Spontaneous Acute Tumor Lysis Syndrome in a DBA/1J Mouse: A Case Report and Review

Abstract

Spontaneous acute tumor lysis syndrome (ATLS) was diagnosed in a 10-month-old female DBA/1J sentinel mouse with leukemic lymphoma. The mouse was unable to maintain balance and died shortly after being observed rolling around in its cage. Disseminated neoplastic disease, including a large cranial mediastinal mass, enlarged lymph nodes and splenomegaly, was present at necropsy. Histopathologic examination revealed widespread massive necrosis of lymphoblastic tumor cells, and widely disseminated microemboli composed of nuclear and cytoplasmic cell debris. Although ATLS is widely recognized as an oncologic emergency in humans, acute lesions of ATLS have not been described. The mechanical obstruction of capillary beds by microemboli originating from disintegrating necrotic tumor cells was the likely cause of clinical signs and death in this mouse. We propose that similar microemboli may contribute to the pathogenesis of the acute renal failure and other clinical signs associated with ATLS in humans. Recognition of spontaneous ATLS in laboratory animals is especially important in studies that assess the efficacy and/or toxicity of anticancer treatments, where early deaths due to ATLS might mistakenly be attributed to a direct test article effect.

Intricate Interplay of Entwined Metabolic and Inflammatory Life-threatening Processes in Tumor Lysis Syndrome Complicating Prostate Cancer: A Systematic Review with a Single Institution Experience

“…Research in animal models proposed additional mechanisms that might explain the higher mortality of TLS. Studies in mice found disseminated microemboli from lysed tumor cells during the histopathological postmortem examination; these result in widespread tissue damage, multiorgan failure, and death [34][35]. Those findings closely mimic the human autopsy findings of disseminated tumor embolism leading to massive tissue organ necrosis and death [36][37].…”

Tumor Lysis Syndrome in Solid Tumors: A Comprehensive Literature Review, New Insights, and Novel Strategies to Improve Outcomes

“…Animal Models: Understanding the Pathophysiology of TLS Despite the aforementioned predisposing factors, animal models of TLS have shown resilience in some mice with heavy tumor burdens, suggesting that heavy tumor burden itself is necessary but not sufficient to cause TLS. This has notably prompted efforts to investigate further pathophysiologic mechanisms of tissue damage that may explain the high mortality of TLS [21][22][23][24][25]. For example, studies in mice revealed that disseminated microemboli composed of debris from lysed tumor cells prompted mechanical micro-obstruction of multiorgan capillary beds, including the kidney tubules, brain, lungs, and elsewhere.…”

Paraneoplastic manifestations of cancer in horses

“…Tumour lysis syndrome results from rapid tumour cell turnover or extensive destruction, and results in the release of intracellular ions and metabolic byproducts into the systemic circulation (Davidson et al 2004;Locatelli and Rossi 2005). The principal metabolic abnormalities in patients with TLS include hyperkalaemia, hyperuricaemia and hyperphosphataemia (causing secondary hypocalcaemia) (Lovelace et al 2003;Davidson et al 2004;Locatelli and Rossi 2005).…”