ABSTRACT
Tumores marrons são lesões resultantes de alterações no metabolismo ósseo em decorrência do hiperparatireoidismo, uma das desordens endócrinas mais comuns no mundo. Os tumores marrons podem ocorrer no hiperparatireoidismo primário, secundário e terciário. Essas lesões ocorrem principalmente nos ossos longos, mas podem afetar os maxilares e apesar de apresentarem características clínicas e microscópicas bem estabelecidas, a patogênese molecular dos tumores marrons ainda não foi elucidada. Recentemente, mutações patogênicas nos genes TRPV4, FGFR1 e KRAS foram descritas em lesões de células gigantes dos maxilares e em fibroma não-ossificante dos ossos longos (FGFR1 e KRAS), lesões que são mímicas histológicas dos tumores marrons do hiperparatireoidismo. O objetivo do presente estudo foi investigar em tumores marrons dos maxilares a presença de mutações nesses genes. Para investigar tais mutações, foi realizado o sequenciamento de Sanger em uma amostra de conveniência composta por 13 tumores marrons dos maxilares associados ao hiperparatireoidismo primário e secundário. Sabendo-se que mutações nos genes analisados levam a ativação da via de sinalização celular MAPK/ERK, a detecção imuno-histoquímica da forma fosforilada da proteína ERK1/2 (pERK1/2) também foi avaliada nessas lesões. Mutações patogênicas no gene KRAS foram detectadas em sete casos (p.G12V n=4, p.G12D n=1, p.G13D n=1, p.A146T n=1). Variantes de significado incerto, p.A134T e p.E37K também foram detectadas. Todas as amostras exibiram sequências selvagens para os genes FGFR1 e TRPV4. A ativação da via MAPK/ERK foi demonstrada pela positividade imuno-histoquímica das células mononucleares dos tumores marrons para pERK1/2. Portanto, mutações no gene KRAS e ativação da via de sinalização celular MAPK/ERK foram detectadas em tumores marrons do hiperparatireoidismo dos maxilares. Tais resultados expandem o espectro de lesões de células gigantes cuja patogênese molecular envolve a sinalização RAS.
Brown tumors are lesions that result from abnormal bone metabolism in hyperparathyroidism, which is one of the most common endocrine disorders worldwide. Brown tumors can occur in primary, secondary and even in tertiary hyperparathyroidism. It occurs mainly in long bones, but occasionally affects the jaws and, despite its well-known clinical and microscopic features, the molecular pathogenesis of brown tumors remains unclear. Recently, pathogenic mutations in TRPV4, FGFR1 and KRAS were described in giant-cell lesions of the jaws and nonossifying fibromas of the bones (FGFR1 and KRAS), which are histologic mimics of brown tumors. The aim of this study was to investigate in brown tumors of the jaws the presence of mutations in these genes. To assess such mutations, a convenience sample of 13 brown tumors of the jaws associated with primary or secondary hyperparathyroidism was targeted by Sanger sequencing. As mutations in these genes are known to activate the MAPK/ERK signaling pathway, the immunostaining of the phosphorylated form of ERK1/2 (pERK1/2) was also assessed in these lesions. KRAS pathogenic mutations were detected in seven cases (p.G12V n=4, p.G12D n=1, p.G13D n=1, p.A146T n=1). KRAS variants of unknown significance, p.A134T and p.E37K, were also detected. All samples showed wild-type sequences for FGFR1 and TRPV4 genes. The activation of the MAPK/ERK signaling pathway was demonstrated by pERK1/2 immunohistochemical positivity of the brown tumors´ mononuclear cells. In conclusion, mutations in KRAS and activation of the MAPK/ERK signaling pathway were detected in brown tumors of hyperparathyroidism of the jaws, expanding the spectrum of giant cell lesions whose molecular pathogenesis involve RAS signaling
Subject(s)
Bone Diseases , Granuloma, Giant Cell , Giant Cells , Extracellular Signal-Regulated MAP Kinases , Hyperparathyroidism , Mutation , Neoplasms , Wounds and Injuries , GenesABSTRACT
Adult xanthogranulomatous disease of the orbit refers to a heterogeneous group of clinical syndromes with differing degrees of systemic involvement and distinct prognoses. The different syndromes all present clinically with progressively enlarging, yellowish lesions of the orbit. Histologically, the lesions are characterized by an inflammatory infiltrate of foam cells and Touton-type multinucleated giant cells. The xanthomatized histiocytes are CD68+, S100-, and CD1a-. There are 4 clinical forms of xanthogranulomatous disease of the orbit: adult xanthogranulomatous disease of the orbit, adult onset asthma and periocular xanthogranuloma, necrobiotic xanthogranuloma, and Erdheim-Chester disease. The treatment of local lesions are treated with systemic corticosteroids and other immunosuppressors. Vemurafenib, tocilizumab, and sirolimus have shown promising results in systemic disease.
