Search

Activating mutations in thyrotropin receptor (TSHR) have been previously described in the context of nonautoimmune hyperthyroidism and thyroid adenomas. We describe, for the first time, a mutation inTSHRcontributing to follicular thyroid carcinoma (FTC) in an adolescent. A 12-year-old girl presented with a right-sided neck swelling, increasing in size over the previous four weeks. Clinical examination revealed a firm, nontender thyroid nodule. Ultrasound scan of the thyroid showed a heterogeneous highly vascular mass. Thyroid function tests showed suppressed TSH [C, p.Ile568Thr) inTSHR. Papillary thyroid carcinomas constitute the most common thyroid malignancy in childhood, while FTC is rare. FTC due toTSHRmutation suggests an underlying, yet to be explored, molecular pathway leading to the development of malignancy. The case is also unique in that the clinical presentation of FTC as a toxic thyroid nodule has not been previously reported in children.

We report a child with short stature since birth who was otherwise well, presenting at 2.8 years with progressive granulomatous skin lesions when diagnosed with severe T cell immunodeficiency. When previously investigated for short stature, and at the time of current investigations, she had no radiological skeletal features characteristics for cartilage hair hypoplasia, but we found a disease causing RMRP (RNase mitochondrial RNA processing endoribonuclease) gene mutation. Whilst search for HLA matched unrelated donor for haematopoietic stem cell transplantation (HSCT) was underway, she developed rapidly progressive EBV-related lymphoproliferative disorder requiring laparotomy and small bowel resection, and was treated with anti-B cell monoclonal antibody and eventually curative allogeneic HSCT. Screening for RMRP gene mutations should be part of immunological evaluation of patients with 'severe and/or combined' T cell immunodeficiency of unknown origin, especially when associated with short stature and regardless of presence or absence of radiological skeletal features.

Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children and accounts for about 5% of all malignant paediatric tumours. β-Catenin, a multifunctional nuclear transcription factor in the canonical Wnt signaling pathway, is active in myogenesis and embryonal somite patterning. Dysregulation of Wnt signaling facilitates tumour invasion and metastasis. This study characterizes Wnt/β-catenin signaling and functional activity in paediatric embryonal and alveolar RMS. Immunohistochemical assessment of paraffin-embedded tissues from 44 RMS showed β-catenin expression in 26 cases with cytoplasmic/membranous expression in 9/14 cases of alveolar RMS, and 15/30 cases of embryonal RMS, whereas nuclear expression was only seen in 2 cases of embryonal RMS. The potential functional significance of β-catenin expression was tested in four RMS cell lines, two derived from embryonal (RD and RD18) RMS and two from alveolar (Rh4 and Rh30) RMS. Western blot analysis demonstrated the expression of Wnt-associated proteins including β-catenin, glycogen synthase kinase-3β, disheveled, axin-1, naked, LRP-6 and cadherins in all cell lines. Cell fractionation and immunofluorescence studies of the cell lines (after stimulation by human recombinant Wnt3a) showed reduced phosphorylation of β-catenin, stabilization of the active cytosolic form and nuclear translocation of β-catenin. Reporter gene assay demonstrated a T-cell factor/lymphoid-enhancing factor-mediated transactivation in these cells. In response to human recombinant Wnt3a, the alveolar RMS cells showed a significant decrease in proliferation rate and induction of myogenic differentiation (myogenin, MyoD1 and myf5). These data indicate that the central regulatory components of canonical Wnt/β-catenin signaling are expressed and that this pathway is functionally active in a significant subset of RMS tumours and might represent a novel therapeutic target.

Ventriculo-peritoneal shunts are used extensively for the management of hydrocephalus and frequently present with complications such as shunt blockage and infection. Cerebrospinal fluid (CSF) eosinophilia and allergic responses to the shunt itself are rare, poorly understood but increasingly recognised complications. Here, the authors describe a child who required multiple shunt revision surgeries due to extensive scalp tenderness overlying the shunt tubing and persistent severe headaches despite having a normal working shunt and no CSF infection or eosinophilia. Histological investigation of excised tissue during the last shunt revision demonstrated fibrosis with scar tissue and chronic inflammatory infiltrate with foreign body giant cells and few abortive granulomata. This was felt to represent a foreign body reaction to the shunt. A hypoallergenic ‘extracted' shunt was trialled (extracted Delta® valve and extracted ventricular and peritoneal catheters; Medtronic) and the child has had no further shunt revisions and is currently asymptomatic 1 year after the insertion.

