- Jonathan W Friedberg, MD
Jonathan W Friedberg, MD
- Professor of Medicine
- James P Wilmot Cancer Center, University of Rochester
- Arnold S Freedman, MD
Arnold S Freedman, MD
- Section Editor — Lymphoproliferative Disorders
- Professor of Medicine
- Harvard Medical School
- R Michael Tuttle, MD
R Michael Tuttle, MD
- Professor of Medicine
- Memorial Sloan Kettering Cancer Center
Primary lymphoma of the thyroid, although rare, should always be considered in the differential diagnosis of patients with thyroid nodules, goiter, and carcinomas, mainly because its prognosis and treatment differ substantially from that of the other disorders. (See "Diagnostic approach to and treatment of thyroid nodules".)
Thyroid lymphomas are nearly always of the non-Hodgkin type as Hodgkin lymphoma of the thyroid is exceedingly rare . Only approximately 2 percent of extranodal lymphomas arise within the thyroid gland, and lymphomas represent no more than 2 percent of all malignant thyroid tumors . In a Danish epidemiologic survey, the annual incidence rate was estimated to be 2.1 per million persons, with a 4:1 female predominance . Most other retrospective series have confirmed this markedly higher frequency of thyroid lymphoma in women [4-7]. The mean and median ages at diagnosis are between 65 and 75 years [3-7].
Preexisting chronic autoimmune (Hashimoto's) thyroiditis is the only known risk factor for primary thyroid lymphoma and is present in approximately one-half of patients. Among patients with Hashimoto's thyroiditis, the risk of thyroid lymphoma is at least 60 times higher than in patients without thyroiditis [3,8,9]. Worldwide, the frequency of thyroid lymphoma appears to be higher in areas with a higher prevalence of thyroiditis.
Lymphoma may also occur more commonly after iodine supplementation . There appears to be no clear association between exposure to ionizing radiation and lymphoma , although individual cases have been described. Chromosomal abnormalities are rare in thyroid lymphomas.
CLASSIFICATION AND PATHOLOGY
Primary thyroid lymphoma is almost always of B-cell lineage [3,6,7]. Occasional patients with T-cell lymphomas have been reported, often in areas endemic for human T-lymphotrophic virus (HTLV)-I-associated adult T-cell leukemia/lymphoma [12,13]. Sixty to 80 percent of thyroid lymphomas are diffuse, large B-cell lymphomas (DLBCL of germinal center type) [4,5,7,14,15]. (See "Classification of the hematopoietic neoplasms".)
- Wang SA, Rahemtullah A, Faquin WC, et al. Hodgkin's lymphoma of the thyroid: a clinicopathologic study of five cases and review of the literature. Mod Pathol 2005; 18:1577.
- Freeman C, Berg JW, Cutler SJ. Occurrence and prognosis of extranodal lymphomas. Cancer 1972; 29:252.
- Pedersen RK, Pedersen NT. Primary non-Hodgkin's lymphoma of the thyroid gland: a population based study. Histopathology 1996; 28:25.
- Skarsgard ED, Connors JM, Robins RE. A current analysis of primary lymphoma of the thyroid. Arch Surg 1991; 126:1199.
- Junor EJ, Paul J, Reed NS. Primary non-Hodgkin's lymphoma of the thyroid. Eur J Surg Oncol 1992; 18:313.
- Logue JP, Hale RJ, Stewart AL, et al. Primary malignant lymphoma of the thyroid: a clinicopathological analysis. Int J Radiat Oncol Biol Phys 1992; 22:929.
- Wolf BC, Sheahan K, DeCoste D, et al. Immunohistochemical analysis of small cell tumors of the thyroid gland: an Eastern Cooperative Oncology Group study. Hum Pathol 1992; 23:1252.
- Holm LE, Blomgren H, Löwhagen T. Cancer risks in patients with chronic lymphocytic thyroiditis. N Engl J Med 1985; 312:601.
- Hyjek E, Isaacson PG. Primary B cell lymphoma of the thyroid and its relationship to Hashimoto's thyroiditis. Hum Pathol 1988; 19:1315.
- Harach HR, Williams ED. Thyroid cancer and thyroiditis in the goitrous region of Salta, Argentina, before and after iodine prophylaxis. Clin Endocrinol (Oxf) 1995; 43:701.
- Calandra DB, Shah KH, Lawrence AM, Paloyan E. Total thyroidectomy in irradiated patients. A twenty-year experience in 206 patients. Ann Surg 1985; 202:356.
- Mizukami Y, Michigishi T, Nonomura A, et al. Primary lymphoma of the thyroid: a clinical, histological and immunohistochemical study of 20 cases. Histopathology 1990; 17:201.
- Ohsawa M, Noguchi S, Aozasa K. Immunologic type of thyroid lymphoma in an adult T-cell leukemia endemic area in Japan. Leuk Lymphoma 1995; 17:341.
- Tsang RW, Gospodarowicz MK, Sutcliffe SB, et al. Non-Hodgkin's lymphoma of the thyroid gland: prognostic factors and treatment outcome. The Princess Margaret Hospital Lymphoma Group. Int J Radiat Oncol Biol Phys 1993; 27:599.
- DiBiase SJ, Grigsby PW, Guo C, et al. Outcome analysis for stage IE and IIE thyroid lymphoma. Am J Clin Oncol 2004; 27:178.
- Burke JS. Are there site-specific differences among the MALT lymphomas--morphologic, clinical? Am J Clin Pathol 1999; 111:S133.
