Alveolar soft part sarcoma occurring on the abdominal wall of a 2-year-old child

Alveolar soft part sarcoma (ASPS) is a rare soft tissue malignant neoplasm that affects young people. It can occur in any region of the body and at any stage of development. But ASPS on the abdominal wall is rarely reported. However, a few cases were reported in children under the age of 10 years. In this study we report a case of ASPS that occurred on the abdominal wall of a 2-year-old patient.     

Pediatric Renal Cell Carcinomas with Xp11.2 Rearrangements Are Immunoreactive for hMLH1 and hMSH2 Proteins

Alveolar soft part sarcoma and pediatric renal cell carcinoma share a similar chromosomal abnormality, t(X;17)(p11.2;q25). Recently, it has been suggested that the inactivation of DNA mismatch repair genes hMLH1 and hMSH2 may play an additional role in the pathogenesis of alveolar soft part sarcoma. Immunohistochemical expression of the proteins hMLH1 and hMSH2 is indicative of the activation status of the corresponding genes. We performed immunohistochemistry for hMLH1 and hMSH2 in 4 cases of pediatric renal cell carcinomas with Xp11.2 rearrangements. All cases showed nuclear immunoreactivity for both proteins, although the staining was patchy. Our study demonstrates that inactivation of the DNA mismatch repair genes hMLH1 and hMSH2 does not appear to play a role in the tumorigenesis of pediatric renal cell carcinomas with Xp11.2 rearrangements.     

Alveolar soft part sarcoma Sehr seltene Ursache eines langsam wachsenden indolenten subkutanen Knotens

Zusammenfassung Fragestellung: Langsam wachsende nicht schmerzhafte subkutane Knoten k?nnen durch unterschiedlichste gut- oder b?sartige mesenchymale Proliferationen verursacht sein. Da sich hinter diesem Zeichen oft ein Malignom verbirgt und bildgebende Analysen nur selten den Weg zur Diagnose weisen, ist eine bioptische Kl?rung dringend erforderlich. Methode: Wir berichten über 3 Patientinnen (Alter 9, 19¹/₁₂ und 23¹/₆ Jahre) bei denen sich hinter einem langsam wachsenden subkutanen Knoten ein nicht embryonales Sarkom (Alveolar soft part sarcoma) verbarg. Ergebnisse: Das Alveolar soft part sarcoma (ASPS) ist ein ausgesprochenes seltenes Malignom. Zum Diagnosezeitpunkt lag bei 2 Patientinnen bereits eine Metastasierung vor. Eine Patientin verstarb noch vor Behandlungsbeginn. Bei der 2. sind Lungenmetastasen trotz multimodaler Therapie 4¹/₂ Jahre nach Diagnosestellung langsam progredient. Die 3. Patientin erhielt nach Resektion eines lokalisierten ASPS am Oberarm postoperativ eine Polychemo- und lokale Strahlentherapie und ist 8 Monate nach der Diagnosestellung ohne Krankheitszeichen. Schlu?folgerung: Das ASPS ist ein langsam wachsender Tumor mit ausgepr?gter Metastasierungstendenz. Die Prognose ist im wesentlichen von der Operabilit?t des Prim?rtumors und dem Vorliegen von Metastasen abh?ngig.      

Alveolar soft part sarcoma: clinical, histopathological, molecular, and ultrastructural aspects

Alveolar soft part sarcoma (ASPS) is a rare soft tissue tumor occurring mainly in the adolescents and young adults. Multimodality treatment has not been effective, and excision remains the mainstay of treatment. Histopathologically, it varies little from case to case. It is composed of organoid aggregates of large polygonal cells with vesicular nuclei and abundant granular, eosinophilic cytoplasm, separated by delicate vascular channels. The line of differentiation of this unique tumor is yet undetermined, although recent advances have led to a better understanding of the genetic events underlying the pathogenesis of this tumor. The histopathological, ultrastructural, immunohistochemical, and genetic aspects of ASPS are discussed.     