Multiple defects in apoptotic pathways have been described in peripheral neuroblastic tumours (NTs). Mitosis-karyorrhexis index (MKI) is a reliable morphological marker identifying favourable and unfavourable NTs. The extent to which apoptotic processes contribute to determine the clinical significance of MKI is still undefined. Apoptosis was investigated in a series of 110 peripheral NTs by comparing MKI to immunohistochemical and molecular apoptotic features. High MKI was found in 55 out of 110 NTs (50%) and was associated with advanced stage (P = 0.007), neuroblastoma (NB) histological category (P = 0.024), MYCN amplification (P0.001), and poor outcome (P = 0.011). Overall survival probability was 45% in patients with high MKI compared to 73% in patients with low MKI. In the same 110 NTs, the expression of Bcl-2, Bcl-XL, Bax and Mcl-1 was studied by immunohistochemistry, but no significant associations were found with clinicohistological features. Microarray analysis of apoptotic genes was performed in 40 out of 110 representative tumours. No significant association was found between the expression of apoptotic genes and MKI or clinicohistological features. Proliferative activity was assessed in 60 out of 110 representative tumours using Ki67 immunostaining, but no significant correlations with MKI or clinicobiological features were found. In NTs, the combination of apoptosis and proliferation as expressed by MKI is a significant prognostic parameter, although neither of them is per se indicative of the clinicobiological behaviour and outcome.

Background: Pericardial effusion and cardiac tamponade are known to be rare but potentially fatal complications of umbilical venous catheterisation, even when the line tip is appropriately placed and is proximal to the right atrium. Highlight of case: We report a fatal case of cardiac tamponade due to the presence of pericardial total parenteral nutrition associated with bilateral pleural effusions in an extremely low birth weight neonate with an umbilical venous catheter. Conclusion: It is important to promptly identify and treat this rare but devastating complication of what is often considered “routine” care. Timely pericardiocentesis should be considered in a preterm baby who deteriorates suddenly and has a central venous catheter in situ.

Subcutaneous granuloma annulare of the penis is rare, with only 10 cases in the world literature. This paper describes the youngest case ever reported and reviews its clinical features and management.

Anaplastic large cell lymphoma (ALCL) is a rare tumor comprising around 10–15% of childhood lymphomas. We describe the case of a female who initially presented with localized skin disease associated with an insect bite. However, she subsequently relapsed with widespread systemic ALK-positive ALCL that included lymphoma deposits in the myocardium, a very rare manifestation. Her disease responded well to chemotherapy but she later developed a fatal relapse in the CNS. We also present data on an immune response to ALK, demonstrating a fluctuation in the levels of circulating antibodies to ALK corresponding to the different phases of her illness. Pediatr Blood Cancer 2008;50:879–881. © 2007 Wiley-Liss, Inc.

We describe a 13-year-old boy who developed acute renal failure associated with Gemella haemolysans pneumonia. At presentation he was found to have macroscopic hematuria associated with lobar pneumonia. Gemella haemolysans was isolated from blood cultures. Renal failure was detected on admission, progressed and dialysis was required until day 18. Renal impairment had resolved by 3 months after the initial presentation. Histopathology of a renal biopsy showed focal proliferative glomerulonephritis, but the predominant abnormality was tubular damage associated with erythrocyte casts in tubular lumina. We believe that tubular damage due to hematuria rather than the glomerular changes was the most likely cause of renal failure.

