Introduction:

Tumor lysis syndrome is a critical oncologic emergency most commonly associated with hematologic malignancies. However, it can also occur in patients with solid tumors, especially following systemic cytotoxic chemotherapy. Prompt identification and management are essential, as this syndrome can rapidly lead to severe metabolic disturbances, acute kidney injury, and multiorgan failure.

Case Presentation:

We describe a 65-year-old woman with a history of metastatic uterine leiomyosarcoma who presented to the emergency department with progressive weakness, lightheadedness, and hypotension, six days after receiving a cycle of doxorubicin and trabectedin with concurrent pelvic radiation. Initial evaluation revealed tachycardia, hypotension, pancytopenia, elevated lactate, rising creatinine, and electrolyte abnormalities including hyperkalemia and hyperuricemia. Imaging identified a necrotic pelvic mass and bilateral hydronephrosis. Tumor lysis syndrome was diagnosed and treated with intravenous fluids, rasburicase, and electrolyte correction. Despite initial efforts, the patient developed worsening kidney function, requiring urgent hemodialysis and admission to the intensive care unit. Her clinical course was further complicated by vasopressor-dependent shock, and ongoing tumor necrosis. Nephrology, oncology, critical care, surgery, and palliative care teams were engaged throughout her hospitalization to provide coordinated management and support.

Conclusion:

This case illustrates the potential for tumor lysis syndrome to occur in solid tumors following chemotherapy and the vital role of emergency physicians in early recognition and initiation of treatment. Multidisciplinary care and early involvement of palliative services are essential in managing these complex, high-acuity cases and ensuring patient-centered outcomes.

Tumor lysis syndrome (TLS) results from rapid malignant cell breakdown with release of intracellular potassium and phosphate and metabolism of nucleic acids to uric acid, producing hyperkalemia, hyperphosphatemia, secondary hypocalcemia, hyperuricemia, and acute kidney injury (AKI). These abnormalities can lead to arrhythmias, seizures, multiorgan failure, and death without prompt recognition and treatment. Uric acid contributes to AKI through renal vasoconstriction, oxidative stress, and intratubular precipitation, particularly in acidic urine and low-flow states. Historically, management relied on aggressive hydration and allopurinol; the availability of rasburicase enables rapid enzymatic degradation of uric acid, improving control of hyperuricemia in high-risk cases.[1-5]

TLS is classically associated with hematologic malignancies, usually within 12–72 hours of initial cytotoxic therapy.[5,7]. In solid tumors, TLS is rare, estimated to represent <1>

We report a case of presumed chemotherapy- and radiation-triggered TLS in metastatic uterine leiomyosarcoma complicated by dialysis-requiring AKI and provide a focused review of previously reported cases.

Oncologic History

A 65 year old woman with metastatic uterine leiomyosarcoma was followed by gynecologic oncology and medical oncology for advanced disease. The diagnosis was established based on histopathologic evaluation of metastatic tissue, consistent with high grade leiomyosarcoma. Surgical debulking was not pursued due to extensive metastatic burden and limited anticipated benefit.

Her treatment course included multiple lines of systemic therapy. Most recently, she had been receiving combination chemotherapy with doxorubicin and trabectedin, along with concurrent pelvic radiation therapy for progressive bulky disease. She had completed several cycles of therapy prior to presentation. Disease progression and tumor burden were the primary reasons for treatment escalation. Acute kidney injury associated with trabectedin, including rare reports of rhabdomyolysis, was considered in the differential diagnosis.

Her clinical course had been complicated by malignant ureteral obstruction requiring bilateral ureteral stent placement. These stents were exchanged periodically. Renal function before admission had remained preserved, with serum creatinine values consistently between 0.5 and 0.8 mg per deciliter and no prior history of chronic kidney disease or electrolyte abnormalities.

Emergency Department Presentation

The patient presented to the emergency department with approximately one week of progressive fatigue, poor oral intake, generalized weakness, and dizziness. At an outpatient oncology visit on the day of presentation, she was noted to be tachycardic and hypotensive and was referred for urgent evaluation.

On arrival at admission time, she appeared acutely ill and volume depleted. Vital signs demonstrated sinus tachycardia with heart rates between 140 and 146 beats per minute and hypotension with systolic blood pressures in the 70 to 80 mm Hg range. She was afebrile and maintained adequate oxygen saturation on room air. Cardiac monitoring confirmed sinus tachycardia without evidence of atrial fibrillation or malignant arrhythmias. Physical examination was notable for dry mucous membranes and lower abdominal tenderness associated with a large palpable pelvic mass. There was no evidence of urinary retention.

Given hypotension in the context of recent chemotherapy and immunosuppression, sepsis was considered, and broad spectrum intravenous antibiotics were initiated after blood and urine cultures were obtained. No clear infectious source was identified during the early hospital course.

