Blistering and aggressive paniculite cutaneous T-cell lymphoma.

BACKGROUND: Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is characterized by atypical T-cells expressing the α/ß T-cell receptor in the subcutaneous fat. Although it is usually indolent, some cases can show an aggressive course. It is usually a disease of the middle-aged, but can rarely affect children. CASE REPORT: We describe the case of a 12-year-old male, previously healthy, who presented a dermatosis disseminated to the four segments consisting of vesicles, blisters, erythematous and hematonecrotic plaques, atrophic scars, associated with edema. The biopsy confirmed limited cutaneous panniculitic T-cell lymphoma with extensive epidermal necrosis. CONCLUSIONS: We report the case of a SPTCL in a child. Although rare in this age group, the diagnosis should be considered in children who present similar conditions and who do not respond to treatment. Diagnosis is made on clinical suspicion and confirmed by histology. We discuss the challenges in its management and how timely diagnosis influences patient survival.

INTRODUCCIÓN: El linfoma de células T tipo paniculitis subcutánea (LCCTP) se caracteriza por la presencia de linfocitos T atípicos que expresan el receptor de células T α/ß en el tejido celular subcutáneo. Aunque generalmente es indolente, algunos casos presentan un curso agresivo. Es mayormente una enfermedad de la mediana edad, rara vez afecta a los niños. CASO CLÍNICO: Se describe el caso de un paciente de sexo masculino de 12 años de edad, previamente sano que presentó una dermatosis diseminada a los cuatro segmentos constituida por vesículas, ampollas, placas eritematocostrosas y hematonecróticas, además de atróficas, asociadas con edema. La biopsia confirmó linfoma cutáneo de células T paniculítico con extensa necrosis epidérmica. CONCLUSIONES: Reportamos el caso de un LCCTP en un paciente pediátrico. Aunque es raro en este grupo de edad, se debe considerar en los niños que presentan cuadros similares y que no responden a tratamiento. El diagnóstico se realiza por sospecha clínica y se confirma por histología. Se discuten los desafíos en su manejo y cómo el diagnóstico oportuno influye en la sobrevida del paciente.

Limited granulomatosis with polyangiitis in children with idiopathic orbital inflammation: a case series and literature review.

Idiopathic orbital inflammation (IOI) is a diagnosis of exclusion, but the exclusion of other inflammatory diseases of the orbit is broad and relies on clinician experience, response to corticosteroid, or biopsy. This study aimed to investigate the presence of granulomatosis with polyangiitis (GPA) in patients initially diagnosed as IOI and describe its clinicopathological features, ANCA status, treatment, and outcome. We performed a retrospective case series study of children diagnosed with limited GPA (L-GPA) in patients with IOI. A systematic review of the literature was performed in children with GPA and orbital mass. Eleven of 13 (85%) patients with IOI had L-GPA. Two additional patients with orbital mass and L-GPA were included in this analysis. The median age was 10 years, and 75% were female. Twelve cases were ANCA positive and 77% were MPO-pANCA positive. Most patients had a poor response to treatment and had a high relapse rate. Based on literature review, 28 cases were found. Most (78.6%) were female with a median age of 9 years. Three patients were misdiagnosed as IOI. Patients with L-GPA more frequently had MPO-pANCA positivity (35%) than children with systemic GPA (18%) and were less often PR3-cANCA positive than patients with systemic GPA (18% vs. 46%). L-GPA accounts for a high prevalence of children diagnosed as IOI. The high prevalence of MPO-pANCA observed in our study may be related to L-GPA rather than with the orbital mass. Long-term follow-up, orbital biopsy, and serial ANCA testing are necessary to exclude GPA in patients with IOI.

Acute lichenoid and varioliform pityriasis in a pediatric patient.

BACKGROUND: Pityriasis lichenoides et varioliformis acuta (PLEVA) is a rare dermatosis recognized as a benign condition of unknown etiopathogenesis. It is more common in pediatric patients and young adults and is characterized by multiple small or large erythematous plaques spread over the trunk and extremities. CASE REPORT: We describe the case of a 5-year-old male, previously healthy, with multiple erythematous lesions that disappeared leaving hypopigmented macules. The biopsy reported histological changes suggestive of mycosis fungoides. After a second revision of lamellae in this hospital, lymphocytic vasculitis (LV) with focal epidermal necrosis consistent with acute pityriasis lichenoides (PL) was identified. CONCLUSIONS: The existing knowledge about PLEVA lacks a consensus in specifying its classification, etiopathogenesis, diagnosis, and treatment, so this clinical condition represents a medical challenge. The diagnosis is made by clinical suspicion and confirmed by histology. The objective of this article was to report a case of PLEVA with an atypical presentation due to its histopathological findings, being the first report showing LV in children, as well as a review of the literature.

