Tumor lysis syndrome in an adolescent with recurrence of abdominal rhabdomyosarcoma: A case report and literature review
It is important to note that the three reported cases of disseminated rhabdomyosarcoma6,7 were initially believed to be hematologic malignancies because of their presentation with lymphadenopathy, metastases to the bone marrow, and spontaneous onset of TLS. Rhabdomyosarcoma with bone marrow involvement without an obvious primary tumor is easily confused with acute leukemia, particularly of the lymphoblastic type.12 However, this disseminated-hematologic presentation of rhabdomyosarcoma differs from the solid abdominal-pelvic tumor, which we describe.
Cairo and Bishop13 categorize patients as either laboratory TLS, depicted by metabolic abnormalities alone, or clinical TLS, occurring when laboratory imbalances lead to significant, life-threatening clinical manifestations. Hyperkalemia may lead to cardiac arrhythmias such as torsades de pointes and cardiac arrest. Obstructive nephropathy can occur from the precipitation of calcium phosphate or uric acid crystals in the renal tubules. Hypocalcemia may cause neuromuscular irritability including tetany, convulsions, and altered mental status.13, 14The 2015 “Guidelines for the management of tumour lysis syndrome in adults and children with haematological malignancies on behalf of the British Committee for Standards in Haematology”4 state there are well-recognized risk factors for the development of TLS including, but not limited to, high tumor burden, tumors with rapid cell turnover, and pre-existing renal impairment. Cairo and Bishop, on behalf of the TLS expert panel consensus of 20102, classify patients as having low-risk disease (LRD), intermediate-risk disease (IRD), or high-risk disease (HRD) based on the risk factors and type of malignancy. All patients with solid tumors are classified into LRD, unless the tumors are bulky or sensitive to chemotherapy, mentioning specifically that neuroblastomas, germ-cell tumors and small cell lung cancers are classified as IRD. Cairo and Bishop take into account the risk factor of renal dysfunction/ involvement, which if present, increases the risk by one level. For example, if the patient has IRD and has renal dysfunction, risk increases to HRD2. However, these guidelines do not mention or address the significance of recurrence in any kind of malignancy with regards to assessing risk for TLS.
The British Committee’s 2015 Guidelines for management of TLS in hematologic malignancies14 provide recommendations for treatment based on the patient’s risk classification (TABLE 3). Children with HRD are recommended to be treated prophylactically with a single dose of 0.2 mg/kg of rasburicase. Patients with IRD are recommended to be offered up to 7 days of allopurinol prophylaxis with increased hydration post initiation of treatment or until risk of TLS has resolved. Patients with LRD are recommended to be managed essentially with close observation. Patients with established TLS should receive rasburicase 0.2 mg/kg/day - duration to depend on clinical response. If the patient is receiving rasburicase, the addition of allopurinol is not recommended, as it has the potential to reduce the effectiveness of rasburicase. Further, rasburicase is to be avoided in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency14.
Our patient likely developed TLS because of a fast growing tumor that caused significant tumor burden and renal involvement, indicated by an elevated phosphorus level. Despite these risk factors, TLS was not anticipated in the case presented; therefore, a uric acid level was not collected at the time of admission. Review of the literature indicates that the incidence of TLS in a solid tumor recurrence is either unheard of, or is likely under-reported and truly unknown. Further, the TLS expert panel consensus of 20102, which provides guidelines on risk assessment for TLS, does not address the risk of TLS in a malignancy recurrence. The British Committee’s 2015 guidelines14 also do not address hyperuricemia prophylaxis in a solid tumor recurrence.
Our case presents a question regarding the degree of risk for the development of TLS in a solid tumor recurrence. If the guidelines had existed at the time of the case presentation and had been applied, our patient would likely be classified as having IRD because of his renal involvement. This classification would have lead to a different course of management when initiating chemotherapy, likely prevented laboratory TLS, and provided more cost effective treatment, as rasburicase is known to be expensive.
On the other hand, it can also be argued that our patient classifies as LRD, considering the rarity of TLS in a solid tumor recurrence, that the patient had no TLS complication with his initial course of therapy, and also had a normal LDH on admission. LDH is sometimes used to assess risk in hematological malignancies, although it is not used to make the diagnosis of TLS2. However, with such an argument, it is assumed that the risk of TLS in a solid tumor malignancy recurrence, with no previous TLS complication, is less than the risk associated with a new-onset solid tumor malignancy when, truly, the actual risk is not known. Again, the question is raised of the degree of risk for the development of TLS in a case of a malignancy recurrence, and also in a pediatric patient with risk factors.
In our patient’s case, close observation allowed for prompt diagnosis, appropriate treatment of laboratory TLS, and prevented clinical symptoms from developing. However, a screening or baseline uric acid level may have lead to a more conservative approach towards hyperuricemia prophylaxis, similar to treating the patient as IRD. Therefore, we recommend that a screening or baseline uric acid level and LDH level be obtained when initiating chemotherapy, even in patients with LRD.
Our patient was never hyperkalemic, likely because of concomitant administration of furosemide in an attempt to improve his decreased urine output. Hyperuricemia dropped from 19.5 mg/dL to less than 0.5 mg/dL within 24 hours, following two doses of 0.15 mg/kg of rasburicase, confirming the efficacy of this therapy in cases of established TLS, as is recommended by the British Committee’s 2015 guidelines.14
