. Ki-67 was >85%. In situ hybridization analysis did not show evidence of EBV. A diagnostic of EBV-negative LEC was made. We present an uncommon type of lip carcinoma, which can represent a diagnostic challenge for clinicians and pathologists. Universidade Estadual de São Paulo (Unesp) Faculdade de Odontologia de Araraquara Medicina Oral Departamento de Diagnóstico e Cirurgia Universidade de São Paulo (USP) Faculdade de Odontologia de Ribeirão Preto Patologia Oral Departamento de Estomatologia Saúde Coletiva e Odontologia Legal Estratégia Saúde da Família Ministério da Saúde do Brasil Universidade de São Paulo (USP) Faculdade de Medicina de Ribeirão Preto Departamento de Patologia e Medicina Legal Universidade Estadual de São Paulo (Unesp) Faculdade de Odontologia de Araraquara Medicina Oral Departamento de Diagnóstico e Cirurgia

Made available in DSpace on 2019-10-03T17:32:09Z (GMT). No. of bitstreams: 0 Previous issue date: 2018-09-01. Added 1 bitstream(s) on 2019-10-04T16:21:12Z : No. of bitstreams: 1 S1981-86372018000300274.pdf: 449225 bytes, checksum: 29715ec72a65b2585bc55b8d7b5df421 (MD5) RESUMO A acantose glicogênica é uma condição benigna, comumente observada durante procedimentos endoscópicos em pacientes idosos, e se apresenta como placas brancas levemente elevadas, freqüentemente encontrada no terço inferior do esôfago. Microscopicamente, a acantose glicogênica é composta por epitélio escamoso hiperplásico com depósitos de glicogênio intracitoplasmático. A acantose glicogênica extra-esofágica é extremamente rara, com apenas três relatos de casos na literatura em língua inglesa. Apresentamos um caso com uma lesão branca diagnosticada como acantose glicogênica, localizada na borda póstero-lateral esquerda da língua, afetando um paciente do sexo masculino de 56 anos. A história médica não foi contribuitória e o paciente não apresentou lesões durante o exame endoscópico do esôfago, estômago e duodeno superior. A acantose glicogênica é uma condição benigna, que deve ser incluída no diagnóstico diferencial na avaliação de lesões brancas orais. É importante também reconhecer precocemente essa condição benigna e descartar a possibilidade de outras doenças mais graves, porém mais estudos são necessários para melhor definir seu potencial de persistência ou recorrência, como observado no presente caso. ABSTRACT Glycogenic acanthosis is a benign condition, commonly observed during endoscopic procedures in older patients, which present as slightly elevated whitish plaques often on the lower third of the oesophagus. Microscopically, glycogenic acanthosis is composed of hyperplastic squamous epithelium with intracytoplasmic glycogen deposits. The extraoesophageal glycogenic acanthosis is extremely rare, with only three case reports in the English-language literature. We report a white lesion showing glycogenic acanthosis-like features located on the left posterolateral border of the tongue, affecting a 56-year-old male patient. The medical history was non-contributory and the patient did not show any lesions during endoscopic examination of the oesophagus, stomach, and upper duodenum. Glycogenic acanthosis is a benign condition, which should be included in the differential diagnosis when assessing oral white lesions. It is important also to recognize this benign condition early and rule out the possibility of other more severe diseases, but further studies were necessary for better define their potential for persistence or recurrence, as observed in the current case. Universidade Estadual Paulista Departamento de Diagnóstico e Cirurgia Universidade de São Paulo Faculdade de Medicina Departamento de Patologia Universidade de São Paulo Faculdade de Odontologia Departamento de Estomatologia, Saúde Coletiva e Odontologia Legal Universidade Estadual Paulista Departamento de Diagnóstico e Cirurgia

Ectomesenchymal chondromyxoid tumor (ECT) is a rare benign neoplasm, often affecting the anterior dorsum of the tongue. To date, approximately 74 cases of lingual ECT have been published. This report describes, for the first time, the morphological and immunohistochemical features of a unique ECT case, which revealed diffuse infiltration by immune cells with a dendritic-like appearance inside the tumor proliferation. The significance of these findings and discussion about the tumor cell-immune cell interactions are presented.

