Case report Acta Medica Academica 2011;40(2):182-186 DOI 10.5644/ama2006-124.22

Case presentation –

Belkisa Izić¹, Amra Čičkušić¹, Senad Izić², Maida Kuljaninović ³, Šekib Umihanić4

1 Department of Radiology and Nuclear Malignant tumors of the thyroid gland account for about 1% of the Medicine, University Clinical Center newly diagnosed malignant tumors each year, and their incidence in Tuzla, Tuzla, Bosnia and Herzegovina women is twice the incidence in men. According to the WHO classi- 2 Department of Anaesthesiology and fi cation (2004) thyroid tumors are divided into: carcinoma of the thy- Reanimatology, University Clinical Center roid, adenoma and similar tumors, and other thyroid tumors which Tuzla, Tuzla, Bosnia and Herzegovina include: , angiosarcomas, and others, as well 3 Department of Pathology, University as primary and plasmacytomas. Primary thyroid lympho- Clinical Centre Tuzla, Bosnia and mas are defi ned as lymphomas which originate in the thyroid gland. Herzegovina Th is study presents the case of a 68-year-old patient with a thyroid 4 Department of Ear, Nose and Th roat lymphoma, which caused compression of the airways. In the patient University Clinical Center Tuzla, Tuzla presented there was reduced activity of the thyroid gland. Th e domi- Bosnia and Herzegovina nant symptoms were: breathing diffi culties, and the en- largement of the thyroid. An ultrasound examination was performed before surgery on the neck, which showed a multinodular thyroid, with compromised and compressed trachea to the right and rear. An emergency surgical procedure was performed to reduce the tumor. Pathohistological diagnosis confi rmed diff use large B cell lymphoma. Corresponding author: Th e aim of the study was to present a patient with a thyroid lymphoma, Belkisa Izić who had previously not had any immunological changes to the gland, Armije BiH 49a that is, she had not had any chronic lymphocyte thyroiditis, but due to 75000 Tuzla the compressive syndrome it was necessary to perform an emergency Bosnia and Herzegovina surgical procedure to reduce the tumor. [email protected] Tel.: + 387 61 739 197 Key words: Th yroid, Lymphoma, Malignant tumor. Fax: + 387 35 303 740 Introduction Malignant tumors of the thyroid gland account for about Received: 13 March 2011 1% of the newly diagnosed malignant tumors each year Accepted: 19 August 2011 (1) and their incidence in women is twice the incidence in men (2). Th ey most oft en occur in older patients where the average age of occurrence is 65 years. According to the WHO classifi cation (2004), thyroid tumors are divided Copyright © 2011 by into: carcinoma of the thyroid, adenoma and similar tu- Academy of Sciences and Arts of Bosnia and Herzegovina. mors, and other thyroid tumors which include: teratomas, E-mail for permission to publish: angiosarcomas, paragangliomas and others as well as pri- [email protected] mary lymphomas and plasmacytomas (3). In the group

