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GASTROINTESTINAL STROMAL TUMORS (GIST) IN NEUROFIBROMATOSIS 1 (NF1) PATIENTS: A CLINICOPATHOLOGIC ANALYSIS OF NINE CAS

GASTROINTESTINAL STROMAL TUMORS (GIST) IN NEUROFIBROMATOSIS 1 (NF1) PATIENTS: A CLINICOPATHOLOGIC ANALYSIS OF NINE CASES. Elena Fumagalli, Paola Coco, Elena Palassini, Palma Dileo,  Rossella Bertulli, Paolo G. Casali . Istituto Nazionale Tumori Milan, Italy. This series.

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GASTROINTESTINAL STROMAL TUMORS (GIST) IN NEUROFIBROMATOSIS 1 (NF1) PATIENTS: A CLINICOPATHOLOGIC ANALYSIS OF NINE CAS

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  1. GASTROINTESTINAL STROMAL TUMORS (GIST) IN NEUROFIBROMATOSIS 1 (NF1) PATIENTS: A CLINICOPATHOLOGIC ANALYSIS OF NINE CASES Elena Fumagalli, Paola Coco, Elena Palassini, Palma Dileo,  Rossella Bertulli, Paolo G. Casali Istituto Nazionale Tumori Milan, Italy

  2. This series • 5 females : 4 males • Median age 51 yrs (range 36-59) • Localized disease in all cases, with multiple lesions in 6 pts • Site: • stomach and duodenum 1pt • duodenum 2 pts • jejunum 1 pt • ileum 4 pts • other 1 pt • Risk stratification: • high 2 pts • intermediate 1 pt • low/very low 6 pts

  3. This series: pts with multifocal disease • 6/9 pts • (5 low risk, 1 high risk) 2 pts 4 pts

  4. Multifocal disease

  5. “The presence of multiple GIST in NF1 might reflect a distinct rate-limiting step in oncogenesis compared with sporadic GIST. While a broad spectrum of inactivating genetic mechanism might lead to suppression of the wild type NF1 allele and GIST formation in NF1 pts, only a limited set of specific activating mutations in KIT/PDGFRA will result in sporadic GIST”

  6. This series: molecular genetics 8 pts: WT 1 pt (gastric + duodenal GIST): PDGFRA exon 18 (D842V) mutation in the gastric GIST; WT in the duodenal GIST

  7. Immunohistochemistry D842V in exon 18 of PDGFRA G A G WC AT C A PDGFRA D842V affecting the A-loop of PDGFRA

  8. KIT & PDGFRA mutations

  9. KIT/PDGFRA KIT/PDGFRA

  10. This series: pts with NET 1 pt: pheochromocytoma 1 pt: pheochromocytoma + ampullary neuroendrocrine tumor neuroendocrine tumour pheocromocitoma

  11. GIST and NET in NF1

  12. SUV 5

  13. SUV 4.5 SUV 4.7

  14. SUV 3.8

  15. PET in NF1

  16. FDG PET distinguishes MPNSTs from benign neurogenic tumours with 100% sensivity and 83% specificity at an SUV cut-off value = 1.8 • SUV level predicts outcome in NF1 pts with MPNSTs • SUV cut-off value = 3 • No correlation with histological grading

  17. Significant difference between mean SUV of malignant and benign tumours • Overlap with SUVmax = 2.5-3.5  lesions should be reviewed clinically • Time for measuring SUV 240 min • FDG PET and PET TC is sensitive and specific for MPNST in NF1 pts • Research with different tracers to predict tumour grade

  18. This series: prognosis 8 pts: alive and well median follow-up = 23 months (range = 6-97 months) 1 pt: metastatic disease (baseline: >5 cm; >10/50 HPF)  death after progression to Imatinib

  19. GIST in NF1: prognosis

  20. This series:1 pt treated preoperatively baseline + 4 w

  21. This series: secondary resistance 1 pt (ileal GIST): Kit exon 17 (D820N) mutation in metastatic lesions; WT in primary tumour D820N cKit ex 17 immunohistochemistry A G A AT r AT T cKIT Mussi et al. Clin Cancer Res 2008:14 July 15

  22. AntiTK activity

  23. Conclusions • Only anecdotal cases of GIST have been reported in NF1, though in the face of a 5-10% risk of developing the disease in this syndrome • WT are predominant, but KIT/PDGFRA mutations are occasionally present (both to KIT and PDGFRA) • NET may be concurrent, in the face of a 1% risk of these diseases in NF1 • Prognosis of WT GIST in NF1, although multifocal, is good, but may be worse for KIT/PDGFRA-mutated GIST • AntiTK are often ineffective, but responses have been occasionally reported (and secondary resistance may arise) • GIST in NF1 are often positive on PET scan, but specificity may be problematic against other lesions, including neurofibromas

  24. elena.fumagalli@istitutotumori.mi.it

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