Screening for neuroblastoma in late infancy by use of EIA (enzyme-linked immunoassay) method: 115000 screened infants in Austria.

The aim of this study was to investigate the feasibility of a neuroblastoma screening programme for children in late infancy, based on collaboration of general paediatricians and practitioners in Austria, using the technique of enzyme-linked immunoassay (EIA) for biochemical analyses. Analysis of catecholamine metabolites in spot urine samples by EIA with high performance liquid chromatography as a backup was undertaken. Austrian infants (median age 8.7 months) were screened. Overall compliance was 30%. The EIA method had a high rate (6.7%) of false-positive results. 28 infants were admitted to hospital. In 15 cases, neuroblastoma was found (four stage 1, five stage 2B, six stage 3). The EIA method can be used for neuroblastoma screening, but requires a backup analytical technique in order to avoid unnecessary hospital admissions. The stage distribution and biological features of neuroblastomas diagnosed by screening at a later age are different from those detected by earlier screening. Screening in late infancy might be of more benefit than early screening.

Insulinoma of the pancreas with insular-ductular differentiation in its liver metastasis--indication of a common stem-cell origin of the exocrine and endocrine components.

We describe an insulinoma of the pancreas in a 56-year-old patient, which showed insular-ductular differentiation in its liver metastasis. Although the primary tumor was uniformly endocrine in nature with insulin production, the metastasis contained two distinct cell types in organoid arrangement. One cell type was insulin-positive and was arranged in islet-like structures; the other was insulin-negative but distinctly pan-cytokeratin and cytokeratin 7 positive and arranged in ducts. In the primary tumor and the metastasis, the tumor cells were surrounded by a desmoplastic stroma. As to the histogenesis of the tumor and its metastasis, we discuss the following possibilities: (1) the tumor cells might derive from a common stem cell that matures into two phenotypically different cell lines, resembling the situation in embryogenesis and (2) one tumor cell type originates from the other by transdifferentiation (metaplasia). We conclude that the parallel occurrence of endocrine and ductal differentiation supports the concept that, under certain conditions, islet cells and ductular cells may also originate from islets and that mixed endocrine/exocrine pancreatic tumors do not necessarily arise from totipotent duct cells but might also have a primary endocrine cell origin.

[Acute appendicitis in non-contrast spiral CT: a diagnostic luxury or benefit?]. / Akute Appendizitis im Nicht-Kontrast-Spiral-CT: diagnostischer Luxus oder Nutzen?

PURPOSE: To evaluate the diagnostic accuracy of thin collimated unenhanced spiral-CT in patients with clinically suspected acute appendicitis and to determine the impact on patient management and overall costs. METHOD: Unenhanced focussed appendiceal spiral-CT was performed in 56 patients (23 women and 33 men) with clinically suspected acute appendicitis. Scans were obtained from the L4 level to the symphysis pubis using 5 mm collimation, 7.5 mm table feed (pitch 1.5) and 4 mm increment without i.v., oral, or rectal contrast material. Prospective diagnoses based on CT findings were compared with surgical (and histopathological) results and clinical follow-up. The effect of spiral-CT on patient management and clinical resources was assessed. RESULTS: 29 patients (10 women and 19 men) underwent appendectomy. Unenhanced spiral-CT was an accurate imaging technique for the initial examination of patients with suspected acute appendicitis with a sensitivity of 95.4% and a specificity 100%, an accuracy of 98.2%, a positive predictive value of 100%, and a negative predictive value of 97.1%. In 27 patients with no evidence of acute appendicitis, an alternative diagnosis could be made in 24 patients by unenhanced spiral-CT. CONCLUSION: Unenhanced spiral-CT is an accurate test to diagnose or to exclude acute appendicitis. Routine appendiceal spiral-CT can improve medical care and reduce the overall costs for patients suspected of having acute appendicitis.

[5 years neuroblastoma screening in Austria: rate of participation, results and a comparison with other screening areas]. / Fünf Jahre Neuroblastom-Screening in Osterreich: Beteiligungsrate, Ergebnisse und ein Vergleich mit anderen Screeningregionen.

In late 1990 a screening program for the early detection of neuroblastoma in infants was introduced in Austria. The program is performed on a voluntary basis in collaboration with general pediatricians and practitioners. Filter strips for urine collection are distributed to parents of infants aged seven to nine months on the occasion of a routine check up. The samples are sent to the laboratory by parents and analysed for vanillylmandelic acid (VMA) and homovanillic acid (HVA). Between January 1991 and December 1995 125,201 infants were screened. The compliance rate was 26.8% for Austria, but great differences were seen for different regions (65% in Carinthia, 10% in Vorarlberg). 30 children were admitted to hospital for investigation of repeatedly elevated urine catecholamines. A neuroblastoma was identified in 16 cases. In 12 of these cases at least one unfavorable prognostic factor was present (stage > or = 3, elevated LDH, unfavorable histology, N-myc amplification, di- or tetraploidy). Neuroblastoma screening of infants aged more than six months seems to detect predominantly those tumors which are unlikely to regress spontaneously. The observation of one false negative case, however, demonstrates that neuroblastomas which become clinically manifest at a later date may remain undetected by early screening. Possible advantages of shifting screening to a later age and repeated screening are discussed.

