Hypercalcemia of Malignancy

Thank you to Dr. Huber for presenting an intersting case where a young male presented with nausea and was found to have hypercalcemia of malignancy from myeloid sarcoma. This brought up several learning points when thinking about the differential for hypercalcemia, the workup and treatments.

Hypercalcemia can be thought of as secondary to:

  • Parathyroid disorders: FHH, adenomas, MEN, primary or tertiary hyperparathyroidism
  • Vitamin D: iatrogenic ingestions, granulomatous disease (TB, sarcoid, etc)
  • Endocrinopathies: adrenal insufficiency, hyperthryoidism, pheochromocytoma, acromegaly
  • Malignancy: leukemia/lymphoma, sarcoma, RCC, osteolytic metastases
  • Medications: thiazides, lithium, vitamin A, theophylline
  • Immobilization
  • Milk-Alkali Syndrome
  • Genetic Disorders: William's syndrome, Murk Jansen syndrome

In working up hypercalcemia, the following is a good approach once hypercalcemia has been confirmed (i.e. correct the calcium for albumin and check an iCal).

 Diagnostic approach to hypercalcemia per UpToDate

Diagnostic approach to hypercalcemia per UpToDate

When thinking about treatment consider the following:

  • Fluids (preferably normal saline) to restore intravascular volume and improve calcium excretion (typically 200-300ml/hour UOP)
  • Loop Diuretics (occasionally used to prevent volume overload)
  • Calcitonin inhibits bone resorption via interference with osteoclast function
  • Bisphosphonates inhibit bone resorption via interference with osteoclast function
  • Glucocorticoids decreases intestinal calcium absorption and VitD production for those with granulomatous disease or lymphoma
  • Denosumab inhibis RANKL
  • Calcimemtrics to reduce PTH in parathyroid disease
  • Dialysis

In this case, the patient was diagnoses with myeloid sarcoma on biopsy. This is considered a type of AML where less than 1% of patients present with extramedullary disease either simulataneously or preceding bone marrow involvement. It is also called granulocytic sarcoma, myeloblastoma or chloroma. According to UpToDate, it should be considered in the differential for "small round, blue cell tumors" and if there are eosinophilic myelocytes on biopsy. It is treated like AML.

 Myeloid sarcoma on hematoxylin-eosin stain revealing "small blue round cells"

Myeloid sarcoma on hematoxylin-eosin stain revealing "small blue round cells"