Translocations and Amplifications of Chromosome 12 in Liposarcoma Demonstrated by the LSI CHOP Breakapart Rearrangement Probe

2008 ◽  
Vol 132 (6) ◽  
pp. 952-957
Author(s):  
Carlynn Willmore-Payne ◽  
Joseph Holden ◽  
Kristi C. Turner ◽  
Alan Proia ◽  
Lester J. Layfield
Keyword(s):  
Signal Amplification ◽  
Myxoid Liposarcoma ◽  
Chromosome 12 ◽  
Round Cell ◽  
High Background ◽  
Molecular Abnormalities ◽  
Not Otherwise Specified ◽  
Myxoid Liposarcomas ◽  
Well Differentiated ◽  
Atypical Lipomatous Tumors

Abstract Context.—Liposarcomas display a number of molecular abnormalities involving chromosome 12. Myxoid and round cell liposarcomas are characterized by t(12;16)(q13; p11) or t(12;22)(q13;q12) translocations. Amplifications occur within the 12q13-15 region of atypical lipomatous tumors and well-differentiated liposarcomas but not lipomas. Objective.—To investigate the performance characteristics of the LSI CHOP Breakapart Rearrangement Probe for the diagnosis of myxoid/round cell liposarcomas and atypical lipomas/well-differentiated liposarcomas. Design.—We investigated a series of lipomatous neoplasms (5 lipomas, 5 well-differentiated liposarcomas, 22 myxoid/round cell liposarcomas, 2 liposarcomas not otherwise specified, and 2 dedifferentiated liposarcomas) and normal myometrium for abnormalities in the q13-15 region of chromosome 12. Cases were studied for the presence or absence of t(12;16)(q13;p11) or t(12;22)(q13;q12) translocations by the LSI CHOP Breakapart Rearrangement Probe. These probes contain a sequence encompassing the SAS and CDK4 genes. Four or more copies of this sequence were considered to represent amplification of these genes. Results.—Rearrangement of the CHOP gene was seen in all evaluable myxoid liposarcomas. Rearrangements were seen in 1 dedifferentiated liposarcoma but not in normal myometrium or lipomas. Probe signal amplification was seen in all 5 well-differentiated liposarcomas and 1 myxoid liposarcoma. No signal amplification was seen in lipomas or myometrium. Conclusions.—Demonstration of translocations t(12; 16)(q13;p11) and t(12;22)(q13;q12) by the LSI CHOP Breakapart Rearrangement Probe appears to correlate with round cell/myxoid liposarcoma. The probe also demonstrated amplification of the 12q13-15 region in well-differentiated liposarcomas, making it useful for the diagnosis of these neoplasms. In a significant percentage of cases, high background fluorescence or poor probe staining made interpretation difficult.

scholarly journals Atypical Lipomatous Tumor/Well-Differentiated Liposarcoma with Myxoid Stroma in a Hereditary Retinoblastoma Survivor

2019 ◽  
Vol 6 (2) ◽  
pp. 79-86
Author(s):  
Travis Peck ◽  
Kalla A. Gervasio ◽  
Paul J.L. Zhang ◽  
Carol L. Shields ◽  
Sara E. Lally ◽  
...  
Keyword(s):  
External Beam Radiotherapy ◽  
Molecular Genetic ◽  
Myxoid Liposarcoma ◽  
Atypical Lipomatous Tumor ◽  
Lipomatous Tumor ◽  
Myxoid Stroma ◽  
Molecular Genetic Data ◽  
Mesenchymal Neoplasm ◽  
Myxoid Liposarcomas ◽  
Well Differentiated

Atypical lipomatous tumor/well-differentiated liposarcoma (ALT/WDL) is an indolent, locally aggressive mesenchymal neoplasm, most often confined to the lower extremities and retroperitoneum and rarely identified in the orbit. Diagnosis of ALT/WDL can be challenging due to its frequent morphologic overlap with benign adipose lesions and other more aggressive liposarcoma subtypes, including myxoid liposarcoma. We describe a 26-year-old female with a history of hereditary retinoblastoma and external-beam radiotherapy to the orbit, who developed orbital liposarcoma. Although initial morphologic assessment raised the consideration of myxoid liposarcoma, subsequent fluorescein in situ hybridization studies demonstrated MDM2 and DDIT3 coamplification without DDIT3 rearrangement, supporting the diagnosis of ALT/WDL with myxoid stroma. The literature review of previously reported orbital myxoid liposarcomas revealed a morphologic overlap of documented tumors with ALT/WDL, dedifferentiated liposarcoma, and pleomorphic liposarcoma with myxoid stroma as well as an absence of immunohistochemical and molecular genetic data supportive of the diagnosis of myxoid liposarcoma. This case emphasizes the potential overlap of ALT/WDL with myxoid liposarcoma and the increasing importance of molecular genetic studies in the diagnosis, prognosis, and management of orbital liposarcoma.

