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Low-grade fibromyxoid sarcoma (LGFMS) is a malignancy with propensity for late relapse that principally affects deep soft tissues of the extremities and trunk. Its occurrence in the lower female genital tract is rare, and thus it may not be always considered in the differential diagnosis. We describe the salient features of 7 vulvovaginal LGFMS identified in the authors' consultation files. Clinical information was obtained from referring pathologists. Archival slides were reviewed, and immunohistochemistry and fluorescence in situ hybridization were performed in cases with available material. Median age was 40 years (range, 34 to 58 y). Primary sites included vulva (n=6) and vagina (n=1). Tumors were 1.2 to 8.7 cm (median, 5.0 cm) in size and grossly circumscribed with firm to focally gelatinous cut surfaces. Microscopically, 5/7 had infiltrative edges. All tumors showed fibrous and myxoid areas, with lobulated myxoid foci in 5/7, comprising storiform, patternless, or (less often) fascicular arrangement of spindled to stellate cells with bland, slender to ovoid nuclei. In all cases, mitoses were <1/2.4 mm 2 , and necrosis was absent. Capillary "arcades" were seen in 3/7. Margins were positive in 3/6. Immunohistochemistry showed positive epithelial membrane antigen in 4/6 and MUC4 in 5/6. Fluorescence in situ hybridization detected FUS rearrangement in 5/7. Both tumors without FUS rearrangement were also negative for EWSR1 rearrangement. All 5 patients with available follow-up were alive and disease-free 10 to 150 months (median, 57 mo) after diagnosis. However, a review of vulvovaginal/pelvic LGFMS previously reported shows recurrences as late as 45 years after initial diagnosis. Pathologists need to be aware that LGFMS can arise in the vulvovaginal region. Tumor lobulation, capillary arcades, and positive MUC4 are helpful features distinguishing LGFMS from other bland myxoid spindle cell neoplasms in the lower female genital tract. Molecular testing can be useful in challenging cases. Complete excision is feasible for most vulvovaginal LGFMS. Long-term surveillance is required as local and/or distant spread can occur decades after diagnosis., Competing Interests: Conflicts of Interest and Source of Funding: D.B.C.’s work is supported by the Ovarian Cancer Research Alliance (Ann Schreiber Mentored Investigator Award; grant no. 650320). The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Inflammatory myofibroblastic tumor is a distinctive, rarely metastasizing mesenchymal neoplasm composed of fascicles of spindle cells with a prominent inflammatory infiltrate. Roughly 50% of inflammatory myofibroblastic tumors harbor ALK receptor tyrosine kinase gene rearrangements. Such tumors are usually positive for ALK by immunohistochemistry. The molecular pathogenesis of ALK-negative inflammatory myofibroblastic tumors is largely unknown. A recent study identified rearrangements of ROS1 (another tyrosine kinase receptor) in a subset of ALK-negative inflammatory myofibroblastic tumors. Immunohistochemistry for ROS1 has been shown to correlate with ROS1 rearrangement in lung adenocarcinomas. The purpose of this study was to determine whether immunohistochemistry for ROS1 could predict ROS1 rearrangement in inflammatory myofibroblastic tumor. In total, 30 inflammatory myofibroblastic tumors were evaluated, including 21 ALK-positive tumors (10 confirmed to harbor ALK rearrangements, with TPM3, CLTC, RANPB2, and FN1 fusion partners) and 9 ALK-negative tumors (including 2 known to harbor ROS1 rearrangements). Immunohistochemistry was performed on whole tissue sections following pressure cooker antigen retrieval using a rabbit anti-ROS1 monoclonal antibody. The results were scored as 'positive' or 'negative,' and the pattern of staining was recorded. Three ALK-negative inflammatory myofibroblastic tumors (including both tumors with known ROS1 rearrangements) showed immunoreactivity for ROS1, whereas all ALK-positive inflammatory myofibroblastic tumors were negative for ROS1. One ROS1-positive inflammatory myofibroblastic tumor (with YWHAE-ROS1 fusion) showed strong, diffuse cytoplasmic and nuclear staining; one case (with TFG-ROS1 fusion) showed weak, diffuse and dot-like cytoplasmic staining; and one case (fusion partner unknown) showed moderate, diffuse and dot-like cytoplasmic staining. Expression of ROS1 correlates with ROS1 gene rearrangement in inflammatory myofibroblastic tumor. These findings suggest that immunohistochemistry for ROS1 may be useful to support the diagnosis of a subset of inflammatory myofibroblastic tumors and may select some clinically aggressive cases for targeted therapy directed against ROS1.

Soft tissue tumours represent a heterogeneous group of mesenchymal lesions and their classification continues to evolve as a result of incorporating advances in cytogenetic and molecular techniques. In the last decade, traditional diagnostic approaches were supplemented with a significant number of reliable molecular diagnostic tools, detecting tumour type specific genetic alterations. Additionally, the successful application of some of these techniques to formalin fixed, paraffin embedded tissue enabled a broader range of clinical material to be subjected to molecular analysis. However, despite all these remarkable advances, the realisation that some of the genetic abnormalities are not fully histotype specific and that certain gene aberrations can be shared among different sarcoma types, otherwise completely unrelated clinically or immunophenotypically, has introduced some drawbacks in surgical pathology practice. One such common example is the presence of EWSR1 gene rearrangements by fluorescence in situ hybridisation (FISH), a test now preferred over the elaborate RT-PCR testing, in a variety of benign and highly malignant soft tissue tumours, in addition to a subset of carcinomas. Furthermore, the presence of identical gene fusions in completely different sarcoma types (i.e., EWSR1-ATF1, EWSR1-CREB1) or in non-mesenchymal malignancies (epithelial or haematological) has raised skepticism as to their diagnostic utility, and their lack of specificity has been compared to the limitations of other ancillary techniques, in particular immunohistochemistry. This review catalogues the main groups of genes that behave in a promiscuous manner within recurrent fusion events in soft tissue tumours. Although we acknowledge that the present molecular classification of soft tissue tumours is much more complex than two decades ago, when EWSR1 gene rearrangements had been described as the hallmark of Ewing sarcoma, we make the strong argument that with very few exceptions, the prevalence of fusion transcripts in most sarcomas is such that they come to define these entities and can be used as highly specific molecular diagnostic markers in the right clinical and pathological context.

