Case Report
A Neurenteric Cyst Presenting as a Brainstem Tumor: Imaging and Clinical Findings Juan Domingo Ly1 Giulio Zuccoli2
Subramanian Subramanian2
Stephanie Greene3
1 Department of Radiology, University of Pittsburgh Medical Center,
Pittsburgh, Pennsylvania, United States 2 Department of Neuroradiology, Children’s Hospital of Pittsburgh of UPMC, Pittsburgh, Pennsylvania, United States 3 Department of Neurosurgery, Children’s Hospital of Pittsburgh of UPMC, Pittsburgh, Pennsylvania, United States 4 Division of Child Neurology, Department of Pediatrics, Children’s Hospital of Pittsburgh of UPMC, Pittsburgh, Pennsylvania, United States 5 Division of Neuropathology, University of Pittsburgh, Pittsburgh, Pennsylvania, United States
Deepa Rajan4
Julia Kofler5
Address for correspondence Juan Domingo Ly, MD, Radiology Residency Program, 200 Lothrop Street, Presby East Wing, Suite E174, Pittsburgh, PA 15213, United States (e-mail:
[email protected]).
J Pediatr Neurol
Abstract Keywords
► neurenteric cyst ► brainstem exophytic tumor ► craniovertebral junction ► MRI ► children
An 11-year-old girl presented with vomiting, nystagmus, and ataxia. MRI showed a partially enhancing medulla oblongata lesion and an adjacent nonenhancing cystic exophytic lesion. An exophytic brainstem tumor was suspected. Histologically, the lesion was identified as a neurenteric cyst (NC). On retrospective review, the NC was connected to the brainstem by a subtle sinus tract. This led to brainstem inflammation which reversed once the cyst was resected. We describe an unreported case of a patient with a NC at the craniocervical junction connected to the brainstem through a sinus tract and discuss the possible embryological abnormality and imaging features.
Introduction Neurenteric cysts (NCs) are rare benign endodermal cystic lesions lined by mucin-secreting epithelium arising from an abnormal connection between the endoderm and ectoderm during the third week of gestation. NCs are a subgroup of the split notochord spectrum. They are often associated with vertebral or alimentary abnormalities.1–4 Symptoms of NCs located in the spine (the most common location) are usually due to cord compression and myelopathy. In our case, however, it was mainly due to inflammation. Magnetic resonance imaging (MRI) is the best imaging study for NC. Most NCs are iso- or hyperintense to cerebrospinal fluid (CSF) on T1-weighted image (T1WI), T2weighted image (T2WI), and fluid-attenuated inversion recovery (FLAIR). They usually show no restriction on diffusion-weighted imaging (DWI) and typically are nonenhan-
received December 7, 2017 accepted after revision February 15, 2018
cing on postcontrast T1WI.5 Preoperative diagnosis is challenging due to the rarity of NCs. The mainstay of treatment is complete surgical excision.6 We present a previously unreported case of a NC leading to chronic brainstem inflammation resulting in initial imaging features resembling an exophytic brainstem tumor. The imaging features, treatment, and a dysembryologic hypothesis are discussed.
Case Presentation The patient was an 11-year-old female who was admitted with a 3-week history of intractable emesis and worsening gait requiring assistance with ambulation. Her initial physical examination was significant for ataxia, right-sided uvula deviation, dysmetria, and vertical nystagmus. She was afebrile. As part of her workup, an unenhanced CT of the head was
Copyright © by Georg Thieme Verlag KG, DOI https://doi.org/ Stuttgart · New York 10.1055/s-0038-1639375. ISSN 1304-2580.
A Neurenteric Cyst Presenting as a Brainstem Tumor
Ly et al.
Fig. 1 (A) Axial T2 FLAIR MRI of the brainstem (white arrow) showing the exophytic neurenteric cyst (white asterisk) abutting the left premedullary cistern. (B) Axial T2 FLAIR MRI of the brainstem showing hyperintense enlargement of the medulla oblongata (black asterisk) mimicking an exophytic brainstem tumor. (C) Axial T2 MRI through the craniocervical junction which demonstrates an exophytic neurenteric cyst (black asterisk) in the premedullary cistern displacing the medulla oblongata (white arrow). (D) Axial T2 MRI of the medulla oblongata demonstrating edema and expansion of medulla (white arrows). There is feathery or striated appearance of the edema. (E) Sagittal postcontrast T1 MRI showing the sinus tract (white arrow) connecting the neurenteric cyst (inferior) to the brainstem lesion (superior). FLAIR, fluid-attenuated inversion recovery; MRI, magnetic resonance imaging.
