Synchronous occurrence of colonic intraepithelial neoplasia and small bowel stromal tumour

Introduction 

Gastrointestinal stromal tumours (GISTs) are the most common non-epithelial tumours of the digestive tract, accounting for 1% of all gastrointestinal malignancies and for 5 to 7% of all sarcomas. They strongly express the KIT (CD117) protein, a type III tyrosine kinase receptor encoded by the c-Kit proto-oncogene [1], [2]. Associations with other primary gastrointestinal neoplasms of different histology have been reported, though not with great regularity [3], [4]. Common aetiology and carcinogenetic mechanisms have been considered as possibly underpinning their association, yet this has not yet been conclusively demonstrated. GISTs is commonly seen to be associated with adenocarcinoma of the stomach [4]. There are only a few reports of synchronous occurrence of GISTs of the small intestine and colorectal neoplasms. We report a rare observation of the synchronous occurrence of a small bowel stromal tumour with intraepithelial neoplasia of the colon.

Case report 

A 52 year old male was admitted to our department presenting with chronic diarrhoea, abdominal pain and weight loss during the two months preceding admission. Clinical examination was normal. Blood count test was normal. Colonoscopy showed a polypoid formation of the sigmoid of 2cm. Histological examination of the biopsies revealed intraepithelial neoplasia (Fig. 1). Abdominal CT scan enhanced by an intravenous contrast agent revealed a kystic lesion of 3cm in the arterial phase imaging, localised in the proximal jejunum (Fig. 2). No hepatic metastasis or locoregional invasions of the colonic tumour were found. Because of the pattern of the lesion, endoscopic resection of the colonic tumour was estimated to bear a high risk. The patient was operated on, undergoing hemicolectomy for the colonic adenoma. Alternative surgery procedures were not considered possible because of the feared existence of adenocarcinoma. Exploration of the kystic lesion showed that it belonged to the first jejunal loop, was richly vascularised and had an exoluminal development. An enucleation of the lesion was conducted. Histological and immunohistochimic examination confirmed the diagnosis of stromal tumour c-Kit positive (Fig. 3a and b). The patient was regularly followed up without any treatment. No evidence of recurrence was observed in CT at three months and nine months after the operation.

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Fig. 1. Colonic high grade dysplasia: architectural disarray with prominent palisading of nuclei.

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Fig. 2. The abdominal CT scan showed a cystic lesion of the jejunum.

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Fig. 3. (a) The mildly pleomorphic spindle tumour cells have elongated, blunt-ended nuclei with evenly distributed delicate chromatin and small nucleoli (H&E, 400×), (b) c-Kit positive (H&E, 400×).

Discussion 

Gastrointestinal stromal tumours encompass most gastric and intestinal mesenchymal tumours earlier designated as leiomyoma, cellular leiomyoma, leiomyoblastoma, and leiomyosarcoma. Because the majority of the mesenchymal tumours of the gastrointestinal tract (except the oesophagus) are GISTs, previous data from gastric synchronous tumours with components of smooth muscle tumours may largely reflect GISTs [5], [6].

The simultaneous development of jejunal GISTs and intraepithelial neoplasia of the colon in our patient raised the question of whether such an occurrence was casual or associated with a causative effect. Theoretically, genetic mutations could play an important role in the pathogenesis of intestinal synchronous tumours; however, no available evidence supports the common genetic mutation of intestinal adenocarcinoma [7].

The transmembrane protein c-Kit acts as a receptor for stem cell growth factor (SCF), which is seen in all gastrointestinal stromal tumours. c-Kit is encoded by the kit proto-oncogene, whose mutations are believed to be the cause of GIST c-Kit can be identified by the antibody CD117 using immunohistochemistry [4], [7]. However, colorectal carcinomas are mostly due to mutations in APC, DCC, p53 and k-ras. There are reports of c-Kit expression in colonic cancer cell lines [8]. Here Bellone et al., have reported over expression of c-Kit and SCF in colorectal cancers, showing that c-Kit activation favours the growth, migration and invasive potential of colon cancer cells [9]. Sammarco et al., have observed c-Kit expression in approximately 30% of colorectal cancer patients. However, other studies have showed that c-Kit expression is very rare in colon cancer cell lines [8].

The association of GISTs and adenocarcinoma is commonly seen in stomach [5]. However, the synchronous occurrence of GIST and adenocarcinoma or other neoplasia at two different sites of the gastrointestinal tract is uncommon. The association of small-bowel GIST and colorectal neoplasia has been described in only four case reports [3], [4], [7], [10]. Wronski et al., reported four cases of GISTs in association with gastric adenocarcinoma, gastric lymphoma and colonic adenocarcinoma [3]. The association of adenocarcinoma of the appendix with jejunal GIST was also reported by Melis et al., who also presented two cases of small bowel GISTs associated with colorectal cancer [7]. More recently, another case of synchronous colorectal adenocarcinoma and GIST in Meckel’s diverticulum was also published [10]. Coexisting GISTs are in most cases very small, asymptomatic tumours detected incidentally during surgery. Curative surgical treatment has been possible in most cases. In the patients described in these reports, the prognosis seems to be related to the colonic tumour.

The coincidence of the two entities can also be explained by several epidemiologic aspects. In Tunisia, the incidence of colorectal cancer is relatively high, estimated at 4/100,000/year [11], yet the incidence of GISTs is not known. The department of pathology of our hospital recently reported 40 cases of GIST, with involvement of the stomach in most cases [12]. Therefore, causality could explain such an association, particularly in the high-risk areas of both GISTs and adenocarcinoma.

Conclusion 

Incidental diagnosis of GISTs during the staging of colonic neoplasia is rare but possible. Surgery must be the first therapeutic approach in patients with non-metastatic small tumours. However, in order to explain the simultaneous development of tumours with different histotypes, molecular biology studies are required.