scholarly journals Managing Liposarcomas: Cutting Through the Fat

2016 ◽  
Vol 12 (3) ◽  
pp. 221-227 ◽  
Author(s):  
Gulam A. Manji ◽  
Gary K. Schwartz
Keyword(s):  
Treatment Plan ◽  
Soft Tissue Sarcomas ◽  
Definitive Treatment ◽  
Round Cell ◽  
Myxoid Liposarcomas ◽  
Well Differentiated ◽  
Third Line ◽  
Line Setting ◽  
Pleomorphic Liposarcomas ◽  
Histologic Subtypes

Liposarcomas are one of the most common of more than 50 histologic subtypes of soft tissue sarcomas that, themselves, are heterogeneous. Liposarcomas fall into four distinct histologic subtypes: atypical lipomatous tumor/well-differentiated liposarcoma, dedifferentiated liposarcoma, myxoid (round cell) liposarcoma, and pleomorphic liposarcoma. Definitive treatment remains surgical resection with negative margins for resectable disease. However, well-differentiated liposarcomas that are large or difficult to operate upon should be followed with close surveillance as long as there is no radiologic concern for a dedifferentiated component. In contrast, first-line chemotherapy with anthracycline with or without ifosfamide, or gemcitabine and docetaxel should be used for inoperable myxoid (round cell) or pleomorphic liposarcomas, which are relatively responsive to chemotherapy. In the second- and third-line setting, myxoid liposarcomas, in particular, seem to be sensitive to trabectedin, which was recently approved by the US Food and Drug Administration (FDA). Eribulin offered a survival benefit when compared with dacarbazine in the third-line setting in liposarcomas (other than the well-differentiated subtype) and is now FDA approved. Recent studies have identified distinct genetic aberrations that not only aid in the diagnosis of liposarcoma subtypes but represent actionable targets. Cyclin-dependent kinase 4 and murine double minute 2 are overexpressed in well-differentiated and dedifferentiated liposarcomas and offer opportunities that are being pursued in clinical trials. It is critical that liposarcomas are not approached by oncologists as one disease entity but rather subclassified into distinct subtypes using histologic and molecular tools before formalizing a treatment plan.

Automated Bright-Field Dual-Color In Situ Hybridization for MDM2: Interobserver Reproducibility and Correlation With Fluorescence In Situ Hybridization in a Series of Soft Tissue Consults

2016 ◽  
Vol 140 (10) ◽  
pp. 1111-1115 ◽  
Author(s):  
Gloria Zhang ◽  
Christopher P. Lanigan ◽  
John R. Goldblum ◽  
Raymond R. Tubbs ◽  
Erinn Downs-Kelly
Keyword(s):  
In Situ Hybridization ◽  
Fluorescence In Situ Hybridization ◽  
Chromosome 12 ◽  
Interobserver Reproducibility ◽  
Bright Field ◽  
Well Differentiated ◽  
Atypical Lipomatous Tumors ◽  
Mdm2 Amplification ◽  
Lipomatous Tumors

