James R. Ryan

A common cytogenetic abnormality and DNA content alterations in dedifferentiated chondrosarcoma

Dedifferentiated chondrosarcoma is an uncommon and aggressive variant of chondrosarcoma. The authors report the flow cytometric characteristics and cytogenetic findings in culture of two cases of dedifferentiated chondrosarcoma. The first case was DNA diploid by flow cytometry but had cytogenetic abnormalities consisting of breaks in the short arms of both chromosomes 1, resulting in deletion in one homolog and recombination in the other. In addition, cells from this tumor showed a balanced translocation between chromosomes 4 and 5, deletion of chromosome 9, and monosomy for chromosome 10. The second case was DNA aneuploid and more complex cytogenetically but had, in common with the first case, rearrangement and translocation at the same band on chromosome 1. These cytogenetic changes are compared with abnormalities previously reported for chondrosarcoma. Possible relationships between the nonrandom chromosomal abnormalities and subclassification among chondrosarcomas are discussed.

Fractures of the distal radial epiphysis in adolescent weight lifters

Wight lifting, as a form of body selfimprovement or for physical conditioning for contact sports, is a popular form of athletic activity in the adolescent male. In 1974, five patients were seen who, because of poor instruction or coaching, sustained fractures of the distal radial epiphysis. Five adolescent males, ranging in age from 14 to 17 years of age, were seen in the emergency department after having sustained fractures of the distal radial epiphysis .(Table I). Two patients had sustained bilat-

The natural history of metastatic synovial sarcoma. Experience of the Southwest oncology group

Of 35 treated cases of metastatic synovial sarcoma, there was a slight male predominance (60%). The median age was 33 years, with 88% of the patients being white. The lower extremity was the most common primary site, occurring in 66% of the cases. The most common metastatic involvement was pulmonary (33 patients), with only three patients having lymph node involvement. The low incidence of lymph node involvement and the poor prognosis when positive lymph nodes are found suggest that prophylactic lymph node resection is unwarranted. The median time from evidence of metastases to death was ten months. The complete and partial response rate to chemotherapy in this series was 50%; however, duration of the response was rather short with recurrence of metastatic disease a median of seven months after response was first noted. The size of the primary lesion was greater than 5 cm in all but one of the cases. The local recurrence rate was 70% in those cases undergoing local resection and 30% in those cases in which local resection plus irradiation to the primary lesion was undertaken. No case in which radical resection of the primary tumor was undertaken had a local recurrence.

Fractures of the Femur Secondary to Low-velocity Gunshot Wounds

Forty-three fractures of the shaft of the femur secondary to low-velocity gunshot wounds were evaluated to determine healing time, fracture alignment after healing, complications, and fracture characteristics. This study confirmed the previous reports of low infection rates and the need for minimal debridement for such fractures. The healing time was faster than that of closed fractures treated by similar means: the average healing time was 144.3 days. Alignment was easy to obtain and maintain, the average angular deformity being 5 degree or less with no rotational deformities. Three characteristic fracture types were noted: the double butterfly configuration of the shaft of the femur, the drill-hole fracture of the distal third of the femur as previously described experimentally, and a third type of fracture with an incomplete fracture secondary to the gunshot wound which acted as a stress riser with a resultant spiral fracture either proximal or distal to the impact site.

Deletion of chromosome 13 in osteosarcoma secondary to irradiation

The cytogenetic analysis of a radiation-induced osteosarcoma in a 31-year-old male is presented. Complex karyotypic changes with numerical and structural abnormalities, including a del(13)(q12.3q21.1), were observed. This deletion may indicate that loss of RB1 gene (locus in 13q14) may be involved in the development of radiation-induced osteosarcoma.

Cytogenetic aberrations and DNA ploidy in soft tissue sarcoma: A southwest oncology group study

