Laboratory Studies
Once the diagnosis of thyroid NHL is established, the following laboratory studies should be obtained:
- Complete blood cell count
- Serum lactate dehydrogenase (LDH)
- Serum beta2-microglobulin
- Bone marrow aspiration and biopsy
- Thyroid function tests
- Antithyroglobulin or antimicrosomal antibodies
The serum LDH and beta2-microglobulin are important because of their ability to help predict the prognosis.[7, 8] The CBC count and bone marrow studies are important as part of the staging evaluation. Because of the high incidence of hypothyroidism, it is important to evaluate thyroid function.
Imaging Studies
In order to help determine the extent of the disease, it is necessary to obtain a chest radiograph and a CT scan of head and neck, chest, abdomen, and pelvis. These are critical tests for determining the stage or extent of disease. Either gallium scanning or positron emission tomography (PET) scanning should be performed in those cases with bulky disease because these can be helpful later on in determining whether any residual abnormality seen on radiographic studies after treatment contains active lymphoma or scar tissue.
Histologic Findings
In current practice, the diagnosis of thyroid lymphoma can be easily established by either fine-needle aspiration (FNA) or needle-core biopsy,[9] thus avoiding extensive surgery, which is usually performed for thyroid carcinoma. With the aid of immunophenotyping, NHL should be easy to distinguish from thyroid carcinoma. Furthermore, the distinction between large cell lymphoma and follicular center cell lymphoma is possible by cytological and immunophenotyping criteria. The major histological types of thyroid NHL are large cell, follicular, mucosa-associated lymphoid tissue (MALT), and, rarely, Burkitt lymphoma.[6] In a recent study from Japan that which evaluated 171 patients with primary thyroid lymphoma,[10] the pathological diagnoses were diffuse large B-cell lymphoma (DLBCL) (43%), DLBCL with MALT lymphoma (8%), MALT lymphoma (47%), and others (2%).
Virtually all primary thyroid lymphomas are of B-cell origin. The most common are the large cell lymphomas. According to Isaacson, thyroid large-cell lymphomas most likely arise from a previously existing MALT lymphoma that undergoes transformation to large cell.[11] The former is an aggressive or high-grade variant, while the low-grade MALT is an indolent type. Similar to other low-grade MALT lymphomas, such as those presenting in the parotid in association with Sj ö gren syndrome, those seen in the thyroid also occur in relationship with an autoimmune disorder, in this case HT. The hypothesis is that chronic antigenic stimulation secondary to the autoimmune disorder leads to chronic proliferation of lymphoid tissue, which eventually undergoes a mutation that leads to the development of lymphoma.
Staging
Determining the extent of disease in NHL is crucial to help predict the prognosis and select treatment. In thyroid lymphoma, however, there is a conceptual problem in the sense that most investigators believe only the early Ann Arbor stages (I-II) can be considered as being of primary thyroid in origin. The explanation for this is that because advanced presentations can represent metastatic lymphoma to the thyroid, rather than primary in the thyroid. Primary thyroid lymphomas have metastatic potential and can present at stage III-IV disease, but since there is no histological marker that can be used to separate those that are primary in the thyroid from those that are metastatic to the thyroid, most literature series, by definition, only include stage I-II cases.
In terms of predicting prognosis, the aggressive thyroid cell types, most commonly the large cell NHLs, can be classified using the International Prognostic Index (IPI).[12] This prognostic system assigns 1 point to each of the following variables:
- Age older than 60 years
- Performance status greater than 1
- Elevated LDH level
- Number of extranodal sites greater than 1
- Ann Arbor stage III-IV
In one study, Ha et al tested the ability of the IPI to predict prognosis in patients with thyroid lymphoma.[6] The 5-year survival rate for those presenting with an IPI of 0 was 86%, versus 50% for those with an IPI of greater than 0. These data include patients treated with either radiation alone, chemotherapy alone, or combined-modality therapy.
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