Initial Investigations

Computed tomography of the abdomen and pelvis demonstrated a large necrotic pelvic mass with bilateral hydronephrosis. (figure 1) Bilateral ureteral stents were visualized in appropriate position. Interval imaging showed improvement in hydronephrosis compared with prior studies. (figure 2) Urology consultation determined that there was no indication for urgent stent exchange or nephrostomy placement, making isolated post renal obstruction an unlikely primary cause of her acute kidney injury.

Figure 11: Contrast-enhanced CT of the abdomen and pelvis

1Axial CT image demonstrates bilateral hydronephrosis with dilated renal collecting systems and perinephric stranding, more prominent on the left side. The ureters appear distended, consistent with obstructive uropathy secondary to pelvic metastatic involvement from uterine leiomyosarcoma. The kidneys show preserved cortical enhancement, and no focal abscess or calculi are identified.

Figure 2: Abdominal axial CT

2Axial CT image demonstrates a large heterogeneous pelvic mass with central areas of necrosis and irregular peripheral enhancement, consistent with metastatic or recurrent uterine leiomyosarcoma. The mass involves the left pelvic sidewall and vaginal cuff region, with compression and probable encasement of the distal ureters, resulting in bilateral hydroureteronephrosis. No evidence of bowel obstruction or free intraperitoneal air is seen.

Initial laboratory evaluation revealed acute kidney injury, with a serum creatinine of 1.34 mg per deciliter and blood urea nitrogen of 81.4 mg per deciliter compared with a previously normal baseline. Over the first several hours of hospitalization, laboratory abnormalities evolved rapidly. Serum potassium increased to a peak of 6.6 mmol per liter. Uric acid was elevated at 8.9 mg per deciliter, phosphorus increased to 5.2 mg per deciliter, and calcium levels were reduced, including a low ionized calcium concentration. Lactate was elevated, and liver enzymes were markedly abnormal, with alanine aminotransferase and aspartate aminotransferase values exceeding ten times the upper limit of normal. Lactate dehydrogenase levels were also elevated, consistent with high tumor turnover and tissue injury. Serial laboratory trends are summarized in Tables 1,2 ad 3.

Table 1: Baseline laboratory values prior to admission3

3Baseline laboratory studies demonstrated preserved renal function and absence of electrolyte abnormalities prior to acute presentation.

Table 2: Laboratory values at admission and early hospitalization4

4Admission laboratories met criteria for laboratory tumor lysis syndrome with concurrent acute kidney injury and evolving clinical TLS.

Table 3: Serial laboratory trends during hospitalization5

5Serial laboratory evaluation demonstrated partial biochemical response to TLS-directed therapy, followed by recurrent renal dysfunction and progressive multiorgan failure.

Clinical Course and Diagnostic Considerations

In the context of recent cytotoxic chemotherapy and radiation therapy, the concurrent presence of acute kidney injury, hyperkalemia, hyperuricemia, hyperphosphatemia, and hypocalcemia raised strong concern for tumor lysis syndrome. At the same time, alternative etiologies were systematically considered, including pre renal azotemia related to hypovolemia and shock, sepsis associated acute tubular necrosis, contrast associated nephropathy, post renal obstruction from malignant compression, and chemotherapy related nephrotoxicity.

The improvement in hydronephrosis with patent ureteral stents, absence of a clear infectious source, preserved renal function prior to admission, and the characteristic constellation of TLS associated biochemical abnormalities supported tumor lysis syndrome as a major contributor to her clinical deterioration rather than an isolated cause.

Aggressive intravenous fluid resuscitation was initiated as tolerated, along with close electrolyte monitoring and administration of rasburicase. Hyperkalemia was treated with standard temporizing measures, including intravenous calcium and insulin with dextrose. Despite these interventions, the patient developed refractory hyperkalemia with worsening acute kidney injury and declining urine output.

Renal replacement therapy was initiated emergently for persistent life threatening electrolyte abnormalities and progressive renal dysfunction. She initially underwent intermittent hemodialysis and was subsequently transitioned to continuous renal replacement therapy due to hemodynamic instability. Her intensive care unit course was complicated by vasopressor dependent shock. Thrombocytopenia and intermittent clotting of the dialysis circuit raised concern for an underlying coagulopathy, and disseminated intravascular coagulation was considered.

Outcome

Despite aggressive supportive care and multidisciplinary management involving nephrology, oncology, critical care, and palliative care teams, the patient’s clinical condition continued to deteriorate. She developed progressive multiorgan failure characterized by persistent hemodynamic instability, worsening hepatic dysfunction, and refractory metabolic derangements. Given the advanced stage of her malignancy, limited oncologic treatment options, and poor overall prognosis, goals of care discussions were held with the patient and her family. A decision was made to transition to comfort focused care. The patient died during the same hospitalization. Renal recovery was not achieved prior to death.

