Yonago Acta medica 2002;45:117–120

A Case of Malignant Gastrointestinal Stromal Tumor of the Transverse
Colon: Evaluation of Proliferation Activity
Satoru Kase, Hironobu Adachi, Mitsuhiko Osaki, Kohei Shomori, Soichiro
Honjo, Eizo Goto, Hideki Yamashita, Hiroki Kawaguchi* and Hisao Ito
Division of Organ Pathology, Department of Microbiology and Pathology, School of Medicine, 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 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 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 malignant
potential, as well as to differentiate between a de novo and a recurrent tumor in thecolonic GIST.
Key words: colon; gastrointestinal stromal tumor; Ki67; mitosis

Gastrointestinal stromal tumors (GISTs) are themost common mesenchymal tumors of thegastrointestinal (GI) tract. They are defined as
c-kit (CD117, stem cell factor receptor)positive mesenchymal spindle or epithelioid
tumor cells in the GI tract. GISTs are mostcommon in the stomach (60–70%), followed by
the small intestine (20–25%). Colorectal
GISTs are relatively rare, frequency being reported at approximately 5% (Miettinen andLasota, 2001). Moreover, the pathobiologicalfeatures of malignant GISTs of the colon remain unclear. Here, we report a case of malignant GISTs which developed in the transverse
colon and the ascending colon, the latter being
detected 2 years after initial surgery. We analyzed the number of mitoses and Ki67 labelingcells in the primary and second GISTs.

Patient Report
The patient was a man in his mid-40’s who
noticed an abdominal tumor without abdominal
pain about 4 years ago. Abdominal ultrasonog-raphy did not reveal significant findings at thattime. A colonic tumor was detected by a barium contrast enema in February 1999. The tumor was surgically removed with partial resection of the transverse colon. Two years aftersurgery, computed tomography revealed thepresence of another tumor in the ascending
colon. The patient underwent surgery again.
The postoperative course was uneventful andthere has been no clinical evidence of tumor
recurrence since.

Pathological findings
The primary tumor was 5.5 × 6.0 cm found in
the transverse colon, whereas the second tumor
was 3.0 × 5.3 cm found in the ascending colon.
Grossly, the primary tumor showed irregularsurfaces with areas of hemorrhage but without
ulceration or necrosis (Fig. 1A). Histologically,
the tumor, from the muscularis propria to theserosa, consisted predominantly of spindle
shaped cells with an eosinophilic cytoplasm andmild nuclear atypia. No skeinoid fibers or epithelioid cells were observed. In addition, theAbbreviations: EMA, epithelial membrane antigen; HPF, high power field; GI, gastrointestinal; GIST,gastrointestinal stromal tumor; NSE, neuron specific enolase

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S. Kase et al.

AB

CDFigs. 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).

tumor did not show metastases to the regional
lymph nodes nor lymphatic invasion. The second tumor showed similar pathological findings. 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 cells
in both lesions were positive for CD117 (Fig.
1C) and vimentin, in contrast to no immunoreactivity for CD34, human muscle actin, αsmooth muscle actin, desmin, S100 protein,neuron specific enolase (NSE) or epithelial
membrane antigen (EMA). Both tumors werediagnosed as GIST from the point of histopathological and immunohistochemical findings. In the primary tumor, nuclear immunoreactivity for Ki67 was observed in approximately 20% of tumor cells (Fig. 1D). On theother hand, only 5% of tumor cells were positive in the second tumor, which showed similar
pathological findings with the primary, except
for tumor size, mitotic figures and the Ki67
labeling index.