performed which revealed a small calcification at the left craniocervical junction (CCJ). A subsequent MRI with and without contrast demonstrated extensive T2 and FLAIR hyperintensity in the brainstem (►Fig. 1A–D). There was a rim-enhancing lesion at the medulla oblongata (►Fig. 1E) and a nonenhancing cystic lesion at the left CCJ displacing the brainstem with an eccentric focus of calcification. The cystic component was isointense on FLAIR (►Fig. 2A). There was no restricted diffusion within the lesion. MR spectroscopy of the brainstem revealed decreased N-acetylaspartate (NAA), lactate, and lipid peaks. The choline and creatinine levels were relatively decreased (►Fig. 2B). These initial findings raised the concern for an exophytic brainstem tumor. The patient underwent surgical excision on the following day via a suboccipital craniectomy and C1 laminectomy. Excision of the left dorsal exophytic cystic component of the mass, including the wall, was performed. The mass was thick, pale gray, and mucinoid with a uniform structure. Intraoperative smear evaluation showed proteinaceous debris and admixed neutrophils, which was interpreted as necrosis. On permanent hematoxylin and eosin (H&E) stained sections, microscopic evaluation revealed fragments of membranous fibrovascular tissue lined by columnar to pseudostratified and partially ciliated epithelium (►Fig. 3). Also present was mucinous material, consistent with cyst content and corresponding to the material misinterpreted as necrosis on the intraoperative evaluation. While there Journal of Pediatric Neurology
were numerous neutrophils within the cyst content, there was only minimal acute and chronic inflammation in the cyst wall. The epithelial lining was immunoreactive for epithelial markers cytokeratin AE1/AE3 and epithelial membrane antigen (EMA) and negative for the astrocytic marker glial fibrillary acidic protein (GFAP), supporting a final pathology diagnosis of NC. No adherent neuroglial tissue was identified on H&E, GFAP, synaptophysin, and Olig2 immunohistochemical stains. There was no evidence of an underlying primary CNS tumor. In a retrospective review of the initial MRI study, we identified a small sinus tract connecting the cystic lesion to the brainstem (►Fig. 1E). Empirical treatment of a brainstem infection was started and consisted of a short-term intravenous broad spectrum antibiotic. Given the extensive vasogenic edema involving the brainstem, corticosteroids were also empirically administered. At 2-month follow-up, MRI demonstrated near-complete resolution of the brainstem imaging abnormalities (►Fig. 2C) and the patient was symptom free.
Discussion NCs are rare benign congenital endodermal cysts thought to develop from the persistence of the neurenteric canal. NCs are more commonly located in the spine than the brain (3:1). They are usually located in the lower cervical spine and upper thoracic spine.
A Neurenteric Cyst Presenting as a Brainstem Tumor
Ly et al.
Fig. 2 (A) Sagittal postcontrast T1 FLAIR MRI at presentation showing the nonenhancing exophytic neurenteric cyst (white arrows) abutting the left premedullary cistern. (B) MR-short echo time spectroscopy of the brainstem showing decreased NAA, lactate, and lipid peaks. Choline (Cho) and creatinine (Cr) levels were relatively decreased. (C) Sagittal postcontrast T1 FLAIR MRI at 2-month follow-up showing near-complete resolution of the brainstem abnormalities. FLAIR, fluid-attenuated inversion recovery; MRI, magnetic resonance imaging; NAA, N-acetylaspartate.
There is not a standardized NC classification system. Wilkins et al7 classified intraspinal NCs based on histological features. In type A cysts, such as this patient’s cyst, the cyst walls consist of a pseudostratified cuboidal or columnar epithelium with or without cilia. Type B cysts have all the characteristics of type A cysts and are additionally arranged in complex glandular structures, usually producing mucin or serous fluid. Type C cysts have type B findings with ependymal or glial tissue. Many developmental theories have been proposed to explain the formation of NCs. During the third week of embryologic development, a trilaminar embryonic disc is
Fig. 3 Representative H&E-stained image of the lesion, demonstrating membranous fibrovascular tissue lined by columnar to pseudostratified epithelium. (200 magnification). H&E, hematoxylin and eosin.
formed via the process of gastrulation. The notochordal process, a mesodermal derivative, is formed between the ectoderm and endoderm. There is a transient communication between the ectoderm and endoderm, called the neurenteric canal, which extends across the notochord. An abnormally persistent neurenteric canal is the underlying common concept of the proposed theories. These theories include: (1) formation of an accessory neurenteric canal with a split notochord, (2) an incomplete separation of the notochord, (3) persistence of the neurenteric canal, (4) an endodermal adhesion to the notochord, and (5) an adhesion between the endoderm and ectoderm that becomes a barrier to the elongating notochord and, thus, splits it.8 In the split notochord hypothesis, the deficiency in the overlying neural plate could allow for an endodermal diverticulum to herniate and cause a persistence of the neurenteric connection, which could be partial or complete. However, no current theory can fully explain the formation of NCs. Importantly, these theories cannot predict NCs in an intracranial location. The notochord extends from the clivus (posterior clinoid process) to the sacrum. As previously mentioned, the transient neurenteric canal extends across the notochord. Hence, an infratentorial NC can be explained by an abnormal persistence of the neurenteric canal which can persist from the clivus to the sacrum. Only the supratentorial NCs cannot be explained by this theory. The presence of a sinus tract is difficult to explain as well. A plausible theory is one based on the split notochord hypothesis. An endodermal invagination may have occurred, with the formation of a small sinus tract that slowly enlarged, leading to chronic drainage from the mucin-producing cyst into the brainstem. The rim-enhancing inflammation of the Journal of Pediatric Neurology
A Neurenteric Cyst Presenting as a Brainstem Tumor
Ly et al.
brainstem mass is attributed to possible chronic mild infection. The exophytic cyst did not enhance or appear inflamed. In addition, the MR spectroscopy characteristics of our patient were very atypical for an exophytic brainstem tumor. The majority of exophytic brainstem tumors are pilocytic in origin with elevation of choline and lactate peaks. NCs are not easily diagnosed on imaging, mainly due to their rarity and variety in appearance. In the brainstem, other more common lesions are usually considered first, including arachnoid or epidermoid cysts, abscesses,9 or even exophytic brainstem tumors such as in this case. With increased reporting and further understanding of NCs, we hope that our experience will make radiologists more familiar with differentiating these benign developmental cysts from other brainstem lesions such as exophytic tumors, chordoma, infection, or other cysts. Ethical Approval Formal consent is not required for this type of study.
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Conflict of Interest None.
Journal of Pediatric Neurology
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