RESUMO
In 2008, we presented three cases of ALK-positive histiocytosis as a novel systemic histiocytic proliferation of early infancy with hepatosplenomegaly and dramatic hematological disturbances. This series of 10 cases (including the original three cases) describes an expanded clinicopathological spectrum and the molecular findings of this histiocytic proliferation. Six patients had disseminated disease: five presented in early infancy with eventual disease resolution, and the sixth presented at 2 years of age and died of intestinal, bone marrow, and brain involvement. The other four patients had localized disease involving nasal skin, foot, breast, and intracranial cavernous sinus - the first three had no recurrence after surgical resection, while the cavernous sinus lesion showed complete resolution with crizotinib therapy. The lesional histiocytes were very large, with irregularly folded nuclei, fine chromatin, and abundant eosinophilic cytoplasm, sometimes with emperipolesis. There could be an increase in foamy histiocytes and Touton giant cells with time, resembling juvenile xanthogranuloma. Immunostaining showed that the histiocytes were positive for ALK, histiocytic markers (CD68, CD163) and variably S100, while being negative for CD1a, CD207, and BRAF-V600E. Next-generation sequencing-based anchored multiplex PCR (Archer® FusionPlex®) performed in six cases identified KIF5B-ALK gene fusion in five and COL1A2-ALK fusion in one. There was no correlation of gene fusion type with disease localization or dissemination. The clinicopathological spectrum of ALK-positive histiocytosis is broader than originally described, and this entity is characterized by frequent presence of KIF5B-ALK gene fusion. We recommend that every unusual histiocytic proliferative disorder, especially disseminated lesions, be tested for ALK expression because of the potential efficacy of ALK inhibitor therapy in unresectable or disseminated disease.
Assuntos
Proliferação de Células , Fusão Gênica , Histiócitos/enzimologia , Histiocitose/genética , Proteínas de Fusão Oncogênica/genética , Adolescente , Adulto , Proliferação de Células/efeitos dos fármacos , Pré-Escolar , Crizotinibe/uso terapêutico , Feminino , Predisposição Genética para Doença , Histiócitos/patologia , Histiocitose/tratamento farmacológico , Histiocitose/enzimologia , Histiocitose/patologia , Hong Kong , Humanos , Lactente , Recém-Nascido , Masculino , Fenótipo , Inibidores de Proteínas Quinases/uso terapêutico , Singapura , Resultado do Tratamento , VitóriaRESUMO
Inherited metabolic disorders are traditionally diagnosed using broad and expensive panels of screening tests, often including invasive skin and muscle biopsy. Proponents of next-generation genetic sequencing have argued that replacing these screening panels with whole exome sequencing (WES) would save money. Here, we present a complex patient in whom WES allowed diagnosis of GM1 gangliosidosis, caused by homozygous GLB1 mutations, resulting in ß-galactosidase deficiency. A 10-year-old girl had progressive neurologic deterioration, macular cherry-red spot, and cornea verticillata. She had marked clinical improvement with initiation of the ketogenic diet. Comparative genomic hybridization microarray showed mosaic chromosome 3 paternal uniparental disomy (UPD). GM1 gangliosidosis was suspected, however ß-galactosidase assay was normal. Trio WES identified a paternally-inherited pathogenic splice-site GLB1 mutation (c.75+2dupT). The girl had GM1 gangliosidosis; however, enzymatic testing in blood was normal, presumably compensated for by non-UPD cells. Severe neurologic dysfunction occurred due to disruptive effects of UPD brain cells.
