Abstract
Gastric mucosa associated lymphoid tissue lymphomas (MALTomas) are well-documented and their management effectively established, but colonic MALTomas are extremely rare and not many know it could occur. We report the first colonic MALToma in the UK. The patient was managed in accordance with gastric MALToma management modalities in accordance with the evidence in the literature. After failure of medical management, a surgical resection was the last and successful option for treatment.
Though gastric MALToma management is well-established, the colonic form of the disease does not act the same and requires a more aggressive approach.
BACKGROUND
Mucosa associated lymphoid tissue (MALT) lymphoma was first used in 1983 by Isaacson et al.1 These lymphomas are a subtype of marginal zone B-cell non-Hodgkin’s lymphoma (NHL) arising from extranodal sites that normally do not have lymphoid tissue. MALT lymphoma, or MALToma, make up 8% of all B-cell lymphomas.2 The disease has a median age of 61 years and a female to male ratio of 1.2:1.2 MALTomas can affect many tissues but the gastrointestinal tract is the commonest site affected by the disease of which gastric MALTomas are the most common.2–4 In contrast, colonic MALToma is very rare and only a handful of cases have been reported over the years.3,4
CASE PRESENTATION
A 45-year-old woman who was treated with chemotherapy for Hodgkin’s disease stage IIB, since been in complete remission, was referred to the outpatients clinic in 2004 with symptoms of watery diarrhoea occasionally mixed with stool and associated with lethargy and weight loss. Clinical examination was unremarkable.
While small bowel studies and duodenal biopsies were negative, a flexible sigmoidoscopy revealed ecstatic blood vessels and an inflamed rectum up to the recto-sigmoid junction. She was subsequently treated with prednisolone suppositories to good effect.
INVESTIGATIONS
Multiple recto-sigmoid biopsies revealed lymphocytic infiltration with microulceration of the mucosa and lymphoepithelial lesions.
Immunohistochemistry demonstrated that the tumour cells were CD20 and CD 79a positive and bcl-2 positive. Staining for light chains revealed an excess of kappa light chain positive plasma cells, while the remaining fragments show moderate lympho-plasmacellular infiltration. The interfollicular area was made up by numerous B cells (CD20 and CD78a) with a low proliferating fraction and brisk reactive T cells (CD3). The B cells infiltrated the muscularis mucosa, while numerous plasma cells were present within the mucosa. In conclusion, these features were consistent with a low grade, non-Hodgkin’s, B-cell lymphoma of MALT type. A definitive diagnosis of inflammatory disease with a superimposed MALToma of the rectum and descending colon was made.
Ultrasound revealed no evidence of lymphadenopathy or lymphoma mass in the abdomen, while a staging CT limited the disease to the rectum and colon with no distant spread.
TREATMENT
As the disease persisted with episodic severe flares of colitis, the patient was commenced on two courses of chlorambucil by the haematologists with disappointing results as her symptoms progressively worsened. The decision was taken for treatment with low dose radiotherapy to the rectum, but unfortunately symptoms did not improve.
Oesophageal-gastroscopy revealed no abnormality and biopsies indicated no evidence of Helicobacter pylori growth. However, a course of H pylori eradication treatment was given in the hope that this colonic MALToma may act similarly to cases reported, where H pylori eradication treatment in H pylori negative patients resulted in subsequent regression of the colonic MALToma. Again the MALToma proved resistant to this treatment method. The decision for surgical intervention was the only option left as a definitive treatment approach.4 A colectomy and, subsequently, an ileo-anal pouch formation was carried out.
OUTCOME AND FOLLOW-UP
Regular pouchoscopies as part of the patient’s follow-ups have all been normal. She is now fit and well and symptom free since her operation.
DISCUSSION
All lymphocytes originate from the bone marrow and are programmed to carry out specific functions by certain lymphoid organs. T and B cells develop within the primary lymphoid tissues (thymus for T cells and bone marrow for B cells) and then circulate to the secondary lymphoid tissues (lymph nodes, spleen, tonsils and MALT).
