Polymorphous low-grade neuroepithelial tumor of the young: case report and literature review

Abstract

Polymorphous low-grade neuroepithelial tumor of the young (PLNTY) typically manifests as an epileptogenic subtype, posing challenges in differential diagnosis. Here, we report an unusual case of a PLNTY in a 14-year-old girl who was admitted to the hospital with acute headache, nausea, and vomiting. The tumor was initially misdiagnosed as ganglioglioma on imaging, and then diagnosed as PLNTY based on surgical and pathologic findings. The patient did not present with typical epileptic symptoms. PLNTY is a rare low-grade brain tumor that occurs in adolescents, with imaging manifestations similar to those of other neuroepithelial tumors, that can easily lead to misdiagnosis. In this article, we discuss the clinical features, imaging manifestations, pathologic findings, and molecular mechanisms of PLNTY in the context of this case, emphasizing the need for early diagnosis and treatment.

Introduction

Polymorphous low-grade neuroepithelial tumor of the young (PLNTY) is a rare low-grade brain tumor, classified as a childhood-type diffuse low-grade glioma by the 2021 WHO Classification of Tumors of the Central Nervous System [1]. First described by Huse et al. in 2017 [2], PLNTY represents a set of solid tumors that predominantly affect adolescents. The clinical manifestations of PLNTY lack clear specificity, and its histologic diversity and low incidence complicate diagnosis. Additionally, there is limited literature on the imaging characteristics of PLNTY; furthermore, most extant studies focus on pathologic analysis, without a comprehensive understanding of its imaging features [3]. This article presents a case with atypical clinical and imaging manifestations, aiming to raise awareness of rarer presentations of PLNTY and provide evidence for clinical differential diagnosis.

Case presentation

A 14-year-old girl presented to Nanhua Hospital with acute headache, nausea, and vomiting lasting over five hours, but lacked classic epileptic signs typically indicative of PLNTY. The patient was admitted to a local hospital for a complete cranial computed tomography (CT), which suggested space-occupying lesions in the right temporal lobe. Additionally, the patient reported having poor mental health, appetite, and sleep since the prior night. She was also lethargic and poorly responsive, with a Glasgow Coma Scale (GCS) score of E3V5M6=14. Laboratory analysis results for the patient are presented in Table 1. A routine blood test showed that the white blood cell count was 15.32 × 10⁹/L; neutrophil ratio was 92.3%; neutrophil count was 14.15 × 10⁹/L; hemoglobin level was 106 g/l; FDP was 17.21 µg/mL; and the plasma D-dimer value was 6.55 mg/L. The nucleic acid test for pneumococcal pneumonia was negative.

Table 1.

Abnormal laboratory findings

	Patient’s results	Normal range
White blood cell (×109/L)	15.32	4.0-10.0
neutrophil ratio (%)	92.3	50-70
Neutrophil (×109/L)	14.15	2.0-7.0
Hemoglobin (g/l)	106	110-165
FDP (µg/mL)	17.21	0-5.0
D-dimer (mg/L)	6.55	0-0.55

The patient was admitted to the hospital and underwent a CT examination, which revealed a cystic mass in the right temporo-parietal lobe, with a visible wall nodule measuring 6.3 cm × 4.7 cm and visible foci of calcification at the edges of the lesion (Figure 1A). To clarify the nature of the lesion, the patient underwent a cranial MRI and enhancement scanning examination (Figure 1B-H). Then, the patient underwent surgical treatment on the second day. During surgery, the brain tissue was found to be slightly swollen, and the cortex appeared grayish. The head of the tumor was exposed. A cerebral puncture needle was inserted into the cystic cavity at the head of the tumor, and about 15 mL of cystic fluid was aspirated. The brain tissue collapsed, and the cortical fistula was to resect the tumor further. Postoperative immunohistochemistry revealed PLNTY.

Figure 1.

Imaging results. A. CT showed a round cystic solid mass in the right temporo-parietal lobe. Two slightly hyperdense nodules were seen in the wall of the capsule; punctate and striated calcifications were seen in the bicuspid nodules. B. A cystic solid mass was seen in the right temporoparietal lobe, with low signal intensity, and a low-signal intensity wall nodule was observed on T1WI. C, E. The cystic component of the mass in the T2-weighted sequence and the wall nodules had high signal intensity. D. The cystic component of the T2-FLAIR sequence and the wall nodule had high signal intensity, and the edge of the lesion was well defined. F. MRI enhancement of the wall nodule showed inhomogeneous enhancement, G, H. No signs of diffusion restriction were seen in the wall nodules.

