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Anders Rydholm

Publications and source records attributed to Anders Rydholm.

17 recordsLinked to original sources
PubMed2006

Gene expression profiles relate to SS18/SSX fusion type in synovial sarcoma.

We applied 27k spotted cDNA microarray slides to assess gene expression profiles in 26 samples from 24 patients with synovial sarcomas (SS). The data were analyzed in relation to histopathologic type, cytogenetic aberrations, gene fusion type and development of distant metastases. Supervised analysis based on gene fusion type in 12 SS with SS18/SSX1 and 9 with SS18/SSX2 revealed significant differences in gene expression profiles. Among the discriminators were several genes that have previously been found to be upregulated in SS, including AXL, ZIC2, SPAG7, AGRN, FOXC1, NCAM1 and multiple metallothioneins. Histopathology and degree of cytogenetic complexity did not significantly influence expression, whereas a genetic signature that related to development of metastases could be discerned, albeit with a high false-positive rate. In conclusion, our findings demonstrate differentially expressed genes for the 2 major gene fusion variants in SS, SS18/SSX1 and SS18/SSX2, and thereby suggest that these result in different downstream effects.

Adolescent↗
PubMed2006

Fine-needle aspiration of neurilemoma (schwannoma). A clinicocytopathologic study of 116 patients.

The preoperative fine-needle aspiration cytology (FNAC) diagnoses in 116 surgically excised neurilemomas were reviewed and compared with the corresponding histopathologic diagnoses made on surgical specimens and with clinical data. In addition, the utility of adjunctive techniques was analyzed and other spindle-cell lesions in the differential diagnoses were discussed. An unequivocal, benign diagnosis was rendered by FNAC in 80 cases, 67 of which were correctly labelled as neurilemoma in a review of the original cytology reports. There were 6 false-positive malignant diagnoses while 23 smears were considered insufficient and 7 inconclusive as to whether benign or malignant. On reevaluation, the diagnostic smears in most cases contained spindle cells with wavy nuclei embedded in a fibrillar, occasionally collagenous, and/or myxoid matrix and Antoni A/Antoni B tissue fragments. A moderate to abundant admixture of round to oval cells was also frequent. Nuclear palisading was seen in 41 smears with distinctive Verocay bodies in 10. Markedly pleomorphic nuclei were seen in smears from 8 ancient and 6 conventional neurilemomas, and slight to moderate nuclear pleomorphism was observed in 38 additional cases. Thus most neurilemomas have distinct cytomorphologic features that allow correct diagnosis. The major problem in FNAC of neurilemoma is to obtain sufficient material. Furthermore aspirates showing predominantly Antoni A features, nuclear pleomorphism, and/or myxoid changes can easily be confused with other types of benign or malignant soft-tissue tumors.

Adolescent↗
PubMed2005

Prognostic significance of chromosome aberrations in high-grade soft tissue sarcomas.

PURPOSE: To investigate whether previously observed correlations between tumor karyotype and risk of metastases could be reproduced in an independent set of high-grade soft tissue sarcomas (STSs). PATIENTS AND METHODS: In a previous study on high-grade STSs with clonal chromosome aberrations, we identified a number of cytogenetic variables, besides tumor grade and size, that were associated with significantly increased risk of metastases. In the present study, we have tested the predictive value of these cytogenetic variables in a new set of 156 high-grade STSs, all located in the extremities or trunk wall. RESULTS: Of the 10 cytogenetic variables that turned out to provide prognostic information in the previous series, encompassing 122 trunk wall or extremity STSs, three were significantly associated with metastases also in the new series. In a final Cox regression analysis including these three cytogenetic variables, as well as tumor grade and size, on the combined series of 278 high-grade STSs, four parameters were found to be significantly associated with metastasis risk: tumor grade 3, tumor size > or = 5 cm, breakpoint in region 1p1, and gain of region 6p1. CONCLUSION: Our findings suggest that independent prognostic information may be gained from cytogenetic analysis of high-grade STS.

Adult↗
PubMed2005

Core-needle biopsy performed by the cytopathologist: a technique to complement fine-needle aspiration of soft tissue and bone lesions.

