Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “RHABDOMYOSARCOMA”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 109 records · Page 6Linked to original sources
PubMedDate not supplied

From the archives of the AFIP. Genitourinary rhabdomyosarcoma in children: radiologic-pathologic correlation.

Rhabdomyosarcoma is the most common tumor of the lower genitourinary tract in children in the first 2 decades of life. Most cases of genitourinary rhabdomyosarcoma are of the embryonal histologic subtype and include tumors of the bladder, prostate, testes and paratesticular sites, penis, perineum, vagina, and uterus. The natural history, pattern of metastatic spread, treatment, and prognosis of childhood rhabdomyosarcoma vary with the anatomic site of the lesion. In children with rhabdomyosarcoma of the bladder or prostate, presenting signs and symptoms include urinary or fecal retention, dysuria, urinary tract infection, and hematuria. Paratesticular rhabdomyosarcoma produces painless scrotal swelling, which may be ignored until the tumor has reached a large size. Vaginal tumors may manifest as a prolapsing mass in the introitus. Radiologic studies of children with genitourinary rhabdomyosarcoma reflect the nonspecific gross features of the tumor, which may be ill defined with infiltrative margins or well circumscribed by a pseudocapsule of compressed tissue. The botryoid variant of embryonal rhabdomyosarcoma results when submucosal tumor produces a polypoid mass resembling a cluster of grapes within a hollow structure. Botryoid morphology is characteristic, but not specific, for rhabdomyosarcoma within the vagina or urinary bladder, since yolk sac tumor and "tumoral" cystitis may have a similar appearance. Invasion of adjacent structures by the primary tumor may make the precise anatomic origin of genitourinary rhabdomyosarcoma difficult to determine on cross-sectional images. Recent refinements in multidisciplinary therapeutic regimens combining chemotherapy, radiation therapy, and surgery have dramatically improved outcome for children with genitourinary rhabdomyosarcoma. Diagnostic imaging plays an important role in monitoring response to therapy.

Adolescent↗
PubMedDate not supplied

Association of ataxia telangiectasia mutated (ATM) gene mutation/deletion with rhabdomyosarcoma.

Rhabdomyosarcoma is a common malignancy in children. There are two major types of rhabdomyosarcomas, the embryonal and the alveolar, differing in cytogenetic and morphologic features. The alveolar type of rhabdomyosarcoma is frequently associated with chromosome translocation t(2; 13) and poor clinical prognosis. Pathogenesis of rhabdomyosarcoma remains obscure, and especially it occurs in the location where skeletal muscle is absent. We report here that there is a high frequency of association of rhabdomyosarcoma with ataxia telangiectasia mutated (ATM) gene mutation/deletion. Totally 17 cases of rhabdomyosarcoma specimens were studied by immunohistochemical or immunofluorescent staining with ATM antibody and revealed that 7 of the 17 cases were negative for ATM expression (41%). Further analyses of rhabdomyosarcoma cell lines with RT-PCR revealed that in Rh30 cells, an alveolar rhabdomyosarcoma cell line, there are three separate deletions/mutations of the ATM mRNA. Western blotting analysis of the Rh30 cellular extract with anti-ATM antibody showed that there is an aberrant form of ATM protein within the Rh30 cells that are smaller than normal control. These results suggest, for the first time, a link of ATM gene deletion/mutation with rhabdomyosarcoma, and since ATM kinase is a crucial regulatory protein in DMA damage repair signaling pathway, and ATM deletion/mutation may contribute to pathogenesis of rhabdomyosarcoma.

Adolescent↗
PubMed1986

Metastatic behavior of rhabdomyosarcoma.

