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Synchronous
colon GIST and adeno-Ca x xx 197
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ANNALS OF GASTROENTEROLOGY 2009, 22(3):197-200

Case Report

Synchronous occurrence of colorectal adenocarcinoma and

colonic gastrointestinal stromal tumor (GIST). A case report
D. Dimitroulopoulos1, Aik. Fotopoulou2, D. Xinopoulos1, N. Arnogiannaki3, D. Korkolis,4
K. Tsamakidis1, D. Kypreos1, S. Bassioukas1, S. Patsavela1, E. Paraskevas1

cases per million and an estimated 5-year survival rate of

SUMMARY
45-65%, GIST’s typically present in older individuals and
The synchronous occurrence of GIST and other primary gas- are most common in the stomach (60%), followed by small
trointestinal malignancies has been rarely reported. We re- intestine (15%), colon and rectum (5%), esophagus, mes-
port the case of an 84 year-old female who presented with a entery and omentum5,6.
rectal blood loss. Total coloscopy revealed a stenotic lesion at
sigmoid colon covered by endoscopically healthy mucosa and
The synchronous occurrence of GIST and other prima-
also a massive polypoid cecal mass. The patient underwent
ry gastrointestinal malignancies has been rarely reported.
left subtotal colectomy and ileorectal J-pouch anastomoses In these cases stomach and small intestine were the most
without diverting stoma. Histologically the sigmoid tumor common locations for the GIST.7-11
met the GIST criteria and the cecal mass was a well differen- In the present case report we describe a 84 year-old
tiated adenocarcinoma. To our knowledge this synchronous woman with GIST of sigmoid colon and synchronous
occurrence is reported for first time in the literature. invasive adenocarcinoma at the ileocecal valve. To our
Keywords: GIST; colon adenocarcinoma; synchronous; colon; knowledge, this synchronous occurrence has not been re-
imatinib ported in the literature.

INTRODUCTION CASE REPORT

Gastrointestinal stromal tumors (GIST’s) have only A 84 year-old Caucasian female, with a recently di-
recently become recognized as a distinct pathologic en- agnosed GIST, located in the colon, was admitted to the
tity. The term was first used in 1983 by Mazur and Clark Gastroenterology department of “Agios Savvas” Cancer
to encompass gastrointestinal and mesenteric non-epithe- Hospital, Athens, Greece, in February 2007. A lower gas-
lial neoplasms that lacked the immunohistochemical fea- trointestinal tract endoscopic examination, performed a
tures of Schwann cells and did not have the ultrastructural month before due to rectal blood loss, was stopped in the
characteristics of smooth muscle cells.1 The vast majority sigmoid colon area because of a great stenosis. Tissue
of GIST’s are positive for CD117 and vimentin in immu- specimens obtained endoscopically from the stenosis were
nohistochemical staining.2-4 stained positive for CD117, CD34 and vimentin.
Their epidemiology still remain incompletely known. The patient’s past medical history included hyperten-
With an annual incidence rainging between 6.8 and 14.5 sion, atrial fibrillation and Alzheimer disease. No history
of malignancy was noted in her family history. Physical
1
Gastroenterology Dept, “Agios Savvas” Cancer Hospital, and rectal digital examination were undiagnostic.
2
Radiation-Oncology Dept, “Ygeia” Hospital, 3Pathology Dept,
“Agios Savvas” Cancer Hospital, 41st Surgical Dept, “Agios Complete blood count, urine tests, standard biochemi-
Savvas” Cancer Hospital cal studies and also serum levels of tumor markers includ-
ing CEA, CA 19-9, AFP, CA125 and CA 15-3 were with-
Author for correspondence:
in normal ranges.
D.Dimitroulopoulos, 35 Parnassou str., 152 34 Halandri-Athens,
Greece, Tel. 0030-210-6892460, E-mail: [email protected] Chest X-ray and upper abdominal ultrasonography
198 D. Dimitroulopoulos, et al

