Biphasic, hyperdiploid breast tumors in children: a distinct entity?

BACKGROUND: The differentiation between a giant fibroadenoma and a phyllodes tumor can be a precarious diagnostic task. However, the distinction between the 2 lesions is important to make, especially since the latter can be malignant and consequently the prognoses differ. PROCEDURE: We used various genetic approaches to study a breast tumor showing features of both entities in a 10-year-old girl with a congenital cerebral malformation and diabetes mellitus. RESULTS: Cytogenetic analysis of cultured tumor cells from 3 different samples revealed a hyperdiploid karyotype: 50-54,XX,+5,+13,+17,+18,+19,+20,+21. High-resolution single nucleotide polymorphism array analysis not only confirmed the trisomies, but also revealed uniparental disomy (UPD) for chromosomes 10, 11, and 22. A consequence of UPD11 was a homozygous deletion in chromosome band 11p15 affecting the PARVA gene; this gene was hemizygously lost in constitutional DNA. Extended analysis of the family revealed that the deletion was inherited, but it did not segregate with breast tumors or congenital malformations. CONCLUSIONS: Combined with the literature data, the findings in the present case strongly suggest that biphasic tumors with high hyperdiploid karyotypes constitute a distinct clinicomorphologic subgroup of benign breast tumors, being particularly common among young children.

Cytogenetic findings in pediatric renal cell carcinoma.

Adenocarcinomas of the kidney are rare childhood tumors. Only 30 cases with chromosomal abnormalities have been reported, and neither their karyotypic characteristics nor the molecular mechanisms behind their pathogenesis are clear, except for a special group of papillary tumors characterized by X-chromosome abnormalities. We have cytogenetically analyzed short-term cultured cells from two pediatric renal carcinomas, one papillary, and one chromophobe renal cell carcinoma, revealing the following karyotypes: 58-60,XX,-X,-1,+7,-8,-9,-11,-14,-15,+17,-18,-19,-21,-22 and 36,X,-X,-1,-2,-5,-6,-9,-10,-13,-17,-21/37,idem,+r/36,idem,-14,+1-2r, respectively. The findings indicate that subsets of pediatric renal cell carcinoma show karyotypes that are similar to their adult counterparts.

Cytogenetic findings and clinical course in a consecutive series of Wilms tumors.

Wilms tumor (WT) is characterized by a nonrandom pattern of chromosome aberrations, but the clinical significance of different cytogenetic patterns is unknown. The present study describes the cytogenetic findings and the clinical course in a cohort of 39 children with WT. Samples for short-term culturing and cytogenetic analysis were obtained during a 15-year period. Clonal chromosome aberrations were detected in 23 samples from 19 patients. Tumors that relapsed more often showed clonal aberrations than did tumors that did not. However, this association my have been due to sampling bias. Among the cases with karyotypically abnormal samples, the modal chromosome number was in the near-diploid range in 10, hyperdiploid/hypotriploid in 8, and hypodiploid in 1. The most common changes were trisomy 12 and gain of 1q material (8 cases each), trisomy/tetrasomy 8 (7 cases), and trisomy 13 (5 cases). None of these frequently occurring abnormalities, or the ploidy level, showed any association with clinical outcome, using tumor relapse as an end-point. Nor could any relationship between cytogenetic features and histopathologic subtype be discerned. Although the number of informative cases was too small for proper evaluation, the present study did not contradict the previous notion that loss of material from the long arm of chromosome 16 is associated with poor clinical outcome. All three patients with deletion of 16q developed metastases.

Pre- and postoperative vomiting in children undergoing video-assisted gastrostomy tube placement.

Background. The aim of this study was to determine the incidence of pre- and postoperative vomiting in children undergoing a Video-Assisted Gastrostomy (VAG) operation. Patients and Methods. 180 children underwent a VAG operation and were subdivided into groups based on their underlying diagnosis. An anamnesis with respect to vomiting was taken from each of the children's parents before the operation. After the VAG operation, all patients were followed prospectively at one and six months after surgery. All complications including vomiting were documented according to a standardized protocol. Results. Vomiting occurred preoperatively in 51 children (28%). One month after surgery the incidence was 43 (24%) in the same group of children and six months after it was found in 40 (22%). There was a difference in vomiting frequency both pre- and postoperatively between the children in the groups with different diagnoses included in the study. No difference was noted in pre- and postoperative vomiting frequency within each specific diagnosis group. Conclusion. The preoperative vomiting symptoms persisted after the VAG operation. Neurologically impaired children had a higher incidence of vomiting than patients with other diagnoses, a well-known fact, probably due to their underlying diagnosis and not the VAG operation. This information is useful in preoperative counselling.

Laparoscopic aided cholecystostomy as a treatment of inspissated bile syndrome.

We report a case of a newborn girl with inspissated bile syndrome (IBS) that did not respond to treatment with oral ursodeoxycholic acid (Ursofalk). A solution was found using laparoscopic aided cholecystostomy with an indwelling catheter for local Ursofalk flushing in the gallbladder and the choledochus. This is the first report of a laparoscopic aided management of IBS without cholecystectomy or exploration of the bile ducts. This minimal invasive approach showed a clear advantage for the patient. There were no complications. The method is recommended in the treatment of IBS.

Cytogenetic and molecular cytogenetic findings in lipoblastoma.

