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Myxoid liposarcoma occurs predominantly in the deep soft tissues of the extremities, and tends to metastasize to a wide range of soft tissue or bone locations. We report a case of myxoid liposarcoma arising in the ankle of a 19-year-old man. A diagnosis of myxoid liposarcoma was made by open biopsy, and a wide resection requiring plastic surgical reconstruction was performed. Cytogenetic analysis of the resected tumor exhibited a reciprocal translocation t(12;16)(q13;p11) as the sole anomaly, which is found in more than 90% of myxoid liposarcoma cases. The patient had no evidence of local recurrence or metastasis within 7 years of follow-up. Although myxoid liposarcoma is rare in the ankle, it should be considered in the differential diagnosis of a painless soft tissue mass in this region., (Copyright © 2012 American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Elastofibroma typically occurs in the subscapular region of elderly individuals and has a high incidence in Kyushu and the surrounding islands in southern Japan. The treatment of this lesion is somewhat controversial., Patients and Methods: Eleven patients with a diagnosis of elastofibroma dorsi were identified from the unit's database. The clinical presentation, diagnosis, and treatment options were evaluated., Results: There were 6 men and 5 women, with a mean age of 66.7 years (range, 49-82 years). Bilateral lesions were found in 2 patients. The mean lesion size was 6.6 cm in greatest dimension (range, 5-9 cm). The mean follow-up of both surgically and conservatively managed patients was 16.4 months (range, 2-69 months). All were diagnosed by magnetic resonance imaging, and early in the series, 1 also underwent an open biopsy to confirm the diagnosis. Five patients underwent marginal excision of the lesion. No recurrence was observed at last follow-up., Conclusions: Magnetic resonance imaging can be used as a first-line investigation of the lesion, and biopsy is not necessary in most cases. We suggest that a conservative "wait-and-watch" attitude is reasonable and may be considered even when patients are symptomatic., (Copyright © 2012 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Mosby, Inc. All rights reserved.)

Background: Pleomorphic malignant fibrous histiocytoma (MFH) is one of the most frequent malignant soft tissue tumors in adults. Despite the considerable amount of research on MFH cell lines, their characterization at a molecular cytogenetic level has not been extensively analyzed., Methods and Results: We established a new permanent human cell line, FU-MFH-2, from a metastatic pleomorphic MFH of a 72-year-old Japanese man, and applied multicolor fluorescence in situ hybridization (M-FISH), Urovysion™ FISH, and comparative genomic hybridization (CGH) for the characterization of chromosomal aberrations. FU-MFH-2 cells were spindle or polygonal in shape with oval nuclei, and were successfully maintained in vitro for over 80 passages. The histological features of heterotransplanted tumors in severe combined immunodeficiency mice were essentially the same as those of the original tumor. Cytogenetic and M-FISH analyses displayed a hypotriploid karyotype with numerous structural aberrations. Urovysion™ FISH revealed a homozygous deletion of the p16INK4A locus on chromosome band 9p21. CGH analysis showed a high-level amplification of 9q31-q34, gains of 1p12-p34.3, 2p21, 2q11.2-q21, 3p, 4p, 6q22-qter, 8p11.2, 8q11.2-q21.1, 9q21-qter, 11q13, 12q24, 15q21-qter, 16p13, 17, 20, and X, and losses of 1q43-qter, 4q32-qter, 5q14-q23, 7q32-qter, 8p21-pter, 8q23, 9p21-pter, 10p11.2-p13, and 10q11.2-q22., Conclusion: The FU-MFH-2 cell line will be a particularly useful model for studying molecular pathogenesis of human pleomorphic MFH.

There is no established optimum treatment for malignant fibrous histiocytoma (MFH) at present, and few MFH cell lines are established. In the present study, we established new MFH cell lines, KHZ-MFH and SFT85-03, and investigated the JAK/STAT (Janus kinase/signal transducer and activator of transcription) signaling pathway. We found that MFH cells secreted high levels of IL-6 and that STAT3 was constitutively activated in these cells. The JAK2 kinase inhibitor, tyrphostin AG490, suppressed the growth of MFH cells and inhibited the secretion of IL-6. Furthermore, blockade of activated STAT3 by forced expression of a cytokine signaling repressor, SOCS3 gene as well as a dominant-negative STAT3 in these cells significantly suppressed their growth. These results indicated that an autocrine mechanism of the JAK/STAT3 signaling pathway could promote the growth of MFH cells and that this pathway could be a therapeutic target of MFH.