Embryonal and alveolar rhabdomyosarcoma probably have the same histogenesis, yet alveolar rhabdomyosarcoma has a considerably worse prognosis and is generally less responsive to treatment. The metastatic behavior of rhabdomyosarcoma in 22 autopsied subjects was analyzed with respect to the histologic subtypes of the tumors to determine whether the more aggressive behavior of alveolar rhabdomyosarcoma was related to greater tumor burden and/or more widely disseminated metastases. Subjects with embryonal rhabdomyosarcoma tended to survive longer and had greater numbers of metastatic sites at autopsy compared to subjects with alveolar rhabdomyosarcoma, but these differences were not statistically significant. In addition, there were no significant differences in the overall distribution of metastases between embryonal and alveolar rhabdomyosarcoma. The most frequent sites of metastases from both types of tumor were soft tissues (73%), serosal surfaces (64%), lymph nodes (64%), lungs (55%), and bone marrow (50%). The findings suggest that the metastatic behavior of rhabdomyosarcoma does not vary as a function of length of survival, mode of therapy, or histologic subtype. We propose that factors such as stage of disease at presentation and location of the primary tumor, rather than histologic subtype, are probably the most important variables governing the therapeutic responsiveness of rhabdomyosarcoma.

Adolescent↗
PubMed1985

Soft-tissue sarcomas in childhood. A study of 262 cases including 169 cases of rhabdomyosarcoma.

Although numerous investigations of soft-tissue sarcomas of childhood have been done, there are still many unsolved problems in the diagnosis, histogenesis, and biological behaviour of such tumours. In the present study, the soft-tissue sarcomas collected at the Paediatric Tumour Registry in Kiel were investigated. There was a total of 262 cases, including 169 (64.5%) in which a definite diagnosis of rhabdomyosarcoma had been made. An analysis of the age distribution showed that rhabdomyosarcoma is more than three times as frequent as non-rhabdomyosarcomatous soft-tissue tumours in the first quinquennium. Rhabdomyosarcoma exhibited male predominance (male-to-female ratio 1.45:1), whereas non-rhabdomyosarcomatous tumours showed an approximately equal sex distribution. Among the cases of rhabdomyosarcoma, the embryonal type clearly predominated (approx. 70%); the alveolar type was less common (approx. 20%). Correlation of histology with prognosis revealed that even tumours showing tiny foci with an alveolar pattern in otherwise solid, undifferentiated rhabdomyosarcoma, must be classified as alveolar rhabdomyosarcoma. Cases of alveolar rhabdomyosarcoma showed a higher incidence of local recurrence, lymph node metastasis, distant metastatic spread, and death, than did cases of embryonal rhabdomyosarcoma. It is concluded that "cytological differentiation" does not improve the prognosis of rhabdomyosarcoma.

Adolescent↗
PubMed1989

Rhabdomyosarcoma in middle-aged and elderly individuals.

In a review of a national series of malignant tumors in middle-aged and elderly individuals (over 40 years of age), in all 107 cases primarily diagnosed and reported to the Swedish Cancer Registry as rhabdomyosarcomas during the period 1972-1981, 4 cases were accepted as botryoid, embryonal or alveolar rhabdomyosarcoma, using light-microscopic criteria for the diagnosis. An electron-microscopic and immunohistochemical analysis was performed on the 4 cases along with 7 cases of botryoid, embryonal and alveolar rhabdomyosarcoma in patients of over 40 years of age obtained from our own files. Rhabdomyoblastic differentiation was established ultrastructurally by the presence of myofilaments and Z-like densities in 10 of these 11 cases. There were tumor cells in the formaldehyde-fixed, paraffin-embedded material which were positively stained for desmin in all cases, for myoglobin in 7/11 cases, for vimentin in 5/11 cases and for actin in all cases, using monoclonal antibodies. The demonstration of desmin by the monoclonal antibody which was used on the formaldehyde-fixed, paraffin-embedded material is of particular value in the diagnosis of rhabdomyosarcoma. Another tumor, located in the minor pelvis, lacked the light-microscopic features of botryoid, embryonal or alveolar rhabdomyosarcoma, but presented ultrastructural and immunohistochemical evidence of a rhabdomyoblastic differentiation. This tumor was epithelioid in appearance and shared features with alveolar soft part sarcoma. The label epithelioid rhabdomyosarcoma is proposed for this tumor. Nine pleomorphic sarcomas were selected from the national series as possible pleomorphic rhabdomyosarcomas because of the presence of ribbon-shaped tumor cells with an eosiniphilic cytoplasm. There was no electron-microscopic or immunohistochemical evidence of a myogenic differentiation in any of these 9 tumors. The present investigation indicates that a pleomorphic type of rhabdomyosarcoma, indistinguishable from embryonal, botryoid and alveolar rhabdomyosarcoma, is extremely rare or non-existent.