Aims:   Occasional cases of well-differentiated and dedifferentiated liposarcoma (LPS) contain myxoid stroma, leading to confusion with other sarcomas. The aim of this study was to analyse the clinicopathological and genetic features of well-differentiated/dedifferentiated LPS with prominent myxoid stroma., Methods and Results:   Fifty-six cases of LPS (22 well-differentiated; 34 dedifferentiated) with prominent myxoid stroma were evaluated. Most arose in the retroperitoneum, abdominal cavity, or spermatic cord. The mean size was 170 mm. Myxoid LPS-like plexiform vessels were conspicuous in 11 cases of well-differentiated LPS. In 22 cases of dedifferentiated LPS, myxofibrosarcoma-like curvilinear vessels were prominent. In other cases, the myxoid component had variably bland or pleomorphic morphology. By immunohistochemistry, staining for MDM2 was positive in 95% of cases, and CDK4 in 78%. Cytogenetics in 13 cases showed ring and giant marker chromosomes. Fluorescence in-situ hybridization showed amplification of 12q13-15 in six cases evaluated. Of 30 patients with follow-up, all but one had local recurrences (up to four), but only one has so far had distant metastases., Conclusions:   Well-differentiated/dedifferentiated LPS with prominent myxoid stroma can closely resemble other sarcoma types, especially myxoid LPS and myxofibrosarcoma. The clinical presentation (large retroperitoneal or abdominal tumour) is a clue to the correct diagnosis; the degree of nuclear atypia helps to exclude myxoid LPS. Immunohistochemistry for MDM2 and CDK4 and genetic analysis can be useful to confirm the diagnosis., (© 2012 Blackwell Publishing Limited.)

Sclerosing epithelioid fibrosarcoma (SEF) is a rare aggressive fibroblastic neoplasm composed of cords of epithelioid cells embedded in a dense collagenous stroma. The reported immunophenotype of SEF is nonspecific. Some SEF cases show morphologic and molecular overlap with low-grade fibromyxoid sarcoma (LGFMS), suggesting a relationship between these tumor types. MUC4 has recently been identified as a sensitive and specific marker for LGFMS; MUC4 expression was also observed in 2 tumors with hybrid features of SEF and LGFMS. We investigated MUC4 expression in SEF and other epithelioid soft tissue tumors to determine (1) the potential diagnostic utility of MUC4 for SEF and (2) the association between MUC4 expression and FUS rearrangement in SEF. Whole sections of 180 tumors were evaluated: 41 cases of SEF (including 29 "pure" SEF and 12 hybrid LGFMS-SEF), 20 epithelioid sarcomas, 11 clear cell sarcomas, 11 metastatic melanomas, 10 perivascular epithelioid cell tumors, 10 alveolar soft part sarcomas, 10 epithelioid angiosarcomas, 10 epithelioid hemangioendotheliomas, 10 epithelioid gastrointestinal stromal tumors, 10 myoepithelial carcinomas, 17 ossifying fibromyxoid tumors, 10 leiomyosarcomas, and 10 biphasic synovial sarcomas. Immunohistochemical analysis was performed after antigen retrieval using a mouse anti-MUC4 monoclonal antibody. Fluorescence in situ hybridization (FISH) was performed on 33 SEF cases using FUS break-apart probes. A subset of cases was also evaluated for EWSR1 and CREB3L2/L1 rearrangements by FISH. Strong diffuse cytoplasmic staining for MUC4 was observed in 32 of 41 (78%) cases of SEF, including all 12 hybrid tumors. FUS rearrangement was detected in 8 of 21 (38%) MUC4-positive cases of SEF with successful FISH studies. The prevalence of FUS rearrangement was similar in hybrid LGFMS-SEF (2 of 6; 33%) and SEF without an LGFMS component (6 of 15; 40%). FUS rearrangement was not detected in any cases of MUC4-negative SEF. Two hybrid tumors had both EWSR1 and CREB3L1 rearrangements. MUC4 expression was also seen in 9 of 10 (90%) biphasic synovial sarcomas, predominantly in the glandular component. All other tumor types were negative for MUC4, apart from focal reactivity in 5 ossifying fibromyxoid tumors, 2 epithelioid gastrointestinal stromal tumors, and 1 myoepithelial carcinoma. MUC4 is a sensitive and relatively specific marker for SEF among epithelioid soft tissue tumors. MUC4 expression occurs more frequently than FUS rearrangement in SEF. The finding of EWSR1 and CREB3L1 rearrangements in 2 cases of hybrid LGFMS-SEF suggests that SEFs are genetically heterogenous. MUC4-positive SEFs with FUS rearrangement are likely closely related to LGFMS. MUC4-positive SEFs that lack FUS rearrangement may be related to LGFMS but could have alternate fusion partners, including EWSR1. SEF without MUC4 expression may represent a distinct group of tumors. MUC4 expression correlates with glandular epithelial differentiation in biphasic synovial sarcoma and is very limited in other epithelioid soft tissue tumors.

Despite their shared predilection for superficial soft tissue of distal extremities and frequent local recurrences, myxoinflammatory fibroblastic sarcoma (MIFS) and hemosiderotic fibrolipomatous tumor (HFLT) have distinct morphologic appearances. Recent studies have identified an identical t(1;10)(p22;q24) in five cases of MIFS and two of HFLT, as well as common amplifications on 3p11-12. To investigate further their potential relationship and to determine the incidence of t(1;10) in a larger cohort, we subjected seven MIFS, 14 HFLT, and three cases with mixed morphology, to molecular and cytogenetic analysis. Fluorescence in situ hybridization (FISH) analysis for rearrangements of TGFBR3 on 1p22 and of MGEA5 on 10q24 was performed in all cases, whereas the status of VGLL3 gene amplification on 3p12.1 was investigated in 12 cases. Conventional karyotyping was performed in one HFLT and two cases with mixed MIFS/HFLT histology. Overall 83% of cases showed rearrangements in both TGFBR3 and MGEA5. All three cases with mixed features of MIFS and HFLT were positive. Cytogenetic analysis performed in three cases confirmed an unbalanced der(10)t(1;10)(p22;q24). VGLL3 gene amplification was noted in 10/12 cases of both histologies. The high incidence of t(1;10) in MIFS and HFLT reinforces a shared pathogenetic relationship. Furthermore, the co-existence of both components either synchronously or metachronously in a primary or subsequent recurrence, suggest either different morphologic variants or different levels of tumor progression of a single biologic entity. FISH analysis for TGFBR3 and MGEA5 rearrangements can be applied as a reliable diagnostic molecular test when confronted with limited material or a challenging diagnosis., (Copyright © 2011 Wiley-Liss, Inc.)