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Gangliosidose GM1/diagnóstico , Gangliosidose GM1/genética , Estudos de Associação Genética , Mosaicismo , Dissomia Uniparental , beta-Galactosidase/genética , beta-Galactosidase/metabolismo , Encéfalo/patologia , Criança , Eletroencefalografia , Ativação Enzimática , Ensaios Enzimáticos , Feminino , Genótipo , Humanos , Neuroimagem , Fenótipo , Células de Schwann/metabolismo , Células de Schwann/ultraestrutura , Pele/patologia , Sequenciamento do ExomaRESUMO
INTRODUCTION: Collagenous gastritis is a rare disease characterized by the subepithelial deposition of collagen bands. Two phenotypes of the disease have been described: a pediatric-onset and an adult-onset type. The adult-onset form is associated with collagenous colitis and autoimmune disorders. No effective treatment has been identified to date. OBJECTIVE: We aim to describe the clinical features and outcomes of patients in our cohort and provide a summary of published pediatric cases with collagenous gastritis and colitis reported to date to gather information that will contribute to improved knowledge of this rare condition. METHODS: A retrospective chart review of all patients with collagenous gastritis and/or colitis who were treated at the Royal Children's Hospital, Melbourne, was performed. A literature review was also conducted. RESULTS: A total of 12 cases of collagenous gastritis were reviewed. Three of 12 (25%) patients had associated collagenous colitis. The most common clinical presentation was iron deficiency anemia. Nine (75%) patients were followed up, and repeat endoscopies were performed in 8 (67%). Iron deficiency anemia resolved in all patients on oral iron supplementation. Histologic improvement was only identified in one patient with the adult phenotype who had been treated with oral corticosteroids and azathioprine. CONCLUSIONS: Collagenous gastritis is a rare condition in children. A small proportion of children develop features of the "'adult" phenotype at a very young age. Patients with collagenous gastritis require long-term follow-up and monitoring of their disease. Further randomized clinical trials are needed to establish an effective therapeutic strategy.
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Colite Colagenosa/diagnóstico , Colite Colagenosa/terapia , Gastrite/diagnóstico , Gastrite/terapia , Adolescente , Biópsia , Criança , Pré-Escolar , Colite Colagenosa/fisiopatologia , Colágeno , Dieta/métodos , Dieta Livre de Glúten , Endoscopia Gastrointestinal/métodos , Feminino , Seguimentos , Mucosa Gástrica/fisiopatologia , Gastrite/fisiopatologia , Humanos , Masculino , Inibidores da Bomba de Prótons/uso terapêutico , Estudos RetrospectivosRESUMO
BACKGROUND: Infantile hemangioma (IH) with minimal or arrested growth (IH-MAG) is becoming increasingly recognized in the literature. It is important to be aware of their existence, because the correct diagnosis is essential for prognostication and treatment and, in the case of facial segmental lesions, the direction of further investigations if PHACE (posterior fossa abnormalities and other structural brain abnormalities; hemangioma(s) of the cervical facial region; arterial cerebrovascular anomalies; cardiac defects, aortic coarctation, and other aortic abnormalities; eye anomalies) syndrome or Sturge-Weber syndrome is suspected. Although the clinical and histologic characteristics of IH-MAG resemble capillary malformations, positive GLUT-1 status is a delineating feature. METHODS: We reviewed nine cases of infants who presented after 2000 with birthmarks showing unique clinical features suggestive of a special variant of IHs. All patients had serial photographs taken demonstrating resolution of the birthmark over time. Five of these cases had skin biopsy performed, all of which confirmed GLUT-1 positivity. RESULTS: This photographic series of IH-MAG demonstrates their unique clinical, histologic, and immunochemistry features. They were nearly fully formed at birth, and their common clinical features included telangiectasia, venules, and matte erythema with light and dark areas. Spontaneous resolution over time without cosmetic disfigurement was the observed natural history in the majority of cases. CONCLUSION: IH-MAG is a unique clinical subset of hemangioma for which close observation is the preferred treatment. When in doubt, a biopsy for histology and GLUT-1 status may be needed to confirm the diagnosis before embarking on unnecessary laser treatment or medical interventions.
Assuntos
Hemangioma/diagnóstico , Neoplasias Cutâneas/diagnóstico , Diagnóstico Diferencial , Feminino , Transportador de Glucose Tipo 1/genética , Hemangioma/genética , Humanos , Lactente , Recém-Nascido , Masculino , Prognóstico , Neoplasias Cutâneas/genéticaRESUMO
OBJECTIVES: Assessment of treatment response in children with celiac disease (CD) after commencing a strict gluten-free diet (GFD) is generally based on the resolution of clinical features and normalization of serology. Recent adult studies have shown that serologic markers do not correlate with mucosal recovery. We aimed (i) to determine whether anti-tissue transglutaminase immunoglobulin (Ig)A (tTG) and anti-deamidated gliadin peptide IgG (DGP) antibodies are sensitive and specific markers of mucosal recovery in children with CD on a GFD for at least 12 months, and (ii) to determine whether a validated dietary questionnaire of compliance can identify patients with mucosal recovery. METHODS: A total of 150 children with biopsy-proven CD were prospectively evaluated with duodenal biopsies at ≥12 months on GFD, paired with repeat tTG and DGP serology. The biopsies were reviewed in a blinded manner by two histopathologists and graded by Marsh criteria. A validated questionnaire of dietary compliance was also administered. RESULTS: Of 150 children recruited, 27 (18%) had positive serology, 97 (65%) had negative serology, and 26 (17%) had equivocal serology. Of the 97 children with negative serology, none had Marsh type 3 enteropathy. Of the 27 patients with positive serology, only 6 had Marsh type 3 changes. The sensitivity and specificity of serology as a marker of significant mucosal pathology was 75 and 85%, respectively, with a positive predictive value of 22% but a negative predictive value of 98%. Of the 129 (86%) questionnaires completed, 88% reported good or excellent compliance with a GFD (negative predictive value 97%). CONCLUSIONS: This study suggests that follow-up using two serological tests in children with CD on a GFD may obviate the need for repeat mucosal biopsy in the majority of patients. A standardized dietary questionnaire may be useful in identifying patients who require further evaluation.