BACKGROUND: Fine-needle aspiration cytology (FNAC) is gaining increased popularity in the diagnosis of musculoskeletal lesions; and, in many patients, a definitive diagnosis can be rendered from aspiration smears alone. The main limitation of FNAC of soft tissue and bone neoplasms is in the evaluation of tissue architecture. In addition cytologic specimens are not always adequate for ancillary studies. METHODS: A consecutive series of 130 patients with soft tissue and bone lesions was examined by core-needle biopsy (CNB) performed by a cytopathologist in conjunction with FNAC. The findings of this combined diagnostic approach were compared with histologic diagnoses made on surgical biopsies and resected specimens from 86 patients. Adequate follow-up was available in all patients. RESULTS: FNAC combined with CNB correctly could identify 77 of 78 malignant lesions and 50 of 52 benign lesions. Only seven patients underwent incisional biopsy. The tumor subtype was determined correctly in 30 of 39 patients (77%) and the malignancy grade was determined in 35 of 39 patients (90%) with primary soft tissue and bone sarcomas compared with the biopsy or operative specimens. CONCLUSIONS: FNAC of musculoskeletal tumors/lesions complemented with CNB combined cytomorphology with tissue architecture and ancillary procedures. In the current study, obtaining FNAC as well as CNB at the same clinic visit and by the cytopathologist made preliminary diagnosis on the day of referral possible. This speeded diagnosis increased the number of correct diagnoses and usually enabled correct subtyping and malignancy grading of sarcomas.

Adult↗
PubMed2005

Intratumor versus intertumor heterogeneity in gene expression profiles of soft-tissue sarcomas.

Soft-tissue sarcomas (STSs) constitute more than 30 histologic entities. In addition, within each entity, tumors are often heterogeneous in macroscopic features, genetic alterations, microscopic appearance, and clinical course. Therefore, there has been concern about whether a single tumor sample can provide a gene expression profile representative of the entire tumor. We used 27-k cDNA microarray slides to assess the importance of intratumor versus intertumor heterogeneity of the gene expression profiles of 2 morphologically heterogeneous STSs. Multiple pieces of tumor (8 and 10 pieces) were obtained from a myxoid variant of malignant fibrous histiocytoma (MFH) and a leiomyosarcoma (LMS), respectively, and the expression patterns were compared with single tumor samples from 20 MFHs and 16 LMSs. Hierarchical clustering analysis of the expression profiles showed that samples from the same tumor clustered together. The average intratumor distance was considerably shorter than the average intertumor distance in both LMS and MFH. In addition, tumor subclusters that distinguished different macroscopic parts of the tumor could be discerned. We concluded that intratumor variability exists but that accurate gene expression profiling also could be obtained using single samples from a large STS.

Adult↗
PubMed2005

Improved prognostication in soft tissue sarcoma: independent information from vascular invasion, necrosis, growth pattern, and immunostaining using whole-tumor sections and tissue microarrays.

In 140 mixed primary soft tissue sarcomas with a median follow-up of 6 years, the prognostic importance of tumor size, tumor depth, grade, necrosis, vascular invasion, and peripheral growth pattern (pushing versus infiltrating) was evaluated on whole-tumor sections. Immunohistochemical expression of Ki-67, p53, cyclin A, bcl-2, beta-catenin, CD44, and P-glycoprotein was determined using tissue microarray from the peripheral growth zone. Local recurrences developed in 17% of the patients and correlated with necrosis, vascular invasion, and cyclin A expression. No local recurrence developed in tumors with a pushing growth pattern, regardless of tumor grade and depth. Metastasis developed in 39% of the patients. Vascular invasion was identified in 36% of the tumors and was the strongest prognostic factor for metastasis with a hazard ratio of 3.5. Growth pattern and tumor necrosis were also strong prognostic factors for metastasis, whereas malignancy grade, tumor size, and tumor depth did not have any independent prognostic value. Immunostaining showed independent prognostic information for Ki-67, beta-catenin, CD44, and P-glycoprotein. The results indicate that whole-tumor sections could facilitate identification of vascular invasion, necrosis, and peripheral growth pattern and that immunohistochemical profiling from the growth zone also provides independent prognostic information for metastasis in soft tissue sarcoma.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2004

Expression profiling using tissue microarray in 211 malignant fibrous histiocytomas confirms the prognostic value of Ki-67.

