Muscle Tumors Research Articles

Apoptosis, bcl-2 Expression, and p53 Expression in Gastrointestinal Stromal/Smooth Muscle Tumors

The authors investigated the relations between outcome and apoptosis, immunohistochemical demonstration of bcl-2 protein, and immunohistochemical staining for p53 protein in patients with gastrointestinal stromal/smooth muscle tumors (GIST). Patients whose tumors demonstrated cellular apoptosis using the terminal deoxynucleotidyl transferase-mediated 2'-deoxyuridine 5'-triphosphate-biotin nick end labeling (TUNEL) assay had an improved survival over those whose tumors did not improve. In contrast, patients whose tumors demonstrated staining for bcl-2 protein had a decreased survival compared with those whose tumors did not demonstrate bcl-2. There was no relation between p53 immunoreactivity and survival. These results suggest that inhibition of apoptosis may be associated with malignant behavior in patients with gastrointestinal stromal/smooth muscle tumors.

Analysis of KIT Mutation and Protein Expression in Fine Needle Aspirates of Gastrointestinal Stromal/Smooth Muscle Tumors

To determine if sequencing the KIT gene could facilitate more definitive FNA diagnosis. Sixteen cases of gastrointestinal stromal/smooth muscle tumor (GIST) in which fine needle aspiration (FNA) was performed (mean age, 67; M/F = 12/4) were studied. DNA was extracted from cytologic preparations from all patients (15 cell blocks, 1 alcohol-fixed smear) and seven subsequent resection specimens. DNA was amplified by polymerase chain reaction, using primers designed to amplify a segment of the KIT gene exon 11 and sequenced on an ABI Prism 377 DNA sequence analyzer (Applied Biosystems, Indianapolis, Indiana, U.S.A.). Immunocytochemical staining for CD 117 (the KIT gene product) was performed on sections from 12 cell blocks and 7 surgical resections. In-frame deletion of exon 11 was detected in eight cases (7 monoalleic, 1 bialleic); a point mutation was found in one case. Mutation was found only in histologically malignant (6 of 10 cases) and borderline GISTs (3 of 4 cases). No mutation was identified in benign tumors. In three cases, scant cellularity or blood precluded sequencing. CD 117 was expressed in 12 of 15 cases. Immunocytochemical staining for CD 117 is useful in confirming a cytologic diagnosis of GIST but does not facilitate diagnosis of malignancy. FNA biopsy specimens are suitable for KIT gene sequencing; detection of a KIT mutation favors a malignant diagnosis, though absence of mutation does not preclude malignancy.

Pax3 functions in cell survival and in pax7 regulation.

In developing vertebrate embryos, Pax3 is expressed in the neural tube and in the paraxial mesoderm that gives rise to skeletal muscles. Pax3 mutants develop muscular and neural tube defects; furthermore, Pax3 is essential for the proper activation of the myogenic determination factor gene, MyoD, during early muscle development and PAX3 chromosomal translocations result in muscle tumors, providing evidence that Pax3 has diverse functions in myogenesis. To investigate the specific functions of Pax3 in development, we have examined cell survival and gene expression in presomitic mesoderm, somites and neural tube of developing wild-type and Pax3 mutant (Splotch) mouse embryos. Disruption of Pax3 expression by antisense oligonucleotides significantly impairs MyoD activation by signals from neural tube/notochord and surface ectoderm in cultured presomitic mesoderm (PSM), and is accompanied by a marked increase in programmed cell death. In Pax3 mutant (Splotch) embryos, MyoD is activated normally in the hypaxial somite, but MyoD-expressing cells are disorganized and apoptosis is prevalent in newly formed somites, but not in the neural tube or mature somites. In neural tube and somite regions where cell survival is maintained, the closely related Pax7 gene is upregulated, and its expression becomes expanded into the dorsal neural tube and somites, where Pax3 would normally be expressed. These results establish that Pax3 has complementary functions in MyoD activation and inhibition of apoptosis in the somitic mesoderm and in repression of Pax7 during neural tube and somite development.

Skeletal Pathologies in a Population of Alouatta palliata: Behavioral, Ecological, and Evolutionary Implications

We examined the pathological conditions in a sample of 200 skulls of Alouatta palliata recovered from Barro Colorado Island (BCI), Panama, to investigate the prevalence of disease and injury in a free-ranging monkey population. Forty-five individuals (22.5%) have some type of nondental pathological condition, indicating that illness and injury are relatively common in this population. Ten individuals, all older adult males, exhibit clear signs of antemortem trauma in the form of healed fractures. We attribute the trauma primarily to fighting, and its frequency (16.4% of adult males) contradicts previous assertions that BCI howlers are nonaggressive. Nine of the 37 scorable immature individuals (24%) have signs of a larval infestation, supporting the suggestion that ectoparasites play an important role in BCI howler mortality. Other pathological conditions in the sample include shifted muscle attachments, periostitis, arthritis, neoplasm, periapical abscesses, and facial deformity, as well as various dental abnormalities.