INTRODUCCIÓN: La pitiriasis liquenoide y varioliforme aguda (PLEVA) es una dermatosis poco frecuente, de etiopatogenia desconocida y evolución autolimitada. Es más común en pacientes pediátricos y adultos jóvenes, y está caracterizada por la presencia de múltiples placas eritematoescamosas pequeñas o grandes, diseminadas en el tronco y las extremidades. CASO CLÍNICO: Se describe el caso de un escolar de 5 años, de sexo masculino, previamente sano, que presentó múltiples cuadros de lesiones eritematosas que desaparecían dejando máculas hipopigmentadas. La biopsia reportó cambios histológicos sugestivos de micosis fungoide. Se realizó una segunda revisión de laminillas, identificando vasculitis linfocítica con necrosis epidérmica focal, consistente con pitiriasis liquenoide aguda. CONCLUSIONES: El conocimiento acerca de la PLEVA carece de un consenso que especifique su clasificación, etiopatogenia, diagnóstico y tratamiento, por lo que esta condición clínica representa un desafío médico. El diagnóstico se realiza por sospecha clínica y se confirma por histología. El objetivo de este artículo fue reportar un caso de PLEVA con presentación atípica por los hallazgos histopatológicos, siendo este el primer reporte de vasculitis linfocítica en niños, y además se realiza una revisión de la literatura.

Acute lichenoid and varioliform pityriasis in a pediatric patient / Vasculitis linfocítica en pitiriasis liquenoide y varioliforme aguda de un paciente pediátrico

Abstract Background: Pityriasis lichenoides et varioliformis acuta (PLEVA) is a rare dermatosis recognized as a benign condition of unknown etiopathogenesis. It is more common in pediatric patients and young adults and is characterized by multiple small or large erythematous plaques spread over the trunk and extremities. Case report: We describe the case of a 5-year-old male, previously healthy, with multiple erythematous lesions that disappeared leaving hypopigmented macules. The biopsy reported histological changes suggestive of mycosis fungoides. After a second revision of lamellae in this hospital, lymphocytic vasculitis (LV) with focal epidermal necrosis consistent with acute pityriasis lichenoides (PL) was identified. Conclusions: The existing knowledge about PLEVA lacks a consensus in specifying its classification, etiopathogenesis, diagnosis, and treatment, so this clinical condition represents a medical challenge. The diagnosis is made by clinical suspicion and confirmed by histology. The objective of this article was to report a case of PLEVA with an atypical presentation due to its histopathological findings, being the first report showing LV in children, as well as a review of the literature.

Resumen Introducción: La pitiriasis liquenoide y varioliforme aguda (PLEVA) es una dermatosis poco frecuente, de etiopatogenia desconocida y evolución autolimitada. Es más común en pacientes pediátricos y adultos jóvenes, y está caracterizada por la presencia de múltiples placas eritematoescamosas pequeñas o grandes, diseminadas en el tronco y las extremidades. Caso clínico: Se describe el caso de un escolar de 5 años, de sexo masculino, previamente sano, que presentó múltiples cuadros de lesiones eritematosas que desaparecían dejando máculas hipopigmentadas. La biopsia reportó cambios histológicos sugestivos de micosis fungoide. Se realizó una segunda revisión de laminillas, identificando vasculitis linfocítica con necrosis epidérmica focal, consistente con pitiriasis liquenoide aguda. Conclusiones: El conocimiento acerca de la PLEVA carece de un consenso que especifique su clasificación, etiopatogenia, diagnóstico y tratamiento, por lo que esta condición clínica representa un desafío médico. El diagnóstico se realiza por sospecha clínica y se confirma por histología. El objetivo de este artículo fue reportar un caso de PLEVA con presentación atípica por los hallazgos histopatológicos, siendo este el primer reporte de vasculitis linfocítica en niños, y además se realiza una revisión de la literatura.

Linfoma cutáneo de células T paniculítico, ampolloso y agresivo / Blistering and aggressive paniculite cutaneous T-cell lymphoma

Resumen Introducción: El linfoma de células T tipo paniculitis subcutánea (LCCTP) se caracteriza por la presencia de linfocitos T atípicos que expresan el receptor de células T α/β en el tejido celular subcutáneo. Aunque generalmente es indolente, algunos casos presentan un curso agresivo. Es mayormente una enfermedad de la mediana edad, rara vez afecta a los niños. Caso clínico: Se describe el caso de un paciente de sexo masculino de 12 años de edad, previamente sano que presentó una dermatosis diseminada a los cuatro segmentos constituida por vesículas, ampollas, placas eritematocostrosas y hematonecróticas, además de atróficas, asociadas con edema. La biopsia confirmó linfoma cutáneo de células T paniculítico con extensa necrosis epidérmica. Conclusiones: Reportamos el caso de un LCCTP en un paciente pediátrico. Aunque es raro en este grupo de edad, se debe considerar en los niños que presentan cuadros similares y que no responden a tratamiento. El diagnóstico se realiza por sospecha clínica y se confirma por histología. Se discuten los desafíos en su manejo y cómo el diagnóstico oportuno influye en la sobrevida del paciente.