Low-grade fibromyxoid sarcoma (LGFMS) is a distinctive fibroblastic neoplasm that is characterized by alternating collagenous and myxoid areas, deceptively bland spindle cell morphology, a whorling architecture, and a t(7;16) translocation involving FUS and CREB3L2. Owing to variable morphology and a lack of discriminatory markers, LGFMS can be difficult to distinguish from benign mesenchymal tumors and other low-grade sarcomas. Gene expression profiling has identified differential upregulation of the mucin 4 (MUC4) gene in LGFMS compared with histologically similar tumors. MUC4 is a transmembrane glycoprotein that functions in cell growth signaling pathways; aberrant MUC4 expression has been reported in various carcinomas. We investigated MUC4 protein expression by immunohistochemistry in LGFMS and in other soft tissue tumors to determine the potential diagnostic use of this novel marker. Whole-tissue sections of 309 tumors were evaluated: 49 LGFMSs (all with FUS gene rearrangement confirmed by fluorescence in situ hybridization), 40 soft tissue perineuriomas, 40 myxofibrosarcomas, 20 cellular myxomas, 20 solitary fibrous tumors, 20 low-grade malignant peripheral nerve sheath tumors, 20 cases of desmoid fibromatosis, 20 neurofibromas, 20 schwannomas, 20 monophasic synovial sarcomas, 20 cases of dermatofibrosarcoma protuberans, 10 myxoid liposarcomas, and 10 extraskeletal myxoid chondrosarcomas. The LGFMS cases included 7 with marked hypercellularity, 4 with prominent hemangiopericytoma-like vessels, 3 with giant collagen rosettes, 3 with epithelioid morphology, 2 with focal nuclear pleomorphism, and 2 with areas of sclerosing epithelioid fibrosarcoma. All 49 LGFMS cases (100%) showed cytoplasmic staining for MUC4, which was usually diffuse and intense. All the other tumor types were negative for MUC4, apart from 6 (30%) monophasic synovial sarcomas. In conclusion, MUC4 is a highly sensitive and quite specific immunohistochemical marker for LGFMS, and can be helpful to distinguish this tumor type from histologic mimics.

Myxoinflammatory fibroblastic sarcoma and hemosiderotic fibrolipomatous tumor are rare, slow-growing soft tissue tumors of the distal extremities with recurrent potential. Recent cytogenetic studies have shown a t(1;10)(p22;q24) or der(10)t(1;10) in combination with aberrations of chromosome 3 in a limited number of cases of both entities. Here we report a case of a 42-year-old female with a soft tissue tumor of the ankle showing hybrid morphologic features of myxoinflammatory fibroblastic sarcoma and hemosiderotic fibrolipomatous tumor, a der(10)t(1;10), and abnormalities of chromosome 3. This hybrid lesion provides further evidence for a close relationship between these 2 tumor types.

INI1 (hSNF5/SMARCB1), a member of the SWI/SNF chromatin remodeling complex located on chromosome 22q11.2, is deleted or/or mutated in strictly defined malignant rhabdoid tumors (MRT) of infancy. Recent studies suggest that some epithelioid sarcomas (ES) also show inactivation of INI1. However, very few cases of ES have been studied, and INI1 expression in other epithelioid malignant neoplasms has not been examined systematically. The purpose of this study was to evaluate the immunohistochemical expression of INI1 in ES compared with histologic mimics. We evaluated 350 tumors: 136 ES, including 64 conventional ("distal") ES, 64 proximal-type ES, and 8 with hybrid features of conventional and proximal-type ES; 54 metastatic carcinomas (22 from lung, 6 breast, 6 stomach, 5 colorectum, 5 kidney, 5 prostate, 5 pancreas); 12 metastatic testicular embryonal carcinomas; 20 metastatic melanomas; 20 epithelioid mesotheliomas; 20 epithelioid angiosarcomas; 10 epithelioid hemangioendotheliomas; 24 epithelioid malignant peripheral nerve sheath tumors (MPNST); 22 myoepithelial carcinomas of soft tissue; 7 anaplastic large cell lymphomas; 5 histiocytic sarcomas; and 10 control MRT of infancy (4 brain, 3 liver, 2 soft tissue, 1 kidney). Immunohistochemistry was performed following pressure cooker heat-induced epitope retrieval using monoclonal antibody BAF47 (BD Biosciences). In total, 127 of 136 (93%) ES cases showed complete absence of INI1 expression, including 58 (91%) conventional ES, 61 (95%) proximal-type ES, and all 8 (100%) hybrid ES. Of the non-ES cases, 12 (50%) epithelioid MPNST also showed loss of INI1, as did 2 (9%) myoepithelial carcinomas and all control MRT cases. INI1 expression was intact in all other tumor types examined. In conclusion, similar to MRT of infancy, loss of INI1 expression is characteristic of both conventional and proximal-type ES, being detected in >90% of cases. Moreover, 50% epithelioid MPNST and occasional myoepithelial carcinomas are also negative for INI1. Immunostaining for INI1 can be used to confirm the diagnosis of ES in the appropriate context. Loss of INI1 expression may also be helpful to distinguish epithelioid MPNST from metastatic melanoma in a subset of cases.

Extraskeletal myxoid chondrosarcoma is a rare soft tissue tumor characterized by a nodular growth pattern with eosinophilic cells usually in a reticular pattern and abundant myxoid stroma. In contrast to other myxoid sarcomas, the majority of extraskeletal myxoid chondrosarcomas harbor a balanced translocation, t(9;22)(q22;q12), that fuses EWSR1 with NR4A3 (also known as CHN). Other less common translocations involving NR4A3 have also been described. We examined the diagnostic utility of fluorescence in situ hybridization for extraskeletal myxoid chondrosarcoma using the LSI EWSR1 break-apart probe (Abbott Molecular/Vysis, Des Plaines, IL, USA). Sixteen cases of extraskeletal myxoid chondrosarcoma with formalin-fixed paraffin-embedded tissue available were retrieved (1991-2007). The mean age at time of presentation was 57 years (range, 30-78). The male to female ratio was 7:1. All cases where either consistent with or highly suggestive of the diagnosis, with most of the primary tumors occurring in the thigh, inguinal or gluteal region. Fifteen of 16 cases were analyzable, of which 14 (93%) were positive for the rearrangement of the EWSR1 locus. In this study, the vast majority of extraskeletal myxoid chondrosarcomas are associated with a rearrangement at the EWSR1 locus (22q12). Fluorescence in situ hybridization is useful to support the diagnosis of extraskeletal myxoid chondrosarcomas and may help to differentiate it from mimics such as other myxoid sarcomas, particularly in limited biopsies.

