Thyroid Lymphoma

Lymphoma is a cancer primarily of the lymph nodes and there are two main types - Hodgkin's lymphoma, and Non-Hodgkin's lymphoma (NHL). Hodgkin's extremely rarely involves the thyroid, but non-Hodgkin's lymphoma accounts for 1-2% of all thyroid cancers.

Primary Thyroid Non-Hodgkin Lymphoma (PTNHL) typically occurs in older aged women. Unlike the more common types of thyroid cancer, radiation is not a factor in the disease, but longstanding Hashimoto's thyroiditis is a common predisposing cause. The incidence of primary thyroid lymphomas in patients with Hashimoto’s thyroiditis is markedly increased; some believe that a pathogenetic link exists between this autoimmune disorder and primary thyroid NHL. The theory suggests that chronic antigenic stimulation secondary to the autoimmune disorder leads to chronic proliferation of lymphoid tissue, which eventually undergoes a mutation that results in the development of lymphoma.

There are 3 common types of PTNHL: the most common is a diffuse large B-cell lymphoma (DLBL), which tends to be aggressive or high grade, and may arise from a pre-existing MALT lymphoma. The second type is a marginal zone B-cell lymphoma type of mucosa associated lymphoid tissue (MALT lymphoma), which tends to be low grade and indolent in behaviour. Finally there is a mixed type (MZL-DLBL). The MZL type is composed of mainly small lymphoid cells with interspersed large lymphoid cells while the DLBL type has just large lymphoid cells.

Presentation

The disease is one of the elderly, and is more than twice as common in women as in men. There is usually a history of a new lump in the neck or a change in a longstanding goitre. As the disease progresses there may be pain, a hoarse voice, or difficulty in breathing and swallowing. The neck mass is hard and the local lymph glands may be enlarged (Fig. 1).

Fig.1: MALT lymphome of thyroid (unusually in a young male patient)Some people may have a history of Hashimoto's thyroiditis, which is an inflammatory condition of the thyroid (see Thyroiditis). Hypothyroidism has been observed in 30-40% of patients with thyroid lymphoma.

Thyroid lymphoma can sometimes spread to the lymph nodes nearby, but it is not common for thyroid lymphoma to spread to the bone marrow. The MALT type can involve the digestive tract.

The diagnosis is not difficult when large highly atypical lymphoid cells are seen on FNA cytology. Thyroid function testing may show hypothyroidism and thyroid autoantibodies may be elevated if the patient has Hashimoto’s thyroiditis. The main diagnostic problem is when the lesion consists solely of small lymphoid cells. In such circumstances the identification as lymphoma and not as Hashimoto's thyroiditis is near impossible without special staining methods (immunocytochemistry).

Treatment

Combined modality therapy is the most common approach for the initial treatment of thyroid lymphomas. The CHOP regimen (cyclophosphamide, doxorubicin, vincristine and prednisone) has been shown to be highly effective for many types of thyroid lymphoma. 

However, MALT lymphoma treated by radiation therapy only, can result in a 96% complete response, with only a 30% relapse rate.

Radiotherapy of at least 40 Gy is the main treatment of thyroid lymphoma when the disease is limited to the thyroid (Stage 1 Disease). It should only be used alone in stage 1 disease. The disease may shrink away after one or two treatments, but it is essential that the patient completes the course of 16-20 treatments or the disease may recur. In any patient with more than stage 1 disease radiation must be combined with chemotherapy.

Chemotherapy is used when there is extensive disease outside the thyroid and usually lasts for six months. The treatments used vary from centre to centre, but the common regimen used is CHOP (cyclophosphamide, doxorubicin, vincristine and prednisolone.) Even though the disease is extensive, cure is still possible with chemotherapy.

Surgery has a limited role in the management generally. However, surgical treatment might be performed for patients with thyroid lymphoma in addition to chemotherapy and radiation, particularly for MALT lymphomas. Surgery might also be used to obtain tissue (biopsy) so as to fully assess the tumour; a core biopsy may be necessary. This may need to be done under general anaesthetic, although local anaesthetic is usually adequate.

It is not usually used as a treatment to remove a thyroid lymphoma, in order to help preserve the function of the thyroid gland, however the lymphoma may only be discovered on examining the pathology after total thyroidectomy.

A patient with proven lymphoma of the thyroid who has respiratory obstruction should be treated wherever possible by endotracheal intubation and chemotherapy with possible radiotherapy and steroids. Such a regimen usually results in a rapid shrinkage of the tumour and will avoid an unnecessary tracheostomy, which should be avoided at all costs.

Thyroid hormone replacement with thyroxine tablets is often required after treatment with radiotherapy or surgery as the thyroid becomes less active. Patients with Hashimoto’s thyroiditis may also need thyroxine to treat the hypothyroidism of this disease.

Staging

Staging of thyroid lymphoma is as follows:

Prognosis

The factors leading to a poor prognosis in thyroid lymphoma are advanced stage of the tumour, large size (>10 cm), as well as spreading to the mediastinum. The overall survival for primary thyroid lymphoma is 50% to 70%, ranging from 80% in stage IE to less than 36% in stage IIE and IVE in 5 years.