Abstract Background: Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is characterized by atypical T-cells expressing the α/β T-cell receptor in the subcutaneous fat. Although it is usually indolent, some cases can show an aggressive course. It is usually a disease of the middle-aged, but can rarely affect children. Case report: We describe the case of a 12-year-old male, previously healthy, who presented a dermatosis disseminated to the four segments consisting of vesicles, blisters, erythematous and hematonecrotic plaques, atrophic scars, associated with edema. The biopsy confirmed limited cutaneous panniculitic T-cell lymphoma with extensive epidermal necrosis. Conclusions: We report the case of a SPTCL in a child. Although rare in this age group, the diagnosis should be considered in children who present similar conditions and who do not respond to treatment. Diagnosis is made on clinical suspicion and confirmed by histology. We discuss the challenges in its management and how timely diagnosis influences patient survival.

Dysferlinopathy misdiagnosed with juvenile polymyositis in the pre-symptomatic stage of hyperCKemia: a case report and literature review.

BACKGROUND: Dysferlinopathy encompasses a group of rare muscular dystrophies caused by recessive mutations in the DYSF gene. The phenotype ranges from asymptomatic elevated serum creatine kinase (hyperCKemia) to selective and progressive involvement of the proximal and/or distal muscles of the limbs. Bohan and Peter criteria are the most widely used for the diagnosis of polymyositis, but they have limitations and can misclassify muscular dystrophies with inflammation as polymyositis. Most dysferlinopathy patients have muscle biopsies with inflammation and thus are vulnerable to misdiagnosis with polymyositis and inappropriate treatment with steroids and immunosuppressors. CASE PRESENTATION: We describe a 14 years-old male patient who was referred for assessment of asymptomatic hyperCKemia (26,372 IU/L). An X-linked dystrophinopathy initially was ruled out by direct genetic testing. Juvenile polymyositis was considered based on muscle biopsy, creatine kinase levels, and electromyography changes. Corticosteroid treatment triggered proximal lower limb muscular weakness, and no full muscular strength recovery was observed after corticosteroid withdrawal. Based on these observations, a limb-girdle muscular dystrophy (LGMD) was suspected, and LGMDR2 was confirmed by whole exome sequencing. CONCLUSION: We report a dysferlinopathy patient who was misdiagnosed with juvenile polymyositis and explore in a literature review how common such misdiagnoses are. With diagnosis based only on routine clinicopathological examinations, distinguishing an inflammatory myopathy from dysferlinopathy is quite difficult. We suggest that before establishing a diagnosis of "definite" or "probable" juvenile polymyositis, according to Bohan and Peter or current ACR/EULAR criteria, a muscular dystrophy must first be ruled out.

Calcinosis cutis congénita tumoral asociada con encefalopatía epiléptica infantil temprana con variante patogénica en el gen FGF12 / Tumorous congenital calcinosis cutis associated with early childhood epileptic encephalopathy with a pathogenic FGF12 gene variant

Resumen Introducción: La calcinosis cutis es el depósito de sales insolubles de calcio en la piel y se clasifica, de acuerdo con su patogénesis, en distrófica, metastásica, idiopática, iatrogénica y calcifilaxis. La calcinosis idiopática se presenta en pacientes sanos y es asintomática; incluye la calcinosis escrotal, la calcinosis nodular de Winer o nódulos calcificados subepidérmicos y la calcinosis tumoral familiar. Esta última es una condición rara que se caracteriza por el depósito de calcio periarticular en pacientes normocalcémicos sin conexión al hueso. Caso clínico: Paciente de sexo masculino de 5 meses de edad, quien al séptimo día de vida fue hospitalizado por ictericia multifactorial, sepsis neonatal tardía y apnea con crisis epilépticas. La evolución fue tórpida, con ingresos hospitalarios por crisis epilépticas de difícil manejo, respuesta parcial a la difenilhidantoína y descontrol electrolítico. Mediante la secuenciación del exoma dirigido se detectó una variante patogénica de sentido equivocado en FGF12 que confirmó el diagnóstico de encefalopatía epiléptica temprana número 47. Además, el paciente presentó dermatosis congénita diseminada a las extremidades inferiores con afección en muslos, asintomática, bilateral y simétrica, constituida por hipopigmentación y fóveas duras a la palpación profunda. La biopsia mostró calcificación distrófica. Conclusiones: Se presenta el caso de un lactante con calcinosis cutis congénita profunda asociada con una variante patogénica en el gen FGF12 y con encefalopatía epiléptica, situación clínica que, a la fecha, no había sido reportada en la literatura.

Abstract Background: Calcinosis cutis is the deposit of insoluble calcium salts in the skin. It is classified according to its pathogenesis in dystrophic, metastatic, idiopathic, iatrogenic, and calciphylaxis. Idiopathic calcinosis is asymptomatic, occurs in healthy patients, and includes scrotal calcinosis, Winer's nodular calcinosis or subepidermal calcified nodules, and familial tumor calcinosis. The latter is a rare condition characterized by periarticular calcium deposition in normocalcemic patients with no bone connection. Case report: The case of a 5-month-old male patient, who on the seventh day of life was hospitalized for multifactorial jaundice, late neonatal sepsis, and apnea with epileptic seizures is described. His evolution was torpid, with hospital admissions due to epileptic seizures that were difficult to manage with partial response to the use of diphenylhydantoin and electrolyte alterations. By means of exome sequencing directed, a pathogenic variant of wrong direction in FGF12 was detected and the diagnosis of early epileptic encephalopathy number 47 was confirmed. Also, the patient showed disseminated congenital dermatosis to lower extremities affecting thighs, asymptomatic, bilateral and symmetrical, constituted by hypopigmentation and fovea hard to deep palpation. The biopsy showed dystrophic calcification Conclusions: The case of an infant with deep congenital cutis calcinosis associated with a pathogenic variant in the FGF12 gene with epileptic encephalopathy is described. To date, this clinical situation has not been previously reported in the literature.