Adult↗
PubMed2004

Inhibition of connective tissue growth factor (CTGF/CCN2) expression decreases the survival and myogenic differentiation of human rhabdomyosarcoma cells.

Connective tissue growth factor (CTGF/CCN2), a cysteine-rich protein of the CCN (Cyr61, CTGF, Nov) family of genes, emerged from a microarray screen of genes expressed by human rhabdomyosarcoma cells. Rhabdomyosarcoma is a soft tissue sarcoma of childhood deriving from skeletal muscle cells. In this study, we investigated the role of CTGF in rhabdomyosarcoma. Human rhabdomyosarcoma cells of the embryonal (RD/12, RD/18, CCA) and the alveolar histotype (RMZ-RC2, SJ-RH4, SJ-RH30), rhabdomyosarcoma tumor specimens, and normal skeletal muscle cells expressed CTGF. To determine the function of CTGF, we treated rhabdomyosarcoma cells with a CTGF antisense oligonucleotide or with a CTGF small interfering RNA (siRNA). Both treatments inhibited rhabdomyosarcoma cell growth, suggesting the existence of a new autocrine loop based on CTGF. CTGF antisense oligonucleotide-mediated growth inhibition was specifically due to a significant increase in apoptosis, whereas cell proliferation was unchanged. CTGF antisense oligonucleotide induced a strong decrease in the level of myogenic differentiation of rhabdomyosarcoma cells, whereas the addition of recombinant CTGF significantly increased the proportion of myosin-positive cells. CTGF emerges as a survival and differentiation factor and could be a new therapeutic target in human rhabdomyosarcoma.

Cell Differentiation↗
PubMed1982

Diagnosis of human childhood rhabdomyosarcoma of antibodies to desmin, the structural protein of muscle specific intermediate filaments.

Four embryonal rhabdomyosarcomas, one tumor diagnosed as an undifferentiated sarcoma, probably a rhabdomyosarcoma, and six different non-muscular sarcomas were investigated with antibodies specific for different intermediate filament types. The tumor cells in the rhabdomyosarcomas and the undifferentiated tumor were stained clearly by antibodies to desmin, the intermediate filament type characteristic of muscle. The staining of tumor cell by antibodies to vimentin, the intermediate filament type characteristic of certain cell types of mesenchymal origin including myoblasts, was different in these 5 cases. In one case of embryonal rhabdomyosarcoma nearly all tumor cells were stained, but in the remaining cases few or no tumor cells were positive with the vimentin antibody. In these rhabdomyosarcomas not only the large rhabdomyoblasts, but also the small undifferentiated cells were labeled by antibodies to desmin. In the latter cell type the desmin filaments were arranged typically in coils. In contrast, tumor cells in the non-muscular mesenchymal sarcomas were stained only by antibodies to vimentin but not by antibodies to desmin or prekeratin. The retention of the desmin marker characteristic of normal muscle in cases of rhabdomyosarcoma not only allowed the undifferentiated desmin-positive sarcoma to be classified as rhabdomyosarcoma but also suggests that the use of antibodies to desmin could be very helpful in the future for the diagnosis of undifferentiated rhabdomyosarcomas.

Adult↗
PubMed1983

Genitourinary rhabdomyosarcoma.

