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The study evaluated the regenerative responses of the lacrimal functional unit (LFU) after lacrimal gland (LG) ablation. The LG of Wistar rats was submitted to G1) partial LG ablation, G2) partial ablation and transplantation of an allogeneic LG, or G3) total LG ablation, (n = 7-10/group). The eye wipe test, slit lamp image, tear flow, and histology were evaluated. RT-PCR analyzed inflammatory and proliferation mediators. The findings were compared to naïve controls after 1 and 2 months (M1 and M2). G3 presented increased corneal sensitivity, and the 3 groups showed corneal neovascularization. Histology revealed changes in the LG and corneal inflammation. In the LG, there was an increase in MMP-9 mRNA of G1 and G2 at M1 and M2, in RUNX-1 at M1 and M2 in G1, in RUNX-3 mRNA at M1 in G1, and at M2 in G2. TNF-α mRNA rose in the corneas of G1 and G2 at M2. There was an increase in the IL-1ß mRNA in the trigeminal ganglion of G1 at M1. Without changes in tear flow or evidence of LG regeneration, LG ablation and grafting are unreliable models for dry eye or LG repair in rats. The surgical manipulation extended inflammation to the LFU.
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Síndromes de Ojo Seco , Inflamación , Aparato Lagrimal , Ratas Wistar , Regeneración , Animales , Aparato Lagrimal/metabolismo , Aparato Lagrimal/patología , Aparato Lagrimal/cirugía , Síndromes de Ojo Seco/metabolismo , Síndromes de Ojo Seco/etiología , Síndromes de Ojo Seco/patología , Ratas , Inflamación/patología , Inflamación/metabolismo , Masculino , Córnea/metabolismo , Córnea/patología , Lágrimas/metabolismo , Metaloproteinasa 9 de la Matriz/metabolismo , Metaloproteinasa 9 de la Matriz/genética , Factor de Necrosis Tumoral alfa/metabolismo , Factor de Necrosis Tumoral alfa/genética , Interleucina-1beta/metabolismo , Interleucina-1beta/genética , Modelos Animales de EnfermedadRESUMEN
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 , Papulosis Linfomatoide , Humanos , Masculino , Persona de Mediana Edad , Biomarcadores de Tumor/análisis , Diagnóstico Diferencial , Inmunohistoquímica , Antígeno Ki-1/metabolismo , Papulosis Linfomatoide/patología , Papulosis Linfomatoide/diagnóstico , Trastornos Linfoproliferativos/patología , Trastornos Linfoproliferativos/diagnóstico , Linfocitos T/patologíaRESUMEN
An 88-year-old male patient presented with a large mass on the left lateral bulbar conjunctiva. The tumor appeared two months after the resection of a conjunctival atypical fibroxanthoma (AFX) performed by a cornea specialist. Magnetic resonance imaging of the orbits showed deep orbital invasion along the lateral rectus muscle. The mass and the entire conjunctival sac were totally excised with lid-sparing orbital exenteration. Histopathological analysis confirmed that the mass was an extension of the AFX. Two weeks after surgery, large B-cell lymphoma was diagnosed in the oropharynx. Chemotherapy was initiated, and after seven months of follow-up, there was no recurrence of the AFX. The authors believe that this is the first report of orbital invasion by AFX.
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Vascular anomalies comprise a wide spectrum of clinical manifestations related to disturbances in the blood or lymph vessels. They correspond to mainly tumors (especially hemangiomas), characterized by high mitotic activity and proliferation of the vascular endothelium, and malformations, endowed with normal mitotic activity and no hypercellularity or changes in the rate of cell turnover. However, the classifications of these lesions go beyond this dichotomy and consist various systems adapted for and by different clinical subgroups. Thus, the classifications have not reached a consensus and have historically caused confusion regarding the nomenclatures and definitions. Cavernous venous malformations of the orbit, previously called cavernous hemangiomas, are the most common benign vascular orbital lesions in adults. Herein, we have compiled and discussed the various evidences, including clinical, radiological, morphological, and molecular evidence that indicate the non-neoplastic nature of these lesions.