The tissue microarray technology is a high-throughput technique that allows studies of multiple markers in large tumor materials. We performed immunohistochemical profiling using tissue microarray and immunostaining for Ki-67, p53, bcl-2, CD44, cyclin A and Pgp in a series of 211 malignant fibrous histiocytomas (MFHs) with correlation to prognosis. Tissue from 50 local recurrences and 20 metastases was available for comparison with the primary tumors. In univariate analysis, Ki-67 was the only immunohistochemical marker significantly correlated with metastasis with a hazard ratio of 1.9. Multivariate analysis, with tumor size, depth, necrosis, vascular invasion, mitotic rate and Ki-67 expression, revealed an independent prognostic value of tumor size and Ki-67. Local recurrences did not differ from the corresponding primary tumors, whereas metastases showed a trend for upregulation of cyclin A and Pgp. In this large series of MFHs, a tumor size greater than 8 cm and a Ki-67 index of more than 20% were strong and independent prognostic factors for metastasis. In contrast, p53, bcl-2, CD44, cyclin A and Pgp, which have previously been suggested as prognostic factors in soft tissue sarcomas, did not show such correlations. Hence, we suggest that proliferation, as measured by Ki-67 index, should be considered as a prognostic marker in clinical management of pleomorphic soft tissue sarcomas.

Adult↗
PubMed2004

Time dependence of prognostic factors for patients with soft tissue sarcoma: a Scandinavian Sarcoma Group Study of 338 malignant fibrous histiocytomas.

BACKGROUND: Prognostic factors for metastasis in soft tissue sarcoma govern decisions regarding adjuvant treatment. However, the significance of initial tumor-related prognostic factors over time is largely unknown. METHODS: The current study included 338 patients with malignant fibrous histiocytoma (MFH) of the extremities or the trunk wall whose tumors were reviewed by the Scandinavian Sarcoma Pathology Review Group. Of these 338 patients, 329 (97%) had high-grade tumors. The median follow-up period was 7 years. Metastases occurred in 110 of 338 of patients after a median follow-up period of 14 months, with roughly one-third (32 of 110) occurring after 2 years. The authors investigated the prognostic significance of tumor size, tumor depth, histologic grade, microscopic tumor necrosis, vascular invasion, mitotic rate, and local tumor recurrence at various time intervals using metastases as an endpoint. RESULTS: On univariate analysis, all investigated factors were found to be correlated with metastases for the entire follow-up period and also for the first 2 years of follow-up; beyond this time point, only size, tumor depth, and local recurrence were significant. On multivariate analysis, necrosis and local tumor recurrence were significant for the entire follow-up duration and also for the first 2 years of follow-up, whereas only tumor depth and local recurrence were significant beyond 2 years of follow-up. For all initial factors, the annual metastasis risks in the high-risk and low-risk groups converged to < 0.1 after 2 years and to near 0 after 5 years. CONCLUSIONS: Prognostic factors for metastasis in MFH were time dependent. The predictive value of the initial prognostic factors was limited to the first 2 years of follow-up. The lack of observed prognostic value beyond 2 years of follow-up probably was attributable to heterogeneity within risk categories as a result of measurement errors and unknown biologic variations.

Adult↗
PubMed2004

The chimeric FUS/CREB3l2 gene is specific for low-grade fibromyxoid sarcoma.

