RESUMO
Syphilis can mimic, clinically and microscopically, many other diseases. By microscopy, typically syphilis presents with plasma cell infiltration, admixed with lymphocytes and macrophages, in lichenoid and/or perivascular/perineural distribution pattern. When exuberant, this inflammatory infiltrate can mimic a lymphoproliferative disorder (LPD), notably plasma cell neoplasia or lymphoma. To date, about 12 cases of secondary syphilis, all but one in extraoral location, suggesting initially a LPD, have been published. Here, to our knowledge, we report an unusual case of intraoral primary syphilis initially suggesting LPD, notably lymphoid hyperplasia (pseudolymphoma); however, mucosa-associated lymphoid tissue (MALT) lymphoma and follicular lymphoma could not be disregarded. Polyclonality of plasma cells on immunohistochemistry, in strict clinical correlation, was essential to arrive at the correct diagnosis.
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Linfoma de Zona Marginal Tipo Células B , Transtornos Linfoproliferativos , Sífilis , Humanos , Sífilis/diagnóstico , Sífilis/patologia , Transtornos Linfoproliferativos/diagnóstico , Transtornos Linfoproliferativos/patologia , Linfoma de Zona Marginal Tipo Células B/patologia , Linfócitos/patologia , Diagnóstico DiferencialRESUMO
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
ABSTRACT: Lymphomatoid papulosis (LyP) belongs to the spectrum of primary cutaneous CD30 + lymphoproliferative disorders, characterized by chronic, recurrent, self-healing papules, small nodules, or ulcers. The clinicopathological features of LyP can mimic overt lymphomas. To date, about 27 intraoral LyP cases have been reported. Of them, only 2 cases were diagnosed as angioinvasive LyP (type E). Herein, we report a 24-year-old Brazilian man who presented a large ulcerated lesion on the hard palate with rapid evolution. Remarkably, there was no involvement of the skin or other mucous membranes. Microscopy revealed a lymphoid infiltrate constituted by medium-sized to large atypical cells, with angiocentric and angiodestructive features. The atypical cells showed immunopositivity for CD3, CD8, CD30, CD56, granzyme B, perforin, and focally for MUM1/IRF4. Ki-67 highlighted almost all atypical lymphoid cells, whereas EBER1/2 was negative. After 2 months of follow-up, the lesion healed completely. Although rare, LyP type E should be included in the differential diagnosis of oral ulcers.
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Papulose Linfomatoide , Neoplasias Cutâneas , Masculino , Humanos , Adulto Jovem , Adulto , Papulose Linfomatoide/patologia , Neoplasias Cutâneas/patologia , Pele/patologia , Diagnóstico Diferencial , Palato/patologiaRESUMO
OBJECTIVES: To assess the influence of estrogen deficiency on tooth eruption rate (TER) and gene expression of estrogen receptor alpha and beta (ERα and ERß) in the odontogenic region of teeth with continuous formation in a rat model. MATERIALS AND METHODS: Ovariectomies (OVX; n = 25) and sham surgeries (SHAM; n = 25) were performed in female Wistar rats when animals were 25 days old. The TER of the lower incisors, both in impeded (hyperfunction condition) and unimpeded (trimmed incisal edge-hypofunction condition) conditions, was evaluated using standardized digital photographs acquired every 48-72 h for 3 weeks (35th-53rd day of life), using a camera coupled to a stereomicroscope. Quantitative real-time PCR was performed to evaluate the relative gene expression of ERα and ERß in the odontogenic region. RESULTS: The OVX group showed a significant reduction in TER when compared to the SHAM group, only in the impeded condition (p = 0.03). There was no statistically significant difference between the groups in ERα gene expression (p = 0.33). ERß showed a significantly higher gene expression in the OVX group (p ≤ 0.05). CONCLUSIONS: Estrogen deficiency decreases TER in teeth under impeded condition. Estrogen deficiency also increases ERß gene expression in the odontogenic region of teeth with continuous formation. CLINICAL RELEVANCE: Hormonal disturbances affecting estrogen levels can cause alterations in dental formation and teeth eruption.
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Anormalidades Dentárias , Erupção Dentária , Ratos , Animais , Feminino , Humanos , Erupção Dentária/fisiologia , Ratos Wistar , Receptor alfa de Estrogênio , Incisivo , Receptor beta de Estrogênio/genética , Estrogênios , Receptores de Estrogênio , OvariectomiaRESUMO
This study aimed to evaluate the density of the dendritic cells (DCs) and macrophages in oral leukoplakia (OL) and proliferative verrucous leukoplakia (PVL) by immunohistochemical analysis. We analysed paraffined tissue samples of PVL (n = 27), OL (n = 20), and inflammatory fibrous hyperplasia (n = 20) as the control group using the immunomarkers for DCs (CD1a, CD207, CD83, CD208 and CD123) and macrophages (CD68, CD163, FXIIIa and CD209). A quantitative analysis of positive cells in the epithelial and subepithelial areas was determined. Our results showed a reduction in CD208+ cells in the subepithelial area of the OL and PVL compared to the control. Additionally, we found a higher density of FXIIIa+ and CD163+ cells in the subepithelial area in PVL compared to the OL and control. Four-way MANOVA revealed a relationship between increased CD123+ cell density in the subepithelial area of "high-risk" samples regardless of disease. Macrophages provide the first line of defence against PVL antigens, suggesting a distinct pattern of innate immune system activation in PVL compared to OL, which may contribute to the complexity and the high rate of malignant transformation in the PVL.