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Hemangioma Cavernoso , Neoplasias Orbitales , Humanos , Hemangioma Cavernoso/diagnóstico por imagen , Hemangioma Cavernoso/patología , Neoplasias Orbitales/diagnóstico por imagen , Neoplasias Orbitales/patología , Órbita/irrigación sanguínea , Órbita/diagnóstico por imagen , Órbita/patología , Malformaciones Vasculares/diagnóstico por imagen , Malformaciones Vasculares/patologíaRESUMEN
OBJECTIVE: Lysosome-associated membrane protein 3 (LAMP3) misexpression in salivary gland epithelial cells plays a causal role in the development of salivary gland dysfunction and autoimmunity associated with Sjögren's disease (SjD). This study aimed to clarify how epithelial LAMP3 misexpression is induced in SjD. METHODS: To explore upstream signaling pathways associated with LAMP3 expression, we conducted multiple RNA sequencing analyses of minor salivary glands from patients with SjD, submandibular glands from a mouse model of SjD, and salivary gland epithelial cell lines. A hypothesis generated by the RNA sequencing analyses was further tested by in vitro and in vivo assays with gene manipulation. RESULTS: Transcriptome analysis suggested LAMP3 expression was associated with enhanced type I interferon (IFN) and IFNγ signaling pathways in patients with SjD. In vitro studies showed that type I IFN but not IFNγ stimulation could induce LAMP3 expression in salivary gland epithelial cells. Moreover, we discovered that LAMP3 overexpression could induce ectopic Toll-like receptor 7 (TLR-7) expression and type I IFN production in salivary gland epithelial cells both in vitro and in vivo. TLR-7 knockout mice did not develop any SjD-related symptoms following LAMP3 induction. CONCLUSION: Epithelial LAMP3 misexpression can be induced through enhanced type I IFN response in salivary glands. In addition, LAMP3 can promote type I IFN production via ectopic TLR-7 expression in salivary gland epithelial cells. This positive feedback loop can contribute to maintaining LAMP3 misexpression and amplifying type I IFN production in salivary glands, which plays an essential role in the pathophysiology of SjD.
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Células Epiteliales , Interferón Tipo I , Proteínas de Membrana de los Lisosomas , Glándulas Salivales , Síndrome de Sjögren , Receptor Toll-Like 7 , Síndrome de Sjögren/inmunología , Síndrome de Sjögren/genética , Síndrome de Sjögren/metabolismo , Animales , Ratones , Interferón Tipo I/metabolismo , Humanos , Células Epiteliales/metabolismo , Receptor Toll-Like 7/genética , Receptor Toll-Like 7/metabolismo , Glándulas Salivales/metabolismo , Glándulas Salivales/inmunología , Proteínas de Membrana de los Lisosomas/genética , Proteínas de Membrana de los Lisosomas/metabolismo , Transducción de Señal , Femenino , Interferón gamma/metabolismo , Línea Celular , Glándulas Salivales Menores/inmunología , Glándulas Salivales Menores/metabolismo , Proteínas de Neoplasias , Proteína 3 de la Membrana Asociada a LisosomaRESUMEN
Progression to aggressive secondary acute myeloid leukaemia (sAML) poses a significant challenge in the management of myeloproliferative neoplasms (MPNs). Since the physiopathology of MPN is closely linked to the activation of interferon (IFN) signalling and that AML initiation and aggressiveness is driven by leukaemia stem cells (LSCs), we investigated these pathways in MPN to sAML progression. We found that high IFN signalling correlated with low LSC signalling in MPN and AML samples, while MPN progression and AML transformation were characterized by decreased IFN signalling and increased LSC signature. A high LSC to IFN expression ratio in MPN patients was associated with adverse clinical prognosis and higher colony forming potential. Moreover, treatment with hypomethylating agents (HMAs) activates the IFN signalling pathway in MPN cells by inducing a viral mimicry response. This response is characterized by double-stranded RNA (dsRNA) formation and MDA5/RIG-I activation. The HMA-induced IFN response leads to a reduction in LSC signature, resulting in decreased stemness. These findings reveal the frequent evasion of viral mimicry during MPN-to-sAML progression, establish the LSC-to-IFN expression ratio as a progression biomarker, and suggests that HMAs treatment can lead to haematological response in murine models by re-activating dsRNA-associated IFN signalling.