[Erosive intervertebral joint lesions. A case of pigmented villonodular synovitis]. / Erosive Intervertebralgelenkläsionen. Ein Fall von pigmentierter villonodulärer Synovitis.

Pigmented villonodular synovitis (PVNS) is a rare proliferative lesion that can affect synovial membranes, tendon sheaths, and bursae. It is usually a monarticular disease of the lower extremities, and so far fewer than 30 cases of spinal involvement have been reported in the literature. We describe a patient with progressive lumbar pain and spinal claudication, in whom a CT scan of the lumbar spine revealed destruction fo facet joints L3 to L5. An open biopsy was performed, which led to the diagnosis fo PVNS. The patient underwent successful surgical resection of the tumour mass and stabilization of segments L3 to S1. Two years after surgery the patient has no signs of recurrence. Differential diagnosis of erosive vertebral joint disease is discussed.

Angiotropic large cell lymphoma presenting as thrombotic microangiopathy (thrombotic thrombocytopenic purpura).

BACKGROUND: Angiotropic large cell lymphoma is a rare lymphoproliferative disorder that affects vessels of almost all organs. Therefore, many different signs and symptoms can be observed and may delay a rapid diagnosis in these patients. However, no association between angiotropic large-cell lymphoma and thrombotic microangiopathy (TMA) has been reported so far. METHODS: The case report describes a 69-year-old female Caucasian who presented with fever, neurologic symptoms, microangiopathic hemolytic anemia, thrombocytopenia, and hyaline thrombi within small vessels. TMA was diagnosed and intense treatment, including plasma exchange and corticosteroid therapy, was initiated. Nevertheless, the patient died 3 days after admission. A postmortem examination including immunohistochemistry and molecular studies was performed. RESULTS: Autopsy revealed angiotropic large cell lymphoma with tumor cell aggregates in small vessels of the brain, myocardium, lungs, liver, small and large intestines, mesenterium, kidneys, and lymph nodes. Immunohistochemical analysis of the tumor cells showed positive reactions with B-cell markers, but negative T-cell and epithelial cell markers. Molecular studies using polymerase chain reaction with primers for the rearranged immunoglobulin heavy chain and the T-cell receptor beta chain gene confirmed the diagnosis of a monoclonal B-cell disorder. CONCLUSION: TMA can occur in association with angiotropic large cell lymphoma and, furthermore, can be its sole clinical manifestation.

Neuroblastoma screening in infants postponed after the sixth month of age: a trial to reduce "overdiagnosis" and to detect cases with "unfavorable" biologic features.

BACKGROUND: Encouraged by Japanese reports of the benefits of screening 6 month-old infants for neuroblastoma, a neuroblastoma screening program was introduced in Austria in 1991. However, because of concerns related to "overdiagnosis" by screening at this age, the screening test was performed at a later age. METHODS: From March 1991 to February 1995 neuroblastoma screening was performed on filter paper urine specimens in 100,043 Austrian infants (median age 8.5 months). Primary analysis of urine catecholamines (vanillylmandelic acid and homovanillic acid was performed by use of an E1A method. Questionable or positive results were confirmed by high performance liquid chromatography (HPLC). A double retest was requested following a positive HPLC result. RESULTS: Twenty-one infants were admitted to a hospital following repeatedly elevated values of vanillymandelic acid (VMA) and/or homovanillic acid (HVA). Eleven infants were found to have neuroblastoma (three stage 1, four stage 2B, four stage 3). Treatment consisted of surgery alone with total or subtotal resection in eight cases, surgery and chemotherapy in two cases, and chemotherapy alone in one case. Biologic features were assessed in all tumors excluding ploidy in one case. The majority of the tumors analyzed were near-triploid (9/10), however, two tumors revealed N-myc amplification. CONCLUSIONS: Our results demonstrate that stage distribution and biologic features of neuroblastomas diagnosed by screening at 8.5 months are different from the results of screening at 6 months. Furthermore, the detection of one neuroblastoma among 9,100 screened infants is significantly lower than the incidence of the Japanese screening program. Our results suggest that screening at an age of 7 to 10 months reduces overdiagnosis and may be of more benefit than earlier screening.