Primary gastrointestinal lymphomas

Vandenberghe E.

Correspondence: vandenberghesec@stjames.ie

Epidemiology and classification

Primary gastrointestinal lymphomas comprise less than 5% of all lymphomas diagnosed in the western world, with a variable geographical and ethnic incidence. The biology and management vary with the main diagnostic (WHO) subtypes which include Gastric MALT lymphomas, Enteropathy associated T-cell lymphoma (EATCL). Other lymphomas which frequently involve the gastrointestinal tract include diffuse large B-cell lymphoma, mantle cell lymphoma and Burkitts lymphoma; but are not considered primary gut lymphomas and will not be covered in this lecture. The pathogenesis of MALT and EATCL lymphomas is linked to abnormal antigen drive (gluten/Helicobacter infection) resulting in chronic inflammation and lymphoma development. The lymphomas are otherwise radically different; MALT lymphomas are indolent B-NHL, which respond to antigen-drive withdrawal and minimal therapy with an overall survival (OS) > 80% at 5 years, whereas EATCL is an aggressive T-cell lymphomas associated with a poor outcome.

Gastric MALT lymphoma

Clinical features: Gastric MALT lymphomas incidence in the Western World is approximately 6 per million, with a median onset at 60 years, slight female predominance and almost invariable association with Helicobacter pylori infection. Patients typically present with non-specific dyspeptic type symptoms and the diagnosis is made gastroscopically. 80% of patients have Stage I/II disease.

Pathology: The pathological appearance is of small- to medium-sized round or minimally irregular cells, with clumped nuclear chromatin, abundant pale cytoplasm and lymphoepithelial lesions. The cells express pan-B markers but are CD5, 10 and 23 negative. The t(11;18(q21;q21) detectable by FISH is pre­sent in up to 50% of cases with PCR-detectable immunoglobulin gene rearrangements in 90% of cases.

Management: H pylori eradication is standard treatment for all patients and in those with disease confined to the mucosa and submucosa results in a durable CR in 70% of cases. For persistant or progressive disease chemotherapy with Chlorambucil +/- Rituximab or loco-regional radiotherapy with 20 Gy are standard approaches. There is no evidence that more intensive therapy results in a better outcome. Life long follow-up should include regular endoscopy.

Enteropathy-associated T cell lymphoma

Clinical features: Coeliac disease (CD) is caused by gluten intolerance resulting in small intestinal sub-villous atrophy and malabsorption of variable severity which is managed with a gluten free diet (GFD). Coeliacs have a 20 fold increased rate of developing lymphoma with 60–75% of them sub-typed as EATCL. Clinical presentation follows 3 patterns (1) development of refractory coeliac disease (RCDII) despite adherence to a GFD (2) acute presentation with gut perforation/acute severe malabsorption despite adherence to a GFD and (3) acute presentation as in (2) with no previous diagnosis of CD. EATCL diagnosis can be challenging as it is usually confined to the small intestine and tissue is usually obtained surgically or by endoscopy (gastroscopy/double balloon entersocopy).

Pathology: EATCL is characterised by a monomorphic population of medium to large cells with round or angulated vesicular nuclei, prominent nucleoli and moderate to abundant, pale-staining cytoplasm with expression of CD3+, CD5+, CD7+, CD8+/-, CD4- and CD103+.

Management: The 5 year OS is 20% with conventional chemotherapy and this poor outcome is thought to be related to poor patient performance status secondary to nutritional deficiency/gastrointestinal surgery and the chemo-refractoriness inherent to T-cell lymphomas. Outcome can be improved using intensive nutritional support and primary chemotherapy followed by an autologous transplantation for patients under the age of 65 resulting in a 5 year OS of between 50–60%.

Refractory coeliac disease: Patients who are diagnosed with an RCDII prodrome are interesting both for insights into EATCL lymphomagenesis and also because they may respond to less intensive therapy, thus reducing the risk of EATCL transformation. RCD II is characterised by sub-villous atrophy, loss of CD8 intra-epithelial lymphocytes and clonal T-lymphocytes with 70% progression to EATCL within 5 years. A small study of patients with RCDII who responded to Cladribine therapy had a 5 year OS of 83% which may be improved further by autologous SCT.

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