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Leucemia Mieloide Aguda , Trastornos Mieloproliferativos , Humanos , Animales , Ratones , Trastornos Mieloproliferativos/tratamiento farmacológico , Trastornos Mieloproliferativos/genética , Trastornos Mieloproliferativos/complicaciones , Leucemia Mieloide Aguda/tratamiento farmacológico , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/patología , Pronóstico , Biomarcadores , Interferones/uso terapéuticoRESUMEN
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 Células B de la Zona Marginal , Trastornos Linfoproliferativos , Sífilis , Humanos , Sífilis/diagnóstico , Sífilis/patología , Trastornos Linfoproliferativos/diagnóstico , Trastornos Linfoproliferativos/patología , Linfoma de Células B de la Zona Marginal/patología , Linfocitos/patología , Diagnóstico DiferencialRESUMEN
ABSTRACT Vascular anomalies comprise a wide spectrum of clinical manifestations related to disturbances in the blood or lymph vessels. They correspond to mainly tumors (especially hemangiomas), characterized by high mitotic activity and proliferation of the vascular endothelium, and malformations, endowed with normal mitotic activity and no hypercellularity or changes in the rate of cell turnover. However, the classifications of these lesions go beyond this dichotomy and consist various systems adapted for and by different clinical subgroups. Thus, the classifications have not reached a consensus and have historically caused confusion regarding the nomenclatures and definitions. Cavernous venous malformations of the orbit, previously called cavernous hemangiomas, are the most common benign vascular orbital lesions in adults. Herein, we have compiled and discussed the various evidences, including clinical, radiological, morphological, and molecular evidence that indicate the non-neoplastic nature of these lesions.
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BACKGROUND: Psoriasis is a common cutaneous disease; however, information about psoriasis-related oral mucosal lesions is scarce in the literature. CASE DESCRIPTION: We report a case of a 73-year-old male patient with cutaneous and oral palatal alterations. An incisional biopsy of these lesions revealed psoriasis. CONCLUSION: The current case highlights the importance of a systematic examination of the oral cavity in psoriasis patients for the appropriate diagnosis and management on the control of these lesions.
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Mucosa Bucal , Psoriasis , Masculino , Humanos , Anciano , Mucosa Bucal/patología , Psoriasis/complicaciones , Psoriasis/diagnóstico , Psoriasis/patología , Diagnóstico Diferencial , BiopsiaRESUMEN
Congenital opticmeningoceles was the term coined to describe large pseudocystic lesions of the intraorbital segment of the optic nerve. This extremely rare congenital anomaly was reported unilaterally only in nonsyndromic patients with fully developed eyes. The authors describe here a 10-month-old girl with a previous diagnosis of Joubert syndrome who presented with the same type of optic nerve malformation in OU. Molecular genetic analysis disclosed a pathogenic variant of the TMEM67 gene which is associated with various types of ciliopathies.
