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Myxoid liposarcoma in a 91-year-old patient Sheffield, Brandon S; Nielsen, Torsten O Nov 19, 2013

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CASE REPORT Open AccessMyxoid liposarcoma in a 91-year-old patientBrandon S Sheffield* and Torsten O NielsenAbstractBackground: Myxoid liposarcoma is a mesenchymal malignancy most commonly presenting in young adults. Thistumor is known for its characteristic chromosomal rearrangement at the DDIT3 locus.Results: We report a case of myxoid liposarcoma in a 91-year-old, the oldest known patient with this disease-entity.FISH analysis of the DDIT3 and FUS loci demonstrate the pathognomonic chromosomal alteration in the setting ofpredominantly round cell histology on biopsy, confirmed by RT-PCR.Conclusion: Myxoid liposarcoma affects mostly young adults but can be seen in the elderly population. Molecular andcytogenetic assays are helpful auxiliaries to histology in the setting of unusual histology and clinical presentation.Keywords: Liposarcoma, Myxoid liposarcoma, Round cell liposarcoma, Advanced age, DDIT3, FUS, FISHBackgroundMyxoid liposarcoma, the second-most common subtype ofliposarcoma, accounts for 10% of soft tissue sarcomas [1].Myxoid liposarcoma tends to occur on extremities, withtwo thirds of cases originating in the thigh [2]. This diseaseaffects a younger demographic than most cancers with peakincidence between ages 30–50 [1], and is the most commonsubtype of liposarcoma in the pediatric age group [3].Typical myxoid liposarcoma histology shows nonpleo-morphic ovoid mesenchymal cells and rare lipoblastsamidst a prominent myxoid stroma, with an intricatelyplexiform vasculature. Round-cell liposarcoma, a high-grade form of myxoid liposarcoma, lacks myxoid matrixleaving closely packed, round mesenchymal cells. Regionsof myxoid and round-cell liposarcoma morphologies oftencoexist (MLS/RCLS).Both morphologies share identical cytogenetic aber-rations and are thus considered as a single pathologicentity [1]. A reciprocal translocation t(12;16) can beidentified in the majority of cases [4] creating an in-framefusion of FUS and DDIT3 that is specific for MLS/RCLS[5]. A small proportion of cases harbor an alternatet(12;22) EWS-DDIT3 rearrangement [6]. Demonstrationof disruption at the DDIT3 locus is an effective diagnostictool for MLS/RCLS [7], with break-apart fluorescentin situ hybridization (FISH) probes commercially available.The most powerful prognostic marker in MLS/RCLS isthe presence of a round cell component comprising greaterthan 5% of the tumor. These high grade round cell liposar-caromas have been shown to behave more aggressively withdecreased overall survival and metastasis free survival [8].Compared with other soft tissue sarcomas, MLS/RCLSis particularly sensitive to radiation therapy [9]. Accordingly,neoadjuvant radiation has been recommended in thetreatment of myxoid liposarcoma [10]. This findingplaces increased significance on accurate diagnosis priorto surgical resection.The following report depicts a case of MLS/RCLS ina rare elderly age demographic while highlighting thesalient diagnostic features of this disease, and the valueof molecular testing in the context of unusual clinicalfeatures and histology.Case presentationA 91-year-old male presented to a local emergency depart-ment complaining of a large mass in the medial thigh thathad grown in size over the preceding several weeks. Themass was otherwise asymptomatic.The patient’s past medical history included atrial fibrilla-tion and hypertension, prostate cancer treated by resec-tion with local recurrence treated by radiotherapy 20 yearspreviously, laryngeal cancer treated by radiotherapy 14 yearspreviously, and finally, separate histories of both colon andanal cancer treated with an abdominal-perineal resection6 years previously. The patient reported a family history ofovarian cancer and multiple prostate cancers.CT scan of the pelvis demonstrated a 19 cm lobulatedmass with complex septations and central necrosis inthe adductor compartment of the left thigh (Figure 1).* Correspondence: Brandon.s.Sheffield@gmail.comDepartment of pathology and laboratory medicine, University of BritishColumbia, 899 West 12th Avenue, Vancouver, British Columbia V5Z 1M9, Canada© 2013 Sheffield and Nielsen; licensee BioMed Central Ltd. This is an open access article distributed under the terms of theCreative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use,distribution, and reproduction in any medium, provided the original work is properly cited.Sheffield and Nielsen Molecular Cytogenetics 2013, 6:50http://www.molecularcytogenetics.org/content/6/1/50Core needle biopsy of the mass under ultrasound guid-ance showed high-grade spindled, ovoid and round cellmorphology. Although a small amount of myxoid matrixand complex vasculature were noted, no