Low-grade fibromyxoid sarcoma (LGFMS) is a variant of fibrosarcoma that was recognized as a distinct tumor entity only quite recently. We previously described a translocation, t(7;16)(q33;p11), that resulted in a fusion of the FUS and CREB3L2 (also known as BBF2H7) genes in two soft tissue tumors that fulfilled morphologic criteria for LGFMS. To delineate the spectrum of tumors that may harbor the FUS/CREB3L2 gene, we selected 45 low-grade spindle cell sarcomas for reverse transcriptase polymerase chain reaction (RT-PCR) and/or fluorescence in situ hybridization (FISH) analyses; none of these tumors had originally been diagnosed as LGFMS. Furthermore, also included were two benign soft tissue tumors and nine high-grade sarcomas with supernumerary ring chromosomes or 7q3 rearrangement and three tumors diagnosed as LGFMS prior to the genetic analysis. Of the 59 tumors analyzed, 12 were FUS/CREB3L2-positive, all of which were diagnosed at histopathologic re-examination as being LGFMS, of both the classical subtype and the subtype with giant collagen rosettes. The breakpoints in the fusion transcripts were always in exons 6 or 7 of FUS and exon 5 of CREB3L2. The results indicated that FUS/CREB3L2 is specifically associated with LGFMS and that RT-PCR or FISH analysis may be useful for the differential diagnosis.

Adolescent↗
PubMed2003

Should tumor depth be included in prognostication of soft tissue sarcoma?

BACKGROUND: Most staging systems for soft tissue sarcoma are based on histologic malignancy-grade, tumor size and tumor depth. These factors are generally dichotomized, size at 5 cm. We believe it is unlikely that tumor depth per se should influence a tumor's metastatic capability. Therefore we hypothesized that the unfavourable prognostic importance of depth could be explained by the close association between size and depth, deep-seated tumors on average being larger than the superficial ones. When tumor size is dichotomized, this effect should be most pronounced in the large size (>5 cm) group in which the size span is larger. METHODS: We analyzed the associations between tumor size and depth and the prognostic importance of grade, size and depth in a population-based series of 490 adult patients with soft tissue sarcoma of the extremity or trunk wall with complete, 4.5 years minimum, follow-up. RESULTS: Multivariate analysis showed no major prognostic effect of tumor depth when grade and size were taken into account. The mean size of small tumors was the same whether superficial or deep but the mean size of large and deep-seated tumors were one third larger than that of large but superficial tumors. Tumor depth influenced the prognosis in the subset of high-grade and large tumors. In this subset deep-seated tumors had poorer survival rate than superficial tumors, which could be explained by the larger mean size of the deep-seated tumors. CONCLUSION: Most of the prognostic value of tumor depth in soft tissue sarcomas of the extremity or trunk wall can be explained by the association between tumor size and depth.

Adolescent↗
PubMed2003

Clustering of deletions on chromosome 13 in benign and low-malignant lipomatous tumors.

Deletions and structural rearrangements of the long arm of chromosome 13 are frequently observed in benign and low-malignant lipomatous tumors, but nothing is known about their molecular genetic consequences. We assessed the karyotypes of 40 new and 22 previously published cases (35 ordinary lipomas, 15 spindle cell/pleomorphic lipomas, 2 myxolipomas, 1 angiomyxolipoma and 9 atypical lipomatous tumors) with chromosome 13-abnormalities, and found bands 13q12-22 to be frequently affected. Twenty-seven cases with structural abnormalities within this region were selected for breakpoint and deletion mapping by metaphase fluorescence in situ hybridization (FISH), using a set of 20 probes. Deletions were found in 23 of 27 cases. The remaining 4 cases had seemingly balanced rearrangements. The breakpoints were scattered but clustered to band 13q14, and in all cases with unbalanced abnormalities, a limited region within band 13q14 was partially or completely deleted. A deletion within band 13q14 was found together with a breakpoint on the other homologue in 5 cases, 4 of which could be tested further with regard to the status of the retinoblastoma (RB1)-gene. In all 4 cases, only 1 copy of the gene was deleted. In addition to the breaks and deletions in the vicinity of the RB1-locus, several other regions of 13q were recurrently affected, e.g., in the vicinity of the hereditary breast cancer (BRCA2; 13q12)- and lipoma HMGIC fusion partner (LHFP; 13q13)- genes. Our findings strongly indicate that deletion of a limited region (approximately 2.5 Mbp) within 13q14, distal to the RB1-locus, is of importance in the development of a subset of lipomatous tumors.