Screening for coeliac disease is recommended for children from certain risk groups, with implications for diagnostic procedures and dietetic management. The risk of a malignant complication in untreated coeliac disease is not considered high in children. We present the case of a girl with type I diabetes who developed weight loss, fatigue, and inguinal lymphadenopathy. Four years before, when she was asymptomatic, a screening coeliac tTG test was positive, but gluten was not eliminated from her diet. Based on clinical examination, a duodenal biopsy, and an inguinal lymph node biopsy were performed, which confirmed both coeliac disease and an anaplastic large-cell lymphoma. HLA-typing demonstrated that she was homozygous for HLA-DQ8, which is associated with higher risk for celiac disease, more severe gluten sensitivity, and diabetes susceptibility. She responded well to chemotherapy and has been in remission for over 4 years. She remains on a gluten-free diet. This is the first case reporting the association of coeliac disease, type I diabetes, and anaplastic large-cell lymphoma in childhood. The case highlights the malignancy risk in a genetically predisposed individual, and the possible role of a perpetuated immunologic response by prolonged gluten exposure.

Pyogenic granuloma (PG), also known as lobular capillary hemangioma, is a benign vascular tumor, most commonly arising on the skin and the oral mucosa. Gastrointestinal localization of PG, except for the oral cavity, is exceptionally rare. We describe a case of ileal PG occurring in a 13-year-old girl, presenting with intestinal obstruction. Histological examination revealed proliferation of capillary-sized vessels, with prominent intravascular component, involving the entire thickness of the intestinal wall. Immunohistochemistry showed positivity for CD31, CD34 and von Willebrand factor, whereas immunostaining for glucose transporter-1 protein (GLUT1) and for human herpes virus 8 (HHV-8) was negative. We suggest that PG should be considered in the differential diagnosis of childhood gastrointestinal polypoid lesions.

We describe in this report what we believe to be the first report of a rare presentation of a very rare tumor, especially in this age group. We highlight the importance of early consideration of malignancy as a cause of chylous ascites in infancy and we discuss different causes of chylous ascites.

Rhabdomyosarcoma (RMS) is a common childhood solid tumor, resulting from dysregulation of the skeletal myogenesis program. Two major histological subtypes occur in childhood RMS, embryonal and alveolar. While chromosomal rearrangements account for the majority of alveolar tumors, the genetic defects underlying the pathogenesis of embryonal RMS remain largely undetermined. A few studies performed on small series of embryonal tumors suggest that dysregulation of RAS function may be relevant to disease pathogenesis. To explore further the biological and clinical relevance of mutations with perturbing consequences on RAS signaling in embryonal RMS, we investigated the prevalence of PTPN11, HRAS, KRAS, NRAS, BRAF, MEK1, and MEK2 mutations in a relatively large cohort of primary tumors. While HRAS and KRAS were found to be rarely mutated, we identified somatic NRAS lesions in 20% of cases. All mutations were missense and affected codon 61, with the introduction of a positive charged amino acid residue representing the most common event. PTPN11 was found mutated in one tumor specimen, confirming that somatic defects in this gene are relatively uncommon in RMS, while no mutation was observed in BRAF and MEK genes. Although no clear association of mutations with any clinical variable was observed, comparison of the outcome between mutation-positive and mutation-negative cases indicated a trend for a higher percentage of patients exhibiting a better outcome in the former. Our findings provide evidence that dysregulation of RAS signaling is a major event contributing to embryonal RMS pathogenesis.

We report the case of a two-year-old girl with end-stage dilated cardiomyopathy who was a status I heart transplant candidate. Partial left ventriculectomy and novel mitral valve repair were performed. Early hemodynamic and functional improvements were maintained at the 18-month follow-up.

Infantile myofibromatosis (IM) is a rare pathological entity characterized by solitary or multiple nodular skin, soft tissues or bony lesions. Craniovertebral (CV) junction lesions are rare. We report the successful management of a solitary IM involving the posterior elements of the CV junction in a 6-month-old child.

Objectives: We observed a cohort of children presenting with rectal bleeding that were identified as having Enterobius vermicularis at colonoscopy and questioned the reliability of conventional diagnostic methods of identifying E. vermicularis. Patients and Methods: The study was retrospective in nature and subjects were investigated by colonoscopy between May 1997 and December 1999. Patients were identified as having E. vermicularis infestation by direct visualisation of the adult worms at colonoscopy. Patients were treated with mebendazole and a record of their clinical response documented. Results: A total of 180 colonoscopic examinations were performed during the study period. E. vermicularis was identified macroscopically in 31 cases (17.2%). The symptom profile of patients with E. vermicularis were abdominal pain, 19 of 26 (73%); rectal bleeding, 16 of 26 (62%); chronic diarrhoea, 13 of 26 (50%) and weight loss, 11 of 26 (42%). Ova cysts and parasites were identified in none of the saline swabs analysed in 20 patients. Sellotape testing was performed in only 4 patients and was negative in all. Of the 26 children, 21 (81 %) demonstrated histopathological features of nonspecific colitis. There was clinical resolution of symptoms in 19 of 23 patients. Conclusions: We suggest that in patients with symptoms suggestive of inflammatory bowel disease, E. vermicularis infestation must be excluded as a common cause of nonspecific colitis. We also suggest that diagnostic tests such as saline swabs and Sellotape testing may be lacking in sensitivity.

