Objectives: To study the different forms of malignant lymphoma complicating coeliac disease in a low-prevalence area, according to extranodal-nodal and extraintestinal-intestinal manifestations.
Subjects and setting: Patients recruited from two University Hospitals (Amsterdam, Leiden) and from PALGA (National Dutch data-bank) over a 16-year period.
Design: Review of hospital charts with respect to clinical presentation and treatment of both coeliac disease and malignant lymphoma. Re-evaluation of morphology and staging by immunoperoxidase, enzyme- and immunohistochemical stainings on unstained and frozen materials.
Main outcome measures: Clinical behaviour and T- or B-cell morphology of extranodal intestinal, extranodal extraintestinal and nodal intestinal disease.
Results: Fourteen cases of enteropathy-associated lymphoma could be traced, 10 with a history of coeliac disease, four primarily presenting with malignant lymphoma. The usual extranodal intestinal lymphoma (eight cases) presented with abdominal pain, weight loss, and malabsorption. Six had atypical disease: four presented with extranodal extraintestinal disease, located in the skin or the respiratory tract; two patients had intractable malabsorption and oedema caused by a nodal intestinal lymphoma. Re-evaluation with additional immunohistochemical stainings in 11 patients showed a pleomorphic malignant infiltrate of histiocyte-like cells of T-cell origin, with a pattern of CD3+; CD4-; CD5 +/-; CD7+ and CD8-. It also established a more appropriate diagnosis in four, an 0.6-year earlier diagnosis in six, and an upgraded stage of disease in two patients. A more extensive spread and poorer outcome appeared to become more probable in the ranking order of extranodal intestinal, extranodal extraintestinal and nodal intestinal lymphoma.
Conclusions: A proper and timely diagnosis of enteropathy-associated lymphoma requires clinical vigilance and unrelentless perseverance to obtain adequate fresh and frozen tissue for histochemical staining. Further research in a larger number of patients is warranted to investigate the relation between the primary site of the lymphoma, i.e. extranodal intestinal, extranodal extraintestinal, or nodal intestinal, and (its impact on) clinical presentation and prognosis.