Cauda equina neuroendocrine tumour complicated by intra-tumoural hemorrhage in a young male: a case report and systematic review of the literature

Introduction

Cauda equina neuroendocrine tumours (CE-NETs) are rare benign lesions accounting for reportedly 3–4% of intradural spinal tumours (1,2). They were previously termed paragangliomas (PGLs), but most recently they have instead been classified as “paraganglioma-like neuroendocrine neoplasms” in the World Health Organization (WHO) tumour classification due to molecular and histopathological differences compared with paragangliomas originating outside the central nervous system (CNS) (1,2). CE-NETs are derived from specialized neural crest cells in the cauda equina/filum terminale region (3). Unlike extra-CNS PGLs, CE-NETs usually arise sporadically rather than inherited and the rate of recurrence following resection is lower (1). Pre-operatively, the diagnosis of CE-NETs is difficult as it resembles other intradural tumours such as ependymomas and neurinomas on magnetic resonance imaging (MRI) (2).

Intra-tumoural hemorrhage in intradural extramedullary (IDEM) tumours is extremely rare, with majority of reported cases in the literature found in spinal schwannomas (4-7). Thus, we share our experience with a rare care of intra-tumoural hemorrhage in a CE-NET causing impending conus medullaris syndrome. Additionally, we conducted a systematic review of existing case reports to highlight the prevalent tumour types, clinical presentation, imaging findings and postoperative course for IDEM tumours with intra-tumoural hemorrhage. We present this article in accordance with the CARE and PRISMA reporting checklists (available at https://jss.amegroups.com/article/view/10.21037/jss-25-128/rc).

Case presentation

A 35-year-old Caucasian male with no previous medical history presented with a 1-day duration of acutely worsening, severe lower back pain with radicular symptoms in the L1 dermatome. The pain was precipitated by weightlifting and on presentation the patient was unable to lie supine due to pain. This was complicated by acute retention of urine, although digital rectal exam revealed an intact anal tone and neurological exam was unremarkable. Prior to this episode, the patient had a 2-year history of insidious lower back pain, of which no appropriate imaging was available and symptoms were managed well conservatively. The patient denied any trauma prior to admission. All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and the Declaration of Helsinki and its subsequent amendments. Written informed consent was obtained from the patient 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.

Radiographs of the lumbar spine showed mildly narrowed intervertebral disc space at L5–S1 but was otherwise normal. MRI of the lumbar spine revealed an IDEM mass lesion adjacent to the conus medullaris at the T12–L1 level. The lesion was hypointense on T2-weighted (T2w) sequence and isointense to mildly hyperintense (minimal enhancement) on T1-weighted (T1w) sequence (see Figure 1). It was compressing on the cauda equina and causing severe spinal canal as well as lateral recess stenosis, although the conus medullaris maintained normal signal intensity. Gradient-echo sequences demonstrated sequelae features of prior intra-tumoural hemorrhage, with the presence of small amount of fluid-fluid level at S1–S2 level representing likely intradural blood products.

Figure 1 MRI images of the lumbar spine showing T12–L1 lesion with sequence as follows: (A) sagittal T2w sequence (with visible fluid levels representing remnant blood products at S1–2 level); (B) sagittal T2w TIRM; (C) sagittal T1w sequence; (D) transverse T2w sequence; (E) transverse T2w MEDIC sequence; (F) transverse T1w sequence. I, inferior; MEDIC, multiple echo data image combination; MRI, magnetic resonance imaging; R, right; T1w, T1-weighted; T2w, T2-weighted; TIRM, turbo inversion recovery magnitude.

The patient underwent a T12/L1 laminectomy and excision of lesion (see Figure 2 for intraoperative imaging). Durotomy was performed at the midline. Intra-operatively, the lesion was mobilised from the dura, and resection of a single efferent and afferent nerve was performed. Grossly, the tumour appeared to be a dark brownish circumscribed nodule, with features of hemorrhage (see Figure 3). Neuromonitoring demonstrated diminished somato-sensory evoked potential (SSEP) from L3–S1 pre-operatively which improved significantly postoperatively. Histopathological examination of the tumour showed sheets of round, mononuclear cells in vascularized stroma with well-differentiated features. Keratin positivity and non-specific staining supported the diagnosis of neuroendocrine tumour over paraganglioma (see Figure 4). There was the presence of marked intra-tumoural hemorrhage which interfered with morphological assessment. Biopsy of adjacent bone tissue was negative for malignancy. Postoperatively, the patient’s lower back pain demonstrated considerable improvement and the patient’s pain was well-controlled with oral analgesia by postoperative day 4. Neurological exam was unremarkable, although patient demonstrated mild left scrotal neuropathic pain, possibly secondary to dissection of the nerve root. The patient was discharged on postoperative day 5.