Tufting enteropathy (intestinal epithelial dysplasia), a rare congenital enteropathy, presents in the first few months of life with chronic watery diarrhoea and impaired growth. The molecular basis for this condition is not known. We report our experience with a case of tufting enteropathy that developed an unusual skeletal dysplasia with an abnormal blood picture. After extensive investigations including repeated gastrointestinal endoscopies and biopsies, the diagnosis of tufting enteropathy was made. During the third year of her life, the patient’s height was static. A full skeletal survey was performed and demonstrated features of generalised skeletal dysplasia, some of them consistent with those of parastremmatic dwarfism. At the age of five years, she developed Coomb’s positive haemolytic anaemia and thrombocytopenia with a negative auto-antibody screen including anti-enterocyte antibodies. There might be generalised matrix (including cartilage matrix protein), basement membrane abnormalities or both. A secondary protein leak might occur in the intestine with autosensitisation and development of autoimmune phenomena. More molecular research is needed to identify a possible link.

We present a case of this uncommon congenital anomaly of the perineum. A 6-month-old baby had a perineal groove excised for cosmetic reasons. The histology showed a strip of squamous epithelium with an intervening area lined by rectal type of mucosa, suggesting an embryological remnant such as urorectal septum.

Congenital melanocytic naevus and neurofibromatosis type 1 are distinct clinical entities. A diagnosis of neurofibromatosis is difficult to make in the presence of a congenital melanocytic naevus because nodules may arise in the naevus that have similar histopathological appearances to neurofibromata. A case is reported where nodules arising from a naevus were examined histologically and were found to have neurofibroma and schwannoma like elements but strong positivity for S100 protein in keeping with dermal melanocytes. Lisch nodules were also said to be found in the patient but may represent nodular naevi of the irides. It is important that histopathological findings are interpreted within a clinical context and S100 protein immunohistochemical stain is valuable in helping to differentiate these two conditions.

We report a case of Peutz-Jeghers syndrome (PJS) in a 2-year old with precocious puberty secondary to a Sertoli-Leydig cell tumour. Family history of PJS and other neoplasms were discovered. The tumour was excised and the STK11 gene deletion identified in both patient and father. Screening revealed hamartomatous gastric polyps, which were removed. Current recommendations for screening of children with PJS begin at age 8 years, based on reported occurrence of complications 1. This report illustrates the importance of considering early screening, along with close clinical review and patient/parent education, for detection of life threatening neoplasms and complications.

We describe the presentation and treatment of an HIV-positive patient with an oral ranula, and review the literature. Ranulas are mucoceles or retention cysts formed by the extravasation of mucus from the sublingual gland, presumably due to continued production of saliva in the presence of ductal obstruction. Oral ranulas in children are rare and the overall prevalence of mucoceles has been reported as 0.08% in children aged 0-12 years. However, there has been a documented increased occurrence in HIV-positive patients. This has been attributed to a blockage of the salivary gland by inflammation and peri-ductal fibrosis following HIV-associated salivary gland disease. Oral lesions may indicate infection with HIV and can also predict progression of HIV to AIDS. The most common oral manifestation is oral candidiasis occurring in 67% of children with HIV. Following this salivary gland disease, periodontal and gingival disease and herpes simplex are the next most common. The exact prevalence of ranulas in an HIV population is not known but the occurrence of a paediatric patient with HIV having at least one oral lesion has been documented as high as 63% and salivary gland disease at 50%. The true extent of the relationship between HIV and ranula is as yet unknown. This represents the only reported case of oral ranula in an HIV-positive patient in the UK.