Transcript especially metachronous GISTs are extremely rare The

同时和异时性多发性
胃肠道间质瘤
Synchronous and metachronous
sporadic multiple GIST
侯英勇
复旦大学附属中山医院病理科
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
Methods
• Retrospectively investigation from archive file of
Zhongshan Hospital
• Dec 2002 to Dec 2009
• 427 primary GIST+195 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
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
• 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)
• 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
• 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
• 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)
• 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
• 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
• 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, Carney’s symdrome and
family GIST.
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