Figure 2 Intraoperative imaging showing identification of laminectomy levels. L, left.

Figure 3 Image showing gross specimen of tumour with features of hemorrhage.

Figure 4 Image of tumour pathology slides showing (A) sheets of round mononuclear cells in vascularised stroma under high-powered microscopy (hematoxylin and eosin staining; magnification, ×400) as well as the following immunohistochemistry profile: (B) negative under S100 stain (marker for Schwann cells and sustentacular cells; IHC staining; magnification, ×400); (C) positive under MNF116 stain (cytokeratin marker; IHC staining; magnification, ×400); (D) positive for synaptophysin stain (neuroendocrine marker; IHC staining; magnification, ×400). IHC, immunohistochemistry.

Systematic review

A search of three different databases (PubMed, EMBASE and Scopus) up to September 2025 was conducted using terms related to ‘intradural extramedullary tumours’ and ‘hemorrhage’, summarized in our search strategy (Appendix 1). Additional articles were identified via citation searching. Two independent authors (M.H.X.Y. and S.J.S.S) filtered case reports based on title and abstract followed by full-text screen. Inclusion criteria included case reports presenting intra-tumoural hemorrhage in IDEM tumours. Exclusion criteria were: (I) age <18 years; (II) non-English study; (III) hemorrhage not intra-tumoural (e.g., subarachnoid, subdural or intramedullary); (IV) hemorrhage of iatrogenic etiology (e.g., anaesthesia complication). The following data were extracted: age/sex, tumour histology, etiology, onset, clinical presentation, MRI features, timing of surgery (defined as duration from onset of symptoms), surgical details (level and completeness of resection), length of stay, latest follow-up duration and postoperative recovery. As this was a systematic review, combined data was synthesized and reported as mean or percentage using simple arithmetic formula, and qualitatively analysed. Meta-analysis was not conducted. All included studies were case reports on rare conditions, hence risk-of-bias assessment was not required.

Discussion

This case report highlights a rare case of intra-tumoural hemorrhage in a spinal neuroendocrine tumour, or CE-NET tumour, previously classified as PGL tumours. In our systematic review, a total of 36 cases of intra-tumoural hemorrhage in spinal IDEM tumours were identified across 34 publications, of which 23 were published more than 10 years ago (6,8-19), while the rest were published within the last 10 years (4,5,7,20-37). All case report characteristics are summarized in Table 1. The mean age was 51.5 years old (range, 28–81 years), with a slight male predominance (58.3% male). The study selection process is summarized in the PRISMA Flowchart (Figure 5).

Figure 5 Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 flowchart.

In the literature, schwannomas accounted for the majority of IDEM tumours with intra-tumoural hemorrhage (20 cases, 55.6%) (4-10,14,18,20,23,25,26,29-32,36,37), followed by ependymomas (7 cases, 19.4%) (11-13,15,21,34) and paragangliomas (3 cases, 8.3%) (17,22,27). One case was reported for each of the following: meningioma, arachnoid cyst, capillary hemangioma and Ewing sarcoma (24,28,33,35). Lastly, 2 cases of metastases were reported (renal cell and hepatocellular carcinoma primaries, respectively) (16,19). Lesions were most frequently located in the thoracolumbar region. Notably, the thoracolumbar junction (T11–L2) accounted for nearly one-third of all cases, making it the single most common site of hemorrhagic IDEM tumours (8,9,12,14,17,19,26,34,36). Similarly, in our patient’s case, the tumour originated from T12-L1 region. CE-NET tumours typically arise from cauda equina nerve roots or filum terminale, with some studies reporting higher incidence in the latter (22). Typical histological features of CE-NET tumours consist of cells with round/oval nuclei and rare mitoses, while key immunohistochemical markers include chromogranin A, synaptophysin or cytokeratin positivity (38). Some studies have used the ‘vascular theory’ to explain the pathophysiology of intra-tumoural hemorrhage, which results from ectatic intra-tumoural vessels undergoing spontaneous thrombosis, leading to tumour necrosis and hemorrhage (39).

