Scary But Innocent Cells—Potentially Helpful Diagnostic Feature for Chronic Lymphocytic Thyroiditis

Summary: Introduction: Chronic lymphocytic thyroiditis (CLT), also known as Hashimoto thyroiditis (HT), is an organ-specific immunologically mediated inflammatory disease. It is the second most common thyroid lesion diagnosed on fine needle aspiration cytology (FNAC). Accurate diagnosis is important as patients may subsequently become hypothyroid and require lifelong thyroxin supplement. Cellular lymphoplasmacytic infiltrate, best when infiltrating follicular epithelial cells, together with aggregates of oncocytic cells are diagnostic features of CLT (Fig. 1A). CLT can be accurately diagnosed in most cases, however, sometimes a definite diagnosis cannot be achieved on FNAC specimens if the histologic features are short for the diagnosis. Materials and Methods: A case of CLT with clusters of ""blast-like"" large lymphoid cells appreciated on Diff-Quik smears raised a concern for lymphoma but lymphoproliferative disorder workup was negative. These lymphoid cells were large, with high nuclear to cytoplasm ratio, simulating blasts (Fig. 1B). They are believed to represent cells from reactive lymphoid follicles, as similar cells can be appreciated in reactive lymph node FNA specimens (Fig. 1D). To evaluate the significance of these large lymphoid cells in CLT, the smears of CLT cytology cases diagnosed between January 2022 and March 2024 were reviewed. Correlation with clinical presentation of hypothyroidism and CLT was performed. Results: Lymphoplasmacytic infiltrate with infiltration of follicular epithelial cells and oncocytes were appreciated in all 35 cases diagnosed as CLT on FNAC. 14 cases out of 35 cases were found to have ""blast-like"" large lymphoid cells present on smears, ranging from ""rare"" (≤ 5/3 HPF) (Fig. 1C) to ""non-rare"" (> 5/3 HPF) in lymphoid-rich areas. 11 of these patients were confirmed to have clinical hypothyroidism due to CLT. These large lymphoid cells were absent in 21 out of 35 cases, and only 7 of these 21 patients were found to be consistent with CLT clinically (Table 1). Conclusions: Lymphocytic infiltration of thyroid follicles is pathognomonic of lymphocytic thyroiditis. Large ""blast-like"" lymphoid cells, admixed with polymorphous lymphoplasmacytic infiltrates, are believed to represent cells from reactive lymphoid follicles, and often more prominent in full blown CLT cases. The presence of these large lymphoid cells shows high correlation rate with clinical presentation of hypothyroidism due to CLT, with a specificity of 82%. If only cases with ""non-rare"" large lymphoid cells present are counted, the specificity of having hypothyroid due to CLT increases to 94%. This feature shows high predictive rate in clinical hypothyroidism and is potentially helpful in diagnosing CLT when other features fall short.