A small number of human epithelioid sarcoma cell lines have been reported, but their characterization at a molecular cytogenetic level is not well known. In this study, a new permanent human cell line, FU-EPS-1, derived from a metastatic epithelioid sarcoma developing in the axillary lymph node of a 21-year-old man is described. This cell line was characterized by use of immunocytochemistry, conventional G-banding analysis, spectral karyotyping (SKY) and comparative genomic hybridization (CGH). FU-EPS-1 cells were round, polygonal or spindle shaped with an abundant cytoplasm, and have been maintained continuously in vitro for over 100 passages during more than 15 months. Histologic features of the heterotransplanted tumors in severe combined immunodeficiency mice were essentially the same as those of the original tumor, revealing a multinodular proliferation of eosinophilic epithelioid and spindle cells. Both in vitro and in vivo, the cells were immunopositive for cytokeratins (AE1/AE3 and CAM5.2), epithelial membrane antigen, vimentin and CD34, but were negative for desmin, S-100 protein, CD31 or factor VIII-related antigen. By G-banding and SKY analyses, FU-EPS-1 revealed a hyperdiploid karyotype with the following chromosomal abnormalities: +i(5)(p10), -8, +13, der(13)t(8;13)(q?;p11), +der(19)t(9;19)(?;?) and del(22)(q13). In addition, CGH analysis identified gains of 5p, 9q, 19q and 22q and a loss of 8p. This study demonstrates the value of molecular cytogenetic techniques such as SKY and CGH in defining genomic alterations in greater detail. The FU-EPS-1 cell line will be exceedingly useful for biologic and molecular pathogenetic studies of human epithelioid sarcoma.

Undifferentiated (embryonal) sarcoma of the liver (UESL) is a rare pediatric liver malignancy that is extremely uncommon in middle-aged individuals. We studied 2 cases of UESL in middle-aged adults (1 case in a 49-year-old woman and the other in a 62-year-old man) by histology, immunohistochemistry, and electron microscopy to clarify the cellular characteristics of this peculiar tumor. One tumor showed a mixture of spindle cells, polygonal cells, and multinucleated giant cells within a myxoid matrix and also revealed focal areas of a storiform pattern in a metastatic lesion. The other tumor was composed mainly of anaplastic large cells admixed with few fibrous or spindle-shaped components and many multinucleated giant cells. In both cases, some tumor cells contained eosinophilic hyaline globules that were diastase resistant and periodic acid-Schiff positive. Immunohistochemically, the tumor cells showed positive staining for smooth muscle markers, such as desmin, alpha-smooth muscle actin, and muscle-specific actin, and also for histiocytic markers, such as alpha-1-antitrypsin, alpha-1-antichymotrypsin, and CD68. Electron microscope examination revealed thin myofilaments with focal densities and intermediate filaments in the cytoplasm of tumor cells. Our studies suggest that UESL exhibits at least a partial smooth muscle phenotype in middle-aged adults, and this specific differentiation may be more common in this age group than in children. Tumor cells of UESL with smooth muscle differentiation in middle-aged adults show phenotypic diversity comparable to those of malignant fibrous histiocytoma with myofibroblastic differentiation., (Copyright 2003 Elsevier Inc.)

Elastofibroma is a rare, benign, slow-growing degenerative pseudotumor that typically occurs in the subscapular region and has been considered a peculiar fibroblastic proliferation with accumulation of abnormal elastic fibers. Very little is known about the cytogenetic and molecular genetic changes in elastofibroma. In the present study, we analyzed DNA copy number changes in 27 elastofibromas by comparative genomic hybridization. DNA was extracted from 22 archival paraffin-embedded tumor tissues and from 5 fresh frozen samples. Nine (33%) of the 27 cases exhibited DNA copy number changes involving one or two chromosomes, whereas the remaining 18 cases exhibited no DNA copy number changes. The majority of the changes were gains (8 cases), whereas 2 cases showed losses. The most common recurrent gains were at chromosomal locations Xq12-q22 (6 cases) and 19 (2 cases). High-level amplifications and recurrent losses were not observed. There was no correlation between DNA copy number changes and the pseudotumor size. The present study has identified a chromosomal region that may contain genes involved in the development of at least some elastofibromas.

