Primary thyroid lymphoma
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# Overview
Primary thyroid lymphoma is almost always of B cell lineage. Preexisting Hashimoto thyroiditis is a known risk factor for the primary thyroid lymphoma and is present among half of the patients. Thyroid lymphoma is rare with an incidence of 0.1-0.2 per 100,000. Common symptoms of primary thyroid lymphoma include painless enlarging  neck mass, hoarseness, Difficulty swallowing, and Difficulty breathing. Classic B symptoms of lymphoma occurs in less than 20% of patients. Physical examination findings consistent with the diagnosis of thyroid lymphoma include abnormal texture of thyroid gland in palpation as well as cervical and/or supraclavicular lymphadenopathy. There is no laoratory findings specific for the diagnosis of primary thyroid lymphoma. Thyroid lymphoma may be difficult to be differentiated from Hashimoto thyroiditis. MRI is useful for defining the extent of extrathyroidal invasion of the primary thyroid lymphoma. The CHOP regimen (cyclophosphamide, doxorubicin, vincristine and prednisone) has been showed high effectiveness for many types of thyroid lymphoma. Radiotherapy is indicated in case of patients with localized, extranodal, marginal zone lymphoma of the thyroid or other indolent histologies (eg, follicular lymphoma, small lymphocytic lymphoma).Surgical intervention might be performed for patients with thyroid lymphoma in addition to chemotherapy and radiation, particularly for MALT lymphomas.

# Historical Perspective
- There is no data available on historical perspective of primary thyroid lymphoma.

# Classification
- Primary thyroid lymphoma is almost always of B cell lineage.
- According to a recent survey, it is of non-hodgkin origin in 98% of the cases.
- Thyroid lymphomas may be classified according to type of cells into subtypes:
Diffuse large B-cell lymphoma with marginal zone which is the most common subtype.
diffuse large B-cell lymphoma without marginal zone, the second most common subtype.
marginal zone -cell lymphoma of mucosa-associated lymphoid tissue
Follicular lymphoma
- Diffuse large B-cell lymphoma with marginal zone which is the most common subtype.
- diffuse large B-cell lymphoma without marginal zone, the second most common subtype.
- marginal zone -cell lymphoma of mucosa-associated lymphoid tissue
- Follicular lymphoma

# Pathophysiology
- The thyroid gland may be affected primarily or secondary to lymphoma elsewhere.
- Thyroid lymphoma refers to the lymphoma that primarily originates from the thyroid tissue.
- Thyroid lymphoma is associated with hashimotos thyroiditis.
- It is understood that thyroid lymphoma is the result of chronic antigenic stimulation secondary to the autoimmune disorder.
- Hashimoto thyroiditis causes chronic proliferation of lymphoid tissue which eventually leads to a mutation and result in lymphoma.
- BRAF and NRAS mutations are associated with thyroid lymphoma.
- MAPK pathway mutations are associated with B cell thyroid lymphoma.
- Macroscopic Findings associated with the diagnosis of primary thyroid lymphoma include:
Variable size
Rubbery mass with fish flesh appearance
- Variable size
- Rubbery mass with fish flesh appearance
- On microscopic histopathological analysis, characteristic findings of thyroid lymphoma are:
- Lymphoepithelial lesion
- Plasma cells
- Thyroid parenchyma displaced by lymphocytes

# Causes
- The exact cause of primary thyroid lymphoma is unclear. However, Hashimoto thyroiditis is a known risk factor for this disorder.

# Risk Factors
- Preexisting Hashimoto thyroiditis is a known risk factor for the primary thyroid lymphoma and is present among half of the patients.
- The evidence for such association is the higher incidence of thyroid lymphoma in areas with a higher prevalence of Hashimoto thyroiditis.

# Screening
- There is insufficient evidence to recommend routine screening for primary thyroid lymphoma.

# Differentiating thyroid lymphoma from Other Diseases
- Primary thyroid lymphoma should be differentiated from other disorders causing enlarging thyroid masses, and compression symptoms. These disorders include other thyroid cancers as well as thyroid follicular adenomas.
- For more information on primary thyroid lymphoma, please click here.