Objectives: Abnormalities of the urachus are rare among children and include a patent tract and cyst formation. These structures can also be affected by infection and abscess development. They are usually diagnosed during infancy and treated by surgical resection. Involvement of this remnant by either benign or malignant tumors is very infrequent. A few cases of mesenchymal tumors, such as desmoid tumor and leiomyoma, involving the urachus have been described in published reports., Methods: We studied an inflammatory myofibroblastic tumor arising from the urachus in a 10-year-old boy. In addition, we reviewed 101 cases of urachal remnants retrieved from the surgical pathology and autopsy files in the Department of Pathology at the Children's Hospital Boston diagnosed in the past 82 years., Results: The urachal inflammatory myofibroblastic tumor showed anaplastic lymphoma kinase (ALK) rearrangement by immunohistochemistry and fluorescence in situ hybridization techniques. No other neoplasms were diagnosed in the analyzed population., Conclusions: We describe an example of inflammatory myofibroblastic tumor involving the urachus. Involvement of the urachus by tumors is rare, but these should be considered in the differential diagnosis of urachal lesions.

Extraskeletal myxoid chondrosarcoma (EMC) is a soft-tissue neoplasm cytogenetically characterized by the translocations t(9;22)(q22;q11-12) or t(9;17)(q22;q11), generating EWS/CHN or RBP56/CHN fusion genes, respectively. In the present study, 18 EMCs were studied both cytogenetically and at the molecular level. Chromosomal aberrations were detected in 16 samples: 13 with involvement of 9q22 and 22q11-12, and three with rearrangements of 9q22 and 17q11. Fifteen cases had an EWS/CHN fusion transcript and three had an RBP56/CHN transcript. The most frequent EWS/CHN transcript (type 1; 10 tumors), involved fusion of EWS exon 12 with CHN exon 3, and the second most common (type 5; two cases) was fusion of EWS exon 13 with CHN exon 3. In all tumors with RBP56/CHN fusion, exon 6 of RBP56 was fused to exon 3 of CHN. By genomic XL PCR and sequence analyses, the breakpoints from 14 cases were mapped in the EWS, RBP56, and CHN genes. In CHN, 12 breakpoints were found in intron 2 and only two in intron 1. In EWS, the breaks occurred in introns 7 (one break), 12 (eight breaks), and 13 (one break), and in RBP56 in intron 6. Repetitive elements such as Alu and LINE sequences seem to have limited, if any, importance in the genesis of EWS/CHN and RBP56/CHN chimeras. Furthermore, there were no chi, chi-like, topoisomerase II, or translin consensus sequences in the introns harboring the translocation breakpoints, nor could the number of topo I sites in EWS, RBP56, and CHN introns explain the uneven distribution of the breakpoints among EWS or CHN introns. Additional genetic events, such as nucleotide insertions, homologies at the junction, deletions, duplications, and inversions, were found to accompany the translocations, indicating that the chromosomal translocations do not require sequence-specific recombinases or extensive homology between the recombined sequences., (Copyright 2002 Wiley-Liss, Inc.)

Tenosynovial giant cell tumor (TGCT) is the most common benign tumor of synovium and tendon sheath. Cytogenetic data indicate that 1p11-13 is the region most frequently involved in structural rearrangements. With the aim of eventually identifying the genes associated with TGCT development, we have investigated 1p11-13 breakpoints using fluorescence in situ hybridization (FISH) analysis, with a panel of yeast artificial chromosome (YAC) probes covering 1p11-21. Twenty-six tumors were analyzed by G-banding, and 24 of these showed a breakpoint in 1p11-13. The cytogenetic findings add to previous observations that, among a variety of translocations involving 1p11-13, chromosome 2 is the most common translocation partner, with a breakpoint in 2q35-37. This aberration was found in eight cases. Other recurrent translocation partners, found in two or three cases, were 5q22-31, 11q11-12, and 8q21-22. Material from 21 tumors was available for FISH analysis, which revealed that the breakpoints clustered to one region spanned by two YAC probes, 914F6 and 885F12 located in 1p13.2, in 18 cases. Bacterial artificial chromosome probes were used to map the recurrent breakpoint on chromosome 2. In four of seven cases there was a breakpoint within the sequence covered by probe 260J21, where the RDC1 gene is located, a gene reported to fuse with HMGIC in lipomas with a 2;12 translocation.

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.

Congenital mesoblastic nephroma (CMN) and infantile fibrosarcoma (IFS) are two pediatric tumors arising in the kidneys and soft tissues of infants, respectively. Recently, a t(12;15)(p13;q25) resulting in ETV6-NTRK3 gene fusion was detected in patients with IFS and in patients with the cellular type of CMN, suggesting a common pathogenetic pathway. We investigated the presence or absence of ETV6 rearrangements and numerical abnormalities of chromosome 11 by using fluorescence in situ hybridization on paraffin-embedded material from five cases of IFS, two of CMN, and one of mixed type (CMN and IFS) found in our files. In three cases of IFS, we found ETV6 gene rearrangement but a normal copy number of chromosome 11. One case each of IFS, the cellular type of CMN, and the mixed type (CMN and IFS) had both abnormalities. In a case of classic CMN, neither trisomy 11 nor gene rearrangement was found. It is possible that trisomy 11 is a later, nonessential event in the pathogenetic process or that this secondary aberration is associated with still-unrecognized clinical or biological characteristics. We confirmed that IFS and the cellular type of CMN are cytogenetically related and can occur synchronously in the same organ.

The current classification of lipomatous neoplasms has been validated by the identification of characteristic cytogenetic and molecular genetic profiles associated with various neoplasms within the family of lipomatous tumors. The review describes characteristic cytogenetic and molecular genetic profiles and discusses their significance. The clinicopathologic features of these tumors, which are described elsewhere, will not be included in this review.

