A systematic review of prevalence, disease characteristics and management of systemic lupus erythematosus in Australia: identifying areas of unmet need.

BACKGROUND: Few epidemiological studies of systemic lupus erythematosus (SLE) have been conducted in Australia, and current management practice and levels of unmet need in this country are not well characterised. AIM: To perform a systematic literature review to identify Australia-specific information on SLE, particularly areas of unmet need. METHODS: MEDLINE, EMBASE and the Cochrane Library were searched (1 January 1990 to 29 November 2013). All articles on prevalence, disease characteristics, management and outcomes of SLE in Australia were included. RESULTS: There is limited published information on SLE in Australia. Of 24 articles included, 18 described results from observational studies, three were narrative reviews, one was a clinical update, and two were medical education articles. In remote regions, SLE was reported to be more prevalent in Aboriginal Australians than non-Aboriginal Australians; information in urban populations is lacking. Asian Australians may be more affected by SLE than non-Asian Australians. Pregnancy outcomes may also be adversely affected. Many Australians with SLE may experience high levels of unmet need, including delayed diagnosis, ongoing symptoms, flares, depression/anxiety, sleeping difficulty and decreased quality of life. Published guidance on the SLE management in Australia is limited and dated. CONCLUSIONS: Published information on SLE in Australia is limited, but suggests that ethnicity may affect the prevalence and disease characteristics and that many Australians with SLE have unmet needs. Improvements in diagnosis, treatment and management are needed to alleviate these needs. Up-to-date guidance on the management of SLE would benefit healthcare professionals and patients.

Entrapment and social problem-solving in suicidal behavior across the adult lifespan.

BACKGROUND: Feelings of entrapment and deficits in social problem-solving skills have been associated with risk for suicidal behavior in the context of depression. However, few studies have examined the effect of age on the association between these risk factors and suicidal behavior across most of the adult lifespan. METHODS: In a three-site study, we tested interactions of age with feelings of entrapment and social problem-solving style in 105 depressed patients with a recent suicide attempt, 95 depressed patients with no history of suicide attempt, and 97 demographically similar non-psychiatric participants (age 16-80). Attempter/non-attempter differences, age interactions, and the relative contribution of entrapment and social problem-solving style to past attempter were examined. RESULTS: Entrapment significantly interacted with age such that it discriminated past attempters from depressed non-attempters better at older ages. Social Problem-Solving Inventory (SPSI) total score and most subscales did not distinguish past attempters, but the SPSI Impulsive Style Problem-Solving was an effective discriminator of past suicide attempts across the full adult lifespan and did not interact with age. In a multipredictor model, both the entrapment by age interaction and SPSI Impulsive Style Problem-Solving score were significant predictors for the classification of attempters. LIMITATIONS: The cross-sectional nature of our research design limited conclusions that may be drawn about individual change over time or cohort effects. CONCLUSIONS: Entrapment did not distinguish past attempters at younger ages but became a better discriminator in middle to late adulthood. An impulsive problem-solving style was associated with past suicide attempts across the full adult lifespan.

Cohort differences in the progression of developmental pathways: evidence for period effects on secular trends of violence in males.

BACKGROUND: Rates of violence in the USA have fluctuated widely over the past few decades. Theorists have examined period and cohort effects, but there appear to be no studies examining these effects on progression in developmental pathways towards violence. OBJECTIVE: To assess whether differences in progression among individuals in the Pittsburgh Youth Study are consistent with period or cohort effects. DESIGN: Multivariate logistic regression was conducted to examine differences between cohorts in the odds of progressing through the developmental pathway towards violence. Adjusted and unadjusted odds ratios (ORs) and corresponding 95% CI are reported. SETTING: Pittsburgh Pennsylvania, from 1987 to 2000. SUBJECTS: Two cohorts of male adolescents from the Pittsburgh Youth Study. The youngest cohort (n = 503) was followed from median ages 7 to 20, and the oldest cohort (n = 506) was followed up from median ages 13 to 25. MAIN OUTCOME MEASURE: The odds of progression along a developmental pathway towards violence. RESULTS: There was no statistically significant difference between the cohorts in progression from minor aggression to physical fighting (OR = 1.13, 95% CI 0.77 to 1.65). However, after adjustment for major risk factors, the oldest cohort was significantly more likely to progress from physical fighting to violence (OR = 2.34, 95% CI 1.39 to 3.92). CONCLUSIONS: These results provide initial evidence that cohort effects, which would be present early in development, do not contribute significantly to later differences in reported violence and raises the possibility of whether period effects can explain these differences.

