Septic shock and hepatic hemorrhage in NTRK-fusion retroperitoneal sarcoma: a case report on oncologic emergencies

Introduction

Retroperitoneal tumors comprise a heterogeneous group of neoplasms that are frequently diagnosed at a late stage due to their deep location and subtle, nonspecific clinical presentations (1). Advances in molecular diagnostics have now revealed distinct subtypes, such as neurotrophic tyrosine receptor kinase (NTRK)-fusion sarcomas (2). These discoveries have paved the way for targeted therapies, which, while promising, also introduce the risk of severe treatment-related complications.

Although targeting NTRK fusion presents a novel therapeutic opportunity, there is a limited number of reports that thoroughly explore the fine balance between effective malignancy management and the risk of life-threatening toxicities. This case underscores the clinical challenge of preventing or mitigating complications—such as septic shock and hemorrhage—while attempting to achieve disease control, highlighting an important gap in current oncologic experience.

The purpose of this report is to present a rare case of a patient with retroperitoneal NTRK-fusion sarcoma who experienced a rapid transition from a stable condition to an oncologic emergency following targeted therapy. Our aim is to emphasize the critical importance of early, multidisciplinary interventions and vigilant monitoring to manage such high-risk situations effectively. We present this case in accordance with the CARE reporting checklist (available at https://acr.amegroups.com/article/view/10.21037/acr-2025-109/rc).

Case presentation

A 71-year-old man with a 7‑month history of retroperitoneal spindle cell sarcoma—confirmed by histopathology and fluorescence in situ hybridization (FISH) demonstrating an NTRK gene fusion—was transferred to our facility with signs of shock. His oncologic history included targeted therapy with anlotinib and doxorubicin chemotherapy, which had been complicated by myelosuppression and chronic tumor necrosis-related exudate from a left lumbosacral mass managed via percutaneous drainage.

In the referring hospital’s emergency department, the patient developed acute abdominal pain and worsening distension. He was evaluated for infectious shock and septicemia, with differential diagnoses including liver abscess and bowel obstruction. Key laboratory findings from that center revealed a markedly elevated white blood cell count, a lactate level of approximately 11.9 mmol/L, and a significant drop in hemoglobin (91 g/L) (Table 1). Abdominal computed tomography (CT) revealed complex retroperitoneal abnormalities and identified a hepatic hemangioma, though no rupture was suspected at that time; moreover, diagnostic paracentesis produced non-bloody fluid.

Shortly after transfer, a bedside ultrasound confirmed the presence of peritoneal fluid. However, within hours, the patient’s condition deteriorated rapidly. He developed a fever of 38 ℃, became markedly agitated, and his oxygenation index dropped to 150. Concurrently, his hypotension worsened, his lactate level surged to 12.5 mmol/L, and his hemoglobin plummeted to 56 g/L. Consequently, he was promptly intubated and initiated on mechanical ventilation. In view of these critical changes, emergent CT imaging was performed, which revealed findings consistent with a ruptured hepatic hemangioma (Figure 1A) as well as invasive, necrotic changes in the left retroperitoneal mass (Figure 1B).

Figure 1 Serial CT findings demonstrating hepatic hemangioma rupture and retroperitoneal tumor response. (A,B) Plain CT on the second day after admission shows a bleeding hepatic hemangioma with perisplenic fluid from rupture (red and white arrows, respectively) (A) and a heterogeneous left lumbosacral retroperitoneal mass invading adjacent muscles and vertebrae, with internal necrosis/hemorrhage (red arrow) (B). (C,D) One week post-embolization, plain CT reveals the embolized hepatic hemangioma featuring a hypovascular core surrounded by high-density iodized oil (red arrow) (C) and markedly reduced abdominal fluid following drainage, while the retroperitoneal mass remains heterogeneous with necrotic foci (red arrow) (D). (E,F) Two weeks post-embolization, contrast-enhanced CT confirms no recurrent bleeding in the hepatic hemangioma (red arrow) (E) and demonstrates minimal enhancement, pronounced necrosis, and persistent loculated fluid in the retroperitoneal lesion (red arrow) (F). CT, computed tomography.

