Head and neck cancer. An aetiopathogenetic study of non-endemic lymphoepithelioma.

An aetiopathogenetic analysis of non-endemic nasopharyngeal carcinoma (NPC) in European and Southern American patient groups was performed. Specifically, the study sought to determine the proportion of Epstein-Barr Virus (EBV)-positive tumour cells in NPC patients in two very different populations (Europe and South America) in areas not associated with a high incidence of NPC. Clinical data (age, sex and onset of clinical disease) were also analyzed. A total of 50 NPC samples, 24 from a European hospital (EH) and 26 from two South American hospitals (SAH), were included. Nuclear staining for Epstein-Barr virus-encoded small RNA (EBER) was performed by in situ hybridization (ISH). Latent membrane protein 1 (LMP1) expression was measured by immunohistochemical (IHC) analysis. A higher incidence of NPC was observed in patients > 40 years of age in EH; in SAH, by contrast, the incidence was higher in patients aged ≤ 40 years. Cervical lymph node metastasis was detected in 31 patients (of whom 84.6% were from SAH). A total of 72% of samples were EBERpositive; the incidence of EBER positivity was greater in type 3 NPCs. EBV was detected in a large proportion of epithelial cells in samples from both EH and SAH (75% vs. 69.2%, respectively). An association was found between EBER detection in lymphocytes and patient origin (p = 0.0001). LMP1 expression was detected in 64% of patients. ISH for the detection of EBER is the most sensitive technique for demonstrating EBV in tumour tissue. The incidence of EBV was not significantly greater in either of the study populations, but was significantly higher in patients with type 3 NPC. Definitive histological diagnosis of NPC was reached earlier in EH than in SAH, where metastases were more frequently diagnosed, suggesting that the disease had reached a more advanced stage by the time treatment was started.

Duodenal intraepithelial lymphocytes of children with cow milk allergy preferentially bind the glycan-binding protein galectin-3.

A breakdown in intestinal homeostasis results in inflammatory bowel diseases including coeliac disease and allergy. Galectins, evolutionarily conserved beta-galactoside-binding proteins, can modulate immune-epithelial cell interactions by influencing immune cell fate and cytokine secretion. In this study we investigated the glycosylation signature, as well as the regulated expression of galectin-1 and -3 in human duodenal samples of allergic and non-allergic children. Whereas galectin-1 was predominantly localized in the epithelial compartment (epithelial cells and intraepithelial lymphocytes) and the underlying lamina propria (T cells, macrophages and plasma cells), galectin-3 was mainly expressed by crypt epithelial cells and macrophages in the lamina propria. Remarkably, expression of these galectins was not significantly altered in allergic versus non-allergic patients. Investigation of the glycophenotype of the duodenal inflammatory microenvironment revealed substantial alpha2-6-linked sialic acid bound to galactose in lamina propria plasma cells, macrophages and intraepithelial lymphocytes and significant levels of asialo core 1 O-glycans in CD68+ macrophages and enterocytes. Galectin-1 preferentially bound to neutrophils, plasma cells and enterocytes, while galectin-3 binding sites were mainly distributed on macrophages and intraepithelial lymphocytes. Notably, galectin-3, but not galectin-1 binding, was substantially increased in intraepithelial gut lymphocytes of allergic patients compared to non-allergic subjects, suggesting a potential role of galectin-3-glycan interactions in shaping epithelial-immune cell connections during allergic inflammatory processes.

Omeprazole-associated changes in the gastric mucosa of children.

AIMS: To describe histological findings in gastric mucosa biopsy specimens of children treated with proton-pump inhibitors (PPIs) for different periods of time. METHODS: Biopsy specimens from 12 children (aged 8 months to 15 years) treated with PPIs and 8 controls were processed for paraffin embedding and stained with H&E as well as inmmunohistochemically for sialyl-Tn antigen. RESULTS: The main changes were related to parietal cells which showed brisk cytoplasmic eosinophilia, apical cytoplasmic protrusions to dilated glands, cytoplasmic and nuclear hypertrophy, dilated intracytoplasmic canaliculi, binucleation and multinucleation. The intracellular canaliculi surface showed strong immunohistochemical reaction for sialyl-Tn antigen, apparently a marker for this structure. Some of the patients were biopsied after a short period of oral or intravenously administered omeprazole; the changes may therefore occur rapidly. CONCLUSIONS: PPIs induce the same changes in the gastric mucosa of children as in adults, but the number of nuclei is increased. These effects have not been reported previously in this age group. It is suggested that the changes result from a combination of effects of PPIs and gastrin release.