unequivocallipoblasts were evident and the tumor was considered tolack differentiation towards any specific lineage (Figure 2a).Immunohistochemical workup was nonspecific, withthe tumor showing positive staining for S-100 and weakstaining for CD34 and BCL-2. No immunoreactivity waspresent for melan-A, pankeratin, desmin, smooth-muscleactin, TLE, CD20, CD43, or CD99. Mitotic figures werenumerous and the Ki67 index was high. With no specificdiagnosis evident after this workup, in the context of bluecell histology for a large soft tissue mass, FISH analysiswas performed for DDIT3, FUS¸ and EWSR1. Break-apartprobes for DDIT3 and FUS demonstrated chromosomalrearrangements at both of these loci (Figures 2b, c),while EWSR1 was intact. RT-PCR confirmed expressionof a type 1 FUSexon7-DDIT3exon2 fusion transcript.The RT-PCR was performed according to previouslyestablished protocols [11], using oligonucleotide primersto exon 6 of FUS (5′-gaacccagaggtcgtggag-3′) and exon 2of DDIT3 (5′-tgctttcaggtgtggtgatg-3′).Based on the pathognomonic molecular findings, adiagnosis of MLS/RCLS was made. The patient wasdiscussed at multidisciplinary tumor board, and of-fered neoadjuvant radiation treatment followed bysurgical excision. Both radiation and surgery were well-tolerated. Final pathology showed a 19 cm lobulatedheterogenous yellow and hemorrhagic mass (Figure 3a).Microscopic sections showed a mixture of high-graderound cell areas similar to that seen at biopsy, as well as re-gions showing a more typical myxoid liposarcoma histologythat had not been evident on the core biopsy (Figures 3b, c),providing morphological confirmation of the diagnosis.Figure 1 Abdomino-pelvic CT scan showing tumor in the leftmedial thigh (*).Figure 2 Core needle biopsy of mass. (a) 20× H&E section showing hypercellularity, and lacking any differentiated morphology. (b) and(c) Fluorescent photomicrographs showing biopsied tumor cells hybridized to commercial break-apart probes specific to the DDIT3 (b) andFUS (c) loci. Probes flank targeted gene sequence showing yellow signal when bound in proximity (intact locus) and showing individual redand or green signals when bound in isolation (rearranged locus). EWSR1 (not shown) was conversely intact with two paired (yellow) signalsper nucleus.Sheffield and Nielsen Molecular Cytogenetics 2013, 6:50 Page 2 of 4http://www.molecularcytogenetics.org/content/6/1/50A search of the medical literature was performed forreports of myxoid and/or round cell liposarcoma in theelderly. Moreau et al. [10] recently published a series of418 MLS/RCLS patients, the oldest being 85 years old atpresentation. To our knowledge, the current case repre-sents the oldest reported age for a patient presenting withprimary myxoid or round cell liposarcoma.DiscussionSeveral facets of myxoid liposarcoma diagnosis andtreatment are highlighted in this case. The diagnosis ofmyxoid liposarcoma in an elderly patient is uncommon,but does occur. Thus an advanced age should not ex-clude myxoid liposarcoma when other clinical, radio-logic, histologic, or molecular findings support thisdiagnosis.Myxoid liposarcoma can show a wide variation ofhistologic patterns, at times within the same tumor [12].This can lead to difficult diagnoses, especially on smallbiopsy specimens. This case highlights the value of mo-lecular diagnosis as an adjunct to histology. FISH isavailable in specialty centers, and is available to mostsurgical pathology labs as it can be performed on stand-ard formalin-fixed, paraffin-embedded tissue sections(shipped to central labs if needed). In the current era ofdiagnostics, molecular confirmation of sarcomas isquickly becoming a standard of care for several typesof sarcomas bearing pathognomonic genetic events.The availability of molecular diagnostic tools may, inpart, contribute to the overall improved outcomes ob-served in sarcoma patients treated at higher volumeinstitutions [13].The accurate preoperative diagnosis of myxoid lipo-sarcoma prioritized neoadjuvant radiotherapy as thenext step in management. This treatment modality hasparticular benefit in myxoid liposarcoma [9]. Accuratediagnosis on biopsy in elderly patients may haveadditional value if poor baseline functioning precludesthe patient as a surgical candidate, as palliative radi-ation may be particularly effective after a diagnosis ofmyxoid liposarcoma.ConclusionMyxoid/round cell liposarcoma is a relatively commonsarcoma among younger adults presenting with a large,deep-seated malignant primary soft tissue mass. However,this tumor can affect older individuals. Molecular cyto-genetic studies can greatly assist diagnosis in cases withunusual clinical and histologic features.ConsentWritten informed consent was obtained from the patientfor publication of this case report and any accompanyingimages. A copy of the written consent is available forreview by the Editor-in-Chief