were normal. Abdominal computed tomography showed or related stem cells, that usually express the KIT protein
wall thickening of ascending colon and cecum in a length (-95%) and, that often harbour mutation of a gene that en-
of more than 7 cm. codes for a type III receptor tyrosine kinase.12-14
Total colonoscopy revealed the already known ste- Although they are the commonest gastrointestinal soft
nosis at sigmoid colon, covered by endoscopically nor- tissue tumors and can originate anywhere in the digestive
mal mucosa and also a massive polypoid mass (diame- tract, colon GIST’s are relatively infrequent.8,15
ter almost 5cm) in ascending colon, close to the ileocecal
valve. On the other hand, the synchronous occurrence of
GIST’s and other primary gastrointestinal malignancies has
Multiple biopsies were obtained with conventional bi- been rarely reported in the literature.7-11,16-22 The vast major-
opsy forceps from the cecal lesion. Histology revealed ity of these synchronous tumors are adenocarcinomas.9
mild/moderate dysplastic alterations from a mixed type
(hyperplastic-adenomatous) colonic polyp. To the best of our knowledge, the synchronous occur-
rence of two independent malignancies of colon, a GIST
The patient underwent left subtotal colectomy and il- and an adenocarcinoma, has never been reported.
eorectal J-pouch anastomosis without diverting stoma 10
days after.

Pathology Report
Pathology department was examined three surgical
specimens. The first one (total length 60 cm), consisted
of a 7 cm lenth portion of small intestine adjoining by the
ileocecal valve, the cecum and a portion of large intestine.
Grossly, was observed a 5x5 cm cecal papillary mass close
to the ileocecal valve with intracanalicular growth. Histol-
ogy revealed a well differentiated adenocarcinoma limit-
ed to the muscularis propria, stage Dukes A and B1. None
of the twelve examined lymph nodes presented metastatic
invasion. The second (8 cm, large intestine) was without
macroscopic alterations.
Gross examination of the third specimen revealed, 8
cm from the distal surgical margin, a 2,8x2,5x2 cm mass Figure 1. Spindle and epitheliod cells. H-E x 400.
producing from the outer muscularis propria to the muco-
sa with a small ulceration and central cystic degeneration
filled with blood. Histologically, the tumor demonstrated
a mixed cell type appearance of a) epithelioid and b) uni-
form spindle cells (Fig. 1) which stained positive for CD
117 (KIT) (Fig. 2) and CD 34, slight positive for SMA
and negative for vimentin, S-100 and desmin, with a mi-
totic activity <3 per 50 high power fields (HPF). None of
the 12 lymph nodes recovered from the specimen showed
evidence of metastatic disease. The final pathological di-
agnosis of this tumor was GIST of low grade malignancy
with no metastatic involvement.

DISCUSSION
At present, GIST’s may be defined as morphologically
spindle cell, epitheloid, or occasionally pleomorphic, mes-
enchymal tumors, originated from interstitial cells of Cajal Figure 2. Spindle and epithelioid cells. CD117 positive x 100.
Synchronous
colon GIST and adeno-Ca 199

The most important manifestation of stromal tumors 2005; 56:51-61.