Lipoblastomas are rare soft tissue tumors that occur primarily in young children. They typically contain variably differentiated adipocytes, primitive mesenchymal cells, myxoid matrix, and fibrous trabeculae. Abnormalities in chromosome 8, leading to rearrangements of the PLAG1 gene, were demonstrated recently in four lipoblastomas. In the present report, we determine the frequency of PLAG1 alterations in 16 lipoblastomas from children aged 13 years or younger, and we also evaluate the stages of lipoblastoma differentiation at which PLAG1 genomic alterations are found. Eleven lipoblastomas (69%), including those with either classic or lipoma-like histology, had rearrangements of the 8q12 PLAG1 region. Another three lipoblastomas had polysomy for chromosome 8 in the absence of PLAG1 rearrangement. Only two cases (13%) lacked a chromosome 8 abnormality. Notably, the lipoblastomas with chromosome 8 polysomy had up to five copies of chromosome 8 as an isolated cytogenetic finding in an otherwise diploid cell. We also demonstrate that PLAG1 alterations are found in a spectrum of mesenchymal cell types in lipoblastomas, including lipoblasts, mature adipocytes, primitive mesenchymal cells, and fibroblast-like cells. This finding is consistent with neoplastic origin in a primitive mesenchymal precursor and with variable differentiation to a mature adipocyte end-point. Hence, our studies provide biological validation for the clinical observation that lipoblastomas can evolve into mature, lipoma-like, lesions. They also suggest that PLAG1 dosage alterations caused by polysomy 8 might represent an alternative oncogenic mechanism in lipoblastoma.

Synovial sarcoma is an aggressive soft-tissue tumor that accounts for up to 10% of soft-tissue sarcomas. Cytogenetically, synovial sarcoma is characterized by the t(X;18)(p11;q11), found in more than 95% of the tumors. This translocation results in rearrangements of the SYT gene in 18q11 and one of the SSX1, SSX2, or SSX4 genes in Xp11, creating a SYT/SSX1, SYT/SSX2, or SYT/SSX4 chimeric gene. It has been shown that patients with SYT/SSX1 fusion genes have a shorter metastasis-free survival than do patients with SYT/SSX2. Previous studies have also suggested that clonal evolution may be associated with disease progression. In the present study, RT-PCR analysis showed that all 64 examined synovial sarcomas from 54 patients had SYT-SSX chimeric genes. SYT/SSX1 was found in 40 tumors from 33 patients, SYT/SSX2 in 23 tumors from 20 patients, and SYT/SSX4 in one case. Two patients had variant SYT/SSX2 transcripts, with 57 bp and 141 bp inserts, respectively, between the known SYT and SSX2 sequences. Patients with tumors with SYT/SSX1 fusions had a higher risk of developing metastases compared to those with SYT/SSX2 fusions (P = 0.01). The reciprocal transcripts SSX1/SYT and SSX2/SYT were detected using nested PCR in 11 of the 40 samples with SYT/SSX1 and 5 of the 23 samples with SYT/SSX2, respectively. Among 20 blood samples, SYT/SSX1 and SYT/SSX2 were detected in one sample each. The t(X;18), or variants thereof, was found cytogenetically in all patients but three. Among 32 primary tumors, the t(X;18) or a variant translocation was the sole anomaly in 10. In contrast, of the seven metastatic lesions that were investigated prior to radiotherapy, only one had a t(X;18) as the sole anomaly; all other tumors displayed complex karyotypes. Cytogenetic complexity in primary tumors was, however, not associated with the development of metastases. Tumors with SYT/SSX2 less often (4/12 vs. 7/15) showed complex karyotypes than did tumors with SYT/SSX1, but the difference was not significant. Combining cytogenetic complexity and transcript data, we found that the subgroup of patients with tumors showing simple karyotypes and SYT/SSX2 fusion had the best clinical outcome (2/8 patients developed metastases), and those with tumors showing complex karyotypes together with SYT/SSX1 fusion the worst (6/7 patients developed metastases). This corresponded to 5-year metastasis-free survival rates of 0.58 and 0.0, respectively (P = 0.02)., (Copyright 2001 Wiley-Liss, Inc.)

Whether fibromatoses are neoplastic or reactive lesions has long been controversial and the relationship, if any, between the superficial and deep forms (desmoid tumors) are poorly understood. Clinical, pathologic, and cytogenetic data of 78 cases of fibromatosis were analyzed and correlated with each other. The results demonstrate that clonal chromosome aberrations are a common feature of this entity, being present in 46% of desmoid tumors, although less frequent in the superficial types (10%). In the deep-seated extra-abdominal fibromatoses, trisomies 8 and 20 and loss of 5q material were the only recurrent features. No correlation between +8 and local recurrence was found. Our findings provide additional evidence for the neoplastic nature of fibromatoses.

Atypical lipomatous tumours (ALTs) represent a distinctive subset of mesenchymal neoplasms featuring mature adipocytic differentiation. Most ALTs are characterized cytogenetically by the presence of supernumerary ring and/or long marker chromosomes derived from the chromosomal region 12q13-15. The 12q13-15 chromosome region contains several genes which may play an important role in human tumorigenesis. A series of ALTs was analysed by investigating the MDM2, CDK4, and HMGI-C genes and their proteins. The study was extended to a series of ordinary lipomas, to determine whether the immunohistochemical investigation of these gene products might play any diagnostic role. Cytogenetic analysis revealed the presence of various cytogenetic aberrations involving the 12q13-15 region in 11/18 (61%) lipomas and of ring chromosomes in all ALTs. Overexpression of mdm2 protein was observed in 6/12 (50%) atypical lipomatous tumours. All lipomas were mdm2-negative. cdk4 overexpression was present in 100% of ALTs. Weak cdk4 immunopositivity was detected in 2/18 (11%) ordinary lipomas in a minority of cells. HMGI-C immunopositivity was observed in 10/12 (83%) ALTs. Positive immunoreactivity was also observed in 8/18 (44%) lipomas. Southern blot analysis revealed amplification of the CDK4 and MDM2 genes in 3/5 ALTs analysed. HMGI-C was amplified in 3/5 cases and was deleted in one case. Mutation analysis of the CDK4 gene did not demonstrate any mutation. These data support the hypothesis that ordinary lipomas may form a molecular genetic and morphological continuum with ALT. At one end of the spectrum are lipomas characterized by 12q13-15 rearrangements and HMGI-C activation and at the other end are ALTs with ring chromosomes, 12q13-15 amplification with overrepresentation of the HMGI-C, CDK4 or MDM2 genes, and aberrant cdk4, mdm2, and HMGI-C protein expression. These findings not only provide insights into the molecular pathogenesis of lipomatous tumours, but also indicate that the immunohistochemical analysis of mdm2 and cdk4 may help to increase diagnostic accuracy., (Copyright 2000 John Wiley & Sons, Ltd.)

