Rhabdomyosarcoma

Rhabdomyosarcomas (RMS) are the most common pediatric soft tissue sarcomas. They resemble developing skeletal muscle and are histologically divided into two main subtypes; alveolar and embryonal RMS. Characteristic genomic aberrations, including the PAX3- and PAX7-FOXO1 fusion genes in alveolar cases, have led to increased understanding of their molecular biology. Here, we determined the effect of genomic copy number on gene expression levels through array comparative genomic hybridization (CGH) analysis of 13 RMS cell lines, confirmed by multiplex ligation-dependent probe amplification copy number analyses, combined with their corresponding expression profiles. Genes altered at the transcriptional level by genomic imbalances were identified and the effect on expression was proportional to the level of genomic imbalance. Extrapolating to a public expression profiling dataset for 132 primary RMS identified features common to the cell lines and primary samples and associations with subtypes and fusion gene status. Genes identified such as CDK4 and MYCN are known to be amplified, overexpressed, and involved in RMS tumorigenesis. Of the many genes identified, those with likely functional relevance included CENPF, DTL, MYC, EYA2, and FGFR1. Copy number and expression of FGFR1 was validated in additional primary material and found amplified in 6 out of 196 cases and overexpressed relative to skeletal muscle and myoblasts, with significantly higher expression levels in the embryonal compared with alveolar subtypes. This illustrates the ability to identify genes of potential significance in tumor development through combining genomic and transcriptomic profiles from representative cell lines with publicly available expression profiling data from primary tumors. © 2009 Wiley-Liss, Inc.

Adverse effects on normal tissue are the principal limiting factor in the use of radiation therapy. Maturing tissues are most susceptible to these side effects, so high-dose applications can be a particularly difficult challenge in children. Intraoperative radiation therapy (IORT) enables the radiation oncologist to displace or shield dose-limiting organs or structures. These first two cases of children treated with IORT suggest that IORT, used alone or in conjunction with external beam irradiation, may be useful in the pediatric age group.

Resection is the only curative treatment option for primary and secondary malignant tumors of the liver. Although curative resection is associated with long-term survival rates, it can only be performed in 10% of patients with primary tumors and 25% of patients with liver metastases. Liver insufficiency is one of the most serious postoperative complications of patients undergoing extensive liver resections. When total liver resection is necessary liver transplant is mandatory, with the burden of long-term immunosuppression and its complications. Among several different strategies to increase the resectability of liver tumors, portal vein occlusion (embolization or ligature), bilateral tumor resection in two stages, and resection combined with loco regional therapy are the most popular. A new strategy for patients with marginally resectable liver tumors previously considered to be unresectable was formally reported by Baumgart et al. in 2011, originally developed by Hans Schlitt in 2...

Objective— To describe a surgical technique for resection of the entire bladder neck, including the trigone and proximal urethra in dogs with invasive tumors causing life-threatening urinary tract obstruction.Study Design— Clinical case reports.Animals— Dogs (n=2) with bladder tumors.Methods— Circumferential excision of the bladder neck and proximal urethra with preservation of the neurovascular pedicles was performed to remove a rhabdomyosarcoma (dog 1) and a transitional cell carcinoma (dog 2) involving the trigone and bladder neck that were causing urinary tract obstruction. Reconstruction of the bladder and proximal urethra included bilateral ureteroneocystostomy. Adjuvant chemotherapy was administered postoperatively to both dogs.Results— Postoperatively, dogs 1 and 2 were continent after 7 and 17 days, respectively, and regained normal urinary function after resolution of a transient pollakiuria. Dog 1 had no evidence of local or regional recurrence; however, a large solitary pulmonary metastatic lesion was diagnosed 8 months later. The dog was euthanatized despite a lack of clinical signs. Dog 2 had at least 1 metastatic lesion in the abdominal wall 6 months later and was euthanatized at 580 days because of renal failure.Conclusion— En-bloc removal of the bladder neck and proximal urethra with preservation of the dorsal vascular and nervous pedicles, although a technically challenging procedure, can be performed without associated urinary incontinence or bladder wall necrosis.Clinical Relevance— In dogs with invasive bladder tumors causing life-threatening urinary tract obstruction, resection of the bladder neck and proximal urethra should be considered as a promising surgical alternative to urinary diversion.

