Ear, Nose & Throat Journal2024, Vol. 103(1) 9–12© The Author(s) 2021Article reuse guidelines:sagepub.com/journals-permissionsDOI: 10.1177/01455613211034595journals.sagepub.com/home/ear
Abstract
Paragangliomas of the thyroid gland are rare and usually they originate from the inferior laryngeal paraganglia. In this case report, we describe the case of a 78-year-old woman who presented with an incidental finding of thyroid nodule dislocating the trachea. After a systemic and radiological evaluation, right lobo-isthmectomy was performed, and the definitive diagnosis of paraganglioma was reached. Diagnosis of these thyroidal lesions could be difficult due to their rarity, to their specific radiological aspects and the need of employing specific histological staining techniques. Once the definitive diagnosis is reached, patients should undergo a systemic and genetic evaluation. Surgery is the gold standard treatment; radiotherapy should be considered when aggressive behavior is suspected. Regular long-lasting follow-up should be proposed to these patients considering the unpredictable behavior of these lesions.
Keywordsthyroid, paraganglioma, ENT, endocrinology
Pheochromocytomas and extra-adrenal paragangliomas are quite rare tumors arising from neural crest tissue that can develop both from parasympathetic and sympathetic paraganglia all around the human body.1
Paragangliomas of the head and neck usually arise from vagal and glossopharyngeal nerves. They are most commonly located at the level of the carotid body and jugular glomus2; they represent about 3% of all extra-adrenal paragangliomas and only 0.06% of all head and neck tumors.3,4 Unusual locations have been reported such as paranasal sinuses, orbits, parathyroid glands, larynx, and the thyroid gland.5
Paragangliomas of the thyroid gland are rare and usually originate from the inferior laryngeal paraganglia. It is hypothesized that inferior laryngeal paraganglia could originate in the context of the thyroid capsule (intrathyroidal paraganglioma), further the hypothesis suggests that inferior laryngeal paraganglia may rest laterally and outside the thyroid gland.6,7
Due to the unusual localization, the neuroendocrine origin and the nonspecific histopathological aspect that could be misinterpreted with other histotypes, the correct diagnosis of paraganglioma in the thyroid gland can prove challenging.
A 78-year-old woman presented to the respiratory clinic complaining of dyspnea following a recent episode of bacterial pneumonia. A follow-up chest computed tomography scan was performed and as collateral finding the presence of an asymmetry of the thyroid gland due to an enlargement of the right lobe was observed. It was described as dishomogeneous density, encircling and dislocating the trachea; these findings were reported by the radiologist as compatible with thyroid goiter. No evidence of pathological lymph nodes of the neck was described (Figure 1A)
At clinical examination a painless lump located within the right lobe of thyroid gland was palpable. An endoscopic laryngeal examination was performed, and no laryngeal lesions were found; vocal fold mobility was normal.
Thyroid markers (TSH, fT3, fT4, and thyroglobulin) were in range. No antithyroglobulin antibodies and no antiperoxidase antibodies were found. In order to better evaluate the lesion, a magnetic resonance imaging (MRI) of the neck and a fine needle aspiration cytology (FNAC) were performed.
The MRI showed a bilobed mass of 30 × 26 × 42 mm with infiltrative margins within the context of the right thyroid lobe. The mass appeared to be iso- or hyperintense in T1-weighted sequences; it presented low signal in DWI sequences and a dishomogeneous contrast enhancement. The lesion appeared to strictly adhere to the tracheal wall and the esophagus, while maintaining a cleavage plane (Figure 1B).
The FNAC showed the presence of clusters with high cellularity of fusiform cells presenting cytoplasm and no colloid was detected; specific immunohistochemistry was performed resulting in a negative profile for TTF1, calcitonin, carcinoembryonic antigen (CEA), and parathormone (PTH) resulting positive only for synaptophysin. On the basis of the cytomorphologic appearance and immunohistochemistry profile, the pathologist suggested an intrathyroidal paraganglioma, but the correlation of this diagnosis with a hormonal profile was suggested (Figure 2).
Sieric PTH and the analysis of urinary metanephrine were in range. Considering the normal ultrasound (US) feature of the left lobe and in order to achieve a definitive diagnosis, a right lobo-isthmectomy was performed.
The histological examination showed the presence of a mass surrounded by a fibrous pseudocapsule in continuity with thyroid tissue, characterized by “zellballen.” Immunophenotype was negative for CK, TTF1, calcitonin, and CEA; it was positive for synaptophysin and chromogranin A. Sustentacular cells positive for S100 were present; the proliferative index evaluated with Ki67 was <3%. A definitive diagnosis of paraganglioma was reached.
