Primary thyroid lymphoma (PTL) is defined as a lymphomatous process involving the thyroid gland without contiguous spread or distant metastases from other areas of involvement at diagnosis [3
]. PTL constitutes 5% of all thyroid malignancies and occurs in less than 1% of all non- Hodgkin's lymphomas [3
]. The majority of patients are middle to old aged women [4
]. Studies have shown that PTL typically arises in the setting of autoimmune thyroiditis and it takes, on an average, 20 to 30 years to develop after the onset of lymphocytic thyroiditis [5
]. A short history of a rapidly enlarging neck mass often associated with dyspnoea, difficulty in swallowing, or voice change is the hallmark presentation of thyroid lymphoma [6
]. Therefore, clinically this may be confused with anaplastic thyroid carcinoma. Hoarseness, respiratory distress, cough and dysphagia were the usual presenting manifestations in our patients.
Hypothyroidism at the time of diagnosis is documented in 30–40% of patients due to replacement of thyroid parenchyma by the lymphomatous process or due to underlying Hashimoto's thyroiditis. Thyrotoxicosis is exceedingly rare [7
]. Seven of our patients at presentation were euthyroid and three were hypothyroid. Circulating antibodies to thyroid peroxidase are positive in 60–80% of patients suggesting underlying lymphocytic thyroiditis as a predisposing factor. In the present series, six patients had significantly elevated thyroid microsomal antibody titer.
Fine needle aspiration has become the procedure of choice for the initial pathological diagnosis of thyroid nodule. However, studies have also shown inconsistent results in the diagnosis of lymphoma of the thyroid. In one series, a correct diagnosis with FNAC was made in 70–80% of patients with thyroid lymphoma [8
], but in others, FNA was suggestive but not diagnostic in only 50–60% of patients [9
]. In the present study, nine out of ten cases (90%) of the cases of PTL were correctly diagnosed by FNA. A primary thyroid non-Hodgkin lymphoma is usually of large cell type [13
] and a diagnosis of large cell lymphoma is easy on FNA and features like lack of cellular cohesion and presence of lymphoglandular bodies in the background are features strongly against a diagnosis of anaplastic carcinoma [14
]. ICC confirms the lymphoid origin of the cells and their B or T- lineage. By contrast, cytological diagnosis of MALT- lymphomas is difficult, because of heterogeneous appearance of the neoplastic infiltrate [14
]. The principal problem with a cytological diagnosis of low- grade lymphoma of the thyroid is its differentiation from HT. The distinguishing features may be the abundance of lymphoid tissue and a high proportion of intermediate centrocyte- like cells in low- grade NHL as compared to HT. False negative results may be due to sampling error also as low- grade B- cell MALT lymphoma originates from HT and the two usually coexist [14
]. Due attention to dual population of lymphoid cells, presence of monocytoid cells in FNA smears and extensive follicular epithelial destruction and the clinical setting enabled us to diagnose three cases of non- Hodgkin's lymphoma of intermediate grade. However, we missed the diagnosis of NHL on FNAC in one case reported as lymphocytic thyroiditis, which on subsequent subtotal thyroidectomy, was reported as non- Hodgkin's lymphoma. FNAC cytomorphology in conjunction with flow cytometric (FC) immunophenotyping has become a reliable and accurate method for the diagnosis and classification of many lymphoproliferative disorders. CD4/CD8 T-cell ratio comparisons are made with cytomorphological diagnoses of reactive, atypical, non-Hodgkin lymphoma, and Hodgkin lymphoma cases [15
PTL frequently present in clinical stage IE and IIE. Treatment is similar to other nodal lymphoma. For patients with intermediate or high-grade lymphoma, the best results are obtained from cyclophosphamide, daunorubicin, vincrstine and prednisolone (CHOP) based chemotherapy. Radiation therapy is used most commonly after 3–6 courses of chemotherapy in form of modified mantle irradiation including thyroid, bilateral neck, supraclavicular area and mediastinum [17
]. Our patients received CHOP based chemotherapy, two of our patients had relapsed with bone marrow involvement and local nodal recurrence. One died of lymphomatous process and other was controlled with radiotherapy. The poor prognostic factors include age more than 60 years, performance status grater than 1, elevated lactate dehydrogenase (LDH) and β2
microglobulin, extranodal sites more than 1 and Ann -Arbor staged III-IV [18
In summary, we report a retrospective study of ten cases of primary thyroid lymphomas. The diagnosis was established by fine needle aspiration in nine cases and one case was misdiagnosed as lymphocytic thyroiditis, which was diagnosed on surgical specimen. The cytological diagnosis of high grade lymphoma is easy and ICC can confirm suspicious cases. The diagnosis of low grade lymphoma is more difficult but clinical and radiological suspicion and cytomorphological features can help reaching the correct diagnosis in such cases.