Duodenal-type follicular lymphoma
Duodenal-type follicular lymphoma is a form of lymphoma in which certain lymphocyte types, the B-cell-derived centrocytes and centroblasts, form lymph node follicle-like structures principally in the duodenum and other parts of the small intestine. It is an indolent disease which on rare occasions progresses to a more aggressive lymphoma that spreads beyond these originally involved sites.
The disorder now termed DFL had been considered to be a follicular lymphoma that develops in one or more sites of the GI tract as well as in various sites outside of the GI tract; this contrasts with other forms of follicular lymphoma which do not involve the GI tract. The disorder was regarded as a subtype of follicular lymphoma termed primary intestinal follicular lymphomas or Primary gastrointestinal tract follicular lymphomas. However, follicular lymphomas of the duodenum and other parts of the small intestine differ from the other forms of primary intestinal lymphomas in that they are indolent, highly localizes disorders that have a low rate of progression to a systemic disease. In consequence, the World Health Organization kept the more widespread primary intestinal lymphomas within the follicular lymphoma category and reclassified duodenal-/small intestinal-localized lymphoma as a distinct disease entity, DFL.
DFL, while currently considered a malignant disease, has many clinical features which are more similar to the benign predecessor of follicular lymphomas viz., in situ follicular lymphoma, than to follicular lymphoma. Like in situ follicular lymphoma, DFL is most commonly a symptom-free disease that is diagnosed incidentally in patients who are undergoing endoscopy for other reasons. Also like in situ follicular lymphoma, DFL may in rare cases regress spontaneously or progress to a more serious and aggressive form.
Presentation
DFL most commonly afflicts middle-aged adults with a male to female ration of ~1. The disease is usually asymptomatic and diagnosed as an unexpected finding when examining patients by upper GI tract endoscopy conducted for other reasons. A minority of patients present vague abdominal symptoms or, rarely, more specific and serious symptoms such as obstructive jaundice caused by tumors in the duodenum which occlude the bile duct. The endoscopic examination typically reveals one or more polyps, nodules, or confluent whitish granules located in various parts of the GI tract which in a study of 54 patients conducted in Japan were distributed as follows: first part of the duodenum, 4 patients; second part of the duodenum, 54 patients; combined third, and fourth part of the duodenum, 31 patients; jejunum, 44 patients; ileum, 17 patients; cecum, 13 patients; colon and rectum, each 2 patients; and stomach and esophagus, no patients. Lesions were limited to the second part of the duodenum in only 7 patients. In some cases, the lesions may be ulcerated.Pathophysiology
DFL is due to the accumulation of monoclonal centrocytes and their precursor centroblasts to form follicle-like structures in the duodenum and other parts of the small intestine. In virtually all cases of the disease, these cells bear a pathological genomic abnormality that is typical of most but not all forms of follicular lymphoma, i.e. a translocation between position 32 on the long arm of chromosome 14 and position 21 on chromosome 18's q arm. This t translocation juxtaposes the B-cell lymphoma 2 gene on chromosome 18 at position q21.33 near to the immunoglobulin heavy chain locus on chromosome 14 at position q21, and in consequence causes the overexpression of this gene's product protein, BCL2 apoptosis regulator CCL20, a chemokine that is a chemoattractant for lymphocytes and 2) MAdCAM-1, a cell adhesion protein on mucosal vascular endothelial cells that binds to the α4β7 homing receptor on lymphocytes. and 3)' C-C chemokine receptor type 6, which is the lymphocyte receptor for CCL20. Working together, these genomic abnormalities are thought to deliver virtually immortalized centrocytes and centroblases to the involved GI tract tissues in duodenal-type follicular lymphoma. Furthermore, The malignant cells in DFL express immunoglobulin heavy chains made from specific rather than various gene segments of the IGH@ region on chromosome 14. In one study, for example, heavy chains made form VH4 and VH5 segments were expressed in a higher percentage of DFL cases than expected. These findings, along with those showing similarities in the profiles of highly expressed genes in DFL and mantle cell lymphoma suggest that DFL, like mantle cell lymphoma, develops as a consequence of chronic inflammation and specific antigen stimulation. In support of this possibility, there have been reports that DFL regresses in patients who are successfully treated for concurrent Helicobacter pylori'' infestation of the GI tract.Diagnosis
Histological examination of the lesions in DFL usually reveals them to be localized to the GI tract mucosa and submucosa. The lesions consist of abnormal germinal center-containing lymphoid follicles overcrowded with a uniformly-sized population of malignant centrocytes and rare centroblasts. The lesions are classified as low grade in 95-100% of cases. Immunochemical analyses indicate that the latter cells express CD20, CD10, BCL6, and CD79A and have a very low proliferation rate as defined by the intensity of their expression of Ki-67. They also overexpress Bcl2 as a consequence of having the t translocation. These findings are similar to those in follicular lymphoma but the malignant cells in DFL generally have fewer genomic abnormalities than those in follicular lymphoma and the profile of overexpressed genes in DFL tissues more closely resemble those in marginal zone than follicular lymphoma tissues. The diagnosis of DFL depends on finding: the cited histological, and immunolochemical abnormalities; the t translocation; and no evidence that the disease ranges outside of the GI tract as evidenced by negative results for, e.g. bone marrow biopsy and CT scan of the abdomen which thereby rule out involvement of the bone marrow and mesenteric as well as other abdominal lymph node, respectively.Differential diagnoses
differs from DFL by having: lesions which commonly lie outside of the GI tract sites outlined in the Presentation section; a histology more often categorized as Grade 3; and malignant cells that express activation-induced cytidine deaminase but not CD27, CCL20, MAdCAM-1, or C-C chemokine receptor type 6.MALT lymphoma differs from DFL by having: lesions which commonly lie in the stomach and other tissues outside of the GI tract sites outlined in the Presentation section ; involvement of malignant B-cells that do not express CD5, CD10, or BCL6 and commonly have a translocation between chromosomes 18 and 11, i.e. t but not the t translocation; and associations with chronic inflammatory diseases and chronic antigen stimulation;
Mantle cell lymphoma differs from DFL by having: only occasional involvement of the GI tract with polyps that on histologic examination may involve the lamina propria and often infiltrate between rather that replacing intestinal glands and malignant cells which commonly express cyclin D1 and a translocation between chromosomes 11 and 14, i.e. t but not the t. translocation.