PhiliPPine Journal of otolaryngology-head and neck Surgery Vol. 27 no. 1 January – June 2012 38 PhiliPPine Journal of otolaryngology-head and neck Surgery UNDER THE MICROSCOPE AbstrAct Eight cases of primary thyroid lymphoma were reported in a tertiary government hospital from January 2005 to August 2011. All patients presented with a diffuse enlargement of both thyroid lobes with associated obstructive symptoms. Five of these cases were extranodal marginal zone lymphoma and three were diffuse large B-cell lymphoma. Clinical features that would favor a thyroid lymphoma include tumor size of greater than 7 cm, obstructive symptoms, clinical hypothyroidism or history of Hashimoto thyroiditis. Thus, these features must be considered in evaluating thyroid nodules during fine-needle aspiration biopsy. Histologically, extranodal marginal zone B-cell lymphoma shows vaguely nodular to diffuse infiltrates of small to intermediate size atypical lymphoid cells infiltrating the thyroid follicles while diffuse large B-cell lymphoma shows sheets of large atypical lymphoid cells infiltrating the thyroid follicular epithelium. Keywords: primary thyroid lymphoma, extranodal marginal zone B-cell lymphoma, diffuse large B-cell lymphoma Primary thyroid lymphoma is a rare neoplasm that comprises 1-5% of all thyroid malignancy and 1-7% of all extranodal lymphomas.1-4 It usually occurs in older individuals with a mean age of 65.1-2 It is more common in females with a ratio of 3-6:1.1,4 A total of eight patients were diagnosed to have a primary thyroid lymphoma among 1,008 malignant thyroidectomy specimens seen by our department from January 2005 to August 2011 with an incidence rate of 0.8% of all thyroid malignancies in our institution. We review these cases. cAsEs There was one male and seven females with a ratio of 1:7. Their ages ranged from 37-86 years old with a median age of 56 years. Of the eight patients, only five had available clinical data. All five had a 1-3 year history of diffuse anterior neck mass and all had obstructive symptoms such as dyspnea and dysphagia. One patient each had weight loss and regional lymph node enlargement. Pre-operative thyroid function tests of 4/5 patients revealed hypothyroidism in one while three were euthyroid. Primary thyroid Lymphoma Correspondence: Dr. Claudine Ann Musngi-Paras Department of Pathology College of Medicine University of the Philippines Manila 547 Pedro Gil St., Ermita, Manila 1000 Philippines Phone (632) 526 4450 Fax (632) 400 3638 Email: claudineparas@yahoo.com Reprints will not be available from the authors. The authors declared that this represents original material that is not being considered for publication or has not been published or accepted for publication elsewhere, in full or in part, in print or electronic media; that the manuscript has been read and approved by all the authors, that the requirements for authorship have been met by each author, and that each author believes that the manuscript represents honest work. Disclosures: The authors signed disclosures that there are no financial or other (including personal) relationships, intellectual passion, political or religious beliefs, and institutional affiliations that might lead to a conflict of interest. Presented at the Case Report Poster Contest (Finalist), Philippine Society of Pathologists Annual Convention, Dusit Hotel, Makati City, Philippines, April 26-28, 2012. Philipp J Otolaryngol Head Neck Surg 2012; 27 (1): 38-40 c Philippine Society of Otolaryngology – Head and Neck Surgery, Inc. Claudine Ann Musngi-Paras, MD1 Ansarie P. Salpin, MD1 Januario D. Veloso, MD1, 2 1Department of Laboratories Philippine General Hospital University of the Philippines Manila 2Department