Primary thyroid lymphoma
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Sahar Memar Montazerin, M.D.[2] Ammu Susheela, M.D. [3]
To review the wikidoc page on thyroid cancer , click here.
Overview
Thyroid lymphomas may be classified according to type of cells into 6 subtypes: non–Hodgkin's B-cell lymphomas, Hodgkin's lymphoma, diffuse large B-cell lymphoma with marginal zone, diffuse large B-cell lymphoma without marginal zone, MALT lymphoma, and follicular lymphoma. Thyroid lymphoma is a rare malignant tumor constituting 1% to 2% of all thyroid malignancies and less than 2% of lymphomas. BRAF and NRAS mutations are associated with thyroid lymphoma. Thyroid lymphoma is rare with an incidence of 1-2 per 100,0000. The factors of poor prognosis for patients with thyroid lymphoma are an advanced stage of the tumor, large size (>10 cm) as well as spreading to 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. Symptoms of thyroid lymphoma include painless rapidly growing neck mass, hoarseness, and difficulty in swallowing. Neck CT scan may be helpful in the diagnosis of thyroid lymphoma. Findings on CT scan suggestive of thyroid lymphoma is a hypodense or heterogeneous enhancement in the thyroid gland. Biopsy may be helpful in the diagnosis of thyroid lymphoma. Findings on biopsy suggestive of thyroid lymphoma include lymphoepithelial lesion and lymphocytes. 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 showed high effectiveness for many types of thyroid lymphoma. However, it is suggested to perform radiation therapy only for MALT lymphoma resulting in a 96% complete response, with only a 30% relapse rate. Surgical treatment might be performed for patients with thyroid lymphoma in addition to chemotherapy and radiation, particularly for MALT lymphoma.
Historical Perspective
Classification
- Primary thyroid lymphoma is almost always of B cell lineage.[1][2][3]
- 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 В-cell lymphoma of mucosa-associated lymphoid tissue
- Follicular lymphoma
Pathophysiology
- Thyroid lymphoma is a rare malignant tumor constituting 1% to 2% of all thyroid malignancies and less than 2% of lymphomas.
- The thyroid may be affected primarily or secondary to lymphoma elsewhere.
- There is increased risk with chronic inflammatory conditions.
- BRAF and NRAS mutations are associated with thyroid lymphoma.
- MAPK pathway mutations are associated with B cell thyroid lymphoma.[4]
- Thyroid lymphoma is associated with hashimoto’s thyroiditis.
- Macroscopic Findings associated with the diagnosis of primary thyroid lymphoma include:[5]
- 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.[2]
Risk Factors
- Preexisting Hashimoto thyroiditis is a known risk factor for the primary thyroid lymphoma and is present among half of the patients.[6][7][2]
- 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 1-2 per 100,0000.
- It typically presents between 50-70 years of age.[8]
- 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.[9]
Prognosis is generally excellent/good/poor, and the 1/5/10-year mortality/survival rate of patients with [disease name] is approximately [#]%.
- 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:[10]
| Stage | Characteristics |
|---|---|
| IE | Lymphoma is located within the thyroid |
| 2E | Lymphoma is located within the thyroid and regional lymph-nodes |
| 3E | Lymphoma is located at both sides of diaphragm |
| 4E | Dissemination of lymphoma |
History and Symptoms
- Common symptoms of primary thyroid lymphoma include:[11][2]
- 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:
- Rapidly growing painless mass in the neck
- Lymphadenopathy
Laboratory Findings
- There is no laoratory findings specific for the diagnosis of primary thyroid lymphoma.[2]
- 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
- Three patterns have been described: nodular (hypoechoic mass), diffuse (mixed echotexture) or mixed. Calcifications are uncommon.
CT
- Goitre, which is hypodense to adjacent muscle
- Heterogeneous enhancement but still less than adjacent muscle
MRI
- T1/T2: iso- to hyperintense
- Pseudocapsule may be present
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.[12]
- 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.[13]
- 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.
References
- ↑ Skarsgard ED, Connors JM, Robins RE (October 1991). "A current analysis of primary lymphoma of the thyroid". Arch Surg. 126 (10): 1199–203, discussion 1203–4. doi:10.1001/archsurg.1991.01410340037006. PMID 1929820.
