Oncologic Emergencies

• Tumor Lysis Syndrome (TLS): Results from massive, rapid tumor cell death releasing intracellular contents into the circulation. When malignant cells undergo lysis (spontaneously or following chemotherapy), they release potassium (K+ 140 mEq/L intracellular), phosphate, and nucleic acids. Hyperkalemia causes cardiac dysrhythmias through altered cellular membrane potentials and conduction abnormalities. Hyperphosphatemia triggers secondary hyperparathyroidism and precipitates with serum calcium as calcium phosphate crystals in renal tubules, causing acute kidney injury (AKI). Uric acid produced from purine metabolism (nucleic acid breakdown) precipitates in acidic urine (tubular pH <6), forming uric acid crystals that obstruct renal collecting ducts. These crystalline depositions in the proximal tubules and collecting ducts cause direct mechanical obstruction and tubular epithelial toxicity, leading to oliguric renal failure. The degree of TLS correlates with tumor burden and cell turnover rate—rapidly dividing leukemias and lymphomas causing TLS more commonly than solid tumors.

• Superior Vena Cava Syndrome (SVCS): Develops when mediastinal tumors (typically lung cancer or lymphoma) cause mechanical obstruction or thrombosis of the superior vena cava (SVC). The SVC has low intraluminal pressure (2-8 mmHg) compared to systemic circulation, making it vulnerable to external compression. Increased venous pressure proximal to the obstruction impairs venous return, reducing cardiac preload and causing elevated venous pressure in head, neck, and upper extremities. Collateral vein development (especially via azygos system) occurs over time but inadequately compensates acutely. Tumor invasion or associated thrombosis (malignancy is prothrombotic through tissue factor expression and platelet activation) compounds the mechanical obstruction. The anatomical narrowness of the SVC at the thoracic inlet makes it a point of vulnerability, particularly for right upper lobe lesions or anterior mediastinal masses.

• Spinal Cord Compression: Occurs when epidural tumor mass, metastatic disease, or vertebral body collapse compresses the spinal cord, interrupting neural transmission. The thoracic spine is most commonly affected (40%), followed by lumbar (35%) and cervical (25%) regions. Mechanical compression directly damages axons and neurons through tissue distortion. Additionally, tumor-associated edema, vascular compromise from displacement of spinal arteries, and ischemia from interruption of microvascular perfusion contribute to neuronal injury. The blood-spinal cord barrier is disrupted by tumor-associated inflammation and vascular endothelial growth factor (VEGF) production, leading to vasogenic edema that potentiates neural dysfunction. Early symptoms reflect dorsal column (proprioception, vibration) and spinothalamic tract (pain, temperature) involvement before motor pathway compression.

• Cardiac Tamponade: Results from malignant pericardial effusion (from primary pericardial involvement, metastatic disease, or post-radiation pericarditis) causing pericardial fluid accumulation exceeding the pericardium's compliance capacity. The pericardium is a non-distensible fibrous sac; rapid fluid accumulation (>250 mL acutely) impairs ventricular filling more severely than gradual accumulation. Elevated intrapericardial pressure (normally 2-5 mmHg) reduces transmural pressure gradient across ventricular walls, decreasing ventricular filling pressures and stroke volume. The right atrium, having the lowest pressure, is compressed first, followed by right ventricle, then left-sided chambers in severe cases. This causes equalization of diastolic pressures and reduced cardiac output, manifesting as hypotension, decreased consciousness, and shock. The low-pressure right heart is preferentially affected, producing characteristic pulsus paradoxus (exaggerated fall in systolic BP >10 mmHg with inspiration).

• Acute Leukostasis: Occurs in acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL) with extremely high white blood cell (WBC) counts (typically >100,000-200,000/μL). Immature leukemic blasts have reduced deformability compared to mature leukocytes and increased adhesion molecule expression (CD11b/CD18 integrins). These rigid, adhesive cells sequester in pulmonary and cerebral microvasculature, causing mechanical obstruction and vascular occlusion. Leukemic cells produce tissue factor and procoagulants, promoting disseminated intravascular coagulation (DIC). Leukocyte-endothelial adhesion triggers inflammatory mediator release (IL-1, TNF-α, leukotriene), causing vascular permeability increases, bleeding, and further microvascular dysfunction. The combination of mechanical obstruction and inflammatory injury produces hypoxic and ischemic injury to lung and brain tissue.

