2026 年 13 巻 p. 289-294
Endodermal cysts typically occur in intradural regions of the ventral spine or posterior cranial fossa. However, they are rarely found in supratentorial regions, especially within the frontal bone. Here, we report a rare case of an intraosseous endodermal cyst in the frontal convexity and discuss its potential pathogenesis in this unusual location. A 54-year-old woman presented with a gradually enlarging, soft, elastic mass in the left frontal region. Neurological abnormalities were not observed. Computed tomography revealed a cystic lesion within the left frontal bone, associated with a bulging contour. The cyst contents appeared hyperintense on T1-weighted magnetic resonance and showed a hypointense component on T2-weighted magnetic resonance imaging. The cyst wall was not enhanced with gadolinium. The cyst and its mucinous content were completely excised from the frontal bone. Intraoperatively, the cyst wall was completely separated from the frontal sinus by a thin bony structure. Histopathological examination revealed that the cyst wall consisted of inflammatory granulation tissue with a ciliated columnar epithelium, consistent with a diagnosis of endodermal cyst. Although the pathogenesis of supratentorial endodermal cysts remains unclear, the location of the cyst in the frontal convexity, as opposed to the anterior cranial base, may suggest a distinct pathogenesis for each endodermal cyst in terms of embryological aspects.
Endodermal cysts (ECs) typically arise from incomplete separation of the endoderm and notochord during fetal development, most commonly occurring in the ventral spinal canal or posterior cranial fossa.1-3) Colloid cysts, neurenteric cysts, and supratentorial EC are all composed of endodermal epithelium and are considered variants of ECs, distinguished primarily by location. However, ECs that arise within the frontal bone are extremely rare and are not well explained by the conventional theory of incomplete separation of the endoderm and notochord. Additionally, ECs that develop in the convexity of the frontal bone are particularly rare among supratentorial ECs.3,4) In this report, we describe a case of EC in the frontal bone and review the possible developmental mechanisms underlying this presentation.
A 54-year-old woman presented with a slowly enlarging, soft, elastic mass in the left frontal region over several years. She had no neurological deficits or history of trauma. Computed tomography imaging revealed a cystic lesion within the left frontal bone, associated with outward bulging of the bone. Additionally, soft tissue density was noted in the ipsilateral frontal sinus. Magnetic resonance imaging showed the cyst content to be hyperintense on T1-weighted images and partially hypointense on T2-weighted images. Contrast enhancement and mucosal thickening were observed in the frontal sinus lesion (Figure 1, from a to h). Before surgery, an otolaryngologist biopsied the paranasal sinus lesion via the nasal cavity, which was diagnosed as paranasal sinusitis.
CT scan images show a cystic lesion in the left frontal bone (a, b), and the lesion was separated from the left frontal sinus by a bony structure (white arrow) (c, d). A soft tissue dense lesion was found in the frontal sinus (c, d). Cyst content reveals hyperintensity on T1-weighted MR images (e) and low intensity on T2-weighted images (f). The cyst wall and contents were not enhanced by Gadolinium administration (g, h). Post-operative CT scan images (i) and MR images (j, k, l) showed that the cystic lesion was completely removed and there were no effects of the cystic removal in the sinus cavity.
CT: computed tomography; MR: magnetic resonance
The frontal bone cyst was surgically excised. The outer cyst wall was attached to the frontal periosteum. After the mucinous or muddy cyst content was partially removed, the cyst wall and remaining cyst content were completely removed under a microscope. The cyst was completely separated from the paranasal sinuses by bony structures with no continuity with the paranasal sinus mucosa. The frontal bone around the cyst wall exhibited a smooth and continuous surface, with the distinct bone present at the border with the frontal sinus (Figure 2). After burring down the surrounding bulging bone, cranioplasty was performed using the outer plate of the right frontal bone within the same incision (Figure 1, from i to l). Histopathological examination of the cyst wall revealed inflammatory granulation tissue with a ciliated columnar epithelial monolayer. The epithelial cells were positive for epithelial membrane antigen (EMA). Periodic acid-Schiff (PAS) staining revealed scattered goblet cells (Figure 3). Histological examination and imaging findings confirmed EC, with no evidence of malignancy. No new neurological deficits occurred after the surgery, and the patient was discharged.
Intraoperative photographs.
The cyst wall detached from the surrounding frontal bone (a). After the cyst wall was partially excised, the mucinous or muddy cyst contents were completely removed (b). After the cyst wall was detached from the frontal bone under a microscope and completely removed, the surrounding frontal bone was exposed (c, d). No defect was found in the surrounding frontal bone, confirming that there was no connection between the cyst and frontal air sinus (e). After cyst removal, cranioplasty for bony defects was performed using a harvested autologous outer plate of the right frontal bone (f).
Histopathological examination demonstrated that the cyst wall is formed mainly by ciliated columnar epithelium (a: Hematoxylin and eosin staining). The ciliated columnar epithelium stained with epithelial membrane antigen staining (b), and mucus in some of the epithelial cells was positive for Periodic acid-Schiff staining (c). All histopathological examinations were imaged at ×400 magnification.
ECs located within the convexity of the frontal bone are exceedingly rare,5) with only a few reported cases, and the mechanism by which they develop has not yet been identified (Table 1). The prevailing theory is that ECs are ectopic cysts consisting mainly of endodermal components that arise as a result of incomplete separation of the endoderm and notochord during embryonic development.1-3) Based on location, ECs are classified as colloid cysts (near the foramen of Monro or pineal gland), neurenteric cysts (in the posterior fossa or spinal canal), or supratentorial ECs (in the supratentorial region). Despite these distinctions, these cyst types are embryologically and histologically similar.6) However, ECs are thought to develop in the spinal canal or posterior cranial fossa because the upper limit of the vertical extent of the notochord is presumed to be the clivus.7) Therefore, this theory is insufficient to explain the development of supratentorial ECs, particularly frontal bone ECs.