Cementoblastoma is a benign ectomesenchymal odontogenic tumor characterized by the formation of cementum mass continuous with the tooth root, preferentially a permanent mandibular first molar. Clinically, the tumor shows a tender, sometimes painful, cortical plate expansion, frequently in male patients under 30 years old. Radiographically, the lesion exhibits a radiopaque mass, surrounding by a thin radiolucent rim, and attached to the tooth root. Microscopically, it is visualized a calcified matrix lined by large hyperchromatic cementoblasts with radiating columns at the periphery. Treatment of choice is surgery. Interestingly, rare cases of residual (after tooth extraction only) and recurrent (after tumor removal plus tooth extraction) cementoblastomas have been reported, which can be misdiagnosed if an appropriate clinicopathological correlation is not considered. Here, we present a rare case of residual cementoblastoma affecting an 18-year-old male patient at level of permanent mandibular first molar. Thus, residual cementoblastoma is an unusual presentation which should be included in the differential diagnosis of cementum-forming and bone-forming tumors affecting the jaws.

Ecstasy is an illicit drug that has been increasingly abused by young people. This synthetic drug has both stimulant and hallucinogenic effects and is usually consumed in a tablet. The side effects of ecstasy use include nausea, muscle cramping, fever, and symptoms mostly linked to muscular tension including jaw pain, facial pain, and headaches. There are few studies assessing the ecstasy effects on the oral mucosa, both clinically and histopathologically. The authors report 2 young women (22- and 27-year-old) who presented multifocal oral erosions and ulcerations. The lesions were painful and covered by a yellow-white pseudomembrane with a bright erythematous halo. By microscopy, it was observed superficial ulceration surrounded by acanthotic squamous epithelium with marked spongiosis, interstitial edema within the corion and perivascular lyphoid infiltrate, suggesting drug-induced oral mucositis. In conclusion, ecstasy use may be associated with the development of oral ulcers, which should be considered in the differential diagnosis when assessing multifocal oral ulcerations, especially in young people.