• Malignant Hypercalcemia: Results from two main mechanisms: (1) PTHrP secretion (paraneoplastic syndrome) causing increased renal calcium reabsorption and bone resorption, or (2) calcitriol (1,25-dihydroxyvitamin D) production by tumor or tumor-associated macrophages. PTHrP activates PTH1R receptors on osteoblasts and renal proximal tubules, mimicking PTH effects. Elevated serum calcium increases glomerular filtration pressure, exceeding the tubular reabsorption capacity, causing nephrogenic diabetes insipidus (NDI)-like state with renal wasting of both calcium and sodium. Hypercalcemia impairs ADH responsiveness, further promoting polyuria. Severe hypercalcemia causes cellular dysfunction through altered Na+/K+-ATPase pump function, altered membrane potential, and impaired neurotransmitter release.

• Tumor Lysis Syndrome (TLS): High-risk malignancies include acute leukemias (particularly ALL and AML), Burkitt lymphoma, high-grade lymphomas (diffuse large B-cell lymphoma, T-cell lymphomas), and rarely solid tumors with high proliferation rates. Risk escalates significantly with high tumor burden, elevated serum uric acid/LDH, elevated creatinine at baseline, hyperuricemia, male gender, and initiation of chemotherapy. Spontaneous TLS can occur in rapidly progressive leukemias before treatment initiation. Secondary TLS occurs following cytotoxic chemotherapy, targeted therapy (e.g., tyrosine kinase inhibitors), or rarely radiation therapy.

• Superior Vena Cava Syndrome (SVCS): Lung cancer (especially small cell and squamous cell histologies) accounts for 40-50% of cases, followed by lymphoma (particularly Hodgkin and mediastinal B-cell lymphomas) at 30-40%, and metastatic breast cancer and germ cell tumors (15-20%). Mediastinal masses are anatomically most likely to compress the SVC. Pre-existing venous catheterization (central venous catheters, pacemakers) and hypercoagulability predispose to thrombotic SVCS. Radiation therapy causing mediastinal fibrosis and chemotherapy (particularly bleomycin) are iatrogenic risk factors.

• Spinal Cord Compression: Most commonly from lung cancer metastases (40%), followed by breast cancer (25%), prostate cancer, lymphoma, and multiple myeloma. Direct extension from primary spinal tumors (meningioma, neurofibroma, ependymoma) or metastatic epidural disease constitute the mechanism. Vertebral body collapse from metastatic disease or multiple myeloma causes mechanical compression. Risk factors include presence of bone metastases, advanced cancer stage, and previous spinal disease.

• Cardiac Tamponade: Lung cancer, breast cancer, lymphoma (especially Hodgkin), mesothelioma, and leukemia most commonly involve the pericardium. Prior mediastinal radiation (Hodgkin lymphoma survivors) significantly increases risk decades later through radiation pericarditis. Malignant pericardial effusions develop in approximately 1% of cancer patients but occur in up to 25% at autopsy, indicating many are clinically silent. Chemotherapy agents (e.g., anthracyclines, 5-fluorouracil, immune checkpoint inhibitors) increase risk through direct cardiotoxicity and pericardial inflammation.

• Acute Leukostasis: Occurs predominantly in acute leukemias, particularly AML with monocytic differentiation (AML-M4/M5) and ALL. Risk dramatically increases with WBC >100,000/μL, though symptomatic leukostasis can occur at lower counts in AML. Hyperleukocytosis (WBC >200,000/μL) nearly always produces symptoms. Risk increases with high blast percentage, young age (immature blasts), and elevated LDH.