Rhabdomyosarcoma is the most common soft tissue malignant neoplasm involving the pelvis of children. Debate still exists over whether the best treatment is pelvic exenteration, radiation and chemotherapy or chemotherapy as the cornerstone to treatment, with diminished needs for extensive surgery and prolonged radiotherapy. Contrariwise, there is little debate over the combined treatment modality for paratesticular rhabdomyosarcoma. We have evaluated and treated 19 children with rhabdomyosarcoma, including 17 with pelvic rhabdomyosarcoma and 2 with paratesticular rhabdomyosarcoma. This retrospective study was done to evaluate treatment regimens for patients with genitourinary rhabdomyosarcoma. For patients with pelvic rhabdomyosarcoma the study was divided into 2 series. In an early series 6 of 7 children had a pelvic exenteration with or without chemotherapy. Of these 7 children 3 are well 15 to 27 years following diagnosis. In a later series of 10 children, when chemotherapy was used more commonly, none underwent pelvic exenteration. Of these 10 patients 7 had chemotherapy or chemotherapy and biopsy only. Only 1 child, who presented with stage IV disease, died in this series. Another child with stage III disease had progressive disease despite chemotherapy and subsequent cystoprostatectomy. Thus, of 9 remaining patients 8 are well from 1 to 8 years. It appears that pelvic rhabdomyosarcoma can be treated effectively with chemotherapy, and limited surgery and radiation. Fortunately, pelvic exenteration can now be limited to a select few.

Antineoplastic Agents↗
PubMed2002

Rhabdomyosarcoma of the head and neck in children.

OBJECTIVE: The purpose of this study was to determine the rhabdomyosarcoma types involving the head and neck (H&N) region in children and their immunophenotype. DESIGN: Anatomic pathology archives at Texas Children's Hospital were searched for all rhabdomyosarcoma cases over a 20-year period. One-hundred and thirty-seven cases were identified, with 50 being H&N cases. The cases were typed according to the Intergroup Rhabdomyosarcoma Study (IRS) criteria. Immunocytochemistry for myogenic and non-myogenic markers was performed on all H&N cases. Electron micrographs from cases (n=32) where ultrastructural examination had been performed at the time of original diagnosis were reviewed. RESULTS: Children with H&N rhabdomyosarcomas had a mean age of 5.3 years (median 4 years). There was a male predilection (1.7M:1.0F). Primary tumor sites were: face NOS (18%), orbit/periorbital (16%), nasal cavity/nose (14%), lymph nodes (12%), paranasal sinuses (10%), parameningeal (10%), parotid gland (6%), neck (6%), infratemporal fossa/zygoma (2%), buccal mucosa (2%), palate (2%), and larynx (2%). Metastatic disease at diagnosis (33% of all cases) occurred in the bone marrow (11%), cerebrospinal fluid (6%), peritoneal fluid (6%), lung (4%), parietal pleura (2%), pleural fluid (2%) and pericardial fluid (2%). Rhabdomyosarcoma types (IRS criteria) were: embryonal (60%), alveolar (classic and solid subtypes, 28%), botryoid (4%), undifferentiated (4%), spindle cell (2%) and anaplastic (2%). Immunocytochemical findings were: polyclonal desmin (96%); myogenin (96%); muscle-specific actin (74%), smooth muscle actin (12%). Nonmyogenic markers included: vimentin (100%), CD99 (16%), p53 (16%), pancytokeratin (10%), NSE (8%), LCA (6%), CD20 (6%), EMA (2%), and NB-84 (0%, neuroblastoma). Undifferentiated sarcoma expressed only vimentin. By ultrastructural examination, 44% had readily identified z-bands and myofilaments, 37% had infrequent to rare myofilaments and z-bands, and 19% had myotubular intermediate filaments. CONCLUSIONS: Distribution of H&N rhabdomyosarcoma IRS types is similar to that for all primary sites, with the exception that embryonal types are modestly increased while alveolar type is mildly decreased. There are many non-myogenic immunocytochemical markers that cross-react with rhabdomyosarcoma. Differentiation between favorable and unfavorable rhabdomyosarcoma types is important for appropriate therapy, and predicting prognosis and survival.

Adolescent↗
PubMed2001

Pleomorphic rhabdomyosarcoma in children: four cases in the pediatric age group.