Lymphoid tissue is frequently found distributed in mucosal surfaces in non-encapsulated patches and is given the term of MALT. In the gut, it is known as gut-associated lymphoid tissue (GALT, primarily Payer’s patches). GALT may be a normal component in the small intestine, which may be multi-focal in distribution and is designed to protect the gut mucosa of potential antigen penetration. It is responsible for eliciting localised immune response because systematic immune response is associated with highly inflammatory reactions that would deleterious to the fragile mucosa.
MALTomas arise from the marginal zone of the lymphoid follicles and are characterised by the presence of a uniform infiltrate of small centrocyte-like lymphocytes and a superficial plasma cell-rich zone. These centrocyte-like cells focally invade and destroy the glandular epithelium forming lymphoepithelial lesions, which are characteristic but not pathognomonic for MALTomas.5
Low grade B-cell non-Hodgkin’s lymphoma arising from extranodal MALT is a recently recognised and clinically distinct entity, with characteristic clinical behaviour, histological features and cytogenetic abnormalities.6 Immunohistochemically, the tumour cells are typically CD20+, CD79a+, CD5−, CD10−, CD23−, CD43+/−, CD11c+/−, and CD21+ and CD35+.2 Cytogenetically there are typically three translocations seen in about 35% of all MALTomas: t(11;18)(q21;q21), t(1;14)(p22q32) and t(14;18)(q32;q21).2
Initially studied extensively in the stomach over the last decade, gastric MALToma is a neoplasm with a very indolent course, an excellent prognosis, has a tendency to remain localised and seldom involves lymph nodes and bone marrow.
Current evidence suggests that there is a strong relationship between chronic inflammatory states and autoimmune diseases in the formation of a MALToma.2,7 Chronic antigenic stimulation, such as stimulation by H pylori, is vital to the growth of MALToma as revealed in the causative relationship that exists between H pylori infection and gastric MALToma.2,8 H pylori infection was found to be positive in more than 90% of gastric MALTomas.2,8 It has been shown that autoimmune diseases increase the risk of lymphoma transformation.2 Diseases like Sjogren’s syndrome, Hashimoto’s thyroiditis and systemic lupus erythematosus often predispose in the development of MALTomas of the salivary glands, thyroid and the respiratory tract.2 Other sites that have been affected by the disease are the thymus, breast, prostate and kidney, but colonic MALToma is not well-recognised.2–4,9,10 Chronic inflammatory states and autoimmune diseases may act as antigenic stimulators for colonic mucosa, although the exact mechanism and underlying pathogenesis involved in the development of this tumour is not yet known. For lymphoma transformation and progression to occur, secondary genetic mutations are necessary.10 A cancer-prone phenotype may also exist in the MALToma patient, a link first noticed by Zucca et al who observed a high incidence of other neoplasm (20%) in patients with low-grade gastric MALToma.11
Recent evidence suggests that H pylori negative colonic MALToma can successfully regress with H pylori eradication treatment (lansoprazole, amoxicillin and clarithromycin).4
Many MALToma patients have localised disease and long survivals.12 Other modalities of treatment besides H pylori eradication treatment have been used, such as chemotherapy, radiotherapy and surgical resection.2,4 Surgical resection is the treatment of choice if eradication treatment fails.4 However, H pylori eradication treatment and surgery are effective for low-grade MALTomas, systematic chemotherapy is the choice for high grade disseminated disease and radiotherapy is an alternatives in some cases.12,13
In conclusion, colonic MALToma should be thoroughly investigated as a deferential diagnosis in patients who present with unexplained lower gastrointestinal symptoms and have either a past history of H pylori or an autoimmune disease. Also, treatment depends on the patient’s condition but eradication treatment should be the first-line management before any further interventions.
After thorough search of the literature, we believe that this is the first case of colonic MALT lymphoma in the UK.
LEARNING POINTS
MALTomas can occur in any part of the intestinal tract and should not be ruled out if there is a high suspicion.
Management is initially with Helicobacter pylori eradication treatment.
Other modalities of treatment should be considered if H pylori eradication treatment fails.
Footnotes
Competing interests: none.
Patient consent: Patient/guardian consent was obtained for publication.
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