Cytopathology and Histopathology

Biography

Biography: Michael Munoz

Abstract

In cases of severe hypercalcemia with greater than 14mg/dl the possibility of malignancy has to be considered. Multiple myeloma cells will increase the release of macrophage inflammatory protein 1 alpha and tumor necrosis factor, which are inflammatory proteins that cause an increase in macrophages which cause an increase in calcitriol. The organs that are frequently affected by the proliferation of plasma cells include kidneys and bone. Kidneys are affected because of the increase in the abnormal protein being filtered through the kidneys that leads to the formation of cast and damage to the glomerulus filtration barrier, which will lead to acute kidney damage 2.

Case Report: A 54-year-old morbidly obese African American female with a medical history of hypertension, anemia, and uterine fibroids presented to the emergency department with generalized abdominal pain for 3 days. The patient rated the pain at five out of ten and described it as a dull cramping pain that waxed and waned. The pain was non-positional and had not been alleviated by anything. She stated that she had nausea associated with the pain and one episode of vomiting. She also had some constipation before the onset of pain. The pain did not radiate anywhere. She denied any recent trauma, diarrhea, fevers, weakness, shortness of breath, chest pain, or any other muscle pains. She also denied having this pain in the past or any recent travel or changes to her current diet. She had some unintentional weight loss but she was not certain how much. She had no prior surgical history. She denied any tobacco, alcohol, or illicit drug use. Vital signs on admission, the patient’s temperature was 97.8°F, heart rate was 100 beats/min, blood pressure was 136/64, respiratory rate was 18 breaths/min, and oxygen saturation was 97%. On physical exam, the patient was alert and oriented Å~3, with mild discomfort but no distress. Her lungs were clear to auscultation with no wheezing or crackles appreciated. Her heart rate and rhythm were regular with no extra heart sounds or murmurs. Her abdomen had normal bowel sounds in all four quadrants, with tenderness upon palpation around the epigastric area, but with no signs of guarding or rebound tenderness. The laboratory test results from the emergency room. Values to note are the patient’s hemoglobin/hematocrit of 8.2/26 and the mean corpuscular volume of 107. The BUN/creatine of 33/3.6 was a significant increase from her last laboratory test result of 16/0.75 from 6 months earlier. The patient’s calcium level was 18.4mg/dL (range, 8.4–10.2mg/dL) with albumin was 3.3g/dL (range, 3.5–5g/dL). Her corrected calcium level was 19mg/dL. The patient’s laboratory results were consistent with macrocytic anemia, hypercalcemia, and acute kidney injury. The patient’s chest X-ray showed no acute cardiopulmonary process. The abdominal CT showed neither masses nor renal stones. The EKG showed sinus tachycardia. The patient’s serum PTH level was decreased to 11pg/mL (normal, 15–65pg/mL), while her PTHrP levels were slightly elevated at 3.4pmol/L (normal, <2.0). Protein electrophoresis was also performed, showing an M spike of 0.2 (0). The patient’s activated vitamin D level was <5ng/mL (normal, 19.9–79.3ng/mL), vitamin A was 7.2mg/dL (normal, 33.1–100mg/dL), TSH was 1.21mIU/L (normal, 0.47–4.68mIU/L), and free T4 was 1.27ng/dL (normal, 0.78–2.19ng/dL). Urine samples were sent out to test for Bence Jones protein, kappa light chains, and lambda light chains. Immune electrophoresis was done as well with the suspicion of multiple myeloma higher in the differentials after the recent information obtained. The patient was found to have Bence Jones protein present in the urine with her electrophoresis coming back positive for an increase in kappa light chains of 806.7mg/L (n=0.33-1.94), with a normal lambda light chain of 0.62mg/L (n=0.57-2.63). Her IgG levels were also low 496mg/dL (n=610-1660). Patients’ bone marrow biopsy performed revealing plasma cells greater than 10 percent.

Discussion: In severe hypercalcemia with a value of greater than 14 the possibility of malignancy has to be addressed. Patients who develop hypercalcemia from malignancy tend to have a worse prognosis. The treatment has to be initiated in an appropriate time manner because delays can lead to severe complications such as arrhythmias, acute kidney injury, and seizures. The first step in management is IV hydration to have a urine output of 150mL/hr and then consider combined calcitonin and bisphosphonate treatment in patients. In refractory cases, in which the calcium will not respond to treatment consider using glucocorticoids and denosumab. Multiple myelomas will affect the bones by causing osteolytic lesions. This occurs by increased activation of osteoclast via RANKL and the down-regulation of osteoblast by decreasing OPG7. The patient illustrated lytic lesions in 2 of her left lower ribs, in both of her forearms and femurs. Kidneys are typically affected because of the increase in the abnormal protein being filtered through the kidneys that eventually lead to the formation of cast and damage to the glomerulus filtration barrier, which will cause an increase in creatine ratio and lead to acute kidney damage 2. This phenomenon was observed in this patient and the damage became so severe that hemodialysis was required. This posed a great challenge because of the need to give fluids to help reduce her calcium while managing her acute kidney injury status, created the need for constant monitoring. Which posed a great risk for the patient in the delay of reducing her calcium levels without causing permanent damage to her kidneys.