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Malignant GIST of the colon

Discussion
Here, we describe a case of GIST in the transverse 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 mitoses than the primary tumor, implying a morestatic nature and lower malignant potential in
the former than in the latter. These pathologicalfindings promptly raised the question of whether the tumor localized in the ascending colon
was 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 develop
for as long as 30 years after the removal ofGISTs as well as gastrointestinal leiomyosarcomas (Salmela, 1968; Ng et al., 1992; Rosai,1996). In this case, the primary tumor did notshow metastases to the regional lymph nodes
nor lymphatic invasion. In addition, the observed pathological findings were similar, and theterm until the clinical detection of the second
tumor was relatively short, which suggested
that the tumor might be de novo.
Rosai (1996) classified GISTs in the following 4 categories; (i) smooth muscle, (ii) neural,(iii) combined and (iv) uncommitted. The present case showed neither smooth muscle nor
neural differentiation by immunohistochemistry. Therefore, the primary and second tumors
were classified as the uncommitted type. Although GIST is a mesenchymal tumor of the GI
tract, colorectal GISTs are relatively uncommon(Miettinen et al., 1995; Miettinen and Losota,2001). Miettinen et al. (2000) reported 37
GISTs of the colon, of which 11 cases showedrecurrence or metastasis. In these 11 cases, themean age was 59.2, and the descending colon
was the most frequent site, followed by thesigmoid colon and the cecum. In 4 cases out of
the 11, extremely frequent mitotic figures, morethan 100 in 50 HPFs, were observed. Moreover, liver metastasis was noted in 6 cases. Recurrence in the colon was not reported. On theother hand, the present case differs from thereport on a few points. The GIST was located in
the transverse colon and occurred in a middleaged man.
Previous studies indicated that the proliferative index evaluated by Ki67 antigen in the nuclei of the tumor cells was the most important
predictor 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 expression in the primary tumor, suggesting that primary GIST might have possessed high proliferative activity compared to the second tumor.
Similar to Ki67 expression, high mitotic figures
and 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 than
5 cm in size. Moreover, previous studies demonstrated a significant correlation between themitotic count and proliferative nuclear antigen
index or Ki67 index (Amin et al., 1993; Seidaland Edvardsson, 1999). The present case showed a higher number of mitotic figures (5/50HPFs) and Ki67 labeling tumor cells in the primary GIST. These factors might also be applicable to GISTs of the transverse colon and useful in evaluating malignant potentials.
In summary, we described a case of malignant GIST of the transverse colon and compared it with a second tumor from a pathobiological viewpoint. The primary GIST showed alarger size and consisted of spindle tumor cellswith a higher number of mitoses and Ki67 labeling 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.

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References
1 Amin MB, Ma CK, Linden MD, Kubus JJ, Zarbo
Rj. Prognostic value of proliferating cell nuclearantigen index in gastric stromal tumors. Correlation with mitotic count and clinical outcome. AmS. Kase et al.

J Clin Pathol 1993;100:428–432.
2 Carrillo R, Candia A, Rodriguez-Peralto JL, Caz
V. Prognostic significance of DNA ploidy andproliferative index (MIB-1 index) in gastrointestinal stromal tumors. Hum Pathol 1997;28:160–165.
3 Miettinen M, Lasota J. Gastrointestinal stromal
tumors-definition, clinical, histological, immunohistochemical, 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 Pathol
2000;24:1339–1352.
5 Miettinen M, Virolainen M, Rikala MS. Gastrointestinal stromal tumours-value of CD34 antigen
in their identification and separation from true
leiomyomas and Schwannomas. Am J Surg Pathol
1995;19:207–216.

120

6 Ng EH, Pollock RE, Romsdahl MM. Prognostic
implications of patterns of failure for gastrointestinal leiomyosarcomas. Cancer 1992;1334–1341.
7 Rosai J. Surgical pathology. 8th ed. St. Louis:
Mosby; 1996.
8 Salmela H. Smooth muscle tumours of the stomach. A clinical study of 112 cases. Acta Chir
Sacnd 1968;134:384–391.
9 Seidal T, Edvardsson H. Expression of c-kit(CD117) and Ki67 provides information about
the possible cell of origin and clinical course ofgastrointestinal stromal tumours. Histopathol
1999;34:416–424.

Received October 7, 2002; accepted October 28, 2002
Corresponding author: Satoru Kase, MD