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Original Article Concomitant Papillary Thyroid Carcinoma and Mucosa-Associated Lymphoid Tissue Thyroid Lymphoma in the Setting of Hashimoto Thyroiditis

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Original Article Concomitant Papillary Thyroid Carcinoma and Mucosa-Associated Lymphoid Tissue Thyroid Lymphoma in the Setting of Hashimoto Thyroiditis Int J Clin Exp Pathol 2018;11(6):3076-3083 www.ijcep.com /ISSN:1936-2625/IJCEP0075602 Original Article Concomitant papillary thyroid carcinoma and mucosa-associated lymphoid tissue thyroid lymphoma in the setting of Hashimoto thyroiditis Xia-Bin Lan1*, Jun Cao1*, Xu-Hang Zhu1*, Zhe Han2, Yu-Qing Huang1,4, Ming-Hua Ge1, Hai-Yan Yang3 Departments of 1Head and Neck Surgery, 2Medical Imaging, 3Lymphoma, Zhejiang Cancer Hospital, Gongshu District, Hangzhou 310022, China; 4Zhejiang Chinese Medical University, Hangzhou, China. *Equal contributors. Received March 7, 2018; Accepted April 13, 2018; Epub June 1, 2018; Published June 15, 2018 Abstract: The simultaneous occurrence of papillary thyroid carcinoma (PTC) and mucosa-associated lymphoid tis- sue (MALT) lymphoma of the thyroid gland is extremely rare, and many questions about their diagnosis and treat- ment remain unsolved. We report three cases of patients with both PTC and MALT thyroid lymphoma in the setting of Hashimoto thyroiditis (HT). Patient characteristics, pre-operative examination, histological findings, treatments, and follow-up were reviewed. In addition, we searched PubMed, Embase, and ISI Web of Science databases for articles published in the English language using the key words “lymphoma” and “thyroid”, and we reviewed almost all the reports about simultaneous occurrence of PTC and MALT thyroid lymphoma. In conclusion, PTC and MALT thyroid lymphoma can exist concomitantly, especially in patients with longstanding HT. These rare cases highlight the importance of close communication between clinicians, histopathologists, and radiologists to ensure that such rare cases are not missed; a multidisciplinary approach and careful surveillance are also needed. Keywords: Papillary thyroid carcinoma, lymphoma, hashimoto thyroiditis, treatment Introduction have been reported in the literature [4-9], diag- nosis and treatment of patients with PTC and Papillary thyroid carcinoma (PTC) is the most MALT thyroid lymphoma is unclear. The aim of prevalent type of thyroid cancer, accounting for this study was to analyze the patients’ clinico- approximately 80%-90% of cases, whereas pri- pathologic characteristics, treatments, and pro- mary thyroid lymphoma (PTL) is very rare, gnosis. accounting for only 0.6% to 5% of all thyroid cancers; and mucosa-associated lymphoid tis- Clinical history sue (MALT) lymphoma is one of the most com- mon subtypes [1]. PTC usually has an indolent Patient 1 biological behavior and a very favorable prog- nosis (20-year survival rate, >90%). MALT thy- A 57-year-old man was referred to us for roid lymphoma also carries a good prognosis enlargement of his thyroid, revealed by neck with a 5-year disease-specific survival rate ultrasonography (US) in November 2012. His >90% [2]. PTC has been described with Ha- medical history was unremarkable. On clinical shimoto’s thyroiditis (HT), but it remains con- examination, he had a palpable 4.0 cm nodule troversial [3] whereas MALT usually arises in a in the left lobe and 2.0 cm nodule in the right background of HT [1]; however, the simultane- lobe. No other abnormal findings were detect- ous occurrence of both malignancies in the ed. Routine laboratory tests were normal, and same patient is extremely rare. We describe hormone evaluation showed euthyroidism but three patients with HT and synchronous oc- antithyroid antibodies were positive (anti-TPO, currence of PTC and MALT thyroid lymphoma. 54.9 IU/mL [normal range, 0 to 34 IU/mL]; anti- To our knowledge, this is one of the largest Tg, 1504.0 IU/mL [normal range, 0 to 115 IU/ case series. As only eight such occurrences mL]). Thyroid US confirmed the presence of a PTC and MALT thyroid lymphoma multinodular goiter; the larger nodule was 4.0 the isthmus of the thyroid gland and showed cm in diameter, hypoechoic, and in the left extensive thyromegaly on both sides. lobe. Also, computed tomography (CT) scan detected multiple nodules. In July 2013, she underwent total thyroidecto- my and bilateral regional lymph node dissec- In January 2013, the patient underwent left tion. Histopathologic examination showed: a thyroidectomy and regional lymph node dissec- 0.8 cm papillary carcinoma in the isthmus of tion, and right partial thyroidectomy. Histo- the thyroid gland, and lymphoid tissue diffuse pathologic examination showed: a 0.8 cm papil- hyperplasia in the peripheral thyroid. Immuno- lary carcinoma in the left lobe with regional histochemistry showed CK (+), EMA (+), CK19 lymph node metastasis, and margin zone lym- (+), HBME1 (partial +), Gly-3/Glypican3 (-), phoma of mucosa-associated lymphoid tissue CD20 (+), CD79a (+), CD3 (partial +), CD43 (par- (MALT) in the left and right lobe, and extensive tial +), CD5 (partial +), CD21 (+), CD23 (+), CD10 lymphocytic infiltration of the thyroid parenchy- (-), bcl-6 (+), bcl-2 (-), Ki-67 (+, <10%), which ma