With immune therapies on the rise, an in-depth understanding of the immunological changes in leukemic bone marrow (BM) niches becomes indispensable. Being an crucial part of the tumor microenvironment (TME) in solid tumours, tumour-associated macrophages are often associated with poor prognosis (Bruni et al. 2020). Yet, in acute myeloid leukaemia (AML) the role of macrophages has not been thoroughly studied. The expression of the M2-markers CD163 and CD206 in the AML BM cell population predicted poor clinical outcome. We identified that this expression emerges from a more mature (CD45 midSSC highHLA-DR +CD14 +CD16 +/-) myeloid cell population (hereafter called AML-associated macrophages - AAM) and not from the leukemic blasts. By employing flow cytometry analysis (FACS) we noted a decrease in the expression of the M1-marker (CD80) and an increase of the M2-markers CD163/CD206on AAM (n=70) compared to healthy donors (HD, n=10). Unsupervised clustering based on the CD163/CD206 levels detected on AAM generated 4 distinct clusters, whereby patients within the CD163 low/CD206 low cluster displayed better overall survival than the other clusters. In vitro, the co-culture of HD-derived M1 macrophages and AML primary/cell lines reduced AML growth via apoptosis induction and cell cycle arrest, while M2-macrophages promoted AML survival and phagocytosis/drug-resistance when treated with FLT3/BCL2 inhibitors. Primary AML cells were also able to repolarize M1- into M2-macrophages, suggesting that leukemic cells actively remodel their microenvironment. Next, we evaluated the impact of M2-macrophages on leukemogenesis in a patient derived xenograft (PDX) model, using the notoriously difficult to engraft primary Acute Promyelocytic Leukaemia (APL) cells (n=7 patient samples). Intra-BM injection of M2-macrophages and retro-orbital transplant of primary APL cells induced full-blown APL in NSGS mice. More strikingly, ex vivo culture of APL cells on M2-macrophages (48h) was sufficient to "train" these cells to engraft and induce fatal APL. Maintenance of self-renewal was shown in a secondary transplant and an enhanced frequency of leukemic stem cells was assessed by in vivo LTC-IC assays. To identify the biological changes acquired by leukemic blasts, we performed RNA sequencing comparing AML/APL samples at diagnosis to cells that were "trained" (48 h) on M2-macrophages or on MS5 mesenchymal BM stromal cells. Gene ontology and gene set enrichment analysis on the genes up-regulated upon M2 co-culture were significantly enriched for cell migration, cell cycle progression and oxidative phosphorylation (OXPHOS) signatures. In line with our RNAseq data, we noted improved in vivo homing of primary APL cells to the BM within 18 h post-transplant upon ex vivo M2 co-culture compared to diagnosis (n=7 APL blasts). Concurrently, we detected increased levels of surface protein expression Integrin-α4 (CD49d) and -α5 (CD49e) on APL/AML blast cells after M2 exposure. The CD49d expression remained high in primary and secondary transplants. Using seahorse measurements, we confirmed the increased respiration capacity (basal and maximum) of primary AML/APL cells (n=7) after exposure to M2 macrophages compared to MS5.FACS analysis revealed that M2-macrophages were able to transfer more mitochondria than MS5 cells to primary AML cells, which could underlie the observed increase in OXPHOS mitochondrial metabolism. Treatment with Etomoxir (50 µM), prevented the gain in functional respiration when AML blast were co-cultured on M2-macrophages, while no changes were observed for MS5 co-cultures, suggesting increased fatty acid oxidation to drive the OXPHO-like state. Finally, we noted that training on M2 macrophages significantly increased colony formation and endowed the cells with long term proliferation in liquid cultures for over 30 days. Overall, we reveal that the frequency of M2-macrophages is up-regulated in a subgroup of AML patients representing a group with poor prognosis. M2 macrophages can support leukemic growth and therapy-resistance, and support fatal APL in PDX models. Even an in vitro exposure to M2 macrophages suffices to alter adhesion, homing and metabolic characteristics of leukemic blasts to allow efficient engraftment and fatal leukemogenesis. Our study uncovers how the TME can contribute to leukemic transformation which provides alternative avenues for therapeutic interventions. Disclosures Silveira: BMS/Celgene: Research Funding; Servier/Agios: Research Funding; Abbvie: Speakers Bureau; Astellas: Speakers Bureau. Quek: BMS/Celgene: Research Funding; Servier/Agios: Research Funding. Mota: Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Astellas: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Technopharma: Speakers Bureau; Bristol Myer Squibb: Speakers Bureau; Bayer: Speakers Bureau; Pfizer: Speakers Bureau; AstraZeneca: Speakers Bureau; Astellas: Speakers Bureau; Ipsen: Speakers Bureau; Amgen: Speakers Bureau.

Hypophosphatemic rickets is a rare genetic disorder involving the regulation of fibroblast growth factor 23 (FGF23), a phosphaturic agent, clinically showing bowing of the legs, short stature and dentoalveolar abscesses. A 7-year-old boy, with previous hypochondroplasia diagnosis, was referred to our pediatric dentistry clinic presenting short stature, bone deformities and sinus tracts at deciduous teeth apex levels not related with trauma, restorations or dental caries. After deciduous teeth extraction, due to root resorption and mobility, light microscopy exhibited typical hypophosphatemic dentin, and micro-computed tomography revealed tubular clefts and porosities throughout the teeth. Laboratory tests confirmed the HR diagnosis, after which the treatment was initiated.