In terms of radiological assessment, MRI is the gold standard for diagnosis of CE-NET tumours. Koeller et al. reported that PGL tumours are typically well-circumscribed masses isointense relative to the spinal cord on T1w sequence and isointense to hyperintense on T2w sequence, although this is not well-established (40). In the event of hemorrhage, a low-signal-intensity rim is usually seen on T2w sequence (40). For our patient, the tumour was largely hypointense on T2w sequence, which could have been contributed by the intra-tumoural hemorrhage. Interestingly, pre-operatively, the tumour was radiologically diagnosed as an IDEM and we were unable to identify the exact tumour type, which is an issue that remains common in the literature given the uncertainty in its radiologic characteristics (2,41). In our systematic review, the MRI findings remained largely varied, with T1w and T2w sequences for different cases ranging from hypo- to hyperintense, while some had heterogenous enhancement, with no classic finding for each tumour type. Thus, it may be difficult to distinguish between tumour types purely from radiological imaging.

In terms of etiology, majority of the intra-tumoural hemorrhage was spontaneous (21 cases, 58.3%) (5,6,8,10,12,15-19,22,25,27,28,30,32-37), while secondary causes included trauma (9 cases, 25%) (4,9,13,20,21,23,24,26,29), strenuous activity (2 cases, 55.6%) (7,12), or anticoagulation/coagulopathy (4 cases, 11.1%) (11,14,20,31). The clinical onset was most often acute (25 cases, 69.4%) (5-7,9-16,18,20-24,26-28,30,31,33), defined as <6 weeks, while a minority presented as acute-on-chronic (8 cases, 19.4%) (8,17,19,25,29,35-37), or chronic (3 cases, 8.3%) presentations (4,32,34). In terms of clinical presentation, almost all cases presented with motor deficit, predominantly paraparesis/paraplegia, as well as bladder and/or sphincter dysfunction. Furthermore, all except for 9 cases presented with severe pain (7,13,22-24,29-31,33). One patient presented with severe respiratory compromise, which resolved postoperatively (30). In our patient’s case, severe back pain was the primary presenting complaint. The 2-year history of insidious back pain likely represented slow growth of the tumour, which may have progressed to severe pain precipitated by the hemorrhage. Jenkins et al. reported similar findings of severe pain possibly incited by intra-tumoural bleed, although the mechanism behind the severity of pain remains unclear (6). Gotecha et al. highlighted that delayed presentation in such tumours (prior to hemorrhage) are common given their indolence (4).

Surgical resection remains the ideal form of management with both diagnostic and therapeutic purposes, since an accurate diagnosis of tumour type can only be obtained histologically. In our systematic review, all cases were managed surgically, with majority of cases undergoing urgent surgery (21 cases, 58.3%) (6-11,13,15,17-23,25,27,28,31,35,36), within 48 hours of symptom onset. Delayed interventions ranged from days to months, with one outlier at 6 years (26). The predominant procedure was laminectomy/laminotomy (30 cases, 83.3%) (see Table 1 for a list of relevant cases). Incomplete resection was rare, and was only reported in one case of metastasis (19). Majority of cases demonstrated good outcomes, with all but one case demonstrating partial to complete motor recovery (19). Bladder and sphincter function improved in most of the affected patients, though persistent deficits were common. Pain resolution was reported in approximately 50% of cases where pain was a presenting symptom, often even in the absence of full neurological recovery (4-6,14,17,18,21,26-28,32,36). While recurrence rate was not evaluated due to paucity of data in this review, the existing literature suggests that gross total resection of CE-NETs remains low even with aggressive tumour characteristics at the start, ranging from 0–7% (42-44). Similarly, our patient experienced a near-complete recovery of his symptoms post-resection of tumour and was discharged early on postoperative day 5. Thus, prognosis following surgical resection of IDEM tumours with intra-tumoural hemorrhage remains desirable.

Conclusions

In conclusion, intra-tumoural hemorrhage in IDEM tumours is rare, especially in a CE-NET tumour. While symptoms can be debilitating and range from severe back pain to significant neurologic deficit, early identification from radiological imaging and histology, followed by early resection, can result in good prognosis. Further cohort studies of such cases will be helpful in justifying these conclusions further.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the CARE and PRISMA reporting checklists. Available at https://jss.amegroups.com/article/view/10.21037/jss-25-128/rc

Peer Review File: Available at https://jss.amegroups.com/article/view/10.21037/jss-25-128/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jss.amegroups.com/article/view/10.21037/jss-25-128/coif). The 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 study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Declaration of Helsinki and its subsequent amendments. Written informed consent was obtained from the patient 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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