Determination of free extracellular levels of methotrexate by microdialysis in muscle and solid tumor of the rabbit.

To determine of the pharmacokinetic profile of methotrexate (MTX) in blood and extracellular fluid (ECF) of VX2 tumor and muscle in rabbits. Microdialysis probes were inserted into VX2 tumor and in muscle tissue. Following intravenous administration of MTX (30 mg/kg), serial collection of arterial blood samples and dialysates of muscle and tumor ECF for 4 h was carried out. Quantitation of MTX and determination of free plasma concentrations was performed by fluorescence polarization immunoassay and ultrafiltration, respectively. Correlations were established between the unbound plasma and ECF MTX concentrations. Total and free plasma concentrations exhibited a parallel three exponential decay in both healthy and tumorigenic animals. Total clearance (8.9 vs 6.5 ml-1.min-1.kg-1) and volume of distribution (4.0 vs 2.9 l.kg-1), however, tended to decrease in the tumor-bearing group. The ECF/plasma AUC ratio equaled 14.2 +/- 8.8% in muscle and 23.9 +/- 15.9% in tumor. The concentration-time profile of muscle ECF MTX was parallel and highly correlated (r = 0.97) to that determined in plasma. In contrast, free MTX plasma levels were not correlated with tumor ECF concentrations (r = 0.564). In addition to the well-known pharmacological variability in the concentration-effect relationship, the important inter-individual variability in tumor exposure to MTX may partly explain that studies in patients with solid tumors have often failed to demonstrate firm correlations between MTX blood pharmacokinetics and the chemotherapeutic response.

Submandibular Rhabdomyoma

A case of recurrent adult rhabdomyoma of the submandibular gland is presented. This is a rare tumor of the skeletal muscle. Approximately 80 cases have been reported. The salient pathologic features are reviewed and a discussion and review of the literature is presented.

Orthopaedic problems in old dogs.

With advancing years a dog may suffer from a variety of conditions of its musculoskeletal system which adversely affect its ability to exercise and may cause it to be retired from activities in work and sport for which it has been trained. Arthritis is common, and in many cases arises from developmental errors suffered in puppyhood, such as hip dysplasia, osteochondrosis and growth plate disorders. Trauma to joints (ligament ruptures, dislocations and fractures) may also be the precursor of degenerative joint changes later in life. It is important, therefore, for all such conditions to be corrected as effectively as possible if joint disease is to be minimised as the dog grows older. Preventive action is also required for some conditions for which correction may not be entirely feasible, so the identification of modes of inheritance is important if those are to be controlled by breeding. Certain spinal disorders also tend to increase in prevalence with age, particularly spondylosis deformans, neoplasms and chronic degenerative radiculomyelopathy. As it happens, spondylosis in mild to moderate degree affects pet dogs very little, but a reduction in spinal flexibility can cause problems for dogs required to be agile in work or sport. In common with other body tissues, neoplasm of the locomotor system increases in occurrence in older dogs, and although the overall incidence of tumours of bones, joints, nervous tissue and muscle is relatively low, these are the most serious of all the limb and spinal conditions encountered because of their life threatening propensities. The treatment required covers a wide range from simple changes of management in order to reduce exercise, to the use of analgesics and anti-inflammatory drugs and to surgery to remove diseased tissue, stabilise joints or reduce pain with forms of arthroplasty or arthrodesis.

Resection of a tumor of the psoas muscle

A 16-year-old boy presented with paresthesias and weakness of the right thigh. A computerized axial tomography scan identified a mass within the right psoas muscle, and a needle biopsy showed a primitive neuroectodermal tumor, which did not respond to two courses of chemotherapy (Adriamycin, vincristine, and cytoxan). An anatomic resection of the psoas muscle and femoral nerve was performed and radiotherapy administered. The boy remains ambulatory and free of disease 2.5 years after resection.

Alveolar soft-part sarcoma. A clinico-pathologic study of half a century.