Made available in DSpace on 2018-12-11T17:13:43Z (GMT). No. of bitstreams: 0 Previous issue date: 2018-03-01 Multiple salivary gland tumors (MSGTs) are most common in the major than minor salivary glands. The most MSGTs are synchronous, either benign or malignant. A 61-year-old woman was referred presenting nine submucosal nodules, firm to fluctuant, being five nodules on the right side and four nodules on the left side of the upper lip. An incisional biopsy was performed. Hematoxylin and eosin staining was performed in 5-µm sections for histopathologic analysis. Immunohistochemical reactions were carried out in 3-µm sections in accordance with manufacturer’s instructions. The histopathological analysis showed focal area containing low-grade polymorphous adenocarcinoma (PAC) and multiple canalicular adenomas (CAs). Immunohistochemical analysis for each lesion was carefully investigated. Here, we present an unusual case of synchronous PAC and multiple CAs of the minor salivary glands, affecting the upper lip, which appears to be the first case showing PAC and CA. Oral Medicine Department of Diagnosis and Surgery Araraquara Dental School Universidade Estadual Paulista (UNESP) Director of Centro Clínico de Cabeza y Cuello Oral Pathology Department of Stomatology Public Oral Health and Forensic Dentistry School of Dentistry of Ribeirao Preto University of Sao Paulo (USP) Oral Medicine Federal University of Juiz de Fora - UFJF/GV, Rua Israel Pinheiro, 2.000, Bairro Universitário Oral Medicine Department of Diagnosis and Surgery Araraquara Dental School Universidade Estadual Paulista (UNESP)

Adenomatoid hyperplasia of the minor salivary glands is an uncommon benign proliferation of mucous glandular tissue. This lesion may clinically resemble a neoplasm of salivary gland origin. We present a case of an adenomatoid hyperplasia of minor salivary glands on the palate. A 42-year-old female patient was referred after presenting with a painless swelling of approximately 1.5 cm diameter in the left side of the hard palate. An excisional biopsy was performed. Microscopically, the specimen presented several lobules of minor salivary gland, all almost constituted by mucinous acini. At the periphery, hyperkeratotic stratified squamous epithelium lining, with mild chronic inflammation in the underlying connective tissue, was observed. The patient continues to be observed, and there has been no evidence of recurrence after 6 months’ of follow up. The adenomatoid hyperplasia pathogenesis remains unknown; however, clinicians should be aware of this condition, which may mimic a salivary gland neoplasm.

Lymphoblastic lymphoma (LBL) is a malignant neoplasia that originates from B or T lymphocyte precursors and comprises approximately 2% of all non-Hodgkin lymphoma cases. Maxillofacial region involvement by LBL is rare. We report a case of a 14-year-old female patient who was referred after complaining of pain, bleeding, and swelling on the right side of the maxilla. Computed tomography showed a solid mass over the entire region, reaching the maxillary sinus and nasal cavity. An incisional biopsy was performed, which revealed large areas of lymphoid proliferation containing small- to medium-sized immature-appearing cells with scarce cytoplasm. Immunohistochemical analysis was positive for PAX5, CD79 a, TdT, CD10, Bcl-2, Bcl-6, and MUM-1; Ki-67 labeling index >96%. EBER 1/2 was negative. The patient was referred to hematologic and oncology service, but unfortunately died after starting chemotherapy. In conclusion, LBL, although rare, should be included in the differential diagnosis of maxillary osteolytic, expansive lesions, especially in pediatric patients.

Objective: To evaluate the immunoprofile differences between regulatory (Tregs) and cytotoxic (CTL) T lymphocytes in oral squamous cell carcinoma (OSCC) affecting young and elderly patients. Study Design: OSCC samples from 12 patients (aged

Epidermoid cysts (ECs) are rare and occur in the head and neck region with an incidence from 1.6% to 7%. In the oral cavity, EC represents less than 0.01% of all cysts. To date, approximately 80 EC cases have been reported. We report a case of a 26-year-old man who developed a large EC in the midline floor of the mouth, leading to speech and swallowing difficulties and causing swelling in the submental region. Ultrasonography and fine needle aspiration confirmed the cystic nature of the lesion. The lesion was surgically excised by intraoral approach, and microscopically revealed an EC associated with extensive elastofibromatous changes in the cystic capsule. The pathogenesis of the abnormal deposition of elastic fibers is unknown; however, degenerative phenomenon, disturbed production, genetic predisposition, or trauma have been considered. To the best of our knowledge, this is the first report of elastofibromatous changes in an intraoral EC.