We observed clonal chromosome abnormalities in two fibrous soft tissue tumors diagnosed as collagenous fibroma (desmoplastic fibroblastoma). The involvement of the same band of the long arm of chromosome 11, 11q12, was observed in both tumors. The presence of hitherto unreported similar chromosomal abnormalities in this tumor supports the neoplastic nature of this lesion. In addition, a possible relationship with fibroma of tendon sheath, which also shows rearrangement of 11q12, is suggested. 11q12 might be a common genetic denominator of benign fibroblastic lesions, such as collagenous fibroma and fibroma of tendon sheath.

Identical near-haploid karyotypes with 28, X, +5, +18, +20, +21, +22 were found in two cases of inflammatory leiomyosarcoma, one of which had been reported previously as malignant fibrous histiocytoma. This abnormality may identify these tumours as a separate entity within this group of sarcomas.

With the aim of identifying objective cytogenetic-morphologic correlations, we evaluated 46 pleomorphic soft tissue sarcomas (mainly diagnosed originally as malignant fibrous histiocytomas) with clonal chromosome aberrations both cytogenetically and morphologically as part of an international collaborative study. By detailed histopathologic examination, most cases could be categorized into specific tumor types. Eight sarcomas were diagnosed as lipogenic (4 pleomorphic, 1 combined pleomorphic and myxoid/round cell, and 3 dedifferentiated liposarcomas), 19 as myogenic [11 leiomyosarcomas, 1 rhabdomyosarcoma, 4 myosarcomas not otherwise specified (NOS), and 3 probable myosarcomas NOS], 8 as myxofibrosarcomas, 1 as a malignant peripheral nerve sheath tumor, 1 as malignant mesenchymoma, 1 as extraskeletal osteosarcoma, I as sarcoma resembling proliferative fasciitis, and 7 as pleomorphic sarcomas NOS. In a three-grade system, 10 tumors were grade 2 and 36 were grade 3. The majority had highly complex karyotypes. A total of 24 recurrent abnormalities (defined by their presence in at least five cases) were detected: ring chromosomes, homogeneously staining regions (hsr) and/or double minute chromosomes (dmin), and structural rearrangement of 22 different chromosome bands or regions. The frequency and distribution of the recurrent karyotypic features were uneven. Grade 3 tumors displayed, on average, more aberrations per case than did grade 2 tumors. Nine of the selected abnormalities, including hsr/dmin and rearrangements of 19p13 and 19q13, were found only among the high-grade tumors. When the tumors were subdivided according to lineage of differentiation, the highest frequency of aberrations was seen in pleomorphic sarcomas NOS, followed by myxofibrosarcomas, myogenic sarcomas, and lipogenic sarcomas. None of the selected rearrangements was, however, specific for any of these subgroups. The sole consistent cytogenetic-morphologic association was that all three dedifferentiated liposarcomas had multiple abnormal clones, at least one of which contained supernumerary ring chromosomes. Due mainly to karyotype complexity, it therefore seems unlikely that cytogenetic analysis can assist in the differential diagnostic subclassification of pleomorphic sarcomas, nor was there any clear-cut indication that the karyotypic picture could be used to predict clinical outcome. Although the mean number of recurrent chromosome aberrations was almost twice as high in sarcomas that gave rise to metastases as among those that did not, no particular aberration was restricted to either of the two subgroups.

Soft tissue lipomatous tumors are morphologically heterogeneous. Various morphologic features are associated with specific chromosomal patterns and clinical features such as age, sex, and tumor site, location, and size. Simple lipomas are known to be karyotypically heterogeneous, but this has not been correlated with clinicopathological features. In 165 cases of solitary soft tissue lipoma, short-term cultures were analyzed cytogenetically. The karyotypes were divided into the following groups: normal karyotype; 12q13-15 aberrations; 6p rearrangements; 13q rearrangements, 8q11-13 aberrations; ring or giant marker chromosomes or both; other aberrations. The tumors were reexamined morphologically without knowledge of the karyotypic or clinical data. An abnormal chromosomal pattern was observed in 129 of 165 cases (78%): in 75 of 90 (83%) lipomas in the extremities and in 43 of 63 (68%) trunk wall lipomas. Chromosomal aberrations were present in 69 of 90 (77%) subcutaneous tumors and in 59 of 64 (80%) deep tumors. A normal karyotype was twice as frequent in tumors in patients under 30 years of age than in those from older individuals (6 of 16 vs. 30 of 149, 40% resp. 20%). Apart from the finding that normal karyotypes were more common in patients younger than 30 years, there was no significant association between cytogenetic pattern and patient sex or age or tumor localization, size, or depth. The pathogenetic basis and clinicopathologic relevance (if any) of the cytogenetic subtypes among benign lipomas remain unexplained.

Recent cytogenetic and molecular genetic investigations in soft tissue tumours have provided us with new insights concerning the mechanisms underlying malignant transformation in mesenchymal tissues. Moreover, some soft tissue tumours now also have a genetic identity, represented by specific chromosome aberrations and by molecular changes related to these chromosome anomalies. Such genomic changes, when evaluated in context with morphology, represent an extremely valuable diagnostic aid to the pathologist. In the future, cytogenetics is bound to play an important diagnostic role, particularly when dealing with lesions showing a borderline morphology as well as with the group of small round cell paediatric malignancies. Moreover, as has been the case for N-myc amplification in neuroblastoma, the existence of a possible prognostic significance of genetic aberrations should be further explored.