Tumor lysis syndrome is a well recognized oncologic emergency characterized by rapid release of intracellular contents following tumor cell breakdown, leading to hyperuricemia, hyperkalemia, hyperphosphatemia, hypocalcemia, and acute kidney injury. It is most commonly described in hematologic malignancies, particularly high grade lymphomas and acute leukemias, where it typically occurs shortly after initiation of cytotoxic therapy. In contrast, TLS remains rare in solid tumors, with the literature largely limited to case reports and small case series.

Uterine leiomyosarcoma is an aggressive, high grade mesenchymal malignancy with a high proliferative rate and a propensity for early metastatic spread. Despite these features, TLS is infrequently reported in this tumor type. Published cases suggest that TLS in uterine leiomyosarcoma is most often associated with extensive tumor burden, high grade histology, and exposure to cytotoxic chemotherapy, and it carries a high risk of morbidity and mortality.

The present case highlights several diagnostic challenges inherent to TLS in solid tumors. The patient developed acute kidney injury and severe electrolyte abnormalities in the setting of recent chemotherapy and radiation therapy, raising immediate concern for TLS. At the same time, multiple alternative and potentially overlapping etiologies for acute kidney injury were present and required careful consideration. These included pre renal azotemia related to hypovolemia and hypotension, sepsis associated acute tubular necrosis, post renal obstruction due to malignant ureteral compression, contrast associated nephropathy from recent imaging, and chemotherapy related nephrotoxicity, particularly in the context of trabectedin exposure.

Importantly, bilateral hydronephrosis was identified on imaging, raising concern for obstructive uropathy. However, bilateral ureteral stents were patent and interval imaging demonstrated improvement in hydronephrosis compared with prior studies. Urologic evaluation did not recommend further decompressive intervention, making isolated post renal obstruction an unlikely primary driver of the acute kidney injury. Similarly, although hypotension and poor oral intake suggested a pre renal component, the degree and rapid progression of metabolic abnormalities could not be fully explained by hypovolemia alone.

The biochemical profile in this case was notable for the simultaneous presence of hyperkalemia, hyperuricemia, hyperphosphatemia, hypocalcemia, and elevated lactate dehydrogenase following cytotoxic therapy. While acute kidney injury alone can contribute to elevations in potassium and uric acid, the concurrence of these abnormalities with elevated phosphorus and low calcium supports a diagnosis of tumor lysis physiology rather than isolated renal failure. Serial laboratory trends further demonstrated dynamic changes consistent with ongoing tumor breakdown rather than static renal dysfunction.

Another notable feature of this case is the timing of TLS. In hematologic malignancies, TLS most commonly occurs at the initiation of chemotherapy. In contrast, this patient developed TLS after several cycles of treatment, during a period of combination chemotherapy and radiation therapy. Delayed TLS has been described in solid tumors and may reflect cumulative tumor necrosis, evolving tumor sensitivity, or progressive renal vulnerability over the course of treatment. This delayed presentation represents an important clinical distinction and may contribute to under recognition of TLS risk in patients who are not receiving first line therapy.

The patient’s course was further complicated by refractory hyperkalemia and progressive acute kidney injury requiring renal replacement therapy. Thrombocytopenia and dialysis circuit clotting raised concern for disseminated intravascular coagulation, which has been described in severe TLS and advanced malignancy. Ultimately, despite aggressive supportive care and multidisciplinary management, the patient developed progressive multiorgan failure and died during the same hospitalization.

From a clinical perspective, this case underscores the importance of maintaining a broad differential diagnosis when evaluating acute kidney injury and metabolic abnormalities in patients with advanced solid tumors. While TLS must be considered as a must not miss diagnosis, premature diagnostic closure should be avoided. Systematic exclusion or contextualization of alternative etiologies is essential, particularly in complex oncology patients with multiple competing risk factors for kidney injury.

From a scholarly standpoint, this case adds to the limited but growing literature on TLS in uterine leiomyosarcoma. Its distinguishing features include delayed onset following multiple treatment cycles, concurrent radiation therapy, and the challenge of differentiating TLS from other causes of acute kidney injury in the setting of malignant ureteral obstruction and systemic illness. These factors highlight the need for heightened vigilance, early laboratory monitoring, and individualized risk assessment in patients with aggressive solid tumors undergoing cytotoxic therapy.

Tumor lysis syndrome should be considered in any oncology patient presenting to the emergency department with signs of metabolic imbalance and recent chemotherapy. While less common in solid tumors, TLS can be life-threatening and requires rapid identification and treatment. Emergency physicians are key in initiating early therapy, consulting appropriate specialties, and supporting patient-centered care through coordination with palliative services.

Ethics declaration: This case report did not require institutional review board approval as all data were de-identified.

Consent to Participate declaration: not applicable.

Consent to Publish declaration: not applicable.

Funding declaration: The authors received no financial support for the research, authorship, or publication of this article.