Plasma cell cheilitis (PCC) is an unusual benign plasma cell proliferative disease of an unknown etiology that clinically presents as erythematous-violaceous plaques, ulcerations, or eruptions often affecting the lower lip. PCC is known to respond poorly to corticosteroid treatment. A 43-year-old male presented with multiple painful hemorrhagic crusts on the lower lip that had developed over 1 month. An incisional biopsy was performed and microscopy showed a bandlike inflammatory cell infiltration composed mainly of plasma cells in the connective tissue. Immunohistochemistry confirmed a reactive nature of plasma cells. Thus, the diagnosis of PCC was established. Initially, the patient was treated with topical corticosteroids over 1 month, but had a relapse 3 months after complete remission. Then, we proposed the use of topical corticosteroids with cryotherapy. No recurrence was observed after 8 months of follow-up. In conclusion, cryotherapy associated with topical corticosteroids appears to be a successful option to control the relapses of PCC.

Background Localized juvenile spongiotic gingival hyperplasia (LJSGH) is a distinct subtype of inflammatory gingival hyperplasia that shows lack of response to traditional periodontal treatment, and after surgical excision, recurrence rate of 6–16% has been reported. Case Report Two girls (11- and 9-year-old) with multifocal red patches along the maxillary and mandibular labial gingiva showed no regression of the lesions after basic periodontal treatment. Surgical excision of focal lesion in each case was performed, which showed typical features of LJSGH. In both cases, the lesions presented recurrence. Hence, cryotherapy sessions in all lesions were performed. Conclusion Cryotherapy appears to be successfully in LJSGH and well received by paediatric patients.

Fatty acid synthase (FASN), the multifunctional enzyme responsible for endogenous fatty acid synthesis, is highly expressed and associated with poor prognosis in several human cancers, including melanoma. Our group has previously shown that pharmacological inhibition of FASN with orlistat decreases proliferation, promotes apoptosis, and reduces the metastatic spread of B16-F10 cells in experimental models of melanoma. While most of the orlistat antitumor properties seem to be closely related to direct effects on malignant cells, its impact on the host immune system is still unknown. The effects of orlistat on the phenotype and activation status of infiltrating leukocytes in primary tumors and metastatic lymph nodes were assessed using a model of spontaneous melanoma metastasis (B16-F10 cells/C57BL/6 mice). Cells from the primary tumors and lymph nodes were mechanically dissociated and immune cells phenotyped by flow cytometry. The expression of IL-12p35, IL-12p40, and inducible nitric oxide synthase (iNOS) was analyzed by qRT-PCR and production of nitrite (NO2−) evaluated in serum samples with the Griess method. Orlistat-treated mice exhibited a 25% reduction in the number of mediastinal lymph node metastases (mean 3.96 ± 0.78, 95% CI 3.63–4.28) compared to the controls (mean 5.7 ± 1.72; 95% CI 5.01–6.43). The drug elicited an antitumor immune response against experimental melanomas by increasing maturation of intratumoral dendritic cells (DC), stimulating the expression of cytotoxicity markers in CD8 T lymphocytes and natural killer (NK) cells, as well as reducing regulatory T cells (Tregs). Moreover, the orlistat-treatment increased serum levels of nitric oxide (NO) concentrations. Taken together, these findings suggest that orlistat supports an antitumor response against experimental melanomas by increasing CD80/CD81-positive and IL-12-positive DC populations, granzyme b/NKG2D-positive NK populations, and perforin/granzyme b-positive CD8 T lymphocytes as well as reducing Tregs counts within experimental melanomas.