• Malignant Hypercalcemia: Associated with squamous cell lung cancer, breast cancer (osteolytic metastases via RANKL), lymphomas (producing calcitriol), multiple myeloma, renal cell carcinoma, ovarian cancer, and endometrial cancer. PTHrP-secreting tumors (PTHrP is ectopically produced) tend toward more severe hypercalcemia. Calcitriol-producing lymphomas (particularly Hodgkin and non-Hodgkin lymphomas) and granuloma-forming conditions produce milder hypercalcemia but are more refractory to treatment.

• Tumor Lysis Syndrome: Symptoms typically begin 12-72 hours after chemotherapy initiation. Hyperkalemia produces cardiac dysrhythmias (palpitations, syncope), muscle weakness, and paresthesias. Patients report weakness progressing to paralysis in severe cases. Hyperphosphatemia is often asymptomatic until secondary hypocalcemia develops, causing tetany, seizures, or cardiac dysrhythmias. Hypocalcemia produces positive Chvostek's sign (facial muscle contraction with tapping on facial nerve) and Trousseau's sign (carpopedal spasm with blood pressure cuff inflation). Hyperuricemia is usually asymptomatic until uric acid nephropathy develops, manifesting as oliguria, elevated creatinine, and flank pain. Acute renal failure develops insidiously with progressive oliguria, azotemia, and fluid overload. Some patients present with no symptoms until sudden cardiac dysrhythmia or seizure occurs.

• Superior Vena Cava Syndrome: Onset is typically insidious over weeks to months but can be acute (hours to days) with thrombotic disease. Facial plethora (reddish facial discoloration) and facial edema are hallmark findings, progressing to neck and upper extremity edema with prominent venous distension. Patients report dyspnea and chest pain, often worse when supine (orthopnea variant). Upper extremity venous collateral pattern becomes visible over anterior chest wall and abdomen. Stridor indicates laryngeal edema from venous congestion. Headache, confusion, and altered consciousness suggest cerebral edema. Arm pain and swelling may be unilateral, indicating asymmetric obstruction. Cough and hemoptysis occur with tracheal/bronchial involvement.

• Spinal Cord Compression: Pain is the earliest symptom in 90% of cases—typically midline or radicular pain that worsens with lying supine, Valsalva maneuver, or percussion over spinous processes (spine percussion tenderness is important sign). Weakness and sensory changes develop progressively, with lower extremities typically affected before upper (depending on lesion level). Radicular pain radiates in dermatomal distribution corresponding to affected nerve roots. Myelopathic symptoms include progressive weakness, spasticity, hyperreflexia, and positive Babinski sign reflecting corticospinal tract involvement. Loss of sphincter control (urinary retention or incontinence, fecal incontinence) indicates cauda equina syndrome or conus medullaris involvement and represents a neurosurgical emergency. Saddle anesthesia (perianal sensory loss) accompanies sphincter dysfunction. Cold feet or loss of temperature sensation may precede motor involvement. Progressive sensory level demonstrates ascending involvement as compression worsens.

• Cardiac Tamponade: Acute presentations feature dyspnea, chest pain, and hypotension. Patients appear anxious and exhibit tachycardia with a narrow pulse pressure. Jugular venous pressure is markedly elevated (>10 cmH₂O), visible in neck with prominent "x" descent on venous pulse (indicating restricted right atrial filling). Pulsus paradoxus is present—systolic blood pressure drops >10 mmHg with inspiration (normal is <10 mmHg). Heart sounds are muffled or distant due to pericardial fluid damping. Kussmaul's sign (paradoxical rise in JVP with inspiration) may occur. Acute tamponade presents with Beck's triad: hypotension, elevated JVP, and muffled heart sounds. Patients in acute tamponade progress rapidly to cardiogenic shock with altered mental status and peripheral hypoperfusion. Chronic pericardial effusions may be asymptomatic or present with gradually worsening dyspnea on exertion.

• Acute Leukostasis: Pulmonary leukostasis presents with acute dyspnea, hypoxemia, and bilateral pulmonary infiltrates on chest imaging mimicking acute respiratory distress syndrome (ARDS). Patients exhibit tachypnea, hypoxemia refractory to supplemental oxygen, and rales on auscultation. Hemoptysis and frothy sputum indicate pulmonary edema. Cerebral leukostasis manifests with altered mental status, confusion, headache, visual disturbances, seizures, coma, or focal neurologic deficits. Fundoscopic examination may reveal retinal hemorrhages or papilledema. Symptoms can progress to loss of consciousness and death within hours without intervention.