Context.—Atypical lipomatous tumors/well-differentiated liposarcomas contain alterations in the 12q13-15 region resulting in amplification of MDM2 and nearby genes. Identifying MDM2 amplification is a useful ancillary test, as the histologic mimics of atypical lipomatous tumors/well-differentiated liposarcomas have consistently shown a lack of MDM2 amplification. Objective.—To assess the interobserver reproducibility of a bright-field assay for MDM2 amplification (dual-color, dual-hapten in situ hybridization [DDISH]) among reviewers with varying degrees of experience with the assay and to assess the concordance of MDM2 DDISH with MDM2 fluorescence in situ hybridization (FISH). Design.—In total, 102 cases were assessed in parallel for MDM2 by FISH and DDISH. MDM2 amplification was defined as an MDM2 to chromosome 12 ratio of 2.0 or greater, whereas an MDM2 to chromosome 12 ratio of less than 2 was nonamplified. Fluorescence in situ hybridization was scored in the routine clinical laboratory and DDISH was evaluated by 3 different pathologists blinded to the final diagnosis and FISH results. Results.—Fluorescence in situ hybridization categorized 27 cases (26%) as MDM2 amplified and 75 cases (74%) as nonamplified; the consensus DDISH diagnosis was 98% concordant with FISH. Agreement between MDM2 DDISH by each reviewer and MDM2 FISH was highly concordant (99%, 98%, and 98%, respectively, for reviewers 1, 2 and 3). The κ agreement of the 3 reviewers scoring DDISH was excellent (κ = 0.949, 0.95, and 0.95, respectively, for reviewers 1, 2, and 3). Conclusions.—This study highlights excellent concordance between DDISH and FISH in MDM2 copy number assessment. Moreover, excellent interobserver reproducibility of the DDISH assay was found among reviewers with varying levels of experience evaluating bright-field assays.

scholarly journals Myxoid liposarcoma of small bowel presenting with intussusception and obstruction: A case report

2022 ◽  
pp. 519-521
Author(s):  
Mohd Monis ◽  
Divyashree Koppal ◽  
Aiman Ibbrahim ◽  
Zeeshan Nahid
Keyword(s):  
Small Bowel ◽  
Intestinal Obstruction ◽  
Leading Edge ◽  
Surgical Excision ◽  
Myxoid Liposarcoma ◽  
Histopathological Analysis ◽  
Contrast Enhanced ◽  
Well Differentiated ◽  
Enhanced Computed Tomography

Gastrointestinal liposarcomas are extremely rare with the most common reported morphological subtype being dedifferentiated liposarcoma and well-differentiated liposarcoma. These tumors are rarely diagnosed preoperatively and diagnosis is only confirmed on histopathological analysis. Treatment of gastrointestinal liposarcomas consists of surgical excision with widely negative margins followed by post-operative irradiation and close follow-up. We report an exceedingly rare case of myxoid liposarcoma of the small bowel (ileum) presenting with an unusual presentation with intussusception and intestinal obstruction. A 42-year-old male presented to the emergency department with features of intestinal obstruction. Contrast-enhanced computed tomography abdomen revealed ileo-ileal intussusception with an endoluminal soft-tissue lesion at the leading edge. The patient was taken for surgical intervention and the involved segment of the bowel along with the lesion was resected and re-anastomosis done. Histological sections of the mass along with immunohistochemistry suggested the pathological diagnosis of myxoid liposarcoma.

Limited Role of TP53 and TP53-Related Genes in Myxoid Liposarcoma

1998 ◽  
Vol 84 (5) ◽  
pp. 571-577 ◽  
Author(s):  
Silvana Pilotti ◽  
Cinzia Lavarino ◽  
Alessandra Mezzelani ◽  
Gabriella Della Torre ◽  
Fabiola Minoletti ◽  
...  
Keyword(s):  
Tumor Progression ◽  
Chromosomal Translocation ◽  
Myxoid Liposarcoma ◽  
P53 Mutation ◽  
Unexpected Finding ◽  
Genetic Changes ◽  
Molecular Features ◽  
Well Differentiated ◽  
Pleomorphic Liposarcomas

Aims Circumstantial evidence suggests that genetic changes may lead to tumor progression within the myxoid liposarcoma tumors (MLTs) carrying non-random chromosomal translocation t(12;16). Methods To address this subject an immunophenotypic analysis, applying antibodies against proteins encoded by TP53, MDM2 and CDK4 genes, complemented by molecular analysis of eight suitable cases, was performed on 104 consecutive cases. Chromosomal translocations were assessed either by cytogenetic analysis or by RT-PCR in 9 suitable cases and chimeric transcripts were found in all cases but two pleomorphic liposarcomas. Results Based on immunophenotyping and tumor site, the case material consisted of three groups. The first one was made up of 92 non-retroperitoneal cases carrying a null p53, mdm2, cdk4 immunophenotype, which remained unchanged over the time of recurrences and along the gamut of histologic subtypes. The second group was represented by five p53+, mdm2-, cdk4- non-retroperitoneal cases, 4 of which were further analysed by PCR-SSCP for p53 mutation. The im-munophenotipic profile of these cases, complemented by the molecular findings, supported a role of TP53 in tumor progression in three high-grade MLTs. The third group, consisting of 7 retroperitoneal cases, showed a heterogeneous immunophenotype, sharing immunophenotypic and molecular features with the well-differentiated/evoluted (dedifferentiated) liposarcoma group. Conclusions TP53 mutations seem to play a role in tumor progression in a few cases of MLTs (2.8%) showing more aggressive histologic characteristics. The unexpected finding that a number of retroperitoneal LMTs display the immunophenotypic profile of the well differentiated/evoluted (dedifferentiated) liposarcomas, deserves further investigation.