Tumorous congenital calcinosis cutis associated with early childhood epileptic encephalopathy with a pathogenic FGF12 gene variant.

Background: Calcinosis cutis is the deposit of insoluble calcium salts in the skin. It is classified according to its pathogenesis in dystrophic, metastatic, idiopathic, iatrogenic, and calciphylaxis. Idiopathic calcinosis is asymptomatic, occurs in healthy patients, and includes scrotal calcinosis, Winer's nodular calcinosis or subepidermal calcified nodules, and familial tumor calcinosis. The latter is a rare condition characterized by periarticular calcium deposition in normocalcemic patients with no bone connection. Case report: The case of a 5-month-old male patient, who on the seventh day of life was hospitalized for multifactorial jaundice, late neonatal sepsis, and apnea with epileptic seizures is described. His evolution was torpid, with hospital admissions due to epileptic seizures that were difficult to manage with partial response to the use of diphenylhydantoin and electrolyte alterations. By means of exome sequencing directed, a pathogenic variant of wrong direction in FGF12 was detected and the diagnosis of early epileptic encephalopathy number 47 was confirmed. Also, the patient showed disseminated congenital dermatosis to lower extremities affecting thighs, asymptomatic, bilateral and symmetrical, constituted by hypopigmentation and fovea hard to deep palpation. The biopsy showed dystrophic calcification. Conclusions: The case of an infant with deep congenital cutis calcinosis associated with a pathogenic variant in the FGF12 gene with epileptic encephalopathy is described. To date, this clinical situation has not been previously reported in the literature.

Background: Introducción">La calcinosis cutis es el depósito de sales insolubles de calcio en la piel y se clasifica, de acuerdo con su patogénesis, en distrófica, metastásica, idiopática, iatrogénica y calcifilaxis. La calcinosis idiopática se presenta en pacientes sanos y es asintomática; incluye la calcinosis escrotal, la calcinosis nodular de Winer o nódulos calcificados subepidérmicos y la calcinosis tumoral familiar. Esta última es una condición rara que se caracteriza por el depósito de calcio periarticular en pacientes normocalcémicos sin conexión al hueso. Caso clínico: Paciente de sexo masculino de 5 meses de edad, quien al séptimo día de vida fue hospitalizado por ictericia multifactorial, sepsis neonatal tardía y apnea con crisis epilépticas. La evolución fue tórpida, con ingresos hospitalarios por crisis epilépticas de difícil manejo, respuesta parcial a la difenilhidantoína y descontrol electrolítico. Mediante la secuenciación del exoma dirigido se detectó una variante patogénica de sentido equivocado en FGF12 que confirmó el diagnóstico de encefalopatía epiléptica temprana número 47. Además, el paciente presentó dermatosis congénita diseminada a las extremidades inferiores con afección en muslos, asintomática, bilateral y simétrica, constituida por hipopigmentación y fóveas duras a la palpación profunda. La biopsia mostró calcificación distrófica. Conclusiones: Se presenta el caso de un lactante con calcinosis cutis congénita profunda asociada con una variante patogénica en el gen FGF12 y con encefalopatía epiléptica, situación clínica que, a la fecha, no había sido reportada en la literatura.

Melanocitosis dérmica adquirida en la mano de un paciente pediátrico / Acquired dermal melanocytosis on the hand of a pediatric patient

Resumen Introducción: Las melanocitosis dérmicas son un grupo de enfermedades dermatológicas pigmentarias asociadas con la proliferación melanocítica. Se clasifican con base en su número y localización profunda a nivel de la dermis; pueden ser congénitas o adquiridas. Caso clínico: Paciente de sexo masculino de 11 años de edad, sin antecedentes de importancia para el padecimiento actual. Inicio con mácula oscura en la palma de la mano izquierda hace 5 años, asintomática, de crecimiento paulatino. A la exploración física, se detectó dermatosis que afectaba la palma izquierda, cara palmar de las falanges proximales del tercer y cuarto dedos, caracterizada por la presencia de mácula grisácea negruzca, bordes difusos e irregulares, no infiltrada ni indurada. En la dermatoscopia se detectó un patrón de pigmento de tono gris acero con áreas de color café, y con evidencia de puntos blanquecinos dentro de estas. En la histopatología se identificaron células fusiformes, con núcleo grande y la presencia de pigmento melánico en su interior, con distribución perivascular y entremezclados con las fibras de colágeno en la dermis superficial y media. Con base en las características clínicas e histopatológicas de la lesión, se concluyó melanocitosis dérmica adquirida de la mano como el diagnóstico definitivo. Conclusiones: Los reportes de casos de melanocitosis dérmica adquiridas atípicas son infrecuentes. La melanocitosis dérmica de la mano es una variante de estas enfermedades, de la que existen menos de 10 casos. Se presenta el primer caso reportado en Latinoamérica hasta el momento, con el objetivo de ampliar el conocimiento de sus características clínico-histológicas y dermatoscópicas.