While fairly complete and reliable incident data on childhood cancers are available from the registries in India, mortality and survival information is not. Information concerning the latter was obtained by the Bangalore cancer registry through active follow-up involving visits to homes of patients. Between 1982 and 1989, 617 cases of cancers in childhood were registered, giving an age-standardized incidence rate of 84.8 and 48.4 per million in male and female children, respectively. Active follow-up provided mortality/survival information in 532 or 86.2 percent of these cases. Overall, observed five-year survival was 36.8 percent (both genders combined) with a relative survival of 37.5 percent when childhood mortality in the general population was taken into account. The five-year relative survival was best for thyroid carcinoma (100 percent) followed by Hodgkin's disease (73 percent) and retinoblastoma (72.9 percent). Survival was comparatively low, being 9.9 percent in acute nonlymphatic leukemia and less than 20 percent in rhabdomyosarcoma and the category grouped as ‘other malignant neoplasms.’ Survival in Hodgkin's disease was influenced by clinical stage at presentation, but was not statistically significant possibly due to small numbers.

Rhabdomyosarcoma is a rare childhood cancer that affects only approximately 300 children per year in the United States. The purpose of this review is to provide the reader a greater understanding of the complex diagnosis, assessment and treatment of rhabdomyosarcoma in children. This review focuses on the new risk classification that is the foundation of all present rhabdomyosarcoma protocols developed by the Children's Oncology Group of the United States and Canada. The new risk classification of low, intermediate and high encompasses the staging and grouping categories that were previously utilized. This review also provides a complete list of diagnostic tests and imaging required to identify rhabdomyosarcoma in any body site. Rapid diagnosis and recognition of this rare disorder will facilitate long-term survival. Rhabdomyosarcoma today has an overall survival of 70%, depending on the site, and in orbital and other sites survival is as high as 90%. The treatment approaches that have led to this doubling in survival over the last 25 years are reviewed. For a practitioner, this review can be used as a reference when a child with a suspicious mass is encountered.

Orbital rhabdomyosarcoma is mesenchymal tumor, presents 10-20% of all rhabdomyosarcoma are usually diagnosed in
children. It presents clinically by rapidly progressive unilateral proptosis. Imaging is fundamental to assessing the extent of
the tumor and the erosion of the bone, but only histology can confirm the diagnosis. The treatment involves a combination
of chemotherapy, radiotherapy and surgery. The challenge is to choose a treatment with good cosmetic and functional
results specially visual function and excellent survival.
Keywords: Orbital; Rhabdomyosarcoma; Histology; Radiotherapy; Chemotherapy; Surgery.

As for rhabdomyosarcoma (RMS) of other anatomic regions, the evaluation of traditional clinicopathological parameters does not allow the unequivocal outcome prediction of the single cases of orbital RMS. We investigated the role of DNA ploidy and immunohistochemical expression of p53, bcl-2, MDR-1 and Ki67 (MIB1) in the prognostic evaluation of orbital rhabdomyosarcomas. The study population consisted of 11 selected cases. Serial sections of each tumor, stained with Feulgen's technique, were analyzed for the DNA content, using the QUANTIMET 500c Leica analyzer, QWINVO200A software. The results were compared with the immunohistochemical expression of p53 (wild plus mutated, W&M and mutated), bcl2, MDR-1 and Ki67 (MIB1), and with follow-up data. The statistical analysis of results showed that the cases of tetraploid and/or multiploid RMS, overexpressing p53 (W&M and mutated) and MDR-1, were characterized by an overall worse prognosis. On the contrary, the tumors with a favourable ...

A rhabdomyoblastic differentiation in a malignant peripheral nerve sheath tumor is unusual and is termed as a malignant triton tumor. A series of 10 such cases with their clinicomorphological features, diagnosed over a 10-year period, is presented. The average age of occurrence was 30 years, with the maximum number of cases in the second decade and with male outnumbering female

1. Curr Probl Surg. 2005 Jan;42(1):12-66. Management of patients with metastatic cancer of unknown primary. Ghosh L, Dahut W, Kakar S, Posadas EM, Torres CG, Cancel-Santiago R, Ghosh BC. Pathology, State University of New York-Brooklyn, Brooklyn, NY, USA. ...

To evaluate the performance of seven different TPS (Treatment Planning Systems: Corvus, Eclipse, Hyperion, KonRad, Oncentra Masterplan, Pinnacle and PrecisePLAN) when intensity modulated (IMRT) plans are designed for paediatric tumours. Datasets (CT images and volumes of interest) of four patients were used to design IMRT plans. The tumour types were: one extraosseous, intrathoracic Ewing Sarcoma; one mediastinal Rhabdomyosarcoma; one metastatic Rhabdomyosarcoma of the anus; one Wilm's tumour of the left kidney with multiple liver metastases. Prescribed doses ranged from 18 to 54.4 Gy. To minimise variability, the same beam geometry and clinical goals were imposed on all systems for every patient. Results were analysed in terms of dose distributions and dose volume histograms. For all patients, IMRT plans lead to acceptable treatments in terms of conformal avoidance since most of the dose objectives for Organs At Risk (OARs) were met, and the Conformity Index (averaged over all ...