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Fator XIIIa , Neoplasias Bucais , Humanos , Neoplasias Bucais/patologia , Subunidade alfa de Receptor de Interleucina-3 , Leucoplasia Oral , Macrófagos/patologia , Transformação Celular Neoplásica/patologiaRESUMO
The primary cutaneous (PC) CD8+ T-cell lymphoproliferative disorders (LPDs) comprise clinically and histopathologically heterogeneous entities including mycosis fungoides, lymphomatoid papulosis, hydroa-vacciniforme-like LPD, subcutaneous panniculitis-like T-cell lymphoma (TCL), PC acral CD8+ TCL, PC CD8+ aggressive epidermotropic cytotoxic TCL, and PC peripheral TCL, not otherwise specified (PTCL-NOS). We describe a 33-year-old man who presented with progressive facial swelling and lower lip involvement 1 year ago. Microscopy revealed an atypical small to medium-sized lymphoid proliferation exhibiting perivascular accentuation, adnexotropism, and apoptotic cell debris, without surface epithelium involvement. The tumor cells were positive for CD3, CD8, granzyme B, perforin, MUM1/IRF4, and TCR-BF1. The Ki-67 labeling index was 48%. EBER1/2 was negative. Additional studies confirmed localized disease. The diagnosis favored PC-PTCL-NOS. Two months after completing chemotherapy, right-sided facial nerve palsy was diagnosed. CD8+ T-cell LPDs should be considered in the differential diagnosis when assessing facial swelling with intraoral involvement.
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Antineoplásicos , Linfoma Cutâneo de Células T , Papulose Linfomatoide , Neoplasias Cutâneas , Adulto , Antineoplásicos/uso terapêutico , Linfócitos T CD8-Positivos/patologia , Nervo Facial/metabolismo , Nervo Facial/patologia , Humanos , Imuno-Histoquímica , Linfoma Cutâneo de Células T/patologia , Papulose Linfomatoide/patologia , Masculino , Paralisia/tratamento farmacológico , Neoplasias Cutâneas/patologiaRESUMO
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
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.
Assuntos
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/imunologiaAssuntos
Hemangioma , Lesões Pré-Cancerosas , Dermatopatias , Neoplasias Cutâneas , Humanos , HiperplasiaRESUMO
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.
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Drogas Ilícitas/efeitos adversos , Mucosa Bucal/efeitos dos fármacos , N-Metil-3,4-Metilenodioxianfetamina/efeitos adversos , Úlceras Orais/induzido quimicamente , Estomatite/induzido quimicamente , Doenças da Língua/induzido quimicamente , Administração Oral , Adulto , Dor Facial/induzido quimicamente , Feminino , Alucinógenos/efeitos adversos , Humanos , Adulto JovemAssuntos
Mucosa Bucal , Boca , Humanos , Hiperplasia/patologia , Boca/patologia , Mucosa Bucal/patologia , FibroseRESUMO
Proliferative verrucous leukoplakia (PVL) is a non-homogenous type of oral leukoplakia, characterized by multifocal white plaques, propensity to recur after treatment, with strong tendency towards malignant transformation. Interestingly, some studies show that, at initial stages, PVL may resemble oral lichen planus (OLP), potentially leading to misdiagnosis. A 52-year-old woman, with a previous OLP diagnosis, was referred to our service for implant installation and follow-up of OLP lesions. After clinicopathological re-evaluation, a diagnosis of PVL (early stage) was made, and a maxillary full-arch implant-supported prosthesis supported by implants was installed. After 6 years of follow-up, the patient developed squamous cell carcinoma around the implants. The current case emphasizes that PVL patients with oral lesions suggesting peri-implantitis or peri-implant mucositis deserve a more meticulous investigation.