182 Belkisa Izić et al.: Case presentation – thyroid lymphoma

of carcinomas the most common in the thy- lem in establishing a diagnosis from smears roid are papillary (80%), follicular (10%), obtained by FNA. In cases of unclear diag- medullary (5-10%) and the exceptionally nosis, if a monomorphic population of small rare anaplastic carcinoma (1-2%) (2), whilst lymphatic cells is found in the smears, it is the frequency of primary lymphoma is 5% necessary to repeat the aspiration to obtain (4). Primary thyroid lymphomas are defi ned suffi cient cells for immunophenotypization as lymphomas which primarily originate in (6). Diff erentiating between EMZBCL and the thyroid, so this defi nition excludes lym- lymphocyte thyroiditis, as well as diff erenti- phomas which aff ect the thyroid whether by ating between other lower level lymphomas metastasis or by direct spreading from the than Hashimoto thyroiditis can sometimes neighboring lymph nodes. Primary thyroid be diffi cult both from cytological smears lymphoma in its late stages may spread to and histological preparations. Although the lymph nodes and other organs, includ- pathological verifi cation is the gold standard ing the gastrointestinal tract, thereby repre- for diagnosis of lymphoma, in rendering a senting a form of mucosa-associated lym- diagnostic decision immunohistochemistry, phoid tissue (MALT) lymphoma (5). fl ow cytometry or genetic molecular analy- Primary thyroid lymphomas are usually sis are still necessary in addition (3). non-Hodgkin type, whilst primary Hodgkin’s Treating large cell lymphomas of the thy- disease is very rare (6). Extranodal marginal roid gland is no diff erent from treatment zone B cell lymphoma (EMZBCL) and dif- of any other lymphoma occurring in the fuse large B cell lymphoma (DLBCL) are lym- lymph nodes (9). Treatment is based on the phomas which most oft en occur in the thy- sub-type of the lymphoma and the scope of roid with areas of morphology of a transient the disease. Today, the trend in treatment of form between these two types of lymphoma. large cell lymphomas is for treatment to be Other, especially follicular lymphomas are selected on the basis of prognostic factors. extremely rate (3). Diff use large cell B lym- Treatment of a disease which is limited to phomas are lymphomas which occur most the thyroid gland is performed by local re- oft en in the lymph nodes, whilst in 30% of gional radiation or surgery. In most patients, cases they can occur as extra-nodal. Th e treatment is mainly by a standard chemo- most common extra-nodal site where lym- therapy regime, which consists of Cyclo- phomas of this type occur is the thyroid (7). phosphamide, , and Th e rapidly growing mass of the thyroid Prednisolone (CHOP) in combination with gland in an older woman should always radiation, and must always be under the su- arouse suspicion of a tumor. In the past it pervision of an oncologist (11). was necessary to perform an open biopsy to Th e goal of this paper is to present a pa- obtain enough tissue for pathohistological tient with thyroid lymphoma, who had not examination (6). However, today diagnosis had any previous immunological disease of is made on the basis of cytological analysis the thyroid gland, that is, chronic lympho- of aspirate changes in the thyroid gland, im- cyte thyroiditis, and in whom it was neces- munocytochemistry, fl ow cytometry, im- sary to perform surgery to reduce the tumor munophenotypization of lymphocytes ob- due to compression syndrome. tained by fi ne needle aspiration (FNA), and fi nally pathohistological analysis and mo- Case presentation lecular genetic analysis (8). If it is a DLBCL lymphoma, that is, a lymphoma with a high Th e patient, aged 68, was sent to our in- degree of malignity, there is usually no prob- stitute for examination. A year earlier, the

183 Acta Medica Academica 2011;40:182-186

diagnosis of hypothyroidism had been es- spiratory insuffi ciency were present, it was tablished in another institution and therapy proposed following consultation that tumor with 1-thyroxin 100 micrograms once a day reduction and tracheotomy be performed. prescribed. On clinical examination, a node Th e pathohistological diagnosis of the tu- was palpitated in the left lobe of the thyroid morous mass was Lymphoma malignum dif- gland, 2 cm in size. Th e follow up fi nding fusum centroblasticum B glandule thyreoide- of the thyroid-stimulating hormone - TSH ae – diff use large cell B lymphoma (fi gure 1). was 9.9 mIU/l (0.27-3.75 mlU/l); Free thy- Immunohistochemical analysis showed that roxine - FT4 17 pmol/l (10-20 pmol/l); Th y- the neoplastic cells were positive for CD20 roglobulin - Tg 0.4 ng/ml (2.0-70 ng/l) and (fi gure 2) and bcl-6, whilst they were nega- thyroglobulin antibodies - TgAt 9.0 IU/ml tive for CD 3, CD 10, CD 23, cyclin D1, TdT (>100 IU/ml). Th erapy was recommended and bcl-2. with 150 micrograms of l-thyroxin once a Post-operative computerized tomography day and control of hormonal status in four of the neck, thorax and abdomen showed the months. remains of the tumorous mass, which went Th ree months later the patient was ad- from the level of the hyoid bone to the left , mitted to our Department of Ear, Nose paralaryngeally and para- and retropharyn- and Th roat for breathing diffi culties, loss of geally, right up to the level of the jugular fos- voice and sudden increase in the size of the sa. It infi ltrated the left half of the supraglot- thyroid gland. Physical examination estab- tic and glottic regions of the larynx, reducing lished that the thyroid gland was enlarged, the air space to a latero-lateral diameter of 2 with multimodal changes, hard, painless mm. In the distal half of the neck to the left , and immobile on swallowing, with bilateral pathologically enlarged lymph nodes were neck . Ultrasound showed visible on the jugular chain about 15 and 24 multimodal changes to the thyroid gland mm in size, which compromised and, it was with a compromised and compressed tra- suspected, also infi ltrated the jugular vein chea on the right and to the front. On both internally. In view of the stage of the illness, sides of the neck there were pockets of en- further therapy was proposed and transfer larged lymph nodes. Th e ultrasound fi nding of the patient to the , Hematology indicated a malignant tumor in the thyroid and Radiotherapy Clinic. During her hos- gland. Since compressive syndrome and re- pitalization she received a second cycle of

