????????? ?????? Synchronous and metachronous sporadic multiple GIST

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???????????????Synchronous and metachronous
sporadic multiple GIST

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Aims

• Sporadic multiple gastrointestinal stromal tumor
  (GISTs) especially metachronous GISTs are
  extremely rare
• The metachronous GISTs raise the challenge in
  adjuvant therapy in imatinib era
• The aim of this study was to investigate the
  clinical, phenotype, genetic characteristic, and
  biological behavior of synchronous and
  metachronous GISTs

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Methods

• Retrospectively investigation from archive file
  of Zhongshan Hospital
• Dec 2002 to Dec 2009
• 427 primary GIST195 consultant patient (622
  cases)
• Thirty-two paraffin blocks of multiple GISTs and
  15 normal tissues were obtained
• Reviewing HE slides
• Immunohistochemical staining
• KIT and PDGFRA gene mutation analysis

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Results

• the frequency of occurrence was 2.4 (15/622)
• There were 5 males and 10 females
• the age at diagnosis ranged from 49 to 84 years
  (mean 66.9 years)
• 13 patients had synchronous GISTs
• the number of GIST were 2 in 11 patients and 3 in
  2 patients
• Two patients was defined as metachronous GIST
• one had a new gastic GIST 7 month after the
  initial duodenal GIST surgery
• one had a new gastric GIST 43 months after the
  initial gastric GIST resection

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• A total of 31 gastric GIST and 1 duodenal GIST
  from 15 patients were available
• The tumor sizes ranged from 0.2 to 12 cm (mean
  2.7 cm)
• The size ratio of different tumors in each
  patient ranged from 1.2 to 12 (median 3.2 and
  mean 5.4)

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• Spindle shaped in 27 (84.3), mixed cell type in
  3 (9.4), and epithelioid cell type in 2 (6.3)
• Histopathological patterns within a patient were
  uniform in 12 patients, 3 patients presented with
  different cell shape in each tumor mass
• Mitotic figures were 0 in 20 GISTs, 1 in 3 GISTs,
  2 in 1 GISTs, 3 in 1 GIST, 4 in 3 GISTs, 5 in 1
  GIST, 7 in 1 GIST, 9 in 1 GIST and 25 in 1 GIST
  per 50 high-power fields
• Nonmalignant in 26 GISTs, low malignant in 6
  GISTs

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• CD117 were positive in 90.6 of multiple GISTs
  (29/32)
• CD34, smooth muscle actin (SMA), S-100 protein,
  and desmin were positive in 90.6, 9.4, 0, and
  0, respectively

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• Twenty six GIST masses from 15 patients showed
  mutations on exon 11 of KIT gene
• 1 tumor showed D842V mutation in exon 18 of
  PDGFRA gene
• 5 GIST masses showed no mutation in examined
  exons, the overall mutation rate was 84.4
  (27/32)

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• There was 11 point mutation involving 557, 559,
  560 and 576 codons respectively
• 8 deletions, of them, 5 involving 557-558 codons
• 4 duplication involving 573-587 codons
• and another 3 were point mutation plus deletion

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• Of the 15 patients
• 6 patients with multiple GIST masses had the same
  genotype with or without gene mutation
• 9 patients were found the different mutation
  type and codon site within each GIST mass
• in patients with 3 GIST masses
• in 2 patients with metachronous GISTs

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• One patient lost follow up
• two patients died of esophageal carcinoma 4 years
  later and one patient died of gastric
  adenocarcinoma 2.1 years later
• 12 patients are still alive at 3 to 51 month
• No patients had any associated clinical
  manifestations of hyperpigmented lesion, systemic
  mastocytosis, or NF-1, Carneys symdrome and
  family GIST.

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In summary

• synchronous and metachronous sporadic multiple
  GISTs experienced indolent clinical course
• most of them presented with polyclonal KIT or
  PDGFRA gene mutation
• multiple GISTs especially metachrounous multiple
  GISTs indicated that in rare situation GIST
  suspected as recurrent or metastatic disease are
  not truly malignant, but polycolonal primaries
• It is challenge for us in imatinib era
• Meticulous evaluations including
  clincopathological, immunohischemical and genetic
  evaluation are helpful for patients to selecting
  therapeutic strategies

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