MicroRNA-206 is differentially expressed in Brca1-deficient mice and regulates epithelial and stromal cell compartments of the mouse mammary gland.

Depletion of Brca1 leads to defects in mouse mammary gland development and mammary tumors in humans and mice. To explore the role of microRNAs (miRNAs) in this process, we examined the mammary glands of MMTV-Cre Brca1(Co/Co) mice for differential miRNA expression using a candidate approach. Several miRNAs were differentially expressed in mammary tissue at day 1 of lactation and in mammary epithelial cell lines in which Brca1 messenger RNA (mRNA) levels have been reduced. Functional studies revealed that several of these miRNAs regulate mammary epithelial cell function in vitro, including miR-206. Creation and analysis of MMTV-miR-206 transgenic mice showed no effect on lactational mammary development and no tumors, but indicates a role in mammary tissue remodeling in mature mice, potentially involving Igf-1 and Sfrp1. These results indicate the potential of miRNAs to mediate the consequences of Brca1 loss and suggest a novel function for miR-206.

Peripheral primitive neuroectodermal tumors in adults: documentation by molecular analysis.

PURPOSE: The Ewing tumor (ET) family of peripheral primitive neuroectodermal tumors (pPNETs) are primitive small round-cell tumors (SRCTs) of the bone and soft tissue that occur predominantly in children and adolescents. However, pPNETs only rarely enter the differential diagnosis of bone and soft tissue SRCTs in adults. Recently, gene fusions between the EWS gene and different members of the ETS transcription factor family have been shown to occur in virtually all pPNETs and thus constitute a pathognomonic marker for this tumor subclass. The aim of the present study was to document EWS/ETS fusion gene expression in suspected pPNETs of adults as objective evidence for the existence of this tumor family in older patients. PATIENTS AND METHODS: The three contributing molecular diagnostic laboratories retrospectively compiled a cohort of all SRCT cases in which EWS/ETS gene fusions had been shown by molecular analysis. This cohort was surveyed for cases that occurred in patients aged 40 years or older, which were then analyzed for their clinical and pathologic features. RESULTS: Nine patients between 40 and 65 years of age were found to have tumors positive for EWS/ETS gene fusions. Standard histopathologic and clinical features of these cases, other than age, were similar to those of childhood pPNETs. Patients were initiated on appropriate therapy after molecular analysis confirmed the diagnosis of pPNET. CONCLUSION: Identification of an EWS/ETS gene fusion is useful in providing objective evidence of the diagnosis of pPNET in patients over the age of 40 years. This diagnosis should be considered in adults who present with bone and soft tissue SRCTs and appropriate biopsy specimens should be collected for molecular analysis at the time of diagnosis.

Prognostic impact of P53 status, TLS-CHOP fusion transcript structure, and histological grade in myxoid liposarcoma: a molecular and clinicopathologic study of 82 cases.