Figure 1 Diff use large cell B lymphoma of thyroid Figure 2 Immunohistochemical analysis - CD20 gland (HE, x 10) positive, x 40.

184 Belkisa Izić et al.: Case presentation – thyroid lymphoma

chemotherapy according to the CHOP re- sue, with resulting mutation leading to the gime, with the addition of monoclonal CD development of lymphoma (9). 20 antibodies. On both occasions she had Until recently there was concern whether iatrogenic neutropenia which was treated the diagnosis of lymphoma could be estab- with granulocyte growth factor and broad lished by analysis of a sample obtained by spectrum antibiotics. Th ere were also raised aspiration. Cha et al. (11) showed that this levels of the enzymes lactate dehydrogenase, approach is successful in 63% patients with aspartate transaminase and creatinine pres- thyroid lymphoma. Aspirates of large cell ent in the serum. Despite the therapy applied lymphomas are typically hypercellular with no regression of the tumorous mass was visible individual lymphatic cells, which recorded, so the patient was still unable to have a cytological appearance, similar or swallow spontaneously, but was fed through identical to lymphoma of other sites, and a nasogastric tube. Aft er two months from in that case it is simple to reach a diagno- admission to hospital in the ENT clinic the sis. In contrast to them, in aspirate smears illness progressed into the front of the upper of the lymphoma marginal zone a mixture mouth and gingiva of the upper jaw, there is found of small atypical lymphocytes, cen- trocytes, monocytoid B cells, immunoblasts was loss of body mass and the patient died. and plasma cells. As a result of the morpho- logical appearance of the cytological smears, Discussion diff erentiating this type of lymphoma and reactive changes in the lymph node is al- Our patient was treated for one year for re- most impossible (3). Th e introduction of duced activity of the thyroid gland, that is, molecule technology has led to defi nite di- hypothyroidism. Th e medical history and agnosis and as a result open thyroid biopsy negative Tg-At fi nding excluded the exis- is no longer performed in modern diagnos- tence of Hashimoto thyroiditis. In a rela- tics (6). Takashima et al. (12) and Daria et tively short period of time the thyroid gland al. (13) described the use of chain reaction increased rapidly in size due to the infi ltra- polymerase in strengthening the immuno- tion of neoplastic cells in the form of diff use globulin heavy chain to establish the diag- nodes, with compression of the airways and nosis of lymphoma. Th e presence of antigen resulting respiratory insuffi ciency. Th is con- CD-20 and heavy chain clonality confi rm dition demanded urgent surgical interven- the diagnosis. tion, that is, total thyroidectomy with bilat- Large cell B lymphoma in two patients eral dissection of the neck. aged 64 and 50 years, without a previous Th e incidence of primary thyroid lym- history of Hashimoto thyroiditis, were de- phoma in patients with Hashimoto thyroid- scribed by Akcala et al. (14), saying that due itis has increased signifi cantly (7, 10). In fact to the sudden increase in size of the thyroid lymphomas in the thyroid gland in almost gland and compression of the respiratory all cases occur on the basis of chronic lym- path, total thyroidectomy was performed phocyte thyroiditis. Graff -Baker et al. be- and CHOP chemotherapy applied. lieve that there is a pathophysiological con- nection between autoimmune disorder and Conclusion thyroid lymphomas. Th e proposed theory supposes that chronic antigen stimulation Th is unusual case of thyroid lymphoma is is a secondary autoimmune disorder which interesting because it occurred in a patient leads to chronic proliferation of lymph tis- who did not have Hashimoto thyroiditis.