Abstract Background: Dermal melanocytosis is a group of pigmentary dermatological diseases associated with melanocytic proliferation, which are classified based on their number and depth at the level of the dermis; they may be congenital or acquired. Case report: An 11-year-old male patient with no history of importance for the current condition started 5 years ago with a dark macula in the left hand palm, which was asymptomatic but grew gradually. On physical examination, dermatoses affecting the left palm, palmar face of proximal phalanges of the third, fourth and fifth fingers, characterized by the presence of blackish greyish macula, diffuse and irregular edges, not infiltrated or indurated were detected. The dermatoscopy identified a pattern of pigment with a greyish-brown tone with brown areas, showing whitish spots inside. In the histopathology, the presence of spindle cells was observed in the superficial and middle dermis, with a large nucleus and the presence of a melanic pigment inside, with perivascular distribution and intermingled with the collagen fibres. Based on the clinical characteristics and the histopathological findings, acquired dermal melanocytosis of the hand was concluded as the final diagnosis. Conclusions: Case reports of atypical acquired dermal melanocytosis are infrequent. Dermal melanocytosis of the hand is a rare variant of these diseases, of which less than 10 cases have been reported. At present, this case of dermal melanocytosis is the first reported in Latin America with the aim to extend the knowledge of its clinical-histological and dermatoscopic characteristics.

Acquired dermal melanocytosis on the hand of a pediatric patient.

Background: Dermal melanocytosis is a group of pigmentary dermatological diseases associated with melanocytic proliferation, which are classified based on their number and depth at the level of the dermis; they may be congenital or acquired. Case report: An 11-year-old male patient with no history of importance for the current condition started 5 years ago with a dark macula in the left hand palm, which was asymptomatic but grew gradually. On physical examination, dermatoses affecting the left palm, palmar face of proximal phalanges of the third, fourth and fifth fingers, characterized by the presence of blackish greyish macula, diffuse and irregular edges, not infiltrated or indurated were detected. The dermatoscopy identified a pattern of pigment with a greyish-brown tone with brown areas, showing whitish spots inside. In the histopathology, the presence of spindle cells was observed in the superficial and middle dermis, with a large nucleus and the presence of a melanic pigment inside, with perivascular distribution and intermingled with the collagen fibres. Based on the clinical characteristics and the histopathological findings, acquired dermal melanocytosis of the hand was concluded as the final diagnosis. Conclusions: Case reports of atypical acquired dermal melanocytosis are infrequent. Dermal melanocytosis of the hand is a rare variant of these diseases, of which less than 10 cases have been reported. At present, this case of dermal melanocytosis is the first reported in Latin America with the aim to extend the knowledge of its clinical-histological and dermatoscopic characteristics.

Introducción: Las melanocitosis dérmicas son un grupo de enfermedades dermatológicas pigmentarias asociadas con la proliferación melanocítica. Se clasifican con base en su número y localización profunda a nivel de la dermis; pueden ser congénitas o adquiridas. Caso clínico: Paciente de sexo masculino de 11 años de edad, sin antecedentes de importancia para el padecimiento actual. Inicio con mácula oscura en la palma de la mano izquierda hace 5 años, asintomática, de crecimiento paulatino. A la exploración física, se detectó dermatosis que afectaba la palma izquierda, cara palmar de las falanges proximales del tercer y cuarto dedos, caracterizada por la presencia de mácula grisácea negruzca, bordes difusos e irregulares, no infiltrada ni indurada. En la dermatoscopia se detectó un patrón de pigmento de tono gris acero con áreas de color café, y con evidencia de puntos blanquecinos dentro de estas. En la histopatología se identificaron células fusiformes, con núcleo grande y la presencia de pigmento melánico en su interior, con distribución perivascular y entremezclados con las fibras de colágeno en la dermis superficial y media. Con base en las características clínicas e histopatológicas de la lesión, se concluyó melanocitosis dérmica adquirida de la mano como el diagnóstico definitivo. Conclusiones: Los reportes de casos de melanocitosis dérmica adquiridas atípicas son infrecuentes. La melanocitosis dérmica de la mano es una variante de estas enfermedades, de la que existen menos de 10 casos. Se presenta el primer caso reportado en Latinoamérica hasta el momento, con el objetivo de ampliar el conocimiento de sus características clínico-histológicas y dermatoscópicas.

Anti-inflammatory and toxicological evaluation of Moussonia deppeana (Schldl. & Cham) Hanst and Verbascoside as a main active metabolite.