PURPOSE: A specific TLS-CHOP fusion gene resulting from the t(12;16) is present in at least 95% of myxoid liposarcomas (MLS). Three common forms of the TLS-CHOP fusion have been described, differing by the presence or absence of TLS exons 6-8 in the fusion product. Type 5-2 (also known as type II) consists of TLS exons 1-5 fused to CHOP exon 2; type 7-2 (also known as type I) also includes TLS exons 6 and 7 in the fusion, whereas type 8-2 (also known as type III) fuses TLS exons 1-8 to CHOP exon 2. We sought to determine the impact of TLS-CHOP fusion transcript structure on clinical outcome in a group of well-characterized MLS cases. We also analyzed P53 status, because this parameter has been found to have a significant prognostic impact in other sarcomas with chromosomal translocations. METHODS: We analyzed TLS-CHOP fusion transcripts by reverse-transcription PCR using RNA extracted from frozen tissue in 82 MLS confirmed previously to harbor a CHOP rearrangement either by Southern blotting or by cytogenetic detection of the t(12;16). Parameters analyzed included age, location, size, percentage of round cell (RC) component, areas of increased cellularity, necrosis, and surgical margins. In 71 (87%) cases, adequate tumor tissue was available for immunohistochemical analysis of P53 status, using DO7 antibody. The Kaplan-Meier method, log-rank, and Cox regression tests were used for survival analyses. RESULTS: Most MLS were >10 cm (73%), arising in the thigh (70%), and localized at presentation (89%). RC component was <5% in 47 (57%) cases and > or =5% in 35 (43%). The TLS-CHOP fusion transcript was type 5-2 in 55 (67%), type 7-2 in 16 cases (20%), and type 8-2 in 8 (10%). One tumor had a unique variant fusion, between exon 6 TLS and exon 2 CHOP. Two other cases (2%) showed an EWS-CHOP fusion transcript. Overexpression of P53 (defined as > or =10% nuclear staining) was detected in 12 (17%) cases. High histological grade (defined as > or =5% RC; P < 0.01), presence of necrosis (> or =5% of tumor mass; P < 0.05), and overexpression of P53 (P < 0.001) correlated with reduced metastatic disease-free survival in localized tumors. The presence of negative surgical margins (P < 0.01) and extremity location (P = 0.02) were found to be significant in predicting local recurrence in the entire group as well as localized cases by univariate and multivariate analysis. Although there was no significant correlation between TLS-CHOP transcript type and histological grade or disease-specific survival, an association was found between the P53 status and type 5-2 fusion (P < 0.01). CONCLUSION: In contrast to some other translocation-associated sarcomas, the molecular variability of TLS-CHOP fusion transcript structure does not appear to have a significant impact on clinical outcome in MLS. Instead, high histological grade (> or =5% RC), presence of necrosis, and P53 overexpression are predictors of unfavorable outcome in localized MLS.

Penetration of neuronal perikarya by capillaries in chronic limbic encephalitis.

In a case of chronic limbic encephalitis in a 57-year-old man many neurons in the pyramidal cell layer of the hippocampus bilaterally were penetrated by ingrowing capillaries. All gradations from slight to moderate indentation of the cell membranes to complete incorporation of the capillaries in the neuronal perikarya were observed. The penetrating capillaries retained their basement membranes. Because of the chronic inflammation there was extensive fibrous gliosis in Ammon's horn. This apparently had an immobilizing effect on these neurons; it is postulated that proliferating capillaries of the active inflammatory process were unable to displace local neurons and instead grew against and through their perikarya.

Interleukin-1beta upregulates MMP-9 expression in stromal cells of human giant cell tumor of bone.