- Ashton-Key M, Biddolph SC, Stein H, et al. Heterogeneity of bcl-2 expression in MALT lymphoma. Histopathology 1995; 26:75.
- Du M, Peng H, Singh N, et al. The accumulation of p53 abnormalities is associated with progression of mucosa-associated lymphoid tissue lymphoma. Blood 1995; 86:4587.
- Lam KY, Lo CY, Kwong DL, et al. Malignant lymphoma of the thyroid. A 30-year clinicopathologic experience and an evaluation of the presence of Epstein-Barr virus. Am J Clin Pathol 1999; 112:263.
- Faulkner A, Maguire P. Teaching ward nurses to monitor cancer patients. Clin Oncol 1984; 10:383.
- Herrmann R, Panahon AM, Barcos MP, et al. Gastrointestinal involvement in non-Hodgkin's lymphoma. Cancer 1980; 46:215.
- Anscombe AM, Wright DH. Primary malignant lymphoma of the thyroid--a tumour of mucosa-associated lymphoid tissue: review of seventy-six cases. Histopathology 1985; 9:81.
- Walsh S, Lowery AJ, Evoy D, et al. Thyroid lymphoma: recent advances in diagnosis and optimal management strategies. Oncologist 2013; 18:994.
- Tupchong L, Hughes F, Harmer CL. Primary lymphoma of the thyroid: clinical features, prognostic factors, and results of treatment. Int J Radiat Oncol Biol Phys 1986; 12:1813.
- Mazzaferri EL, Oertel YC. Primary malignant thyroid lymphoma and related lymphoproliferative disorders. In: Endocrine tumors, Mazzaferri EL, Samaan NA (Eds), Blackwell Scientific, Boston 1993. p.348.
- Jennings AS, Saberi M. Thyroid lymphoma in a patient with hyperthyroidism. Am J Med 1984; 76:551.
- Zeki K, Eto S, Fujihira T, et al. Primary malignant lymphoma of the thyroid in a patient with long-standing Graves' disease. Endocrinol Jpn 1985; 32:435.
- Matsuzuka F, Miyauchi A, Katayama S, et al. Clinical aspects of primary thyroid lymphoma: diagnosis and treatment based on our experience of 119 cases. Thyroid 1993; 3:93.
- Mikosch P, Würtz FG, Gallowitsch HJ, et al. F-18-FDG-PET in a patient with Hashimoto's thyroiditis and MALT lymphoma recurrence of the thyroid. Wien Med Wochenschr 2003; 153:89.
- Podoloff DA. Is there a place for routine surveillance using sonography, CT, or MR imaging for early detection (notably lymphoma) of patients affected by Hashimoto's thyroiditis? AJR Am J Roentgenol 1996; 167:1337.
- Takashima S, Nomura N, Noguchi Y, et al. Primary thyroid lymphoma: evaluation with US, CT, and MRI. J Comput Assist Tomogr 1995; 19:282.
- Kim HC, Han MH, Kim KH, et al. Primary thyroid lymphoma: CT findings. Eur J Radiol 2003; 46:233.
- Carbone PP, Kaplan HS, Musshoff K, et al. Report of the Committee on Hodgkin's Disease Staging Classification. Cancer Res 1971; 31:1860.
- Evans TR, Mansi JL, Bevan DH, et al. Primary non-Hodgkin's lymphoma of the thyroid with bone marrow infiltration at presentation. Clin Oncol (R Coll Radiol) 1995; 7:54.
- Pyke CM, Grant CS, Habermann TM, et al. Non-Hodgkin's lymphoma of the thyroid: is more than biopsy necessary? World J Surg 1992; 16:604.
- Sun TQ, Zhu XL, Wang ZY, et al. Characteristics and prognosis of primary thyroid non-Hodgkin's lymphoma in Chinese patients. J Surg Oncol 2010; 101:545.
- Friedberg MH, Coburn MC, Monchik JM. Role of surgery in stage IE non-Hodgkin's lymphoma of the thyroid. Surgery 1994; 116:1061.
- Harrington KJ, Michalaki VJ, Vini L, et al. Management of non-Hodgkin's lymphoma of the thyroid: the Royal Marsden Hospital experience. Br J Radiol 2005; 78:405.
- Cha H, Kim JW, Suh CO, et al. Patterns of care and treatment outcomes for primary thyroid lymphoma: a single institution study. Radiat Oncol J 2013; 31:177.
- Ha CS, Shadle KM, Medeiros LJ, et al. Localized non-Hodgkin lymphoma involving the thyroid gland. Cancer 2001; 91:629.
- Katna R, Shet T, Sengar M, et al. Clinicopathologic study and outcome analysis of thyroid lymphomas: experience from a tertiary cancer center. Head Neck 2013; 35:165.
- Niitsu N, Okamoto M, Nakamura N, et al. Clinicopathologic correlations of stage IE/IIE primary thyroid diffuse large B-cell lymphoma. Ann Oncol 2007; 18:1203.
- Mian M, Gaidano G, Conconi A, et al. High response rate and improvement of long-term survival with combined treatment modalities in patients with poor-risk primary thyroid diffuse large B-cell lymphoma: an International Extranodal Lymphoma Study Group and Intergruppo Italiano Linfomi study. Leuk Lymphoma 2011; 52:823.
- Watanabe N, Noh JY, Narimatsu H, et al. Clinicopathological features of 171 cases of primary thyroid lymphoma: a long-term study involving 24553 patients with Hashimoto's disease. Br J Haematol 2011; 153:236.