is their indolent, slow growing nature. They are general- 9. Wronski M, Ziarkiewicz – Wrobeewska B, Gornicka B, et
ly found within the deeper stroma and the submucosa, and al. Synchronous occurrence of gastrointestinal stromal tu-
mors and other primary gastrointestinal neoplasms. World J
are often incidentally discovered during imaging studies.
Gastroenterol 2006; 12: 5360–5362.
Symptomatic lesions have manifestation that depend on tu- 10. Lin Y-L, Tzeng J-E, Wei C-K, Lin C-W. Small gastrointes-
mor size, location and growth pattern.23-25 Tumors less than tinal stromal tumor concomitant with early gastric cancer:
2 cm are generally asymptomatic while tumors with diam- A case report. World J Gastroenterol 2006; 12: 815–17.
eter more than 4 cm are associated with symptomatic dis- 11. Melis M, Choi EA, Anders R, Christiansen P, Fichera A.
ease.26 Bleeding is the most common symptom at presenta- Synchronous colorectal adenocarcinoma and gastrointesti-
tion and may take place either into abdominal cavity or into nal stromal tumor (GIST). Int J Colorectal Dis 2007;22:109-
gastrointestinal tract lumen, as in the present case27. 114.
12. Kindblom LG, Remotti HE, Aldenborg F, Meis-Kindblom
Localized GIST’s risk assessment profile, according to JM. Gastrointestinal pacemaker cell tumor (GIPACT): gas-
the NIH consensus report of 2002, is based on the prima- trointestinal stromal tumors show phenotypic characteristics
ry tumor diameter and the mitotic count. Thus, a mitotic of the interstitial cells of Cajal. Am J Pathol 1998; 152:1259–
1269.
index over 5 per 50 HPF or size more than 5 cm are con-
13. Sarlomo-Rikala M, Kovatich AJ, Barusevicius A, Miettinen
sidered as unfavorable prognostic factors.28 M. CD 117: a sensitive marker for gastrointestinal stromal
Surgery is the standard of care for primary, localized, tumors that is more spicific than CD 34. Mod Pathol 1998;
11:728–734.
non-metastatic disease and provide 5-year survival rates
14. Hirota S, Isozaki K, Moriyama Y, et al. Gain-of-function
ranging between 45% and 65%.4,29,30 Imatinib, a tyrosine mutations of c-kit in human gastrointestinal stromal tumors.
kinase inhibitor, is widely used in the treatment of ad- Science 1998;279: 577–580.
vanced and metastatic GIST’s and has been recently em- 15. Mucciarini C, Rossi G, Bertolini F, et al. Incidence and clin-
ployed in the neo adjuvant and adjuvant set-up with en- icopathologic features of gastrointestinal stromal tumors. A
couraging results. Another therapeutic agent, sutinib, is population-based study. BMC Cancer 2007; 7:230 [Epub
approved for the treatment of imatinib-resistant tumors ahead of print].
and a large spectrum of new small molecule inhibitors are 16. Efstathios P, Athanasios P, Papaconstantinou I, et al. Coexis-
tence of gastrointestinal stromal tumor (GIST) and colorectal
in the pipeline eg. nilotinib, everolimus.31-34
adenocarcinoma: A case report. World J Surg Oncol 2007;
5:96-101.
REFERENCES 17. Kover E, Faluhelyi Z, Bogner B, Kalmar K, Horvath G, Tor-
noczky T. Dual tumours in the GI tract: synchronous and
1. Mazur MT, Clark HB. Gastric stromal tumors: Reappraisal metachronous stromal (GIST) and epithelial/neuroendocrine
of histogenesis. Am J Surg Pathol 1983; 7: 507-519. neoplasms. Magy Onkol 2004; 48:315–321.
2. Noguchi T, Sato T, Takeno S, et al. Biological analysis of 18. Agaimy A, Wuensch PH. Gastrointestinal stromal tumours
gastrantestinal stromal tumors. Oncol Rep 2002; 9:1277- in patients with other-type cancer: a mere coincidence or an
1282. etiological association? A study of 97 GIST cases. Z. Gas-
3. Miettinen M, Sobin LH, Sarlomo-Rilcala M. Immunohisto- troenterol 2005; 43:1025–1030.
chemical spectrum of GIST’s at different sites and their dif- 19. Kaffes A, Hughes L, Hollinshead J, Katelaris P. Synchronous
ferential diagnosis with a reference to CD 117 (KIT). Mod primary adenocarcinoma, mucosa-associated lymphoid tissue
Pathol 2000; 13:1134–1142. lymphoma and a stromal tumor in a Helicobacter pylori-infect-
4. Blay JY, Bonvalot S, Casali P, et al. Consensus meeting for ed stomach. J Gastroenterol Hepatol 2002; 17:1033–1036.
the management of gastrointestinal stromal tumors. Report of 20. Usui M, Matsuda S, Suzuki H, Hirata K, Ogura Y, Shirai-
the GIST Consensus Conference of 20-21 March 2004, un- shi T. Somatostatinoma of the papilla of Vater with multiple
der the auspices of ESMO. Ann Oncol 2005; 16:566 –578. gastrointestinal stromal tumors in a patient with von Reck-
5. Reddy P, Boci K, Charbonneau C. The epidemiologic, health- linghausen’s disease. J Gastroenterol 2002; 37:947– 953.
related quality of life, and economic burden of gastrointesti- 21. Liu SW, Chen GH, Hsieh PP. Collision tumor of the stomach:
nal stromal tumours. J Clin Pharm Ther 2007; 32:557-565. a case report of mixed gastrointestinal stromal tumor and ad-
6. Judson I. Gastrointestinal stromal tumours (GIST): biology enocarcinoma. J Clin Gastroenterol 2002; 35:332–334.
and treatment. Ann Oncol 2002; 13(Suppl 4): 287-289. 22. Huilgol RL, Young CJ, Solomon MJ. The gist of it: Case re-
7. Maiorana A, Fante R, Maria Cesinaro A, Adriana Fano R. ports of a gastrointestinal stromal tumour and a leiomyoma
Synchronous occurence of epitelial and stromal tumors in of the anorectum. ANZ J Surg 2003;73:167–169.
the stomach: a report of 6 cases. Arch Pathol Lab Med 2000; 23. DeMatteo RP, Lewis JJ, Leung D, Mudan SS, Woodruff JM,
124:682–686. Brennan MF. Two hundred gastrointestinal stromal tumors:
8. Urbanczyk K, Limon J, Korobowicz E, et al. Gastrointesti- recurrence patterns and prognostic factors for survival. Ann
nal stromal tumors. A multicenter experience. Pol J Pathol Surg 2000; 231:51-58.
200 D. Dimitroulopoulos, et al