ETHNOPHARMACOLOGICAL RELEVANCE: Moussonia deppeana, known as Tlachichinole, is a Mexican medicinal plant used for treatment of inflammatory diseases, influenza, diarrhea, gastrointestinal disorders and arthritis. AIM OF THE STUDY: In this paper the antioxidant and anti-inflammatory activities as well as the acute and sub-acute toxicological effects were evaluated for the ethanolic extract from aerial parts of M. deppeana, also its phytochemical analysis is described. MATERIALS AND METHODS: Phytochemical analysis and compound isolation were performed with thin layer chromatography. The chemical identification of the main compound was performed by (1)H NMR (COSY, NOESY, HSQC and HMBC) spectra. In vitro antioxidant capacity and total phenolic content for the ethanolic extract and its primary fractions was determined by DPPH and Folin-Ciocalteu reagent. Acute and subacute toxicity tests were evaluated on Balb/C mice. Finally acute anti-inflammatory evaluation was tested for a local (TPA) and systemic (carrageenan) murine model. RESULTS: The main compound isolated from the ethanolic extract of M. deppeana was Verbascoside, which was isolated from F3 and was identified by (1)H NMR and COSY data. Furthermore oleanolic and ursolic acids were isolated from primary fractions F1 and F2. Ethanolic extract showed IC50 = 6.71mg/mL for DPPH test and 664.12µg QE/mL for the total phenolic content. The LD50 value was >2g/kg by i.g. route in male and female mice. Sub-acute administration (28 days) of the ethanolic extract (1g/kg) did not cause lethality or alter any hematological and biochemical parameters, in addition, histological analysis of the major organs exhibited no structural changes. Anti-inflammatory activity of the ethanolic extract showed an ED50 = 1.5mg/ear and 450mg/kg for TPA and carrageenan test, respectively. Primary fractions generated moderate local and systemic anti-inflammatory activity. CONCLUSION: The ethanolic extract from the aerial parts of M. deppeana did not cause any lethality or adverse effect in either of the acute and sub-acute toxicity tests. This exhibited an important local and systemic anti-inflammatory activity and also moderate antioxidant capacity. Moreover, the primary fraction F2 was more active for the TPA model while the primary fraction F3 was most active in the carrageenan model in vivo. The main compound isolated from F3 was verbascoside; on the other hand also ursolic and oleanolic acids were isolated from F1 and F2.

A proteomic approach of pediatric astrocytomas: MiRNAs and network insight.

Pediatric astrocytomas, a leading cause of death associated with cancer, are the most common primary central nervous system tumors found in children. Most studies of these tumors focus on adults, not on children. We examined the global protein and microRNA expression pattern by 2D SDS-PAGE, mass spectrometry (MALDI-TOF), and RT(2) miRNA PCR Array System. Proteomic studies revealed 49 proteins with changes on the expression. Interactome showed that vimentin, calreticulin, and 14-3-3 epsilon protein are hub proteins in these neoplasms. MicroRNA analyses demonstrated for the first time novel microRNAs involved in the astrocytoma biology. In conclusion, our results show that novel proteins and microRNAs with expression changes on pediatric astrocytoma could serve as biomarkers of tumor progression. BIOLOGICAL SIGNIFICANCE: Astrocytomas are tumors that progress rapidly and that invade surrounding tissues. Although some drugs have been developed to treat these neoplasms, the mortality of patients is still very high. In this study, we describe for the first time, to our knowledge, some proteins and miRNAs associated with the biology of astrocytic tumors that could be postulated as possible diagnostic or prognostic biomarkers. Altogether, our results indicate that large-scale analyses allow making a fairly accurate prediction of different cellular processes altered in astrocytic tumors.

[Survival of patients with malignant astrocytomas according to the expression of Ki67 antigen in a pediatric hospital]. / Sobrevida de los pacientes con astrocitoma de alto grado que expresan el antígeno Ki67, atendidos en un hospital de pediatría.

BACKGROUND: Pediatric patients with malignant gliomas and same histological diagnosis respond distinctly to treatment. It is thus necessary to determine other factors that may influence the response to treatment and survival. Over expression of the Ki67 protein has been associated with poor treatment response. The aim of this study was to determine if the expression of this antigen influences survival of patients treated for malignant gliomas in the CMN SXXI Pediatrics Hospital. METHODS: We included patients with anaplasic astrocitoma or glioblastoma multiforme seen at our hospital between 1995 and 2005. We determined the expression of Ki67 by immunohistochemistry and correlated the findings with tumor histology and patient survival. RESULTS: Of the 21 patients studied, 12 overexpressed antigen Ki67. There was no significant association between over expression of Ki67 and survival, although we observed a clinical association. Over expression of Ki67 correlated with more aggressive histology. Being under the age of 11 was a poor prognostic factor. Overall survival was 49% at 120 months. CONCLUSIONS: Being young (under 11 years) is a marker of poor prognosis among pediatric patients with anaplasic astrocytoma or glioblastoma multiforme. Overexpression expression of antigen Ki67 is associated with histology and may be associated with poor survival among patients treated in our hospital.

