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Revista chilena de anatomía

Print version ISSN 0716-9868

Rev. chil. anat. vol.19 n.3 Temuco Dec. 2001 



*Paulo Vera-Cruz; **Carlos Zagalo; ***Ana Félix; ****Sónia Pratas & **Jorge Rosa Santos

* Ear Nose and Throat Department, S. José Hospital, Lisbon, Portugal.
** Head and Neck Department, Portuguese Institute of Oncology, Lisbon, Portugal.
*** Morphologic Pathology Department, Portuguese Institute of Oncology, Lisbon, Portugal.
**** Endocrinology Department, Portuguese Institute of Oncology, Lisbon, Portugal.

  SUMMARY: Intrathyroidal paragangliomas are very rare tumours. We report a case of a 32 year-old woman with a mass in the right lobe of the thyroid gland, without other symptoms. The first diagnosis was a thyroid medullary carcinoma, after fine-needle aspiration. The therapeutical option was right hemithyroidectomy. Histological pattern and immunohistochemical study were compatible with paraganglioma. We emphasise the diagnostic difficulties and the importance of immunohistochemical markers.

KEY WORDS: 1. Thyroid tumours; 2. Medullary thyroid carcinoma; 3. Hyalinizing trabecular adenoma; 4. Hürthle-cell neoplasm; 5. Carcinoid tumor; 6. Thyroid paraganglioma.


Paragangliomas are very rare neuroendocrine tumors (Brownlee & Shockley, 1997 and Laguette et al., 1997) corresponding to 0.012% of all head and neck tumors (Pessey et al., 1994) with familiar pattern (Portmann, 1992), originating from the autonomic nervous system chemoreceptor cells (Thomassin et al., 1993 and Al Ebrahim et al., 1997). Paragangliomas of head or neck are branchiomeric paragangliomas considered "chromaffin" (Brownlee & Shockley and Pessey et al., 1997). No familial predisposition was described for intrathyroidal paragangliomas (Mitsudo et al., 1987, Brownlee & Shockley, Haegert, 1974, Hughes et al., 1997 and Laguette et al.).

Hughes et al. reviewed the literature and found approximately twenty cases of intrathyroidal paraganglioma. Since then six more cases have been reported (Bizollon et al., 1997, Laguette et al. and Kronz et al., 2000)

They are very vascular (Al Ebrahim et al., 1997) with many arteriovenous shunts (Portmann et al., 1992 and 1995) and develop near the autonomic nervous system and its branches, where there is normal paraganglionar tissue (Laguette et al.). They can also develop in unusual sites where there isn't normal paraganglionar tissue such as the thyroid, soft palate or cavernous sinus (Pessey et al.).

Intrathyroid paraganglioma is thought to arise from the inferior laryngeal paraganglia, that may be included in the thyroid capsule (Brownlee & Shockley; Laguette et al. and Kronz et al.).

All paragangliomas of the thyroid gland are nonfunctional (Hughes et al.). We did not found, in the bibliographic revision, association with multiple endocrine neoplasms.

Usually, the first diagnosis for this entity is a thyroid medullary carcinoma Brownlee et al., Hughes, Kronz et al. Mitzudo et al.), hyalinising trabecular adenoma (Bizollon et al., Chetty et al., 1994 and Hughes et al.), Hürthle-cell neoplasm (Laguette et al.) or a metastatic carcinoid tumor (Chetty et al. and Laguette et al.). Normal calcitonin serum level may be helpfull to exclude a diagnosis of thyroid medullary carcinoma.

The correct diagnosis is established by morphology and by immunohistochemical markers (Martinez- Madrigal et al., and Hughes et al.) an to exclude neuroendocrine tumors.

Immunohistochemical studies using antibodies such as chromogranin, Leu 7, synaptophysin and neuron-specific enolase (NSE) are commonly used. Antibodies to S-100 protein are used to identify nerve cells, staining also melanocytes, chondrocytes and Langerhans cells (Martinez- Madrigal et al., and Milroy & Ferlito, 1995).When epithelial markers such as thyroglobulin and carcinoembryonic antigen are negative, we can exclude Hürthle-cell neoplasm, metastatic carcinoid tumor, metastatic carcinoma, hyalinising trabecular adenoma, poorly differentiated carcinoma and atypical follicular adenoma Laguette et al.).

The clinical presentation of intrathyroid paraganglioma varies from asymptomatic to the presence of thyroid tumor accompanied with swallowing difficulties, pain, hoarseness, stridor or hemoptysis (Haegert et al., Mitzudo et al., Brownlee & Shockley, Hughes et al. and Laguette et al.) Because the duration of symptoms, prior to diagnosis, is not given in the reported cases, it's difficult to know the natural history of these tumors. Malignant potential must be considered in the diagnosis and treatment approach Brownlee & Shockley.

