Atypical teratoid/rhabdoid tumor of the spine.

SUMMARY: Atypical teratoid/rhabdoid tumor (AT/RT) is a highly malignant central nervous system neoplasm usually seen in young children and infants. Prognosis for AT/RT is poor, with most patients dying within 1 year of presentation. AT/RT most commonly occurs intracranially. Location in the spine, though previously reported, is rare, and imaging findings have not been emphasized in the past. We present a case of AT/RT occurring in the thoracolumbar spine of a child and review available clinical and imaging findings in previously reported cases of spinal AT/RT.

Hypercellular/heterotopic ganglia in omphalomesenteric duct remnants.

Omphalomesenteric duct remnants (ODR) including Meckel diverticula often present with symptoms of bowel obstruction. Their histologic features are varied and include heterotopic gastrointestinal mucosa and/or pancreatic tissue within the wall. Abnormalities of the submucosal plexus of Meissner, however, have not been documented in the literature. Thus, we have examined a number of ODR for evidence of ganglion abnormalities. Fifty-three cases of ODR were retrieved from our archives, along with 25 nonduodenal small bowel control specimens obtained from autopsies of patients without clinical or pathologic evidence of enteropathy. Histologic criteria for the diagnosis of abnormal hypercellular/heterotopic ganglia (HHG) in ODR were defined as a single submucosal ganglion/plexus containing > 10 neurons, or > 5 submucosal ganglions per high-power (x 40) field, or heterotopic ganglion cells within the muscularis mucosa or the lamina propria. HHG, histologically indistinguishable from intestinal neuronal dysplasia type B, were found in more than half of the ODR (ODR: 51.9%, n = 50 vs. control: 4%, n = 25, P = 3.6 x 10(-6), particularly those excised for obstructive complications (ODR with acute abdomen: 65.7%, n = 35, vs. ODR without acute abdomen: 33.3%, n = 15, P = 0.035). HHG were present in equal numbers of inflamed and noninflamed ODR (inflamed: 53.6%, n = 28, vs. noninflamed: 59.1%, n = 22, P = 0.70). A similar incidence was found in ODR with heterotopia and without (with heterotopia: 61.1%, n = 18, vs. without: 53.1%, n = 32, P = 0.59). ODR frequently contained HHG histomorphologically similar to those found in intestinal neuronal dysplasia, type B (IND-B). The overrepresentation of HHG in symptomatic ODR patients suggests an association with bowel obstruction. The data did not demonstrate a relationship with either inflammation or heterotopia.

Consistency of isochromosome 7q and trisomy 8 in hepatosplenic gammadelta T-cell lymphoma: detection by fluorescence In situ hybridization of a splenic touch-preparation from a pediatric patient.

Hepatosplenic gamma-delta (gammadelta) T-cell lymphoma is a rare but increasingly recognized lymphoid malignancy predominantly affecting young adult males. It is not well appreciated in the pediatric population. We report the third case of this aggressive lymphoma in a child as well as additional support for the consistency of the recently discovered cytogenetic abnormalities, isochromosome 7q and trisomy 8, which in this case were documented using fluorescence in situ hybridization (FISH) of a touch-preparation of the spleen.

Familial megacecum and colon in the rat: a new model of gastrointestinal neuromuscular dysfunction.

Gastrointestinal motility disorders are of considerable clinical importance in humans and animals. Abnormalities of smooth muscle and the enteric nervous system have been described. We have identified and characterized a new mutant stock of rats that develops severe megacecum and colon with pseudo-obstruction, Familial Megacecum and Colon (FMC). The inheritance pattern of FMC was characterized by selective breeding. Gastrointestinal motility was evaluated radiographically. Complete pathologic evaluations, including ultrastructural examination and staining of colonic segments for acetylcholinesterase, peripherin, vasoactive intestinal peptide, substance P, nitric oxide synthase, and somatostatin, were performed. Spontaneous contractility and contractile force in isolated colonic muscle strips were examined. Familial megacecum and colon is inherited as an autosomal recessive trait. The markedly dilated cecum and proximal portion of the colon are followed by a short, funnel-shaped segment and distal portion of the colon with normal or slightly reduced lumen. Although clinical features and gross anatomic changes of the colon resemble those of Hirschsprung's disease in humans and animals, aganglionosis is not a feature of FMC. An increase in somatostatin staining was observed in dilated regions of bowel. The spontaneous contractile frequency and contractile force were diminished in the affected colon. Familial megacecum and colon is a new mutant, distinct from previously described hereditary and targeted mutant rodent models that develop megacecum and colon as a result of distal colonic dysfunction. The functional or morphologic defect(s) that result in colonic dysfunction in rats with FMC was not determined. The disease may result from an absence or overexpression of a single or group of neurotransmitters or their respective neurons, receptor abnormalities, or defects in the intestinal pacemaker system.