Patterns of tumor response to trabectedin (ET743) in myxoid liposarcomas

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 9511-9511 ◽  
Author(s):  
F. Grosso ◽  
G. D. Demetri ◽  
J. Y. Blay ◽  
I. Judson ◽  
A. Le Cesne ◽  
...  
Keyword(s):  
Tumor Response ◽  
Chromosomal Translocation ◽  
Myxoid Liposarcoma ◽  
Treatment Interruption ◽  
Tumor Shrinkage ◽  
Minor Response ◽  
Myxoid Liposarcomas ◽  
The Moment ◽  
A Minor ◽  
Tissue Alterations

9511 Background: Trabectedin (T) is a marine-derived agent found to be active in ovarian cancer and sarcomas. Among sarcomas, activity has been notable in leiomyosarcomas and liposarcomas. Since liposarcomas are a heterogeneous group, including well/de-differentiated, pleomorphic, and myxoid/round cell subtypes, we have noted particularly interesting patterns of responsiveness to T in myxoid liposarcomas, which are associated with t(12;16)(q13;p11) or t(12;22)(q13;q12) chromosomal translocations, resulting in CHOP-TLS or CHOP-EWS fusion products. Methods: 15 cases of myxoid liposarcomas treated with T at the Istituto Nazionale Tumori, Milan, were retrospectively reviewed. In most cases, T was given as a 24-hr continuous infusion every 21 days, at dose levels from 1.0 to 1.5 mg/sqm. 108 courses were delivered, with a median of 5 courses per patient (range 2–20). Observations made in this series were shared with five other institutions having treated myxoid liposarcoma cases with T, all of which also report a significant response rate, for a total of 44 pts. A centralized radiological review of all pts is ongoing. Results: In the Milan series, early tissue alterations in tumors were observed in 14 patients, mainly with a decrease in tumor density on CT scan and/or decrease in contrast enhancement on MRI. These changes were followed by tumor shrinkage amounting to a conventional PR/CR in 8 (pending final review), while 3 others have responses which continue to evolve. Progression followed treatment interruption in one patient, with a minor response occurring at treatment restart. Treatment is continuing in 12 pts (median duration of therapy in excess of 5 months). Further results of the central radiological review from all centres will be reported. Conclusions: Tumor response to T seen in myxoid liposarcoma appears to be marked by early radiological alterations in tumor tissue, often preceding tumor shrinkage, which may be delayed. A selective mechanism of action for this chromosomal translocation-related sarcoma is suggested, and is being actively investigated at the moment. [Table: see text]

Rechallenge with trabectedin in patients with locally advanced or metastatic soft tissue sarcoma following drug holiday: The experience of the French Sarcoma Group (FSG).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 10062-10062 ◽  
Author(s):  
Esma Saada ◽  
Chahineze Rahal ◽  
Isabelle Ray Coquard ◽  
Antoine Italiano ◽  
Christine Chevreau ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Objective Response ◽  
Locally Advanced ◽  
Soft Tissue Sarcomas ◽  
Myxoid Liposarcoma ◽  
Median Number ◽  
Drug Holiday ◽  
Who Grade ◽  
Well Differentiated ◽  
Number Of Cycles