of this journal.Competing interestsThe authors declare that they have no competing interest.Authors’ contributionsBSS Assisted in interpreting the diagnostic biopsy, compiled the case report,and wrote the manuscript. TON Issued pathological diagnosis of the biopsyand resection specimens, performed cytogenetic and molecular workup,edited the manuscript, and supervised the project. Both authors read andapproved the final manuscript.AcknowledgementsWe would like to acknowledge Marina Pacheco and Angela Goytain forassistance with the gross photography and molecular testing. Molecularstudies were supported by funding from the Liddy Shriver SarcomaInitiative. We would like to thank the UBC Anatomical Pathology residencyprogram for their continued support.Received: 5 September 2013 Accepted: 23 October 2013Published: 19 November 2013Figure 3 Excision of mass. Gross photo showing 19 cm yellow, hemorrhagic mass (a), featuring regions with typical myxoid liposarcoma,10× H&E (b), and typical chicken-wire vasculature highlighted by CD31 immunohistochemical stain (c).Sheffield and Nielsen Molecular Cytogenetics 2013, 6:50 Page 3 of 4http://www.molecularcytogenetics.org/content/6/1/50References1. Antonescu C, Ladanyi M: Myxoid liposarcoma. In Pathology and genetics oftumours of soft tissue and bone. Edited by Fletcher CDM, Unni KK, Mertens F.Lyon: IARC Press; 2002:40–43 [Kleihues P and Sobin LH (Series Editors):World Health Organization classification of tumors].2. Moore Dalal K, Kattan MW, Antonescu CR, Brennan MF, Singer S: Subtypespecific prognostic nomogram for patients with primary liposarcoma ofthe retroperitoneum, extremity, or trunk. Ann Surg 2006, 44(3):381–391.3. Alaggio R, Coffin CM, Weiss SW, Bridge JA, Issakov J, Oliveira AM, Folpe AL:Liposarcomas in young patients: a study of 82 cases occurring in patientsyounger than 22 years of age. Am J Surg Pathol 2009, 33(5):645–658.4. Sreelantaiah C, Karakousis CP, Leong SPL, Sandberg AA: Cytogeneticfindings in liposarcoma correlate with histopathologic subtypes.Cancer 1991, 69:2484–2495.5. Antonescu CR, Elahi A, Humphrey M, Lui MY, Healey JH, Brennan MF,Woodruff JM, Jhanwar SC, Ladanyi M: Specificity of TLS-CHOP rearrangementfor classic myxoid/round cell liposarcoma. J Mol Diagn 2000, 2:132–138.6. Aman P, Panagopoulos I, Lassen C, Fioretos T, Mencinger M, Toresson H,Hoglund M, Forster A, Rabbits TH, Ron D, Mandahl N, Mitelman F:Expression patterns of the human sarcoma-associated fenes FUS andEWS and the genomic structure of FUS. Genomics 1996, 37:1–8.7. Narendra S, Valente A, Tull J, Zhang S: DDIT3 Gene break-apart as amolecular marker for diagnosis of myxoid liposarcoma- assay validationand clinical experience. Diagn Mol Pathol 2011, 20(4):218–224.8. Antonescu CR, Tschernyavsky SJ, Decuseara R, Leung DH, Woodruff JM,Brennan MF, Bridge JA, Neff JR, Goldblum JR, Ladanyi M: Prognostic impactof p53 status, TLS-CHOP fusion transcript structure, and Histologic gradein myxoid liposarcoma: a molecular and clinicopathologic study of 82cases. Clin Cancer Res 2001, 7:3977–3987.9. Chung PWM, Deheshi BM, Ferguson PC, Wunder JS, Griffin AM, Catton CN,Bell RS, White LM, Kandel Ram O, Sullivan B: Radiositivity translates intoexcellent local control in extremity myxoid liposarcoma. Cancer 2009,115:3254–3261.10. Moreau LC, Turcotte R, Ferguson P, Wunder J, Clarkson P, Masri B, Isler M,Dion N, Werier J, Ghert M, Deheshi B: Myxoid/round cell liposarcoma(MRCLS) revisited: an analysis of 418 primarily managed cases. Ann SurgOncol 2012, 19:1081–1088.11. Powers MP, Wang WL, Hernandez VS, Patel KS, Lev DC, Lazar AJ, Lopez-TerradaDH: Detection of myxoid liposarcoma-associated FUS-DDIT3 rearrangementvariants including a newly identified breakpoint using an optimized RT-PCRassay. Mod Pathol 2010, 23(10):1307–1315.12. Fritchie KJ, Goldblum JR, Tubbs RR, Sun Y, Carver P, Billings SD, Rubin BP:The expanded histologic spectrum of myxoid liposarcoma with an emphasison newly described patterns. Am J Clin Pathol 2012, 137:229–239.13. Gutierrez JC, Perez EA, Livingstone AS, Franceschi D, Koniaris LG: Shouldsoft tissue sarcomas be treated at high-volume centers? An analysis of4205 patients. Ann Surg 2007, 245(6):952–958.doi:10.1186/1755-8166-6-50Cite this article as: Sheffield and Nielsen: Myxoid liposarcoma in a91-year-old patient. Molecular Cytogenetics 2013 6:50.Submit your next manuscript to BioMed Centraland take full advantage of: • Convenient online submission• Thorough peer review• No space constraints or color figure charges• Immediate publication on acceptance• Inclusion in PubMed, CAS, Scopus and Google Scholar• Research which is freely available for redistributionSubmit your manuscript at www.biomedcentral.com/submitSheffield and Nielsen Molecular Cytogenetics 2013, 6:50 Page 4 of 4http://www.molecularcytogenetics.org/content/6/1/50

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