Rapid enlargement of a cervicomedullary junction neurenteric cyst with de novo fluid-fluid level formation

Abstract

Background:

Neurenteric cysts are rare congenital lesions that usually follow an indolent course. In cystic lesions, a fluid-fluid level generally indicates hemorrhage; in neurenteric cysts, it is seldom reported and poorly understood. Prior explanations rested largely on imaging and intraoperative inference. We report a cervicomedullary junction neurenteric cyst that enlarged rapidly after indolent growth, with a de novo fluid-fluid level in the absence of hemorrhage, and propose a histopathologically supported mechanism.

Case Description:

A 52-year-old man presented with posterior neck pain and dizziness. Magnetic resonance imaging demonstrated a 22-mm cystic lesion. Imaging 17 years earlier showed a 14-mm lesion. Over the next month, the cyst enlarged to 26 mm, developing a de novo fluid-fluid level and perilesional edema. Although suspected, hemorrhage was not confirmed at surgery or on histopathology; the cyst contained viscous proteinaceous fluid. The resected cyst wall showed foam cell clusters, interpreted as indirect evidence of prior wall disruption. Complete resection was achieved without neurological deterioration or recurrence at 8 months.

Conclusion:

A fluid-fluid level in a neurenteric cyst does not necessarily indicate hemorrhage. It may instead reflect a rise in intracystic pressure from chronic mucin secretion that progressively compromises the cyst wall, allowing osmotic influx of cerebrospinal fluid that drives rapid enlargement and dilutes the upper layer. To the best of our knowledge, this is the first report in which foam cell clusters provide histological support for such a non-hemorrhagic mechanism in a neurenteric cyst. Interval growth or perilesional edema may precede deterioration and should prompt consideration of timely intervention.

INTRODUCTION

Neurenteric cysts are benign congenital lesions of endodermal origin that arise from the abnormal persistence of the neurenteric canal during early embryogenesis.[14] They occur throughout the neuraxis, accounting for approximately 0.3–0.5% of spinal tumors and 0.15–0.35% of all intracranial tumors.[14] Within the spinal canal, neurenteric cysts most often occur ventral to the spinal cord, whereas intracranial lesions typically arise in the posterior fossa, predominantly along the midline and ventral to the brainstem.[8,14] Clinically, these lesions usually follow an indolent course, with reported growth occurring gradually over months to years.[1,7,12]

Radiologically, neurenteric cysts typically appear homogeneous on computed tomography (CT) and magnetic resonance imaging (MRI), although their density and signal intensity vary according to the protein concentration of the cystic fluid.[2,6,14] In cystic lesions, fluid-fluid levels generally reflect intracystic hemorrhage;[15] however, they have rarely been described in neurenteric cysts.[5,7,11,12]

The clinical significance and underlying mechanisms of fluid-fluid level formation in neurenteric cysts remain unclear. Herein, we report a rare case of a cervicomedullary junction neurenteric cyst demonstrating long-term indolent growth, followed by rapid enlargement, accompanied by the de novo appearance of a fluid-fluid level in the absence of hemorrhage. This case highlights the potential significance of such imaging changes and the need for further investigation into their pathophysiological basis.

CASE DESCRIPTION

A 52-year-old man with no significant medical or trauma history presented with a 1-month history of posterior neck pain and dizziness. Neurological examination revealed no focal deficits. Head CT showed a hyperdense cystic lesion located ventral to the cervicomedullary junction, without associated vertebral anomalies [Figure 1a]. Follow-up CT 1 month later demonstrated stratification of the cyst contents, with the dorsal portion appearing isodense and the ventral portion appearing hypodense [Figure 1b], in contrast to the previously homogeneous hyperdense appearance. CT also revealed focal hyperdense areas suggestive of calcification within the cyst [Figure 1c]. A retrospective review of a head CT performed 17 years earlier for headache evaluation identified a 14-mm hyperdense lesion at the same location [Figure 1d], indicating prolonged indolent growth before the recent rapid enlargement within a single month.