Pleomorphic rhabdomyosarcoma is considered rare and controversial, especially in children. Although pleomorphic rhabdomyosarcoma has been observed in children, its sparcity has taken it out of current childhood rhabdomyosarcoma classifications. We report four pediatric cases of pleomorphic rhabdomyosarcoma, review morphologic, immunohistochemical, and ultrastructural features, and discuss the rare need to include this category in children. The Soft Tissue Registry of the Armed Forces Institute of Pathology was searched for cases coded as "pleomorphic rhabdomyosarcoma" from 1970 to the present. Only cases in patients less than 21 years old were included. Clinical data, morphology, and immunohistochemical stains were reviewed and follow-up was obtained. Electron microscopy was performed on two cases. Molecular analysis by polymerase chain reaction was performed on one case with available material. Of four patients included, there were three boys and one girl. Patient ages ranged from 9 months to 10 years (median, 4.5 years). Tumors were located on the chest wall (n = 2) and one each on the upper and lower extremities. Tumor size ranged from 4.0 to 10.0 cm (median, 7 cm). Grossly, the tumors were lobulated and circumscribed. Microscopically, architectural patterns varied from solid to fascicular or storiform. All tumors had large, often multinucleated, polygonal, spindled or strap-like rhabdomyoblasts with abundant eosinophilic cytoplasm. Nuclear characteristics ranged from hyperchromatic to vesicular. Most tumor cells had large prominent nucleoli. Background rhabdomyoblasts varied from spindled to polygonal. No tumors displayed areas typical of embryonal or alveolar rhabdomyosarcoma. All tumors exhibited atypical mitotic figures. Immunohistochemistry revealed that the tumors were positive for the following markers: desmin (3/4), myoglobin (4/4), myoD1 (3/3), myf4 (3/3), and MSA (4/4). The two cases studied by electron microscopy both showed evidence for skeletal muscle differentiation. One case showed no evidence for a t(2;13) or t(1;13) translocation. Two patients were alive with no evidence of disease at 12 and 25 years. One patient was dead of disease at 9 years. Pleomorphic rhabdomyosarcoma is rare but exists in children. The diagnosis should be considered in pleomorphic sarcomas exhibiting skeletal muscle differentiation, which are otherwise devoid of typical areas or chromosomal changes of embryonal or alveolar rhabdomyosarcoma.

Antibodies, Monoclonal↗
PubMed2000

Progress in the diagnosis and treatment of rhabdomyosarcoma and related soft tissue sarcomas.

Advances in the diagnosis and treatment of rhabdomyosarcoma and related soft tissue sarcomas continue in the Intergroup Rhabdomyosarcoma Study Group (IRSG) and European cooperative groups. The use of molecular biology techniques in soft tissue sarcomas are redefining the classic pathology of these small blue cell tumors. Improvements in imaging, radiotherapy, and surgery, in part, deserve credit for the better survival seen in all cooperative trials. These advances confound the interpretation of consecutively run chemotherapy trials using historical comparisons. The IRSG has reported improvement in the prognosis of both nonmetastatic and metastatic embryonal rhabdomyosarcoma as attributable to three, three-drug regimens that use cyclophosphamide at 2.2 g/m2 in either maintenance or induction and maintenance therapy. Patients of any age with metastatic, nonembryonal, and those over 10 years of age with metastatic embryonal rhabdomyosarcoma continue to have a poor prognosis, which even megatherapy has failed to change. The doublet of ifosfamide and etoposide in combination with vincristine, actinomycin D, and cyclophosphamide at 2.2 g/m2 achieved a remarkable 3-year survival of 58% in patients with metastatic rhabdomyosarcoma and undifferentiated soft tissue sarcoma. The topoisomerase I inhibitor, topotecan, has recently been found by the IRSG to have a 57% overall response rate in patients with metastatic alveolar rhabdomyosarcoma. Topotecan has completed testing with cyclophosphamide in a phase II window study in newly diagnosed patients with metastatic disease and has been incorporated into a randomized trial in intermediate risk patients in IRSG-V. Molecular studies in IRSG-V will be applied in the detection of occult bone marrow metastases and the evaluation of resection margins at initial and second-look surgery. Long-term follow-up will be required in patients with gross residual sarcoma randomized to conventional and hyperfractionated radiotherapy in IRSG-IV to assess late effects. Although older patients with unfavorable histology and metastatic disease continue to have a poor prognosis, the overall 5-year survival of children and adolescents with nonmetastatic and metastatic rhabdomyosarcoma is approaching 80%. As molecular discoveries advance the diagnosis and detection of rhabdomyosarcoma, it is hoped that the futuristic molecular based treatment strategies in development and early testing will further improve survival in high-risk patients with metastatic soft tissue sarcoma.

