Gastrointestinal lymphomas: Morphology, immunophenotype and molecular features

Abstract

Primary gastrointestinal lymphoma comprises 10-15% of all non-Hodgkin lymphomas and encompasses 30-40% of the total extranodal lymphomas. Approximately 60-75% of cases occur in the stomach, and then the small bowel, ileum, cecum, colon and rectum. Lymphoid neoplasms may consist of mature B, T and less commonly extranodal NK/T cells. Of these, the two most frequently encountered histologic subtypes are extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma), where Helicobacter pylori infection is implicated in a number of cases, and diffuse large B cell lymphoma. Several B cell lymphomas are associated with chromosomal aberrations. Enteropathy-associated T cell lymphoma, type I in particular, usually arises in a background of celiac disease. T cell gene rearrangement confirms clonality. NK/T cell neoplasms are invariably associated with Epstein-Barr virus infection and are often aggressive; thus, differentiation from a benign NK-cell enteropathy is paramount. Although incidence of other hematopoietic malignancies in the gastrointestinal tract such as plasma cell myeloma associated with amyloidosis, plasmablastic lymphoma, Hodgkin disease, histiocytic sarcoma and mast cell sarcoma is extremely rare, these entities have been documented, with the latter two demonstrating aggressive clinical behavior. Endoscopic ultrasonography is an important adjunct in disease staging and follow-up. Conservative antibiotic treatment of stage I MALT lymphomas with associated Helicobacter pylori infection achieves good clinical outcome with high remission rate. Chemotherapy, radiation and rarely surgery are reserved for advanced diseases or cases resistant to conservative therapy and those not associated with Helicobacter pylori infection.

Keywords: Gastrointestinal lymphomas; MALT lymphoma; NK/T-cell enteropathy.

Figure 1

Hypothesized pathways of mucosa-associated lymphoid tissue (MALT) lymphomagenesis with possible transformation to diffuse large B-cell lymphoma (DLBCL)

Figure 2

Left: Lymphoepithelial lesions - where atypical small lymphocytes infiltrate the glandular epithelium [Hematoxylin and eosin (H&E), 400×]; Right: MALT lymphoma associated with H. pylori gastritis with prominent expansion of submucosa by neoplastic lymphoid cells (H&E, 40×)

Figure 3

DLBCL (left), large tumor cells with vesicular chromatin, prominent nucleoli and moderate to abundant amount of cytoplasm (H&E, 400×). The image on the right shows a Burkitt lymphoma with the characteristic “starry sky” appearance and frequent mitotic figures (H&E, 400×)

Figure 4

Type II EATL showing monomorphous, neoplastic lymphoid infiltrate (H&E, 500×). The inset image (upper left, H&E, 20×) demonstrates involvement of surface epithelium

Figure 5

The CD3/CD20 stain, a polymer cocktail consisting of anti-mouse/alkaline phosphatase and anti-rabbit/horseradish peroxidase demonstrates diffuse infiltration of CD3 positive neoplastic T cells (red), whereas, only rare CD20 positive B cells (brown) are present (top left, IHC, 100×). The tumor cells co-express CD8 (top right, IHC, 100×) and CD56 (bottom left, IHC, 100×) and show a high (~80-90%) proliferation index as evident by tumor cell nuclei staining for Ki-67 (bottom right, IHC, 100×)