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Anomalías Múltiples , Anomalías del Ojo , Enfermedades Renales Quísticas , Femenino , Humanos , Lactante , Enfermedades Renales Quísticas/complicaciones , Enfermedades Renales Quísticas/diagnóstico , Enfermedades Renales Quísticas/genética , Anomalías Múltiples/diagnóstico , Anomalías Múltiples/genética , Anomalías Múltiples/patología , Cerebelo/anomalías , Anomalías del Ojo/complicaciones , Anomalías del Ojo/diagnóstico , RetinaRESUMEN
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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Papulosis Linfomatoide , Neoplasias Cutáneas , Masculino , Humanos , Adulto Joven , Adulto , Papulosis Linfomatoide/patología , Neoplasias Cutáneas/patología , Piel/patología , Diagnóstico Diferencial , Hueso Paladar/patologíaRESUMEN
PURPOSE: The study aimed to evaluate the clinical and tissue response to a hollow polymethylmethacrylate orbital implant with a multiperforated posterior surface in an animal model after evisceration. METHODS: Sixteen New Zealand rabbits had their right eye eviscerated. All animals received a hollow polymethylmethacrylate implant 12 mm in diameter that is multiperforated in its posterior hemisphere. The animals were divided into four groups, and each one had the eye exenterated at 7, 30, 90, and 180 days post-evisceration. Clinical signs were assessed daily for 14 days post-evisceration and then every 7 days until 180 days. Inflammatory pattern, collagen structure, and degree of neovascularization generated with implant placement were analyzed with hematoxylin-eosin, picrosirius red, and immunohistochemistry staining. RESULTS: There were no signs of infection, conjunctival or scleral thinning, or implant exposure or extrusion in any animal during the study. On day 7, the new tissue migrated into the implant and formed a fibrovascular network through the posterior channels. Inflammatory response reduced over time, and no multinuclea-ted giant cells were found at any time. CONCLUSION: Hollow polymethylmethacrylate orbital implants with a multiperforated posterior surface enable rapid integration with orbital tissues by fibrovascular ingrowth. We believe that this orbital implant model can be used in research on humans.
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Implantes Orbitales , Polimetil Metacrilato , Humanos , Conejos , Animales , Materiales Biocompatibles , Evisceración del Ojo , Implantación de PrótesisRESUMEN
We report the case of a 64-year-old male patient with a 5 month history of proptosis, motility limitation and vision loss in OD. Visual acuity (VA) was 20/200 in OD and 20/20 in OS. CT showed a large, round, intraconal lesion, with bony density and no apparent connection to adjacent orbital walls. MRI showed a T1-weighted hypointense lesion surrounded by a contrast enhancing capsule. The orbital tumor was excised through a lateral orbitotomy revealing a nodular, round, osseous structure. Histological examination disclosed well-formed lamellar bone trabeculae, with no necrosis or mitosis figures. Immunohistochemical staining was negative for MDM2 and CDK4. After 3 years, there was no evidence of tumor recurrence and VA had improved to 20/30. Intraconal osteomas with no clear attachment to orbital walls are extremely rare. We are aware of a few reported cases in the lid, hand, thigh, tongue, pterygopalatine fossa and brain. To the authors' knowledge, this is the first report in English literature of an orbital intraconal osteoma without any visible relation to the orbital walls.
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Neoplasias Orbitales , Osteoma , Masculino , Humanos , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Osteoma/diagnóstico por imagen , Osteoma/cirugía , Neoplasias Orbitales/diagnóstico por imagen , Neoplasias Orbitales/cirugía , Tomografía Computarizada por Rayos X , Imagen por Resonancia MagnéticaRESUMEN
ABSTRACT Purpose: The study aimed to evaluate the clinical and tissue response to a hollow polymethylmethacrylate orbital implant with a multiperforated posterior surface in an animal model after evisceration. Methods: Sixteen New Zealand rabbits had their right eye eviscerated. All animals received a hollow polymethylmethacrylate implant 12 mm in diameter that is multiperforated in its posterior hemisphere. The animals were divided into four groups, and each one had the eye exenterated at 7, 30, 90, and 180 days post-evisceration. Clinical signs were assessed daily for 14 days post-evisceration and then every 7 days until 180 days. Inflammatory pattern, collagen structure, and degree of neovascularization generated with implant placement were analyzed with hematoxylin-eosin, picrosirius red, and immunohistochemistry staining. Results: There were no signs of infection, conjunctival or scleral thinning, or implant exposure or extrusion in any animal during the study. On day 7, the new tissue migrated into the implant and formed a fibrovascular network through the posterior channels. Inflammatory response reduced over time, and no multinucleated giant cells were found at any time. Conclusion: Hollow polymethylmethacrylate orbital implants with a multiperforated posterior surface enable rapid integration with orbital tissues by fibrovascular ingrowth. We believe that this orbital implant model can be used in research on humans.
