Perinucleolar Compartment (PNC) Prevalence as an Independent Prognostic Factor in Pediatric Ewing Sarcoma: A Multi-Institutional Study.

The perinucleolar compartment (PNC) is a small nuclear body that plays important role in tumorigenesis. PNC prevalence correlates with poor prognosis and cancer metastasis. Its expression in pediatric Ewing sarcoma (EWS) has not previously been documented. In this study, we analyzed 40 EWS tumor cases from Caucasian and Hispanic patients for PNC prevalence by immunohistochemical detection of polypyrimidine tract binding protein and correlated the prevalence with dysregulated microRNA profiles. EWS cases showed staining ranging from 0 to 100%, which were categorized as diffuse (≥77%, n = 9, high PNC) or not diffuse (<77%, n = 31) for low PNC. High PNC prevalence was significantly higher in Hispanic patients from the US (n = 6, p = 0.017) and in patients who relapsed with metastatic disease (n = 4; p = 0.011). High PNC was associated with significantly shorter disease-free survival and early recurrence compared to those with low PNC. Using NanoString digital profiling, high PNC tumors revealed upregulation of eight and downregulation of 18 microRNAs. Of these, miR-320d and miR-29c-3p had the most significant differential expression in tumors with high PNC. In conclusion, this is the first study that demonstrates the presence of PNC in EWS, reflecting its utility as a predictive biomarker associated with tumor metastasis, specific microRNA profile, Hispanic ethnic origin, and poor prognosis.

Tumor tritón maligno en región mandibular y cervical / Malignant triton tumor in the mandibular and cervical region

Introducción: El tumor tritón maligno es una neoplasia rara en la que se encuentran células rabdomioblásticas en un tumor maligno de la vaina de nervios periféricos, que se caracteriza por su agresividad y mal pronóstico. La localización en la cabeza y el cuello es poco frecuente. La inmunohistoquímica juega un papel importante en el diagnóstico. Objetivo: Describir un tumor tritón maligno de tamaño inusual. Presentación del caso: Paciente femenino, de 16 años, es referida al servicio de cirugía maxilofacial del Instituto Nacional de Pediatría, Ciudad de México, con un diagnóstico de tumor neuroectodérmico en región facial y cervical de un año de evolución. Clínicamente el tumor era exofítico, multilobulado, con zonas extensas de necrosis, superficie de varias tonalidades y un tamaño aproximado de 18 x 10 x 12 cm. Se realizó una biopsia e inmunohistoquímica que confirmó el diagnóstico de tumor tritón maligno. La paciente fue intervenida quirúrgicamente, procedimiento con el cual se eliminó totalmente la lesión, con márgenes de seguridad. La paciente presentó una evolución tórpida, con desenlace fatal al cabo de seis meses del tratamiento. Conclusiones: El tumor tritón es una neoplasia agresiva y su detección oportuna orienta al cirujano a ofrecer al paciente un tratamiento adecuado(AU)

Introduction: Malignant triton tumor is a rare neoplasm in which rhabdomyoblasts are present in a malignant tumor of the peripheral nerve sheath. This condition is characterized by its aggressiveness and bad prognosis. Location in the head and neck is infrequent. Immunohistochemical testing plays an important role in its diagnosis. Objective: Describe an unusually large malignant triton tumor. Case presentation: A case is presented of a female 16-year-old patient referred to the maxillofacial surgery service of the National Institute of Pediatrics in Mexico City with a diagnosis of neuroectodermal tumor of one year's evolution in the facial and cervical region. In clinical terms, the tumor was exophytic, multilobed, with extensive areas of necrosis, a surface in several shades of color and an approximate size of 18 x 10 x 12 cm. Biopsy and immunohistochemical testing confirmed the diagnosis of malignant triton tumor. The patient underwent surgery in which the lesion was totally excised with a safety margin. Evolution was clumsy, with a fatal outcome at six months of treatment. Conclusions: Triton tumor is an aggressive neoplasm whose early detection makes it possible for surgeons to provide an appropriate treatment(AU)

Ketogenic Diet Provided During Three Months Increases KCC2 Expression but Not NKCC1 in the Rat Dentate Gyrus.