Adolescent↗
PubMed2003

Potent oncolytic activity of multimutated herpes simplex virus G207 in combination with vincristine against human rhabdomyosarcoma.

Replication restricted oncolytic viruses such as multimutated herpes simplex virus type 1 (HSV-1) G207 represent a novel and attractive approach for cancer therapy, including pediatric solid tumors. Rhabdomyosarcoma is the most common soft-tissue sarcoma of childhood and is often diagnosed already as an advanced disseminated disease. Despite aggressive therapeutic approaches, the prognosis for patients with metastatic rhabdomyosarcoma remains grim. Therefore, there is a need for novel effective drugs with superior safety and efficacy profile. In this study, we showed marked in vitro activity of HSV-1 G207 against embryonal and alveolar rhabdomyosarcoma cells. All human embryonal (KF-RMS-1, RD, and CCA) and alveolar RMS (KFR, Rh28, Rh30, and Rh41) cell lines were highly sensitive to cytotoxic and replicative effects of G207 even at a multiplicity of infection of 0.01, except embryonal Rh1 rhabdomyosarcoma cells, which were efficiently killed only upon multiplicity of infection of 1.0. i.v. G207 treatment of xenotransplanted KFR and KF-RMS-1 tumors in mice led to significant tumor growth inhibition of both tumor entities, whereas intraneoplastic G207 treatment additionally resulted in complete tumor disappearance in 25% of animals. No difference has been found between alveolar and embryonal types of rhabdomyosarcoma. Combination treatment of both cell lines with G207 and vincristine led to strongly enhanced in vitro cytotoxicity without affecting infection efficiency and replication of G207 in KFR as well as in KF-RMS-1 cells. In vivo combination treatment using i.v. G207 and vincristine resulted in complete regression of alveolar rhabdomyosarcoma in five of eight animals and significant growth inhibition of embryonal rhabdomyosarcoma. Taking into consideration the proven safety of G207 in humans, we suggest that G207 alone and in combination with vincristine should be additionally evaluated as a potential agent against human rhabdomyosarcoma.

Animals↗
PubMed1994

The diagnosis and classification of childhood rhabdomyosarcoma.

Although the typical subtypes of embryonal, botryoid, alveolar, and pleomorphic rhabdomyosarcoma are easily recognized by simple light microscopic examination, poorly differentiated forms are difficult to diagnose and classify. The availability of markers connoting simple myogenous or skeletal muscle differentiation has contributed tremendously to the diagnosis of even poorly differentiated rhabdomyosarcoma. Definition of typical and minimal ultrastructural criteria has also been instrumental. Proper classification of rhabdomyosarcoma into subtypes with prognostic significance has been a difficult task. Although most pathologists have accepted the original classification scheme of embryonal, botryoid, alveolar, and pleomorphic rhabdomyosarcoma, they have used variable histologic criteria to define the various subtypes. Most of the major discrepancies occurred in the definition of embryonal versus alveolar rhabdomyosarcoma, especially in those cases that required establishment of minimal criteria. For example, poorly differentiated round-cell rhabdomyosarcoma has frequently been erroneously classified as embryonal, because of the absence of an alveolar pattern. This variety has been recognized as a form of alveolar (solid alveolar) rhabdomyosarcoma by the National Cancer Institute (NCI) scheme. Comparative analysis of several proposed classification schemes has led to the establishment of well-defined criteria for the major subtypes of rhabdomyosarcoma and to the recognition of subtypes with prognostic significance.

Child↗
PubMed1996

The diagnostic potential of the chromosome translocation t(2;13) in rhabdomyosarcoma: a Pcr study of fresh-frozen and paraffin-embedded tumour samples.