Subject(s)
Histiocytosis/pathology , Orbital Diseases/pathology , Adrenal Cortex Hormones/therapeutic use , Adult , Antibodies, Monoclonal/therapeutic use , Combined Modality Therapy , Diagnosis, Differential , Disease Management , Erdheim-Chester Disease/diagnosis , Erdheim-Chester Disease/pathology , Erdheim-Chester Disease/therapy , Histiocytosis/diagnosis , Histiocytosis/therapy , Humans , Immunosuppressive Agents/therapeutic use , Necrobiotic Xanthogranuloma/diagnosis , Necrobiotic Xanthogranuloma/pathology , Necrobiotic Xanthogranuloma/therapy , Orbital Diseases/diagnosis , Orbital Diseases/therapy , Radiotherapy, AdjuvantABSTRACT
En este artículo se presenta el caso de un paciente con diagnóstico histológico de encefalitis por virus de inmunodeficiencia humana - (VIH), con múltiples coinfecciones incluyendo oportunistas. Es un caso llamativo, pues claramente la incidencia de dicha enfermedad ha decrecido ostensiblemente en la era post terapia antiretroviral de gran efectividad (TARGA). Es un paciente masculino heterosexual de 63 años con conductas sexuales de riesgo, que ingresó a un hospital de cuarto nivel con síntomas respiratorios y durante su hospitalización se le diagnosticó VIH / SIDA estadio C3, múltiples infecciones tales como: hepatitis B, neurosífilis, criptococosis sistémica, toxoplasmosis cerebral, histoplasmosis cutánea, candidiasis y herpes oral; recibió tratamiento y falleció 27 días después por criptococosis diseminada. Se le practicó autopsia y se observó en sustancia blanca del sistema nervioso central numerosos nódulos microgliales, linfocitos perivascular y células gigantes multinucleadas sin formación de granulomas, característicos de la encefalitis por VIH. Este paciente es un ejemplo de la historia natural por VIH en estadío avanzado con compromiso del sistema nervioso central.
In this paper we describe the case of a patient with histological diagnosis of human immunodeficiency virus (HIV) encephalitis, which also had multiple co-infections. It is a striking case, because of the incidence of this disease has markedly decreased in the post Highly Active Antiretroviral Therapy HAART era. The patient was a heterosexual male of 63 years old engaged in risky sexual behavior, who was admitted to a reference hospital with respiratory symptoms. During hospitalization He was diagnosed with stage C3 HIV/AIDS, multiple infections such as Hepatitis B, Neurosyphilis, systemic cryptococcosis, cerebral toxoplasmosis, cutaneous histoplasmosis, oral herpes and candida infections; He received appropriate treatments for all of the above, however He died 27 days later by disseminated cryptococcosis. He underwent autopsy and in central nervous system in the white matter were observed numerous microglial nodules, perivascular lymphocytes and multinucleated giant cells without granuloma formation. These giant cells are characteristics of HIV encephalitis. This patient is an example of the natural history of HIV infection that progressed to an advanced stage of AIDS.
ABSTRACT
El Osteoblastoma (OB) es un tumor benigno formador de tejido óseo de aparición muy rara en los maxilares. Su diagnóstico puede ser un gran reto para el patólogo bucal, ya que las características histopatológicas se asemejan a otros tumores más frecuentes en el macizo maxilofacial; por lo que es importante conocer a profundidad sus características clínicas, radiográficas e histopatológicas que nos conduzcan al diagnóstico asertivo de OB. Hasta los actuales momentos la última recopilación de casos de OB maxilares publicados en la literatura fue hecha por Morelos et al hasta el año 2011, quien obtuvo 88 casos. El objetivo de esta investigación fue realizar una revisión bibliográfica exhaustiva de casos documentados hasta la fecha en revisiones sistemáticas previas, obteniéndose 119 casos de OB maxilares. Adicionalmente, se aporta un caso más de OB de maxilar superior a la literatura académica...
Osteoblastoma is a rare bone-forming tumor that very rarely involves the jaws. The diagnosis should be very difficult to oral pathology expert because their histopathologic features are resembled with other bony tumors of the maxillofacial region. Therefore, is very important have depth knowledge about the clinical, radiographic and histopathologic features of OB, to make the correct diagnosis. Before this report, the last collection of maxillary OB cases was made by Morelos et al until the year 2011; they obtained 88 cases in their study. The main aim of this research was provide a systematic review of previously published cases; the result was 119 cases of maxillary OB. In addition, this paper added one more case of this rare lesion to the academic literature...