of Pathology College of Medicine University of the Philippines Manila PhiliPPine Journal of otolaryngology-head and neck Surgery Vol. 27 no. 1 January – June 2012 PhiliPPine Journal of otolaryngology-head and neck Surgery 39 UNDER THE MICROSCOPE Macroscopic examinations of all eight thyroidectomy specimens showed diffuse enlargement of both thyroid lobes with sizes ranging from 11 to 15 cm in widest diameter. Histopathologic diagnosis revealed diffuse large B-cell lymphoma (Figure 1, A-D) in three patients and extranodal marginal zone B-cell lymphoma in five patients. (Figure 2, A-E) Immunohistochemical staining with CD3, CD5 and CD20 confirmed the diagnosis. of patients younger than 60 years old, comparable with the previous study done in the Philippines. The tumor size is usually large at the time of diagnosis between 8-14 cm according to the previous Philippine study between 11-15 cm in our series and between 2-15 cm with a median size of 7 cm in other studies.3,7 Due to the rapid growth of the tumor, compression of the adjacent organs causes obstructive symptoms such as dyspnea and dysphagia. Derringer et al. reviewed 108 cases of primary thyroid lymphoma with 72% having obstructive symptoms.7 Hypothyroidism is seen in up to 67% of cases of primary thyroid lymphoma.3 A history of Hashimoto thyroiditis has a relative risk of Figure 1. Diffuse large B-cell lymphoma. A. H and E stain shows large atypical lymphocytes infiltrating the thyroid follicles (10x). b. Large atypical lymphocytes (40x). Figure 2. A. Extranodal marginal zone B-cell lymphoma (10x). There were nodular and diffuse proliferation of small to medium size lymphocytes infiltrating the thyroid follicle. In here, we can also appreciate the remnants of Hashimoto thyroiditis characterized by oncocytic changes of the follicular cells (arrow). Figure 2. b. Extranodal marginal zone B-cell lymphoma (40x). Lymphoepithelial lesion showing neoplastic cells within the follicle (arrow). Figure 1. c,D. Immunohistochemical staining showed diffuse and strong cytoplasmic membrane staining for CD20 and negative for CD3. A b thyroid follicles (H & E stain lymphocytes infiltrating the thyroid follicles (10x) Large atypical lymphocytes (40x) cD 20 cD 3 DIscUssION The clinical features that would favour primary thyroid lymphoma include women in the sixth decade, a history of Hashimoto thyroiditis and rapid growth of a firm diffuse thyroid mass.1,2,6 A study in the Philippines (1994-1998) showed a lower mean age than foreign data with 55% of cases occurring in the less than 60-year-olds (Range= 49-69 years) with a male to female ratio of 1:1.25.6 The present series had 60% Extranodal marginal zone b-cell lymphoma (10x). Extranodal marginal zone b-cell lymphoma (40x) c D PhiliPPine Journal of otolaryngology-head and neck Surgery Vol. 27 no. 1 January – June 2012 UNDER THE MICROSCOPE 40 PhiliPPine Journal of otolaryngology-head and neck Surgery rEFErENcEs Abbondanzo S, Aozasa K, Boerner S, Thompson LDR. Primary Lymphoma and Plasmacytoma. 1. In: DeLellis RA, Lloyd RV, Heitz PU, Eng C, editors. World Health Organization Classification of Tumours: Tumours of Endocrine Organs. Lyon (France): IARC press; 2004. p. 109-110 Niitsu N, Okamoto M, Nakamura N, Nakamine H, Bessho M, Hirano M. Clinicopathologic 2. correlations of stage IE/IIE primary thyroid diffuse large B-cell lymphoma. Ann Oncol. 2007 Jul; 18(7): 1203-8. Thieblemont C, Mayer A, Dumontet C, Barbier Y, Callet-Bauchu E, Felman P, Berger F, Ducottet X, 3. Martin C, Salles G, Orgiazzi J, Coiffier B. Primary thyroid lymphoma is a heterogenous disease. J Clin Endocrinol Metab. 2002 Jan; 87(1): 105-11. Ansell SM, Grant CS, Habermann TM. Primary thyroid lymphoma. 4. Semin Oncol. 