Assuntos
Doença Celíaca/imunologia , Duodeno/patologia , Gliadina/imunologia , Imunoglobulina A/sangue , Imunoglobulina G/sangue , Mucosa Intestinal/patologia , Transglutaminases/imunologia , Adolescente , Biomarcadores/sangue , Doença Celíaca/dietoterapia , Doença Celíaca/patologia , Criança , Pré-Escolar , Dieta Livre de Glúten , Feminino , Proteínas de Ligação ao GTP , Humanos , Lactente , Masculino , Cooperação do Paciente , Valor Preditivo dos Testes , Estudos Prospectivos , Proteína 2 Glutamina gama-Glutamiltransferase , Inquéritos e QuestionáriosRESUMO
Focal cortical dysplasia is a common cortical malformation and an important cause of epilepsy. There is evidence for shared molecular mechanisms underlying cortical dysplasia, ganglioglioma, hemimegalencephaly, and dysembryoplastic neuroepithelial tumor. However, there are no familial reports of typical cortical dysplasia or co-occurrence of cortical dysplasia and related lesions within the same pedigree. We report the clinical, imaging, and histologic features of six pedigrees with familial cortical dysplasia and related lesions. Twelve patients from six pedigrees were ascertained from pediatric and adult epilepsy centers, eleven of whom underwent epilepsy surgery. Pedigree data, clinical information, neuroimaging findings, and histopathologic features are presented. The families comprise brothers with focal cortical dysplasia, a male and his sister with focal cortical dysplasia, a female with focal cortical dysplasia and her brother with hemimegalencephaly, a female with focal cortical dysplasia and her female first cousin with ganglioglioma, a female with focal cortical dysplasia and her male cousin with dysembryoplastic neuroepithelial tumor, and a female and her nephew with focal cortical dysplasia. This series shows that focal cortical dysplasia can be familial and provides clinical evidence suggesting that cortical dysplasia, hemimegalencephaly, ganglioglioma, and dysembryoplastic neuroepithelial tumors may share common genetic determinants.
Assuntos
Epilepsia/diagnóstico , Epilepsia/genética , Predisposição Genética para Doença/genética , Malformações do Desenvolvimento Cortical/diagnóstico , Malformações do Desenvolvimento Cortical/genética , Adolescente , Adulto , Criança , Epilepsia/etiologia , Feminino , Humanos , Lactente , Masculino , Malformações do Desenvolvimento Cortical/complicações , Linhagem , Adulto JovemAssuntos
Tosse , Infecções por Mycobacterium não Tuberculosas/diagnóstico , Infecções por Mycobacterium não Tuberculosas/tratamento farmacológico , Sons Respiratórios , Doenças Torácicas/diagnóstico , Doenças Torácicas/tratamento farmacológico , Antibacterianos/uso terapêutico , Biópsia , Broncoscopia , Diagnóstico Diferencial , Diagnóstico por Imagem , Feminino , Humanos , LactenteRESUMO
Bullous dermolysis of the newborn is an inherited mechano-bullous disorder classed as a rare subtype of dystrophic epidermolysis bullosa. Fewer than 30 cases of bullous dermolysis of the newborn have been reported in the literature and the pathogenesis of the disease is poorly understood. Only a minority of cases have had pathogenic mutations identified. We present a case of a neonate born to non-consanguineous Caucasian parents with an exon 54 (c.5017G > A, p.G1673R) mutation reported as one mutant allele in a case of recessive dystrophic epidermolysis bullosa (generalized other).