Sobrevida de los pacientes con astrocitoma de alto grado que expresan el antígeno Ki67, atendidos en un hospital de pediatría / Survival of patients with malignant astrocytomas according to the expression of Ki67 antigen in a pediatric hospital

Antecedentes: Los pacientes pediátricos con astrocitomas de alto grado con mismas histologías presentan respuestas diferentes a idéntico tratamiento. Es necesario identificar los factores que influyen en el pronóstico y respuesta al mismo. La sobreexpresión de la proteína Ki67 se ha asociado con respuestas poco favorables. El objetivo fue determinar si la expresión de este antígeno influye en la sobrevida de los pacientes con astrocitoma de alto grado del Hospital de Pediatría del Centro Médico Nacional Siglo XXI. Métodos: Se incluyeron pacientes con astrocitoma anaplásico o glioblastoma multiforme atendidos entre 1995 y 2005. Por inmunohistoquímica se determinó la expresión del antígeno Ki67 en las muestras de tejido tumoral y se correlacionó con la histología tumoral y la sobrevida de los pacientes. Resultados: De 21 pacientes, 12 sobreexpresaron el antígeno Ki67. No se encontró asociación estadísticamente significativa entre la sobreexpresión del antígeno Ki67 y la sobrevida, aunque sí clínica. Se encontró asociación estadísticamente significativa entre la sobreexpresión del Ag Ki67 y el grado de malignidad del tumor. La edad menor de 11 años resultó un factor de mal pronóstico. La sobrevida global fue de 49 % a 120 meses. Conclusiones: La edad menor de 11 años fue un factor de mal pronóstico en los pacientes estudiados con astrocitoma o glioblastoma multiforme. La sobreexpresión del antígeno Ki67 está asociada con la histología y pareciera tener relación con la sobrevida de los pacientes pediátricos con astrocitoma.

BACKGROUND: Pediatric patients with malignant gliomas and same histological diagnosis respond distinctly to treatment. It is thus necessary to determine other factors that may influence the response to treatment and survival. Over expression of the Ki67 protein has been associated with poor treatment response. The aim of this study was to determine if the expression of this antigen influences survival of patients treated for malignant gliomas in the CMN SXXI Pediatrics Hospital. METHODS: We included patients with anaplasic astrocitoma or glioblastoma multiforme seen at our hospital between 1995 and 2005. We determined the expression of Ki67 by immunohistochemistry and correlated the findings with tumor histology and patient survival. RESULTS: Of the 21 patients studied, 12 overexpressed antigen Ki67. There was no significant association between over expression of Ki67 and survival, although we observed a clinical association. Over expression of Ki67 correlated with more aggressive histology. Being under the age of 11 was a poor prognostic factor. Overall survival was 49% at 120 months. CONCLUSIONS: Being young (under 11 years) is a marker of poor prognosis among pediatric patients with anaplasic astrocytoma or glioblastoma multiforme. Overexpression expression of antigen Ki67 is associated with histology and may be associated with poor survival among patients treated in our hospital.

[Prognostic and survival factors among pediatric patients with ependymomas]. / Factores pronósticos y sobrevida de pacientes pediátricos con ependimomas.

BACKGROUND: Ependymomas constitute the third most common intracranial tumors in children. Risk factors include age, location, extent of surgical excision, and radiation therapy. Recently, chromosomal imbalances have been described. OBJECTIVE: Determine global survival of patients with ependymomas according to different prognostic factors. METHODS: We reviewed the medical charts of every pediatric patient with ependymoma from 1996 to 2005. Genomic imbalances were determined using comparative genomic hybridization (CGH). Survival was calculated using the Kaplan and Meier method. We used the Log Rank test for each risk factor. Death risk was calculated by odds ratio (OR). RESULTS: We included 24 patients. Global survival was 58.04%. The presence of chromosomal imbalances, particularly in chromosome 21, significantly affected survival Being under 5 years of age, anaplastic histology, chemotherapy other than ICE (ifosfamida-carboplatin-etoposide) and partial resection increased the risk of death. CONCLUSIONS: Known risk factors were confirmed in our study, including chromosomal imbalances. We describe a new chromosomal imbalance in chromosome 21 among 30% of study participants.

Factores pronósticos y sobrevida de pacientes pediátricos con ependimomas / Prognostic and survival factors among pediatric patients with ependymomas

Antecedentes: El ependimoma es el tercer tumor intracraneano más frecuente en pediatría. Los factores que influyen en el pronóstico son la localización, la edad del paciente, la resección quirúrgica y el tratamiento con radioterapia. Recientemente se ha descrito la presencia de alteraciones cromosómicas en el tumor como factor de mal pronóstico. El objetivo de esta investigación fue determinar la sobrevida de pacientes pediátricos con ependimoma de acuerdo con los diferentes factores pronósticos. Métodos: Se revisaron los expedientes de pacientes pediátricos con ependimoma de 1996 a 2005. Se determinaron las alteraciones cromosómicas mediante hibridación genómica comparativa. Se calculó la sobrevida de acuerdo con el método Kaplan-Meier y prueba de log rank de acuerdo a cada factor pronóstico. Se calculó el riesgo de morir para cada factor de acuerdo con la razón de momios. Resultados: Se incluyeron 24 pacientes. La sobrevida global fue de 58.04%. La presencia de alteraciones cromosómicas, particularmente en el cromosoma 21, afectó significativamente la sobrevida. La edad menor a cinco años, la histología anaplásica, la quimioterapia diferente a ifosfamida-carboplatino-etopósido y la resección parcial aumentaron el riesgo de morir. Conclusiones: Se confirman los factores descritos anteriormente en la literatura, incluyendo alteraciones cromosómicas. Se describe un nuevo desbalance en el cromosoma 21 en 30% de los pacientes.