Expression of C-kit in Ewing Family of Tumors: A Comparison of Different Immunohistochemical Protocols

Ewing sarcoma is a small round blue cell tumor with a high incidence of metastasis and poor survival. The tyrosine kinase receptor, c-kit, is a growth factor receptor that is expressed in a variety of tumors including Ewing sarcoma. Blockade of c-kit by imatinib mesylate (Gleevec; Novartis Pharmaceuticals Corp, East Hanover, NJ) has been successfully used in the treatment of chronic myelogenous leukemia and gastrointestinal tumors. Detection of c-kit expression in Ewing sarcoma indicates a possible role of c-kit in tumor progression and a potential use of anti-c-kit therapy in Ewing sarcoma. Ki-67 is a proliferation marker found at all stages of the cell cycle. Expression of c-kit and Ki-67 was studied in 17 patients with Ewing sarcoma. Sections from paraffin-embedded tumor samples were immunostained, using standard immunohistochemical protocols, with c-kit and Ki-67 monoclonal antibodies, polyclonal c-kit antibody without antigen retrieval, and c-kit polyclonal antibody with antigen retrieval. Eleven out of 17 cases (65%) stained with c-kit monoclonal antibody; the staining was diffuse in 6/17 (35%) cases. C-kit expression did not correlate with Ki-67 proliferation rates. Using the polyclonal c-kit-antibody without antigen retrieval methods, c-kit expression was demonstrated in 1/11 (9%) cases. Incorporating antigen retrieval methods, c-kit expression increased to 53%. Concordance between monoclonal antibodies in detecting c-kit expression was observed in 12/17 cases (71%). We conclude that c-kit is variably expressed in Ewing sarcoma, using either monoclonal or polyclonal antibodies. Detection of c-kit expression in Ewing sarcoma improves with the use of antigen retrieval methods.     

Cooperative Ewing's Sarcoma Studies 81/86: pathologico-anatomic and immunohistochemical findings and differential diagnosis of Ewing sarcoma

158 cases of the Cooperative Ewing's Sarcoma Trials (CESS 81/86), which have been documented at the Pediatric Tumor Registry, Kiel, were studied by conventional light microscopy and immunohistochemistry. There were 77 cases of typical Ewing's sarcoma with 70 cases being located in the skeleton and 7 in soft tissues. Of the 14 cases of atypical Ewing's sarcoma 7 cases each were localized in bone and in soft tissue, respectively. In contrast to typical Ewing's sarcoma, cells of atypical Ewing's sarcoma were larger and displayed more heterochromatin. Both, typical and atypical Ewing's sarcoma reacted positively for vimentin. Other stains were negative, notably the neuron specific enolase (NSE). In 55 cases a diagnosis of malignant peripheral neuroectodermal tumor (MPNT) was made. Histologically most of these tumors resembled atypical Ewing's sarcoma. By immunohistochemistry positive reactions were found for NSE, vimentin, protein S-100, neurofilaments and glial fibrillary acidic protein. In 3 cases a diagnosis of small cell osteosarcoma was made. There were 2 cases of undifferentiated sarcoma of bone, 2 cases of soft tissue sarcoma of undetermined histogenesis and 2 cases of rhabdomyosarcoma. Of the 4 tumors which could be investigated for response to polychemotherapy, 1 each corresponded to grade II and III, respectively, and 2 to grade IV according to the classification of histologic grade of regression established by Salzer-Kuntschik et al. (1983).     

Developmental Pattern of Thy-1 Immunoreactivity in the Human Kidney and the Application to Pediatric Renal Neoplasms

The localization of Thy-1, a surface membrane lipoglycoprotein, was investigated using a monoclonal antibody specific for human Thy-1 (HB-2S-1). The localization of Thy-1 during development was established in a series of five fetal, three childhood, and two adult normal kidneys. In this series, Thy-1 immunolocalization progressed from mesangial and endothelial cell staining in the 16- to 17-week fetuses to similar staining along with staining of the parietal epithelium of the capsule and proximal tubule staining in the 20- to 24-week fetuses. Glomerular mesangial cell and endothelial cell staining was absent by 9 months postnatally when the adult pattern of staining was apparent. The localization of Thy-1 during development was also compared with a series of pediatric renal tumors including 14 Wilms' tumors, 3 congenital mesoblastic nephromas, 1 clear cell sarcoma, and 1 pediatric renal cell carcinoma. Thy-1 staining was demonstrated in epithelial tubules of Wilms' tumors and in the spindle-shaped cells of congenital mesoblastic nephroma correlating with Thy-1 immunoreactivity in the kidney proximal tubule and fetal medullary stroma, respectively. Thy-1 staining was absent in the anaplastic epithelial Wilms' tumor, the renal cell carcinoma, and the clear cell sarcoma. This staining pattern fails to provide evidence that these tumors may arise from the medullary mesenchyme or the differentiated     

