A 76-year-old male patient had been previously admitted to the cardiology department for replacement of a right ventricular lead on a double-chamber pacemaker. The patient had a history of transcatheter aortic valve implantation (TAVI) for bicuspid aortic valve (BAV III), with no complications following the operation. Fifteen days after this hospitalization, he was referred to the emergency department with progressive onset of dyspnea and desaturation to 85% on room air, associated with worsening of his general condition that has been progressive since his hospital discharge. He denied fever, chills, or night sweats. At the emergency department, blood tests revealed hyperkalemia at 5.2 mmol/L with preserved renal function and an inflammatory syndrome (C reactive protein 33 mg/L without hyperleukocytosis). Based on these test results, a chest CT scan was performed, revealing bronchopneumopathy predominantly in the right upper lobe segment, leading to the initiation of treatment with amoxicillin-clavulanic acid 1g every 8 hours.

The patient’s past medical history was relevant for type 2 diabetes mellitus, Hashimoto’s thyroiditis, heart failure due to dilated hypokinetic heart disease, atrial fibrillation, and chronic myelomonocytic leukemia (CMML-0) diagnosed in 2021. The patient had undergone TAVI in 2021 for severe aortic valve disease with tight aortic narrowing and 30% LVEF complicated by BAV III post-TAVI along with implantation of a double-chamber pacemaker. He had no drug or food allergies and his family history was noncontributory. He was on apixaban 5 mg twice daily, levothyroxine 25 ug per day, furosemide 40 mg daily, spironolactone 50 mg daily, bisoprolol 1.25 mg daily, ramipril 1.25 mg daily, insulin LISPRO, 4-4-4, and insulin glargine 32 units at night.

On physical examination, blood pressure was 110/70 mmHg, heart rate was 89 beats/minute, the patient was afebrile and oxygen saturation was 94% (two liters of oxygen with nasal goggles). He was alert and oriented. Mucous membranes were moist and slightly discouloured. Heart sounds were regular without murmurs or rubs and, pulses were normal. Lung sounds were diminished with crackles in the right hemithorax. The abdomen was distended with a palpable splenomegaly.

Twenty-four hours after admission, the patient’s general condition deteriorated abruptly, with the onset of drowsiness and psychomotor retardation. A broad biological workup was performed, revealing hypercalcemia at 4.18 mmol/L (normal value 2.20-2.70 mmol/L) associated with hyperphosphatemia (1.88 mmol/L), hyperuricemia (1455 µmol/L), and a deterioration in renal function with GFR 37mL/min vs. 74 ml and creatinine at 153 vs. 86 umol/L. His albumin (33 g/L), magnesium, and ammonia were within normal range as well as coagulation tests and thyroid-stimulating hormone. Liver function tests were within the normal range except for lactate dehydrogenase (248 UI/L). In addition, we noted the development of hyperleukocytosis (11.4x10⁹/L), elevated C-reactive protein (58 mg/L), hemoglobin 9.1 g/dl, and platelets (87x10⁹/L). The electrocardiogram showed a known left bundle branch block and sinus tachycardia with anterior ST segment sub-shift and normal QT interval.

The patient was scoped and intensive hydration with physiological solution (2 liters), and treatment with calcitonin 100 IU every 6h, and zoledronic acid 3 mg were initiated. The patient was then transferred to the nephrology intensive care unit, where hyperhydration and antibiotics were continued. The patient underwent two sessions of hemodialysis, which normalized the serum calcium levels (2.54 mmol/L). He was then readmitted to our department for further etiological work-up of malignant hypercalcemia.

The remainder of the laboratory investigations showed diminished PTH at 4.6 (normal value 18.5-88 ng/L), phosphorus 1.78 mmol/L (normal value 0.87-1.50), vitamin 25-0H vitamin D at 8 µg/L (normal value 30-80 ug/L), 1-25-OH within normal range, and PTH-related protein (PTHrP) elevated 15.3 pmol/L (normal value <1.5 pmol/L). Angiotensin-converting enzyme and ferritin were within normal limits. We were therefore faced with a non-PTH-dependent hypercalcemia. In this clinical and biological context, a neoplastic origin was initially considered. A thoraco-abdominal scan revealed an extensive diffuse peritoneal carcinosis with perihepatic ascites, bilateral cardiophrenic pseudonodular tissue lesions probably of secondary origin, supra- and subdiaphragmatic adenopathies, and non-hypermetabolic splenomegaly probably associated with known CMML. Investigations were completed by PET scan describing an intense hypermetabolism of diffuse abdominopelvic peritoneal carcinosis, right pleural foci suspicious for malignancy associated with low-grade pleural effusion, multiple supra- and subdiaphragmatic adenopathies (lymphomatous or metastatic origin), and non-hypermetabolic splenomegaly linked with his known CMML. A biopsy of a peritoneal carcinosis nodule was performed.

Forty-eight hours later, the patient developed a severe hypotension associated with marbling and drowsiness. Laboratory blood tests revealed hyperleukocytosis (31.21x10⁹/L), polynuclear neutrophils (38.68 x10⁹/L), monocytes 5.74 x10⁹/L, and acute anuric renal failure (GFR 14 ml/min and creatinine 351 umol/L). Further testing revealed hyperkalemia associated with metabolic acidosis and hyperlactatemia. Corrected calcium was normal, phosphorus was 2.39 mmol/L (normal value 0.87-1.5), and uric acid was 1091 umol/L (normal value 208-428). He was transferred to the intensive care unit.

Upon admission to the intensive care unit, the patient underwent extra-renal purification with Prismaflex for acute renal failure secondary to spontaneous lysis syndrome as well as treatment with rasburicase. He was on dialysis for a total of 9 days and recovered urine production after the addition of diuretics. During his stay in intensive care, the patient received several probabilistic antibiotic treatments for a persistent fever. Antibiotics were finally suspended as all microbiological samples came back negative. The result of the biopsy confirmed the diagnosis of diffuse large-cell B lymphoma. The corticosteroid therapy that was initiated on admission was continued, along with two doses of rituximab. Then, in the absence of improvement, chemotherapy with vincristine and cyclophosphamide was initiated.

Despite aggressive treatment, the patient experienced a sudden episode of desaturation. Considering the lack of improvement and his poor prognosis, the decision of treatment escalation was not pursued. Active measures were discontinued and palliative support started. The patient expired shortly thereafter.