Assuntos
Colágeno Tipo VII/genética , Epidermólise Bolhosa Distrófica/genética , Epidermólise Bolhosa Distrófica/patologia , Heterozigoto , Humanos , Recém-Nascido , Masculino , Mutação de Sentido IncorretoRESUMO
Cholinergic nerves are identified by labelling molecules in the ACh synthesis, release and destruction pathway. Recently, antibodies against another molecule in this pathway have been developed. Choline reuptake at the synapse occurs via the high-affinity choline transporter (CHT1). CHT1 immunoreactivity is present in cholinergic nerve fibres containing vesicular acetylcholine transporter (VAChT) in the human and rat central nervous system and rat enteric nervous system. We have examined whether CHT1 immunoreactivity is present in nerve fibres in human intestine and whether it is colocalised with markers of cholinergic, tachykinergic or nitrergic circuitry. Human ileum and colon were fixed, sectioned and processed for fluorescence immunohistochemistry with antibodies against CHT1, class III beta-tubulin (TUJ1), synaptophysin, common choline acetyl-transferase (cChAT), VAChT, nitric oxide synthase (NOS), substance P (SP) and vasoactive intestinal peptide (VIP). CHT1 immunoreactivity was present in many nerve fibres in the circular and longitudinal muscle, myenteric and submucosal ganglia, submucosa and mucosa in human colon and ileum and colocalised with immunoreactivity for TUJ1 and synaptophysin confirming its presence in nerve fibres. In nerve fibres in myenteric ganglia and muscle, CHT1 immunoreactivity colocalised with immunoreactivity for VAChT and cChAT. Some colocalisation occurred with SP immunoreactivity, but little with immunoreactivity for VIP or NOS. In the mucosa, CHT1 immunoreactivity colocalised with that for VIP and SP in nerve fibres and was also present in vascular nerve fibres in the submucosa and on epithelial cells on the luminal border of crypts. The colocalisation of CHT1 immunoreactivity with VAChT immunoreactivity in cholinergic enteric nerves in the human bowel thus suggests that CHT1 represents another marker of cholinergic nerves.
Assuntos
Sistema Nervoso Entérico/metabolismo , Proteínas de Membrana Transportadoras/imunologia , Proteínas Vesiculares de Transporte de Acetilcolina/metabolismo , Especificidade de Anticorpos/imunologia , Biomarcadores/metabolismo , Criança , Sistema Nervoso Entérico/patologia , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Gânglios/metabolismo , Gânglios/patologia , Humanos , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , Linfócitos/metabolismo , Linfócitos/patologia , Músculos/metabolismo , Músculos/patologia , Fibras Nervosas/enzimologia , Fibras Nervosas/metabolismo , Óxido Nítrico Sintase/metabolismo , Transporte Proteico , Substância P/metabolismo , Sinaptofisina/metabolismo , Tubulina (Proteína)/metabolismo , Peptídeo Intestinal Vasoativo/metabolismoRESUMO
We report 3 cases of a previously uncharacterized form of histiocytosis presenting in early infancy and showing ALK immunoreactivity. The patients presented with pallor, massive hepatosplenomegaly, anemia, and thrombocytopenia. Liver biopsy showed infiltration of the sinusoids by large histiocytes with markedly folded nuclei, fine chromatin, small nucleoli, and voluminous lightly eosinophilic cytoplasm that sometimes was vacuolated or contained phagocytosed blood cells. One patient developed cutaneous infiltrates that morphologically resembled juvenile xanthogranuloma. The histiocytes were immunoreactive for histiocytic markers (CD68, CD163, lysozyme), S100 protein, ALK (membranous and cytoplasmic pattern), and dendritic cell markers (fascin, factor XIIIa), but not CD1a and langerin. One case successfully analyzed by molecular techniques revealed TPM3-ALK fusion. Thus the spectrum of diseases exhibiting ALK translocation should be expanded to include ALK(+) histiocytosis. The disease in the 3 patients (2 having been given chemotherapy) resolved slowly over many months.
