Thyroid Paraganglioma: a Clinical Case e35 Case report Clin Ter 2013; 164 (1):e35-39. doi: 10.7417/CT.2013.1519 Difficulties in the Diagnosis of Thyroid Paraganglioma: a Clinical Case P.G. Calò1, M.L. Lai2, E. Guaitoli3, G. Pisano1, P. Favoriti3, A. Nicolosi1, G. Pinna4, S. Sorrenti3 1Department of Surgical Sciences, University of Cagliari; 2A.O.U. Presidio di Monserrato, Cagliari; 3Department of Surgical Sciences, Sapienza, University of Rome; 4Endocrinology, Nuova casa di cura Decimomannu, Cagliari, Italy Abstract the thyroid capsule (5, 7). With rare exceptions, they are en- docrinologically silent, (4, 8) and the cytological evaluation Thyroid Paragangliomas are exceptionally rare tumors and only could be difficult, due to the possible misinterpretation as 35 documented cases have been reported in the literature. We report medullary thyroid carcinomas (MTCs) or other primary or an additional unusual male case of thyroid Paraganglioma associated metastatic thyroid carcinomas (4-7). to a chronic lymphocytic thyroiditis and a papillary microcarcinoma. A differential diagnosis with MTCs and follicular A 45-year-old man presented with a solitary thyroid nodule. Physi- thyroid neoplasms, should be made using colour flow-dop- cal examination revealed a smooth, well-circumscribed, firm, mobile, pler characteristics, elastosonography or PET and studying painless thyroid nodule in the right lobe measuring 3 cm. Ultrasound molecular markers like the germline activating RET muta- examination showed a 40 mm hypoechoic, non-homogeneous nodule tions documented in 95-98% of hereditary MTCs (8-10). with peri- and intra-nodular vascular flow. An ultrasound-guided fine The first reported thyroid PGL was described by Haegert needle aspiration biopsy was performed showing the presence of in 1974 (11). To our knowledge, only 35 documented cases atypical cells (Thy 3). He underwent a total thyroidectomy associated of thyroid PGLs have been reported to date, and in only four to VI level lymphectomy. Histology showed a thyroid Paraganglioma cases male patients were involved (4, 6, 12). Before surgery, associated to a chronic lymphocytic thyroiditis and a papillary micro- only 20 PGLs were submitted to cytological examination carcinoma measuring 0.3 cm in the greatest dimension. (1, 4, 13, 14). Thyroid Paraganglioma is an elusive tumor. It is difficult to Herein we report an additional unusual male case of diagnose and should be included in the differential diagnosis of all thyroid PGL associated to a chronic lymphocytic thyroiditis neuroendocrine tumors of the thyroid, even those arising in men or and a papillary microcarcinoma. behaving in a locally aggressive fashion. Clin Ter 2013; 164(1):e35-39. doi:10.7417/CT.2013.1519 Case report Key words: neuroendocrine tumor, paraganglioma, thyroid neo- plasm A 45-year-old man presented with a solitary, asympto- matic nodule in the right thyroid lobe; the nodule was in- Introduction cidentally discovered by a cervical ultrasound examination performed for other reasons. Paraganglioma (PGL) is an uncommon neoplasm that The patient’s family history revealed colon carcinoma arises from widely dispersed specialized neural crest cells in his dead sister; there was no family history of thyroid that are associated with autonomic ganglia (1-5). The ma- disease. His personal medical history was negative for jority of thyroid tumors are of the differentiated papillary neck irradiation and he did not have hypertension, flushing, thyroid cancer (PTC) histotype comprising about 90% of all diarrhea or other symptoms related to catecholamines thyroid cancers. The thyroid gland is one of the anatomic hypersecretion. There was no clinical evidence of thyroid sites in which paraganglia are not normally located and dysfunction, with no signs of compression of the adjacent paraganglioma is exceptionally uncommon (1, 2). In the structures or dysphonia. world’s literature only 35 cases of PGL have been reported to Physical examination revealed a smooth, well-circum- date, only 4 of those have been reported in men, it has been scribed, firm, mobile, painless thyroid nodule in the right suggested that PGL occurs predominantly in women (6). lobe measuring 3 cm without palpable cervical lymph no- Thyroid PGLs are thought to arise from the inferior des. The left lobe was unremarkable. Blood pressure was laryngeal paraganglia, which are sometimes situated within normal. Indirect laryngoscopy showed normal mobile vocal Correspondence: Prof. Salvatore Sorrenti. Department of Surgical Sciences, Sapienza, University of Rome, Italy. Viale Regina Elena, 324, 00161 Rome, Italy. Tel./Fax: +39-0649972448. E-mail: [email protected] Copyright © Società Editrice Universo (SEU) e36 P.G. Calò, et al. folds. Hormone dosages (TSH, FT3, FT4 and Calcitonin) were within normal ranges and anti-peroxidase and anti- thyroglobulin antibodies were undetectable. Ultrasound examination showed a 40 mm hypoechoic, non-homogeneous nodule in the right thyroid lobe with remarkable peri- and intra-nodular vascular flow; neither nodules in the left lobe nor neck lymph node enlargement were evident. A 99mTc thyroid scan showed a “cold” no- dule in the right lobe, which corresponded to the palpable lump. An ultrasound-guided fine needle aspiration biopsy was performed showing the presence of atypical cells (Thy 3), organized in rare solid nests of cells with mild cytologic atypia allowing the diagnosis of “indeterminated follicular lesion” (Fig. 1). He underwent a total thyroidectomy asso- Fig. 1. Fine needle aspiration biopsy: presence of atypical cells (Thy ciated to VI level lymphectomy because the intraoperative 3), organized in rare solid nests of cells with mild cytologic atypia al- aspect suggested a thyroid carcinoma. Surgery was very lowing the diagnosis of “indeterminated follicular lesion”. HE 400x. difficult, due to the presence of a firm neoplasm that spread outside the thyroid capsule, adhering to the surrounding neck structures, in particular to right laryngeal recurrent nerve and trachea. The thyroid gland seemed “easy to bleed” and Histology showed a relatively well circumscribed tumor, surgical excision plans could not be clearly identified but measuring 3 cm in diameter, which did not exhibit a cap- the laryngeal recurrent nerves and the parathyroid glands sule and spread beyond the thyroid capsule. The neoplasm were seen and preserved. There were no postoperative was composed of sheets and solid nests of cells, negative complications. at immunohistochemistry for thyroglobulin, calcitonin, Fig. 2. Histological examination: panel A:HE 40X, panel B: S-100 100X, panel C: Thyroglobulin 40X, panel D: Chromogranin 10X, panel E: Synaptophysin 40X. Thyroid Paraganglioma: a Clinical Case e37 TTF1 and positive for chromogranin, synaptophysin, NSE; hyalinizing trabecular adenoma and medullary carcinoma, S-100 was focally expressed (Fig. 2). On the basis of these especially when it exhibits a nesting pattern of growth (1, findings the final diagnosis of PGL was made. A chronic 7, 13, 16, 19). Particularly, it is important to differentiate lymphocytic thyroiditis and a papillary microcarcinoma thyroid PGLs from medullary cancer, especially because measuring 0.3 cm in the greatest dimension were also of the treatment and prognostic implications. In contrast to found. The cervical lymph nodes were not involved. The most medullary thyroid cancers, PGLs stain negative for patient was discharged on the second postoperative day and cytokeratin, CEA and CT (4). substitutive treatment with L-thyroxine was undertaken. He FNAB- Tg protein and FNAB- Tg mRNA /FNAB- CT is alive and well without evidence of recurrent disease 18 mRNA can be helpful in cases in which cytology resulted months after surgery. inadequate or when the cytological diagnosis is inconsistent with patient’s clinical parameters. FNAB-C, Tg/CT mRNA and Tg protein determination Discussion in the fine-needle washout are safe in the diagnosis of me- dullary thyroid carcinoma (20-23). Thyroid PGLs are exceptionally rare tumors and, to our Our case stained positive for S-100 and synaptophysin knowledge, only 35 documented cases have been reported and negative for thyroglobulin, calcitonin, TTF1, P63 and in the literature (7, 13); nevertheless, in the head and neck CEA, leading to the diagnosis of thyroid PGL. region PGLs arising from the carotid body and larynx are It has been demonstrated that PGLs are generally benign not so uncommon, very often occurring also near the thyroid lesions, but the occurrence of malignant PGLs has also been (1, 2). Etiology of such an unusual finding is unclear. In fact, reported (1, 18). The differential diagnosis between benign paraganglia are not normally present in the thyroid gland; and malignant PGL is difficult and cellular criteria for the most prevailing point of view is that during embryoge- malignancy have not been defined yet (1). The criteria for nesis inferior laryngeal paraganglia is being occasionally malignancy include metastasis, necrosis, uniform cytological incorporated into the gland, where it gives rise to thyroid atypia and vascular invasion (1, 12, 13). Unlike malignant PGL (1, 2, 4, 12, 15). neoplasms elsewhere, local infiltration is not indicative of All the reported cases occurred in females, with the malignancy (1, 14). Several authors suggest that there are exception of four males, and the majority were between 40 no histological differences between benign and malignant and 60 years of age (range 9-73) (3, 7, 13, 15-17). Our case