Fig. 4.23 Coeliac disease. The non-neoplastic mucosa distant from an anaplastic large cell intestinal T-cell lymphoma displays villous atrophy, crypt hyperplasia (A) and an increase in cytologically unremarkable intraepithelial lymphocytes (B) without evidence of lymphoma. Both the lymphoma (ALCL) and the intraepithelial lymphocytes (IEL) share the same dominant T-cell clone (C) and the same aberrant immunological phenotype.

band-like or patchy microscopic lesions entirely confined to the mucosa {303}. Fibrosis and admixed inflammatory cells are constant features of the pleomorphic medium and large cell and the anaplas-tic large cell ITL types; in the former, an abundance of eosinophils may mask the neoplastic infiltrate {1731}. In contrast, the monomorphic small to medium-sized variant characteristically lacks fibrotic changes and inflammatory background {307}.

Histopathology of the enteropathic mucosa

In the vast majority of cases, the macro-scopically normal intestinal mucosa shows features of coeliac disease, i.e. increase in normal appearing intraepithe-lial lymphocytes (IEL), villous atrophy, and crypt hyperplasia {794}, which has prompted O'Farrelly and co-workers to coin the term 'enteropathy associated T-cell lymphoma' {1383}. An increase in normal appearing IEL (duodenum / jejunum, > 40/100 enterocytes; ileum, > 20/100 enterocytes) represents the single most important feature suggestive of coeliac disease {1172}. The severity of these enteropathic changes is highly variable and similar to coeliac disease; they are most pronounced proximally and improve distally so that the lower jejunum and ileum may appear normal. Furthermore, enteropathy may be minimal or absent if the patient is on a gluten free diet, or if enteropathic sites are missed because of their patchy distribution. Occasionally, the non-neoplastic mucosa in ITL shows a strikingly intense or florid intraepithelial lymphocytosis {2142}.

Immunological phenotyping

Similarities of the immunophenotypes in normal or activated (reactive) intraepithelial lymphocytes (IEL) and the tumour cells in ITL provide an important part of evidence that ITL cells are the neoplastic counterpart of IEL. The expression of the HML-1 defined aEp7 (CD103) on nonneoplastic IEL and in > 50% of ITL, but not in resting peripheral blood T-cells, strongly supports this view {1802}. The vast majority of normal IEL are resting cytotoxic CD3+CD8+CD4-CD2+CD7+ CD5low TIA-1+ T-cells using the a|3 T-cell receptor, but minor subsets such as CD4-CD8- or CD56+ are present as well as predominantly CD4-CD8- yS T-cells {1113, 304}. In ITL, most cases are

CD3+CD4-CD8-CD7+CD5- and co-express the cytotoxic granule-associated protein TIA-1, often together with the activation-dependent cytotoxic molecule granzyme B {305, 382}. Some correlations between ITL morphology and phe-notype exist; pleomorphic medium and large cell lymphomas and lymphomas of anaplastic large cell histology are often CD4-CD8-, the latter express CD30+ but are always ALK1 negative; the monomor-phic small to medium-sized variant is frequently associated with a CD56+CD8+ phenotype {307}.

Cytologically normal IEL abundantly present in the intact enteropathic mucosa in ITL, in ulcerative jejunitis, and in refractory coeliac disease share an identical aberrant phenotype with ITL and are monoclonal, as demonstrated by PCR {103}. They therefore are considered a neoplastic population which, in the absence of concurrent overt ITL, may represent the first step in ITL lymphomagenesis ('intraepithelial lymphoma') and may have already persisted for years {238}.

ITLdiagnosis of endoscopic biopsies

Most cases of ITL are diagnosed on surgical resection specimens. In a minority however, endoscopic biopsies, usually taken from the stomach, duodenum, or colon, are available. These patients frequently have a longer than 6 months history of abdominal pain and weight loss. Some of them are clinically suspected to have inflammatory bowel disease, and occasionally patients had already been biopsied with the diagnosis of IBD or an unclear inflammatory process, thus emphasizing the challenging task of ITL diagnosis in endoscopic biopsies. The immunohistochemical demonstration of an aberrant phenotype is essential in diagnosing ITL, especially in cases which lack overt cytological atypia and/or invasiveness. Furthermore, the neoplastic infiltrate may be subtle or superficial and therefore easily overlooked in routinely stained sections.

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Why Gluten Free

Why Gluten Free

What Is The Gluten Free Diet And What You Need To Know Before You Try It. You may have heard the term gluten free, and you may even have a general idea as to what it means to eat a gluten free diet. Most people believe this type of diet is a curse for those who simply cannot tolerate the protein known as gluten, as they will never be able to eat any food that contains wheat, rye, barley, malts, or triticale.

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