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 n

ormal 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 (mea

n 66.9 years) • 13 patients had synchronous GISTs • the number of GIST were 2 in 11 patients and 3 in 2 p

atients • 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 sam

e 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 l

ater 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 manifestatio

ns 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, immu

nohischemical and genetic evaluation are helpful for patients to selecting therapeutic strategies