Multiple primary sporadic gastrointestinal stromal tumors in the adult: an underestimated entity.
OBJECTIVE
Gastrointestinal stromal tumors (GIST) are commonly regarded as solitary tumors. The occurrence of multiple lesions is considered an extraordinary event restricted to pediatric GISTs and rare hereditary conditions. Beyond these well-defined situations, the presentation of multiple synchronous lesions is commonly viewed as the result of the metastatic spreading of a single primary GIST. Based on this axiom, patients with multifocal disease are classified as advanced stage and treated as such. Whether, indeed, the detection of several lesions in sporadic adult GIST patients may be suggestive of phenomena of tumor multiplicity still needs to be clarified.


METHODS
From a multicentric series of 442 consecutive cases, 26 of which with advanced disease, we selected 5 patients who presented up to three distinct GIST nodules. Five additional cases with similar characteristics were also contributed by two other institutions. The clonal relationship between the synchronous lesions was assessed by comparing KIT/PDGFRA mutation and microsatellite pattern.


RESULTS
An independent origin of the synchronous lesions was established in 6 of 10 cases. Notably, in one patient, one lesion arose in the peritoneum, which is ordinarily regarded as a site of metastasis.


CONCLUSIONS
Our data indicate that a significant fraction of GIST patients with multifocal presentation are actually affected by multiple primary tumors, suggesting that mesenchymal GIST precursor cells of these individuals are somehow primed to transformation. Thus, in the presence of multifocal GIST manifestations, an accurate characterization of the different tumor sites should be undertaken for a proper patient staging and therapy planning.
Gasparotto
Daniela
D
Experimental Oncology I, CRO National Cancer Institute, Aviano, Italy.
Rossi
Sabrina
S
Bearzi
Italo
I
Doglioni
Claudio
C
Marzotto
Alessandra
A
Hornick
Jason L
JL
Grizzo
Alessandra
A
Sartor
Chiara
C
Mandolesi
Alessandra
A
Sciot
Raf
R
Debiec-Rychter
Maria
M
Dei Tos
Angelo Paolo
AP
Maestro
Roberta
R
D000368:Aged; D000369:Aged, 80 and over; D000595:Amino Acid Sequence; D005260:Female; D046152:Gastrointestinal Stromal Tumors / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D006801:Humans; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D009154:Mutation; D009378:Neoplasms, Multiple Primary / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics; D017479:Receptors, Platelet-Derived Growth Factor / Q000235:genetics
D019009:Proto-Oncogene Proteins c-kit; D017479:Receptors, Platelet-Derived Growth Factor