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© 2001 American Society for Clinical Oncology
Two Unusual Sites of Colon Cancer Metastases and a Rare Thyroid LymphomaCase 3. Primary T-Cell Lymphoma of the Thyroid Arising in a Background of Hashimoto's ThyroiditisSt Francis Hospital, Evanston, and Metropolitan Group Hospitals General Surgery Residency at Chicago, University of Illinois, Chicago, IL A 72-year-old man presented with a 10-month history of progressively enlarging thyroid mass, despite adequate thyroid suppression therapy. Over a 2-month interval the patient developed neck pressure, difficulty swallowing, and voice changes due to rapid increase in size of the mass. He denied any history of neck radiation. Physical examination revealed a large, hard, bilateral thyroid mass with significant neck engorgement and deviation of the laryngeal cartilage. Laboratory evaluation revealed a normal thyroid panel and an antimicrosomal antibody titer of 600 U/mL (normal range, < 2 U/mL). His human immunodeficiency virus work-up was negative. A thyroid ultrasound showed a large hyperechoic mass (Fig1). A computed tomography (CT) scan of his neck revealed bilateral thyroid enlargement and a large tumor of the right lobe (Fig 2). The thyroid scan showed only minimal thyroid uptake compared with a previous normal scan a year earlier. A fine-needle aspiration (FNA) and core needle biopsy revealed atypical lymphocytic infiltration with vascular invasion. These findings were suggestive of thyroid lymphoma, but the results of flow cytometry and gene rearrangement were inconclusive.
Because of the rapidly enlarging and symptomatic mass and lack of diagnosis, the patient underwent a right hemithyroidectomy. Pathologic examination revealed extensive replacement of the thyroid gland by a mixture of small and medium-sized cleaved cells, which were infiltrating the residual follicles (lymphoepithelial lesion, Fig 3). The majority of the atypical lymphocytes were found by immunoperoxidase stains to be T cells (Fig 4), with only sparse uptake of B-cell staining (Fig 5). Flow cytometry showed a T-cell population, which was positive for CD4 (helper cells) with anomalous loss of CD7 cells.
Results of the staging work-up, which included a CT scan of the chest, abdomen, and pelvis, were negative. The remaining postoperative course was uneventful. The patient was further treated with six cycles of chemotherapy (cyclophosphamide, doxorubicin, vincristine, and prednisone [CHOP]) and radiation of the neck and superior mediastinum with 50 Gy. He was still tumor-free at his 12-month follow-up. Primary lymphoma of the thyroid accounts for only 2% to 4% of thyroid malignancies and less than 2% of extranodal lymphomas.1 The vast majority are intermediate- or high-grade B-cell non-Hodgkin’s lymphomas predominately of diffuse large-cell or immunoblastic morphology.1 The second most common histologic type is lymphoma originating from mucosa-associated lymphoma tissue (MALT).1 Other less frequently encountered types include Hodgkin’s disease, Burkitt’s lymphoma, and plasmacytoma.1,2 Primary T-cell lymphoma of the thyroid is extremely rare, with only a few cases reported in the literature.3-7 Hashimoto’s thyroiditis and thyroid lymphoma frequently co-exist. The incidence of Hashimoto’s thyroiditis in patients with thyroid lymphoma ranges between 40% and 80%.2 One out of 200 patient with pre-existing Hashimoto’s thyroiditis will develop thyroid lymphoma, carrying an overall 60- to 80-fold higher risk than the general population.3 There is also evidence that large-cell lymphomas probably evolve from persistent low-grade MALT malignant lymphomas, suggesting a morphologic progression from chronic lymphocytic thyroiditis to low-grade MALT lymphoma and subsequently to high-grade large-cell lymphomas.1 Although histologic evidence of Hashimoto’s thyroiditis in the presence of primary T-cell lymphoma of the thyroid has been previously described,3,7 this is the first reported case in the Western literature with documented elevation of the antimicrosomal titer. The significance of the relationship between Hashimoto’s thyroiditis and thyroid lymphoma remains obscure. Hashimoto’s thyroiditis is an autoimmune disease, which is associated with dysfunction of suppressor T cells (CD8-positive T cells). This defect allows the overgrowth of the helper T cells (CD4-positive), which in turn activate the B cells in the thyroid to produce antithyroid antibodies.3,5 It is possible that chronic stimulation of the CD4 T cells might lead to development of the malignant clones. This may explain development of the T-cell lymphoma in our case, as