The Pax3–FKHR fusion protein is present in alveolar rhabdomyosarcoma and results from the t (2; 13)(q35; q14) chromosomal translocation. Its oncogenic activity is dependent on a combination of protein–DNA and protein–protein interactions mediated ...

Objective The aim of this study was to identify novel genes following genomic DNA copy number changes using a genome-wide array-based comparative genomic hybridization (array-CGH) analysis in uterine leiomyosarcoma (ULMS). Methods Genomic DNA copy number changes were analyzed in 15 cases of ULMS from St Mary’s Hospital of the Catholic University of Korea. The paraffin-fixed tissue samples were micro-dissected under microscope, and DNA was extracted. Array-based CGH and genomic polymerase chain reaction were carried out with statistical analyses such as hierarchical clustering and Gene Ontology. Results All of 15 cases of ULMS showed specific gains and losses. The percentage of average gains and losses were 8.4 and 16.6 %, respectively. The analysis limit of average gains and losses was 40 %. The regions of high level of gain were 1q23.3, 7p14.2, 7q34, 7q35, 7q36.3, 13q34, and 16p13.3. And the regions of homozygous loss were 2q21.1, 2q22.1, 2p23.2, 12q23.3, 4q21.22, 4q34.3, 11q24.2, 12q23.3, 13q13.1, 13q21.33, and 14q24.3. In ULMS samples, recurrent regions of gain were 1p36.33, 1p36.32, 5q35.3, 7q36.3, and 8q24.3 and recurrent regions of loss were 1p31.1–p31.3, 1p32.1–p32.3, 2p12, 2p13.3, 2p14, 2p16.2–p16.3, 2q12.1–q12.3, 2q21.1–q21.2, 2q22.2–q22.3, 2q34, 2q36.1–q36.3, 5q21.3, 5q23.3, 5q31.1, 6p11.2, 6p12.1, 10q11.23, 10q21.2–q21.3, 10q23.2, 10q23.31, 10q25.1–q25.2, 10q25.3, 10q26.13, 10q26.2–q26.3, 11p11.2, 11p11.12, 11p12, 11p13, 11p15.4, 11q23.1–q23.2, 11q23.3, 13q14.12, 13q14.13–13q14.2, 13q14.2, 13q14.2, 13q14.3, 13q21.33, 13q22.1–q22.3, 14q24.2, 14q24.3, 14q31.1, 14q32.33, 15q11.2–q13, 15q14, 16q22.3, 16q23.1, 16q23.2, 16q24.1, 20p12.1, and 21q22.3. Representative frequently gained BAC clones encoded genes were HDAC9, CRR9, SOX18, PTPRN2, SKI, SOLH, and KIAA1199. The genes encoded by frequently lost BAC clones were LOC150516 and AMY2A. A subset of cellular processes from each gene were clustered by Gene Ontology database. Conclusions The present study using array-CGH analyses sought a deeper elucidation of the specific genomic alterations related to ULMS. The high resolution of array-CGH combined with human genome database would give a chance at identifying relevant target genes.

Histologic grading has been considered the most important prognostic factor for soft tissue sarcomas. Several grading systems have been proposed based on the assessment of morphologic features in heterogeneous groups of sarcomas. Currently, the French Federation of Cancer Centers (FNCLCC) and the National Cancer Institute (NCI) grading systems are the most commonly used. These systems are based on a few morphologic predictors of biologic behavior, which is justifiable because of the rarity of soft tissue sarcomas. Nonetheless, over- or underestimation of prognosis may occur because of an uneven representation of specific sarcomas with rather distinct biologic behaviors among studies of grading systems. In addition, lack of standardization of morphologic criteria and frequent omission of the influence of clinical factors on the final survival analyses preclude universal acceptance of a particular grading system. New advances in diagnostic imaging, quantitative morphometric technologies, cytogenetics, and molecular genetics, allied with alternative analytic data systems, may provide better validation, reproducibility, and prognostic capabilities for current and future grading systems. This article summarizes and critically analyzes the various important grading systems that have thus far been proposed and suggests alternatives for the elaboration of more reproducible systems with higher predictive capabilities.