Initially it was difficult to recognize the present case as a T-lineage lymphoma under the light microscopy, because follicular invasion by atypical small lymphocytes, i.e. lymphoepithelial lesion, mimics MALT-type B-cell lymphoma. A lymphoepithelial lesion is a significant morphologic finding in the diagnosis of MALT-type B-cell lymphoma, however, is not specific for MALT-type B-cell lymphoma and similar intraglandular or intraepithelial invasion of small lymphocytes can be seen in Hashimoto's thyroiditis, Sjogren's disease, and enteropathy-type T-cell lymphoma (9
Among thyroid T cell lymphomas reported previously, lymphoepithelial lesion-like change has been described in only 3 cases (5
) (). Including the present case, all of them were associated with Hashimoto's thyroiditis. It is well known that MALT-type B-cell lymphoma arose in the background of chronic inflammation and autoimmune disease and some of them transformed to large B-cell lymphoma. In the thyroid gland, Hashimoto's thyroiditis markedly increases the risk of malignant lymphoma of thyroid gland and most of associated lymphomas are either MALT-type B-cell lymphoma or large B-cell lymphoma. Although there is no consensus about pathogenetic relation between Hashimoto's thyroiditis and primary thyroidal T-cell lymphoma, association of Hashimoto's thyroiditis with thyroid T-cell lymphoma in present case indicate that at least a part of thyroid T-cell lymphoma has a pathogenetic relation with Hashimoto's thyroiditis. Close association of follicular epithelial cells and neoplastic lymphocytes simulating lymphoepithelial lesion of marginal zone B-cell lymphoma may be characteristic finding of this type of T-cell lymphoma.
Summary of the primary thyroid T-cell lymphomas showing lymphoepithelial lesions
Because the infiltrated lymphocytes are phenotypically of helper T-cell origin with a background of Hashimoto's thyroiditis, it suggests that helper T-cell activation induced by chronic inflammation could lead to peripheral T-cell lymphoma of themselves as well as MALT-type B-cell lymphoma. However, further study may be required in CD8+ cytotoxic T-cell lymphomas arising in the background of Hashimoto's thyroiditis like the present case. These lymphoepithelial lesions in the present case are similar to those of enteropathy-type T-cell lymphoma; both individual T-lymphoma cells invade thyroid follicular epithelium or intestinal crypt epithelium. Both primary thyroid T-cell lymphoma and enteropathy-type T-cell lymphoma may be tumors of intraepithelial T-lymphocytes. Both are frequently associated with underlying autoimmune diseases such as celiac disease or Hashimoto's thyroiditis.
On the absence of a reliable immunohistochemical marker of clonality of T-lymphocytes, genetic study is the most useful method to detect the presence of a dominant T-cell clone in a lymphocytic infiltrate (2
). In recent days, gene rearrangement of immunoglobulins and TCR can be used as a marker of thyroid lymphoma, particularly when the histologic and immunohistochemical diagnosis of malignant lymphoma is inconclusive. The sensitivity of detecting thyroid lymphoma by the Southern blot method is about 85% in Matsuzuka's series (13
), while the sensitivity by PCR is 75% in Torlakovic's series (8
). In Signoretti's series, sensitivity rate was elevated up to 95% of the T-cell lymphoma using all Vγ1-8, Vγ9, Vγ10, Vγ11, and Jγ1/Jγ2 primers (14
). Here, the present case was confirmed as T-cell lymphoma because it showed TCR-γ gene rearrangement, in which monoclonality was detected in Vγ11 region. This diverges from that of other conventional T-cell lymphomas which usually show monoclonalities in Vγ1-8 region.
Treatment has not yet been fully established and no survival statistics still exist for thyroid T-cell lymphoma. The patients underwent surgery, chemotherapy and radiation, combined therapy or untreated in the reports. The choice is cyclophosphamide, daunorubicin, vincristine and prednisolone (CHOP) based chemotherapy (15
). Peripheral T-cell lymphoma is known to take worse prognosis than does B-cell lymphoma. However, though cases reported are rare, none of the cases of the primary thyroid T-cell lymphomas except for one died from the disease (16
). Even in Okamoto's report, cytotoxic TIA-1 expressing T-cell lymphoma showed partial spontaneous regression before diagnostic hemithyroidectomy (17
Here, we report the second case of cytotoxic T-cell lymphoma in the thyroid gland, and unique association between thyroid follicles and neoplastic T-lymphocytes, i.e. lymphoepithelial lesion, may be characteristic feature of this type of cytotoxic T-cell lymphoma.