Lipoblastoma is a rare benign tumor that arises from embryonic adipose tissue and usually occurs in young children. Here, we present a review of available cytogenetic data and the karyotypes of 10 new cases of lipoblastoma, of which 7 could be studied further by fluorescence in situ hybridization (FISH) with regard to the involvement of the PLAG1 gene. All seven tumors with clonal aberrations harbored breakpoints in 8q11 approximately q13, in agreement with literature data. Including previously published cases, 33/40 (82%) lipoblastomas had rearrangement of the 8q11 approximately q13 region. These rearrangements target the PLAG1 gene, which becomes upregulated through promoter swapping. FISH revealed that five of seven cases in our series had a rearrangement of the PLAG1 gene. Occasionally, there can be difficulties in distinguishing a lipoblastoma from a conventional lipoma or a myxoid liposarcoma. As 8q11 approximately q13 rearrangements have been reported in only 3% of conventional lipomas and never in myxoid liposarcoma, cytogenetic analysis or FISH for the PLAG1 gene can provide useful differential diagnostic information.

Fusion of the tumor-suppressor gene CHEK2 and the gene for the regulatory subunit B of protein phosphatase 2 PPP2R2A in childhood teratoma.

We characterized the molecular genetic consequences of a balanced chromosome translocation t(8;22)(p21;q12), which occurred as the sole cytogenetic aberration in short-term cultured cells from an intrathoracic mature teratoma in a 15-year-old girl. Fluorescence in situ hybridization and reverse transcription-polymerase chain reaction disclosed that t(8;22) resulted in the fusion of the genes PPP2R2A and CHEK2, with an inserted fragment belonging to class I endogenous retrovirus-related sequences at the junction. Sequencing of the two genes did not reveal any additional mutation. None of the three detected PPP2R2A/CHEK2 fusion transcripts resulted in an in-frame PPP2R2A/CHEK2 chimerical open reading frame; however, in all of them, the known open reading frame of CHEK2 was preserved. Thus, promoter swapping leading to deregulated CHEK2 expression would be the most likely oncogenic mechanism. Whereas inactivating mutations of CHEK2 previously have been described in a variety of sporadic tumors and in inherited cancer-predisposing syndromes, PPP2R2A, encoding a regulatory subunit of the multimeric enzyme phosphatase 2, has not been directly implicated in tumorigenesis. Our findings suggest that deregulation of CHEK2 and/or PPP2R2A is of pathogenetic importance in at least a subset of germ cell tumors.

Complications of video-assisted gastrostomy in children with malignancies or neurological diseases.

AIM: To test the hypothesis whether the administration of cytostatic drugs close to surgery in children with malignancies influences the rate of postoperative complications. METHOD: Included in the study were 27 children with malignancies and a control group of 27 neurologically impaired children. All the children had nutritional problems and underwent a video-assisted gastrostomy (VAG) operation during the period 1997-2002. The children were postoperatively followed up. All complications were documented according to a protocol by a specially trained nurse and correlated to the time elapsed from completion of the last preoperative or the first postoperative cytostatic drug treatment. The complications in the two groups were compared. RESULTS: The children with malignant diseases did not have more postoperative complications of the VAG than those having neurological defects. There was no correlation to complications regarding timing of the operation and administration of cytostatic drugs. CONCLUSION: This study revealed no aggravated influence of cytostatic drug treatment on early postoperative problems of VAG. The timing of cytostatic drug administration in relation to the surgical intervention did not influence the frequency of postoperative complications.

Closure after gastrostomy button.

A gastrostomy device is removed from the gastrostoma when no longer needed. The aim of the study was to test the hypothesis of whether it is possible for the surgeon to decide which stoma has to be closed with a gastroraphy and which to leave for a spontaneous closure within a reasonable period of time. Out of a cohort of 321 patients, who had been operated with a video-assisted gastrostomy, we included all the 48 patients having had their gastrostomy button removed. These patients were carefully followed and the closure of the gastrostoma was registered. According to the institutional routine we waited at least 3 months after the removal of the gastrostomy device before suggesting to the child's guardians an operative closure of the stoma. In 26 patients the stoma closed within 3 months, whereas in 22 patients a surgical gastroraphy was performed. We found no differences between the two groups regarding the patients' diagnoses, the duration of the gastrostoma use or patient's age at the time of removal of the gastrostomy device. This study rejected the hypothesis of predictability of the gastrostoma closure. Thus, we recommend a routine expectance after the removal of a gastrostomy device for at least 1 month. If no spontaneous closure occurs, then a gastroraphy should be performed.

Relapses in Wilms tumour.

During an 18-year period, 54 children were treated for Wilms tumour (WT). Thirteen of them, 6 boys and 7 girls, had a relapse. Mean age at diagnosis was 50 months, range 5-233 months. The investigations revealed stage I in 5 cases, stage II in 2, stage III in 3, stage IV in 1 and stage V in 2.The histology was favourable in 6 cases, intermediate in 4 and unfavourable in 3. Clonal chromosome aberrations were detected in 8 cases. The mean time to first relapse was 17 months, range 1-76 months. The location was the local region in 3 cases, other kidney in 3, lungs in 7 and skeletal in 2. A second relapse occurred in 6 patients and a third relapse in 2 patients. Seven patients died after a mean follow-up of 84 months, range 42-180 months, from primary treatment. The 6 surviving children had no evidence of disease after a mean follow-up of 70 months, range 42-120 months, after treatment ended. High stage at diagnosis, unfavourable histologic subtype and occurrence of nephroblastomatosis were found not only in the children with relapse. No significant correlations were found when comparing the karyotypic features with clinical outcome. All 3 tumours with deletions of chromosome arm 16q metastasized.