Assuntos
Receptores de Activinas Tipo II/metabolismo , Histiócitos/patologia , Histiocitose/patologia , Biópsia , Proliferação de Células , Feminino , Humanos , Lactente , Recém-Nascido , Fígado/patologia , Transporte Proteico , Pele/patologiaRESUMO
Multiple endocrine neoplasia 2B (MEN2B) is a rare syndrome caused by an activating mutation of the RET gene, leading to enteric gangliomatosis. This child presented with constipation at 1-mo old, was diagnosed with MEN2B by rectal biopsy at 4 mo, had thyroidectomy at 9 mo and a colectomy at 4 years. We studied the extent of neuronal and nerve fibre proliferation and which classes of enteric nerves are affected by examining the colon with multiple neuronal antibodies. Resected transverse colon was fixed, frozen, sectioned and processed for fluorescence immunohistochemistry labelling with antibodies against TUJ1, Hu, ChAT, NOS, VIP, SP and CGRP and cKit. Control transverse colon was from the normal margin of Hirschsprung (HSCR) colon (4-year-old) and a child with familial adenomatous polyposis (FAP, 12 year). Myenteric ganglia were increased in size to as wide as the circular muscle. There was a large increase in nerve cells and nerve fibres. ChAT-, NOS-, VIP- and SP-immunoreactive nerve fibres all increased in the myenteric ganglia. NOS-IR nerves preferentially increased in the muscle, while VIP and SP increased in submucosal ganglia and mucosal nerve fibres. The density of ICC was normal. RET overactivation in MEN2B lead to a large increase in intrinsic nerve fibres in the myenteric and submucosal ganglia, with a relative increase in NOS-IR nerve fibres in the circular muscle and VIP and SP in the submucosal ganglia and mucosa. The changes were associated with severe constipation resulting in colectomy at 4 years.
RESUMO
Objective: To characterize the clinical features and neuropathology associated with recessive VAC14 mutations. Methods: Whole-exome sequencing was used to identify the genetic etiology of a rapidly progressive neurological disease presenting in early childhood in two deceased siblings with distinct neuropathological features on post mortem examination. Results: We identified compound heterozygous variants in VAC14 in two deceased siblings with early childhood onset of severe, progressive dystonia, and neurodegeneration. Their clinical phenotype is consistent with the VAC14-related childhood-onset, striatonigral degeneration recently described in two unrelated children. Post mortem examination demonstrated prominent vacuolation associated with degenerating neurons in the caudate nucleus, putamen, and globus pallidus, similar to previously reported ex vivo vacuoles seen in the late-endosome/lysosome of VAC14-deficient neurons. We identified upregulation of ubiquitinated granules within the cell cytoplasm and lysosomal-associated membrane protein (LAMP2) around the vacuole edge to suggest a process of vacuolation of lysosomal structures associated with active autophagocytic-associated neuronal degeneration. Interpretation: Our findings reveal a distinct clinicopathological phenotype associated with recessive VAC14 mutations.
RESUMO
Whole-exome sequencing of two brothers with drug-resistant, early-onset, focal epilepsy secondary to extensive type IIA focal cortical dysplasia identified a paternally inherited, nonsense variant of DEPDC5 (c.C1663T, p.Arg555*). This variant has previously been reported to cause familial focal epilepsy with variable foci in patients with normal brain imaging. Immunostaining of resected brain tissue from both brothers demonstrated mammalian target of rapamycin (mTOR) activation. This report shows the histopathological features of cortical dysplasia associated with a DEPDC5 mutation, confirms mTOR dysregulation in the malformed tissue and expands the spectrum of neurological manifestations of DEPDC5 mutations to include severe phenotypes with large areas of cortical malformation.
RESUMO
Succinate dehydrogenase (SDH)-deficient renal carcinoma has been accepted as a provisional entity in the 2013 International Society of Urological Pathology Vancouver Classification. To further define its morphologic and clinical features, we studied a multi-institutional cohort of 36 SDH-deficient renal carcinomas from 27 patients, including 21 previously unreported cases. We estimate that 0.05% to 0.2% of all renal carcinomas are SDH deficient. Mean patient age at presentation was 37 years (range, 14 to 76 y), with a slight male predominance (M:F=1.7:1). Bilateral tumors were observed in 26% of patients. Thirty-four (94%) tumors demonstrated the previously reported morphology at least focally, which included: solid or focally cystic growth, uniform cytology with eosinophilic flocculent cytoplasm, intracytoplasmic vacuolations and inclusions, and round to oval low-grade nuclei. All 17 patients who underwent genetic testing for mutation in the SDH subunits demonstrated germline mutations (16 in SDHB and 1 in SDHC). Nine of 27 (33%) patients developed metastatic disease, 2 of them after prolonged follow-up (5.5 and 30 y). Seven of 10 patients (70%) with high-grade nuclei metastasized as did all 4 patients with coagulative necrosis. Two of 17 (12%) patients with low-grade nuclei metastasized, and both had unbiopsied contralateral tumors, which may have been the origin of the metastatic disease. In conclusion, SDH-deficient renal carcinoma is a rare and unique type of renal carcinoma, exhibiting stereotypical morphologic features in the great majority of cases and showing a strong relationship with SDH germline mutation. Although this tumor may undergo dedifferentiation and metastasize, sometimes after a prolonged delay, metastatic disease is rare in the absence of high-grade nuclear atypia or coagulative necrosis.
