Intractable Hypercalcemia With Mandibular Ameloblastoma

Authors:
Babusai Rapaka, MD, and Stacy Higgins, MD
Emory University School of Medicine

Citation:
Rapaka B, Higgins S. Intractable hypercalcemia with mandibular ameloblastoma. Consultant. 2018;58(3):124-125.

A 72-year-old woman presented with increased somnolence and worsening jaw pain. She had noted associated decreased appetite, weight loss, fatigue, abdominal pain, and severe constipation over the past 2 weeks. Her medical history was significant for biopsy-proven benign ameloblastoma, which had been diagnosed 1 year previously and had been managed conservatively with analgesics.

Physical examination. At presentation, the patient’s pulse rate was 110 beats/min, blood pressure was 144/102 mm Hg, temperature was 36.9°C, and respiratory rate was 16 breaths/min, with an oxygen saturation of 100% on room air. The patient was lethargic and frail and appeared older than her stated age. She had a hard and mildly tender mass measuring 10 × 7 cm on her right lower mandible, with the tongue shifted left, making her unable to close her mouth (Figure 1). Her airway was patent. Cardiac examination revealed sinus tachycardia. She was oriented to person and place, with normal bilateral deep tendon reflexes in the upper and lower extremities.

Diagnostic tests. Laboratory tests revealed leukocytosis (white blood cell count, 12,400/µL; reference range, 4000-10,800/µL), a hemoglobin level of 14 g/dL (reference range, 11.5-15.5 g/dL), a potassium level of 4.1 mEq/L (reference range, 3.4-5.1 mEq/L), a creatinine level of 0.8 mg/dL (reference range, 0.4-1.0 mg/dL), a calcium level of 14.3 mg/dL (reference range, 8.9-10.3 mg/dL), an albumin level of 4.0 g/dL (reference range, 3.5-5.0 g/dL), and a parathyroid hormone (PTH) level of 5.0 pg/mL (reference range, 12-88 pg/mL).

Electrocardiography showed sinus tachycardia and normal PR interval, QT interval, and QRS complex. Computed tomography identified a mixed solid/cystic heterogeneous mass measuring 8.5 × 7.1 × 13.4 cm invading the right mandible (Figure 2).

Hypercalcemia treatment was initiated with fluid replacement and calcitonin, which led to initial clinical and laboratory improvement. However, her hypercalcemia proved resistant to medical therapy. Long-term bisphosphonates were forgone given the risk of jaw osteonecrosis in the setting of possible resection.

Given the negative results of a malignancy workup and her uncontrollable hypercalcemia, a diagnosis of malignant hypercalcemia from her ameloblastoma was considered. Her PTH-related peptide (PTHrP) level was normal at 26 pg/mL (reference range, 14-27 pg/mL). A repeated biopsy of her mandibular mass confirmed benign ameloblastoma.

NEXT: Outcome of the Case and Discussion

Outcome of the case. The patient underwent resection of the ameloblastoma via a right hemimandibulectomy, after which her hypercalcemia resolved within 24 hours without further therapy. Her constipation resolved, her lethargy and somnolence improved, and she was discharged after tolerating a regular diet.

At a 3-month follow-up visit, the patient was tolerating soft food with no subsequent jaw pain or dysphagia. Her calcium level remained within normal limits.

Discussion. Hypercalcemia occurs in 3 ways: increased osteoclastic bone resorption, increased gastrointestinal tract absorption, or decreased renal excretion. The most common etiologies for hypercalcemia are primary hyperparathyroidism and hypercalcemia of malignancy. In 30% of people with malignancy, hypercalcemia occurs due to skeletal metastases or indirectly through production of a humoral factor as the tumor causes increased osteoclastic bone resorption.^1,2 PTHrP is the most common cause of humoral hypercalcemia in malignancy.^2,3 However, PTHrP assays are not very sensitive, and normal values cannot rule out the presence of humoral hypercalcemia. A more reliable indicator is the suppression of endogenous PTH with hypercalcemia and a low calcitriol level, since these findings indicate ectopic production of PTH.⁴

The treatment of hypercalcemia is focused on reducing the associated symptoms while simultaneously addressing the underlying pathology.

Humoral hypercalcemia in most cases presents as severe hypercalcemia (serum calcium > 14.0 mg/dL) and is treated with a multifactorial approach.² Volume expansion with normal saline increases renal calcium excretion and reduces hypercalcemia symptoms secondary to dehydration such as nausea, vomiting, anorexia, and polyuria. Calcitonin with zoledronic acid or pamidronate further reduces serum calcium by direct osteoclast inhibition.² Calcitonin aids in the immediate reduction of serum calcium, whereas bisphosphonates generally take 48 to 72 hours to take effect and to maintain long-term control of hypercalcemia.² These temporizing measures stabilize the patient for definitive therapy via excision of the malignancy or chemotherapy.

Ameloblastoma is a rare tumor thought to arise from remnants of dental lamina, the developmental organ of enamel.^3,5 It most commonly occurs in persons aged 30 to 40 years, without gender or race predilection.⁵ The mandible is most commonly affected, but ameloblastomas also have been noted to originate in the maxilla.⁵ These indolent tumors lead to reactive bone formation and enlargement of the jaw.

It is extremely rare for ameloblastoma to cause hypercalcemia, and the presence of hypercalcemia typically signals malignant transformation.^6,7 Mechanisms of humoral hypercalcemia in ameloblastoma are not well understood, but the most effective therapy still is symptomatic treatment of hypercalcemia with tumor resection.^3,5

References:

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3. Lo TEN, Villafuerte CV III, Acampado LT. Overwhelming hypercalcaemia in mandibular ameloblastoma. BMJ Case Rep. 2014;2014:bcr2014205491.
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5. McClary AC, West RB, McClary AC, et al. Ameloblastoma: a clinical review and trends in management. Eur Arch Otorhinolaryngol. 2016;273(7):1649-1661.
6. Ohtsuru M. Expression of parathyroid hormone-related protein in ameloblastomas. Tokai J Exp Clin Med. 2005;30(4):233-239.
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