Here, we report a colonic gastrointestinal stromal tumor (GIST) in a middle-aged man above 40. A histologically similar second tumor was detected 2 years after initial surgery. The primary GIST, measuring 5.5 ? 6.0 cm, consisted of spindle tumor cells with a higher number of mitoses and Ki67 labeling index (about 20%) than those of the second tumor, implying a de novo GIST. These markers might be useful in evaluating malignant potential, as well as to differentiate between a de novo and a recurrent tumor in the colonic GIST

Adachi, Hironobu

Goto, Eizo

Honjo, Soichiro

Ito, Hisao

Kase, Satoru

Kawaguchi, Hiroki

Osaki, Mitsuhiko

Shomori, Kohei

Yamashita, Hideki

Yonago Acta Medica

Tottori University Research Result Repository

117A Case of Malignant Gastrointestinal Stromal Tumor of the TransverseColon:  Evaluation of Proliferation ActivitySatoru Kase, Hironobu Adachi, Mitsuhiko Osaki, Kohei Shomori, SoichiroHonjo, Eizo Goto, Hideki Yamashita, Hiroki Kawaguchi* and Hisao ItoDivision of Organ Pathology, Department of Microbiology and Pathology, School of Medi-cine, Tottori University Faculty of Medicine, Yonago 683-8503 and *Clinic of Surgery,National Yonago Hospital, Yonago 683-8518 JapanHere, we report a colonic gastrointestinal stromal tumor (GIST) in a middle-aged manabove 40.  A histologically similar second tumor was detected 2 years after initial surgery.The primary GIST, measuring 5.5 × 6.0 cm, consisted of spindle tumor cells with ahigher number of mitoses and Ki67 labeling index (about 20%) than those of the secondtumor, implying a de novo GIST.  These markers might be useful in evaluating malignantpotential, as well as to differentiate between a de novo and a recurrent tumor in thecolonic GIST.Key words:  colon; gastrointestinal stromal tumor; Ki67; mitosisYonago Acta medica 2002;45:117–120Abbreviations:  EMA, epithelial membrane antigen; HPF, high power field; GI, gastrointestinal; GIST,gastrointestinal stromal tumor; NSE, neuron specific enolaseGastrointestinal stromal tumors (GISTs) are themost common mesenchymal tumors of thegastrointestinal (GI) tract.  They are defined asc-kit (CD117, stem cell factor receptor)-positive mesenchymal spindle or epithelioidtumor cells in the GI tract.  GISTs are mostcommon in the stomach (60–70%), followed bythe small intestine (20–25%).  ColorectalGISTs are relatively rare, frequency being re-ported at approximately 5% (Miettinen andLasota, 2001).  Moreover, the pathobiologicalfeatures of malignant GISTs of the colon re-main unclear.  Here, we report a case of malig-nant GISTs which developed in the transversecolon and the ascending colon, the latter beingdetected 2 years after initial surgery.  We ana-lyzed the number of mitoses and Ki67 labelingcells in the primary and second GISTs.Patient ReportThe patient was a man in his mid-40’s whonoticed an abdominal tumor without abdominalpain about 4 years ago.  Abdominal ultrasonog-raphy did not reveal significant findings at thattime.  A colonic tumor was detected by a bari-um contrast enema in February 1999.  The tu-mor was surgically removed with partial resec-tion of the transverse colon.  Two years aftersurgery, computed tomography revealed thepresence of another tumor in the ascendingcolon.  The patient underwent surgery again.The postoperative course was uneventful andthere has been no clinical evidence of tumorrecurrence since.Pathological findingsThe primary tumor was 5.5 × 6.0 cm found inthe transverse colon, whereas the second tumorwas 3.0 × 5.3 cm found in the ascending colon.Grossly, the primary tumor showed irregularsurfaces with areas of hemorrhage but withoutulceration or necrosis (Fig. 1A).  Histologically,the tumor, from the muscularis propria to theserosa, consisted predominantly of spindleshaped cells with an eosinophilic cytoplasm andmild nuclear atypia.  