Figure 1:

Temporal computed tomography (CT) changes in the cervicomedullary junction lesion. (a) The initial CT at presentation shows a hyperdense lesion ventral to the cervicomedullary junction. (b) The follow-up CT 1 month later shows stratification of the cyst contents, with isodensity in the dorsal portion and hypodensity in the ventral portion. (c) Focal hyperdense areas suggestive of calcification are identified within the cyst on a different slice of the follow-up CT. (d) A CT scan obtained 17 years earlier, identified on retrospective review, shows a 14-mm hyperdense lesion at the same location.

MRI at presentation demonstrated a 22-mm cystic lesion. The contents showed homogeneous hyperintensity on T1-weighted images (T1WI) [Figure 2a] and mild hyperintensity on T2-weighted images (T2WI) [Figure 2b]. MRI performed 1 month later demonstrated interval enlargement of the cyst to 26 mm with the de novo appearance of a fluid-fluid level on T1WI [Figure 2c and 2d], T2WI [Figure 2e and 2f], and fluid-attenuated inversion recovery (FLAIR) [Figure 2g], representing a marked change from the previously homogeneous signal intensity. The cyst wall showed no contrast enhancement on contrast-enhanced T1WI [Figure 2h]. Nodular hypointense areas were identified in the dorsal portion of the cyst on susceptibility-weighted images (SWI) [Figure 2i], corresponding to the focal hyperdense areas on CT. Edematous changes extended from the medulla oblongata to the upper cervical spinal cord [Figure 2e and f], suggesting compression of the median anterior medullary and spinal vein posterior to the cyst [Figure 2h].

Figure 2:

Temporal magnetic resonance imaging (MRI) changes and de novo fluid-fluid level formation. (a) At initial presentation, the cyst shows homogeneous hyperintensity on the T1-weighted image (T1WI). (b) At initial presentation, the cyst shows mild hyperintensity on the T2-weighted image (T2WI). (c, axial; d, sagittal) One month later, follow-up MRI demonstrates interval enlargement with the de novo appearance of a fluid-fluid level on T1WI. (e, axial; f, sagittal) A fluid-fluid level is also seen on T2WI, accompanied by perilesional edema extending from the medulla oblongata to the upper cervical spinal cord. (g) A fluid-fluid level is observed on the fluid-attenuated inversion recovery (FLAIR) image. (h) The cyst wall shows no contrast enhancement, and the median anterior medullary and spinal vein is identified posterior to the cyst on the contrast-enhanced T1WI. (i) Nodular hypointense areas are observed in the dorsal portion of the cyst on the susceptibility-weighted image (SWI).

The preoperative differential diagnosis comprised a neurenteric cyst with suspected intracystic hemorrhage and a hemorrhagic arachnoid cyst. Surgical excision was performed through a left lateral suboccipital craniotomy combined with C1 hemilaminectomy in the lateral position. Intraoperatively, the cyst contained cloudy, highly viscous fluid [Figure 3a], and the cyst wall was thin and translucent [Figure 3b]. A small amount of debris was identified during the aspiration of the cyst contents [Figure 3c]. Notably, despite the preoperative suspicion of intracystic hemorrhage based on imaging findings, no intraoperative evidence of hemorrhage was identified. Frozen section analysis was consistent with a neurenteric cyst. The cyst wall, which was partially adherent to adjacent venous structures [Figure 3d], was carefully dissected and resected as completely as possible [Figure 3e]. Postoperative MRI confirmed the complete removal of the lesion [Figure 3f]. Histopathological examination confirmed the diagnosis of a neurenteric cyst [Figure 4]. No recurrence was observed at 8 months postoperatively.

Figure 3:

Intraoperative findings and postoperative magnetic resonance imaging. (a) Cloudy and viscous contents (asterisk) are visible intraoperatively. (b) The cyst wall is thin and translucent, with no evidence of hemorrhage. (c) A small amount of debris (arrow) becomes apparent during aspiration of the cyst contents. (d) The cyst adheres to the anterior spinal vein (arrowhead). (e) The cyst is carefully dissected and removed as completely as possible. (f) The postoperative sagittal T2-weighted image confirms complete removal of the lesion.

