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Ronald de Vreeze, research physician Daphne de Jong Petra Nederlof Henrique Ruijter Rick Haas

Multifocal myxoid liposarcoma, metastasis or second primary tumor? A molecular biological analysis. Ronald de Vreeze, research physician Daphne de Jong Petra Nederlof Henrique Ruijter Rick Haas Frits van Coevorden. Introduction. Multifocality 1% soft tissue sarcomas

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Ronald de Vreeze, research physician Daphne de Jong Petra Nederlof Henrique Ruijter Rick Haas

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  1. Multifocal myxoid liposarcoma, metastasis or second primary tumor? A molecular biological analysis. • Ronald de Vreeze, research physician • Daphne de Jong • Petra Nederlof • Henrique Ruijter • Rick Haas • Frits van Coevorden

  2. Introduction • Multifocality 1% soft tissue sarcomas • Liposarcoma 20% of all malignancies in adults • The multifocal (lipo)sarcoma = Myxoid round cell liposarcoma Introduction

  3. Definition • Multifocal (myxoid lipo)sarcoma: • The presence of sarcoma at two separate sites, before the manifestation of disease in sites where sarcomas most commonly metastasizes, in particular the lungs Introduction

  4. Purpose • Molecular biological differentiation between metastasis and 2nd primary tumors • In case of 2nd primary: • Optimal local treatment: Radiotherapy • Surgery • In case of metastasis: • Systemic treatment : Chemotherapy • Marginal resection Introduction

  5. Methods • N=15 • Clinical data afterwards inconclusive • Histopatologic classification not distinctive • Translocation analysistype translocation: difference or similarity in subsequent lesion can give information: clonal or 2nd primary • Loss of heterozygosity analysisdifference in pattern can give information: clonal or 2nd primary Methods

  6. Translocation frequency 7-2 (type I) 20% 8-2 (type III) 10% Other types 10% Methods

  7. Translocation frequency 7-2 (type I) 20% 5-2 (type II) 60% 8-2 (type III) 10% Other types 10% Methods

  8. Loss of heterozygosity • Clinics already introduced at • Head / neck & lung tumors • Multifocal breast cancer Methods

  9. Loss of heterozygosity (LOH) • 12 markers spread over 11 chromosomes • Patterns of loss of heterozygosity LOH ratio < 0,5 Methods

  10. Strategy of analysis of clonality • 1)Translocation • 2)Loss of heterozygosity Methods

  11. Strategy of analysis of clonality Translocation Concordant rare fusion transcript (i.e.7-2 8-2, 5-3) Different fusion transcripts at different sites Fusion transcript 5-2 LOH analysis Discordant LOH/AI (LOHx – LOHy) Concordant LOH/AI (LOHx – LOHx) Discordant LOH ≥ 2 LOH or ≥ 3 AI ≥ 1 LOH + ≥ 1 AI ≤ 1 LOH or ≤ 2 AI ≤1 LOH or ≤2 AI ≥1 LOH + ≥ 1 AI ≥2 LOH or ≥ 3 AI Second primary Metastasis Metastasis? Second Primary? Metastasis Second primary Methods

  12. Results • N=15 • Primary localization • Lower extremity 14 • Upper extremity 1 • Localization 2nd lesion • Extremity 4 • Abdominal wall 4 • Retroperitoneal 3 • Head/Neck 1 • Other 3 • Median time to 2nd lesion 25 (0-82) Results

  13. Patients Results

  14. Patients 1 15 Results

  15. Patients Results

  16. Patients Results

  17. Translocation Results

  18. Loss of Heterozygosity Results

  19. Loss of Heterozygosity Results

  20. Results Results

  21. Results • Clonal 8/15 • Suggestive for clonal relation 7/15 • Not in a single case development of independent second primary tumors was found Results

  22. Conclusions • It is highly suggestive that: multifocal myxoid/ round cell liposarcoma are metastasized tumors • Primary curative surgical approach is probably not rational • Treatment strategy designed for metastasized disease is more appropriate Conclusions

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