Hypercalcemia- Leukocytosis Syndrome: A Rare Ominous Indicator in Lung Cancer

Introduction:

Paraneoplastic syndromes are signs and symptoms that occur in association with malignancy at sites distant from the primary tumor or metastases. They occur in approximately 10% of patients with lung cancer (1).

Case:

A 59-year-old male with a history of tobacco abuse, COPD, and Stage IV Lung Adenosquamous cancer with brain metastases status post chemotherapy presented with weakness and lethargy. Patient was normotensive and on room air. Clinical exam was significant for confusion with noted chronic cachexia. Labs most prominent were a WBC count of 46.8 (16.3 1mo prior, 44.6 3wks prior) , Cr of 1.9, Ca of 11.9 , and Lactic acid of 3.7. Imaging was consistent with an increase in his RUL cavitary lesion with pleural based lesions and 11 metastatic deposits throughout the brain. He was admitted and started on aggressive intravenous fluids. Furthermore, infectious workup was initiated and empiric antibiotics administered for possible pneumonia. By day 3 of admission his creatinine, calcium, and lactic acid normalized but his wbc continued to trend up to 98.6 despite negative infectious workup. His severe metastatic disease burden along with his failure to thrive carried a poor prognosis. Subsequently, a family meeting was held and he was transitioned to comfort measures. Patient passed away shortly thereafter.

Discussion:

The case clearly demonstrates poor prognostic indicators with hypercalcemia and severe leukocytosis in the setting of end stage lung adenosquamous carcinoma. Classically, paraneoplastic hypercalcemia is associated with PTHrP production in Squamous Cell carcinoma. Overall incidence of hypercalcemia in lung cancer ranges from to 8%-12% with median survival time (MST) of 3.8 months (1,2).Paraneoplastic Leukocytosis meanwhile is most often associated with adenocarcinoma (42%) and squamous cell carcinoma (36%) with incidence ranging between 16 and 30% and MST of 1.9 months (1,2). Nonetheless, the combination of these two known as Hypercalcemia-Leukocytosis syndrome has been identified an independent clinical entity with an even shorter median survival time in comparison with leukocytosis or hypercalcemia alone of 1.5 months (2). The incidence of this was studied to be 0.5% over a 10 year interval (2). Given this rare occurrence, it is prudent for clinicians to recognize this clinical syndrome and the very poor prognosis it bears .

1. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4127595/

G.R. Mundy, K.J. Ibbotson, S.M. D'Souza, E.L.Simpson, J.W. Jacobs, T.J. MartinThe hypercalcemia of cancer. Clinical implications and pathogenic mechanismsN Engl J Med, 310 (1984), pp. 1718-1727

1. .https://www.sciencedirect.com/science/article/pii/S0169500203004549?via%3Dihub Hypercalcemia-leukocytosis syndrome associated with lung cancer