Surgical excision, without elective neck dissection, is the preferred treatment for these lesions (Brownlee & Shockley)


A 32-year-old woman presented with an asymptomatic mass on the right side of the neck with progressive growth, during 3 months.

There was no past history of thyroid disorder or neck irradiation. Family history was unremarkable particularly regarding to thyroid diseases.

Objective examination revealed a tumor on the right lobe of the thyroid, painless to palpation and with mobility during swallowing.

No clinical or laboratory evidence of thyroid impairment was found. Ultrasonography (Fig. 1) showed a nodule with 28x24 mm on the right lobe of the thyroid and scintigraphy with Tc-99m determined that it was a "cold" nodule.

A fine-needle aspiration citology suggested that the diagnosis could be medullary carcinoma but the blood calcitonin level was normal.


Fig. 1. Ultrasonography. Intrathyroid solid tumor (28x24 mm).
Fig. 2. Zellballen patern (x400).

A right hemithyroidectomy was performed with identification and preservation of the right recurrent laryngeal nerve. Frozen section performed intraoperatively was inconclusive regarding the histological type. Immediate post-operatory period was normal but about 3 hours after surgery bilateral vocal cord palsy in adduction was noticed, demanding tracheotomy. After a complete neurological examination, no other neurologic alterations or pathology was detected. After 27 days, the patient totally recovered the vocal cord function and was decannulated.

Histological study of the surgical specimen revealed a well circumscribed neoplasm with a nesting (Zellballen) pattern, composed of large cells, with regular nuclei and small nucleoli and eosinophylic cytoplasm (Fig. 2). The stroma was poor and delicate with numerous blood vessels. There was cytoplasmatic positivity to NSE (Fig. 3) and sustentacular cells were positing with S100 protein antibody. Glial Fibrillary Acidic Protein (GFAP), Calcitonin and Epithelial Membrane Antigen (EMA) antibodies were negative in the neoplasm. Electron microscopy revealed sheets of tumor cells with irregular nuclei, cytoplasm with enlarged mitochondria (sometimes with dense inclusions), Golgi's systems and small cisterns of rough endoplasmic reticulum. Neurosecretory granules are scattered in the cytoplasm, being very prominent in some cells, with an average diameter of 125 nm (Fig. 4).

Fig. 3. Positive immunostaining for N.S.E. (Neuron-Specific-Enolase) (x400).
Fig. 4. Electron microscopy. Cytoplasmatic neurosecretory granules (x55.900).

The final diagnosis was a thyroid paraganglioma. The patient was full examined in order to look for the presence of other lesions in other organs, but the CT scans did not revealed any other tumor. After decannulation the patient is well, without evidence of recurrence for 4 years.


Most of the patients with an intrathyroidal paraganglioma present an asymptomatic mass in the thyroid and seldom have dysphagia or hoarseness. It is possible to make a misdiagnosis with other thyroid tumors, particularly with medullary thyroid carcinoma. That was suggested in our case after cytology (fine-needle aspiration).

The final diagnosis is usually established on the examination of surgical specimen. Light microscopy, electron microscopy and immunohistochemical study, are important to support the diagnosis. Microscope findings include nesting (Zellballen) pattern of the tumor cells, S100 protein positivity of the sustentacular cells and negativity of other neuroendocrine markers are helpful for the correct diagnosis.

It is important to be aware of this rare entity when making the differential diagnosis of tumors in the neck.

The postoperative vocal cord palsy remains unexplained. There were no intraoperatory incidents. The right recurrent nerve was identified and preserved; the left lobe of the thyroid gland wasn't even explored.

RESUMEN: Los paragangliomas de la glándula tiroides son tumores poco frecuentes. Se presenta un caso clínico de una mujer de 32 años de edad, con una masa en el lóbulo derecho de la glándula tiroides, sin otros síntomas. El diagnóstico inicial, al que se llegó por citopunción, fue de carcinoma medular de tiroides. La opción terapéutica fue de hemitiroidectomía. Los estudios anatomopatológicos de la pieza operatoria y la histoquímica fueron compatibles con un paraganglioma. Se pone de manifiesto las dificultades del diagnóstico y la importancia de la imunohistoquímica.

PALABRAS CLAVE: 1. Tumores tiroídeos; 2. Carcinoma medular de tiroides; 3. Adenoma trabecular hialinizante; 4. Neoplasma de Hürthle; 5. Tumor carcinoide; 6. Paraganglioma de tiroides.

Corresponce to:
Dr. Paulo Vera-Cruz
Hospital de S. José,
Serviço de Otorrinolaringologia
Rua José António Serrano,
1050 Lisboa

Tel. +351.21.8841883

Recibido : 24-09-2001
Aceptado: 05-11-2001


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