Figure 4:

Histopathological findings of the resected cyst. (a) Hematoxylin and eosin (H&E) staining shows the cyst wall lined by a single layer of columnar epithelium with foam cell clusters (arrow). (b) Immunohistochemical analysis shows the epithelial lining to be positive for epithelial membrane antigen (EMA). (c) The epithelial lining is positive for Mucin 5AC (MUC5AC). (d) Prussian blue staining for hemosiderin is negative, indicating the absence of prior hemorrhage.

DISCUSSION

Neurenteric cysts typically follow an indolent clinical course, with reported growth occurring gradually over months to years.[1,7,12] In our patient, a head CT scan performed 17 years before diagnosis was retrospectively available, providing an uncommon opportunity to observe the long-term behavior of such a lesion. Over the preceding 17 years, the cyst showed indolent growth from 14 to 22 mm, consistent with the typical clinical course of neurenteric cysts. This indolent course was abruptly interrupted by a 4-mm expansion within a single month, from 22 to 26 mm, representing a marked acceleration of growth. This sudden acceleration was accompanied by the de novo appearance of a fluid-fluid level and extensive perilesional edema, the latter most plausibly attributable to venous congestion secondary to compression of the adjacent median anterior medullary and spinal vein by the enlarging cyst. Although progressive growth of intracranial neurenteric cysts has been documented in previous reports,[9,11] these cases were characterized by continuous progression observed from the time of initial detection, without documentation of a preceding indolent phase. The most directly comparable previous report is that of Takahashi et al.,[11] who documented a craniocervical junction neurenteric cyst showing continuous growth over 4 years with progressive fluid-fluid level formation. To the best of our knowledge, however, the present case is unusual in documenting an indolent phase abruptly transitioning to active rapid growth in an intracranial neurenteric cyst, accompanied by the de novo appearance of a fluid-fluid level and extensive edema in the absence of hemorrhage.

The radiological appearance of neurenteric cysts is largely determined by the protein concentration of their cystic contents.[2,14] On CT, these lesions typically show hypodensity; however, isodensity, or even hyperdensity, can be observed when the cyst contains highly proteinaceous or mucin-rich material, as in the present case. MRI provides superior tissue characterization, although the signal intensity varies with protein content.[2,14] Hayashi et al.[6] demonstrated that higher protein concentrations yielded progressive T1 shortening and relative T2 shortening, resulting in T1 hyperintensity and T2 hypointensity. Although intracystic hemorrhage was initially suspected based on imaging findings, neither intraoperative inspection nor histopathological examination revealed evidence of hemorrhage such as hemosiderin deposition or neovascularization, indicating that hemorrhage is unlikely to account for the fluid-fluid level. While intracystic debris has been reported as a possible mechanism underlying fluid-fluid level formation,[12] the limited quantity observed in our case is unlikely to have produced a stratified appearance. Taken together, these findings indicate that the fluid-fluid level in our case most likely reflects a heterogeneous distribution of proteinaceous material within the cyst, and dynamic changes in protein concentration therefore represent the most plausible mechanism.

Such dynamic changes in protein concentration imply an active alteration of the intracystic environment rather than passive accumulation of secretory material. To account for the abrupt transition from long-term indolent growth to rapid enlargement, we propose a pathophysiological mechanism involving progressive compromise of cyst wall integrity and secondary osmotic imbalance. The chronic secretion of mucinous material by the epithelial lining[14] may have gradually elevated intracystic pressure over time, eventually exceeding the biomechanical tolerance of the cyst wall. This process may have produced microscopic disruptions of the wall, allowing an osmotic influx of cerebrospinal fluid into the cyst cavity. Such a mechanism would account for the rapid volumetric expansion, dilution of the protein concentration in the upper layer, and subsequent formation of a fluid-fluid level.[6,11]