Summary of Previous Reports on an Endodermal Cyst in the Frontal Bone
| Author | Year of Publication | Age/Sex | Location |
|---|---|---|---|
| Bavetta et al. (12) | 1996 | 28/Male | Right anterior cranial fossa |
| Neckrysh et al. (13) | 2006 | 72/Female | Right anterior cranial fossa |
| Kurabe et al. (4) | 2011 | 86/Male | Convexity in left frontal bone |
| Arishima et al. (7) | 2016 | 45/Male | Right anterior cranial fossa |
| Chakraborty et al. (5) | 2016 | 71/Male | Extensive from the anterior cranial fossa to the frontal bone |
| Kalfas and Scudieri (14) | 2020 | 40/Female | Convexity in the left front-parietal bone |
| Oshima et al. (9) | 2021 | 65/Male | Left anterior cranial fossa |
| Present case | 54/Female | Convexity in the left frontal bone |
Supratentorial ECs may arise from remnants of Seessel's pouch.6) Seessel's pouch is an endodermal diverticulum that appears as a temporary protrusion of the fetal pharynx, located anterior to the pharyngeal membrane and caudal to the pituitary gland. Therefore, midline anterior cranial base lesions-such as anterior cranial base ECs-can be explained by the ectopic development involving Seessel's pouch. Accordingly, ectopic ECs require adhesion to ectodermal structures at specific developmental sites. However, this hypothesis is less satisfactory in explaining lesions located in the convexity of the frontal bone, where the cyst is distant from the anterior cranial base. This discrepancy may be addressed by considering the possibility of abnormal migration of adherent endodermal cells to the ectoderm via the neuroenteric tract.3) Alternatively, the development of frontal bone ECs may be linked to the fact that the frontal bone originates from neural crest cells of the ectoderm.8) In summary, the mechanisms of EC development can be broadly divided into 4 categories, determined by differences in the timing of endoderm-ectoderm adhesion:4) those derived from Seessel's pouch, endodermal-neuroectoderm adhesion, endodermal-notochodal adhesion, and endodermal-neural crest adhesion. These categories may explain the diverse anatomical locations of ECs (Figure 4). In addition to these hypotheses, there have been reports of ectopic implantation or splitting of endodermal tissue into the frontal bone or intraosseous region following trauma with fractures.9) In the present case, the absence of a history of injury or trauma may reduce the likelihood of acquired ectopic implantation into the convexity of the frontal bone. Thus, although several hypotheses regarding the development of ECs exist, the concept of ECs attaching to the ectoderm remains central to understanding their development. The fact that the frontal bone-unlike other cranial convexity bones-is derived from the neural crest of the ectoderm is another embryological feature that supports the developmental mechanism of supratentorial frontal ECs in the absence of ectodermal separation.
A schematic figure illustrating the differential pathogenesis expected for trauma of intracranial, intraspinal canal, and cranial endodermal cyst.
In the present case, an EC located in the convexity of the frontal bone was discovered in middle age due to its gradual growth, and sinusitis was observed on the same side as the frontal air sinus.
Although Rathke's cleft cyst (RCC) is an ectodermal-originated cyst, we speculated that the phenomenon in the present case occurred through a mechanism similar to that observed in some RCC cases. Namely, mucosal thickening of the sphenoid sinus has been reported in approximately 16.7% of RCC cases, and this thickening is considered inflammatory in nature.10) The frequency of mucosal thickening in the sphenoid sinus is reportedly higher in RCCs than in pituitary neuroendocrine tumors, which also occur in the same anatomical region. This is believed to result from primary inflammation caused by the RCC, which subsequently enlarges slowly and induces paranasal sinusitis in adjacent structures.11) It is possible that ECs undergo repeated growth due to chronic inflammation, leading to associated sinusitis. Although one could argue that ECs grow as a result of inflammation spreading from sinusitis, this is less plausible when the cyst and sinus are anatomically separated by the frontal bone. A more reasonable explanation is that the slow expansion of the cyst itself induces inflammation in adjacent sinus structures.
It is difficult to distinguish ECs from mucoceles of the frontal air sinus with histopathological analysis, because they both may have ciliated epithelium and be positive PAS and EMA immunostaining associated with inflammatory change. However, in our case, preoperative image and intraoperative findings showed that the frontal bone around the cyst wall exhibited a smooth and continuous surface, with distinct bone present at the border with the frontal sinus. Therefore, we concluded that the cyst was not mucocele resulting from acquired separation of the frontal sinus but rather an EC in the frontal convexity bone.
As mentioned above, we reported an extremely rare case of an EC developing in the convexity of the frontal bone. Given that the frontal bone is derived from the neural crest, we hypothesize that one of the potential pathogenetic mechanisms may involve endodermal-neural crest adhesion. Future studies should investigate the embryological mechanisms underlying ectopic endodermal cyst development, particularly the role of endodermal-neural crest adhesion. The location of the cyst in the frontal convexity, as opposed to the anterior cranial base, may suggest a distinct pathogenesis for each EC in terms of embryological aspects. Further accumulation of cases is needed to properly elucidate the pathogenesis of EC.
The authors would like to thank Editage (www.editage.jp) for English language editing.
No funds were received in support of this work. The authors made a declaration of conflict of interest to the Japan Neurosurgical Society Office.
Informed consent was obtained from the patient for the publication of this case report.
Author Toshihiro Takami is one of the Editorial Board members of the Journal.
This author was not involved in the peer-review or decision-making process for this paper.