24. Pidhorecky I, Cheney RT, Kraybill WG, Gibbs JF. Gastroin- therapy: the gastrointestinal stromal tumor model. Ann Surg
testinal stromal tumors: current diagnosis, biologic behavior 2006;244:176–184.
and management. Ann Surg Oncol 2000; 7: 705–712. 30. van der Zwan SM, DeMatteo RP. Gastrointestinal stromal
25. Miettinen M, Sarlomo-Rikala M, Lasota J. Gastrointestinal tumor: 5 years later. Cancer 2005; 104:1781–1788.
stromal tumors: recent advances in understanding of their 31. Hornick JL, Fletcher CD. The role of KIT in the manage-
biology. Hum Pathol 1999; 30:1213-1220. ment of patients with gastrointestinal stromal tumors. Hum
26. Ludwig DJ, Traverso LW. Gut stromal tumors and their clin- Pathol 2007; 38:679 –687.
ical behavior. Am J Surg 1997;173:390-394. 32. Gupta P, Tewari M, Shukla HS. Gastrointestinal stromal tu-
27. Miettinen M, Sobin LH, Lasota J. Gastrointestinal stromal mor. Surg Oncol 2008 [Epub ahead of print].
tumors of the stomach: a clinicopathologic, immunohisto- 33. Weisberg E, Wright RD, Jiang J, et al. Effects of PKC412,
chemical and molecular genetic study of 1765 cases with nilotinib, and imatinib against GIST-associated PDGFRA
long-term follow-up. Am J Surg Pathol 2005; 29:52-68. mutants with differential imatinib sensitivity. Gastroentero-
28. Fletcher CD, Berman JJ, Corless C, et al. Diagnosis of gas- logy 2006;131:1734–1742.
trointestinal stromal tumors: A consensus approach. Hum 34. von Mehren M. Beyond imatinib: second generation c-KIT
Pathol 2002; 33:459–465. inhibitors for the management of gastrointestinal stromal tu-
29. Gold JS, Dematteo RP. Combined surgical and molecular mors. Clin Colorectal Cancer 2006; 6 Suppl 1: S30 –S34.

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