Prospects for targeted therapy of synovial sarcoma

Synovial sarcoma is a distinct tumor with unique promise for targeted therapy. It has a diagnostic translocation and a potentially informative fusion protein. It has moderate chemosensitivity, with about 50% response rates to regimens containing ifosfamide and doxorubicin. Therapeutic advances are unlikely to occur by continuing to lump synovial sarcomas in trials with other soft tissue sarcomas and adjusting traditional agents; rather, attention should be turned toward prospective molecular targets and investigation or development of novel agents to exploit them. The SYT-SSX fusion protein that results from the X,18 translocation is an appealing target, as are the proteins overexpressed in synovial sarcoma: bcl-2, EGFR, and HER-2/neu.     

Cytogenetic abnormalities in 42 rhabdomyosarcoma: a United Kingdom Cancer Cytogenetics Group Study.

BACKGROUND: Rhabdomyosarcomas are the most common type of pediatric soft tissue sarcoma. The cytogenetic literature on RMS is biased towards the less common alveolar subtype (ARMS), which is frequently associated with specific translocations and the PAX3/7-FKHR fusion genes. Relatively few karyotypes are reported for the embryonal subtype (ERMS). The aim of this study was to further cytogenetic knowledge of RMS subtypes. PROCEDURE: Representative examples of all karyotypes from UKCCG; member laboratories were reexamined and their histopathologies reviewed through the United Kingdom Children's Cancer Study (Group) (UKCCSG). Molecular evidence for the PAX3/7-FKHR fusion genes was available for five ERMS and seven ARMS cases and compiled with the karyotypes. RESULTS: Clonal chro mosome aberrations were characterized for 25 ERMS and 17 ARMS cases. Thirty-six percent of the ERMS cases involved translocation breakpoints in the 1p11-q11 region. Ten of the seventeen cases of ARMS showed cytogenetic evidence for the t(2;13)(q35;q14), consistent with molecular data available from four of these. Two further ARMS cases revealed a PAX3-FKHR and a variant PAX7-FKHR fusion gene product that were not detected cytogenetically. CONCLUSIONS: Many of the karyotypes from both subtypes were complex. The frequent involvement of the 1p11-1q11 region and gain of chromosomes 2, 8, 12, and 13 in ERMS may be functionally significant. There was no evidence for involvement of the PAX3/7-FKHR genes in ERMS, and cryptic involvement was found in some ARMS. There were no consistent chromosomal rearrangements associated with apparently translocation negative ARMS cases.     

Pilot trial of tumor-specific peptide vaccination and continuous infusion interleukin-2 in patients with recurrent Ewing sarcoma and alveolar rhabdomyosarcoma: an inter-institute NIH study

BACKGROUND: Patients with recurrent Ewing sarcoma and alveolar rhabdomyosarcoma have poor prognoses and limited therapeutic options. We have investigated the use of peptide pulsed vaccination in an attempt to immunologically target the breakpoint region of tumor specific fusion proteins expressed in these tumors. PROCEDURE: Sixteen patients with recurrent, translocation positive, Ewing sarcoma, and alveolar rhabdomyosarcoma underwent apheresis for collection of peripheral blood mononuclear cells. Following countercurrent centrifugal elutriation, an apheresis product comprised predominantly of monocytes but containing small numbers of circulating immature dendritic cells was pulsed with peptides derived from the breakpoint region of the fusion proteins. Vaccines were administered intravenously concomitant with continuous intravenous rhIL-2 at 9 x 10(6) IU/m(2)/day. RESULTS: Toxicity was limited to IL-2 related effects and was generally mild. Following vaccination, all patients showed progressive disease, most in a rapid fashion following the first vaccine. One patient showed evidence of an immunologic response and another showed a mixed clinical response. Patients enrolled on this tumor vaccine trial showed significant immunosuppression and large bulky tumors. CONCLUSIONS: Peptide vaccination as administered in this trial did not alter the dismal clinical outcome for patients with recurrent pediatric sarcomas. Future trials of tumor vaccines in this population should target patient populations with improved immune competence and smaller tumor burdens. Furthermore, optimization of the antigen presenting cell populations may be important for inducing immune responses to peptide antigens.     