• Malignant Hypercalcemia: Mild hypercalcemia (11-12 mg/dL) may be asymptomatic, found only on laboratory screening. Moderate hypercalcemia (12-14 mg/dL) produces polyuria and polydipsia from nephrogenic diabetes insipidus, with patients reporting excessive thirst despite fluid intake. Nausea, vomiting, and anorexia are nearly universal. Constipation develops from reduced GI motility and dehydration. Patients exhibit progressive mental status changes—confusion, lethargy, irritability—reflecting hypercalcemia's neurotoxic effects. Severe hypercalcemia (>14 mg/dL) causes stupor, seizures, coma, and cardiac dysrhythmias. Nephrolithiasis can develop from hypercalciuria. Muscle weakness and fatigue reflect altered neuromuscular junction transmission.

• Tumor Lysis Syndrome: Diagnosis relies on clinical context (initiation of chemotherapy in high-risk malignancy) combined with specific laboratory abnormalities. Hyperkalemia (K+ >5.5 mEq/L) is detected on serum chemistry; severe symptomatic hyperkalemia exists at K+ >6.5 mEq/L with ECG changes. Electrocardiographic findings with progressive hyperkalemia include peaked T waves (at K+ 5.5-6.5), PR prolongation, QRS widening, and loss of P waves (at K+ >7), progressing to sine-wave pattern and asystole. Hyperphosphatemia is defined as phosphate >4.5 mg/dL; TLS-associated values often exceed 10 mg/dL. Secondary hypocalcemia develops as calcium phosphate complexes precipitate; corrected calcium <7 mg/dL indicates severe hypocalcemia. Calculate

Tumor lysis syndrome (NCCN supportive-care and Cairo-Bishop framework)

• Immediate stabilisation: aggressive isotonic IV crystalloid to maintain high urine output is the single most important intervention; treat hyperkalemia with IV calcium gluconate for membrane stabilisation (if ECG changes), then insulin/dextrose and a potassium binder.
• Urate-lowering therapy: xanthine oxidase inhibitor (allopurinol) for prophylaxis in intermediate risk; recombinant urate oxidase (rasburicase) for high risk or established TLS, since it degrades existing uric acid to allantoin rather than merely blocking its formation.
• Escalation: renal replacement therapy for refractory hyperkalemia, oliguric AKI, or symptomatic hyperphosphatemia.
• Contraindicated: rasburicase in G6PD deficiency (hemolysis, methemoglobinemia); routine urinary alkalinization (promotes calcium-phosphate deposition); calcium repletion for asymptomatic hypocalcemia.

Malignant hypercalcemia (ASCO guideline on hypercalcemia of malignancy)

• First: volume expansion with isotonic saline. Then calcitonin for rapid but transient (tachyphylaxis) lowering, bridging to an IV bisphosphonate (zoledronic acid) or RANKL antibody (denosumab), which is preferred in renal impairment or bisphosphonate-refractory disease.
• Glucocorticoids (prednisone) for calcitriol-mediated hypercalcemia of lymphoma. Dialysis for severe hypercalcemia with renal failure. Loop diuretics only for volume overload.

Malignant spinal cord compression (NCCN CNS/ASTRO palliative radiotherapy guidance)

• Dexamethasone immediately, before or concurrent with urgent whole-spine MRI — do not delay steroids for imaging. Definitive therapy is decompressive surgery followed by radiotherapy in surgical candidates with instability or good performance status (Patchell trial), otherwise radiotherapy alone.