10062 Background: Trabectedin (T) is a marine-derived alkaloid used to treat advanced soft tissue sarcomas (STS) after ifosfamide and/or anthracyclins failure. Since then, the FSG evaluated the clinical benefit in re-administrating T after an initial hold, either medically indicated or upon patient’s request. Methods: Following an online request, clinical and histopathological data were collected from six centers of the FSG who declared to have rechallenged patients. Baseline data were collected and analyze will be used. Results: From 1999 to 2011, 49 pts with T drug holiday have been identified (26 male/ 23 female), with a median age of 50 y [23-75]. Most frequent histotypes were: myxoid liposarcoma (18, 36.7%), leiomyosarcomas (13, 26.5 %) and well-differentiated/dedifferentiated liposarcoma (9, 18%). WHO grade were 1 in 14 (29%), 2 in 19 (39%) and 3 in 5 (10%) pts respectively. Patients who had a maximum of 2, 3 or 4 therapeutic sequences (TS) with T (drug-holiday and rechallenge) were 41/49 ,7/49 and 1/49 respectively. Median number of cycles for 1, 2, 3 and 4 TS were 7 [3-21], 6 [2-30], 6 [2-9] and 6. Median total number of cycles was 15 [6-43]. Median duration of drug-holiday for 1, 2 and 3 TS were 11 [3-91], 7 [2-29] and 4 months [1-5]. Grade 3-4 toxicities incidence decreased with the number of TS (occurred in 36%, 29%, 14% and 0% of pts with 1, 2, 3 and 4 TS) as well as mean T dose per cycle (1.3 mg/m², 1.2 mg/m², 1.1 mg/m² and 1.1 mg/m² for TS 1, 2, 3, 4). Efficacy decreased with number of TS (Number of CR/PR/SD/PD were 1 (2%)/15 (31%)/33 (67%)/0 for TS1; 0/4 (8%)/29 (59%)/16 (3%) for TS2; 0/1 (14%)/2 (29%)/4 (57%) for TS3 and 0/0/0/1(100%) for TS4). Median overall survival was 5.0 y [2.7-7.3] since T introduction, and 1.5 y [0.1-4.8], 0.8 y [0.5-1.3] and 0.6 y following 2nd, 3rd and 4th T reintroduction respectively. Objective response after TS2 were seen in 4 cases of grade 1 sarcomas. Conclusions: Due to the lack of cumulative toxicities over time with T, its rechallenging in responding patients to T (no progression under T) have to be considered in advanced STS.

scholarly journals Myxoid liposarcoma and round cell liposarcoma-Cytological and morphometric study.

1999 ◽  
Vol 38 (6) ◽  
pp. 504-510
Author(s):  
Tomoko SHIMADA ◽  
Mikiko ISHII ◽  
Junichi KAWANO ◽  
Tohru AKAMINE ◽  
Takashi KOJIMA ◽  
...  
Keyword(s):  
Myxoid Liposarcoma ◽  
Morphometric Study ◽  
Round Cell

scholarly journals Clinical and Molecular Spectrum of Liposarcoma

2018 ◽  
Vol 36 (2) ◽  
pp. 151-159 ◽  
Author(s):  
Alex Thomas John Lee ◽  
Khin Thway ◽  
Paul H. Huang ◽  
Robin Lewis Jones
Keyword(s):  
Malignant Tumors ◽  
Treatment Options ◽  
Chromosomal Translocation ◽  
Myxoid Liposarcoma ◽  
Adipocytic Differentiation ◽  
Well Differentiated ◽  
Pharmaceutical Agents ◽  
Active Investigation ◽  
Treatment Sensitivity

Liposarcomas are rare malignant tumors of adipocytic differentiation. The classification of liposarcomas into four principal subtypes reflects the distinct clinical behavior, treatment sensitivity, and underlying biology encompassed by these diseases. Increasingly, clinical management decisions and the development of investigational therapeutics are informed by an improved understanding of subtype-specific molecular pathology. Well-differentiated liposarcoma is the most common subtype and is associated with indolent behavior, local recurrence, and insensitivity to radiotherapy and chemotherapy. Dedifferentiated liposarcoma represents focal progression of well-differentiated disease into a more aggressive, metastasizing, and fatal malignancy. Both of these subtypes are characterized by recurrent amplifications within chromosome 12, resulting in the overexpression of disease-driving genes that have been the focus of therapeutic targeting. Myxoid liposarcoma is characterized by a pathognomonic chromosomal translocation that results in an oncogenic fusion protein, whereas pleomorphic liposarcoma is a karyotypically complex and especially poor-prognosis subtype that accounts for less than 10% of liposarcoma diagnoses. A range of novel pharmaceutical agents that aim to target liposarcoma-specific biology are under active investigation and offer hope of adding to the limited available treatment options for recurrent or inoperable disease.

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