Giant cell tumor (GCT) of bone is a progressive, potentially malignant process that destroys skeletal tissue. It consists of multinucleated giant cells, which are hypothesized to be derived from a monocyte/macrophage lineage and mononuclear stromal cells, and the precise relationship of these cells is not fully understood. Recently, we demonstrated that the production of matrix metalloproteinase-9 (MMP-9) in GCT stromal cells is regulated by certain factor(s) secreted by the multinucleated giant cells. In the present study, we evaluated for the presence of interleukin-1beta (IL-1beta) and attempted to establish its possible role for the induction of MMP-9 in GCT stromal cells. Using enzyme-linked immunosorbent assay (ELISA), we have demonstrated that the primary GCT cultures secrete both IL-1beta and MMP-9. The addition of monoclonal antibody (mAb) against IL-1beta partially abrogated, but did not abolish, MMP-9 expression. Our results on gelatin zymography, reverse transcriptase-polymerase chain reaction (RT-PCR), and immunofluorescence showed that GCT stromal cells did not express MMP-9, although treatment with IL-1beta induced MMP-9 expression in a dose-dependent manner, and the secretion peaked 24 h after stimulation and then plateaued. Studies with cycloheximide, a protein synthesis inhibitor, demonstrated that de novo protein synthesis is required for IL-1beta induced MMP-9 expression. Moreover, nuclear run-on analysis has revealed that IL-1beta significantly increased MMP-9 gene transcription in GCT stromal cells. The data suggest that IL-1beta secreted by the multinucleated giant cells in GCT may be one of the factors responsible for the induction of MMP-9 at the transcriptional level in GCT stromal cells in vivo. We conclude that GCT has a self-stimulatory system for the production of MMP-9, and the ability of stromal cells to produce MMP-9 with appropriate stimuli, such as IL-1beta, and possibly in concert with other cytokines may contribute to the aggressive and potentially malignant behavior of GCT.

Expression of 72 kDa and 92 kDa type IV collagenases from human giant-cell tumor of bone.

Basement membrane forms widespread barriers to tumor invasion. It has been shown that tumor-secreted, basement membrane-degrading enzymes, namely metalloproteinases (MMPs) play an important role in tumor invasion and metastasis. In this study, we determined the enzymatic activity, content, and mRNA of both the 72 kDa (MMP-2) and 92 kDa (MMP-9) MMPs in primary cultures of human giant-cell tumor of bone (GCT) in vitro and in tissue extracts (in vivo). Gelatin zymography showed the presence of lytic bands at M(r) 121,000, 92,000, and 72,000, and these enzymatic activities were inhibited by EDTA, an inhibitor of MMPs. Western blots with antibodies specific for MMP-2 and MMP-9 confirmed the presence of MMP-2 and MMP-9 both in vitro and in vivo, but GCT cells at late passage showed only MMP-2. Northern blots using labeled cDNA probes specific for these molecules revealed the presence of 3.1 kb transcript for MMP-2 and a 2.9 kb transcript for MMP-9. Using specific antibodies to 72 kDa and 92 kDa type IV collagenases, we studied their cellular distribution by immunohistochemical means. Stronger immunoreactivity was found for 92 kDa type IV collagenase than 72 kDa type IV collagenase in the giant cells. It appears, therefore, that MMP-9 may play an important role in the malignant behavior of GCTs and suggests a potential therapeutic role for protease inhibitors in attempting to minimize the invasive behavior of GCTs.

Regulation of MMP-9 (92 kDa type IV collagenase/gelatinase B) expression in stromal cells of human giant cell tumor of bone.

Matrix metalloproteinases (MMPs) play an important regulatory role in tissue morphogenesis, cell differentiation, tumor invasion and metastasis. Several authors have reported a direct correlation between the production of 72 kDa (MMP-2) and 92 kDa (MMP-9) type IV collagenases/gelatinases and the metastatic potential of cancer cells. Recently, we have identified the expression of both MMP-2 and MMP-9 in primary cultures of human giant cell tumor (GCT) of bone in vitro, and in tissue extracts in vivo. Interestingly, MMP-9 is not secreted by late-passaged GCT cells. It is possible that the production of MMP-9 is regulated by certain factor(s) secreted by the multinucleated giant cells in the primary culture. In order to test this hypothesis, the effect of primary-culture-conditioned medium on the expression of MMP-9 by late-passaged mononuclear stromal cells was examined. Adding conditioned medium from the primary GCT culture to the late-passaged stromal cells induced MMP-9, as evidenced by the presence of lytic bands at M(r) 92,000 and 72,000 on a gelatin zymogram. These enzyme activities were inhibited by EDTA, a well-known inhibitor of the MMPs. We confirmed these results by Western blotting using specific antibodies and RT-PCR for MMP-2 and MMP-9. Immunofluorescence studies with specific antibodies to MMP-9 further confirmed its expression by the passaged stromal cells cultured in the primary-culture-conditioned medium. The data indicate that MMP-2 and MMP-9 are produced by the mononuclear stromal cells when cultured in GCT primary-culture-conditioned medium. This suggests that multinucleated giant cells in primary cultures secrete a factor(s) that stimulates stromal cells to produce MMP-9, which, in turn, may contribute to the aggressive behavior of GCT.