Assuntos
Carcinoma de Células Renais/enzimologia , Carcinoma de Células Renais/patologia , Neoplasias Renais/enzimologia , Neoplasias Renais/patologia , Succinato Desidrogenase/biossíntese , Adolescente , Adulto , Idoso , Carcinoma de Células Renais/genética , Análise Mutacional de DNA , Feminino , Humanos , Imuno-Histoquímica , Neoplasias Renais/genética , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Succinato Desidrogenase/genética , Análise Serial de Tecidos , Adulto JovemAssuntos
Carcinoma de Células Renais/genética , Tumores do Estroma Gastrointestinal/genética , Mutação em Linhagem Germinativa , Neoplasias Renais/genética , Proteínas de Membrana/genética , Succinato Desidrogenase/deficiência , Adulto , Carcinoma de Células Renais/patologia , Feminino , Tumores do Estroma Gastrointestinal/metabolismo , Humanos , Neoplasias Renais/patologiaRESUMO
OBJECTIVES: Our purpose was to study the relation between gastroesophageal reflux (GER) and esophagitis in infants with persistent distress. STUDY DESIGN: Infants (n = 125, 79 boys; median age, 4.2 months) with persistent distress and clinical symptoms suggestive of GER and esophagitis were retrospectively studied. All had undergone esophageal 24-hour pH monitoring and had upper gastrointestinal biopsy specimens taken. RESULTS: There were 65 (48%) infants with inflammatory changes found in at least one upper gastrointestinal biopsy specimen, of whom 32 (25.6%) had esophagitis; 11 infants with esophagitis also had gastritis or duodenitis. Although infants with frequent regurgitation (n = 65) had significantly more frequent GER episodes per 24 hours (P <.03) and greater fractional reflux time (P <.001) than infants without, this was not associated with histologic esophagitis (P =.33). Of the 32 infants with esophagitis, 9 had abnormal pH monitoring and 23 had nonreflux esophagitis. A separate group of 23 infants had abnormal pH monitoring but no esophagitis. Diagnostic agreement between pH monitoring and esophageal histologic features was poor (kappa = 0.07). CONCLUSION: Esophagitis occurred in one quarter of infants with persistent distress. Abnormal esophageal pH monitoring did not reliably predict esophagitis, suggesting a nonacid peptic cause in some of these infants.
Assuntos
Esofagite/etiologia , Refluxo Gastroesofágico/complicações , Esofagite/epidemiologia , Esofagite/patologia , Esôfago/metabolismo , Feminino , Humanos , Concentração de Íons de Hidrogênio , Lactente , Recém-Nascido , Masculino , Monitorização Fisiológica , Prevalência , Prognóstico , Reprodutibilidade dos Testes , Estudos RetrospectivosRESUMO
OBJECTIVES: Children occasionally have dysphagia in the absence of an apparent primary cause. Esophageal eosinophilia is sometimes seen in these patients at the time of upper endoscopy but its significance is not clear. Although eosinophilia is regarded by some as a histologic hallmark of childhood reflux esophagitis, it may in fact signal a primary eosinophilic esophagitis in children with dysphagia. Our aim was to evaluate esophagitis, acid reflux determined by pH probe, and esophageal eosinophilia in children with the primary complaint of dysphagia. METHODS: A retrospective study was performed in 42 children, admitted for investigation of dysphagia, in whom no primary cause could be found. Twenty-one children (mean age +/- SD, 10.1 +/- 4.0 years) had esophageal eosinophilia and 21 children (8.3 +/- 4.7 years) did not. Clinical, endoscopic, manometric and esophageal pH parameters in these two groups were compared. RESULTS: Patients with esophageal eosinophilia were more often male (p<0.01) with a history of allergy (p<0.001) and food bolus obstruction (p<0.05) requiring endoscopic removal. Their esophageal mucosa appeared wrinkled and thickened at endoscopy with basal cell proliferation, and large numbers of eosinophils in esophageal mucosal biopsies. Continuous esophageal pH records and motility studies, when obtained, were similar in both groups and were within normal values. CONCLUSION: Children with dysphagia who have esophageal eosinophilia are unlikely to have pathologic gastroesophageal reflux.