In the period from 1923 to 1986 our pathologists examined pathologic material from 102 patients with alveolar soft-part sarcoma (ASPS). Followup clinical data is available for 91. Median followup is 7 years (range 1 month to 27 years). Local recurrence was only found if residual disease was left at the time of the original excision. Survival in those patients who presented without metastases was 77% at 2 years, 60% at 5 years, 38% at 10 years and 15% at 20 years (median 6 years). No survival advantage could be demonstrated for patients who received chemo and/or radiotherapy, although numbers are small and staging not uniform. An evaluation by electron microscopy and immunohistochemistry cannot confirm recent claims that ASPS is a muscle tumor. ASPS is an unusual neoplasm; the primary therapeutic option is aggressive surgical excision. Survival even with the development of metastases can be long.

Oculomotor disturbances due to idiopathic inflammatory orbital pseudotumor

Oculomotor disturbance (OMD) versus localization was especially studied retrospectively in 21 cases of idiopathic orbital pseudotumor (IOPT). The 13 cases with OMD and diplopia comprised eight of acute and subacute myositis, two of diffuse IOPT, two of orbital apex syndrome, one of dacryoadenitis. The eight cases without diplopia were: five diffuse IOPT, two dacryoadenitis, one acute myositis. Diplopia as a sign of IOPT should be emphasized. It is most often transient. Only two of our patients had residual diplopia, one had OMD and amaurosis.Cases of myositis are the most interesting manifestations of IOPT with regard to OMD. They need special attention in comparison with the motility disturbances seen in the other etiologies of extraocular muscle enlargement.Deficient contractibility of an enlarged rectus muscle is typical of an acute myositis or a rare tumor of an extraocular muscle (lymphoid or metastatic). Limitation of extensibility is typical of Graves' myopathy, of myositis of a superior oblique or...

Inhibitory effect of zinc on nickel subsulfide carcinogenesis in Fischer rats

The effects of zinc oxide (ZnO) and zinc acetate (ZaAcet) administered i.m. together with nickel subsulfide (Ni 3S 2), a potent muscle carcinogen, were observed over 66 weeks in male F344/NCr rats. The rats (20/group) received a single injection of 2.5 mg Ni 3S 2 (equal to 31 μmol Ni) alone or combined with different molar proportions of ZnO or ZnAcet (8–60 μmol Zn) into both thighs. One more group of rats given i.m. Ni 3S 2 received s.c. ZnO (60 μmol Zn) at the nape of the neck. Control rats were treated with i.m. ZnO (60 μmol Zn) or the injection vehicle, water. In rats given Ni 3S 2 alone the incidence of local tumors reached 100% in 40 weeks. In rats treated locally with Ni 3S 2 + ZnO or ZnAcet, the tumor incidence at week 40 was only 40–60%; it reached 85–100% in 66 weeks, with no significant differences among the treatments. Treatment with i.m. Ni 3S 2 + s.c. ZnO resulted in 100% muscle tumors at week 58. One local tumor was found in rats given ZnO alone and none in the water injected animals. Statistical analysis revealed highly significant differences in the tumor occurrence rates between rats treated with Ni 3S 2 alone and rats treated with Ni 3S 2 combined with ZnO or ZnAcet, whereas the final tumor incidences at week 66 were not different. The first tumors were found at weeks 24–31 regardless of the treatment. Hence, administration of zinc slows the carcinogenic process induced by nickel. This effect has a systemic character and is produced by both water-soluble and insoluble zinc compounds despite their different retention times in the muscle. The half-lives of ZnO and ZnAcet in the muscle were approx. 24 days and 2.5 days, respectively; that of Ni 3S 2 was 21 days. Zinc in either form exerted no appareent influence upon the retention of nickel at the injection site and did not significantly affect the early local cellular reactions to nickel.

Tumors of skeletal muscle

The most common tumors arising in muscle are soft tissue sarcomas, fibromatoses, and hemangiomas. Rhabdomyosarcoma is primarily a tumor of childhood and adolescence and arises most commonly in extramuscular sites. Most intramuscular rhabdomyosarcomas are alveolar. Increased diagnostic accuracy and the recognition of malignant fibrous histiocytoma have changed understanding of adult, intramuscular, pleomorphic rhabdomyosarcoma. Immunohistochemistry is playing an increasingly important role in the diagnosis of rhabdomyosarcoma, and the correlation between the histologic features and clinical behavior of rhabdomyosarcoma is under investigation. Because of their diversity and overlapping histologic features, muscle tumors are a challenge for the pathologist and require intensive study by current techniques.

A study on serum cancer-suppressive peptide.

