Cytology of Hashimoto’s Thyroiditis Coexistent with Papillary Thyroid Carcinoma

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Cytology of Hashimoto’s Thyroiditis Coexistent with Papillary Thy-roid Carcinoma: A Case Report

Cheng-Chieh Chen, Yu-Chun Chen, Chih-Ping Li, Yuh-Yu Chou and Chin-Cheng Lee

Department of Pathology and Laboratory Medicine, Shin Kong Wu Ho Su Memorial Hospital, Taipei, Taiwan

The co-existence of cytological evidence for Hashimoto’s thyroiditis (HT) and papillary thyroid car-cinoma (PTC) is uncommon in routine practice. We present the case of a 56 year-old female who presented with bilateral thyroid nodules and PTC was suspected based on the fine needle aspiration cytology. Smears showed high cellularity, neoplastic cells with squamoid cytoplasm and enlarged nuclei with pseudoinclusions. Hurthle cells and lymphocytes were also noted. Colloid was scant. Histopathological examination revealed HT with PTC. There was no evidence of metastasis. Cy-totechnicians and pathologists should be vigilant for the presence of neoplastic cells in smears dur-ing routine screening that show Hurthle cells and lymphocytes.

Key words: Hashimoto’s thyroiditis, papillary thyroid carcinoma, fine needle aspiration cytology, Hurthle cells, lymphocytes

Introduction

The majority of primary thyroid cancers are papillary thyroid carcinomas (PTC) and there is a higher incidence in females than males. However, evidence of papillary thyroid carcinoma and Hashimoto’s thyroiditis do not commonly co-exist on cytological examination. The incidence of neoplasia in Hashimoto’s thyroiditis diag-nosed by fine needle aspiration cytology is 4% [1]. Thy-roidectomy is the treatment of choice and thyroxine (T4) replacement is usually needed thereafter. We report the case of a 56 year-old female patient with cytological findings suggestive of papillary thyroid carcinoma but later diagnosed with both Hashimoto’s thyroiditis and papillary thyroid carcinoma following pathological ex-amination.

Case Report

A 56 year-old female patient presented to our outpatient department complaining of hot flushes and was found to

have bilateral thyroid nodules on physical examination. She had no significant past medical history. Laboratory tests were consistent with hypothyroidism (thyroxine: 3.4 µg/dl; thyroid stimulating hormone: 107.3 µIU/ml). Antithyroglobulin antibody (ATA) and antimicrosomal antibody (AMA) were not tested. Papillary thyroid car-cinoma was initially suspected based on ultrasonogra-phy-guided fine needle aspiration cytology. Cytological smears showed high cellularity (Fig. 1a), multiple neo-plastic cell nests with enlarged nuclei (Fig. 1b) and ma-lignant cells with squamoid cytoplasms (Fig. 1c). Hurthle cell nests and lymphoid cells were also noted (Fig. 1d). Pseudoinclusions of malignant cells and papil-lae with fibrovascular cords were not seen. Right total thyroidectomy and left near total thyroidectomy were performed and further histological examination revealed the co-existence of Hashimoto’s thyroiditis (Fig. 2a) with papillary thyroid carcinoma (Fig. 2b). A postopera-tive radioiodine (I-131) whole body scan showed no evidence of metastasis. On recent follow-up, the patient remains well after surgery no palpable neck masses and continues on thyroxine (T4) and thyroglobulin supple-mentation.

Received: February 3, 2008 Revised: March 10, 2008 Accepted: May 14, 2008 Address reprint requests and correspondence to: Dr. Chin-Cheng Lee, Department of Pathology and Laboratory Medicine, Shin Kong Wu Ho Su Memorial Hospital, 95, Wen Chang Road, Taipei, Taiwan Tel: 886-2-28332211 ext 2121 Fax: 886-2-28389360E-mail: cclee6666@yahoo.com.tw

Case Report

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Fig. 1. (a) Fine needle aspiration cytology examination showing an admixture of epithelial cells and lymphoid cells. (Liu stain, x 100) (b) Crowded abnormal cell nests with enlarged nuclei. (Liu stain, x 400) (c) Smears showing neoplastic cells with squamoid cytoplasm. (Liu stain, x 400) (d) Hurthle cell changes and lymphoid cells are noted. (Liu stain, x 400)

Fig. 2. (a) Subsequent histological examination reveals oncocytic follicular epithelial cells with lymphocytic infil-tration. (H&E, x 100) (b) Tumor cells with papillary structure are also found. (H&E, x 100) (c) Immunohistochemical (IHC) staining of oncocytes is negative for cytokeratin 19. (IHC, x 400) (d) Neoplastic cells stain positively for cy-tokeratin 19. Note the cytoplasmic staining of malignant cells. (IHC, x 400)

Cytology of Hashimoto’s Thyroiditis Coexistent with Papillary Thyroid Carcinoma

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Discussion

It is estimated that approximately 70 to 75 percent of thyroid carcinomas will be PTC [2]. Fine needle aspi-ration cytology of the thyroid is the most cost-effective diagnostic tool. The initial gold standard management of papillary thyroid carcinoma larger than 1.0 cm in di-ameter is total thyroidectomy followed by radioiodine ablation. Following surgery, the majority of patients should receive exogenous thyroid hormone sufficient to suppress plasma levels of thyroid stimulating hormone. Recurrences can occur many years after initial therapy and therefore clinical follow-up should be life-long.