BACKGROUND: Ependymomas constitute the third most common intracranial tumors in children. Risk factors include age, location, extent of surgical excision, and radiation therapy. Recently, chromosomal imbalances have been described. OBJECTIVE: Determine global survival of patients with ependymomas according to different prognostic factors. METHODS: We reviewed the medical charts of every pediatric patient with ependymoma from 1996 to 2005. Genomic imbalances were determined using comparative genomic hybridization (CGH). Survival was calculated using the Kaplan and Meier method. We used the Log Rank test for each risk factor. Death risk was calculated by odds ratio (OR). RESULTS: We included 24 patients. Global survival was 58.04%. The presence of chromosomal imbalances, particularly in chromosome 21, significantly affected survival Being under 5 years of age, anaplastic histology, chemotherapy other than ICE (ifosfamida-carboplatin-etoposide) and partial resection increased the risk of death. CONCLUSIONS: Known risk factors were confirmed in our study, including chromosomal imbalances. We describe a new chromosomal imbalance in chromosome 21 among 30% of study participants.

Clinical and molecular parameters for risk stratification in Mexican children with medulloblastoma.

BACKGROUND: Clinical, histological, and more recently, molecular factors have been described as important in survival of the patient with medulloblastoma. Best survival results include aggressive chemotherapeutic protocols. More exact risk analysis may differentiate patients who require aggressive treatments from those with low risk who may respond adequately to less aggressive protocols. METHODS: Twenty six patients were included over a 10-year period and were followed for at least 5 years. Personal variables were obtained from their clinical records. Immunochemistry studies were performed on their formalin-fixed paraffin-embedded tissues. Statistical analysis included chi(2) test, odds risk, linear regression models, and Kaplan-Meier survival analysis. RESULTS: Metastatic disease and chemotherapy with VP16-carboplatin reduce the patient's probability of survival, whereas anaplastic histology increases the probability of death. Global survival and disease-free survival were 66.6 and 45.02%, respectively. Only two patients overexpressed the ERBB2 protein, and no significant difference was found in survival in terms of ERBB2 overexpression. CONCLUSIONS: Risk stratification has become very important in medulloblastoma. We found an increased hazard of death when metastatic disease was present. Gene expression in Mexican children requires a larger sample in order to be analyzed.

Hemocromatosis neonatal. Informe de tres casos de autopsia / Neonatal hemocrhomatosis. Report of three autopsy cases

Introducción. La hemocromatosis neonatal es una enfermedad que se inicia in utero, caracterizada por fibrosis acentuada o cirrosis y siderosis hepática y extrahepática intensas, pero sin afección del sistema fagocítico mononuclear. Los datos clínicos importantes son falla hepática grave al nacimiento e hipoglicemia. El diagnóstico se hace básicamente por exclusión cuando se reúne al menos dos de los criterios clinicopatológicos establecidos por Knisely. La biopsia de mucosa oral, la resonancia magnética de hígado y de bazo también son útiles en el diagnóstico. Material y método. En el Departamento de Patología del Hospital de Pediatría del Centro Médico Nacional, Siglo XXI del Instituto Mexicano del Seguro Social, que es un hospital de tercer nivel de atención, en un análisis retrospectivo de los casos de autopsia de recién nacidos realizadas en 1989 a 1997 se seleccionaron aquellos cuya enfermedad principal fuera hepática. Se estableció cualitativamente el grado de siderosis en los cortes de hígado y bazo. En el Instituto Nacional de Investigaciones Nucleares se determinó la cantidad de hierro y cobre por medio de fluorescencia de rayos X, principalmente de hígado y bazo, en tejidos fijados en formol, tanto en los casos problema como en dos controles. Resultados. De las 210 autopsias realizadas en recién nacidos, sólo se encontraron cuatro con hepatopatía como enfermedad principal, sin diagnóstico clínico etiopatogénico. En tres de éstos se hizo el diagnóstico anatomopatológico de hemocromatosis neonatal, todos fueron varones, con edades de 29, seis y 36 días, uno de ellos asociado a síndrome de Down. La razón de concentración de hierro en hígado/bazo en los casos de hemocromatosis fue superior a 1.5 en hígado, a diferencia de lo que ocurrió en dos casos control en los cuales fue menor de 1. Conclusiones. Los casos que se presentan muestran la utilidad de la autopsia para establecer un diagnóstico de certeza, ésta nos permitió identificar tres casos de hemocromatosis neonatal, entidad actualmente bien caracterizada. Esta enfermedad evoluciona rápidamente hacia la muerte y no hay más tratamiento que ofrecerles que medidas de apoyo y a veces el trasplante hepático. Se debe alertar a la familia sobre el riesgo de que ocurra esta enfermedad en hijos subsecuentes. La razón de la concentración de hierro en hígado y bazo, en un resultado no descrito previamente que apoya el diagnóstico, ya que descarta otras siderosis secundarias