well as a previous report of CD4-positive lymphoma.3 Thyroid lymphomas occur frequently in elderly women and typically present as a rapidly enlarging, painless mass, which can cause dysphagia (40% to 50%), voice changes (25% to 30%), and occasionally symptoms of upper airway obstruction. Physical examination usually reveals a large, firm mass. Clinically, primary thyroid lymphoma poses a diagnostic and therapeutic challenge because it can be confused with an anaplastic thyroid carcinoma. FNA can be suggestive of thyroid lymphoma in 60% of cases,8 although distinction of thyroid lymphoma from Hashimoto’s thyroiditis is not always possible. New techniques, such as flow cytometry, light-chain restriction, and gene rearrangement studies, have enhanced the diagnostic efficacy of FNA. Ultrasound, CT, and magnetic resonance imaging have been advocated for the assessment of local invasion and distant spread.9 Recently, gallium-67 scanning was reported to be positive only in anaplastic carcinoma and thyroid lymphoma and not in follicular and papillary carcinomas, which suggests that it may have a role in the diagnosis of thyroid lymphoma.10 The choice of treatment in primary thyroid lymphoma is based on the histologic subtype of the neoplasm, the stage, and tumor bulk, as well as the other associated comorbid factors. The current treatment of stage IE and IIE thyroid lymphoma involves a combined approach with chemotherapy (CHOP) and radiation.11 Stage IE MALT-type or other low-grade thyroid lymphomas can be optimally treated with regional radiation alone because they tend to remain localized.1 Advanced thyroid lymphomas are treated primarily with chemotherapy with or without regional radiation. The role of surgery is primarily diagnostic. The improved accuracy of FNA with the use of ancillary techniques previously mentioned and the efficacy of chemotherapy and radiation therapy diminish the role of surgery. It is the surgeon’s responsibility, however, to ensure appropriate collection of the FNA specimen, so that these additional techniques can be performed using the aspirate material.12 Open biopsy is indicated when the diagnosis cannot be obtained by percutaneous techniques. Surgical debulking should be considered only in patients with stage IE disease without extrathyroid extension or in life-threatening situations, such as in patients who present with symptoms of upper airway obstruction.13 In general, T-cell lymphomas are associated with worse prognosis than B-cell lymphomas. Overall 5-year survival for stages IE and IIE varies from 35% to 74%.14 Poor prognostic factors that require more aggressive therapy are tumor size greater than 10 cm, dysphagia, mediastinal involvement, and non-MALT origin.1 REFERENCES 1. Pasieka JL: Anaplastic cancer, lymphoma, and metastases of the thyroid gland. Surg Oncol Clin North Am 7: 707-720, 1998[Medline] 2. Singer JA: Primary lymphoma of the thyroid. Am Surg 64: 334-337, 1998[Medline] 3. Abdul-Rahman Z, Gogas HJ, Tooze JA, et al: T-cell lymphoma in Hashimoto’s thyroiditis. Histopathology 29: 455-459, 1996[Medline] 4. Dunbar JA, Lyall M, MacGillivray JB, et al: T-cell lymphoma of the thyroid. BMJ 2: 679, 1977 5. Coltrera MD: Primary T-cell lymphoma of the thyroid. Head Neck 21: 160-163, 1999[Medline]
6.
Forconi F, Bocchia M, Marconcini S, et al: CD30 positive (non-anaplastic) peripheral T-cell lymphoma of the thyroid gland. Haematologica 84: 946-948, 1999
7.
Yamaguchi M, Ohno T, Kita K: Gamma/delta T-cell lymphoma of the thyroid gland. N Engl J Med 336: 1391-1392, 1997 8. Klyachkin ML, Schwartz RW, Cibull M, et al: Thyroid lymphoma: Is there a role for surgery? Am Surg 64: 234-238, 1998[Medline] 9. Takashima S, Nomura N, Noguchi Y, et al: Primary thyroid lymphoma: Evaluation with US, CT and MRI. J Comput Assist Tomogr 19: 282-288, 1995[Medline] 10. Higashi T, Ito K, Nishikawa Y, et al: Gallium-67 scanning in the evaluation of thyroid malignancy. Clin Nucl Med 13: 792-799, 1988[Medline] 11. Doria R, Jekel JF, Cooper DL: Thyroid lymphoma: The case for combined modality. Cancer 73: 200-206, 1994[Medline] 12. Pasieka JL: Hashimoto’s disease and thyroid lymphoma: Role of the surgeon. World J Surg 24: 966-970, 2000[Medline] 13. Ansell SM, Grant CS, Habermann TM: Primary thyroid lymphoma. Semin Oncol 26: 316-323, 1999[Medline] 14. Junor EJ, Paul J, Reed NS: Primary non-Hodgkin’s lymphoma of the thyroid. Eur J Surg Oncol 18: 313-321, 1992[Medline] This article has been cited by other articles:
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Copyright © 2001 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
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