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 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 codons 4 duplication involving 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