The chromosomal translocation t(2;13)(q35;q14) has been reported in alveolar paediatric rhabdomyosarcoma. The rearrangement leads to the juxtaposition of the PAX-3 and FORKHEAD genes and the production of a fusion protein with putative transcriptional regulatory activity. The diagnostic potential of this translocation has been examined using a reverse transcription polymerase chain reaction (RT-PCR) assay to detect translocations in both fresh-frozen and archival formalin-fixed, paraffin-embedded rhabdomyosarcoma. A total of 25 tumours and one cell line were examined. PAX-3-FORKHEAD chimeric mRNAs were amplified by PCR in 8 of 15 cases of alveolar rhabdomyosarcoma. Translocations were detectable in both fresh-frozen tissues (4 of 7) and paraffin-embedded tumours (3 of 7) and in the alveolar rhabdomyosarcoma cell line. Our study confirms that the t(2;13) translocation is not present in embryonal rhabdomyosarcomas, but can be detected in nearly half of alveolar rhabdomyosarcomas, whether fresh-frozen or paraffin-embedded. The PCR-based t(2;13) translocation assay can aid in the diagnosis of rhabdomyosarcoma, but cannot replace a careful histopathological evaluation. It may contribute in further characterizing an otherwise undifferentiated small cell tumour, where it may be indicative of clinical behaviour.

Blotting, Southern↗
PubMed2002

Genomic gains and losses are similar in genetic and histologic subsets of rhabdomyosarcoma, whereas amplification predominates in embryonal with anaplasia and alveolar subtypes.

In this investigation, we selected PAX3/FKHR and PAX7/FKHR fusion transcript-positive and -negative alveolar rhabdomyosarcomas (ARMSs) and embryonal rhabdomyosarcomas (ERMSs) with and without anaplastic features, to ascertain genomic imbalance differences and/or similarities within these histopathologic and genetic rhabdomyosarcoma (RMS) variants. Comparative genomic hybridization (CGH) and fluorescence in situ hybridization (FISH) studies were performed on 45 rhabdomyosarcoma specimens consisting of 23 ARMSs and 22 ERMSs (12 ERMS cases were included from an earlier study). The anaplastic variant of RMS has not previously been subjected to CGH analysis. Overall, the most prominent imbalances were gain of chromosomes or chromosomal regions 2/2q (40%), 7/7q (31%), 8/8p (53%), 11/11q (31%), 12q13-15 (49%), 13q14 (22%), and 20/20p (31%), and loss of 1p36 (27%), 3p14-21 (22%), 9q21-22 (33%), 10q22-qter (18%), 16q (27%), 17p (22%), and 22 (22%). These gains and losses were distributed equally between ARMS and ERMS histologic subtypes (excluding 7/7q and 11/11q gain that were observed chiefly in ERMS), demonstrating that these entities are similar with respect to recurrent genomic imbalances. Moreover, genomic imbalances were also evenly distributed among the ARMS fusion transcript subtypes, providing evidence for a genetic kinship despite the absence of a fusion transcript in some cases. Genomic amplification was detected in 26% and 23% of the ARMS and ERMS cases, respectively (with nearly all of the latter subset exhibiting anaplastic features). One amplicon, involving 15q25-26, corresponds to the locus of the insulin-like growth factor type I receptor (IGF1R) gene. Amplification of IGF1R was confirmed molecularly in the cases exhibiting a 15q25-26 amplicon. In summary, these results indicate that genomic gains and losses involve alike chromosomes with similar frequencies within the histopathologic and genetic subtypes of rhabdomyosarcoma, that genomic amplification is frequent not only in the alveolar histologic subtype of rhabdomyosarcoma but also in ERMS with anaplasia, and that amplification of IGF1R possibly plays a role in the development or progression of a subset of rhabdomyosarcomas.

Adolescent↗
PubMed1999

Cadherin-11 is highly expressed in rhabdomyosarcomas and during differentiation of myoblasts in vitro.

