Abstract:Neurenteric cysts (NCs) are rare congenital anomalies originating from the endoderm. While they are most commonly found in the posterior fossa, NCs can occasionally occur in the supratentorial region. These cysts typically show benign histopathological features and rarely undergo malignant transformation. Only a few such cases have been documented in the literature. This study presents the case of a 55-year-old male with a one-month history of headache and diplopia. Magnetic resonance imaging (MRI) revealed a 49 x 41 x 54 mm solid mass in the left parietal and frontal lobes, extending into the frontal, sphenoid, and ethmoid sinuses as well as the left orbit. The mass was associated with significant brain edema and mass effect. Histopathological examination of the resected specimen revealed remnants of a neurenteric cyst wall with squamous metaplasia and malignant transformation into squamous cell carcinoma (SCC). This study highlights the importance of thorough histopathological evaluation after surgical removal of brain SCCs to accurately identify the primary origin. Proper diagnosis can prevent unnecessary post-surgical investigations aimed at ruling out metastatic disease.Keywords : Neurenteric cyst, malignant transformation, squamous cell carcinoma, squamous metaplasiaIntroduction :Neurenteric cysts (NCs), also known as endodermal or enterogenous cysts, are rare congenital anomalies originating from the endoderm1,2. These cysts are covered by a columnar or cuboidal epithelium similar to that found in the gastrointestinal and respiratory tracts 2. They typically contain mucoid substances and protein 3.Although NCs can occur anywhere along the central nervous system (CNS), they are most commonly found in the spine4. Spinal NCs are approximately three times more prevalent than intracranial ones5. Among intracranial NCs, the majority are found in the posterior fossa, while supratentorial NCs are rare6–8. These cysts often present with neurological symptoms by compressing adjacent structures and cranial nerves8,9. Headaches have been reported in nearly half of these patients10.The exact mechanism underlying NC formation remains unclear. However, it is hypothesized that these cysts arise from the failure of the neurenteric canal, a temporary duct connecting the amniotic cavity to the yolk sac during the third week of gestation, to close properly. This incomplete fusion results in the displacement of endodermal cells and ultimately leading to the formation of NCs 9,11. NCs are often associated with other abnormalities that share a similar pathogenesis, such as spinal anomalies, dermal defects, and abdominal or thoracic cysts 9,11. Additionally, recent research has suggested that KRAS mutations may play a role in the development of NCs12.Although NCs are generally benign, malignant transformation is a rare but documented possibility 10. Most reported cases of malignant transformation have been histologically identified as adenocarcinomas 13–18. However, this study presents a rare case of an NC that underwent malignant transformation to squamous cell carcinoma.