The expression of WT1 in the differentiation of rhabdomyosarcoma from other pediatric small round blue cell tumors.

The WT1 gene encodes a transcription factor implicated in normal and neoplastic development. The purpose of this study was to evaluate the diagnostic utility of a commercial WT1 antibody on a variety of pediatric small round blue cell tumors (SRBCT). A mouse monoclonal antibody (clone: 6F-H2, DAKO) raised against the N-terminal amino acids 1-181 of the human WT1 protein was tested. Microscopic sections from 66 specimens were stained using an antigen retrieval protocol with trypsin. The tumors included peripheral neuroectodermal tumors (PNET/Ewing's), neuroblastomas, desmoplastic small round cell tumors (DSRCT), lymphomas, Wilms' tumors, and rhabdomyosarcomas (RMS). One RMS case was investigated by Western blot analysis and RT-PCR to confirm the antibody specificity. A strong cytoplasmic staining was demonstrated in all RMS (11/11). The Western blot analysis confirmed the WT1 protein in the tissue, and the RT-PCR confirmed the presence of WT1 mRNA in the peripheral blood and tissue of one RMS patient. The Wilms' tumors had a variable nuclear and/or cytoplasmic positivity in most (17/24) cases. All PNET/Ewing's were negative. The nuclei of two lymphoblastic lymphomas stained strongly. A weak nuclear or cytoplasmic staining was reported in a few DSRCT (3/5), lymphomas (2/10), and neuroblastomas (2/8). This is a useful antibody in the differentiation of RMS from other SRBCTs. A strong cytoplasmic staining favors an RMS, and a strong nuclear staining is suggestive of a Wilms' tumor. A role for WT1 in the pathogenesis of rhabdomyosarcomas is raised. The limited sampling precludes any conclusions regarding the value of tissue or peripheral blood analysis for WT1 mRNA in patients with rhabdomyosarcoma.

Sarcoma of the mitral valve causing coronary arterial occlusion in children.

Primary tumors of the cardiac valves are rare. One of the most common reasons that left-sided cardiac tumors come to clinical attention is embolization to the systemic circulation. We present two children who suffered left coronary arterial occlusion due to embolization of a sarcoma of the mitral valve. A 6-year-old female who had been admitted to the hospital after cerebrovascular embolization of a fragment of sarcoma of the mitral valve experienced sudden cardiovascular collapse due to occlusion of the left coronary artery. She was placed on extracorporeal membrane oxygenation, and underwent coronary embolectomy and resection of the tumor from the mitral valve and its tendinous cords. Left ventricular function did not improve, and she underwent orthotopic heart transplantation. On follow-up 32 months after transplant, the patient is well, with no evidence of recurrence of or metastasis from the tumor. The tumor arose from the leaflets and tendinous cords of the mitral valve, and was composed grossly of multiple white nodules. Histopathologic evaluation disclosed fragments composed predominantly of peripheral spindle cells in an extensive fibromyxoid stroma. The mildly pleomorphic cells of the tumor gradually blended with adjacent pieces of the mitral valvar leaflet and tendinous cords. Immunohistochemical studies revealed strong staining for vimentin, smooth muscle actin, muscle specific actin, and myoglobin, suggesting myogenic differentiation. The other patient was a 2 1/2-year-old female who died suddenly at home. Grossly and histologically, the tumor was essentially identical to the first case, and there was a 3 cm string-like extension passing into the orifice of the left coronary artery. To put the cases in context, we compare them with other descriptions of this rare type of tumor.

Central nervous system Sjögren's syndrome in a child: case report and review of the literature.

We describe a case of pediatric Sjögren's syndrome with progressive neurologic involvement. At age 4 years, she had been diagnosed with Melkersson-Rosenthal syndrome. After being stable with facial diplegia and swelling for 5 years, she acutely presented with diplopia, vertigo, and ataxia. Cranial magnetic resonance imaging (MRI) showed a left dorsal midbrain lesion. Serologic and histopathologic findings confirmed primary Sjögren's syndrome. She responded well to intravenous methylprednisolone, with subsequent clinical improvement and MRI resolution. This report reviews the pediatric literature and underscores the importance of considering Sjögren's syndrome in a child with unexplained facial weakness and in the differential diagnosis of pediatric stroke.