Tumor lysis syndrome

• Oliguric acute kidney injury (EMERGENCY): urate and calcium-phosphate crystal obstruction of tubules; signalled by rising creatinine with falling urine output despite hydration; may require dialysis.
• Fatal dysrhythmia (EMERGENCY): hyperkalemia and hypocalcemia together destabilise the myocardium; peaked T waves progressing to QRS widening and sine wave are the warning findings.
• Tetany and seizures: calcium sequestration by phosphate; Chvostek and Trousseau signs precede overt seizure.
• Rasburicase-induced hemolysis/methemoglobinemia (EMERGENCY) in G6PD deficiency: hydrogen peroxide generated by urate oxidation cannot be detoxified; look for a falling hemoglobin with cyanosis unresponsive to oxygen.

Superior vena cava syndrome

• Laryngeal or tracheal edema and cerebral edema (EMERGENCY): venous hypertension transudation; stridor, obtundation, or seizure define the small subset needing intervention before tissue diagnosis.
• Stent thrombosis or migration after endovascular therapy: recurrent facial plethora.

Spinal cord compression

• Irreversible paraplegia and neurogenic bladder (EMERGENCY): ischemic infarction of the cord; ambulatory status at the time of treatment is the strongest predictor of final function, so any new weakness or urinary retention demands same-day imaging.
• Corticosteroid toxicity: hyperglycemia, insomnia/psychosis, GI bleeding, and with prolonged use immunosuppression.

Cardiac tamponade

• Pulseless electrical activity arrest (EMERGENCY): obstructive shock from abolished diastolic filling; narrowing pulse pressure with rising JVP precedes collapse.
• Pericardial decompression syndrome: paradoxical pulmonary edema or ventricular dysfunction after rapid, large-volume drainage.

Leukostasis

• Intracranial hemorrhage and hypoxemic respiratory failure (EMERGENCY): microvascular plugging plus endothelial injury; new focal deficit or oxygen-refractory hypoxemia.
• DIC, especially in acute promyelocytic leukemia: tissue factor release; falling fibrinogen with rising D-dimer.
• Differentiation syndrome with ATRA/arsenic (EMERGENCY): cytokine release causing fever, weight gain, and infiltrates — treat with dexamethasone.

Hypercalcemia

• Nephrogenic diabetes insipidus with prerenal AKI, coma, and short QT arrhythmia (EMERGENCY).
• Bisphosphonate/denosumab toxicity: hypocalcemia, osteonecrosis of the jaw; denosumab discontinuation can cause rebound bone turnover.

• Rasburicase plus G6PD deficiency is the classic trap: a Mediterranean or African-descent patient with Burkitt lymphoma who becomes cyanotic and anemic after urate oxidase. Screen for G6PD before giving it; use allopurinol instead.
• Steroids before the scanner: in suspected malignant cord compression, the single best next step is IV dexamethasone, then urgent MRI of the entire spine (multilevel disease is common). Choosing "MRI first" or "plain films" loses the point.
• Ambulatory status at presentation predicts ambulatory status afterward — this is the association examiners test for cord compression, and it is why back pain plus any weakness in a cancer patient is never an outpatient problem.
• Do not alkalinize the urine in TLS. Aggressive isotonic fluid is the answer; bicarbonate raises the risk of calcium-phosphate precipitation and is no longer recommended.
• SVC syndrome is usually not the immediate emergency it looks like: unless there is stridor or altered mental status, obtain a tissue diagnosis before radiation, because small cell lung cancer and lymphoma respond to chemotherapy. Facial plethora, chest wall collaterals, worse when supine is the buzzword cluster.
• Leukostasis: never transfuse packed red cells into an untreated blast crisis — raising hematocrit raises viscosity and can precipitate stroke. Platelets are safe. Hydroxyurea or induction chemotherapy is the definitive move.
• Tamponade physiology: pulsus paradoxus, Beck's triad, electrical alternans with low voltage on ECG, and diastolic right atrial/ventricular collapse on echo. Give fluids and drain; diuretics and nitrates are the wrong answers.
• Hypercalcemia of malignancy: saline first, calcitonin for speed, bisphosphonate (or denosumab if renal failure) for durability, per the ASCO guideline. Suppressed PTH with elevated PTHrP points to squamous cell lung cancer; elevated calcitriol points to lymphoma and responds to glucocorticoids. Short QT, not long QT, is the ECG finding.