Monoclonal Antibody MB2: a Potential Marker for Ewing's Sarcoma and Primitive Neuroectodermal Tumor

The smalt round-cell tumors of childhood present difficulties in diagnosis when differentiation is not apparent. Immunohistochemislry is helpful; however, the only antigen consistently detected in Ewing's sarcoma is vimentin, which may also he detected in the other types of small-cell neoplasms. The monoclonal antibody (MAb) MB2 is marketed as a B-lymphocyte marker that can be used on paraffin-embedded tissue. To determine its specificity, we performed immunohistochemical staining on pediatric tumors with MB2. These included 55 cases of small round-cell tumors (lymphomas, Ewing 's sarcoma, peripheral primitive neuroectodermal tumors [PNET], neuroblastomas, rhabdomyosarcomas, and nephroblastomas). MB2 positivity was detected in all B-cell lymphomas and in seven of nine cases of Ewing's sarcoma and three of three PNET. In neuroblastomas only differentiating ganglion cells were positive. In rhabdomyosarcomas only large rhabdomyoblasls were positive. Blastema of nephroblastomas was negative. Thus, in cases of poorly differentiated small round-cell tumors, MB2 was positive in all B-cell lymphomas, most Ewing's sarcomas and all cases of PNET. Lymphomas were distinguished by staining for leukocyte-common antigen and PNET by neuron-specific enolase. Therefore, the addition of MB2 to a discrete panel of antibodies may prove useful in the diagnosis of Ewing's sarcoma and PNET.     

Monoclonal antibody MB2: a potential marker for Ewing's sarcoma and primitive neuroectodermal tumor

The small round-cell tumors of childhood present difficulties in diagnosis when differentiation is not apparent. Immunohistochemistry is helpful; however, the only antigen consistently detected in Ewing's sarcoma is vimentin, which may also be detected in the other types of small-cell neoplasms. The monoclonal antibody (MAb) MB2 is marketed as a B-lymphocyte marker that can be used on paraffin-embedded tissue. To determine its specificity, we performed immunohistochemical staining on pediatric tumors with MB2. These included 55 cases of small round-cell tumors (lymphomas, Ewing's sarcoma, peripheral primitive neuroectodermal tumors [PNET], neuroblastomas, rhabdomyosarcomas, and nephroblastomas). MB2 positivity was detected in all B-cell lymphomas and in seven of nine cases of Ewing's sarcoma and three PNET. In neuroblastomas only differentiating ganglion cells were positive. In rhabdomyosarcomas only large rhabdomyoblasts were positive. Blastema of nephroblastomas was negative. Thus, in cases of poorly differentiated small round-cell tumors, MB2 was positive in all B-cell lymphomas, most Ewing's sarcomas and all cases of PNET. Lymphomas were distinguished by staining for leukocyte-common antigen and PNET by neuron-specific enolase. Therefore, the addition of MB2 to a discrete panel of antibodies may prove useful in the diagnosis of Ewing's sarcoma and PNET.     

Alveolar soft part sarcoma—radiologic patterns in children and adolescents

Background

Alveolar soft part sarcoma is a rare but highly malignant tumour and little is known about its radiologic pattern in children.

Objective

To describe the radiologic features of alveolar soft part sarcoma in children and adolescents.

Materials and methods

We retrospectively analysed the clinical and imaging data of six children age 7–17 years at diagnosis, with histologically or genetically proven alveolar soft part sarcoma.

Results

The tumours were located deep within muscles of the limbs (n?=?4), in chest wall muscle (n?=?1) and in the orbit (n?=?1). High-flow feeding arteries, large drainage veins and intense enhancement were consistent findings by all imaging modalities. At MRI, all tumours demonstrated high signal intensity on T2-weighted images and high or iso-intense signal on T1-W imaging compared to muscle. In tumours larger than 70 mm in one dimension (n?=?3/6), large vessels converging toward the tumour centre led to a highly vascularised central stellar area pattern. Five children demonstrated synchronous (n?=?4/5) and metachronous (n?=?1/5) lung metastases.

Conclusion

Alveolar soft part sarcoma should be suggested when a highly vascularised, intramuscular mass demonstrating large feeding and drainage vessels converging toward a central stellar area is seen in children, especially if synchronous lung metastases are present.