# Epidemiology and Demographics
- Thyroid lymphoma is rare with an incidence of 0.1-0.2 per 100,000.
- It typically presents between 50-70 years of age.
- Females are more commonly affected with anaplastic thyroid cancer than males. The females to male ratio are approximately 2-8 to 1.

# Natural History, Complications and Prognosis
- Common complications of primary thyroid lymphoma include Vocal cord paralysis, Dyspnea, Dysphagia and Metastasis.
- Factors associated with poor prognosis for patients with thyroid lymphoma are an advanced stage of the tumor, large size  (>10 cm) as well as spreading to mediastinum.

# Diagnosis

## Diagnostic Study of Choice

## Diagnostic Criteria
- There are no established criteria for the diagnosis of primary thyroid lymphoma.
- ultrasound guided fine needle aspiration is used for he initial diagnosis of thyroid nodule histology.

## Staging
- Staging of thyroid lymphoma is showed in the table below:

## History and Symptoms
- Common symptoms of primary thyroid lymphoma include:
Painless enlarging  neck mass
Hoarseness
Difficulty swallowing
Difficulty breathing
- Painless enlarging  neck mass
- Hoarseness
- Difficulty swallowing
- Difficulty breathing
- Classic B symptoms of lymphoma occurs in less than 20% of patients.

## Physical Examination
- Common physical examination findings of primary thyroid lymphoma include:
Thyroid has a firm to hard texture in palpation and is fixed to the surronding tissues.
Cervical and/or supraclavicular lymphadenopathy may also be present.
- Thyroid has a firm to hard texture in palpation and is fixed to the surronding tissues.
- Cervical and/or supraclavicular lymphadenopathy may also be present.

## Laboratory Findings
- There is no laoratory findings specific for the diagnosis of primary thyroid lymphoma.
- Laboratory findings helpful for the diagnosis of Hashimoto thyroiditis include high serum concentrations of antithyroid peroxidase or antithyroglobulin antibodies.

## Electrocardiogram
- There are no ECG findings associated with primary thyroid lymphoma.

## X-Ray
- There are no x-ray findings associated with primary thyroid lymphoma.

## Echocardiography or Ultrasound
- Thyroid lymphoma may be difficult to be differentiated from Hashimoto thyroiditis.
- Three sonographic patterns are reported and include nodular, diffuse and mixed subtypes.
- Nodular lymphoma has a very uniform and hypoechoic pattern that may be sufficiently hypoechoic to be pseudo-cystic. The border of the tumor is well defined, and the borderline may be "broccoli-like" or "coastline-like" irregular.
- Diffuse lymphoma has an indistinguishable border from non-lymphomatous part of thyroid and otherwise is similar to goiter. Internal echoes are also of exceedingly low intensity.
- The mixed lymphoma showes multiple, patchy hypoechoic lesions, with enhanced posterior echoes in each lesion.

## CT
- CT findings associated with the diagnosis of primary thyroid lymphoma include solitary nodule, multiple nodules, and diffuse enlargement.
- A characteristic finding ob CT imaging is "donut sign," observed when the lymphoma completely encircles the trachea.

### MRI
- MRI is useful for defining the extent of extrathyroidal invasion of the primary thyroid lymphoma.

## Other Imaging Findings
- There are no other imaging findings associated with primary thyroid lymphoma.

## Other Diagnostic Studies
- There are no other diagnostic studies associated with primary thyroid lymphoma.

# Treatment

## Medical Therapy
- Combined therapy with chemoradiation is indicated in patients with localized, early-stage diffuse large B cell lymphoma.
- The CHOP regimen (cyclophosphamide, doxorubicin, vincristine and prednisone) has been showed high effectiveness for many types of thyroid lymphoma.
- Radiotherapy is indicated in case of patients with localized, extranodal, marginal zone lymphoma of the thyroid or other indolent histologies (eg, follicular lymphoma, small lymphocytic lymphoma).

## Surgery
- Surgery is not the treatment of choice for primary thyroid lymphoma.
- Surgical intervention might be performed for patients with thyroid lymphoma in addition to chemotherapy and radiation, particularly for MALT lymphomas.

## Primary Prevention
- There are no established measures for the primary prevention of primary thyroid lymphoma.

## Secondary Prevention
- There are no established measures for the secondary prevention of primary thyroid lymphoma.