Ketogenic diet, a high fat and low carbohydrate diet, has been used as a non-pharmacological treatment in refractory epilepsy since 1920. In recent years, it has demonstrated to be effective in the treatment of numerous neurological and non-neurological diseases. Some neurological and neuropsychiatric disorders are known to be caused by gamma-aminobutyric acid (GABA)-mediated neurotransmission dysfunction. The strength and polarity of GABA-mediated neurotransmission are determined by the intracellular chloride concentration, which in turn is regulated by cation-chloride cotransporters NKCC1 and KCC2. Currently, it is unknown if the effect of ketogenic diet is due to the modulation of these cotransporters. Thus, we analyzed the effect of a ketogenic diet on the cation-chloride cotransporters expression in the dentate gyrus. We estimated the total number of NKCC1 immunoreactive (NKCC1-IR) neuronal and glial cells by stereology and determined KCC2 labeling intensity by densitometry in the molecular and granule layers as well as in the hilus of dentate gyrus of rats fed with normal or ketogenic diet for 3 months. The results indicated that ketogenic diet provided during 3 months increased KCC2 expression, but not NKCC1 in the dentate gyrus of the rat. The significant increase of KCC2 expression could explain, at least in part, the beneficial effect of ketogenic diet in the diseases where the GABAergic system is altered by increasing its inhibitory efficiency.

Are apoptosis-determining techniques useful to establish an early diagnosis of acute graft-vs-host disease in pediatric patients under treatment with multiple drugs?

BACKGROUND: There are no pathognomonic histopathological features to distinguish acute graft-vs-host disease (aGVHD) from skin drug reactions (SDRs) in pediatric patients with multiple drug regimens that have received blood transfusions and/or transplants. We aimed to determine if the addition of apoptosis markers is helpful to distinguish aGVHD from SDRs in these patients. METHODS: Skin biopsy specimens from patients with a clinical diagnosis of aGVHD or SDRs were evaluated for the presence of apoptotic bodies, satellitosis, interface damage, vasculitis, and inflammatory infiltrate on H&E stain. Information was completed with apoptotic markers (transferase-mediated dUTP nick end-labeling [TUNEL], bcl-2, and caspase-3). RESULTS: The skin biopsy specimens of 32 patients with aGVHD and 11 with SDRs were included for study. Only the number of apoptotic keratinocytes per 10 high-power fields (hpf) showed a significant difference between both groups (P = 0.02); the presence of ≥4 apoptotic keratinocytes per 10 hpf was identified as the optimal cut-off point to discriminate aGVHD from SDRs. No SDRs cases had follicular apoptotic cells. TUNEL, bcl-2, and caspase-3 determination showed no difference between both groups. CONCLUSIONS: The presence of ≥4 apoptotic keratinocytes per 10 hpf (in aGVHD) and the absence of follicular apoptotic cells (in SDRs) might be a useful marker to distinguish between them.

Systemic BK Virus Infection in a Pediatric Patient With Severe Combined Immunodeficiency.

Human BK virus (BKV) infection is known to occur mostly during childhood with the establishment of latent infection with no tissue damage or clinical manifestations. However, conditions causing immunosuppression can lead to increased virus replication and tissue damage. Although the tissues most commonly involved are the kidneys, bladder, ureters and, to some extent, brain tissue, there are some reports that suggest that BKV may cause multisystemic infections. In this case, a 12-month-old child was seen to suffer from multiple gastrointestinal infections. This prompted a search for immunodeficiencies, which revealed the presence of severe combined immunodeficiency. The child was eventually hospitalized and continued showing recurrent bouts of gastroenteritis as well as lower respiratory infection. After multiple antibiotic courses, he developed acute kidney injury, a hemophagocytic syndrome, and eventually respiratory failure, which led to his death a year later. Autopsy findings revealed the presence of a disseminated BKV infection involving the kidneys, ureters, leptomeninges, and pancreas. Analysis of the literature failed to show any previous case of BKV pancreatitis. The present case suggests that BKV can damage more tissues than previously reported and may be responsible for systemic infections in immunosuppressed patients.

Mycobacterium tuberculosis as a cause of mandibular osteomyelitis in a young woman: a case report.

BACKGROUND: Tuberculosis is considered an emerging disease worldwide; in the last 10 years, its incidence has increased to more than 9.6 million cases of active tuberculosis. In 2014, it resulted in 1.5 million patient deaths. However, oral presentation with bone involvement occurs in less than 3% of all reported cases and rarely arouses clinical suspicion on initial presentation. CASE PRESENTATION: A 15-year-old Mexican girl who had a previous diagnosis of neurofibromatosis presented to our hospital with pain and swelling in the region of the left mandibular body since November 2011. A clinical examination revealed pain in the mandibular region, a mass of soft consistency that seemed to involve bone, and a fistula with discharge of intraoral purulent material. Additionally, tachycardia and hyperthermia were observed. The left submental and submandibular regions had a 12-cm-diameter swelling, which was well-delineated and nonerythematous. The final diagnosis was established by real-time polymerase chain reaction. CONCLUSIONS: The final diagnosis of rare cases of tuberculous osteomyelitis in the jaw can be established by deoxyribonucleic acid (DNA) identification of Mycobacterium tuberculosis in the lesion. Simple and fast complementary diagnosis by real-time polymerase chain reaction is a fundamental approach to establishing early and effective pharmacological and surgical treatment.

