Histochemical diagnosis of Hirschsprung´s disease at our institution was introduced in the 1970s, calretinin imunohistochemistry on formalin fixed tissue was newly added in 2015. Employing both ...methods we were able to confirm Hirschsprung´s disease in 13 patients and exclude it in 34 patients since then. Calretinin seems highly reliable and easy to evaluate, it is not influenced by patient´s age, associated genetic features or the length of agangliosis. The number of inadequate samples was very low (3.8%). Histochemistry is useful as an adjunct tool to correct equivocal findings of calretinin staining and to facilitate diagnosis of short and ultra-short Hirschsprung´s disease. Serial biopsies from distal rectum and adjacent large bowel were obtained to assess the length of agangliosis preoperatively. The results of calretinin imunohistochemistry correlated very well with the findings in the colectomy specimens. In contrast, the length of affected bowel detected by histochemistry was often underestimated because acetylcholinesterase activity always diminishes orally irrespective of the length of aganglionic portion.
Eosinophilic enteritis is one of the eosinophilic gastrointestinal disorders characterised by various clinical symptoms. Histopathologic proof of dense eosinophilic infiltration is the cornerstone ...for the diagnosis. There is no consensus on how dense the infiltration should be, and cut-off values of the eosinophilic count in HPF have not been defined yet. Therapy for eosinophilic enteritis is based on an elimination diet and corticosteroid treatment. Herein the authors report a case of 14-year-old boy who suffered from acute abdominal pain. Computer tomography of the abdomen revealed a thickening of the duodenal wall mimicking a tumour, which seemed to infiltrate the gallbladder and omentum. Histopathological examination of samples taken during laparoscopy showed eosinophilic infiltration and sclerotic changes of the gallbladder and duodenum. Follow-up endoscopy proved extensive eosinophilic infiltration of the gastrointestinal tract: eosinophilic esophagitis, duodenal ulcer with dense eosinophilic presence and eosinophilic proctitis. The patient recovered after dietary restrictions and prednisone.
We report a patient with somatic retardation and woolly hair appearance who suffered from recurring episodes of watery mucous diarrhea, impaired liver functions, and failure to thrive. He manifested ...with severe infection courses, including hepatitis of unknown origin complicated by liver failure at 4 months, bronchopneumonia at 4 years, and life-threatening sepsis with septic shock at 8 years of age. Esophagogastroduodenoscopy and colonoscopy were performed at 4 years to rule out inflammatory bowel disease (IBD), and only signs of nonspecific colitis were evident. Immunology workup revealed slight reduction in CD4+ naive subsets and impaired T cell response to mitogens. Massive parallel sequencing (also termed next-generation sequencing – NGS) targeting a panel of primary immunodeficiency-related genes was used to examine the patient’s DNA. NGS analysis revealed two heterozygous variants in the TTC37 gene. Nonsense p.Arg1201* and missense p.Leu1505Ser variants in exons 34 and 42, respectively, were evaluated as pathogenic based on in silico predictions, their rare occurrence in the general population, and the fact that both mutations had already been described in patients with trichohepatoenteric syndrome (THES). As clinical features in our patient were in accordance with this diagnosis, we consider our findings as causative. THES could be a life-threatening condition, particularly in children who develop liver disease or severe infection courses. THES can have a similar clinical presentation as does very early-onset inflammatory bowel disease (VEO-IBD) and is often assigned to this group. Although IBD is generally regarded as a polygenic disease, some children with VEO-IBD are known also to have diseases with monogenic etiologies, as in THES. Targeted NGS is an efficient tool for establishing an accurate dia gnosis in VEO-IBD patients.
Background: Eosinophilic esophagitis (EoE) is a chronic, progressive inflammatory disease of the esophagus characterized by local eosinophilic infiltration accompanied by symptoms of esophageal ...dysfunction. The aim of this study was to characterize features of EoE dia gnosed regionally and to describe local strategies for its treatment. Methods: The observational survey retrospectively analyzed a data set of child patients with histologically proven EoE from five pediatric endoscopy centers. This analysis focused on describing their general situation (age, gender, symptoms) and also aimed to investigate any possible linkage between age and symptoms or length of dia gnosis period. Demographic features; clinical symptoms; laboratory, endoscopic, and histopathological findings; and chosen treatment of patients were recorded and analyzed. Results: From January 2010 to September 2020, 33 new cases of EoE were reported. Strong association of EoE with male sex is consistent with the results from formerly published studies (81.8%). The median age of symptom onset was 7 years, while the median age for dia gnosis was almost 13 years. The most common symptoms were reflux symptoms in general (39.4%), followed by vomiting (36.4%), and dysphagia (33.3%). Examination for sensitization to food allergens was performed on 23 (69.7%) patients with dia gnosed EoE. Out of these, 17 (51.5% of all cases) were found to be sensitive to some allergens. Most of this subgroup (and 48.5% of all cases) were examined by specific IgE testing, and just 2 (6.1% of all cases) patients were tested only by skin prick tests. Another allergic comorbidity was present in 75.8% of patients, and the most common of these were bronchial asthma and allergic rhinoconjunctivitis (45.5% and 42.2%, respectively). More than two-thirds of patients (69.7%) had abnormal macroscopic findings during dia gnostic endoscopy, and the most common were longitudinal furrows and white exudates. The most common initial modality of treatment was to use proton-pump inhibitors (PPI; 93.9%), followed by food elimination (75.8%) and then by corticosteroid administration (63.6%). The vast majority of patients treated with corticosteroids received a topical preparation (90.9%). Conclusion: This is the first retrospective study on pediatric patients with EoE in the Czech Republic. We found similar features of EoE as reported in formerly published works elsewhere. Collecting long-term prospective observational data in a national EoE register of patients in the Czech Republic would significantly improve our knowledge of this disease.