The mechanism of fluid-fluid level formation in neurenteric cysts remains incompletely understood. Shakudo et al.[10] proposed a conceptually similar mechanism involving thinning of the cyst wall and osmotic permeation of cerebrospinal fluid, although they were unable to obtain direct histological confirmation. More recently, Takahashi et al.[11] attributed the progressive dilution of cyst contents to increased secretion of low-protein fluid by the cyst wall epithelium, based primarily on the intraoperative observation of no gross communication between the cyst and the subarachnoid space. These complementary hypotheses have advanced the understanding of cyst behavior; however, neither has been substantiated by direct histological evidence, and microscopic disruptions of the cyst wall do not necessarily manifest as macroscopic communication observable during surgery. In the present case, examination of the resected cyst wall demonstrated foam cell clusters, representing macrophages that have engulfed extravasated mucin. Although microscopic disruption of the cyst wall is difficult to identify directly on hematoxylin and eosin-stained sections, foam cells can serve as indirect indicators of prior wall disruption. Such a cellular reaction is not expected to develop in response to intraoperative manipulation alone, indicating that the disruption occurred during the preoperative clinical course. Foamy macrophages and xanthogranulomatous change have themselves been described in neurenteric cysts,[1,9] but have not been connected to a non-hemorrhagic process of wall compromise; where a mechanism was proposed, it was attributed to a cycle of hemorrhage and inflammation.[9] The distinctive contribution of the present case is not the finding of foam cells but their interpretation as a histological correlate of the wall disruption that earlier studies could only postulate. These histological findings thus provide tangible support for the proposed mechanism of progressive cyst wall compromise underlying the rapid enlargement observed in the present case.

Recognition of the proposed mechanism presupposes that the lesion has been correctly identified, and the diagnosis may not be evident before surgery. The imaging appearances of intracranial cystic lesions overlap considerably, and the differential diagnosis includes arachnoid, ependymal, epidermoid and dermoid cysts, as well as cystic neoplasms.[1] In the present case, the fluid-fluid level raised the possibility of a hemorrhagic arachnoid cyst. Among the cystic neoplasms, hemangioblastoma warrants specific consideration at this site, since a neurenteric cyst has been mistaken preoperatively for a cystic hemangioblastoma,[3] although a mural nodule is reported to be identifiable in every cystic hemangioblastoma and to show contrast enhancement.[13] The operative approaches differ. A neurenteric cyst is removed as completely as possible while limiting spillage of its contents into the subarachnoid space, whereas a hemangioblastoma requires the feeding arteries to be interrupted before the lesion is excised en bloc,[13] so that a procedure undertaken as cyst wall resection may reach the mural nodule before vascular control has been established. Because preoperative imaging may not be conclusive in a cystic lesion of this region, the differential diagnosis should be considered before surgery to allow the operative strategy to be adapted to the lesion encountered.

The present case also has implications for the duration of follow-up. The 17-year interval documented here shows that an indolent phase may be interrupted unpredictably by rapid enlargement; a lesion managed conservatively therefore warrants sustained radiological surveillance. Reported recurrence rates for neurenteric cysts range from 11.9% to 37%,[11] with recurrence occurring between 4 months and 14 years after surgery,[14] even after complete macroscopic resection.[4] This latency argues for prolonged rather than limited postoperative surveillance. Although the lesion was resected as completely as possible and no recurrence has been observed, the follow-up remains early at 8 months. Continued surveillance is planned.

CONCLUSION

The emergence of a fluid-fluid level and dynamic changes in MRI signal intensity in neurenteric cysts should not be dismissed as incidental findings or attributed solely to hemorrhage. Rather, such changes may reflect dynamic alterations in cyst content composition and the intracystic milieu, potentially driven by compromised cyst wall integrity and osmotic influx of cerebrospinal fluid, signaling a transition from an indolent to an active phase of cyst enlargement. When these radiological findings are accompanied by interval growth or perilesional edema, they may serve as early indicators of impending clinical deterioration. Recognition of such features should prompt close clinical and radiological surveillance, with early consideration of surgical intervention.

Ethical approval:

The Institutional Review Board approval is not required.

Declaration of patient consent:

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given consent for their images and other clinical information to be reported in the journal. The patient understand that the patient’s names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship:

Nil.

Conflicts of interest:

There are no conflicts of interest.

Use of artificial intelligence (AI)-assisted technology for manuscript preparation:

The authors confirm that there was no use of artificial intelligence (AI)-assisted technology for assisting in the writing or editing of the manuscript and no images were manipulated using AI.

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