Small bowel gastric metaplasia: a report of three cases in children.

AIMS: To report three children displaying gastric metaplasia antral pyloric type of the small bowel mucosa. METHODS: Analysis of clinical, histopathological and immunohistochemical data. RESULTS: The first patient was a 14-year-old girl with history of chronic intestinal pseudo-obstruction and chronic jejunitis; the second patient was a 6-year-old girl with a long-lasting jejunostomy; and the third patient was a 5-year-old girl with ileal-rectal anastomosis. The foci of gastric metaplasia were obvious with H&E-stained sections. The cells at the gastric metaplasia mucosa proved to be MUC-1 and sialyl-Tn positive by immunohistochemistry and they were in a pattern that was different from that of the adjacent mucosa; the cells were autofluorescent in H&E-stained sections. CONCLUSIONS: Gastric metaplasia of the small bowel mucosa in these cases seems to have resulted from chronic inflammation and persistent regenerative activity. This has rarely been reported outside Crohn disease, and if ever in children.

Extrahepatic biliary atresia with cartilaginous metaplasia in the gallbladder remnants.

Extrahepatic biliary atresia (EBA) is a chronic inflammatory process leading to fibrous obliteration of the biliary tree. Cartilaginous metaplasia within the remaining walls of the biliary main ducts in EBA has been reported once, although as cartilage heterotopia. A similar finding is presented here, but in the gallbladder of an infant with the full-blown manifestations of EBA; it is proposed that the alteration results from metaplasia of local connective tissue. Also of note is the complete disappearance of smooth muscle cells in the walls of the biliary tree in EBA, a fact which seems to be missing in the description of the pathology in these cases.

Tumores de la cavidad oral y huesos maxilares en pediatría. Revisión de 122 pacientes / Oral cavity and maxillary bone tumors in pediatrics. Review of 122 patients

Se presenta un estudio retrospectivo de 122 pacientes con tumores que se manifestaron en la cavidad oral, con localización inicial en maxilares o partes blandas (se excluyeron los tumores de la cara sin compromiso bucal). La edad promedio fue 9 años y 6 meses (rango de 1 día a 17 años). El 62 por ciento se presentó en varones. La localización inicial de los tumores fue en hueso en el 53 por ciento de los casos y en partes blandas en el 47 por ciento; 82 pacientes tuvieron lesiones benignas y 40 lesiones malignas. Las manifestaciones al ingreso fueron: tumor palpable o visible (39 por ciento), tumor más dolor (22 por ciento), dolor (19 por ciento) y otros como caída de dientes, parálisis, fiebre o asímetría facial (20 por ciento). La rutina de estudio comprendió radiografía panorámica de maxilar, centellografía ósea (gammacámara con Tecnesio 99), tomografía axial computada (TAC) y resonancia nuclear magnética (RNM). Los pacientes fueron tratados en forma multidisciplinaria siendo la cirugía (punción aspiración con aguja fina, biopsia y/o resección)el procedimiento inicial en la mayoría de ellos. De acuerdo al algoritmo todos los pacientes con lesión ósea fueron estudiados con Rx simple y TAC, 89 por ciento de positividad en ambas, previas a la biopsia por punción. De igual menera en los tumores de partes blandas la TAC mantuvo su utilidad, no así la Rx simple que fue reeplazada por la ecografía cuando se detectó ausencia de compromiso óseo. Las lesiones benignas predominaron (78/122) a nivel de hueso o de partes blandas. la curación en ella fue la regla. En lo que respecta a los tumores, primarios de la región (11/40) correspondieron inicialmente a partes blandas y raramente a hueso, en los que fue frecuente el compromiso metastático o multicéntrico.