Colonic inflammation found at diagnosis of juvenile retention polyps in pediatric patients.

OBJECTIVE: The finding of colonic inflammation concurrently with a juvenile retention polyp (JRP) may have prognostic value. However, the significance of abnormal mucosal histology with JRP has not been evaluated. We evaluated the significance of mucosal histology at the time of JRP removal with respect to future development of inflammatory bowel disease (IBD) and polyp recurrence. METHODS: The medical records of patients who had an endoscopic polypectomy performed at the Children's Hospital of Philadelphia (CHOP) from 1/1/87 through 4/30/98 were retrospectively reviewed. RESULTS: JRP was histologically identified in 96 patients. A total of 54 patients had colonic mucosal biopsies: 30 (55.6%) had normal histology and 24 (44.4%) had colitis. Of the 24 patients with colitis, 14 patients (58.3%) had inflammation at the polyp site. Twelve of these patients had additional inflammation elsewhere in the colon. Nine (37.5%) had inflammation elsewhere in the colon; however, biopsies around the polyp site were not obtained. One patient with inflammation did not have the location of the polyp documented. Four patients (16.7%) had IBD at the time of polypectomy; two were diagnosed prior and two coincident with JRP. None have subsequently been diagnosed with IBD. There was no difference in polyp recurrence between those with or without inflammation (16.7% [4/24] vs 10.0% [3/30]). The mean follow-up period was 72.4 months (range, 5-142 months). CONCLUSIONS: In our experience, histological mucosal inflammation is a common finding with JRP. This inflammation may be a precursor for the development of JRP but has no predictive value for polyp recurrence. This colitis does not seem to be associated with IBD.

Significance of lymphoid follicles and aggregates in gastric mucosa of children.

This study was designed to evaluate the significance of gastric lymphoid follicles (LF) and aggregates (LA) in children with and without Helicobacter pylori (HP) infection. All 605 antrum biopsies performed during 1994 were reviewed and classified according to the presence or absence of inflammation, LF, or LA. HP was searched with a DiffQuik stain in all biopsies showing gastritis, LF, or LA. Gastritis was diagnosed in 80 biopsies (16 with LF, 18 with LA and 46 without LA or LF). Identification of HP in these biopsies was as follows: (a) cases with LF: 12/16; (b) cases with LA: 3/18; (c) cases without LF or LA: 8/46. The biopsies without gastritis had a higher frequency of LA (65/525) than of LF (2/525). HP was not identified in any case without gastritis. The presence of LF with histologic gastritis had the strongest correlation with HP (R = 0.5, p < 0.00001). LF with gastritis had a positive predictive value of 75% for HP and the absence of LF had a negative predictive value of 82.8% (sensitivity 52%; specificity 92%). LA with gastritis had no significant correlation with HP. From these results we conclude that lymphoid follicles should be distinguished from lymphoid aggregates. Lymphoid follicles can rarely be present in an otherwise normal gastric mucosa; however, they are more frequently found in cases of gastritis and are strongly associated with HP infection. Lymphoid aggregates are not significantly associated with HP infection and may be a component of the normal gastric lymphoid tissue.

Multiple vascular and bowel ruptures in an adolescent male with sporadic Ehlers-Danlos syndrome type IV.

Ehlers-Danlos syndrome (EDS) type IV is a heritable disorder resulting from mutations in the COL3A1 gene that cause deficient production of type III collagen. Clinical manifestations of EDS type IV include hypermobility of small joints, excessive bruisability, thin translucent skin, poor wound healing, bowel rupture, and vascular rupture that is often fatal. A 14-year-old male without a family history of EDS died following multiple bowel and abdominal blood vessel ruptures. Even in areas apart from rupture sites, the bowel wall was thin because of diminished submucosa and muscularis propria. Similarly, the walls of blood vessels in bowel submucosa and elsewhere in the abdomen varied in thickness, and contained frayed and fragmented elastic tissue fibers. Fibroblasts cultured from the patient's skin secreted reduced quantities of type III collagen that was explained by a point mutation in one copy of the COL3A1 gene. EDS type IV should be strongly suspected in any patient with otherwise unexplainable bowel and/or vessel rupture.