In response to his deteriorating condition, the patient underwent emergent transarterial embolization, which promptly stabilized his hemodynamics. On post-embolization day 6, bedside ultrasound-guided peritoneal drainage evacuated approximately 2,250 mL of chronic blood-tinged fluid. A subsequent non-enhanced abdominal CT confirmed effective occlusion of the ruptured hepatic hemangioma—with no active hemorrhage detected (Figure 1C)—although the retroperitoneal lesions remained largely unchanged (Figure 1D).

By day 14, a repeat combined plain and contrast-enhanced CT demonstrated sustained embolization efficacy, as evidenced by the absence of internal enhancement in the hemangioma (Figure 1E). However, the retroperitoneal mass exhibited features of necrosis with loculated fluid collections (Figure 1F). Consequently, CT-guided drainage of the retroperitoneal fluid was performed, successfully evacuating dark red, blood-tinged material.

Throughout his hospitalization, the patient received comprehensive supportive care—including broad-spectrum anti-infective therapy (initially meropenem and vancomycin, later adjusted per culture results), blood transfusions, mechanical ventilation, and continuous hemodynamic monitoring. With gradual improvement in laboratory parameters (see Table 1), he was transitioned to oral medications and ultimately discharged in stable condition on day 20. The chronological sequence of major clinical events and therapeutic interventions is outlined in Table 2.

Although this report focuses primarily on the acute management phase, limited follow-up data from the patient suggest a favorable short-term recovery. Twelve months post-discharge, telephone follow-up revealed that the patient had resumed independent activities of daily living, reported minimal residual fatigue, and had not experienced any further hemorrhagic or infectious complications. He also expressed improved emotional resilience and adherence to oncologic outpatient visits. Nevertheless, ongoing surveillance and functional assessments remain essential to monitor potential delayed adverse effects, including hepatic function compromise or tumor progression, which may emerge beyond the initial recovery window.

All procedures performed in this case were in accordance with the institutional ethics and with the Declaration of Helsinki and its subsequent amendments. Written informed consent was obtained from the patient and his family for the publication of this case report and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

Discussion

This case highlights the rapid deterioration of a patient with advanced NTRK-fusion retroperitoneal sarcoma who developed a life-threatening oncologic emergency. The patient’s progression—from a stable condition to septic shock and a ruptured hepatic hemangioma—was tracked using a comprehensive integration of clinical, laboratory, and serial imaging data. The application of prompt interventional radiologic techniques, such as transarterial embolization, proved critical in managing these complications.

One significant strength of this report is our detailed documentation of the clinical trajectory and the timely, targeted intervention that facilitated hemorrhage control and hemodynamic stabilization. The use of early contrast-enhanced imaging and biomarkers like lactic acidosis to guide urgent care adds to the clinical relevance of our findings. However, as a single-case study with limited long-term follow-up, the generalizability of these results remains constrained. There is also an inherent limitation regarding the complexity in distinguishing overlapping clinical features in oncologic emergencies.

While this case represents a unique convergence of vascular and oncologic emergencies, similar clinical patterns have been observed in other reports involving targeted therapies. For example, tyrosine kinase inhibitors (TKIs) used in gastrointestinal stromal tumors and renal cell carcinomas have been associated with hemorrhagic risks due to fragile neovascular structures. Multikinase inhibitors such as pazopanib and regorafenib have demonstrated both efficacy and vascular toxicity in sarcoma subtypes, reinforcing the need to anticipate systemic complications alongside tumor control (3).

Targeted therapies, particularly agents like anlotinib, have increasingly become a cornerstone in the management of advanced sarcomas (4). Previous studies emphasize their efficacy, but also warn of their immunosuppressive and pro-hemorrhagic risks (5,6). In contrast to most reports that focus solely on tumor control, our case is distinctive in illustrating a simultaneous vascular emergency. Recent literature suggests that NTRK fusions may enhance pro-angiogenic signaling through abnormal vascular endothelial growth factor pathways, thereby increasing vascular fragility (7)—a finding that aligns closely with the complications observed in our patient.