Extra copies of chromosomes 7, 8, 12, 19, and 21 are recurrent in adamantinoma.

Adamantinoma of long bones is a rare neoplasm predominantly involving the tibia. Cytogenetic studies of adamantinoma are few. Cytogenetic or molecular cytogenetic analysis of four adamantinomas, and a review of eleven cases in the literature reveals extra copies of chromosomes 7, 8, 12, 19, and 21 as recurrent in this neoplasm. Adamantinoma may be confused with a variety of primary and metastatic epithelial and mesenchymal neoplasms. Observation of these aneuploidies may be useful in establishing the diagnosis of adamantinoma.

Primary monophasic synovial sarcoma of the pleura: five cases confirmed by the presence of SYT-SSX fusion transcript.

This study reports five cases of primary pleural monophasic synovial sarcomas and assesses the role of the SYT-SSX fusion transcript in the differential diagnosis. Patients had a mean age of 47 years with no gender predilection. Chest pain and pleural-based masses with effusions characterized the clinical presentations. Each patient underwent a complete surgical resection of the mass. The mean follow-up was 9 months, available in four patients. They were all alive, with no evidence of disease. Histologically, neoplasms were composed of densely packed fusiform cells focally alternating with less cellular areas. No epithelial differentiation was identified at the hematoxylin and eosin level. Keratin and epithelial membrane antigen reactivity was focal and present in four and two tumors, respectively. There was no immunoreactivity for CD34. RT-PCR studies for the presence of a SYT-SSX1 or SYT-SSX2 fusion transcript were positive in every tumor. In comparison, 10 localized fibrous tumors were immunohistochemically negative for keratin and epithelial membrane antigen and positive for CD34. A SYT-SSX fusion transcript was not identified in any of five localized fibrous tumors tested. Identification of the synovial sarcoma-specific chimeric transcript (SYT-SSX1 or SYT-SSX2), in conjunction with immunoperoxidase studies, can be extremely helpful in identifying cases of pleural monophasic synovial sarcoma.

Primary malignant neuroepithelial tumors of the kidney: a clinicopathologic analysis of 146 adult and pediatric cases from the National Wilms' Tumor Study Group Pathology Center.

Primary malignant neuroepithelial tumors of the kidney (NETKs) comprise a group of primitive, highly malignant neoplasms that histologically and clinically are not well characterized. A large cohort of 146 of these tumors, occurring in adults and children, has been collected at a single depository site, the National Wilms' Tumor Study Group (NWTSG) Pathology Center. The authors undertook a systematic retrospective review of the histologic, ultrastructural, and clinical features of these tumors, based on materials collected by the NWTSG and the consultation files of one of the authors (J.B.B.). Histologic features were generally those of primitive neural tumors with varying amounts of rosettes and neuropil; however, a large proportion of cases displayed unusual features such as spindle cells, ganglion cells, clear cell sarcoma-like foci, rhabdoid cells, epithelioid cells, and organoid foci. CD99 staining had been performed on 69 cases and showed membranous staining in 65. The NETKs were present in patients with a wide age spectrum, ranging from 1 month to 72 years (median, 18 years). EWS/FLI1 fusion analysis using reverse transcriptase-polymerase chain reaction and immunohistochemical stains for cytokeratin, chromogranin, and epithelial membrane antigen were performed successfully on a subset of 45 cases with available paraffin blocks. Only 13 of the 45 were fusion-positive, and there was no correlation between fusion status and histology, presence of rosettes, ultrastructural features, or cytokeratin positivity. CD99-negative cases were usually fusion-negative (six of seven cases), and all three chromogranin-positive cases were fusion-negative. Tumor staging, performed on 72 clearly defined and quantifiable cases by using NWTSG criteria, indicated that these are aggressive tumors, because only six were Stage 1, compared with 16 Stage 2, 31 Stage 3, and 19 Stage 4 lesions. The authors conclude that NETKs are a somewhat diverse group of generally aggressive, high-grade lesions that may present in a wide age range and are difficult to characterize without immunohistochemistry and cytogenetics/molecular biology.