[The Mexican Board of Pathology: microscopy examination before and after digital microscopy]. / Consejo Mexicano de Médicos Anatomopatólogos: su examen de microscopia, antes y después de su digitalización.

INTRODUCTION: The examination carried out by the COMMAP for the certification process assessed pathologist formed in dissimilar institutions. In 2007 COMMAP's governing body in turn, decided to digitize it. The purpose of this study is to investigate whether the conversion to virtual slides in the microscopy section, compared with the traditional have had an impact on the scores of the candidates. METHOD: The slides were scanned with high resolution. The virtual microscope is a standard computer screen where there is a program (Aperio Scope Image Viewer) that can display the scanned slides. The results of the microscopy section of the past nine years were compared; two groups were formed: 1) those without digitized examination, and 2) with it. The results were compared by Student t-test and Mann-Whitney. RESULTS: Of a 461 results 240 belonged to the first group and 221 to the second one. On a scale of 1-10, the average scores were 6.6 and 6.8, respectively (p > 0.6 and > 0.5).The minimum and maximum scores were also similar in each group. CONCLUSIONS: According to the results, the digitized exam in the COMMAP's certification process shows no difference between the digitized and the conventional versions.

Polypoid arteriovenous malformation in the jejunum of a child that mimics intussusception.

Polypoid arteriovenous malformations, which are localized in the colon, are extremely rare in adults, with only 7 cases published to date. Here we present the case of a 6-year-old girl with a jejunal polypoid tumor that a sonogram and a computed tomographic scan have shown to resemble intussusception. Histologically, numerous large ectatic veins intermixed with small-caliber arteries, venules, arterioles, and capillaries were observed in the intestinal wall. A retrospective computed tomographic scan 3-dimensional angiographic reconstruction demonstrated that this may be a diagnostic characteristic. Clinical and morphologic comparisons with previously reported cases were discussed.

Medallion-like dermal dendrocyte hamartoma: a new clinically and histopathologically distinct lesion.

Dermal dendrocyte hamartomas are extremely rare; only two examples have been described with clinical features different from our cases and with incomplete immunohistochemical characterization. We report three female patients presenting a medallion-shaped, well-defined, slightly atrophic and asymptomatic congenital lesion. All 3 patients showed a fusiform-cell proliferation. Immunohistochemistry was positive for CD34, factor XIIIa, and fascin. Electron microscopy showed typical features of dermal dendrocytes. We believe that the lesions described represent a new, clinically and histopathologically distinct lesion originating in dermal dendrocytes. We propose to name it medallion-like dermal dendrocyte hamartoma.

Indeterminate cell histiocytosis. Clinical and pathologic study in a pediatric patient.

Indeterminate cell histiocytosis is a rare disorder involving altered homing mechanisms of the cutaneous histiocytic/dendritic system. It has been described predominantly in adults, with less than a dozen cases in children. A 13-year-old adolescent girl presented with a 4-year history of asymptomatic erythematous nodules and plaques, measuring from 1 to 5 cm in diameter, that were located mainly on the trunk and proximal portions of her limbs. A skin biopsy showed dermal diffuse infiltration of histiocytic cells. Most of the histiocytic cells were strongly positive for S100 protein. No Birbeck granules were found. Treatment with topical steroid was ineffective. After 6 months of pure coal tar and 5% 5-fluorouracil cream, an almost total clearing of lesions was observed. An accurate diagnosis of this condition is mandatory in order to avoid unnecessary treatments. Conservative management is also discussed.

Cerebral malignant nerve sheath tumor, triton tumor variant: case report.

A case of a cerebral malignant triton tumor in a 3-year-old boy with a 2-month history of frontal headache and no clinical evidence of neurofibromatosis is reported. The computed tomography (CT) scan showed a large, irregular tumor in the right parietooccipital lobe. A partial surgical resection was performed. Histologically, the tumor was highly cellular and consisted of spindle cells with hyperchromatic and pleomorphic nuclei. Focally, neoplastic cells with rhabdomyoblastic features were found. The immunohistochemical study showed that tumor cells were positive for S-100 protein and CD57, and the rhabdomyoblasts expressed desmin, Myo-D1, and myoglobin. During the postoperative period, a massive intraparenchymal hemorrhage was identified and surgical drainage was performed. The patient worsened and died 10 days after the first surgery. Postmortem study was not authorized. Six cases of cerebral malignant nerve sheath tumor have been described; however, primary intraparenchymal malignant triton tumor has not been previously described.

Streptococcal exanthem in a blaschkolinear pattern: clinical evidence for genetic mosaicism in hypomelanosis of ito.

