There are two pairs of parathyroid glands, superior and inferior, which are both juxtathyroidal in location. While an ectopic parathyroid can be identified at any location between the mandible and the mediastinum, the ectopic location of the parathyroid tissue in the mediastinum is uncommon1.  Most of the reported cases of an ectopic mediastinal parathyroid tissue/adenoma present with clinical features of hyperparathyroidism (elevated serum calcium etc.). Radiological studies are then used to identify the source of increased parathyroid hormone. In our case, the patient did not have symptoms of hyperparathyroidism. A mass was identified in the mediastinum during a work-up of conditions unrelated to hyperparathyroidism. After the FNA diagnosis, the clinical lab results were obtained and showed mildly elevated serum calcium and markedly elevated PTH.

A cytologic diagnosis of an ectopic parathyroid with no known clinical information can be difficult. The major differential diagnosis consideration should include WDNET, thyroid, and lymphoid tissue.

PARATHYROID Vs. WDNET:

Our patient had a history of WDNET arising in the background of AMAG. WDNET associated with AMAG usually has an indolent clinical course, and lymph node metastasis is uncommon. On a FNA specimen, the distinction between parathyroid vs. WDNET can be very difficult based on cytomorphology alone. Most WDNETs arrange in a more dyshesive pattern than seen in this case. IHC profile is certainly the key to arrive the correct diagnosis. While both are positive for cytokeratin and neuroendocrine markers, positive staining for GATA3 and PTH supports the diagnosis of parathyroid tissue. Also, TTF1 can be helpful in this scenario as it is positive in 50% of WDNET of pulmonary origin. Similarly, CDX2 would be positive in two-thirds of WDNETs of intestinal origin2.

PARATHYROID Vs. THYROID

Parathyroid gland is composed of three types of epithelial cells: chief cells, oxyphil cells, and clear cells. The chief cells can mimic follicular cells of the thyroid, and oxyphil cells can resemble the Hürthle cells of the thyroid3. Architecturally, both can show flat sheets/ clusters as well as “microfollicular” and “macrofollicular” patterns. It had been reported that a diverse mixture of architectural features in the same lesion may be suggestive of a parathyroid lesion over thyroid lesions4. The background on the smears may provide diagnostic clues. The presence of hemosiderin laden macrophages, abundant colloid, and paravacuolar granules favors thyroid origin5. The IHC is helpful to make this distinction of parathyroid vs. thyroid. Parathyroid cells are positive for PTH and neuroendocrine markers. GATA-3 is a transcription factor that is reliable in distinguishing thyroid from parathyroid in this setting (nuclear staining)6. Takada et Al, has shown that parathyroid lesions stain for GATA-3, PTH, Chromogranin A, and TTF-1 as 98.8%, 56.1%, 87.8%, and 0% respectively6. Follicular cells of thyroid are positive for TTF-1, thyroglobulin and PAX82. On FNA, often only chief cells are seen which closely resemble follicular cells of thyroid. If parathyroid lesion is suspected at the time of FNA, a needle rinse to measure PTH can be performed.

PARATHYROID Vs LYMPHOCYTES

Most FNA smears of a lymphoid lesion contain characteristic lymphoglandular bodies7 in the background. Lymphocytes have higher nuclear/ cytoplasmic ratio and are much more dispersed and dyshesive when compared to parathyroid cells. Lymphocytes are positive for CD45 and negative for cytokeratin.

In conclusion, the entity of ectopic parathyroid should be included in the differential consideration when mediastinal lesions of unknown origins are sampled by FNA. Most of these patients may have clinically symptomatic hyperparathyroidism; however clinically asymptomatic patients should not be excluded from the differential. If cytomorphology is suggestive of parathyroid, IHC can confirm the diagnosis, and clinical workup of serum calcium and parathormone levels may be helpful.