Discussion

TLS is a well-recognized oncologic emergency resulting from rapid destruction of malignant cells and the subsequent release of intracellular contents into the circulation [1,2]. The resulting metabolic abnormalities, including hyperuricemia, hyperkalemia, hyperphosphatemia, and secondary hypocalcemia, may lead to acute kidney injury, cardiac arrhythmias, seizures, multiorgan dysfunction, and death. Although TLS is frequently encountered following initiation of cytotoxic therapy in hematologic malignancies, spontaneous TLS occurring in the absence of anticancer treatment remains uncommon, particularly among patients with solid tumors [4-6].

The pathophysiology of spontaneous TLS is not completely understood. Proposed mechanisms include rapid tumor proliferation exceeding vascular supply, spontaneous tumor necrosis, extensive tumor burden, impaired renal clearance of metabolic byproducts, and increased cellular turnover [9,10]. These factors may result in the abrupt release of potassium, phosphate, and nucleic acid metabolites, producing the characteristic metabolic abnormalities observed in TLS. Unlike treatment-related TLS, spontaneous TLS may be difficult to recognize because patients frequently present before a malignancy has been diagnosed [4].

Among solid tumors, spontaneous TLS has been reported in small-cell lung cancer, hepatocellular carcinoma, breast cancer, germ cell tumors, colorectal cancer, and metastatic melanoma [4,5,9]. Reports involving gynecologic malignancies remain exceptionally rare [11]. Ovarian carcinoma is not traditionally considered a high-risk malignancy for TLS; however, advanced disease with extensive tumor burden, bulky pelvic masses, carcinomatosis, or massive ascites may create conditions favorable for spontaneous cellular breakdown and metabolic collapse [4,9].

Our patient presented with several classic risk factors associated with spontaneous TLS, including a bulky pelvic mass measuring more than 16 cm, malignant ascites, metastatic disease on cytologic evaluation, and severe metabolic derangements accompanied by acute kidney injury [4]. The absence of chemotherapy exposure or other recognized triggers strongly supported the diagnosis of spontaneous TLS. Notably, these findings developed before exposure to chemotherapy, radiation therapy, corticosteroids, or any other recognized trigger for treatment-related TLS. The absence of alternative explanations, together with fulfillment of Cairo-Bishop criteria, strongly supported the diagnosis of spontaneous TLS.

The diagnosis of ovarian carcinoma was initially established through integration of clinical, radiographic, cytologic, and serologic findings. Tumor marker evaluation demonstrated a CA-125 level of 445 U/mL and a CA125:CEA ratio of 121.6. According to contemporary gynecologic oncology practice and National Comprehensive Cancer Network recommendations, a markedly elevated CA125:CEA ratio may support a Müllerian primary when tissue acquisition is limited or when neoadjuvant treatment must be initiated before definitive surgical staging [8]. In this setting, the combination of malignant ascites, elevated CA-125, and a large pelvic mass strongly favored advanced ovarian carcinoma.

One of the most important aspects of this case was the prompt recognition of TLS despite the absence of a known malignancy. Initial symptoms, including abdominal distension, dyspnea, and oliguria, were nonspecific and could easily have been attributed solely to massive ascites or obstructive processes. However, recognition of the characteristic metabolic abnormalities led to early initiation of intravenous hydration, rasburicase therapy, electrolyte management, and close monitoring. These interventions resulted in rapid improvement of renal function and correction of metabolic abnormalities without requiring renal replacement therapy.

Acute kidney injury is among the most serious complications of TLS and is a major contributor to mortality [4,12-14]. In previously reported cases of spontaneous TLS associated with solid tumors, progression to dialysis-dependent renal failure has been frequently described [5,6]. In contrast, our patient experienced complete recovery of renal function, with serum creatinine improving from 4.09 mg/dL at presentation to 0.89 mg/dL within five days. Early recognition and administration of rasburicase likely played a critical role in preventing irreversible kidney injury [2,3].

The subsequent oncologic course further distinguishes this case from previously reported cases of spontaneous TLS in solid tumors. Following neoadjuvant carboplatin-paclitaxel chemotherapy and interval cytoreductive surgery, pathology demonstrated a complete pathologic response. Follow-up PET/CT demonstrated no evidence of metabolically active residual or metastatic disease, and CA-125 normalized to 5.2 U/mL. This favorable outcome contrasts with the historically poor prognosis associated with spontaneous TLS in solid tumors [4,9].

The favorable outcome observed in this patient contrasts with the historically poor prognosis associated with spontaneous TLS in solid tumors. Published series have reported mortality rates substantially higher than those observed in treatment-related TLS, largely because diagnosis is often delayed and patients frequently present with advanced disease and severe metabolic disturbances. This case illustrates that aggressive supportive management combined with timely multidisciplinary oncologic care can result not only in recovery from TLS but also in excellent long-term oncologic outcomes.