Adult↗
PubMed2003

Elastofibroma dorsi has distinct cytomorphologic features, making diagnostic surgical biopsy unnecessary: cytomorphologic study with clinical, radiologic, and electron microscopic correlations.

Elastofibroma dorsi (EFD) is a relatively rare soft tissue mass, probably of reactive nature. The lesion is typically located near the inferior margin of the scapula or between the inferior part of scapula and the chest wall in elderly women. Although location of the tumor together with the age/sex of the patients and radiologic findings is often suggestive of the diagnosis, tissue examination has been considered necessary to confirm the diagnosis. Although the histologic features of EFD are well known, there are only four single case reports of the cytologic findings in the English language literature. We describe the cytologic features of EFD in five patients with correlations to clinical, radiologic, histologic, and electron microscopic findings. The current study suggests that the fine-needle aspiration (FNA) features are highly diagnostic, permitting a firm diagnosis of EFD in a typical clinical setting and eliminating the need for preoperative histologic examination.

Aged↗
PubMed2003

Fusion, disruption, and expression of HMGA2 in bone and soft tissue chondromas.

Soft tissue and skeletal chondromas are rare entities, and only 21 cases with abnormal karyotypes have been reported. A survey of these, and 10 new cases reported herein, showed that the 12q13-15 segment is nonrandomly involved in structural rearrangements in chondromas. The HMGA2 (HMGI-C) locus in 12q15 is frequently rearranged in other benign mesenchymal tumors, and this study aimed at characterizing the expression of HMGA2 in chondromatous tumors. The material consisted of 8 soft tissue and 6 skeletal chondromas, as well as of 14 skeletal chondrosarcomas. All cases had been cytogenetically analyzed. Expression of HMGA2 could be assessed by RT-PCR in 8 chondromas and 13 chondrosarcomas. HMGA2 was expressed in 4 of six soft tissue chondromas, all displaying 12q-rearrangements at cytogenetic analysis. A truncated transcript (exons 1-3), but not a full-length (exons 1-5) transcript, was detected in three of them, suggesting activation through an intragenic rearrangement. One soft tissue chondroma had a t(3;12)(q27;q15), and the RT-PCR analysis revealed an HMGA2-LPP fusion transcript, composed of HMGA2 exons 1-3 and LPP exons 9-11. An identical fusion transcript previously has been identified in lipoma and pulmonary chondroid hamartoma. In the fourth soft tissue chondroma, a full-length transcript was detected, indicating expression of at least one intact allele. Both skeletal chondromas expressed HMGA2. In one of them, a full-length transcript was detected, even though 12q was cytogenetically unaffected. A truncated or full-length transcript was found in 8 of 13 chondrosarcomas, 4 of which displayed 12q rearrangements. Possibly, cryptic rearrangements were present among the many complex marker chromosomes in the remaining 4 cases.

Adolescent↗
PubMed2002

Prognostically important chromosomal aberrations in soft tissue sarcomas: a report of the Chromosomes and Morphology (CHAMP) Study Group.

Cytogenetic analysis has not only provided important information on the pathogenesis of soft tissue tumors but, by disclosing distinct chromosomal rearrangements in different histopathological entities, has also come to serve as a valuable diagnostic tool. Little is known as yet about the potential prognostic impact of cytogenetic features detected in these tumors. A total of 239 benign and 221 malignant soft tissue tumors with clonal chromosome aberrations were subdivided according to general karyotypic features, such as degree of complexity and ploidy level, and rearrangements of specific chromosomal regions. The cytogenetic variables were analyzed regarding clinical outcome, using time to metastasis as the end point. Selected variables were then compared with established clinicopathological predictors of metastasis development. When the entire material was considered, 167 of 268 investigated cytogenetic variables were associated with clinical outcome. Focusing on the subset of 151 patients with high-grade sarcoma, 17 variables were identified that, besides grade and size, were associated with increased risk of metastasis development. A final Cox regression analysis identified five independent cytogenetic predictors of adverse outcome; breakpoints in chromosome regions 1p1, 1q4, 14q1, and 17q2, and gain of regions 6p1/p2. An increasing effect on metastatic risk was seen with increasing involvement of the selected cytogenetic variables, even when different histopathological types were studied separately. We conclude that cytogenetic data provide independent prognostic information in soft tissue sarcomas. Furthermore, our results point to specific areas of the genome harboring genes that may influence the metastatic potential of sarcoma cells.

