Histopathological findings in livers of patients with urea cycle disorders.

Background: Urea cycle disorders (UCD) are caused by genetic defects in enzymes that constitute the hepatic ammonia detoxification pathway. Patients may present with variable clinical manifestations and with hyperammonaemia. Liver abnormalities have been associated with UCD, but only a few reports on the histopathological findings in the liver of UCD patients have been published.

Ectodermal dysplasia-skin fragility syndrome due to a new homozygous internal deletion mutation in the PKP1 gene.

Ectodermal dysplasia-skin fragility syndrome (ED-SFS) is a rare autosomal recessive genodermatosis resulting from mutations in the PKP1 gene, encoding the desmosomal plaque protein plakophilin-1 (PKP1). Mutations in PKP1 may manifest with skin fragility and erosions, patches of scale crust on the trunk and limbs, peri-oral cracking and inflammation, hypotrichosis, palmoplantar keratoderma with painful fissuring and other somewhat variable ectodermal anomalies. Ten cases of the syndrome have been reported.

Gastrointestinal polyps in McCune Albright syndrome.

Background: McCune Albright syndrome (MAS), a disorder caused by somatic activating mutations in the GNAS gene, usually presents with cutaneous, skeletal, and endocrine manifestations. While focal lesions involving multiple tissues have been identified in MAS, almost nothing is known about gastrointestinal lesions in this disease.

Methods: Two MAS patients with perioral freckling, resembling Peutz-Jeghers syndrome (PJS), and two MAS patients without similar pigmentation underwent gastrointestinal endoscopy to establish if they had coexisting hamartomatous polyposis.

Rapid detection of SMARCB1 sequence variation using high resolution melting.

Background: Rhabdoid tumors are rare cancers of early childhood arising in the kidney, central nervous system and other organs. The majority are caused by somatic inactivating mutations or deletions affecting the tumor suppressor locus SMARCB1 [OMIM 601607]. Germ-line SMARCB1 inactivation has been reported in association with rhabdoid tumor, epitheloid sarcoma and familial schwannomatosis, underscoring the importance of accurate mutation screening to ascertain recurrence and transmission risks.

Low grade fibromyxoid sarcoma: problems in the diagnosis and management of a malignant tumour with bland histological appearance.

Aims: To review the clinicopathological features and highlight the problems in the diagnosis and management of low grade fibromyxoid sarcomas (LGFMS).

Methods: Three cases of LGFMS were studied with histology and immunohistochemistry, and cytogenetics in one. The features and problems were compared with those in the literature.

Rhabdoid tumour: a malignancy of early childhood with variable primary site, histology and clinical behaviour.

Aims: To correlate the immunostaining for INI1 protein and mutations in INI1 gene in possible rhabdoid tumours (RT) and atypical teratoid/rhabdoid tumours (AT/RT) seen at the Royal Children's Hospital in the last 10 years, and to study the clinicopathological features of those patients with negative nuclear staining.

Methods: Twenty tumours showing suggestive histological and/or immunohistochemical features of RT and AT/RT were selected. Immunohistochemistry for INI1 and molecular investigations for INI1 mutations were performed.

Oesophagitis in children: reflux or allergy?

The prevalence of eosinophilic oesophagitis appears to be increasing in many countries, sometimes rapidly, although this may be partly due to increased disease recognition. Histological methods of assessment and diagnostic criteria vary considerably between major clinical centres. Oesophagitis with over 20 intraepithelial eosinophils per high power field is more likely to be due to allergy than gastro-oesophageal reflux induced acid-peptic mucosal injury.

Squamous cell carcinomas in children and young adults: a new wave of a very rare tumor?

Background: Squamous cell carcinomas (SCCs) seem to have become more common recently. This study aims to check whether the increase is real and to review possible etiologic factors and problems in diagnosis.

Methods: Patients with SCC were identified from anatomical pathology files over 30 years.

X-linked cardiomyopathy presenting as contracted endocardial fibroelastosis.

We report a case of familial contracted endocardial fibroelastosis (EFE) in a young boy presenting at 14 months of age with severe heart failure. A previous echocardiogram showed normal left ventricular (LV) size and systolic function. The family history was suggestive of X-linked cardiomyopathy.

Heterozygous tx mice have an increased sensitivity to copper loading: implications for Wilson's disease carriers.

Wilson's disease carriers constitute 1% of the human population. It is unknown whether Wilson's disease carriers are at increased susceptibility to copper overload when exposed to chronically high levels of ingested copper. This study investigated the effect of chronic excess copper in drinking water on the heterozygous form of the Wilson's disease mouse model--the toxic milk (tx) mouse.

Segmental haemangioma of infancy of the lower limb with skeletal overgrowth.

A female infant presented at 3 months of age with vascular lesions involving the left lower limb and left side of the vulva. At birth, the left leg was thinner than the right, but equal in length. She had macular, reticulate, bluish discolouration covering most of the skin of the involved leg with superimposed cherry-red papules, most dense over the proximal portion.

Multiple endocrine neoplasia type 2B diagnosed on suction rectal biopsy in infancy: a report of 2 cases.

Suction rectal biopsies in a newborn and a 10-month-old infant presenting with intestinal obstruction showed marked increase in neurons and nerve bundles in the submucosa. Although there were no syndromic features or a positive family history, mutation analysis of the RET proto-oncogene showed a de novo germline Met918Thr mutation in both patients, confirming the diagnosis of multiple endocrine neoplasia type 2B (MEN 2B). Thyroidectomy was performed at 9 and 14 months, showing medullary carcinoma and focal prominent C-cell hyperplasia, respectively.

[Metanephric stromal tumor: a pathologic study of two cases].

Objective: To study the clinicopathologic features of metanephric stromal tumor (MST), with emphasis on diagnostic criteria.

Methods: The clinicopathologic findings in 2 cases of MST were analyzed and the literature of this entity was reviewed.

Results: Cases of MST were unilateral and mostly centered in renal medulla.

Lymphatics in the alimentary tract of children in health and disease: study on mucosal biopsies using the monoclonal antibody d2-40.

Primary intestinal lymphangiectasia and intestinal lymphatic hypoplasia are 2 causes of protein-losing enteropathy in children and share many common clinical features. For the diagnosis of lymphatic hypoplasia on endoscopic biopsies of the intestine, i.e.

The pluripotency homeobox gene NANOG is expressed in human germ cell tumors.

Background: The NANOG gene, a member of the homeobox family of DNA binding transcription factors, was recently identified in a screen for pluripotency-promoting genes. NANOG overexpression in murine embryonic stem cells is sufficient to maintain self-renewal and to block differentiation. The NANOG gene is located on human chromosome 12p13, a region frequently duplicated in human tumors of germ cell origin and in cultured human embryonic stem cells.

Radionuclear transit to assess sites of delay in large bowel transit in children with chronic idiopathic constipation.

Purpose: Chronic idiopathic constipation (CIC) with soiling in children may result from slow colonic transit (SCT) or anorectal dysfunction and/or psychological problems known as functional fecal retention (FFR). Evidence is accumulating that SCT and FFR need different treatments, but they are poorly distinguished by solid marker studies. The authors used radionuclear transit scintigraphy to categorize children with CIC as having either FFR or SCT.