Gastric Lymphomas and Other Gastric Malignancies

Abstract

On endoscopy, gastric lymphomas present polypoid mass, ulcerative infiltration, or hypertrophic thick folds. At times, however, the features are nonspecific with mucosal hyperemia or irregular erosions. Tumor stage as well as histologic subtypes, which are the most important prognostic and therapeutic factors, should be determined by endoscopic procedures.

Gastric carcinoids can be classified by histologic grade and clinical conditions. Type I and II tumors present multiple, small, localized polyps associated with hypergastrinemia, either secondary to chronic atrophic gastritis or as part of Zollinger-Ellison syndrome, and have low malignant potential. By contrast, large solitary (type 3) and poorly differentiated carcinomas (type 4) are not associated with hypergastrinemia and commonly metastasize.

Rarely, metastatic tumors to the stomach are found in melanoma and lung and breast cancers. Polypoid masses mimicking submucosal tumors are common endoscopic features.

13.1 Gastric Lymphomas

13.1.1 Definition

Gastric lymphomas manifest either primary gastric lymphoma or gastric metastasis of systemic lymphoma. Primary gastric lymphoma is defined by that the tumor presents extranodal localization and, after routine staging procedures, constitutes the predominant disease localization in the stomach. It accounts for 1–5% of all primary gastric malignancies. Tumor stage as well as histologic subtype is the most important prognostic factor.

13.1.2 Staging Systems

The Ann Arbor stage and TNM classification (Table 13.1) were proposed to describe the depth of tumor invasion, extent of nodal involvement, and local tissue infiltration by lymphoma [1].

Table 13.1 Staging systems for gastrointestinal lymphomas

13.1.3 Endoscopy

Endoscopic features of gastric lymphomas can be categorized into three different types: (1) exophytic with polypoid masses, (2) ulcero-infiltrative, and (3) hypertrophic with large, nodular folds (Fig. 13.1). However, at times, the features are nonspecific with mucosal hyperemia, edema, friability, or erosions. Gastric lymphomas should be differentiated from other gastric diseases including gastric carcinoma, rugal hypertrophic gastritis, acute gastric mucosal lesions, or NSAID-induced gastritis.

Fig. 13.1

Endoscopic features of gastric lymphomas. (a) exophytic mass, (b) ulcerative infiltration, (c) hypertrophic thick folds, (d) ill-defined hyperemia and erosions

Deep biopsies are often required because gastric lymphomas arise from subepithelial lymphoid tissue. In addition, tumor samples should be obtained sufficiently for an accurate histologic subtyping of lymphomas by specific molecular or genetic markers.

13.1.4 Histological Subtypes

13.1.4.1 Gastric Extranodal Marginal Zone B-Cell Lymphoma of MALT

Extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissues (MALT) is a B-cell non-Hodgkin lymphoma with perifollicular, marginal zone growth of small lymphocytes. MALT lymphoma is the most common type of gastric lymphomas. Helicobacter pylori (H. pylori) is the main causative agent, and more than 90% of cases are associated with the infection.

Endoscopic findings of gastric MALT lymphoma vary from minimal mucosal changes to ulceration or masses mimicking gastric carcinoma (Fig. 13.2). Because there is no unique appearance indicating MALT lymphoma, endoscopic biopsy should be taken in any suspicious lesions.

Fig. 13.2

Gastric MALT lymphoma. (a) Hyperemic, irregular erosions. (b) Hypoechoic thickening of mucosal layer (T1m). (c) Rugal hypertrophy. (d) Hypoechoic tumoral infiltration in the submucosa (T1sm). (e) Ulceration with fold changes. (f) Submucosal invasion of tumors (T1sm). (g) Ulcerative mass. (h) Hypoechoic tumor infiltration in the muscularis propria (T2). (i) Diffuse infiltration with friability. (j) Irregular outer border of the muscularis propria (T2)

Stage is the most important prognostic factor of gastric MALT lymphoma. Endosonography is the only technique that visualizes the layers of the gastric wall. It enables to define depth of tumor invasion (T1-4) and metastasis to regional lymph nodes (N0-1).

H. pylori eradication is highly effective in treating gastric MALT lymphomas [2]. Tumors confined to the mucosa or submucosa (I1E) regress more frequently than that with deeper invasion. H. pylori eradication is not successful in regression of higher stage MALT lymphoma.