Immunohistochemical analysis indicated the expression of CD34 (diffuse+ in some areas), glial fibrillary acidic protein (GFAP) (+), P53 (partially+, wild-type), S-100 (+), actin (-), Ki-67 (about 1%+), neuron-specific enolase (NSE) (partially+), Syn (+), IDH-1 (-), and epithelial membrane antigen (EMA) (±). Combined with the hematoxylin-eosin (H&E) staining pattern analysis, the diagnosis was suggestive of PLNTY (WHO grade 1) (Figure 2). Postoperatively, the cranial CT and MRI were on the first day after surgery, and the mass was found to be reduced in size compared with the pre-operatively. Postoperative review revealed the size of the mass to be 4.5 cm × 2.6 cm × 4.3 cm. The original wall nodule was not observed; a small amount of new epidural hematoma was present on the right parietal side, and soft tissue edema of the scalp was found on the right temporal-parietal side (Figure 3). Postoperatively, the patient’s postoperative headache, dizziness, nausea, and vomiting symptoms were relieved. To date, the girl has been followed up for 20 months. She recovered well postoperatively and had no recurrence of seizures thus far.

Figure 2.

Pathologic features of PLNTY. A. Tumor cells infiltrating and growing, visible as slender blood vessels, focal with oligodendroglioma-like components (round nuclei, perinuclear halos, chicken-claw-like vessels) (magnification ×200). B. Extensive foci of calcification (scattered or fused calcifications) (magnification ×200). C. GFAP (+) (magnification ×200). D. CD34 was diffusely strongly positive, with scattered cells in branched protrusions (magnification ×200). E. Ki-67 (+) about 1%. F. IDH-1 (-) (magnification ×200). Bars, each 50 μm.

Figure 3.

Post-operative CT and MRI images acquired on the first day after surgery. A. The right temporoparietal cystic mass was found to be reduced in size, the wall nodules had disappeared, and a small epidural hematoma was observed in the right temporoparietal region. B. The mass was hyposignalized on T1-weighted images, and there was a new lesser pneumoperitoneum in the lesion. C. The lesion had high signal intensity on T2-weighted images, and no wall nodules were seen. D. Enhanced scan with mild enhancement at the edge of the lesion.

Discussion

Clinical characteristics of PLNTY

The strong epileptogenic propensity of PLNTY can cause patients to experience early-onset epilepsy or refractory epilepsy [4,5]. PLNTYs may also be accompanied by headaches and focal neurologic deficits [6,7]. The clinical presentation of the present case differs from previous literature reports in that this patient was admitted with sudden onset of dizziness and headache, accompanied by nausea and vomiting, and did not present with typical seizure symptoms. PLNTY -is a neuroepithelial tumor that mostly appears in children and adolescents, is more likely in females, and is rare in adults [8-10].

Ganglioglioma, which is most common in children and young adults, occurs predominantly in the temporal lobe. On imaging, 44-80% of gangliogliomas present as cystic lesions [11]. The reported case is a 14-year-old adolescent female whose lesion occurred in the temporal lobe, with a predominantly cystic component, which led us to suspect a ganglioglioma.

PLNTY is typically considered a benign tumor [2,3,12-16]. There have also been reports of a 41-year-old male patient diagnosed with PLNTY, who was subsequently diagnosed with ependymoma and ultimately died from tumor progression and postoperative complications [7]. In a survey conducted by Huse et al., seven out of eight patients who underwent gross total resection of PLNTY achieved disease-free status over a mean follow-up period of 50.6 months. Interestingly, only one patient exhibited potential tumor recurrence - evident from the imaging results - 36 months after surgery [2]. This result highlights the importance of surgical resection in the management of PLNTY, especially for achieving disease-free status. While PLNTYs are typically benign, the risk of malignant transformation cannot be overlooked.

Pathologic features and molecular mechanisms of PLNTY

The 2021 WHO classification of Central Nervous System (CNS) tumors has introduced new categories based on molecular characteristics [17]. Within the WHO CNS5 classification, diffuse gliomas are grouped into adult and pediatric types [18]. The pediatric type has similar histologic morphology, but a significantly different prognosis [1]. The WHO CNS5 categorizes pediatric-type diffuse low-grade gliomas (pDLGG) into four specific tumor types: I) diffuse astrocytoma with MYB- or MYBL1 alterations; II) angiocentric glioma (AG); III) PLNTY; and IV) diffuse low-grade glioma with MAPK pathway alterations [19]. PLNTY exhibits several distinct characteristics, such as the presence of oligodendroglial-like cells in the temporal lobes and cortical/subcortical regions, dense calcification, infiltrative growth pattern, and diffuse expression of CD34 [16,20-22].