A consistent, pathognomonic translocation, most commonly a balanced reciprocal translocation, t(X;18) (p11.2;q11.2), is found in more than 90% of synovial sarcomas. We report here a secondary chromosome change, der(22)t(17;22)(q12;q12), in addition to the primary t(X;18)(p11.2;q11.2) in a biphasic synovial sarcoma that occurred in the thigh of a 34-year-old woman. Although the karyotype of the primary tumor exhibited 46,X,t(X;18)(p11.2;q11.2), the recurrent tumor showed 46,X,der(X)t(X;18)(p11.2;q11.2),der(22) t(17;22)(q12;q12). The SYT-SSX1 fusion transcript was demonstrated in the primary and recurrent tumors using a reverse transcriptase polymerase chain reaction (RT-PCR). Southern blot analysis also confirmed that the detected messages were derived from the SYT-SSX fusion gene. However, we could not detect the EWS-E1AF fusion gene that has been reported to be generated through a t(17;22)(q12;q12) by RT-PCR. Furthermore, fluorescence in situ hybridization (FISH) with cosmid probes corresponding to loci flanking the EWSR1 region demonstrated no split of chromosome 22 in all analyzed interphase nuclei. To our knowledge, this is the first reported case of synovial sarcoma in which an additional (secondary) chromosome change, der(22)t(17;22)(q12;q12), has been demonstrated.

Only a small number of human synovial sarcoma cell lines have been reported, and of those, not all have been fully characterized, especially at the molecular level. We describe here the establishment and characterization of a new human cell line, FU-SY-1, which originated from a monophasic fibrous synovial sarcoma arising in the supinator muscle of a 31-year-old woman. This cell line propagated continuously in vitro for 73 serial passages for more than 36 months. FU-SY-1 cells in vitro were rather small, exhibited a spindle or polygonal shape without conspicuous pleomorphism, and expressed c-Met and hepatocyte growth factor (HGF) as determined by immunocytochemistry. Cytogenetically, FU-SY-1 cells maintained a consistent karyotype: 47, X, +7, t(X;18)(p11.2;q11.2), the same as that of the original tumor specimen. Reverse transcriptase-polymerase chain reaction (RT-PCR) demonstrated a SYT-SSX fusion transcript and expression of c-Met and HGF mRNA in FU-SY-1 cells. A subsequent sequence analysis using the PCR products confirmed that the detected messages were derived from the SYT-SSX1 fusion gene. This cell line, FU-SY-1, established from a monophasic fibrous synovial sarcoma, may therefore be a useful tool for investigation of the mechanisms of tumorigenesis and progression in human synovial sarcomas.

Ossifying fibromyxoid tumor (OFMT) of soft parts is a recently described, rare but morphologically distinctive soft tissue tumor. The histogenesis of this lesion remains uncertain, although several immunohistochemical and ultrastructural features suggest that it is an unusual neural tumor, possibly of Schwann cell origin. We report here a case of a malignant variant of OFMT that occurred in the foot of a 52-year-old man. The karyotype of a pulmonary metastasis exhibited the following complex numeric and structural aberrations:72 approximately 74,XXY,-5,+6,+del(8)(p21),del(9)(p22),+10,der(11)t(3;11)(p21;p15),del(12) (q13),der(13)t(5;13)(q13;q34),+18,+19,+20,-22 [cp10]. A kidney metastasis exhibited the following karyotypic abnormalities: 46,XY,add(3)(p11),+der(3)t(3;?;11)(3qter-->3p11::?::11q13-->11qter), -5,del(8)(p21),add(9)(q22),del(9)(p22),der(11)t(3;11)(p21;p15),del(12)(q13),+der(13)t(5;13) (q13;q34),-22. To our knowledge, this is the first reported case of OFMT in which clonal chromosomal aberrations have been shown.

Histopathological differentiation between dermatofibrosarcoma protuberans (DFSP) and dermatofibroma (DF) is often difficult, because both neoplasms share some clinical features and the presence of a storiform pattern. In the present study, we investigated the usefulness of comparative genomic hybridization (CGH) in the diagnosis of these entities by examining 12 DFSP and 12 DF cases. The most frequent DNA sequence copy number changes detected in 10 (83%) of 12 DFSP cases (mean, 1.9 aberrations/tumor; range, 0-3) consisted of gains of 17q22-qter (10 tumors), 22q13 (nine tumors), and 8q24.1-qter (three tumors). High-level amplification, which was detected in three tumors, was seen only in chromosome 17, with 17q23-q25 as the minimal common region. Loss of DNA sequences was not found in DFSP cases. In contrast, two (17%) of the 12 DF cases (mean, 0.5 aberrations/tumor; range, 0-4) showed DNA sequence copy number changes, although recurrent gains and losses and high-level amplifications were not observed. Gains were more common than losses in DF. Overrepresentation of 17q and 22q sequences was a common finding in DFSP but not in DF. Thus, CGH seems to be useful for distinguishing DFSP from DF in most cases.