T cell lymphoma of the thyroid gland in celiac disease

Most lymphomas of the thyroid gland are almost exclusively classified as the B cell type (1), although a T cell lymphoma has been reported (2). Thyroid lymphomas occur predominately in elderly women, are often associated with chronic thyroiditis and appear to have a reasonably good prognosis (1,3). B cell-type lymphomas are believed to be mucosa-associated lymphomas that have been derived from lymphoid cells (3). T cell lymphomas have been reported in a limited number of anatomical sites, including cutaneous and nasopharyngeal regions (4,5). In addition, these rare peripheral T cell lymphomas have been localized in the intestine and a rare hepatosplenic variety has been recently proposed in a revised European-American classification of lymphoid neoplasms (6,7). For both the intestinal and hepatosplenic types, linkages with adult celiac disease have also been described (8,9). Previous reports (10-12), including a study from Vancouver (13), have detailed clinical features of celiac-associated autoimmune thyroid disease, including altered thyroid function and the relatively frequent association with both dermatitis herpetiformis and a complicating intestinal lymphoma. In one investigation (13), thyroid disease was detected in 16 of 96 consecutively evaluated patients with celiac disease, or almost 20%. It was hypothesized that thyroid diseases may be observed commonly in celiac disease, possibly due to shared embryological origins of the thyroid gland and the gastrointestinal tract or common immunopathological features. In the present report, a woman with biopsy-defined celiac disease and a prior diagnosis of chronic thyroiditis with biochemical evidence of thyroid gland hypofunction developed a diffusely enlarged thyroid gland. Subsequent biopsies revealed infiltration with atypical lymphoid cells characterized with immunohistochemical studies as a T cell type lym-

ver (13), have detailed clinical features of celiac-associated autoimmune thyroid disease, including altered thyroid function and the relatively frequent association with both dermatitis herpetiformis and a complicating intestinal lymphoma.In one investigation (13), thyroid disease was detected in 16 of 96 consecutively evaluated patients with celiac disease, or almost 20%.It was hypothesized that thyroid diseases may be observed commonly in celiac disease, possibly due to shared embryological origins of the thyroid gland and the gastrointestinal tract or common immunopathological features.
In the present report, a woman with biopsy-defined celiac disease and a prior diagnosis of chronic thyroiditis with biochemical evidence of thyroid gland hypofunction developed a diffusely enlarged thyroid gland.Subsequent biopsies revealed infiltration with atypical lymphoid cells characterized with immunohistochemical studies as a T cell type lym-BRIEF COMMUNICATION HJ Freeman.T cell lymphoma of the thyroid gland in celiac disease.Can J Gastroenterol 2000;14(7):635-636.Previous studies have reported the association between celiac disease and T cell lymphoma of the intestine as well as hepatosplenic lymphoma, a specialized peripheral type of T cell lymphoma.In this report, a 66year-old woman with dermatitis herpetiformis and biopsy-defined celiac disease developed a thyroid mass that proved to be a T cell lymphoma.A T cell lymphoma in the setting of celiac disease appears to be unique.The thyroid gland, due to its shared embryological developmental links with the gastrointestinal tract, is possibly another site of extranodal lymphoma linked to celiac disease.
phoma.Although chronic thyroiditis may be complicated by lymphoma, a T cell type lymphoma in the setting of celiac disease without evidence of intestinal lymphoma is unique.

CASE PRESENTATION
A 66-year-old woman with dermatitis herpetiformis was initially evaluated in 1994 for diarrhea and weight loss.Small intestinal biopsies showed a severe 'flat' mucosal lesion, typical of untreated celiac disease, and she was treated with a gluten-free diet alone.Her diarrhea resolved and she regained 10 kg.Repeat small intestinal biopsies in 1995 showed normalization of the villous structure.In 1996, thyroid gland hypofunction was suggested by an increased level of thyroid stimulating hormone.Thyroid microsomal antibodies were strongly positive -1:25,600.Thyroid replacement therapy was not administered.She had no gastrointestinal symptoms, and results of a small intestinal barium study were normal.In 1997, she was re-evaluated, and a diffusely enlarged thyroid gland was initially detected.No peripheral lymphadenopathy was evident.Open surgical biopsy revealed diffuse infiltration of the thyroid gland with atypical lymphoid cells (Figure 1).Immunophenotyping was positive for CD3, a marker of T cell differentiation.Two weeks later after diagnosis, she suffered a fatal myocardial infarction.

DISCUSSION
This report serves to document a rare form of thyroid lymphoma of the T cell variety that occurred in the setting of biopsy-defined celiac disease, underlying chronic thyroiditis and dermatitis herpetiformis.In earlier studies of celiac disease as well as dermatitis herpetiformis (10)(11)(12), including a prior report in this journal from this hospital ( 13), the apparent relationship between celiac disease, dermatitis herpetiformis and thyroid disease, particularly chronic thyroiditis, was noted.In addition, in the latter report (13), the relatively frequent complication of an intestinal lymphoma was reported in three of 16 celiac patients with thyroid disease.In a single previous report from Japan, a T cell lymphoma was recorded in a patient with a prior diagnosis of chronic thyroiditis (2).In their study, lymphoma cells were also shown to react with gamma-type, but not beta-type, T cell receptors, and DNA analysis revealed clonal rearrangement of the T cell receptor gamma-chain gene.Studies were not described to determine whether celiac disease was present in that patient.However, these immunophenotypical characteristics are reminiscent of changes that have been reported in the intestinal T cell type lymphoma (8) that has been closely linked with celiac disease (14-16) as well as the recent description (9) of a rare peripheral T cell hepatosplenic variety of lymphoma that has been described in a single patient with biopsy-defined celiac disease complicated by fulminant liver failure.This case illustrates another form of extranodal lymphoma that may be linked to celiac disease.