A peptide which was isolated from serum of cancer-bearing mice has an activity to kill cancer cells in vitro, but little effect on bone marrow cells. This peptide was named Serum Cancer-Suppressive Peptide (SCSP). SCSP can be crystallized and still has the activity to kill the cancer cells. It consists of more than ten kinds of amino acids with molecular weight about 2000-3000 daltons estimated by SDS-polyacrylamide gel electrophoresis. An antiserum was prepared from rabbits immunized with SCSP and the corresponding IgG could be obtained from the antiserum. The titers of SCSP in some cells of the normal and cancer-bearing mice were estimated by passive hemagglutination method. The results showed that the SCSP titer in spleen is much higher than those in muscle, liver and ascites tumor cells. The results suggest that SCSP is probably produced by spleen cells.

Fetal rhabdomyoma of the tongue, with a discussion of the two histologic variants of this tumor

Fetal rhabdomyomas are rare benign tumors of skeletal muscle that must be distinguished histologically from various sarcomas, including rhabdomyosarcoma. They have recently been subdivided into two histologic variants myxoid and cellular fetal rhabdomyomas, respectively. This article describes the sixth fetal rhabdomyoma to be reported in the oral regions, illustrates the histologic features of the two types, and discusses the means of distinguishing these lesions from various other conditions with which they may be confused.

Differential diagnosis of spindle cell tumours by electron microscopy--personal experience and a review.

Electron microscopy has its value and its limitations in refining the histogenetic diagnosis of certain spindle cell tumours. The ultrastructural diagnostic features of neural tumours, muscle tumours, fibrous histiocytomas, fibrosarcomas, monophasic synovial sarcoma and spindle-cell squamous carcinoma are reviewed and illustrated.

Selective promoting activity of phorbol myristate acetate in experimental skin carcinogenesis.

Experiments were undertaken to study the effect of promotion treatment on epidermal tumour induction pattern in precancerous mouse skin. Swiss albino mice were given a single s.c. injection of 0-5 mg 20-methylcholanthrene in the right scapular region. Six weeks later, 1-83 nmol of phorbol myristate acetate (PMA) was applied biweekly on the reactive skin. Histopathology of the induced tumours showed early appearance of squamous cell carcinomas and rhabdomyosarcomas. Fibrosarcoma, the most common tumour type induced on MCA injection alone, was absent. Trichoepithelioma, a benign tumour, was induced in PMA-treated mice. This gives new evidence of the selective action of PMA, enhancing the induction of epithelial and muscle tumours, with concurrent inhibition of fibroblastic tumours.

Distribution of glutamine hexosephosphate aminotransferase in rat tissues; changes with state of differentiation

The activity of glutamine hexosephosphate aminotransferase ( L-glutamine: D-fructose 6-phosphate aminotransferase, EC 2.6.1.16) was determined with an improved assay method in some three dozen rat tissues: adult, developing and neoplastic. The highest activities (20–200 units/g) were seen in colon, mammary (during late lactation), submaxillary, sublingual and parotid glands, placenta and liver. The activity increased strikingly along the length of the intestine; glucose feeding inhibited it in ileum and colon. In liver and intestine the activity increased with age but in brain, muscle, heart and kidney the activity was considerably higher during fetal (7.1–12.8 units/g) than in adult life (0.8–3.5 units/g). Renal, mammary and muscle tumors (but not hepatomas) had much higher activities (4–20.5 units/g) than the cognate normal adult tissue. The distribution pattern among tissues indicates that glutamine hexosephosphate aminotransferase is of general importance to all growing, undifferentiated tissues and of special importance to the differentiated function of particular adult organs. The latter are organs which engage in glycoprotein secretion. The results support the assumption that glutamine hexosephosphate aminotransferase activity is essential for glycoprotein synthesis.

Tumors of muscles and synovial tissues.

Tumors of muscles and synovial tissues.

Electron microscopy in head and neck oncology.

A systematic investigation of tumours of the ear, nose and throat has been carried out, with particular attention to tumours arising from the squa-mous epithelium, salivary glands, glomus jugulare, neurogenic tumours, muscle tumours, granular cell myoblastoma, malignant lymphoma. Some of their main ultrastructural features were described and summarized. Surface cellular changes and changes in ker-atinization and alteration of the basal membrane were noted in squamous cell carcinoma of the larynx and oesophagus. Amorphous granules characterize the granular cells of granular cell myoblastoma. An incidental finding of this tumour in the trachea, associated with carcinoma of the larynx, is described. Striated myoblasts or filamentous myoblasts were found to be of assistance in the differential diagnosis of anaplastic sarcoma. Virus particles were found in a case of malignant lymphoma of the tonsil. The age of miracles in electron microscopy has come—and gone. We do not expect that electron microscopy, or a si...

Tumors of Bones and Muscles of the Lower Extremities

Tumors of Bones and Muscles of the Lower Extremities