Adamantinoma-like Ewing's sarcoma: genomic confirmation, phenotypic drift.

Ewing's sarcoma, a highly malignant neoplasm, is characterized by an 11;22 translocation [t(11;22) (q24;q12)], resulting in the fusion of genes FLII and EWS. Adamantinoma of extragnathic bones, a low-grade malignant neoplasm with epithelial features, is not typically considered in the differential diagnosis of Ewing's sarcoma. In this study, three osseous Ewing's sarcomas with histological, immunohistochemical, or ultrastructural epithelial features were subjected to reverse transcription-polymerase chain reaction and sequencing studies for the Ewing's sarcoma molecular rearrangement. (Two of the three cases were originally described as adamantinomas or nontypical Ewing's sarcoma before the availability of genetic characterization.) In addition, traditional cytogenetic analysis and a unique combined interphase molecular cytogenetic/ immunocytochemical approach with bicolor 11;22 translocation breakpoint flanking probes (cosmids) and pancytokeratin antibodies were performed on one neoplasm. At(11;22) (q24;q12) was found in one neoplasm and a type II EWS/FLI-1 fusion transcript was detected in all three neoplasms. The combined genetic/immunocytochemical approach revealed the presence of the 11 ;22 translocation in the nuclei of cytokeratin immunoreactive cells. These genotypic and phenotypic findings delineate a novel Ewing's sarcoma histologic variant, "adamantinoma-like Ewing's sarcoma."

Translocation t(1;3)(p36.3;q25) is a nonrandom aberration in epithelioid hemangioendothelioma.

The cytogenetic findings for two epithelioid hemangioendotheliomas are reported. An identical chromosomal translocation involving chromosomes 1 and 3 [t(1;3)(p36.3;q25)] was detected in both cases of epithelioid hemangioendothelioma, possibly representing a characteristic rearrangement for this histopathologic entity. The presence of clonal karyotypic abnormalities supports a neoplastic origin for the epithelioid variant of hemangioendothelioma. Identification of the 1;3 translocation may be useful diagnostically. Should additional studies confirm these data, this could lead to the identification of the gene(s) central to this neoplastic process.

Transcriptional regulation of MMP-9 expression in stromal cells of human giant cell tumor of bone by tumor necrosis factor-alpha.

We determined whether certain factor(s) secreted by multinucleated giant cells, which is of monocyte/macrophage lineage in giant cell tumor of bone (GCT), regulate the induction of matrix metalloproteinase (MMP)-9 expression in mononucleated stromal cells. Our data derived using enzyme linked immunosorbant assays (ELISAs) suggest that the GCT cells in primary culture produce both MMP-9 and tumor necrosis factor-alpha (TNF-alpha). Further, the MMP-9 expression in GCT primary cultures was partially abrogated by neutralizing antibody to TNF-alpha, suggesting that TNF-alpha secretion by the multinucleated giant cells may be one of the factors responsible for the production of MMP-9 by the stromal cells in vivo. In order to confirm this we examined the role of TNF-alpha on the induction of MMP-9 expression in bone GCT stromal cells. These cells express MMP-2, but not MMP-9. However, treatment of these cells with TNF-alpha induced the expression of MMP-9 in a concentration-dependent manner. Kinetic experiments revealed that the secretion of MMP-9 peaked 12 h post TNF-alpha stimulation. Immunofluorescence studies confirmed the expression of MMP-9 after stimulation of GCT stromal cells with TNF-alpha. Further, TNF-alpha-induced MMP-9 expression was completely blocked with neutralizing antibody to TNF-alpha, thereby demonstrating the specificity. In addition, the induction of MMP-9 expression by TNF-alpha was completely abrogated in the presence of cycloheximide, a protein synthesis inhibitor, suggesting that de novo protein synthesis may be required. Nuclear run-on analysis demonstrated that treatment of GCT stromal cells significantly enhanced the MMP-9 gene transcription. Together, our data suggest that TNF-alpha secreted by the multinucleated giant cells up-regulates MMP-9 expression in GCT stromal cells by the induction of certain transcription factors, which in turn enhanced the rate of transcription of MMP-9 gene. These studies also suggest the existence of an essential cell-cell interaction in the regulation of MMP-9 expression in GCT.