The abrupt symptom escalation in our patient appears to have been driven by multifactorial pathology. Initially, nonspecific symptoms such as abdominal distension masked the evolving crisis. Subsequent imaging and clinical decline revealed that factors including tumor necrosis, possible perforation, and secondary infection played roles in precipitating septic shock. Notably, the rupture of a hepatic hemangioma—a vascular anomaly likely exacerbated by the pro-angiogenic environment inherent to NTRK-fusion tumors and further weakened by targeted therapy—was a central contributor to the patient’s hemorrhage. The early development of lactic acidosis served as a crucial warning sign, advocating for early diagnostic and therapeutic intervention (8).

Given the severity of complications observed, proactive measures should be integrated into clinical workflows when managing patients with NTRK-fusion sarcomas. These may include pre-treatment vascular imaging, stratification of hemorrhagic risk based on tumor location and enhancement patterns, and early interventional consultation. Monitoring biomarkers such as lactate, hemoglobin, and inflammatory indices can offer early warnings for septic or hemorrhagic progression. Moreover, modifying dosages or scheduling breaks during antiangiogenic therapy in high-risk patients may mitigate toxicity without substantially compromising efficacy.

This case underscores the need for heightened clinical vigilance in sarcoma patients, especially those receiving antiangiogenic therapies such as anlotinib. It calls for the early incorporation of contrast-enhanced imaging or angiographic studies when unexplained shock or vascular complications are suspected. The success of transarterial embolization in controlling hepatic hemorrhage in this setting suggests that minimally invasive interventions can significantly reduce the morbidity associated with more invasive procedures like laparotomy (9). Moving forward, it is imperative to refine diagnostic protocols and establish robust, multidisciplinary management strategies that address both the oncologic and vascular emergencies in these high-risk patients.

Patient perspective

I was initially overwhelmed by fear and uncertainty when I experienced severe complications during my treatment. The sudden onset of abdominal pain and the need for emergency interventions were frightening, but the medical team’s quick actions and compassionate explanations helped me feel safe and involved in my care.

Now that I have recovered, I deeply appreciate the coordinated efforts of the doctors, nurses, and all the specialists involved. Their prompt response and interdisciplinary approach not only stabilized my condition but also restored my hope and confidence in the treatment plan.

Conclusions

Clinicians managing advanced retroperitoneal sarcomas, especially those harboring NTRK fusions, should maintain a high index of suspicion for oncologic emergencies during targeted therapy. Key practice recommendations include: (I) prioritize early contrast-enhanced imaging when new abdominal symptoms or hemodynamic instability arise. (II) Incorporate multidisciplinary evaluation, including oncology, radiology, and interventional specialists, at the first signs of deterioration. (III) Utilize transarterial embolization promptly in cases of suspected hemorrhage, favoring minimally invasive over surgical approaches when feasible. (IV) Monitor lactate and hemoglobin trends closely as early indicators of shock and internal bleeding. (V) Design individualized prevention protocols, including risk stratification and tailored therapy schedules, for patients with vascular-rich tumors or prior bleeding episodes. Although this report is based on a single case, our findings reinforce the importance of early intervention and warrant further research in larger cohorts.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the CARE reporting checklist. Available at https://acr.amegroups.com/article/view/10.21037/acr-2025-109/rc

Peer Review File: Available at https://acr.amegroups.com/article/view/10.21037/acr-2025-109/prf

Funding: This study was supported by the Science & Technology Development Fund of Tianjin Education Commission for Higher Education (No. 2020KJ191) and Tianjin Key Medical Discipline (Specialty) Construction Project (No. TJYXZDXK-032A).

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://acr.amegroups.com/article/view/10.21037/acr-2025-109/coif). T.W. reports that this research was funded by the Science & Technology Development Fund of Tianjin Education Commission for Higher Education (No. 2020KJ191). Y.L.W. reports that this research was funded by Tianjin Key Medical Discipline (Specialty) Construction Project (No. TJYXZDXK-032A). The other authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All procedures performed in this case were in accordance with the institutional ethics and with the Declaration of Helsinki and its subsequent amendments. Written informed consent was obtained from the patient and his family for the publication of this case report and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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