- ↑ 2.0 2.1 2.2 2.3 2.4 Pedersen RK, Pedersen NT (January 1996). "Primary non-Hodgkin's lymphoma of the thyroid gland: a population based study". Histopathology. 28 (1): 25–32. doi:10.1046/j.1365-2559.1996.268311.x. PMID 8838117.
- ↑ Vardell Noble, Victoria; Ermann, Daniel A; Griffin, Emily K; Silberstein, Peter T (2019). "Primary Thyroid Lymphoma: An Analysis of the National Cancer Database". Cureus. doi:10.7759/cureus.4088. ISSN 2168-8184.
- ↑ Aggarwal, Nidhi; Swerdlow, Steven H; Kelly, Lindsey M; Ogilvie, Jennifer B; Nikiforova, Mariana N; Sathanoori, Malini; Nikiforov, Yuri E (2012). "Thyroid carcinoma-associated genetic mutations also occur in thyroid lymphomas". Modern Pathology. 25 (9): 1203–1211. doi:10.1038/modpathol.2012.73. ISSN 0893-3952.
- ↑ Dundar, Halit Ziya; Sarkut, Pinar; Kirdak, Turkay; Korun, Nusret (2016). "Primary thyroid lymphoma". Turkish Journal of Surgery. 32 (1): 75–77. doi:10.5152/UCD.2015.2935. ISSN 1300-0705.
- ↑ Holm LE, Blomgren H, Löwhagen T (March 1985). "Cancer risks in patients with chronic lymphocytic thyroiditis". N. Engl. J. Med. 312 (10): 601–4. doi:10.1056/NEJM198503073121001. PMID 3838363.
- ↑ Hyjek E, Isaacson PG (November 1988). "Primary B cell lymphoma of the thyroid and its relationship to Hashimoto's thyroiditis". Hum. Pathol. 19 (11): 1315–26. doi:10.1016/s0046-8177(88)80287-9. PMID 3141260.
- ↑ Holm, Lars-Erik; Blomgren, Henric; Löwhagen, Torsten (1985). "Cancer Risks in Patients with Chronic Lymphocytic Thyroiditis". New England Journal of Medicine. 312 (10): 601–604. doi:10.1056/NEJM198503073121001. ISSN 0028-4793.
- ↑ Hedhili, F.; Kedous, S.; Jbali, S.; Attia, Z.; Dhambri, S.; Touati, S.; Chebbi, A. Goucha; El May, A.; Gritli, S. (2015). "Primary thyroid lymphoma: Case report and review of the literature". Egyptian Journal of Ear, Nose, Throat and Allied Sciences. 16 (2): 171–173. doi:10.1016/j.ejenta.2015.05.002. ISSN 2090-0740.
- ↑ {{cite book | last = Edge | first = Stephen | title = AJCC cancer staging manual | publisher = Springer | location = New York | year = 2010 | isbn = 978-0-387-88440-0 }
- ↑ Katna, Rakesh; Shet, Tanuja; Sengar, Manju; Menon, Hari; Laskar, Siddharth; Prabhash, Kumar; D'Cruz, Anil; Nair, Reena (2013). "Clinicopathologic study and outcome analysis of thyroid lymphomas: Experience from a tertiary cancer center". Head & Neck. 35 (2): 165–171. doi:10.1002/hed.22928. ISSN 1043-3074.
- ↑ Cha H, Kim JW, Suh CO, Kim JS, Cheong JW, Lee J, Keum KC, Lee CG, Cho J (December 2013). "Patterns of care and treatment outcomes for primary thyroid lymphoma: a single institution study". Radiat Oncol J. 31 (4): 177–84. doi:10.3857/roj.2013.31.4.177. PMC 3912230. PMID 24501704.
- ↑ Peixoto, Rita; Correia Pinto, João; Soares, Virgínia; Koch, Pedro; Taveira Gomes, António (2017). "Primary thyroid lymphoma: A case report and review of the literature". Annals of Medicine and Surgery. 13: 29–33. doi:10.1016/j.amsu.2016.12.023. ISSN 2049-0801.