Small cell sweat gland carcinoma of childhood.

Small cell sweat gland carcinoma appears to represent a very unusual histological type of sweat gland anlage tumour presenting in children. The differential diagnosis from other small blue cell tumours involving the skin is often difficult. The present report confirms the original observation describing two patients of 2 and 5 years of age harbouring cutaneous tumours. The histology of these lesions showed a monomorphic proliferation of small cells with a high mitotic rate and areas of necrosis. Immunohistochemically, the cells were negative for desmin, cytokeratin 7, cytokeratin 20, Cam 5.2, CD99, chromogranin, CD56, synaptophysin, and S-100, and focally positive for the pancytokeratin marker AE1/AE3, carcinoembryonic antigen (one case), and neurone specific enolase (one case). The prognosis of this type of tumour seems to be good. As more cases are added, the clinical pathological spectrum of the lesion will become better defined.

Angiocentric immunoproliferative lesion and angiocentric lymphoma of lymph node in children. A report of two cases.

AIM: To report two examples of an angiocentric immunoproliferative lesion (AIL) and angiocentric angiodestructive lymphoma (AL) presenting in lymph nodes in children. Most commonly involving extranodal sites, AIL/AL rarely presents in the spleen and lymph nodes. METHODS/RESULTS: Case 1 presented as a cervical lymphadenopathy in a 3 year old girl being treated for pre-B cell acute lymphoblastic leukaemia. Histological and immunohistochemistry studies revealed an Epstein-Barr virus positive (EBV+), large B cell (CD20 and CD30+) AIL with large areas of necrosis, the whole resembling lymphomatoid granulomatosis. Case 2 presented as a large supraclavicular lymphadenopathy in a 13 year old boy. Histology and immunohistochemistry revealed an EBV-, large T cell (CD45RO, CD56, and CD30+) AL, presenting the features of so called angiocentric T cell/natural killer cell lymphoma, nasal type. CONCLUSIONS: The term AIL/AL refers to a heterogeneous group of conditions not unique to a particular type of lymphoid cell. These lesions are easily recognised by the histopathologist because of their extremely unusual angiocentric pattern. Although rare, AIL/AL may present as nodal lesions in children ab initio.

Extracutaneous infantile haemangioma is also Glut1 positive.

AIM: To investigate whether extracutaneous infantile haemangioma-like tumours are immunohistochemically similar to cutaneous infantile haemangiomas. METHODS: Mammary, salivary gland, liver (one each), and placental (two cases) capillary haemangiomas and typical examples of cutaneous (eight cases) infantile haemangioma were investigated immunohistochemically for alpha smooth muscle actin and Glut1, a proposed marker for the skin localised lesion. Positive internal controls included red blood cells, perineurium, trophoblast, and endothelial cells of the placental capillaries. Extralesional vessel endothelium acted as a negative control (except in the placenta). The liver haemangioma and both chorioangiomas presented in patients with Beckwith-Wiedemann syndrome. RESULTS: The endothelial cells of all the vascular lesions were Glut1 positive. These were consistently surrounded by a rim of alpha smooth muscle actin positive pericytic cells. Controls reacted appropriately. CONCLUSIONS: All infantile haemangiomas were immunohistochemically positive for Glut1: expression of this molecule was not limited to infantile haemangiomas of the skin. These tumours comprise proliferations of both endothelial and pericytic cells. The association with Beckwith-Wiedemann syndrome may provide a clue to the molecular genetics of infantile haemangioma.

Expression of cytokeratins 7 and 20 in Helicobacter pylori-associated chronic gastritis in children.