The low-fat and fat-free spindle cell lipomas (SCLs) are rare and often mistaken for other benign and malignant morphological mimics, because of the fact that the diagnosis relies on its non-lipogenic component analysis. Here, we report the clinicopathological features of two oral SCLs (low-fat and fat-free variants). Both lesions presented clinically as an asymptomatic nodule, which initially yielded diagnostic difficulties on the morphological analysis alone. One case was diagnosed as low-fat SCL on the lower lip in a 29-year-old man, and the other as fat-free SCL on the buccal mucosa in a 46-year-old man. In both cases, immunohistochemistry showed strong positivity for CD34 and, remarkably, retinoblastoma (Rb) protein was deficient. Mast cell (MC) tryptase and toluidine blue stain highlighted numerous MCs distributed throughout all tumor stroma. Alpha-SMA and desmin were negative. S100 evidenced scarce adipocytes only in the low-fat SCL case. Conservative surgical treatment was performed and no recurrence was noticed in about 2-year of follow-up in both cases. Because of the potential pitfalls, careful morphological analysis of the tumor stroma in the low-fat/fat-free SCL diagnosis, supported by immunohistochemistry (especially CD34, Rb and MC tryptase), is strongly recommended. To the best of our knowledge, these are the first and second cases reported of fat-free and low-fat SCL in the oral cavity.

Made available in DSpace on 2019-10-06T16:34:04Z (GMT). No. of bitstreams: 0 Previous issue date: 2019-01-01 Introduction: Epidermoid cysts (ECs) are rare and occur in the head and neck regions with an incidence from 1.6 to 7% of all cysts. In the oral cavity, approximately 80 ECs have been reported, representing less than 0.01% of all cysts. Case report: We report a case of a 26-year-old man who developed a large EC in the midline floor of the mouth causing nodular swelling in the submental region and speech and swallowing difficulties. The lesion was surgically excised by intraoral approach and microscopically revealed an EC associated with extensive elastofibromatous changes in the cystic capsule. Conclusion: Oral EC with extensive elastofibromatous changes is a finding extremely rare. The meaning of this finding is unknown, but a traumatic origin or deposit disorder of elastic fibers is suggested. To the best of our knowledge, intraoral EC with elastofibromatous changes has not been reported to date. Oral Medicine Department of Diagnosis and Surgery Araraquara Dental School São Paulo State University (UNESP) Department of Pathology and Forensic Medicine Ribeirão Preto Medical School (FMRP/USP) University of São Paulo Universidade Vale do Rio Verde (UninCor) Oral Pathology Department of Stomatology Public Oral Health and Forensic Dentistry Ribeirão Preto Dental School University of São Paulo (FORP/USP) Oral Medicine Department of Diagnosis and Surgery Araraquara Dental School São Paulo State University (UNESP)

Background M2 macrophages are often detected in oral squamous cell carcinoma (OSCC), which, influenced by hypoxic conditions, appear to have high angiogenesis-inducing capacity. However, the effects of immunosenescence on tumor-associated macrophages (TAMs) and angiogenesis in OSCC are unknown. Methods Fifty-seven OSCCs were divided into 3 groups (I: 65 years [n = 20]). Immunohistochemistry for CD68 and CD163 (TAMs), and CD34 and D2-40 for microvessel density (MVD), microvessel area (MVA), and total vascular area (TVA) were performed. Results All groups showed similar clinicopathological and immunohistochemical findings. Similar CD68 and CD163 expression, confirmed a M2 phenotype. MVD, MVA, and TVA were similar, however, with significant predominance of blood vessels. No significant correlation between macrophage and angiogenic markers was observed. Conclusions A similar TAM and angiogenesis profile suggests the participation of other mechanisms, instead immunosenescence, in young and elderly OSCC patients.

Made available in DSpace on 2021-06-25T11:11:05Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-04-01 Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) 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 n = 14) or absence (OIFHNL n = 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 (p = 0.015). The prevailing reticular pattern observed was CD207high for OLP (p = 0.0329). A statistically significant difference in the expression of CD1a and CD207 was observed for intraepithelial vs subepithelial areas (p = 0.024 and p=0.015, for CD1a and CD207, respectively). Significant correlations were also observed between the expression of CD1a + 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, CD1a + and CD207+ cells appear to be more essential to immunopathogenesis of OLL than to the pathogenesis of OLP. Oral Medicine Department of Diagnosis and Surgery São Paulo State University (UNESP) School of Dentistry Department of Orthodontics and Pediatric Dentistry São Paulo State University (UNESP) School of Dentistry Department of Pathology and Forensic Medicine Ribeirão Preto Medical Scholl (FMRP/USP) University of São Paulo Oral Pathology Department of Stomatology Public Oral Health and Forensic Dentistry Ribeirão Preto Dental School (FORP/USP) University of São Paulo, Avenida do Café, S/N Oral Medicine Department of Diagnosis and Surgery São Paulo State University (UNESP) School of Dentistry Department of Orthodontics and Pediatric Dentistry São Paulo State University (UNESP) School of Dentistry FAPESP: 2016/11419-0 FAPESP: 2017/01438-0