Cyclopamine-induced holoprosencephaly and associated craniofacial malformations in the golden hamster: anatomic and molecular events.

Holoprosencephaly is a complex congenital malformation of the brain and is often associated with a spectrum of facial anomalies ranging from normocephaly or nondiagnostic changes to cleft lip/palate (premaxillary dysgenesis), cebocephaly, ethmocephaly, and cyclopia. The primary insult is thought to occur during gastrulation, when prechordal mesenchyme and overlying anterior neural plate undergo complex developmental interactions. Exposure to cyclopamine, a steroid isolated from the desert plant Veratrum californicum, causes holoprosencephaly in mammalian embryos. We have begun to study the pathogenesis of cyclopamine-induced holoprosencephaly and associated craniofacial anomalies in Syrian golden hamsters (Mesocricetus auratus). Embryos were exposed to a single maternal dose of cyclopamine during gastrulation on embryonic day (E) 7.0. By E13.0, 62% of fetuses showed craniofacial malformations, including premaxillary dysgenesis, ocular hypotelorism, and cebocephaly. Facial anomalies were associated with absence of the premaxilla and abnormalities of the midline cranial base, particularly the ethmoid and sphenoid bones. Histological sections from cyclopamine-treated embryos at earlier stages showed marked deficiency of cranial mesenchyme derived from the rostral neural crest. Expression of two transcription factors, HNF-3 beta and Hox-b5, which have been implicated in specification of rostral and caudal neural crest cells, respectively, were examined immunohistochemically. Treatment with cyclopamine caused a transient loss of HNF-3 beta immunoreactivity in prechordal mesenchyme, but had no effect on Hox-b5 expression. The findings suggest that an early event in the pathogenesis of cyclopamine-induced holoprosencephaly may be altered expression of selected proteins in the prechordal mesenchyme and floor plate with secondary impaired development of the adjacent neural plate and cranial neural crest.

Induction and subcellular localization of two major stress proteins in response to copper in the fathead minnow Pimephales promelas.

In the present study we characterize the stress response induced by copper in the fathead minnow, Pimephales promelas. The fathead minnow epithelial cell line ATCC CCL 42 was used to examine the induced synthesis and subcellular localization of the two major stress proteins, stress 70 and cpn60. Western blot analysis demonstrated increased stress70 in cells exposed to 400 and 500 microM Cu. Two-dimensional analysis revealed three isoforms of stress70, one of 70 kDa and two of 72 kDa, at the highest Cu concentration. Chaperonin60 abundance did not change over the same range of Cu concentrations. Indirect immunofluorescence microscopy revealed that stress70 localized in the cytoplasm, particularly in the paranuclear region. Chaperonin60 was localized in mitochondria. Further, when we examined the stress response elicited by Cu in fathead minnow larvae in vivo, we found that Cu induced the stress response at nominal Cu concentrations that were more than an order of magnitude lower that in the cell culture. This disparity between the concentration of Cu, which induced the stress response in cells in culture and in vivo, may be the result of differences in Cu complexation that alter its availability, uptake and toxicity.

Increasing incidence of focal-segmental glomerulosclerosis among adult nephropathies: a 20-year renal biopsy study.

Studies and textbooks from the 1970s and early 1980s list focal-segmental glomerulosclerosis (FSGS) as accounting for 10% to 15% of cases of idiopathic nephrotic syndrome in adults, although a recent review by D'Agati (Kidney Int 46:1223-1241, 1994) reported an approximately sevenfold increase in the incidence of FSGS from 1974 to 1993 in an active renal biopsy practice. To investigate possible changes in the incidence of FSGS in our renal biopsy practice, we reviewed reports from all nontransplant, adult (> or = 18 years) renal biopsies received in our laboratory from 1974 to 1993, which comprised 7,420 cases. All diagnoses of membranous nephropathy (MN), minimal change nephropathy (MCN), and FSGS made in each year were compiled; cases clearly or suspicious of being secondary to an underlying systemic disease, glomerulonephritis, or drug reaction were excluded. Relative frequencies of MN, MCN, and FSGS among these three diseases and among all biopsies were calculated for each year of the study. Regression analysis showed a significant (P < 0.001) increase in the odds of a diagnosis of FSGS over the study period: 7.6% per year among all biopsies and 6.8% per year among cases of MN, MCN, and FSGS only. Among all biopsies, the yearly incidence of FSGS increased from 4.0% +/- 0.6% (mean +/- SD) during the period between 1974 and 1979 to 12.2% +/- 2.0% during the period from 1987 to 1993. The odds of a diagnosis of MN (mean yearly incidence, 9.5% +/- 1.9%) did not vary significantly over the study period while the odds of a diagnosis of MCN (mean yearly incidence, 4.0% +/- 1.2%) declined at a rate of 2.2% per year (P < 0.03). Frequencies of diagnosis of MN, MCN, and FSGS by two pathologists were almost identical. Review of available slides from cases of FSGS revealed 21 (none before 1980) with characteristic histologic features of the collapsing glomerulopathy (CG) variant of FSGS. No more than four cases of CG were observed in any year of the study, and CG accounted for 4.7% of total FSGS cases for which diagnostic slides were available. Compared with 42 patients with non-CG FSGS, the CG cohort showed a greater percentage of black patients (86% v 38%), significantly higher mean levels of serum creatinine (3.8 +/- 2.7 mg/dL v 1.9 +/- 1.5 mg/dL) and urinary protein (14.3 +/- 9.6 g/24 hr v 7.7 +/- 5.8 g/24 hr) at the time of renal biopsy, and a greater likelihood of and more rapid progression to end-stage renal failure.(ABSTRACT TRUNCATED AT 400 WORDS)