Due to the presence of two different clones of cells in early embryogenesis, numerous congenital and acquired dermatoses have a linear distribution following the lines of Blaschko. Acquired inflammatory skin diseases are rarely observed in linear patterns. Our patient was born with macrocephaly, left eye glaucoma, and a left facial and contralateral corporal hemihypertrophy, cerebral dysgenesis, and skeletal abnormalities. Hypopigmented S-shaped linear macules on the trunk and linear streaks on the arms and legs were compatible with hypomelanosis of Ito. At 5 years of age the patient presented with an erythematous follicular exanthem compatible with scarlet fever exclusively in the lines of Blaschko. This fact suggests a genetic mosaicism.

Retinoblastoma infiltrativo difuso de presentación poco frecuente: caso clínico / Low frequent presentation of diffuse infiltrative retinoblastoma

Se presenta un caso poco frecuente de retinoblastoma infiltrativo difuso en un joven de 14 años de edad y se discute sobre el abordaje diagnóstico y revisión de la literatura.

Lupus eritematoso neonatal: informe de caso / Neonatal lupus erythematosous: a case report

Introducción. El lupus eritematoso neonatal es una enfermedad que se define por la presencia de auto-anticuerpos maternos de tipo IgG transmitidos por vía transplacentaria causando daño fetal o neonatal con datos clínicos característicos. Aunque la presencia de estos auto-anticuerpos es altamante sensible, no es específica para el desarrollo de la enfermedad, de la cual su incidencia es desconocida. Caso clínico. Paciente femenino de 1 mes de vida extrauterina, hija de madre con dermatitis en cara no especificada. Inició su padecimiento en la primera semana de vida con lesiones dermatológicas en cuello, que se diseminaron a cara, cráneo, tronco y extremidades, eritematosas, de forma anular, con centro blanquecino y descamación fina, además de úlceras en carrillo y paladar. La biometría reportó plaquetas de 45,000/mm al cubo. Pruebas de función hepática y electrocardiograma normales. Los anticuerpos anti-Ro y anti-La resultaron positivos ++++. La biopsia cutánea mostró dermis papilar con infiltrado inflamatorio perivascular y en la interfase compatible con lupus eritematoso neonatal. Conclusión. Se reporta el caso de un paciente con lupus neonatal con lesiones dermatológicas y hematológicas, no pudiéndose demostrar bloqueo cardiaco ciongénito ni afección hepática y en cuya madre se pensó y diagnosticó lupus eritematoso sistémico por el cuadro de su hijo

Papilomatosis respiratoria recurrente y carcinoma broncogénico multicéntrico asociado a HPV 11/6. Presentación de un caso y revisión de la literatura / Recurrent respiratory papillomatosis and multicentric bronchogenic carcinoma associated with HPV 11/6. Report of a case and review of the literature

Un niño de 12 años de edad, con papilomatosis respiratoria recurrente desde los 8 meses de edad, fue sometido a más de setenta resecciones y falleció con una lesión pulmonar destructiva basal derecha. En la autopsia se encontró extensa papilomatosis que afectaba laringe, traquea y bronquios principales y se extendía a bronquiolos terminales y alveolos. El parenquima pulmonar tenía focos de carcinoma epidermoide, ocasionalmente mezclado con celulas malignas mucoproductoras, y se encontró una metástasis en un ganglio hiliar derecho. Las sondas biotiniladas para ADN del virus del papiloma humano 11/6 hibridizaron tanto con las lesiones papilomatosas como con las áreas de carcinoma. Los pacientes con papilomatosis respiratoria que desarrollan carcinoma broncogénico a partir de papilomatosis bronquiolo alveolar son mas jovenes y tiene un curso clínico mas agresivo, con diseminación metástasica, mientras que en los pacientes, no fumadores y no radiados, que desarrollan carcinoma laringotraqueal, el tumor muestra solo agresividad local

Cytomegalovirus infection in children: frequency, anatomopathologic characteristics and underlying risk factors in 1618 autopsies

The aim of this study was to determine the frequency of cytomegalovirus (CMV) infection in children with postmortem study. The records of 1618 autopsies performed during 1980 - 1989 at the Hospital Infantil de Mexico Federico Gomez were reviewed. Characteristic cytomegalovirus inclusion bodies were identified, in one or several organs, in 47 cases (2.9 per cent of the autopsies). None of these cases was cultured for viruses prior to ar at the time of autopsy. Of the 47 cases, 24 (51 per cent) with CMV were younger than 3 months of age. In eight cases, the infection was juged as generalized and considered the cause of death. Two of these patients were premature and the infection was most probably intrauterine. The risk factor most frequently identified was secondary immunosuppression. The lung was the most common affected organ, followed by kidney, adrenals, pancreas, liver, brain and salivary glands. In seven cases the inclusion bodies were seen in the brain and in three others periventricular calcifications without inclusion bodies were observed. Although not a rarity in Mexico, CMV infection is not often suspected. Additional studies are needed in order to determine the prevalence of CMV infection in Mexico