Constitutional mismatch repair-deficiency and whole-exome sequencing as the means of the rapid detection of the causative MSH6 defect.

BACKGROUND: Cases of children with more than one type of cancer either diagnosed simultaneously or successively, rarely occur in pediatric oncology. A second malignant neoplasm may be caused by mutagenic effects of the treatment of the primary malignancy and/or may point towards an underlying genetic cancer susceptibility syndrome. One example of such a syndrome is constitutional mismatch repair-deficiency, (CMMR-D) which carries an increased risk of various tumors including childhood hematologic malignancies and Lynch syndrome associated tumors. Timely diagnosis of CMMR-D is crucial, since this diagnosis has implications for the entire family. PATIENT: We report the case of a 15-year-old girl who was born to consanguineous parents. At the age of 20 months she was diagnosed with a T-cell non-Hodgkin lymphoma. Treatment was given according to NHL-BFM 95. 12 years later, an invasive adenocarcinoma of the colon was surgically removed which relapsed shortly afterwards. METHODS: Whole-exome sequencing of germline DNA was employed to rapidly detect the underlying mutation in this suspected CMMR-D patient. RESULTS: After a short turnaround time of less than 3 weeks, the diagnosis of CMMR-D could be confirmed by the identification of a homozygous 29-bp deletion in MSH6 (exon 6), which was confirmed by independent methods. CONCLUSIONS: We demonstrate that "bed-side" whole-exome sequencing is both feasible and cost-effective and may be the method of choice to rapidly uncover the genetical basis of (inherited) diseases.

Effects of soluble TNF receptor II (sTNF-RII), IL-1 receptor antagonist (IL-1ra), tumor load and hypermetabolism on malnutrition in children with acute leukemia.

OBJECTIVE: Soluble tumor necrosis factor receptor II (sTNF-RII) and interleukin-1 receptor antagonist (IL-1ra) might modulate nutritional status in acute leukemia since they are inhibitors of tumor necrosis factor-alpha and interleukin-1 that can induce tissue wasting. On the other hand, tumor load and hypermetabolism may induce malnutrition. We determined whether serum levels of sTNF-RII and IL-1ra are upregulated to prevent overt malnutrition and whether tumor load and hypermetabolism induce overt malnutrition. METHODS: We examined 31 children with newly diagnosed acute leukemia and correlated sTNF-RII, IL-1ra, tumor load and energy expenditure to anthropometric characteristics (weight, weight for height, height, body mass index, fat free mass) and serum protein concentrations (albumin, transferrin, prealbumin). As controls, 68 healthy children were examined for anthropometric characteristics; 33 healthy controls were included for cytokine analysis and biochemical indices. RESULTS: We found no correlations between sTNF-RII, IL-1ra, tumor load and energy expenditure and anthropometric characteristics or protein concentrations. Mean sTNF-RII level was significantly, mean IL-1ra level slightly increased (223% and 113% of the controls). 29% of the children had a high tumor load (> 100.000/microl white blood cells) and 53% had hypermetabolism (resting energy expenditure > 110% of predicted). Anthropometric characteristics were similar to those in controls, however, serum protein concentrations were decreased. CONCLUSION: sTNF-RII and IL-1ra are upregulated in children with leukemia and may therefore prevent overt malnutrition. Tumor load and hypermetabolism do not induce overt malnutrition. The children presented with an early stage of malnutrition as evidenced by low serum protein concentrations but normal anthropometric characteristics.

Pseudomembranous colitis: diagnosis by computed tomography.

Although the diagnosis of pseudomembranous colitis is generally straightforward in the appropriate clinical setting, patients may manifest clinical symptoms more suggestive of abdominal infection than of intestinal disease. Because these patients may have computed tomography (CT) as their first examination, it becomes important to recognize colonic changes that may reflect the presence of pseudomembranous colitis. We present two cases of this entity diagnosed by CT findings.

Anorectal giant condyloma acuminatum (Buschke-Loewenstein tumor): CT and radiographic manifestations.

Giant condyloma acuminatum (Buschke-Loewenstein tumor) is an unusual variety of venereal wart characterized by a large size, cauliflower-like appearance, and locally invasive nature. CT examination of two patients with anorectal giant condylomata revealed the papillomatous and invasive nature of the lesion and the extent of tumor; there was infiltration of the subcutaneous tissue, perirectal fascial planes, and luminal narrowing with marked thickening of the rectal wall. The pathologic specimens showed benign histologic findings in one case and a mixed pattern with areas of malignant degeneration in the other. CT accurately demonstrated the exact location and extent of the lesions. The presence of malignant degeneration in this inherently invasive lesion can be established only on histologic examination.

Metrizamide examination of traumatic lumbar nerve root meningocele.

Demonstration of traumatic lumbosacral root avulsion is a rare clinical entity because the bony pelvis offers support and protection to the nerve roots against stretching and rupture. Major vehicular trauma producing unstable pelvic fractures allows lumbosacral root avulsion to occur, and the 18th well-documented case is reported. Delay in diagnosis of several months is common. Demonstration of traumatic meningoceles is important, and metrizamide offers better visualization of the root than does iodophendylate. Absence of the root in the meningocele is equated with avulsion.

Steroid-induced thoracic lipomatosis: paraspinal involvement.

Fat deposition of masslike proportion in the thoracic paraspinal area due to elevation of corticosteroids has not been well documented. Three cases are reported that demonstrate lower thoracic paraspinal widening on routine radiographs, subsequently proven to be fat by computed tomography. All three patients were cushingoid. Computed tomography offered a convenient way to document fat accumulation in an unusual location when other more serious processes were being considered.