Hashimoto’s thyroiditis was originally named struma lymphomatosa and was described by Hakaru Hashimoto in a German surgical publication in 1912 [3, 4] where he described four women with goiters that ap-peared to have become lymphoid organs. The main his-tological characteristics of Hashimoto’s thyroiditis in-clude lymphoid follicular centers, diffuse lymphocytic infiltration, degenerated thyroid epithelial cells and prominent fibrosis. The association between Hashi-moto’s thyroiditis and papillary thyroid carcinoma has been noted before and common pathophysiological pathways have been explored. Akhtar and colleagues have suggested that Hashimoto’s thyroiditis and papil-lary thyroid carcinoma may originate from the same pluripotent stem cells called solid cell nests (SCNs). This is based on shared immunohistochemical positivity for p63 in both Hashimoto’s thyroiditis and papillary thyroid carcinoma [5].

Although cytological evidence of Hashimoto’s thy-roiditis co-existing with papillary thyroid carcinoma has been described before [6], it has been rarely seen in our native academic literature. The frequency of carcinoma in Hashimoto’s thyroiditis varies between 0.5 to 23.7%

[6] and the sensitivity of cytology in the diagnosis of papillary thyroid carcinoma is 92% in Hashimoto’s thy-roiditis [7]. As observed in our study, salient cytological findings in such a patient include a high cellularity, mul-tiple Hurthle cell nests, multiple neoplastic cells with enlarged nuclei and squamoid cells (neoplastic cells with squamoid cytoplasm) [8-11]. Pseudoinclusions of ma-lignant cells are also found, as are lymphocytes and scant colloid. The differential diagnosis based on these cytological features includes Hashimoto’s thyroiditis, Hurthle cell tumor, papillary thyroid carcinoma and ma-lignant lymphoma. A Hurthle cell tumor can be excluded due to lack of tight clusters of Hurthle cells with uniform size and shape. The nuclei of Hurthle cell tumors are usually large, vary in size and may contain prominent nucleoli. Moreover, oncocytes, normal follicular cells and lymphoid cells can also be identified in the current subject, and this picture is not consistent with one of malignant lymphoma. A monomorphic population of large atypical lymphoid cells and lymphoglandular bod-ies is usually also seen in the image of malignant lym-phoma. Papillary thyroid carcinoma was initially sus-pected due to the presence of neoplastic cells with pleomorphic and enlarged nuclei, pseudoinclusions (Fig. 3) and some squamoid cells. This diagnosis was later confirmed. Further histological sections of both thyroid glands revealed obvious lymphocytic infiltration and lymphoid follicle hyperplasia. Most follicular cells demonstrated oncocytic change and a small encapsu-lated, cystic tumor measuring 0.5 cm in diameter was found in the left thyroid tissue. Sections of the left lobe of the thyroid also show the papillary structure lined by enlarged neoplastic cells with pseudoinlclusions (Fig. 4). There is a small amount of lymphocyte infiltration in the papillary cords. There is essentially no indication of ma-lignancy in sections of the right lobe of the thyroid. Hashimoto’s thyroiditis with concurrent papillary thy-roid carcinoma is thought to be the diagnosis.

Fig. 3. Intranuclear pseudoinclusions of malignant cells are noted. (arrow) (Liu stain, x 400)

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Fig. 4. Pseudoinclusions of tumor cells are also found upon histological examination. (arrow) (H&E, x 400)

Szporn and colleagues state that cellular swirls can

be found in 17% of cytological specimens deemed to show papillary thyroid carcinoma. Cellular swirls are tumor cell aggregates that are concentrically organized [12] but none were identified in our study. Lymphocytic infiltration, which is taken to be indicative of Hashi-moto’s thyroiditis, can occur in 58% of patients with papillary carcinoma [13]. Nasser and colleagues state that immunocytochemical staining for cytokeratin 19 will be positive in most cases of papillary thyroid carci-noma, with a sensitivity of 92% and specificity of 97%. Hashimoto’s thyroiditis is negative for cytokeratin 19 [14]. In our patient, immunohistochimical staining for cytokeratin 19 was clearly negative in regions of Hashimoto’s thyroiditis (Fig. 2c) and positive in areas of papillary thyroid carcinoma (Fig. 2d). The possibility of associated neoplasm can not be definitely ruled out even though background changes are suggestive of Hashi-moto’s thyroiditis. Cytotechnicians and pathologists must be vigilant for the presence of neoplastic cells in routine smears exhibiting Hurthle cells and lymphocytic infiltration.