No skeinoid fibers or epi-thelioid cells were observed.  In addition, theS. Kase et al.118tumor did not show metastases to the regionallymph nodes nor lymphatic invasion.  The sec-ond tumor showed similar pathological find-ings.  Mitotic figures were relatively frequent[5/50 high power fields (HPFs)] in the primarytumor (Fig. 1B), but less frequent in the secondtumor.Immunohistochemically, most tumor cellsin both lesions were positive for CD117 (Fig.1C) and vimentin, in contrast to no immuno-reactivity for CD34, human muscle actin, α-smooth muscle actin, desmin, S100 protein,neuron specific enolase (NSE) or epithelialmembrane antigen (EMA).  Both tumors wereFigs. 1A–D.A:  Gastrointestinal stromal tumor.  Tumor is brownish and well circumscribed, and located from themuscularis to the serosa of the transverse colon.B:  Gastrointestinal stromal tumor.  Formalin-fixed, paraffin-embedded tissue section of the tumor in thetransverse colon shows spindle cells possessing mild nuclear atypia and clear nucleoli.  Mitotic figure isnoted (arrow) (hematoxylin and eosin stain; original magnification × 100).C:  Immunohistochemistry for CD117.  CD117 immunoreactivity is shown in the cytoplasm of tumor cells(hematoxylin counterstain; original magnification × 200).D:  Immunohistochemistry for Ki67.  Tumor cells show nuclear immunoreactivity for Ki67 (hematoxylincounterstain; original magnification × 200).diagnosed as GIST from the point of histo-pathological and immunohistochemical find-ings.  In the primary tumor, nuclear immuno-reactivity for Ki67 was observed in approxi-mately 20% of tumor cells (Fig. 1D).  On theother hand, only 5% of tumor cells were posi-tive in the second tumor, which showed similarpathological findings with the primary, exceptfor tumor size, mitotic figures and the Ki67labeling index.A BC DMalignant GIST of the colon119DiscussionHere, we describe a case of GIST in the trans-verse colon, followed by a second tumor in theascending colon 2 years after initial surgery.The second GIST was smaller in size, and had alower number of Ki67 labeling cells and mito-ses than the primary tumor, implying a morestatic nature and lower malignant potential inthe former than in the latter.  These pathologicalfindings promptly raised the question of wheth-er the tumor localized in the ascending colonwas truly recurrent or de novo developed GIST.It is well known that the most common sites formetastases of malignant GISTs are in the liverand peritoneum.  These metastases can developfor as long as 30 years after the removal ofGISTs as well as gastrointestinal leiomyosarco-mas (Salmela, 1968; Ng et al., 1992; Rosai,1996).  In this case, the primary tumor did notshow metastases to the regional lymph nodesnor lymphatic invasion.  In addition, the observ-ed pathological findings were similar, and theterm until the clinical detection of the secondtumor was relatively short, which suggestedthat the tumor might be de novo.Rosai (1996) classified GISTs in the follow-ing 4 categories; (i) smooth muscle, (ii) neural,(iii) combined and (iv) uncommitted.  The pres-ent case showed neither smooth muscle norneural differentiation by immunohistochemis-try.  Therefore, the primary and second tumorswere classified as the uncommitted type.  Al-though GIST is a mesenchymal tumor of the GItract, colorectal GISTs are relatively uncommon(Miettinen et al., 1995; Miettinen and Losota,2001).  Miettinen et al. (2000) reported 37GISTs of the colon, of which 11 cases showedrecurrence or metastasis.  In these 11 cases, themean age was 59.2, and the descending colonwas the most frequent site, followed by thesigmoid colon and the cecum.  In 4 cases out ofthe 11, extremely frequent mitotic figures, morethan 100 in 50 HPFs, were observed.  More-over, liver metastasis was noted in 6 cases.  