13.1.4.2 Diffuse Large B-Cell Lymphoma

Excluding gastric MALT lymphoma, diffuse large B-cell lymphoma (DLBCL) accounts for approximately 60% of all gastric lymphomas. Gastric DLBCL is an aggressive lymphoma that might arise de novo or from MALT lymphoma transformation. Endoscopy features include exophytic mass, ulcerative infiltration, or hypertrophic thick folds (Fig. 13.3).

Fig. 13.3

Diffuse large B-cell lymphoma. (a) exophytic mass, (b–d) ulcerative mass, (e–f) hypertrophic thick folds

13.1.4.3 Mantle Cell Lymphoma

Primary gastrointestinal mantle cell lymphoma is rare with a frequency of 4–9% of all gastrointestinal non-Hodgkin lymphomas. It was first described, so-called, as multiple lymphomatous polyposis (Fig. 13.4). Typically, multiple lymphomatous polyps in various diameters involve several digestive tracts. Some of the lesions are ulcerative.

Fig. 13.4

Multiple lymphomatous polyposis of mantle cell lymphoma. (a) Ulcerated gastric mass, (b) duodenal polyps, (c, d) colonic mass with numerous small polyps

13.1.4.4 Enteropathy-Type T-Cell Lymphoma

Enteropathy-associated T-cell lymphoma (EATL) is a rare form of aggressive T-cell lymphoma accounting for less than 1% of non-Hodgkin lymphomas. EATL can be divided into two types. Type I is the most common and highly associated with adult-onset celiac disease. This type mostly presents with malabsorption, weight loss, and celiac disease-related symptoms. Type II may occur sporadically and has no association with celiac disease. This type presents often with obstruction or perforation of the small bowel.

Most EATL are localized in the proximal small intestine, particularly in the jejunum. However, the tumors may occur at the ileum, colon, or stomach. When T-cell lymphomas develop in the stomach, they are usually associated with infection by human T-lymphotropic virus type 1.

EATL is often multifocal and may show mucosal flattening or ulceration on endoscopy (Fig. 13.5). Occasionally, the tumor forms an ulcerative mass that invades the intestinal wall. Rarely, EATL present as a bulky mass or as a submucosal tumor.

Fig. 13.5

Enteropathy-type T-cell lymphoma. (a) Multiple, erosive, and superficial infiltration of enteropathy-associated T-cell lymphoma in the duodenum, (b, c) ulcerative T-cell lymphoma

13.2 Other Gastric Malignancies

13.2.1 Gastric Neuroendocrine Tumors (Gastric Carcinoids)

13.2.1.1 Definition

Gastrointestinal neuroendocrine tumors (NETs; gastric carcinoids) are categorized into: (1) well-differentiated NETs, (2) well-differentiated neuroendocrine carcinomas, and (3) poorly differentiated neuroendocrine carcinomas. Neuroendocrine carcinomas are defined as the tumors with vascular invasion, invasion into the deeper walls, or with distant metastasis.

13.2.1.2 Clinicopathological Classification

Gastric NETs can be classified into four types based on histologic grade and underlying clinical conditions (Table 13.2) [3]. Histologically, the tumors are graded as G1, G2, or G3 on the basis of proliferative activity (Ki-67 index, mitotic rate).

Table 13.2 Clinicopathological characteristics of neuroendocrine neoplasms of the stomach

13.2.1.3 Endoscopy

The vast majority of gastric NETs manifests as multifocal, small gastric polyps in the atrophic gastric mucosa (type 1) or as part of Zollinger-Ellison syndrome (type 2) (Fig. 13.6). By contrast, type 3 gastric NETs or poorly differentiated carcinoma (type 4) presents as solitary ulcerative mass. Endosonography is a procedure to visualize tumor size and depth of intramural invasion.

Fig. 13.6

Types of gastric carcinoids. (a–c) Multifocal small polyps of type 1, (d) hypoechoic small tumor within the deep mucosa, (e, f) type 3 with solitary intramural mass, (g) ulcerative mass of type 4, poorly differentiated carcinoma

13.2.2 Gastric Metastasis from Malignancies of Other Organs

Metastatic tumors to the stomach are rarely found in melanoma and lung and breast cancers [4]. Clinical manifestation includes gastrointestinal bleeding or anemia. Polypoid masses with erosions or ulcerations are common endoscopic features (Fig. 13.7). The metastatic tumors may present multiple lesions located in the upper part of the stomach, which mimic submucosal tumors at times.

Fig. 13.7

Gastric metastasis. (a, b) Exophytic masses with dark pigments (melanoma), (c) multiple ulceration (lung cancer), (d) ulcerofungating mass (lung cancer), (e) hemorrhagic mass (hepatocellular carcinoma)