Rhabdomyosarcomas bear a morphological and genetic resemblance to developing skeletal muscle. Apart from myogenic marker genes (bHLH factors, myosin, actin), cell adhesion molecules such as N-cadherin and N-CAM have been reported to be expressed both in rhabdomyosarcomas and during myogenesis. The present study demonstrates the expression of another cadherin, cadherin-11, in rhabdomyosarcomas and during differentiation of myoblasts in vitro: cadherin-11, a predominantly mesenchymal cell adhesion molecule, is highly expressed in embryonal rhabdomyosarcomas and alveolar rhabdomyosarcomas, which do not bear the Pax-3-FKHR fusion previously described. Cadherin-11 is down-regulated in normal skeletal muscle and after myotube formation in vitro. The results of this study suggest that cadherin-11 might be involved in myogenesis and that rhabdomyosarcomas may re-express or fail to down-regulate cadherin-11. Since alveolar rhabdomyosarcomas bearing the t(2;13) translocation do not express cadherin-11, it is postulated that Pax-3 and cadherin-11 might be linked and involved in the same myogenic pathway.

Animals↗
PubMed2004

Rhabdomyosarcomas are potential target of MAGE-specific immunotherapies.

The search for alternative strategies of therapy remains a major issue for most neoplastic diseases. The expression of several tumor antigens makes human rhabdomyosarcomas, which are the most frequent form of soft tissue tumor in children, a good candidate for tumor-specific immunotherapy. To assess the feasibility of this approach, we evaluated the ability of rhabdomyosarcoma cell lines to process and present the MAGE-A tumor antigens to effectors of the immune system. To this end, we investigated recognition of MAGE-A-positive rhabdomyosarcoma cells by HLA-B*3701-restricted T cells specific for a MAGE-A-derived peptide. Low level of HLA expression impaired recognition of the tumor cells. Therefore, to obtain HLA expression avoiding the use of IFN-gamma and TNF-alpha, which could affect the proteasome activity, a rhabdomyosarcoma line was transduced by a retroviral vector encoding the HLA-B*3701 allele. Recognition of the infected cells was then observed also in the absence of IFN-gamma and TNF-alpha treatment, thus demonstrating that rhabdomyosarcoma cells were indeed able to naturally process and present the MAGE-A antigens. These results demonstrate that rhabdomyosarcoma cells expressing MAGE-A can be targets of tumor-specific effectors, suggesting the feasibility of clinical protocols of specific immunotherapy also for the treatment of rhabdomyosarcoma.

Antigens, Neoplasm↗
PubMed1982

The ultrastructure of poorly differentiated rhabdomyosarcomas: a case report and literature review.

The ultrastructure of a case of rhabdomyosarcoma is reported, and the world literature on the ultrastructure of rhabdomyosarcomas is reviewed. The reported case was first observed as an undifferentiated malignancy originating in the maxillary antrum of a 46-year-old white woman and later showed differentiated cells in metastatic sites. A specific feature of the sarcomere within a representative malignant cell is necessary and sufficient for diagnosis of rhabdomyosarcoma by ultrastructure. Examples of specific features include thick and thin filaments in a hexagonal array, an unambiguous Z line, or A bands with H and M bands. The presence of thick and thin filaments without additional features of the sarcomere indicate a myogenous origin, either leiomyosarcoma or rhabdomyosarcoma. Other ultrastructural features observed in rhabdomyosarcomas, for which the diagnosis is confirmed by the presence of diagnostic ultrastructural features or by the presence of cross-striations observed by light microscopy, include large irregularly shaped nuclei with projections and invaginations, free ribosomes closely associated with filaments, rough endoplasmic reticulum that is often dilated, glycogen, and external lamina, prominent nucleoli, and pleomorphic mitochondria. When this spectrum of features is present, the possibility of rhabdomyosarcoma cannot be excluded, and a diligent search for the diagnostic components of the sarcomere should be made. Small intercellular junctions, pinocytotic vesicles, and paranuclear cilia occurred in the poorly differentiated metastasis of this case; the presence of these nonspecific features permits neither diagnosis nor exclusion of rhabdomyosarcoma.

Breast Neoplasms↗