A Rare Case of Water Clear Cell Parathyroid Adenoma Escaping Sestamibi Scan and Neck Ultrasound – A Diagnostic Conundrum of a Rare Pathological Entity with a Rare Presentation

Introduction:
Parathyroid water-clear cell hyperplasia (WCCH) and water-clear cell adenoma (WCCA) are extremely rare causes of primary hyperparathyroidism (PHPT). WCCH contributes to <1% of all PHPT however WCCA is exceptionally rare and has been reported only in less than 30 case reports.

We are presenting a very rare indolent pathological entity with a very rare presentation escaping common diagnostic measures of Sestamibi scan and neck ultrasound.

Case Description:
A 63-year-old female presented for evaluation of severe osteoporosis with a T-score of -3.6. Laboratory workup revealed elevated parathyroid hormone (PTH) of 122 pg/ml (reference range 12-88 pg/ml), Normal calcium 9.8 mg/dl, Normal vitamin D 50 ng/ml, and normal magnesium 2.2 mg/dl. 24-hour urine calcium was 421 mg/24H. Diagnosis was consistent with normocalcemic PHPT and meeting surgical criteria with osteoporosis and high urine calcium. Sestamibi scan did not identify any focal activity. CT H&N revealed an 8 mm mass inferior and posterior to right thyroid lobe with partial washout and slightly different enhancement compared to thyroid gland. Neck ultrasound (US) reported that previously noted tissue activity on the CT H&N is not visualized and most likely represents normal thyroid tissue. Patient was referred to otolaryngology surgery and underwent four gland explorations, including right inferior and left superior parathyroidectomy. Pathology of superior parathyroid gland revealed parathyroid water clear cell adenoma. 3-month Postoperative PTH 29.4 pg/ml and calcium level of 9.3 mg/dl.

Discussion:
Solitary parathyroid adenoma (SPA) attributes to 80-85% of PHPT. Majority of cases is due to Chief cell adenomas, less frequent pathologies include oxyphil cell adenoma, lipoadenoma, WCCA or mixed type.

Scientific literature regarding WCCA presentation and diagnosis is blurred due to its rarity. 

Clinical presentation of WCCA resembles other etiologies of PHPT, though some data suggest that is frequently indolent and manifests with mild PHPT.

Literature suggests that WCCA has low biochemical activity and most cases had normal to mildly elevated calcium-our patient support this hypothesis-. Hypercalcemia does not manifest until significant growth of the adenoma, though few reported cases manifested with hypercalcemia.

Unlike other SPA where Sestamibi scan sensitivity is 91%, literature suggests possibility of false-negative results with WCCA which is hypothesized to be attributed to its different histology of glycogen-rich vacuolized cytoplasm that leads to fast Sestamibi wash-out, for the same reason data suggest that US is more decisive given high water content of cells -Our patient didn’t follow this rule and escaped Sistamibi and US though seen on CT- which still makes the diagnosis of WCCA a conundrum.

Some cases underwent surgical excision based on clinical diagnosis which led to revision of PHPT and/or hypercalcemia. There is no available data suggesting different long-term follow-up regimens for WCCA compared to other SPA.

Further literature with longer follow-up is needed for this extremely rare entity for a comprehensive understanding of its natural course.