Thyroid Lymphoma Workup

The diagnosis of thyroid non-Hodgkin lymphoma (NHL) is established by histologic examination of a tumor sample. Laboratory and imaging studies are conducted to establish the stage and prognosis. Thyroid function must also be assessed.

Once the diagnosis of thyroid non-Hodgkin lymphoma (NHL) is established, the following laboratory studies should be obtained:

• Complete blood count (CBC)
• Serum lactate dehydrogenase (LDH) level
• Serum beta2-microglobulin level
• Bone marrow aspiration and biopsy
• Thyroid function tests
• Antithyroglobulin or antimicrosomal antibodies

The serum LDH and beta2-microglobulin levels are important because of their ability to help predict the prognosis and differentiate between indolent and aggressive lymphoma. ^[13] The CBC and the bone marrow studies are important as part of the staging evaluation. Evaluation of thyroid function is important because of the high incidence of hypothyroidism in these cases. ^[12]

It is necessary to perform chest radiography and computed tomography (CT) of the head and neck, the chest, the abdomen, and the pelvis. (See the image below.) These are critical tests for determining the stage or extent of disease.

Rapidly enlarging thyroid mass occurring in association with neck adenopathy.

In cases involving bulky disease, either gallium scanning or positron emission tomography (PET) should be performed. These modalities can be helpful later on in determining whether any residual abnormality seen on radiographic studies after treatment contains active lymphoma or just scar tissue.

In current practice, the diagnosis of thyroid lymphoma can be easily established by means of either fine-needle aspiration (FNA) or core-needle biopsy, ^[13] thus obviating the extensive surgery usually performed for thyroid carcinoma. With the aid of immunophenotyping, non-Hodgkin lymphoma (NHL) should be readily distinguishable from thyroid carcinoma. Furthermore, the distinction between large-cell lymphoma and follicular center-cell lymphoma can be made on the basis of cytologic and immunophenotyping criteria.

The major histologic types of thyroid NHL are as follows:

• Large-cell lymphoma
• Follicular lymphoma
• Mucosa-associated lymphoid tissue (MALT) lymphoma (MALToma)
• Burkitt lymphoma (rare)

The presence of κ and λ free light chain restriction on flow cytometry of the aspirated material has been reported as an indicator of lymphoma in suspected thyroid nodules with a 75% sensitivity and 88.4% specificity. ^[14]  A retrospective analysis of 26 patients reported an observation of B-cell predominance, defined as B- to T-cell ratio (CD-19 to CD-4 ratio) of more than 2.0 on flow cytometry of FNA specimens in lymphomas as opposed to other lymphoproliferative diseases.

In one of the largest studies of primary thyroid lymphoma, which included 2215 patients, the distribution of pathological diagnoses was as follows: ^[10]

• Diffuse large B-cell lymphoma (DLBCL) - 58.8% 43%
• DLBCL with MALToma - 15.5% 8%
• Follicular lymphoma - 10.2%
• NHL not otherwise specified (NHL-NOS) - 6.3%
• Hodgkin lymphoma - 1.2%
• T-cell NHL - 0.5%
• MALToma - 47%
• Other - 2%

Determining the extent of disease in NHL is crucial for helping establish the prognosis and select treatment. In thyroid lymphoma, however, a conceptual problem arises in that most investigators have tended to believe that only thyroid lymphomas that are in the early Ann Arbor stages (ie, I-II) can be considered as being of primary thyroid origin.

The explanation for this view is that advanced presentations can represent a lymphoma metastasizing to the thyroid rather than a primary thyroid lymphoma. Primary thyroid lymphomas have metastatic potential and can present in stages III-IV in 2-7% of cases. However, there is no histologic marker that can be used to separate those that are primary in the thyroid from those that are metastatic to the thyroid; thus, most literature series, by definition, include only stage I-II cases.

For the purposes of prognosis, the aggressive thyroid cell types (most commonly the large-cell NHLs) can be classified on the basis of the International Prognostic Index (IPI). ^[15] This prognostic system assigns 1 point to each of the following variables:

• Age older than 60 years
• Performance status > 1
• Lactate dehydrogenase (LDH) level > 1 times normal
• Number of extranodal sites > 1
• Ann Arbor stage III-IV

Point totals and risk grouping in IPI are as follows:

• 0 or 1: Low risk
• 2: Low intermediate risk
• 3: High intermediate risk
• 4 or 5, high risk

In 2020, a study by Ha et al tested the ability of the IPI to predict the prognosis for patients with thyroid lymphoma. A 5-year overall survival and 5-year progression-free survival PFS for patient Patients with a low IPI score of 0–1 were 80.6% and 68.9%respectively. while for patients with an IPI score of 2–3, the 5-year OS and 5-year PFS were 51.1 and 47.3%, respectively. ^[16]