References

1. Carson HJ, Castelli MJ and Gattuso P: Incidence of neoplasia in Hashimoto’s thyroiditis: A fine-needle aspi-ration study. Diagn Cytopathol 1996; 14: 38-42.

2. Jemal A, Siegel R, Ward E, et al: Cancer statistics, 2006. CA Cancer J Clin. 2006: 56; 106-30.

3. Utiger RD: The taxonomy of Hashimoto. Clinical Thy-

roidology 2004: 16; 21-40. 4. Hashimoto H: Zur Kenntniss der Lymphomatosen

Veranderung der Schilddruse (Struma lymphomatosa). Arch Klin Chir 1912; 97: 219-48.

5. Akhtar M and Scognamiglio T: Solid cell nests: role in thyroid disease. Adv Anat Pathol 2007; 14: 141-2.

6. Patil PV, Godhi AS and Sant AN: Fine needle aspiration cytology of papillary carcinoma thyroid with Hashimoto’s thyroiditis--report of two cases. Indian J Pathol Microbiol 1997; 40: 165-8.

7. Pisanu A, Piu S, Cois A, et al: Coexisting Hashimoto's thyroiditis with differentiated thyroid cancer and benign thyroid diseases: indications for thyroidectomy. Chir Ital 2003; 55: 365-72.

8. Nguyen GK, Ginsberg J and Crockford PM: Fine-needle aspiration biopsy cytology of the thyroid. Its value and limitations in the diagnosis and management of solitary thyroid nodules. Pathol Annu 1991; 25: 63-91.

9. Orell S and Philips J: Problems in fine needle biopsy of the thyroid. Pathology 2000; 32: 191-8.

10. DeMay RM, ed. The art & science of cytopathology, Chicago: ASCP Press, 1996: 703.

11. Kini SR, ed. Guide to clinical aspiration biopsy, New York: Igaku-Shoin, 1997.

12. Szporn AH, Yuan S, Wu M, et al: Cellular swirls in fine needle aspirates of papillary thyroid carcinoma: a new diagnostic criterion. Mod Pathol 2006; 19: 1470-3.

13. Tamimi DM: The association between chronic lympho-cytic thyroiditis and thyroid tumors. Int J Surg Pathol 2002; 10: 141-6.

14. Nasser SM, Pitman MB, Pilch BZ, et al: Fine-needle aspiration biopsy of papillary thyroid carcinoma: diag-nostic utility of cytokeratin 19 immunostaining. Cancer (Cancer Cytopathol) 2000; 90: 307-11.

Cytology of Hashimoto’s Thyroiditis Coexistent with Papillary Thyroid Carcinoma

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橋本氏甲狀腺炎合併甲狀腺乳突癌之細胞學檢查：一案例報告

陳正杰 陳毓君 黎治平 周玉瑜 李進成

新光吳火獅紀念醫院 病理檢驗科

橋本氏甲狀腺炎合併甲狀腺乳突癌在臨床細胞形態學檢查中並不常見。本案例為一位五十六歲女

姓病患，臨床症狀為兩側甲狀腺結節。細針抽吸細胞學檢查初步懷疑甲狀腺乳突癌。顯微鏡下顯

示細胞量多，及具類鱗狀樣細胞質 (squamoid cytoplasm) 、細胞核增大伴隨偽包含體

(pseudoinclusion)之惡性細胞。也可發現何氏細胞(Hurthle cell)及淋巴球，但膠質(colloid)很少。病

理組織檢查證實為橋本氏甲狀腺炎合併甲狀腺乳突癌。並無發現癌症轉移之證據。細胞醫檢師或

病理醫師例行篩檢時，應更留意富含何氏細胞及淋巴球之抹片中出現惡性細胞之可能性。

關鍵詞：橋本氏甲狀腺炎、甲狀腺乳突癌、細針抽吸細胞學檢查、何氏細胞、淋巴球

收稿日期：97 年 2 月 3 日 修稿日期：97 年 3 月 10 日 接受日期：97 年 5 月 14 日 通訊作者：李進成主任 新光吳火獅紀念醫院病理檢驗科 台灣台北市士林區文昌路 95 號 電話：(02) 28332211 轉 2121 傳真：(02) 28389360 E-mail：cclee6666@yahoo.com.tw

案例報告