185 Acta Medica Academica 2011;40:182-186

Th e surgery was performed because of com- 6. Lerma E, Arguelles R, Rigla M, Otal C, Cubero pression of the airways caused by the rapid JM, Bagué S, Carreras AM, et al. Comparative fi ndings of lymphocytic thyroiditis and thyroid increase in size of the thyroid gland due to lymphoma. Acta Cytol. 2003;47(4):575-80. infi ltration by neoplastic cells. Aft er two 7. Tupchong L, Hughes F, Harmer CL. Primary lym- rounds of chemotherapy there was no re- phoma of the thyroid: clinical features, prognostic gression of the disease and the patient died. factors, and results of treatment. Int J Radiat On- col Biol Phys. 1986;12(10):1813-21. Confl ict of interest: Th e authors declare that they 8. Detweiler RE, Katz RL, Alapat C, el-Naggar A, have no confl ict of interest. Th is study was not spon- Ordonez N. Malignant lymphoma of the thyroid: sored by any external organisation. a report of two cases diagnosed by fi ne-needle as- piration. Diagn Cytopathol. 1991;7(2):163-71. Authors’ contributions: Conception and design: BI 9. Graff -Baker A, Sosa JA, Roman SA. Primary thy- and SI; Acquisition, analysis and interpretation of roid lymphoma: a review of recent developments data: BI and AČ; Draft ing the article: BI and ŠU, Re- in diagnosis and histology-driven treatment. Curr vising it critically for important intellectual content: Opin Oncol. 2010;22(1):17-22. AČ and MK. 10. Kebapcilar L, Alacacioglu I, Comlekci A, Ozcan MA, Piskin O, Kargi A, et al. Primary thyroid lym- phoma: case series with literature review. J BUON. References 2009;14(2):295-9. 1. Ruiz Allison AG, Vassilpoulou-Sellin R. Endo- 11. Cha C, Chen H, Westra WH, Udelsman R. Prima- crine Malignancies. In: Pazdur R, editor. Medical ry thyroid lymphoma: can the diagnosis be made Oncology a Comprehensive Review. New York: solely by fi ne-needle aspiration? Ann Surg Oncol. PRR Huntington; 1993. p. 349-58. 2002; 9(3):298-302. 2. Jameson JL, Weetman AP. Disorders of the Th y- 12. Takashima S, Takayama F, Saito A, Wang Q, Hi- roid gland. In: Braunwld E et al. editor. Harrison´s daka K, Sone S. Primary thyroid lymphoma: di- Principles of Internal Medicine. New York: Mc- agnosis of immunoglobulin heavy chain gene Graw-Hill; 2001. p. 2060-84. rearrangement with polymerase chain reaction 3. DeLellis RA, Lloyd RV, Heitz PU, Eng C. World in ultrasound-guided fi ne-needle aspiration. Th y- Health Organisation Classifi cation of Tumors. Tu- roid. 2000;10(6):507-10. mours of Endocrine Organs. France: IARC Press; 13. Doria R, Jekel JF, Cooper DL. Th yroid lymphoma. 2004. Th e case for combined modality therapy. . 4. Belal AA, Allan A, Kandal A, et al. Primary thy- 1994;73(1):200-6. roid lymphoma: a retrospective analisis of prog- 14. Akcali Z, Sakalli H, Noyan Z, Kayaselcuk F, Ozyil- nostic factors and treatment outcome for local- kan O. Primary thyroid lymphoma: report of two ized intermediate and high grade lymphoma. Am cases. East Afr Med J. 2004; 81(7):378-80. J Clin Oncolo. 2001;24(3):299-305. 5. Kocjan G (ed). Th yroid. In: Clinical Cytopathol- ogy of the Head and Neck. London: Greenwich Medical Media; 2001. pp. 99-105.

186