Answer: Paraganglioma

Histology: The tumor had a broad pushing front and is surrounded by a thin fibrous capsule. The tumor cells are arranged in a prominent nesting pattern, and the nests were separated by a delicate stroma with thin-walled vessels. The tumor cells had round to oval vesicular nuclei and occasional small nucleoli. Mitotic activity is low. There is no evidence of amyloid deposition or C-cell hyperplasia in the surrounding thyroid tissue.>

Immunohistochemically, the tumor cells are strongly immunoreactive for chromogranin A. An S-100 immunohistochemical stain demonstrated strong staining in compressed spindled cells at the periphery of the cellular nests. The tumor cells are not immunoreactive for calcitonin, cytokeratin AE1:AE3, cytokeratin CAM 5.2, CEA, TTF-1 or thyroglobulin.

Discussion: Extra-adrenal paraganglia of the autonomic nervous system reside at consistent anatomic locations in the head and neck. In turn, tumors derived from these paraganglia (i.e. paragangliomas, PGs) occur at highly predictable sites. Indeed, based on their location and radiographic characteristics, PGs of the head and neck are usually recognized without difficulty. Occasionally paraganglia of the head and neck are displaced into adjacent structures. Paraganglia of the larynx, for example, have been identified in the capsule of the thyroid. Tumors derived from these displaced paraganglia (i.e. paraganglioma of the thyroid) are exceptionally rare, entirely unanticipated, and easily misdiagnosed. At the morphologic level, thyroid PG is confused with various metastatic and primary thyroid neoplasms. Most problematic of all, thyroid PG resembles medullary thyroid carcinoma. Both tumors are characterized by a prominent nesting pattern of growth, immunohistochemical staining for neuroendocrine markers, and the ultrastructural presence of neurosecretory granules. Not surprisingly, the diagnosis of thyroid PG is rarely established preoperatively by fine needle aspiration or intraoperatively by frozen section. Even after review of the permanent sections, thyroid PG is often mistaken as medullary carcinoma. The true prevalence of thyroid PGs may not be reflected in the limited number of cases so far reported. Almost certainly, a proportion of presumed medullary thyroid carcinomas actually represent misdiagnosed thyroid PGs.

The distinction of medullary thyroid carcinoma and thyroid PG usually requires a battery of immunohistochemical stains including markers of epithelial, neural and hormonal differentiation. In contrast to most medullary thyroid carcinomas, thyroid PGs tend to demonstrate S-100 staining in sustentacular cells compressed at the periphery of the cell nests; and they lack staining for cytokeratin, CEA, and calcitonin. Unfortunately, even an exhaustive immunohistochemical evaluation may not always provide a definitive diagnosis. Some laryngeal PGs are calcitonin positive; and conversely, some medullary thyroid carcinomas contain S-100 positive sustentacular cells.

The distinction of thyroid PGs and medullary thyroid carcinoma is important and carries weighty treatment and prognostic implications. Thyroid PGs are best treated by complete surgical excision. In contrast to medullary thyroid carcinoma, total thyroidectomy is not indicated for tumors confined to a single lobe of the thyroid, neck dissection is not necessary, radiation therapy is of questionable benefit, and the use of serum calcitonin and CEA levels to monitor residual/recurrent disease is unwarranted. In further contrast to medullary thyroid carcinoma, thyroid PGs consistently behave in a benign fashion. In all reported cases with known follow-up, patients were alive and well following surgical resection.