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Pathologic Features of Prognostic Significance in Primary Retroperitoneal Liposarcoma

Pathologic Features of Prognostic Significance in Primary Retroperitoneal Liposarcoma. Amanda J. Cannell 1 , Sally M. Burtenshaw 1 , Martin E. Blackstein 2 , Peter Chung 3 , Charles N. Catton 3 , Rebecca A. Gladdy 1 , Carol J. Swallow 1 , Brendan C. Dickson 4.

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Pathologic Features of Prognostic Significance in Primary Retroperitoneal Liposarcoma

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  1. Pathologic Features of Prognostic Significance in Primary Retroperitoneal Liposarcoma Amanda J. Cannell1, Sally M. Burtenshaw1, Martin E. Blackstein2, Peter Chung3, Charles N. Catton3, Rebecca A. Gladdy1, Carol J. Swallow1, Brendan C. Dickson4 Departments of Surgery1, Medical Oncology2, Radiation Oncology3, and Pathology and Laboratory Medicine4, Mount Sinai Hospital and Princess Margaret Cancer Centre, University of Toronto; Toronto, ON Canada

  2. INTRODUCTIONRetroperitoneal liposarcoma • Conventional histotypes are well-differentiated (WD) and dedifferentiated (DD) liposarcoma • MDM2 amplification and protein over-expression • Myxoid/ round cell liposarcoma • Pleomorphic liposarcoma • Spindle cell (fibrosarcoma-like)

  3. RATIONALE Predicting behaviour of primary retroperitoneal liposarcoma (RP LPS) is challenging • Conventional indicators not applicable (e.g., TNM) • Local recurrence is predominant clinical challenge • Lack of consensus on prognostic indicators • Clinical and surgical attributes inconsistent • Pathologic • FNCLCC grade • Low-grade (LG-) versus high-grade (HG-) dedifferentiation

  4. RATIONALEBackground - FNCLCC grading system DIFFERENTIATION MITOTIC COUNT NECROSIS

  5. RATIONALEBackground - Differentiation Well-differentiated • Lipoma-like • Sclerosing • Inflammatory Dedifferentiated • Low-grade (LG-DD) • High-grade (HG-DD) DIFFERENTIATION Well-differentiated Dedifferentiated High-grade Low-grade

  6. OBJECTIVE Review of institutional experience with RP LPS to assess variables of potential prognostic significance • Pathologic • Fédération Nationale des Centres de Lutte Contre le Cancer (FNCLCC) grading system • Tumour differentiation, mitotic index, necrosis • Histotype • Well-differentiated vs Dedifferentiated • Extent of dedifferentiation • Low-grade vs high-grade DIFFERENTIATION Well-differentiated Dedifferentiated High-grade Low-grade MITOTIC COUNT NECROSIS

  7. OBJECTIVE Review of institutional experience with RP LPS to assess variables of potential prognostic significance • Pathologic • Fédération Nationale des Centres de Lutte Contre le Cancer (FNCLCC) grading system • Tumour differentiation, mitotic index, necrosis • Histotype • Well-differentiated vs Dedifferentiated • Extent of dedifferentiation • Low-grade vs high-grade DIFFERENTIATION Well-differentiated Dedifferentiated High-grade Low-grade MITOTIC COUNT NECROSIS

  8. OBJECTIVE Review of institutional experience with RP LPS to assess variables of potential prognostic significance • Pathologic • Fédération Nationale des Centres de Lutte Contre le Cancer (FNCLCC) grading system • Tumour differentiation, mitotic index, necrosis • Histotype • Well-differentiated vs Dedifferentiated • Extent of dedifferentiation • Low-grade vs high-grade DIFFERENTIATION Well-differentiated Dedifferentiated High-grade Low-grade MITOTIC COUNT NECROSIS

  9. OBJECTIVE Review of institutional experience with RP LPS to assess variables of potential prognostic significance • Pathologic • Fédération Nationale des Centres de Lutte Contre le Cancer (FNCLCC) grading system • Tumour differentiation, mitotic index, necrosis • Histotype • Well-differentiated vs Dedifferentiated • Extent of dedifferentiation • Low-grade vs high-grade DIFFERENTIATION Well-differentiated Dedifferentiated High-grade Low-grade MITOTIC COUNT NECROSIS

  10. METHODS • Cases identified from prospective database • Jan 1996 to Dec 2013 • Pathology review of all RP sarcomas (pre-treatment biopsy and resections) • College of American Pathologists: synoptic criteria, incl: • FNCLCC Grading • Extent of dedifferentiation, based on WHO criteria • Statistical analysis by SPSS • Chi-squared and Kaplan Meier curves (log-rank)

  11. STUDY POPULATION • Inclusion Criteria • Primary RP LPS treated with curative intent • Unequivocal diagnosis, based on: • Histomorphology • IHC for MDM2 • FISH for MDM2 • Exclusion • Other diagnosis (e.g., lipoma, leiomyosarcoma)

  12. STUDY COHORT

  13. RESULTSClinical Summary

  14. RESULTSPathologic Features

  15. RESULTSPathologic Features (cont)

  16. RESULTSSurvival analysis Disease Specific Survival Local Recurrence n=104 % Recurrence % Survival n=104 5 yr: 84% 5 yr: 26% Follow Up Time (Months) Follow Up Time (Months) Median Follow Up Time: 50 Months (5 – 218)

  17. RESULTSHistotype (WD vs DD) Disease Specific Survival Local Recurrence n=30 n=74 % Recurrence n=74 % Survival n=30 p<0.01 p=0.01 Follow Up Time (Months) Follow Up Time (Months)

  18. RESULTSFNCLCC Grade (1, 2, 3) Disease Specific Survival Local Recurrence n=31 n=68 n=5 n=68 % Survival % Recurrence n=5 n=31 p=0.03 p=0.01 Follow Up Time (Months) Follow Up Time (Months)

  19. RESULTSExtent of Differentiation (LG vs HG) Disease Specific Survival Local Recurrence n=56 n=56 n=18 % Recurrence % Survival n=18 p=0.24 p=0.91 Follow Up Time (Months) Follow Up Time (Months)

  20. DISCUSSION • Weaknesses • Small series • Retrospective review • Strengths • Pathology review using modern criteria and diagnostic techniques • Single institution

  21. CONCLUSIONS • Histotype (WD vs DD) is a dominant prognostic indicator DIFFERENTIATION Well-differentiated Dedifferentiated High-grade Low-grade MITOTIC COUNT NECROSIS

  22. CONCLUSIONS • Histotype (WD vs DD) is a dominant prognostic indicator • FNCLCC grade is prognostic • Grade I vs Grade II/III DIFFERENTIATION Well-differentiated Dedifferentiated High-grade Low-grade MITOTIC COUNT NECROSIS

  23. CONCLUSIONS • Histotype (WD vs DD) is a dominant prognostic indicator • FNCLCC grade is prognostic • Grade I vs Grade II/III DIFFERENTIATION High-grade Low-grade Well-differentiated Dedifferentiated High-grade Low-grade MITOTIC COUNT NECROSIS • LG-DD vs HG-DD no prognostic value • Confusing terminology of limited value for RP LPS

  24. Thank you CTOS 2014 Berlin

  25. PATTERNS OF RECURRENCE p = 0.14 p < 0.01

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