Primary Paraganglioma of Thyroid Gland: A Clinicopathologic and Immunohistochemical Analysis of Three Cases with a Review of the Literature

Abstract

Thyroid paraganglioma is an extremely rare tumor and frequently mistaken for other thyroid neoplasms. Increased awareness of its potential presentation in thyroid and its characteristic features is essential for avoiding diagnostic and therapeutic pitfalls. We describe here three additional cases of primary thyroid paraganglioma and analyze their clinical findings and pathological characteristics. Patients included two women and one man presenting with asymptomatic thyroid nodules. Radiological examinations were nonspecific and none had been diagnosed correctly before surgery. On intraoperative frozen section consultation they were all misdiagnosed as carcinomas, either primary or metastatic. However, the permanent sections showed features consistent with paraganglioma. Of note, two cases displayed extension into adjacent thyroid tissues, one of which exhibited increased mitotic activity, confluent tumor necrosis and vascular invasion. Immunohistochemically, the neoplastic chief cells expressed chromogranin, synaptophysin, neuron-specific enolase and CD56, whereas the sustentacular cells were highlighted by S100 protein. All three patients were well with normal hormone secretion, without local recurrence or distant metastasis at last follow-up (range 10-47 months). We further reviewed the literature to summarize the characteristics of this distinctive entity. Albeit being very rare, paraganglioma should be included in the differential diagnosis of hypervascular thyroidal neoplasms. Accurate diagnosis relies on the histopathogical findings and adjunctive immunohistochemcial studies. To date, all the reported cases have pursued a benign course. Although atypical features seem to have no association with clinical behavior, long time postoperative surveillance with biochemical screening of hormone secretion, cervical ultrasonography and whole-body CT scan is recommended.

A registry-based study of thyroid paraganglioma: histological and genetic characteristics

“…As illustrated by our study, the most important clinical technique for differentiating thyroid paraganglioma from other histologies is IHC. We reviewed the literature finding 48 available case reports (Basu & Viswanathan 2011, Phitayakorn et al 2011, Armstrong et al 2012, Capel 2012, Castelblanco et al 2012, Costinean et al 2012, Evankovich et al 2012, Kieu et al 2012, Mohyuddin et al 2013, Yu et al 2013. Similar to our cases, true thyroid paragangliomas are characterized by immunohistochemical positive staining for chromogranin A (30 of 30 investigated tumors/case), synaptophysin (21/21), S-100 (27/28), and neuron-specific enolase (18/18).…”

“…In our series, preoperative reports of results of fine-needle cytology, which was performed in three cases, were not suspicious in any case for paraganglioma, but showed atypical cells as observed in follicular neoplasias or adenomas (Table 1). Other thyroid neoplasias easily mistaken for thyroid paraganglioma include follicular and papillary carcinoma as well as non-paraganglial neuroendocrine neoplasias, chief of which is medullary thyroid carcinoma (Skiadas et al 2001, Zantour et al 2004, Yano et al 2007, Yu et al 2013. As illustrated by our study, the most important clinical technique for differentiating thyroid paraganglioma from other histologies is IHC.…”

“…Thyroid paraganglioma is a rare entity with approximately 60 cases that are reported, including our series (LaGuette et al 1997, Yano et al 2007, Ferri et al 2009, González Poggioli et al 2009, Basu & Viswanathan 2011, Phitayakorn et al 2011, Varsavsky et al 2011, Armstrong et al 2012, Capel 2012, Castelblanco et al 2012, Costinean et al 2012, Evankovich et al 2012, Kieu et al 2012, Mohyuddin et al 2013, Yu et al 2013. A major question is whether the rare entity of thyroid paraganglioma is of practical clinical relevance.…”

“…Interestingly, two of our paraganglioma patients are males, which is in contrast to the results in the reviewed literature (Basu & Viswanathan 2011, Phitayakorn et al 2011, Armstrong et al 2012, Capel 2012, Castelblanco et al 2012, Costinean et al 2012, Figure 11 Electropherograms of SDHB and SDHA sequence variants identified in cases 1, 3, and 4. Evankovich et al 2012, Kieu et al 2012, Mohyuddin et al 2013, Yu et al 2013.…”

Primary thyroid paraganglioma mimicking medullary thyroid carcinoma: A case report

“…On ultrasonography, TP typically appears as a solid hypoechoic nodule, showing no significant differences from other common types of thyroid neoplasms. Computed tomography (CT) generally displays a thyroid mass of low density, and thus TPs are usually mistaken as benign tumors (4). Surgery is generally the recommended treatment method, and few cases involving local recurrence or metastasis following surgical mass excision have been reported.…”