Concerning molecular genetic alterations, most PLNTY cases are caused by a mutation in the BRAF V600E gene, which accounts for approximately 60% of all mutations. For the diagnosis of PLNTY, these unique clinicopathologic characteristics and molecular genetic alterations are important [23]. PLNTY shows low rates of mitosis, necrosis, and microvascular proliferation, distinguishing it from similar tumors such as pleomorphic xanthoastrocytoma (PXA), ganglioglioma, pilocytic astrocytoma, and dysembryoplastic neuroepithelial tumor (DNET). In contrast to these tumors, PLNTY commonly exhibits alterations in BRAF or FGFR2/FGFR3, resulting in a low Ki-67 labeling index, consistent with its classification as a low-grade tumor [24].

Imaging manifestations of PLNTY

PLNTY tends to predominantly appear mainly in the cerebral hemispheres, with the temporal lobe being the most common location, followed by the occipital, frontal, and parietal lobes. These tumors usually have clearly defined boundaries and are most often seen in the right temporal lobe, with only a small percentage found in the ventricles [3,19,25]. A distinctive feature of PLNTY is the presence of a delineated mass in the temporal lobe that shows central calcifications, peripheral cysts, and a mix of signals on imaging tests. Specific neuroimaging patterns are strongly suggestive of the presence of PLNTY [6], including a poorly defined cortical lesion with a “salt and pepper” appearance on T2-weighted imaging and calcification on CT scans [26,27].

The most important imaging feature in our patient was a large capsule containing small nodules and visible calcifications in the temporoparietal lobes. This specific feature, which comprised cysts with a mural nodule tumor, is commonly seen in various intracranial neoplastic lesions such as ganglioglioma, pilocytic astrocytoma, hemangioblastoma, and pleomorphic xanthoastrocytoma [28]. Considering the patient’s age, tumor location, and imaging findings, our initial MRI report was suggestive of ganglioglioma. However, upon further examination, the final pathologic diagnosis revealed the lesion to be PLNTY. It is crucial to distinguish PLNTY from other common brain tumors such as ganglioglioma, oligodendroglioma, pilocytic astrocytoma, DNET, and PXA, whose characteristics are described below.

Ganglioglioma: Ganglioglioma is a unique type of brain tumor composed of glial cells and differentiated neurons. Although rare, it accounts for a small percentage of all primary brain tumors, with the majority affecting individuals under 30 years old [29]. Around 50% gangliogliomas show a cyst with a mural nodule on radiological examination. Other presentation comprises a solid tumor with low-to-intermediate T1-weighted (T1W) and high T2W signal or masses with predominant T1 hyperintensity [30].

Oligodendroglioma: Oligodendroglioma mainly occurs in adulthood, with incidence peaking between the ages of 40 and 60 years [31]. There is a high incidence of calcification in oligodendrogliomas that is visible on non-enhanced CT in up to 90% of cases [32]. Understanding these associations can aid in diagnosing and managing patients with this type of brain tumor [33].

Pilocytic astrocytoma: This is the most common type of glioma in children, and often presents with cysts or forms a tumor nodule within a cyst [34]. This variant is more prevalent in cerebellar and hemispheric tumors. Pilocytic astrocytomas affect the optic pathways, optic nerve, and chiasm, including fusiform masses [35].

Dysembryoplastic neuroepithelial tumor (DNET): Fine calcifications are often present in DNETs, and although they do not show the characteristic “salt and pepper sign” commonly associated with PLNTY, DNETs usually display a distinct demarcation and a multinodular appearance resembling a “soap bubble” [36]. Localized thinning of the skull covering the tumor may aid in the diagnosis of DNET in some cases. The T2-FLAIR mismatch sign is seen in 72.7% of all DNET cases [37].

Pleomorphic xanthoastrocytoma (PXA): This is an exceptionally rare yet typically benign form of astrocytic tumor, and it tends to occur primarily among those in the third decade of life [38]. Two-thirds of tumors are predominantly solid, often accompanied by peritumoral edema, and some cases may be associated with corpus callosum hypoplasia [39]. PLNTY may be more invasive and more likely to undergo malignant transformation than PXA [40].

Conclusion

PLNTY is a class of adolescent low-grade neuroepithelial tumors with good prognosis. Definitive diagnosis of PLNTY is important to avoid over-treatment and improve the quality of survival in pediatric and adolescent patients. Given that PLNTY and other low-grade gliomas share some overlap in histologic morphology and genetic abnormalities, there are currently no specific diagnostic criteria for PLNTY in clinical practice. Diagnosis requires a comprehensive assessment based on clinical history, imaging characteristics, histologic features, and molecular characteristics. Analysis and screening of larger numbers of cases is necessary to provide a more reliable and adequate scientific basis for clinical diagnosis and treatment and to improve prognosis.

Disclosure of conflict of interest

None.

Abbreviations

PLNTY

Polymorphous low-grade neuroepithelial tumor of the young

GG

Ganglioglioma

CNS

Central Nervous System

pDLGG

Pediatric-type diffuse low-grade gliomas

DNET

Dysembryoplastic neuroepithelial tumor

PXA

Pleomorphic xanthoastrocytoma