Adolescent↗
PubMed2002

DNA ploidy in soft tissue sarcoma: comparison of flow and image cytometry with clinical follow-up in 93 patients.

In soft tissue sarcoma, the prognostic importance of DNA ploidy status is limited. One possible explanation may be technical; small non-diploid stemlines will be diluted in relation to the presence of normal diploid cells and may not be detected by flow cytometry (FCM). We assessed DNA ploidy status in 93 tumors with both FCM and image cytometry (ICM). ICM may permit the exclusion of non-relevant cells. The ability of the two methods to detect non-diploid stemlines was compared, as were the prognostic consequences. The patients (54 males) had a median age of 69 years. Surgical procedures were performed on all patients. None of the patients had received preoperative radiotherapy or chemotherapy. FCM and ICM were performed with standard methods. The prognostic value was assessed with univariate and multivariate analysis. In 82 of the 93 tumors, a concordant ploidy status by FCM and ICM was found. In 5 FCM type 1-2 tumors (diploid), the identification of non-diploid stemlines by ICM did not influence the metastatic rates. Increasing tumor size, histotype other than liposarcoma, increasing malignancy grade, tumor necrosis, and ICM non-diploidy were univariate prognostic factors for metastasis. In a multivariate analysis, only tumor size larger than 9 cm was a prognostic factor. In about 10% of the tumors, a discrepancy between FCM and ICM ploidy status was found, but we could not find a consistent prognostic consequence of this. Neither FCM nor ICM ploidy status was an independent prognostic factor.

Adolescent↗
PubMed2002

Correlation between clinicopathological features and karyotype in 100 cartilaginous and chordoid tumours. A report from the Chromosomes and Morphology (CHAMP) Collaborative Study Group.

The evaluation of chondroid lesions requires full integration of clinical, radiographic, and pathological data; tumour typing is often a challenge for the diagnostic pathologist. Although a variety of chromosomal abnormalities have been documented in chondroid lesions, the potential usefulness of cytogenetic analysis remains unclear. This study has critically reviewed and analysed 117 karyotyped samples from 100 patients with cartilaginous and chordoid tumours. Cases were selected based on successful chromosomal analysis and adequacy of clinical, radiographic, and pathological information. To ensure objective evaluation, the cytogenetic results were correlated in a double-blind setting with consensus diagnoses independently determined on each case, after complete review of the histological, radiographic, and clinical findings. Karyotypic aberrations were identified in 41/92 cartilaginous tumours (5/11 osteochondromas, 2/3 chondromyxoid fibromas, 0/4 chondroblastomas, 11/29 chondromas, 0/3 chondroid tumours of undetermined malignant potential, 22/40 chondrosarcomas and 1/2 miscellaneous cartilaginous lesions) and 5/8 chordomas. Complex karyotypic changes were a feature of malignant tumours (chondrosarcoma and chordoma) and of chondrosarcoma among cartilaginous tumours, where they correlated with high tumour grade. Among primary well-differentiated cartilaginous lesions of bone, the finding of an abnormal karyotype was consistently associated with a grade 1 chondrosarcoma diagnosis. Among karyotypically abnormal cartilaginous tumours, loss of distal 8q was associated with osteochondroma, +5 with synovial chondroma/chondromatosis and parosteal or soft tissue chondroma, alterations of chromosome arm 6q with chondromyxoid fibroma, +7 with bone chondrosarcoma, and 17p1 alterations with grade 3 chondrosarcoma. Alterations involving 12q13 characterized synovial chondroma/chondromatosis in the chondroma group and myxoid chondrosarcoma of bone in the chondrosarcoma group. In conclusion, cytogenetic abnormalities in chondroid lesions are common and are not randomly distributed. They are associated with malignancy/tumour grade as well as with specific diagnoses in many cases, and can therefore be of potential value for tumour typing.

Adolescent↗