Helicobacter pylori gastric infection induces structural changes in the gastric epithelium. Among them, variations in the expression of cytokeratins have been reported in adult patients. In the present study, we describe the expression of CK7 and CK20 in gastric samples taken from the antrum in three groups of pediatric patients: (A) Helicobacter pylori-associated chronic gastritis (mean age: 11.4 years); (B) previous H. pylori chronic gastritis patients (mean age: 9.4 years); and (C) controls (mean age: 8.8 years). In all, the presence of sulfomucins was assessed with Alcian blue-periodic acid-Schiff pH 1.0. Immunoreactivity was graded as absent (0), weak (1+), moderate (2+), or intense (3+), in accordance with the intensity of the staining, and its distribution as focal or diffuse. CK7 reactivity was 2+ either focal or diffuse in all group A biopsies. The reactivity was more evident in the cells at the neck of the glands, in the areas with more inflammatory infiltrates, decorating long vertical segments of epithelium. In groups B and C, CK7 reactivity was also focal and 1+ at the cells of the necks of the glands. However, group B presented longer vertical segments of positive cells as compared to group C, and shorter than those of group A. The deeper glandular structures were focally 1+ in both groups. CK20 expression was comparable in all three groups, depicting a 2+ diffuse reactivity at the surface epithelium and interposed pits with absence or focal reactivity at the neck and coiled gland areas. Ki-67 immunostaining paralleled that of the CK7. Staining for sulfated mucosubstances was positive in two of five cases of groups A and B, and in none of the cases of group C. We conclude that: (1) the long segments of CK7-positive glandular necks in H. pylori cases most probably indicate intense regenerative activity during active inflammation; (2) eradication of H. pylori does not warrant ad integrum restitution since long segments of Ki-67+, CK7+ cells at the germinative compartment of the glands (as well as cells with sulfomucins) were still recognizable in ex- H. pylori patients; (3) finally, differing from what happens in adults, children somehow manage to maintain fully differentiated CK20+ superficial epithelium while the H. pylori is in action.

Quiste meníngeo intraorbitario asociado a tejido cerebeloso heterotópico / Cystic meningeal intraorbitary association tissue cerebrose heterotopy

Presentamos el caso de una niña de 14 meses con colomboma coroideo bilateral y proptosis paraaxial progresiva del ojo izquierdo, en la que se halló un quiste meníngeo en la órbita izquierda con tejido cerebeloso ectópico. La lesión se resolvió hallar otros dos casos similares en la literatura, describiendo tejido cerebeloso ectópico en la órbita

Patología tumoral de ovario en edad pediátrica: experiencia del Hospital de Niños "Superiora Sor María Ludovica" / Pediatric ovarian tumors

Se evalúan 44 pacientes ingresadas en el período comprendido entre 1984-2001 con patología ovárica. El 79,5 por ciento (n=35) correspondieron a tumores y el 20,5 por ciento (n=9) a lesiones quísticas. Dentro del primer grupo 31/35 correspondieron a tumores germinales y 16/31 fueron teratomas maduros. Luego de evaluación clínica, imaginológica y de marcadores tumorales en aquellos con marcadores positivos y contenido mixto o sólido se realizó Punción Aspiración con Aguja Fina (PAAF) para corroborar diagnóstico. La conducta inicial fue la cirugía en 32/34 tumores y en 9/9 lesiones quísticas no tumorales. El 67 por ciento de las últimas ingresó con cuadro abdominal agudo por lo que recibió cirugía de urgencia. De obtenerse el diagnóstico sin cuadro de abdomen agudo y con marcadores tumorales negativos se utilizó la vía laparoscópica en 3 pacientes (2 quistes simples y 1 teratoma maduro). De las 15 pacientes con tumores germinales malignos 11 recibieron quimioterapia de acuerdo a protocolos SIOP (consecutivos por el tiempo de estudio) y 2 recibieron radioterapia luego de haberse diagnosticado disgerminoma. Sólo 2 pacientes, por considerarse los tumores irresecables al ingreso, recibieron quimioterapia preoperatoria. La sobrevida global fue del 94.5 por ciento (33/35) y la sobrevida libre de reactivaciones del 90 por ciento (31/35). Las dos pacientes fallecidas correspondieron al período inicial del estudio (1984-5) ingresando con diagnóstico tardío. Cinco pacientes (34 por ciento) de las portadoras de tumores malignos y que recibieron quimioterapia se han casado y tres de ellas tienen actualmente 5 hijos sanos que se controlan en nuestro Hospital

Tuberculosis perinatal / Perinatal tuberculosis

Se presenta el caso de una recién nacida con tuberculosis. Las manifestaciones que motivaron la consulta fueron fiebre y rechazo del alimento. Se agregaron dificultad respiratoria, hepatoesplenomegalia, distensión abdominal (ascitis), plaquetopenia. La bibliografía sobre tuberculosis congénita y perinatal es una entidad que debe ser considerada entre los diagnósticos diferenciales del recién nacido infectado.