Soft tissue tumours represent a heterogeneous group of mesenchymal lesions, and their classification is the subject of continuous debate. Chromosome analysis, molecular cytogenetics and molecular assays may become increasingly useful in diagnosis, and this review summarises advances in the cytogenetic characterisation and classification of soft tissue tumours. Among the group of fibrous lesions, superficial fibromatosis exhibits trisomy 8. This genomic change is also observed in desmoid fibromatosis in association with trisomy 20. Trisomy 11 is the most frequently observed chromosomal aberration in congenital fibrosarcoma. Dermatofibrosarcoma protuberans and giant cell fibroblastoma share a translocation t(17;22), which supports the concept of the existence of a common differentiation pathway. Adipose tissue tumours is the group in which integration of genetics and pathology has been most fruitful. Ordinary lipomas cytogenetically show an abnormal karyotype in about half the cases. Genomic changes of the 11q13 region are observed in hibernoma. Lipoblastoma exhibits a specific 8q rearrangement in 8q11-q13. Loss of material from the region 16q13-qter and 13q deletions are observed in spindle cell/pleomorphic lipomas. The well-differentiated liposarcoma/atypical lipoma group is characterised karyotypically by the presence of one extra ring and/or extra giant chromosome marker. Myxoid and round cell liposarcoma share the same characteristic chromosome change: t(12;16)(q13;p11) in most cases. In the group of smooth muscle lesions most data are derived from uterine leiomyomas, which can be subclassified cytogenetically into seven different types. Half of all leiomyomas are chromosomally normal; the other half have one of six possible consistent chromosome changes. Alveolar rhabdomyosarcoma is characterised cytogenetically by two variant translocations t(2;13)(q35;q14) and t(1;13)(p36;q14). Among tenosynovial tumours, the localised type of giant cell tumour of tendon sheath exhibits two different karyotypic changes. One involves 1p11 in a translocation with chromosome 2 or with another chromosome. A second type involves 16q24. Synovial sarcoma is characterised cytogenetically by a translocation occurring between chromosome 18 and presumably two adjacent loci on the X chromosome. In neural tumours, abnormalities of chromosome 22 have been reported in benign schwannomas and perineuriomas. Malignant peripheral nerve sheath tumours exist in two main forms: sporadic and associated with the NF-1 syndrome. Karyotypes are very complex, but chromosomes 17q and 22q are very often involved. Clear cell sarcoma is characterised cytogenetically and molecularly by a translocation t(12;22)(q13;q12). The Ewing's sarcoma/peripheral neuroectodermal tumour category shows a central karyotypic anomaly represented by the translocation t(11;22). The two variants t(21;22) and t(7;22) are found in some cases. Among cartilaginous lesion, the most frequently described anomaly is the t(9;22)(q22;q12) in extraskeletal myxoid chondrosarcoma. Intra-abdominal desmoplastic small round cell tumour is characterised by a t(11;22)(p13;q12).

The high mobility group proteins (HMGs) are a class of low molecular weight, nonhistone, nuclear proteins that bind DNA and function as transcription cofactors. This class includes the HMGI family members HMGI-C and HMGI(Y). Both are not significantly expressed in differentiated adult tissues, including fat, but their expression is induced in proliferating and transformed cells. Their involvement in the development of lipomatous tumors has been recently demonstrated for HMGI-C, which is encoded by a gene located at 12q15, the chromosomal segment often rearranged in ordinary lipomas. The same chromosomal segment is consistently amplified in the ring and giant marker chromosomes of atypical lipomatous tumors (ALTs), a term used to designate tumors previously labeled as well differentiated liposarcomas or atypical lipomas. The involvement of HMGI(Y) is strongly suspected as the gene coding for HMGI(Y) is located at 6p21, a chromosomal segment rearranged in a subset of ordinary lipomas. HMGI-C or HMGI(Y) protein expression was analyzed immunohistochemically in a group of 39 well differentiated adipose neoplasms (19 lipomas and 20 ALTs) of known karyotype using polyclonal antibodies raised against a recombinant protein (HMGI-C) and against a synthetic peptide (HMGI(Y)). The results of this study demonstrate that HMGI proteins are commonly expressed in well differentiated adipose neoplasms. Seventeen of twenty ALTS (85.0%), all of which had ring or giant marker chromosomes with amplification of 12q13-15, strongly expressed HMGI-C. HMGI-C expression was detected in 7 of 11 ordinary lipomas (63.6%) with alterations at 12q14-15 and in one case with an abnormal karyotype that included double minute chromosomes. HMGI-C immunoreactivity correlates with 12q13-15 chromosomal alterations (P = 0.001). HMGI(Y) reactivity was demonstrated in only two ordinary lipomas: one with 6p21 rearrangement and one with normal karyotype. No significant HMGI(Y) expression was found in the ALT group. The finding of aberrant expression of HMGI proteins in well differentiated adipose neoplasms in association with 12q13-15 and 6p21 chromosomal changes supports the proposed pathogenetic role of this group of proteins in the development of adipose tissue tumors.

Recent cytogenetic and molecular genetic investigations in solid tumors in general, and in soft tissue tumors in particular, have provided us with a wealth of information. We have gained new insights in how tumors may arise, and some soft tissue tumors besides their identification by pathology now also have a genetic identity. This genetic identity is defined by: specific chromosome changes and by molecular changes related to the chromosome anomalies. However, much work remains to be done. In soft tissues as in other solid tumors many tumor types await the first or more extensive chromosome investigation, and in those in which nonrandom, especially simple chromosome changes emerge, molecular studies are to be undertaken starting from the breakpoints. Those tumors that seem to deviate chromosomally or molecularly from the expected, because of already established genetic changes, must be more thoroughly investigated by both pathologists and geneticists. The same accounts for the molecular investigation of chromosomally normal tumors known to show subtypes with specific chromosomal changes: e.g. lipoma, leiomyoma.

Cytogenetic analysis of a soft tissue chondroma revealed monosomy 6 and rearrangement of chromosome 11. Previously described 12q13-q15 involvement was not found. Aberrations of chromosomes 6 and 11, however, have been reported before in this type of benign cartilaginous tumor.

Cytogenetic investigations have already shown the nonrandom involvement of region 1p11-p13 in the localized and diffuse forms of tenosynovial giant cell tumors. We describe a new case of modular tenosynovitis with rearrangement of 16q24. Our findings and the data from the literature strongly indicated band 16q24 as an important new breakpoint for the localized as well as diffuse forms of tenosynovial giant cell tumors.

