Collision tumors in the gastrointestinal tract: a rare case series.

A collision tumor is one where histology shows the presence of two distinct primaries involving the same organ without intermixture of individual cell types, ie, a side by side pattern. Here we present three rare cases of collision tumors involving the stomach and transverse colon. There were two cases of collision tumors involving the stomach, one of which was a combination of adenocarcinoma and low-grade non-Hodgkin's (mucosa-associated lymphoid tissue) lymphoma, and the other showed the presence of non-Hodgkin's lymphoma involving the entire stomach wall along with adenocarcinoma infiltrating the muscle layer. The third case comprised a mucinous adenocarcinoma and carcinoid tumor in the large gut.

Cases 1 and 2

The coexistence of a gastric adenocarcinoma and a primary gastric lymphoma occurs rarely, as evidenced by the paucity of relevant case reports.1–4 However, there might be some causal relationship with infections caused by Helicobacter pylori and Epstein-Barr virus.3,5

Case 1 was a 55-year-old Indian man who presented with hematemesis and a sensation of fullness in the upper abdomen. On ultrasound there was gross thickening of the gastric wall along with enlarged gastric lymph nodes. The patient underwent total gastrectomy and esophagojejunostomy. Histology of the specimen confirmed the presence of an infiltrating gastric carcinoma and mucosa-associated lymphoid tissue (MALT) lymphoma.

Case 2 was a 67-year-old Indian man who presented with a sensation of fullness in the abdomen, and a history of anorexia and weight loss. A total gastrectomy specimen showed the presence of adenocarcinoma invading the muscle layer and non-Hodgkin’s lymphoma involving the entire thickness of the stomach wall.

Pathological findings

In case 1, the gross gastric specimen measured approximately 14 × 7 × 2 cm. In the distal part of the stomach, an ulceroproliferative growth with a maximum diameter of 4 cm was seen, involving the entire thickness of the wall. Multiple large lymph nodes, each measuring approximately 1.5 × 1 cm, were seen in the lesser curvature. A section from the stomach showed moderately differentiated adenocarcinoma involving the muscle layer along with lymphoid cells distributed diffusely throughout the gastric wall (Figure 1). Lymphoid follicles with a germinal center and lymphoepithelial lesions were also identified in the specimen, and multiple curved bacteria-like bodies were seen on the mucosal surface of gastric wall. H. pylori was suspected but could not be confirmed because of lack of silver staining at our facility at that time. Immunohistochemistry of the carcinomatous area was cytokeratin-positive, confirming adenocarcinoma (Figure 2), and the lymphoid cells showed CD20 positivity, confirming non-Hodgkin’s lymphoma (Figure 3). The final diagnosis was of a collision tumor comprising moderately differentiated adenocarcinoma and non-Hodgkin’s lymphoma.

Figure 1

Case 1: Adenocarcinoma and lymphomatous portion (hematoxylin and eosin staining, high power).

Figure 2

Case 1: Adenocarcinomatous portion showing cytokeratin positivity.

Figure 3

Case 1: CD20 positivity shown by lymphomatous portion.

In case 2, the gross specimen measured about 10 × 6 ×2 cm, with an ulceroproliferative growth involving the prepyloric region of the stomach. The section from the stomach showed both adenocarcinomatous and lymphoid elements (Figure 4). The lymphoid cells were distributed diffusely throughout the stomach wall, and were confirmed to be

Figure 4

Case 2: Adenocarcinoma with lymphoma.

CD20-positive on immunohistochemistry (Figure 5). The final diagnosis was of a collision tumor comprising adenocarcinoma and non-Hodgkin’s lymphoma.

Figure 5

Case 2: Lymphoid portion of the tumor showing CD20 positivity.

Case 3

Adenocarcinoma is the commonest malignancy of the colon, with collision tumors at this site being extremely rare. Reports of a combination of two independent tumor phenotypes in the colon have included adenocarcinoma with carcinoid, with transitional cell carcinoma,6 and with lymphoma.7–9,12 Possible explanations include simultaneous proliferation of two different cell lines, a common origin for pluripotent precursor stem cells that differentiate into two components, and chance apposition of two unrelated tumors.12

Case 3 was a 65-year-old Indian man with symptoms of hematochesza, anorexia for 5 months, epigastric pain, a lump in the epigastrium, and loose stools for 2–3 months. He underwent total colectomy and the specimen showed the presence of a collision tumor on histological examination.

Gross pathological examination showed an ulceroproliferative growth measuring 7.6 cm in the transverse colon. This was a mucinous tumor containing irregular glands lined by mucinous epithelium with large areas of extracellular mucin material consistent with adenocarcinoma, with an adjacent area showing monomorphic cells in solid nests, consistent histopathologically with a diagnosis of carcinoid tumor (Figure 6). Immunohistochemistry showed the carcinoid area to be chromogranin-positive (Figure 7). The final diagnosis was of a collision tumor comprising adenocarcinoma and carcinoid tumor.

Figure 6

Case 3: Carcinoid and adenocarcinomatous portion (hematoxylin and eosin staining, high power).

Figure 7

Case 3: Chromogranin positivity of carcinoid portion.

Discussion

A neoplasm consisting of more than one type of neoplastic tissue is called a mixed tumor, with two possible subtypes, ie, combined and composite. In the composite tumor, two neoplastic components are intimately intermingled, whereas in the combined tumor, two separate components are present with a distinct interface between them. A further subset of the combined tumor is the so-called collision tumor.

Certain types of tumor, including lymphoma, gastrointestinal stromal tumor, and carcinoid, can occur in collision with gastric adenocarcinoma.10,11 H. pylori plays an important role in the development of both gastric adenocarcinoma and MALT lymphoma. However, genetic instability may possibly be the precipitating factor for such malignancies.24

To our knowledge, there have been 35 cases of gastric collision tumor composed of epithelial and nonepithelial malignant neoplasm reported in the literature.19 The average age of onset for collision tumor is 61 (range 42–80) years and the most frequent combination is adenocarcinoma and malignant lymphoma.12–19 A relationship between H. pylori and MALT lymphoma has been hypothesized because of observation of regression of the lymphoma component with antibiotic treatment for H. pylori.20 In our case series, collision tumors in the stomach presented as a combination of adenocarcinoma and lymphoma. We also suspected H. pylori invasion in case 1, although this could not be confirmed.

Immunohistochemistry shows that MALT lymphoma is positive for CD20, CD21, CD35, and CD79a, with some cases also positive for Bcl-2. CD5 negativity is useful for the diagnosis of MALT lymphoma.25 At our facility, we were only able to test for CD20. In case 2, we demonstrated CD20 positivity, which suggests a diagnosis of non-Hodgkin’s lymphoma.27

Due to the lack of any large series with long-term follow-up, the prognosis of such tumors has not been properly clarified. However, it seems that the survival rate is similar to that of patients with gastric adenocarcinoma but worse than that of patients with MALT-type lymphoma without gastric adenocarcinoma.21 The incidence of a carcinoid tumor of the gastrointestinal tract coexisting with an adenocarcinoma has been reported to be 0.3%–4.3%.19 Most cases of mixed tumor consisting of adenocarcinomatous and carcinoid components arise from the colon in patients with longstanding ulcerative colitis. The possible mechanism for development of adenocarcinoma from longstanding colitis is probably dysplastic changes triggered by the ongoing inflammatory process, whereas carcinoid rarely arises from ulcerative colitis.26 Reports of tumors arising de novo are few.22 In our small case series, we did not see any features of ulcerative colitis. In mixed adenocarcinoid tumors, the prognosis and overall survival depends upon the glandular component.23