Indeterminate cell histiocytosis is a rare disease belonging to the group of malignant histiocytic diseases. The disease predominantly affects the skin. The disease appeared in the described patient ...at the age of 80 years. Morphs began to develop on the skin and rapidly spread over the whole body including the face. Only the hands and feet were left uncovered. The patients skin samples were taken from 2 sites for histological examination. The resulting conclusion was indeterminate cell histiocytosis. The treatment we chose was analogous to the procedures for Langerhans cell histiocytosis. We chose PUVA phototherapy as the first-line treatment. This treatment is frequently efficient for skin forms of Langerhans cell histiocytosis. In the described case, however, PUVA phototherapy did not influence the disease activity at all. As the second-line treatment, we used low-energy electron beam irradiation in the total dose of 36.2 Gy. This treatment had a positive impact, morphs began to diminish and slowly disappear from the skin. But they have not disappeared completely, therefore we assessed the treatment effect of the radiotherapy itself as partial remission of the disease. Within the third-line treatment, we used 2-chlorodeoxyadenosine in a dose of 5 mg/m2/per day, administered via subcutaneous injection over 5 consecutive days in monthly intervals. There were three cycles of this treatment administered overall. The treatment with 2-chlorodeoxyadenosine was tolerated without any adverse effects. The patient aged 82 years was only administered 3 cycles of 2-chlorodeoxyadenosine. When after the 3rd cycle the skin was free from any pathological morphs and only some pigmentation spots remained, we finished the treatment. The skin expressions of indeterminate cell histiocytosis completely disappeared after electron beam irradiation and the following administration of 3 cycles of 2-chlorodeoxyadenosine. The remission was short, however, after 6 months the disease recurred and the treatment is planned to resume. We assume the disease regresses following administration of 2-chlorodeoxyadenosine, but more than 3 treatment cycles will probably be needed to reach a longer-term response.Key words: electron beam irradiation - indeterminate cell histiocytosis - 2-chlorodeoxyadenosine.
Medulloblastoma, an embryonal neuroectodermal tumor of the cerebellum, is the most common malignant brain tumor in children. There are approximately 15 cases diagnosed in the Czech Republic each ...year. The recent World Health Organization classification recognizes several histopathological subtypes of medulloblastoma: classical, desmoplastic/ nodular with its extensive-nodularity variant, and anaplastic/ large-cell variant. Further molecular analysis identified four basic subgroups of medulloblastoma: WNT, SHH, Group 3, and Group 4. The subgroup of SHH meduloblastoma is associated with somatic mutations of SHH, PTCH1, SUFU, SMO and TP53, while the most common mutations found in infants up to three years of age were PTCH1 and SUFU. The majority of medulloblastomas are sporadic diseases, whereas only about 5- 10% of all cases occur in connection with hereditary genetic syndromes.
We present a case of a 21-months old girl diagnosed with a localized posterior fossa tumor. The histopathological examination revealed a desmoplastic/ nodular medulloblastoma. The treatment comprised a radical exstirpation of the tumor followed by adjuvant chemotherapy. With the use of array-CGH, a partial biallelic deletion of the SUFU gene (locus 10q24.32) was detected in the tumor DNA, whereas a monoallelic deletion was found in the peripheral lymphocyte DNA of the patient. These findings were confirmed by an independent qPCR method. Monoallelic germline deletion of SUFU was also identified in the patients mother, who was a healthy carrier. Pedigree of the family suggested a transition of the germline deletion of SUFU, since another brain tumors (including one case diagnosed before the age of three years) were identified in previous generations.
Germline mutations in SUFU gene are believed to predispose to infant desmoplastic/ nodular medulloblastomas, basal cell carcinomas and meningiomas. The susceptibility gene shows autosomal dominant inheritance with an incomplete penetrance. There is no evidence-based surveillance strategy suggested for the carriers of germline SUFU mutations/ deletions so far. Our recommendation is based both on a family history of our patient and similar cases described in the literature. Since the germinal mutations in SUFU are responsible for up to 50% of all desmoplastic medulloblastomas in children under three years of age, genetic testing of SUFU should be encouraged in this population of patients.
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