RESUMO Objetivo: Avaliar a resposta tecidual e clínica a um implante orbitário de polimetilmetacrilato, oco e multiperfurado em sua porção posterior em modelo animal após evisceração. Métodos: Dezesseis coelhos da raça Nova Zelândia foram submetidos à evisceração do globo ocular direito. Todos receberam implante oco de polimetilmetacrilato de 12 mm de diâmetro, multiperfurado em sua semiesfera posterior. O estudo foi dividido em avaliação clínica e histopatológica. A avaliação clínica foi diária até 14 dias pós-evisceração e, a cada sete dias, até completar 180 dias. Os animais foram divididos em grupos de quatro animais e cada um foi submetido à exenteração com 07, 30, 90 e 180 dias e depois à eutanásia. A análise histopatológica teve por fim caracterizar o padrão inflamatório, a estrutura do colágeno e o grau de neovascularização. Para isso, além da tradicional coloração pela hematoxilina-eosina, utilizou-se o corante Picrosirius Red (PSR) e imuno-histoquímica com o marcador CD 34. Resultados: Não houve sinais de infecção, afinamento conjuntival ou escleral, exposição ou extrusão do implante em nenhum animal durante o estudo. Já no sétimo dia, o tecido neoformado migrou para dentro do implante formando uma rede fibrovascular através dos canais posteriores. A resposta inflamatória diminuiu ao longo do tempo avaliado e não foram encontradas células gigantes multinucleadas. Conclusão: O implante analisado permite a sua integração aos tecidos orbitários pelo crescimento fibrovascular em seu interior. Os autores acreditam que este modelo de implante orbital pode fazer parte de testes com humanos.
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Purpose: Xanthogranulomatous pyelonephritis (XGP) is a chronic and severe infection of the kidney. We aimed to review the main clinical, imaging, and histological findings and to assess predictors of surgical complications or hospitalization >10 days (no deaths reported). Materials and Methods: We retrospectively searched all patients with XGP treated at our institution from 2005 to 2019, with 57 patients enrolled. Clinical data were retrieved by a single reader, computed tomographic (CT) examinations by two radiologists, and histopathological specimens by an experienced pathologist. Results: The patients' mean age was 44.3 ± 16.2 years and 41 (71.9%) were female. The most common symptoms were flank/lumbar pain (89.5%), fever (43.9%), and recurrent urinary tract infection (43.9%). The mean time until the presumptive diagnosis was 365.1 days and the median hospitalization period was 11 days. Blood tests showed anemia (78.9%), leukocytosis (43.6%) with left shift (21.6%). Urinalysis showed hematuria (75.6%), bacteriuria (40.9%), and leukocytes (93.2%). Urine cultures showed Escherichia coli in 14.8%, Proteus mirabilis in 7.4%, while 59.3% were negative. Of 40 patients with CT examinations, 38 (95%) presented with hydronephrosis and perinephric inflammatory changes (PIC) and 22 (55%) with Bear Paw sign. PIC was the only independent predictor at multivariate analysis for surgical complications. For prolonged hospitalization, fever and PIC were independent predictors at univariate, but only fever at multivariate analysis. Conclusions: XGP is a worrisome condition, with unclear pathophysiological mechanisms. Fever and PIC at CT examinations were predictors of poor outcomes.