Jakob Briner

Lichen Sclerosus et Atrophicus Causing Phimosis in Boys: A Prospective Study with 5-Year Followup After Complete Circumcision

We prospectively investigated 100 pediatric patients suffering from phimosis and found a 10% incidence of lichen sclerosus et atrophicus. This condition usually can be diagnosed preoperatively because of its classic manifestation of severe phimosis due to a sclerotic, whitish ring at the tip of the prepuce, which in our cases was accompanied by sclerogenous glanular lesions. To our knowledge our study represents the first evidence that the development of secondary phimosis with no apparent reason in school-age boys is highly suggestive for lichen sclerosus et atrophicus. Complete circumcision is the therapy of choice because it completely removes all affected tissue and it allows spontaneous regression or resolution of glanular lesions. There has been no recurrence after 5 years of followup.

Human herpesvirus type 6 and cytomegalovirus in AIDS-associated Kaposi's sarcoma: No evidence for an etiological association☆

Epidemiological studies indicate that acquired immune deficiency syndrome (AIDS)-associated Kaposis sarcoma (KS) may be caused by an infectious, preferentially sexually transmitted agent. Herpesviruses infections are common sexually transmitted diseases in homosexual men, who are also the main risk group for developing Kaposis sarcoma. To evaluate a possible role of human herpesvirus-6 (HHV-6) and cytomegalovirus (CMV) in the development of AIDS-associated KS, we investigated cutaneous AIDS-associated KS in 26 AIDS patients using the polymerase chain reaction (PCR) and immunohistochemistry (IHC) to detect the presence of HHV-6 and CMV. Human herpesvirus-6 was detected in nine of 26 Kaposis sarcoma specimens (all cases were HHV-6 subtype B) and in eight of 27 normal skin specimens from human immunodeficiency virus (HIV) seropositive and HIV seronegative patients (one case was HHV-6 subtype A and seven cases were HHV-6 subtype B). In two of four patients showing HHV-6 in KS of the skin, the virus also was detected in other investigated tissues, such as heart, lung, liver, kidney, and adrenals. Cytomegalovirus was detected only in AIDS-associated KS (seven of 26 KS specimens) and not in normal skin tissues of HIV-seropositive and HIV-seronegative patients. Cytomegalovirus was detected in other organs of those patients showing CMV in Kaposis sarcoma. Our data indicate that the presence of HHV-6 and CMV in AIDS-associated KS most likely reflects disseminated viral infection. Human herpesvirus-6 and CMV may be cofactors but not the only causative agents for the development of AIDS-associated KS.

Comparative genomic hybridization analysis of hepatoblastoma reveals high frequency of X-chromosome gains and similarities between epithelial and stromal components

Hepatoblastoma (HB) is the most common liver tumor in childhood and differs in its environmental risk factors and genetic background from hepatocellular carcinoma. HB is associated with inherited conditions such as familial adenomatous polyposis and Beckwith-Wiedemann syndrome, suggesting the importance of genetic abnormalities in the pathogenesis and progression of this disease. It has a very polymorphous morphology. A diverse range of cytogenetic alterations has been reported to date, the most frequent being trisomy 2 and trisomy 20. Thirty-five HB specimens from 31 patients (22 purely epithelial, 4 purely mesenchymal, 9 mixed) were examined by comparative genomic hybridization (CGH), a technique that enables us to screen the entire tumor genome for genetic losses and gains. Our aims were as follows: (1) to characterize chromosome abnormalities that appear in this tumor and (2) to identify possible differences between different histologic subtypes of HB. We found significant gains of genetic material, with very little difference in the number and type of alterations between the different histologic components of HB. The most frequent alterations were gains of Xp (15 cases, 43%) and Xq (21 cases, 60%). This finding was also confirmed by fluorescent in situ hybridization performed on nuclei extracted from 6 specimens. Other common alterations were 1p-, 2q+, 2q-, 4q-, and 4q+. We found no difference between different histologic subtypes, a finding that may be in agreement with the hypothesis of a common clonal origin for the different components. An hitherto-unreported high frequency of X chromosome gains may support the assumption that X-linked genes are involved in the development of this neoplasm.

Elevated concentration of IGF II in brain tissue from an infant with macrencephaly

and vitamin A in pediatric dialysis. J PEDIATR 1981;98:434435. 5. Armstrong VW, Buschmann U, Ebert R, et al. Biochemical investigations of CAPD: plasma levels of trace elements and ainin0 acids and impaired glucose tolerance during the course of treatment, int J Artif Org 1980;3:237-241. 6. Thomson NM, Stevens B J, Humphrey T J, etal. Comparison of trace elements in peritoneal dialysis, hemodialysis, and uremia. Kidney Int 1983;23:9-14. 7. Lawler MR, Klevay LM. Copper and zinc in selected foods. J Am Diet Assoc 1984;84:1028-1030. 8. Joffe G, Etzioni A, Levy J, et al. A patient with copper deficiency anemia while on prolonged intravenous feeding. Clin Pediatr 1981;20:226-228. 9. Cordano A, Baertl GM, Graham GG. Copper deficiency in infants. Pediatrics 1964;34:324-327. 10. Dunlap WM, James GW, Hume DM. Anemia and neutropenia caUsed by copper deficiency. Ann Intern Med 1974; 80:470-476. 1 i. Zidar BL, Shadduck RK, Zeigler Z, et al. Observations on the anemia and neutropenia of known copper deficiency. Am J Hematot 1977;3:177-185. 12. Aifrey AC, Rudolf H, Smythe WR. Mineral metabolism in uremia. Kidney lnt 1975;7:

Detection and typing of human papillomavirus in biopsy and cytological specimens by polymerase chain reaction and restriction enzyme analysis: A method suitable for semiautomation

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MALIGNANT MELANOTIC NEUROECTODERMAL TUMOR OF INFANCY: A Case Report

89. 13. Zumkley H, Bertram HP, Lison A, et al. Aluminum, zinc and copper concentrations in plasma in chronic renal insufficiency. Nephroiogy 1979;12:18-21. 14. Baum M, Powell D, Calvin S, et al. Continuous ambulatory peritoneal dialysis in children: a comparison with hemodialysis. N Engl J Med 1982;307:1537-1542. 15. Fennetl RS, Orak 3K, Garin EH, etal . Continuous ambulatory peritoneal dialysis in a pediatric population. Am J Dis Child 1983;137:388-392.

Squamous-cell carcinoma arising in a non-irradiated child with recurrent respiratory papillomatosis

Screening for high‐risk human papillomavirus (HPV) types allows the detection of women at a high risk of cervical squamous carcinomas, thereby defining a subset of patients targeted for more intensive screening and follow‐up. Thirty‐four cervical biopsy specimens and isolated cells from cervical smears of normal women or women diagnosed with high‐grade intraepithelial lesion (HGSIL) were screened for the presence of HPV by in situ hybridization (ISH) and/or by polymerase chain reaction (PCR). The exact HPV type was determined using a novel restriction typing method. The detection of HPV was facilitated greatly by the use of a PCR‐enzyme‐linked immunosorbent assay (ELISA)‐based method. HPV was detected by PCR in 32% of the biopsy specimens, whereas only 23% had a positive staining by ISH. In one case, a double infection was detected by ISH as well as by PCR. In two cases, the presence of HPV was detected by both methods but the exact type was different. Analyzing cells isolated from cervical smears by the PCR‐ELISA technique or by PCR followed by agarose gel electrophoresis, HPV was detected only in patients with HGSIL and not in the control group. The PCR system is more sensitive than conventional ISH, and the PCR‐ELISA system presented in this study is efficient in screening large series of cytological samples. Furthermore, this system allows exact HPV typing on the microtiter plate. These innovations may allow the application of HPV detection and typing as a routine screening method to identify patients with a high risk of developing cervical neoplasia.

Structural alteration of the insulin-like growth factor II-gene in Wilms tumour

We present a case of melanotic neuroectodermal tumor in the maxilla that followed an aggressively malignant course. In the first biopsy the tumor showed a classical histological picture, while in the last biopsy only malignant undifferentiated cells were evident. The tumor recurred twice after excision, and in spite of radiotherapy and various chemotherapeutic measures the patient died within 16 months of onset. Similar cases reported in the literature are discussed.

Wnt signaling pathway analysis in renal cell carcinoma in young patients

We describe a patient with recurrent respiratory papillomatosis (RRP) associated with human papilloma virus (HPV), who developed a fatal squamous cell carcinoma of the lung. At the age of 1 year he presented with hoarseness, dyspnoea and inspiratory stridor but the diagnosis of RRP was made only 1 year later. At the age of 4 years he was tracheostomized because of upper airway obstruction. In spite of multiple surgical excisions and topic treatment with 5-fluoruacil the papillomata extended to the lung parenchyma. At the age of 16 years he developed a squamous-cell carcinoma of the lung and died 4 months later. Transformation to pulmonary carcinoma is a rare complication in non-irradiated patients with lung papillomatosis. We found only 11 similar cases in the literature.

Modern diagnostic methods in the Ewing's sarcoma family: Six patients with histologic soft tissue tumors*

In this study messenger ribonucleic acid (mRNA) and DNA of five Wilms tumours were investigated. As expected, the level of insulin-like growth factor (IGF) II-mRNA was elevated up to 50 times in tumour tissue as compared to normal adjacent kidney tissue. In addition, genomic DNA was isolated and digested with appropriate restriction enzymes. Southern blots were prepared and hybridized to IGF II-cDNA probes. Additional bands were present in one of the five Wilms tumours compared to normal tissue. The results indicate a rearrangement of the IGF II-gene on one of the two chromosomes. It is speculated, that this change is responsible for the elevated IGF II expression which may be a factor contributing to tumour growth.