Migration of ganglion cell precursors in the ileoceca of normal and lethal spotted embryos, a murine model for Hirschsprung disease.

BACKGROUND: Dopamine-beta-hydroxylase-nlacZ transgenic mice are useful for studies of enteric neurodevelopment. Expression of the transgene provides a histochemical marker for neuroblasts in wild-type embryos and embryos homozygous for the lethal spotted (ls) allele that are born with aganglionosis coli and serve as a model for the human birth defect, Hirschsprung disease. Neuroblasts, derived from the vagal neural crest, colonize the gut in a cranial-to-caudal manner. However, migration of neuroblasts in ls/ls gut is impaired when neuroblasts reach the ileocecal junction and attempt to colonize the large intestine. To learn more about neuroblast migration through this specific region of the intestinal tract, a detailed light and electron microscopic study of neuroblast colonization of the developing ileoceca from wild-type, ls/+, and ls/ls embryos was conducted. EXPERIMENTAL DESIGN: The ileoceca from wild-type, ls/+, and ls/ls, dopamine-beta-hydroxylase-nlacZ embryos (E10.5-E13.5) were treated with a histochemical substrate for the transgene product and examined by light and electron microscopy. RESULTS: Five stages of ileocecal development were defined based on distinctive gross, light, and electron microscopic features. At each stage, neuroblasts had different ultrastructural features than other mesenchymal cells. Initial colonization of the colon was different from other parts of the gut, in that a string of "pioneer" neuroblasts populated the mesenteric border of the proximal colon before circumferential invasion. Subsequently, neuroblasts were arranged in intersecting linear groups of contiguous cells that radiated around the cecum and proximal colon. In ls/ls embryos, transition from neuroblast extension along the mesenteric border to cecal invasion was delayed profoundly. However, the ultrastructural features of neuroblasts and adjacent mesenchyme were indistinguishable in ls/ls and wild-type embryos. CONCLUSIONS: This study supports the hypothesis that impaired migration of neuroblasts in ls/ls embryos is not limited to the presumptive aganglionic segment, but begins at the ileocecal junction. Migration of neuroblasts from the ileum into the proximal colon follows a different pattern than movement of neuroblasts through the small intestine. The biological bases for these differences may account for the defects observed in ls/ls mice and/or may affect the pathogenesis of human Hirschsprung disease.

Resection of primary schwannoma of the liver not associated with neurofibromatosis.

A 38-year-old woman developed right upper quadrant pain due to a mass in the left lobe of the liver. The tumor was resected along with segment 3 of the left lobe. Histologic examination and immunochemistry supported a diagnosis of benign schwannoma. No metastatic disease was present, and the patient has been well for more than 18 months after surgery without recurrence. This is the first reported case of successful resection of a schwannoma of the liver in a patient without von Recklinghausen's disease.

Glomerular disease and urinary Sézary cells in cutaneous T-cell lymphomas.

We report three cases of biopsy-documented renal glomerular disease occurring in patients with cutaneous T-cell lymphomas. One patient had immunoglobulin A (IgA) nephropathy and another had membranous nephropathy. The remaining patient had an immune complex glomerulonephritis without immunofluorescent evidence of IgA, but with mesangial deposits and a clinical course notable for stable renal function, minimal proteinuria, and episodic gross hematuria of renal origin. These three cases, along with IgA nephropathy in two of the four previously reported cases, suggest a possible association between cutaneous T-cell lymphoma and this glomerular lesion. In addition, Sézary cells were observed in the urine of two patients, one without evidence of glomerular disease. The prognostic value of this new observation is unknown.