What is the most likely diagnosis in a 58‑year‑old woman with metastatic HER2‑positive breast cancer who, after a dose of trastuzumab and pertuzumab, develops oliguria, acute kidney injury, hyperkalemia, hyperuricemia, hyperphosphatemia, hypocalcemia, elevated lactate dehydrogenase, metabolic acidosis and high lactate?

Tumor Lysis Syndrome

This patient has tumor lysis syndrome (TLS), characterized by the classic tetrad of hyperkalemia, hyperuricemia, hyperphosphatemia, and hypocalcemia following chemotherapy initiation in a patient with high tumor burden metastatic breast cancer.

Clinical Presentation Matches TLS Diagnostic Criteria

The patient presents with the complete metabolic profile of TLS as defined by established diagnostic criteria 1, 2:

• Hyperkalemia (6.4 mmol/L) - the most immediately life-threatening abnormality 1
• Hyperuricemia (13 mg/dL) - markedly elevated from nucleic acid degradation 1, 2
• Hyperphosphatemia (1.64 mmol/L) - from intracellular phosphate release 1, 3
• Hypocalcemia (1.73 mmol/L) - secondary to calcium-phosphate precipitation 1, 3
• Acute kidney injury (GFR 38 ml/min, oliguria) - from crystal deposition in renal tubules 1, 2
• Elevated LDH (2473 U/L) - marker of massive cell turnover 1, 2
• Metabolic acidosis (pH 7.11) - from renal dysfunction and cellular breakdown 1

Why TLS and Not the Other Diagnoses

Light chain deposition disease would not present acutely after a single chemotherapy dose and would not explain the constellation of hyperkalemia, hyperuricemia, and hyperphosphatemia occurring simultaneously 2.

Rhabdomyolysis could explain hyperkalemia, elevated LDH, and acute kidney injury, but would present with markedly elevated creatine kinase (not mentioned), myoglobinuria, and would not cause hyperuricemia at 13 mg/dL or hyperphosphatemia in this pattern 1.

Tubulointerstitial nephritis from trastuzumab/pertuzumab would not cause the acute metabolic derangements seen here, particularly the severe hyperuricemia and hyperphosphatemia 4. These HER2-targeted agents cause cardiac toxicity, not this metabolic syndrome 4.

Myeloma kidneys is not consistent with metastatic breast cancer and would not present acutely after chemotherapy initiation with this specific metabolic profile 2.

TLS in Solid Tumors: An Important Recognition

While TLS is classically associated with hematologic malignancies, it occurs in solid tumors with high tumor burden, particularly after treatment initiation 5. In a case series of 19 patients with solid tumor TLS, 42% had lung cancer as the primary tumor, and mortality reached 63% despite treatment 5. The development of TLS in solid tumors is associated with increased mortality, making early recognition critical 5.

Critical Management Priorities

The hyperkalemia at 6.4 mmol/L is the most immediately life-threatening abnormality requiring urgent treatment to prevent fatal cardiac arrhythmias 1, 3. Treatment should include:

• Aggressive fluid resuscitation with crystalloids to improve renal perfusion and increase excretion of potassium, phosphorus, and uric acid 1
• Rasburicase for severe hyperuricemia to prevent further uric acid crystal deposition 1, 2
• Urgent treatment of hyperkalemia with calcium gluconate (for cardiac membrane stabilization), insulin/glucose, and potentially dialysis 1, 3
• Early dialysis is recommended given the severity of electrolyte abnormalities, renal dysfunction (GFR 38), and metabolic acidosis 1, 3

Common Pitfall

Do not delay treatment while waiting for additional confirmatory tests. The clinical presentation with the complete metabolic tetrad occurring acutely after chemotherapy in a patient with high tumor burden is diagnostic 1, 2. Hypocalcemia treatment should be reserved for patients with ECG changes or neuromuscular irritability symptoms, as calcium administration can worsen calcium-phosphate precipitation 1.

The elevated lactate (10.9 mmol/L) likely reflects both tissue hypoperfusion from the acute illness and potentially anaerobic metabolism from the tumor burden, which decreases with tumor lysis 3.