Spindle cell lipoma (SCL) and pleomorphic lipoma constitute a spectrum of lipomatous lesions with distinctive clinicopathological features. Multiple variants of SCL have been reported including fibrous, plexiform, vascular, pseudoangiomatous, low-fat/fat-free, and myxoid changes. This paper describes an unusual patient with a 1-cm submucosal nodular lesion excised from the buccal mucosa of a 55-year-old woman with classic histopathological and immunohistochemical features of "low-fat" plexiform SCL with prominent myxoid stroma, which initially suggested a soft-tissue myxomatous lesion other than SCL. The current lesion exhibited microscopically few adipocytes supported by network-like myxoid proliferations with retraction artifacts from the surrounding stromal connective tissue. Immunohistochemistry was positive for vimentin, CD34, CD10, and S100, the latter only on adipocytes. The Ki-67 was

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.

Polymorphous adenocarcinoma (PAC) represents the second most common malignancy of the minor salivary glands. Uncommonly, intratumoral crystalloid deposits may be visualized in PAC. The main types include tyrosine-rich, collagenous, and amylase crystalloids. Here, we reported a case of a 49-year-old black female who was referred complaining of swelling on the hard palate. Clinically, a nodular lesion was observed measuring 4 cm in greater diameter, well-delimited, asymptomatic, and covered by normal-appearing oral mucosa, with time of evolution of 2 years. After incisional biopsy, microscopic examination revealed low-grade PAC containing foci of tyrosine-rich crystalloid deposits. Immunohistochemical analysis revealed positivity for CK AE1/3, CK7, vimentin, α-smooth muscle actin, and Bcl-2, S100, and focally for p53, GFAP, and CD10. The patient was referred to a reference service for treatment, and there has been no evidence of recurrence after 8 months’ of follow-up.

Squamous cell carcinoma (SCC) is the most frequent malignant neoplasm of the oral cavity. SCC presents several histologic variants, such as clear cell, signet-ring, basaloid, desmoplastic, verrucous, cuniculatum, lymphoepithelial, and pigmented. This latter is a rare variant of oral SCC. We present a case of pigmented oral SCC, emphasizing its differential diagnosis. A 60-year-old male patient was referred presenting with a nodular lesion, reddish coloration, 3 cm in diameter, asymptomatic, and arising from the lateral border of the tongue. Microscopically, typical SCC was revealed, and in addition to the tumor cells, dendritic cells with dark intrinsic pigments were found surrounding the tumor cells. The pigments were negative for Ziehl-Neelsen and periodic-acid Schiff stains, and positive for Fontana-Masson stain. To date, only 16 cases of pigmented oral SCC have been reported, with variable clinical presentation despite detection of melanin in these tumors.

Oral focal mucinosis (OFM) is a rare connective tissue disorder characterized by myxoid degeneration due to the overproduction of hyaluronic acid. Sometimes, other mesenchymal lesions with myxoid differentiation may create diagnostic difficulties when assessing OFM. Here, we report a case of gingival OFM. A 58-year-old woman presented in our service complaining of a painless gingival lesion 10 months ago. Intra-oral examination revealed a nodular, sessile and smooth surface lesion, located in the buccal gingiva, at level of the teeth #22 and #24. An excisional biopsy was performed, and microscopic analysis showed a well-defined, nonencapsulated area of myxomatous connective tissue surrounded by collagenous connective tissue. Alcian blue stain was positive. Immunohistochemical analysis revealed positivity only for vimentin and α-smooth muscle actin. The final diagnosis was OFM. The lesion did not present recurrence after 4 months’ of follow-up. OFM should be included in the differential diagnosis of gingival nodular lesions.