1999 Jun;26(3):316-23. Pasieka JL. Anaplastic cancer, lymphoma, and metastases of the thyroid gland. 5. Surg Oncol Clin N Am. 1998 Oct;7(4):707-720. Liwag AA, Sedurante MB. A case of primary thyroid lymphoma seen at the university of the 6. Philippines-Philippine general hospital. Philipp J Int Med. 2004 Jan-Feb; 42(1): 45-49. Derringer GA, Thompson LDR, Frommelt RA, Bijwaard KE, Heffess CS, Abbondanzo SL. Malignant 7. lymphoma of the thyroid gland: a clinicopathologic study of 108 cases. Am J Surg Pathol 2000 May; 24(5):623-39. Matsuzuka F, Miyauchi A, Katayama S, Narabayashi I, Ikeda H, Kuma K, Sugawara M. Clinical 8. aspects of primary thyroid lymphoma: diagnosis and treatment based on our experience of 119 cases. Thyroid. 1993 Summer ; 3(2): 93-9. Das DK, Gupta SK, Francis IM, Ahmed, MS. Fine needle aspiration cytology diagnosis of non-9. Hodgkin lymphoma of thyroid: a report of four cases. Diagn Cytopathol 1993 Dec; 9(6.): 639-45. Klyachkin ML, Schwartz RW, Cibull M, Munn RK, Regine WF, Kenady DE, et al. Thyroid lymphoma: 10. Is there a role for surgery? Am Surg 1998 Mar; 64(3): 234-8. up to 80x compared to the general population in developing primary thyroid lymphoma.4 Extranodal marginal zone B-cell lymphoma is the morphologic variant associated with Hashimoto thyroiditis. In our series, only one patient was hypothyroid out of four for whom clinical data was available. Fine needle aspiration has become the procedure of choice for the initial pathological diagnosis of thyroid nodules. In one series, a correct diagnosis with FNAB was made in 70-80% of patients with thyroid lymphoma,8 but in others, FNAB was suggestive but not diagnostic in only 50-60% of patients.9-10 In the present series, only one out of five cases of PTL was correctly diagnosed by FNAB. Data was not available for the three other cases. The sensitivity of FNAB in the diagnosis of primary thyroid lymphoma in our institution is lower compared to the foreign literature. Ancillary procedures such as immunohistochemical staining and molecular genetic testing can increase diagnostic accuracy, especially in cases of Extranodal Marginal Zone B-cell lymphoma since it resembles a reactive lymph node in cytology specimens. Cytologically, diffuse large B-cell lymphoma shows a cellular aspirate which consists of large atypical lymphoid cells (2-3x larger than mature small lymphocyte) with scattered small cytoplasmic fragments of lymphocytes in the background. There are scanty to absent follicular cells. Extranodal marginal zone B-cell lymphoma shows cellular aspirate which consists of small to intermediate-size lymphoid cells. Some cells show abundant, pale cytoplasm (monocytoid appearance). This cytologic features overlap with chronic lymphocytic thyroiditis. However, the absence of tangible body macrophages, activated follicle-center cells and spectrum of lymphocytes in all stages of maturation favor extranodal marginal zone B-cell lymphoma. Immunophenotyping is often required to aid in the definitive diagnosis. Clinical features that would favor a thyroid lymphoma include tumor size of greater than 7 cm, obstructive symptoms, clinical hypothyroidism or a history of Hashimoto thyroiditis. Thus, these features must be considered in evaluating thyroid nodules during FNAB. Immunohistochemistry and molecular techniques can be used as adjunct in these cases when cytology specimens are equivocal for lymphoid malignancy. cD 20 cD 3 cD 5 Figure 2, c-E. Extranodal marginal zone B-cell lymphoma. Diffuse and strong cytoplasmic membrane expression of CD20 (20x). Negative for CD3 (10x). Negative for CD5 (10x). Diffuse and strong cytoplasmic membrane expression of cD20 (20x) Negative for cD3 (10x) Negative for cD5 (10x) c D E