diagnostic of HT. Immunohistochemistry supports the diagnosis of MALT lymphoma. CT showed CK (+), CD20 (+), CD79a (+), CD10 (-), scan of head, chest, abdomen, pelvis and bone bcl-2 (+), bcl-6 (low +), Ki-67 (10% +), CD21 (+), marrow aspiration showed no evidence of lym- CD3 (+), CD5 (+), CyclinD1 (-), CD43 (+), CD23 phoma. Because PTL was confined to the thy- (+), Kappa/κ (+), Lambda/λ (+), which supports roid (stage IE), and she had already undergone the diagnosis of MALT lymphoma. Postope- total thyroidectomy, no other treatment was ratively, thyroxine treatment was initiated and a recommended. The patient was then treated staging procedure followed, including CT of with post-operative thyroid hormone suppres- head, chest, abdomen, and pelvis; serum pro- sive therapy. She is asymptomatic now. tein electrophoresis; serum lactate dehydroge- nase and β2- microglobulin levels; and bone Patient 3 marrow biopsy, which was negative. Thus a stage of IE was confirmed based on the Ann A 61-year-old woman with thyroid enlargement Arbor staging. In May 2013, he accepted radio- of two years of duration was seen in our hospi- therapy of 30Gy/15F in order to exterminate tal for progressive enlargement of the thyroid the residual lymphoma tissue. He was then gland without any discomfort. She had a his- treated with a thyroid-stimulating hormone tory of cervical carcinoma and underwent ra- (TSH) -suppressive dose of thyroxine. Follow-up diation and chemotherapy with no relapse. evaluation for PTL and PTC was negative, and Routine laboratory tests were normal and hor- he remains asymptomatic now. monal examination was normal too. However, antithyroid antibodies were positive (anti-TPO, Patient 2 265.7 IU/mL [normal range, 0 to 34 IU/mL]; anti-Tg, 1000.0 IU/mL [normal range, 0 to 115 A 43-year-old woman was admitted to our hos- IU/mL]). Thyroid ultrasonography revealed a pital for thyroid cancer surgery in July 2013. hypoechoic mass in the right thyroid lobe with She had no special medical history except diameter of 3.0 cm (TI-RADS 4b) and a small hypothyroidism 2 year ago and accepted thy- nodule in the left thyroid lobe (TI-RADS 2). roxine replacement therapy. In May 2013, she went to another hospital for US examination In December 2013, she underwent right thy- which revealed a small calcific nodule in the roidectomy. Histopathologic examination sh- isthmus of the thyroid gland. She underwent owed two neoplastic lesions: a 0.15 cm papil- ultrasound-guided fine-needle aspiration (FNA) lary carcinoma, and lymphoid tissue diffuse biopsy of this nodule and was diagnosed with hyperplasia in the rest of the right thyroid lobe. PTC. Then she was referred to our hospital for Immunohistochemical staining was performed: thyroid operation. Routine laboratory tests CD20 (+), CK (lymphoid epithelial lesions +), were normal, and hormone evaluation show- CD79a (+), CD3 (separately +), CD5 (separately ed euthyroidism but antithyroid antibodies +), CD21 (+), CD23 (+), CD43 (separately +), were positive (anti-TPO, >600.0 IU/mL [normal CD10 (-), bcl-6 (partly low +), bcl-2 (partly +), range, 0 to 34 IU/mL]; anti-Tg, 149.3 IU/mL Ki-67 (20%-30% +), CyclinD1 (-), Kappa/κ (+), [normal range, 0 to 115 IU/mL]). Review of US Lambda/λ (+), which supports the diagnosis of revealed a palpable 1.4 cm calcific nodule in MALT lymphoma. Positron emission computed 3077 Int J Clin Exp Pathol 2018;11(6):3076-3083 PTC and MALT thyroid lymphoma Table 1. Summary of prior reported cases of coexisting PTC and MALT thyroid lymphoma Age Stage of MALT Series (references) Clinical presentation HT Discovery method Treatment Prognosis (years)/sex thyroid lymphoma Derringer et al. [4] 3 patients NA NA NA NA NA NA De Melo et al. [5] 61/Male Fast thyroid enlargement Yes Postoperative pathological Stage IE Surgery and radioactive iodine No recurrence in 2.0 years examination and IHC Vassilatou et al. [6] 51/Female A palpable 2.0-cm nodule in the right lobe Yes Postoperative pathological Stage IE Surgery and radioactive iodine No recurrence in 14 months examination and IHC Cheng et al. [7] 59/Male Multiple thyroid nodules Yes Postoperative pathological Stage IE Surgery and radioactive iodine No recurrence in 7.0 years examination and IHC Nam et al. [8] 81/Female Thyroid nodule and hoarseness Yes Postoperative pathological Stage IE Surgery No recurrence in 1.0 year examination and IHC Shen et al. [9] 25/Female A palpable 1.2-cm nodule in the right lobe Yes Postoperative pathological Stage IE Surgery, radioactive iodine No recurrence in 2.0 years examination and chemotherapy Cao et al. (our study) 57/Male A palpable 4.0-cm nodule in the left lobe and Yes Postoperative pathological Stage IE Surgery and radiotherapy No recurrence in 4.5 years 2.0 cm nodule in the right lobe. examination and IHC 43/Female Nothing unusual Yes Postoperative pathological Stage IE Surgery No recurrence in 4.0 years examination and IHC 61/Female A palpable 3.0-cm nodule in the right lobe Yes Postoperative pathological Stage IE Surgery and radiotherapy No recurrence in 3.5 years examination and IHC (NA) not available, (PTC) papillary thyroid carcinoma, (MALT) mucosa-associated lymphoid tissue, HT (hashimoto’s Thyroiditis), IHC (immunohistochemical).
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