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Prótese Dentária Fixada por Implante , Leucoplasia Oral , Líquen Plano Bucal , Humanos , Feminino , Pessoa de Meia-Idade , Líquen Plano Bucal/diagnóstico , Líquen Plano Bucal/patologia , Leucoplasia Oral/diagnóstico , Leucoplasia Oral/patologia , Diagnóstico Diferencial , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/diagnóstico , Progressão da Doença , Peri-Implantite/diagnóstico , SeguimentosRESUMO
BACKGROUND: Previous studies have shown that at least a of intraoral eosinophilic ulcer is best classified as a CD30 + T-cell lymphoproliferative disorder (LPD), with histopathology reminiscent of lymphomatoid papulosis (LyP) of the skin. Microscopically, a mixed population of inflammatory cells, often including eosinophils and varying numbers of atypical lymphoid cells, frequently expressing CD30, is typical for LyP, whose clinicopathological spectrum includes type A, B, C, D, E, and LyP with DUSP22/IRF4 rearrangement. To date, about 27 intraoral LyP cases have been reported. Of them, 7 cases were diagnosed as LyP type C, which is frequently confused with anaplastic large cell lymphoma (ALCL) on histopathology. METHODS: A 60-year-old male was referred for a one-month history of a tongue ulcer. RESULTS: Microscopy showed numerous subepithelial atypical large lymphoid cells, which expressed CD4 (with partial loss of CD3, CD5, and CD7), CD8 (few cells), CD30 (about 50%, in non-diffuse pattern with size variability), TIA-1, and Ki-67 (85%), without staining for CD56, ALK, LMP1, and EBER1/2, concerning for a diagnosis of ALCL. However, after three weeks, the lesion completely healed. CONCLUSION: We present here a rare case of intraoral CD30+ T-cell LPD that we believe is the oral counterpart of cutaneous LyP type C.
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Antígeno Ki-1 , Papulose Linfomatoide , Humanos , Masculino , Pessoa de Meia-Idade , Biomarcadores Tumorais/análise , Diagnóstico Diferencial , Imuno-Histoquímica , Antígeno Ki-1/metabolismo , Papulose Linfomatoide/patologia , Papulose Linfomatoide/diagnóstico , Transtornos Linfoproliferativos/patologia , Transtornos Linfoproliferativos/diagnóstico , Linfócitos T/patologiaRESUMO
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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Actinomycosis is an uncommon, subacute to chronic, suppurative bacterial infection caused by Actinomyces Israelii. About 3% of all actinomycosis cases occur in the tongue, often affecting adult patients (mean age, 50 years). The clinical characteristics of actinomycosis can resemble malignant or benign tumors, and other infectious diseases. A 56-year-old woman was referred presenting an ulcerated lesion on the tongue 1 year ago. Intraoral examination revealed an edematous nodular lesion with an ulcerated surface, slightly symptomatic, on the midline dorsum of posterior tongue, suggesting nodular median rhomboid glossitis. Cytology smear was negative for fungus. After excisional biopsy, histopathological examination showed a chronic inflammatory infiltrate supported by a fibrovascular connective tissue stroma, and at the deepest part, broad basophilic areas surrounded by neutrophils, containing numerous filamentous bacilli, which were highlighted by Gram and Groccott-Gomori staining. The final diagnosis was lingual actinomycosis. Oral amoxicillin treatment (8/8 h for 2 weeks) was started, and after 1-month complete resolution was observed. Lingual actinomycosis is a rare lesion that must be recognized by dentists, because its early diagnosis and correct treatment reduce the possibility of a clinical complication that compromises the patient's quality of life. Noteworthy, when located on the midline dorsum of posterior tongue, actinomycosis can simulate nodular median rhomboid glossitis, expanding its spectrum of clinical differential diagnosis.
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Granular cell tumor (GCT) is an uncommon benign neoplasm derived from Schwann cells, frequently affecting the oral cavity, skin, and gastrointestinal tract. On microscopy, pseudocarcinomatous squamous hyperplasia (PSH) and perineural involvement are potential diagnostic pitfalls. GCT should be differentiated from non-neural GCT (NN-GCT). A 13-year-old male patient was referred presenting a nodular lesion on the upper lip several months ago. After excisional biopsy, microscopy revealed GCT without PSH but presenting multifocal perineural involvement. By immunohistochemistry, ALK was negative, whereas Rb and INI1 expression was intact. Moreover, with few intraoral NN-GCTs being assessed, recent studies suggest that acquired dermal NN-GCT subgroup seems to correspond to ALK-rearranged variants of epithelioid fibrous histiocytoma. Accordingly, further research on this topic is strongly encouraged.
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Necrotizing sialometaplasia (NS) is a rare, self-limiting, necrotizing inflammatory lesion, often involving the minor salivary glands of the palate. NS occurs often in men (60%) older than 45 years. Commonly, it presents as an ulcerative lesion, measuring 1 to 3 cm in diameter, with an evolution time of a few weeks or days, simulating malignancy. However, in some instances, the mucosal surface is intact, thus emphasizing the importance of considering NS in the differential diagnosis of oral ulcerative and non-ulcerative lesions. To date, 12 cases of non-ulcerated NS in the palate have been reported. Here, we report a 50-year-old male patient who presented a non-ulcerated, asymptomatic, nodular swelling 3 months ago, located on the hard palate, clinically suggesting salivary gland tumor or lymphoproliferative disorder. After biopsy, a diagnosis of non-ulcerated NS was established. After 4 weeks, the lesion evolved with complete resolution. After literature review, notably, unlike ulcerated NS, the non-ulcerated NS affected patients a decade younger (33 years vs. 45 years), with marked female predilection (83% vs. 40%) and not uncommon bilateral presentation (33% vs. 10%). NS should be considered in the differential diagnosis of ulcerative and non-ulcerative lesions affecting the palate.