Soft tissue tumors commonly show cytogenetic abnormalities, some of which are tumor specific. Lipomatous tumors represent the largest category of soft tissue neoplasms, and numerous karyotypic aberrations have been identified. However, clear-cut correlation between morphology and karyotype has not been undertaken on a systematic basis in a double-blind setting. The morphological features and histological diagnosis of 178 lipomatous neoplasms were reviewed independently without knowledge of the clinical data. The consensus diagnoses were then correlated with the clinical findings and compared with the tumors' karyotypes, using G-banded preparations from short-term cultures. The data were collated by a multicenter collaborative group of pathologists, geneticists, and surgeons. Clonal chromosomal abnormalities were identified in 149 cases studied (84%) and, to a large extent, the karyotype correlated with the morphological diagnosis. Specifically, 26 (96%) of 27 myxoid liposarcomas and its poorly differentiated variants showed a t(12;16); 29 (78%) of 37 atypical lipomatous tumors (including 5 dedifferentiated cases) showed ring chromosomes; 74 (80%) of 93 subcutaneous and intramuscular lipomas had karyotypic aberrations affecting mainly 12q, 6p, and 13q; 7 of 8 spindle cell and pleomorphic lipomas had aberrations of 16q; 3 lipoblastomas showed 8q rearrangements; and 2 hibernomas showed 11q abnormalities. We conclude that cytogenetic abnormalities are common in lipomatous tumors, correlate reliably with morphological sub-type in many cases, and can be of diagnostic value in histologically borderline or difficult cases.

Three cases of extraskeletal myxoid chondrosarcoma with typical histologic and ultrastructural features were investigated cytogenetically. All three cases showed a reciprocal chromosome translocation characterized as t(9;22)(q22-31)(q11-12), thus confirming the findings in three previously karyotyped cases of extraskeletal myxoid chondrosarcoma in the literature. These data add significantly to the evidence of t(9;22) being diagnostic for extraskeletal myxoid chondrosarcoma. Other previously published cases with a range of complex karyotypes were less well defined morphologically. In cases with limited diagnostic material this karyotype might facilitate distinction from myxoid liposarcoma, which consistently shows t(12;16). Clear cell sarcoma, Ewing's sarcoma/primitive neuroectodermal tumor, and desmoplastic round cell tumor also show involvement of chromosome 22 with formation of a hybrid gene between the Ewing's sarcoma gene on band q12 and a transcription factor gene. Whether rearrangement of the Ewing's sarcoma gene is also present in extraskeletal myxoid chondrosarcoma is not clear at present. Cloning of the (9;22) translocation might provide important clues to the pathogenesis of this type of chondrosarcoma.

Specific chromosome abnormalities characterize benign and malignant adipose tissue tumors and are of great diagnostic and clinical importance. Lipoblastoma is a rare benign adipose tumor that mimics myxoid liposarcoma histologically. Although only a few lipoblastomas have been investigated cytogenetically, it is increasingly clear that these adipose tissue tumor generally show rearrangements of 8q11-q13 region but lack the t(12;16) that allows these tumors to be distinguished from myxoid liposarcomas.

A typical case of alveolar soft-part sarcoma was examined using ultrastructural, immunohistochemical and cytogenetic methods. Immunohistochemical stains were performed on frozen sections and showed strong desmin expression with the three anti-desmin antibodies used. In addition, the tumour cells were weakly positive for vimentin and myosin. Neural markers were negative. Chromosomal analysis showed consistent involvement of 17q25--an abnormality which has been reported in another alveolar soft-part sarcoma. The histogenesis of alveolar soft-part sarcoma is still debatable but our findings support a myogenic origin. The finding of an apparently identical chromosomal abnormality in two of three thus far examined cases of alveolar soft-part sarcoma is of interest and must await further confirmation, but it may result in the identification of a chromosomal marker for this enigmatic tumour and thus pave the way for further molecular elucidation.

Cytogenetic analysis of a rare adipose tissue tumor, hibernoma, a benign proliferation of the brown fat, is presented for the first time. A complex translocation involving bands 1p36, 2q33, 5q22, and 11q13 was found as the sole chromosome abnormality.

It has been established that nonrandom chromosome rearrangements are characteristic of specific types of neoplasia. We present six new cases of sarcoma that had in common the same chromosome abnormality, i.e., a balanced translocation between chromosomes X and 18, t(X;18)(p11.2;q11.2), and evaluate the 15 cases with this translocation in the literature. The histological diagnosis was synovial sarcoma in 19 cases and malignant fibrous histiocytoma and fibrosarcoma in the remaining two tumors, respectively. The translocation was found in tumors of both the biphasic and monophasic types, as well as in poorly differentiated synovial sarcoma. The two nonsynovial sarcomas with the t(X;18) were described as spindle cell tumors but failed to show the presence of cytokeratins by immunohistochemical stains. Even with the numerous variabilities on which this test depends, the cytogenetic analysis holds great promise as a tool for the diagnosis of synovial sarcoma.

Chromosome analysis of a congenital or infantile fibrosarcoma from the lower left leg of a 3-week-old baby girl showed only numerical changes involving chromosomes 11, 17 and 20. As three more cases with similar combinations of trisomies of the same chromosomes have been described, this report confirms that adult and congenital fibrosarcoma are cytogenetically different and trisomy 11 may be the key-event.

A cytogenetic study of extraskeletal myxoid chondrosarcoma cells revealed a complex t(9;22;15)(q31;q12.2;q25) as a primary chromosome change. A reciprocal translocation involving identical breakpoints on chromosomes #9 and #22 in this tumor has been reported in the literature. We suggest that the breakpoints 9q31 and 22.q12.2 are associated with extraskeletal myxoid chondrosarcoma, a comparatively rare tumor of adulthood.

Cytogenetic studies were performed on a fibrosarcoma of a newborn. Only numerical chromosome changes (+8, +11, +20) were identified in this rare but distinct soft tissue sarcoma that occurs in children less than 5 years old.

A cytogenetic study was performed on short-term cultures from fresh surgical specimens obtained from 41 patients with soft-tissue sarcomas of various histologic origins. The results demonstrated that myxoid liposarcomas (five tumors) were associated with a specific translocation between chromosomes 12 and 16 and that synovial sarcomas (six tumors) were associated with a specific translocation between the X chromosome and chromosome 18. These chromosomal data have been used to differentiate myxoid liposarcoma from other myxoid tumors exhibiting a non-characteristic histologic picture, as well as to ascertain the diagnosis of synovial sarcoma in undifferentiated soft-tissue sarcomas. The results to date indicate that identification of specific chromosomal changes in sarcomas may provide a new diagnostic criterion for these tumors and possibly improve prognostication with regard to survival and response to treatment.