Primary thyroid lymphoma (PTL) is a rare type of thyroid cancer. It arises from special blood cells called lymphocytes. PTL accounts for 1 to 5% of all thyroid cancers, 1 to 2% of all lymphomas outside of lymph nodes, and has an annual incidence of 2 cases per one million people. There are several different kinds of lymphoma, but the vast majority of patients are diagnosed with non-Hodgkin’s lymphoma (NHL). Determining the exact type of the lymphoma is important for treatment choice and prognosis.
Symptoms and signs
Patients typically present with a rapidly growing thyroid mass and may experience hoarseness, difficulty breathing or, less commonly, significant swallowing problems. The growth of the thyroid tends to be much faster in patients with PTL than in those with other thyroid malignancies, with the exception of anaplastic thyroid carcinoma. Patients may also present with “B symptoms”, which are commonly associated with lymphoma. These B symptoms include fevers, night sweats, weight loss, and/or generalized itching.
PTL is three times more common in women than men. It typically occurs between the ages of 50 and 80 years with a peak incidence in the late 60’s. Patients with chronic lymphocytic thyroiditis (Hashimoto’s thyroiditis) are at an increased risk of developing PTL. However, most patients with Hashimoto’s do not develop PTL.
Despite its rarity, PTL should always be considered for any rapidly growing goiter or thyroid nodules. The best way to make a diagnosis is by performing a biopsy. FNA biopsy is often not able to get enough cells to make an exact diagnosis. In these cases, core needle biopsy or open surgical biopsy may be necessary. Core-needle biopsy can be performed with ultrasound guidance, and involves a needle stick in the neck. The needle used in the core biopsy is a special needle and is larger than the one used with the FNA. It samples a thin “core” of the thyroid gland (approximately 1 tenth of an inch thick). This “core” of thyroid is then prepared on a slide and sent to the pathologist to examine under the microscope. Since the core biopsy specimen is very small, it may sometimes be too small. If there is any question of diagnosis, surgical biopsy is the next step.
A surgical biopsy can be performed with either sedation and local anesthesia or general anesthesia. A small incision is made over the thyroid and a piece of thyroid is removed. The sampled piece is much larger than the core biopsy, and can be sent to the pathologist who can evaluate it, to determine the subtype of lymphoma. Surgical biopsy is safe, and can be done as an outpatient procedure.
Additional evaluation — A number of laboratory studies are useful in evaluating patients with PTL. In addition to obtaining standard serologic chemistries, blood levels of LDH and β2 microglobulin may be checked, as they can help predict a patient’s prognosis for non-Hodgkin’s lymphoma. Thyroid function tests may be somewhat useful, due to the high incidence of hypothyroidism in patients with PTL.
Imaging — A full neck (cervical) ultrasound is a standard initial imaging study in patients with thyroid disease and masses. A clear diagnosis cannot be made on ultrasound alone.
Once the diagnosis of PTL has been established, imaging of the entire body is necessary in order to stage the patient accurately. Computed tomography (CAT scan) of the head, neck, chest, abdomen and pelvis are often used to see if there is disease anywhere else in the body. Special tests, such as fluorodeoxyglucose positron emission tomography (FDG-PET) scanning appears to be a good imaging modality for assessing the extent of PTL. However, FDG-PET scanning can be inaccurate in patients with Hashimoto’s thyroiditis, where local inflammation can lead to false increased uptake in the thyroid gland, and therefore false positive results.
Appropriate treatment for patients with PTL depends on the type of lymphoma.
Most PTL is treated successfully with chemotherapy. A common regimen includes CHOP (cyclophosphamide, doxorubicin, vincristine, prednisolone). A more recently approved treatment includes rituximab alone or in combination with other chemotherapy agents such as CHOP (called R-CHOP) or CVP (cyclophosphamide, vincristine, prednisone) (called R-CVP).
External beam radiation
For control of local disease in the neck, or for types of lymphoma which are very slow-growing and are Stage 1, external beam radiation can be successful. Radiation may also be useful for patients with lots of disease. For example, patients with large tumors and compressive symptoms, may have radiation to shrink the tumor and hopefully relieve these symptoms.
Chemotherapy for PTL is so successful that surgery is rarely required for treatment. Occasionally, a patient may present with a thyroid nodule, which is found to be a PTL after surgical resection. Sometimes an operation has to be done for extreme situations. For example, a tracheostomy tube (a tube placed through the skin in the neck into the trachea) may be need if a tumor is blocking the windpipe.
Prognosis and staging of PTL
PTL is staged based on the Ann Arbor staging criteria, with up to 90% of patients presenting with early stage disease. Lymphomas that affect organs outside of the lymph system (i.e. in organs outside of the lymph nodes) have E added to their stage (for example, stage IIE).
Stage IE – lymphoma is contained within the thyroid gland
Stage IIE – lymphoma has spread outside the thyroid to nearby lymph nodes
Stage IIIE – lymphoma has spread to lymph nodes on both sides of the diaphragm
Stage IVE– lymphoma has spread throughout the body.
The prognosis varies based on the stage at diagnosis. However, in general, patients who present with stage IV disease do worse than those presenting at earlier stages.