Re-currence in the colon was not reported.  On theother hand, the present case differs from thereport on a few points.  The GIST was located inthe transverse colon and occurred in a middle-aged man.Previous studies indicated that the prolifera-tive index evaluated by Ki67 antigen in the nu-clei of the tumor cells was the most importantpredictor of clinical behavior in GISTs (Carrilloet al., 1997; Seidal and Edvardsson, 1999).However, GISTs of the transverse colon havenot been evaluated enough.  We confirmed thatabout 20% of tumor cells showed Ki67 expres-sion in the primary tumor, suggesting that pri-mary GIST might have possessed high prolifer-ative activity compared to the second tumor.Similar to Ki67 expression, high mitotic figuresand tumor size might be also considered to beaggressive factors in GISTs (Amin et al., 1993;Rosai, 1996).  According to Amin et al. (1993),malignant gastric stromal tumors were greaterthan 5/50 HPFs in mitotic count and more than5 cm in size.  Moreover, previous studies dem-onstrated a significant correlation between themitotic count and proliferative nuclear antigenindex or Ki67 index (Amin et al., 1993; Seidaland Edvardsson, 1999).  The present case show-ed a higher number of mitotic figures (5/50HPFs) and Ki67 labeling tumor cells in the pri-mary GIST.  These factors might also be appli-cable to GISTs of the transverse colon and use-ful in evaluating malignant potentials.In summary, we described a case of malig-nant GIST of the transverse colon and compar-ed it with a second tumor from a pathobiol-ogical viewpoint.  The primary GIST showed alarger size and consisted of spindle tumor cellswith a higher number of mitoses and Ki67 la-beling index than those of the second tumor,implying a de novo development.Acknowledgments:  The authors thank Mr. N. Itakiand Miss M. Kajimura for their technical support.References 1 Amin MB, Ma CK, Linden MD, Kubus JJ, ZarboRj.  Prognostic value of proliferating cell nuclearantigen index in gastric stromal tumors.  Correla-tion with mitotic count and clinical outcome.  AmS. Kase et al.120J Clin Pathol 1993;100:428–432. 2 Carrillo R, Candia A, Rodriguez-Peralto JL, CazV.  Prognostic significance of DNA ploidy andproliferative index (MIB-1 index) in gastrointes-tinal stromal tumors.  Hum Pathol 1997;28:160–165. 3 Miettinen M, Lasota J.  Gastrointestinal stromaltumors-definition, clinical, histological, immuno-histochemical, and molecular genetic featuresand differential diagnosis.  Virchows Arch 2001;438:1–12. 4 Miettinen M, Sarlomo-Rikala M, Sobin LH,Lasota J.  Gastrointestinal stromal tumors andleiomyosarcomas in the colon.  Am J Surg Pathol2000;24:1339–1352. 5 Miettinen M, Virolainen M, Rikala MS.  Gastro-intestinal stromal tumours-value of CD34 antigenin their identification and separation from trueleiomyomas and Schwannomas.  Am J Surg Pathol1995;19:207–216. 6 Ng EH, Pollock RE, Romsdahl MM.  Prognosticimplications of patterns of failure for gastro-intestinal leiomyosarcomas.  Cancer 1992;1334–1341. 7 Rosai J.  Surgical pathology.  8th ed.  St. Louis:Mosby; 1996. 8 Salmela H.  Smooth muscle tumours of the stom-ach.  A clinical study of 112 cases.   Acta ChirSacnd 1968;134:384–391. 9 Seidal T, Edvardsson H.  Expression of c-kit(CD117) and Ki67 provides information aboutthe possible cell of origin and clinical course ofgastrointestinal stromal tumours.  Histopathol1999;34:416–424.Received October 7, 2002; accepted October 28, 2002Corresponding author:  Satoru Kase, MD

A Case of Malignant Gastrointestinal Stromal Tumor of the Transverse Colon: Evaluation of Proliferation Activity

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A Case of Malignant Gastrointestinal Stromal Tumor of the Transverse Colon: Evaluation of Proliferation Activity

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