Neurofibromatosis tipo 1. La necesidad de un reconocimiento clínico precoz / Type 1 neurofibromatosis. The need of an early diagnosis

La neurofibromatosis tipo 1 (NF-1) es una entidad claramente relacionada con la aparición de neoplasias en los niños. La NF-1 ha sido demostrada como factor pronóstico adverso ante neoplasias de nervios periféricos y del sistema nervioso central. El retraso diagnóstico y con ello la disminución en los porcentajes de resecabilidad, son factores que atentan contra la curación de estos pacientes. Por ello nos pareció oportuno revisar los criterios de diagnóstico, menejo y derivación para detectar en tiempo útil al portador de NF 1 e ingresarlo en seguimiento prospectivo, intentando de esa manera disminuir la morbimortalidad por tumores que ellos presentan.

Liver pathology in children with AIDS: a comparison between the South American and North American population.

Liver tissue from autopsies of twenty-nine cases of children with AIDS were collected from three major South America (S.4) pediatric hospitals. The hepatopathologic findings were classified in the same fashion as in a series of sixty-one children with AIDS from North America (NA): inflammation, non-specific, lymphoproliferative disorders, and giant cell transformation. By comparing both groups. we noted that the SA children were Younger at time of death consistent with a more rapid progression of the disease. Opportunistic infections varied with a higher prevalence of Cytomegalovirus (CMV) infection in SA children. The histopathologic features of CMV in the liter of SA children were associated with a conspicuous inflammation absent in the NA group. Finally, different non-specific hepatic changes were found in SA children, including one case of peliosis hepatis.

The clinical and histological spectrum of esophagitis in pediatrics. Some keys to its links to gastritis.

UNLABELLED: The purpose of our study was to assess the clinical and histological spectrum of esophagitis, seeking possible links between esophagitis and gastritis particularly Helicobacter pylori-associated, in pediatric patients. MATERIAL AND METHODS: We retrospectively studied 66 sequential and 63 gastric biopsies from 66 patients fulfilling the histological diagnosis of "esophagitis". Cases were arranged in two groups: G1 (H. pylori negative): N = 44 (27 m; 17 f), mean age 7.3 y (range 7-9 m-18 y) and G2 (H. pylori positive): N = 22 (16 f; 6 m), mean age 12.8 y (range 7-16 y). RESULTS: The bases for performing endoscopy and biopsies were as follows: in G1 (N44) symptoms of gastroesophageal reflux (GER) in 24 cases and non-GER in 20 cases; in G2 (N = 22): symptoms of GER in 13 and non-GER in 9 cases. Esophageal endoscopic findings for G1 patients included: normal mucosa 39; esophagitis 3; congestive mucosa and esophagitis 1 each. Stomach endoscopic findings for G1 patients were normal mucosa 29; nodular antrum 7; congestive mucosa 4; ulceration 2; unknown 2. G2 children revealed nodular antrum 19; congestive antrum 2; normal mucosa 1. Histology of esophageal biopsies in G1 was esophagitis grade 1,35; grade 2,4; grade 3, 4, and grade 5, 1. G2 showed esophagitis grade 1,20, and grade 2,2. The histologic findings of the gastric biopsies were as follows: G1 (N = 41): normal mucosa 23; mild chronic gastritis 6; mucus depletion in the superficial 5; mild acute gastritis 3; hemorrhage 1; insufficient tissue 3. G2: chronic gastritis associated with H. pylori with or without follicular hyperplasia 21; mild gastritis 1.