We performed cytogenetic analysis and determined DNA content by flow cytometry (FCM) on freshly disaggregated tumor biopsies from 45 patients with soft tissue sarcomas (STS). Cytogenetically aberrant clones characterized 30 (67%) tumors, with the remaining 15 yielding normal karyotypes with or without nonclonal aberrations. No tumors with multiple unrelated clones were observed. Among the 30 tumors with clonally abnormal karyotypes, 21 (70%) had near-diploid stemlines, six were near-triploid and three were near-tetraploid. Ten of the clonally aberrant tumors contained nonrandom chromosomal translocations characteristic of histologic subtypes. Overrepresentation of chromosomes 7 and 8 were common numerical aberrations. Structural aberrations most often involved chromosomes 1, 7, 9, 12, and 14. Clustering of breaks in 9p resulting in partial loss of the short arm was frequent. Unstable aberrations including rings, dicentrics, large markers, small numbers of double minutes, and telomeric associations were seen in nine tumors. With FCM, 27 (60%) tumors had aneuploid DNA content and 18 (40%) were DNA diploid. Of those 18 DNA diploid tumors, 11 showed clonal karyotypic aberrations. In addition, apparent discrepancies between the results of the cytogenetics and FCM with respect to ploidy pattern were seen in 13 samples; 11 had DNA content in the peritriploid to peritetraploid range but the corresponding karyotype was normal or near-diploid. When the findings of the cytogenetics and DNA content analyses were combined, an abnormal cell population by one or both methods was detected in 38 (84%) tumors. The concurrent application of standard cytogenetics and DNA ploidy by FCM provide complementary information confirming a high incidence of genetic alterations in STS.

Flow cytometric analysis of P-glycoprotein expression and drug efflux in human soft tissue and bone sarcomas.

Twenty-two fresh surgical specimens of human sarcomas (soft tissue and bone) from 20 patients were analyzed by flow cytometry for the expression of drug resistance-related P-glycoprotein (P-gp) and cellular daunorubicin (DNR) accumulation with or without the presence of DNR efflux blockers. Single-cell suspensions prepared from the tumor specimens were analyzed by dual-color flow cytometry after reaction with MRK-16 (anti-P-gp) and anti-CD45 (pan-leukocyte) antibodies. MRK-16 reactivity of tumor cells was evaluated after exclusion of CD45-positive cells by electronic gates. Parallel samples were incubated with DNR alone or in combination with DNR efflux blockers, verapamil (VPL), or dipyridamole (DPD) for determination of cellular DNR accumulation and the effect of the efflux blockers. Extensive heterogeneity was observed in both P-gp expression and DNR accumulation of the tumor specimens examined. Eight of the 22 tumor specimens had significant numbers of P-gp-positive cells. In three of the eight P-gp-positive tumors, cellular DNR accumulation was significantly increased by co-incubation with the efflux blockers VPL or DPD. These results indicate that both quantitative and functional analysis of P-gp expression may be essential in determining the cellular drug resistance phenotype of tumor cells and its correlation with therapeutic outcome.

Primary embryonal rhabdomyosarcoma of long bone. Case report and review of the literature.

We report a case of primary embryonal rhabdomyosarcoma of long bone, presenting as a lytic destructive bone tumor in the right femoral diaphysis of a 7-year-old girl. To our knowledge, this is only the third report of this entity. The neoplasm was a pure embryonal rhabdomyosarcoma with numerous rhabdomyoblasts. Immunohistochemistry confirmed the diagnosis: The cells were reactive with antibodies directed against desmin, muscle-specific actin, and myoglobin. No other neoplastic mesenchymal component was present within the tumor. Although rare, primary rhabdomyosarcoma, along with Ewings tumor and osteosarcoma, should be considered in the differential diagnosis of malignant bone tumors in childhood.

Vincristine neurotoxicity with residual equinocavus deformity in children with acute leukemia

Vincristine has been demonstrated to be a neurotoxic agent with distal axonal degeneration progressing proximally. Five children with acute lymphoblastic leukemia developed bilateral peroneal nerve palsies with equinocavus deformities. Three developed fixed contractures requiring surgical correction. One patient was braced prior to development of fixed deformity and the other had physical therapy preventing fixed deformities and did not require surgery. All of the children obtained complete return of peroneal nerve function. Proper bracing and/or physical therapy at the time of diagnosis of neurologic deficit will prevent fixed contractures and the necessity for surgery.

Acute myeloid leukaemia with t(8;16)(p11;p13) in a child after intrauterine X‐ray exposure

We describe t(8;16)(p11;p13) acute myeloid leukaemia (AML‐M4) in a 12‐year‐old white male with a history of prenatal X‐ray exposure. He had skin and bone involvement and some of the leukaemic blasts showed haemophagocytosis, characteristic features seen in t(8;16) AML. 20% of the reported cases of t(8;16)(p11;p13) AML are therapy‐related and this case further supports the possible role of the ionizing radiation in the development of this disorder.