Paragangliomas are rare tumors originating from neural crest tissue.8 Their localization in the head and neck districts is unusual; the most commonly affected areas are the carotid body and the glomus jugulare. Less than 70 cases of thyroid paragangliomas have been reported in the literature since its first description by Van Miert in 1964.9
Usually, in head and neck districts, paragangliomas arise from the parasympathetic system and they are not associated with increased production of metanephrine as occurred in our patient.10 For that reason, this kind of tumor may be asymptomatic for a long time and, as in this case, diagnosis is accidental.
Due to the similarity of thyroid paragangliomas with other common thyroid nodules, the first step of the diagnostic workup is usually US with associated FNAC.11 Unfortunately, the US aspect of these kinds of lesions is not helpful in suggesting the definitive diagnosis; meanwhile, FNAC can be strongly suggestive of paraganglioma if performed with good quality the cytomorphological aspect alone cannot, in most cases, provide a definitive diagnosis. The pathologist should consider immunohistochemistry staining to confirm or exclude the diagnosis.12 Molecular features of paragangliomas, based on current literature, are summarized in Table 1.13
In case of suspected thyroid paraganglioma on the basis of the cytological result, an assessment of plasmatic and urinary metanephrine should be performed even if hypersecretion of catecholamines is an infrequent occurrence in this district.2 The correct assessment of catecholamines secretion is fundamental in order to prevent intraoperative complications. In fact, patients with increasing catecholamines levels are characterized by the presence of hypertension and low blood volume; moreover, there is a risk of catecholamine storm resulting in hemodynamic instability during surgery.10,14 Serum calcitonin and CEA levels should be measured in order to exclude a medullary carcinoma of the thyroid gland.
If the diagnosis is not obtained with a cytological examination, an intraoperative examination can be performed. Yu et al suggested that the intraoperative examination allowed the correct diagnosis in 8 of 39 cases thyroid paragangliomas; meanwhile, others were misdiagnosed as medullary thyroid carcinoma, follicular thyroid carcinoma, or metastatic disease to the thyroid gland.13
Considering the challenge in reaching a correct diagnosis of this kind of thyroid lesion, in the majority of cases, it is obtained with a definitive histological examination after surgery of the mass. At traditional histology, paragangliomas are characterized by the presence of nests of principal cells, “zellballen,” surrounded by sustentacular cells with pale cytoplasm and with elongated nuclei and indistinct cytoplasm. The histological aspect of thyroid paraganglioma could easily be confused with other neuroendocrine tumors such as C-cell tumors (C-cell hyperplasia and medullary thyroid carcinoma) and follicular-derived tumors (follicular and papillary thyroid carcinoma).12-16 Hence, immunohistochemistry staining has been shown to be extremely important (the molecular profile is summarized in Table 1).15
When a diagnosis of paraganglioma has been obtained, it is of great importance considering that this tumor could be the first sign of systemic disease. Up to 25% of paragangliomas may be present in the setting of a hereditary systemic syndromes such as MEN 2A or MEN 2B, Von Hippel-Lindau disease, neurofibromatosis type I, or hereditary paraganglioma syndrome.17-18 Early identification of a hereditary syndrome allows for early screening for other associated tumors and detection of other family members with a high risk of presenting the same genetic mutation.19
Genetic testing is recommended in the following situations:
Some groups of patients with paragangliomas are at low risk of presenting hereditary disease; this is the case of patients with diagnosis after the age of 50 (risk <2%) as happened in our clinical case.17
The treatment of choice is surgical excision with a total or subtotal thyroidectomy depending on the malignancy of neoplasm. This characteristic is assessed considering the presence of metastasis to lymph nodes or other organs.20
When an aggressive behavior is present an adjuvant radiotherapy treatment on laterocervical lymph nodes may be considered.13
Patients with a diagnosis of thyroid paraganglioma should undergo regular and long-term clinical and imaging follow-ups considering its unpredictable behavior and consistent recurrence reported between 5 and 15 years after initial surgery.21
In conclusion, thyroid paraganglioma is a rare event; its correct diagnosis challenging because of its nonspecific cytological and histological features. Immunohistochemistry staining is fundamental to achieve the final diagnosis. Urinary and blood metanephrine should be performed, and a genetic consultation should be considered. Treatment is mainly surgical, but radiotherapy may be considered if characteristics of malignancy are present. Long-term postoperative surveillance should be performed in view of high risk of recurrence even after just 5 years.
Consensus was obtained by the patient involved in the case report.
The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
The author(s) received no financial support for the research, authorship, and/or publication of this article.
Massimo Campagnoli https://orcid.org/0000-0001-9715-015X
1 ENT Division, University of Eastern Piedmont, Novara, Italy
2 Pathological Anatomy Division, University of Eastern Piedmont, Novara, Italy
Received: June 01, 2021; revised: June 28, 2021; accepted: July 06, 2021
Corresponding Author:Massimo Campagnoli, ENT Division, University of Eastern Piedmont, Via Ettore Perrone 18, Novara 28100, Italy.Email: campagnoli_massimo@yahoo.it