Contribution of molecular genetic data to the classification of sarcomas.

Many sarcomas are characterized by specific recurrent chromosomal translocations which provide powerful diagnostic tumor markers. Since 1992, the genes involved by almost all of these translocations have been cloned, inaugurating a new era in the study of sarcomas. At the biological level, these chromosomal translocations produce highly specific gene fusions, usually encoding aberrant chimeric transcription factors. Clinically, the correlation of these translocation-derived genetic markers and discrete histopathologic entities has been remarkable. Fusion gene detection has confirmed and refined the nosology of several sarcoma groups. The overall effect has been to strengthen certain pathological concepts rather than to revolutionize. The focus of this brief review is the recent impact that the cytogenetic and molecular detection of these translocations has had on sarcoma diagnosis and classification.

Cytogenetic and pathologic aspects of Ewing's sarcoma and neuroectodermal tumors.

Diagnostic classification of poorly differentiated, round cell, primitive neuroectodermal neoplasms, including Ewing's sarcoma, peripheral neuroepithelioma, Askin's tumor, and esthesioneuroblastoma, is challenging to the surgical pathologist using conventional histopathologic approaches because of very similar and overlapping morphologic and cytologic features. Furthermore, distinguishing these neoplasms from neuroblastoma, embryonal rhabdomyosarcoma, small cell osteogenic sarcoma, and non-Hodgkin's lymphoma can be difficult. This paper describes and reviews the cytogenetic and molecular genetic changes in these tumors and demonstrates how the ability to detect these changes has enabled a greater understanding of the histogenesis, classification, diagnosis, and prognosis of these neoplasms.

Recurrent anomalies of 6q25 in chondromyxoid fibroma.

Chondromyxoid fibroma is a rare benign bone tumor most commonly arising in the metaphysis of long bones in young adults. Histopathologically, chondromyxoid fibroma may be difficult to distinguish from other cartilaginous neoplasms. Recently, a pericentric inversion of chromosome 6 [inv(6)(p25q13)] has been proposed as a specific genetic marker for chondromyxoid fibroma. In this study, cytogenetic and spectral karyotypic analyses of 2 chondromyxoid fibroma cases showed clonal abnormalities of chromosome 6 but at a breakpoint on the long arm (q25) distal to that described in the pericentric inversion. These findings suggest that several distinct breakpoints on chromosome 6 are nonrandomly involved in chondromyxoid fibroma.

Chromosomal abnormalities in clear cell sarcoma. Implications for histogenesis.

Cytogenetic analysis was performed on three specimens of clear cell sarcoma, a rare neoplasm of uncertain histogenesis. Chromosomal analysis of clear cell sarcoma has not been reported previously. Two of the specimens analyzed consisted of the primary foot lesion and subsequent lymph node metastasis in a 29-year-old male. The other specimen was a primary foot lesion in a 61-year-old male. Clonal abnormalities were detected in all three of the specimens. The significance of these results with regard to the origin of this uncommon neoplasm is discussed.