Imaging manifestations of papillary glioneuronal tumors

PGNT is a rare WHO grade I glial neuron tumor that accounts for 0.02% of all central nervous system tumors. The age of onset is 4–75 years old, the peak is of onset is 20–30 years old, and there is no significant sex predominance [2, 6]. The male-to-female ratio of patients in this group was 1:1.1, with an average age of 22.5 years, and the age of onset was 3–43 years, which is consistent with the literature. The minimum length diameter of the lesions was approximately 15 mm, the maximum length diameter was approximately 80 mm, and the median length was 45 mm, which is consistent with the average diameter of 138 PGNT lesions reported by Ahmed et al. [4].

PGNT usually presents with nonspecific clinical manifestations [7]. Headache, nausea, and vomiting caused by increased intracranial pressure are common initial symptoms, followed by seizures. Acute symptoms or focal neurological deficits rarely occur during the natural course of PGNT, possibly because it is a low-grade tumor with slow growth. Over time, its clinical symptoms are related to the progress of intracranial pressure or space-occupying effects [2, 8]. The initial symptoms of the patients in this group included epilepsy, headache, vomiting, dizziness, limb weakness, hearing symptoms, blurred vision, convulsion, stare blankly, etc., which occurred alone or in combination, consistent with previous reports.

PGNTs tend to occur in the supratentorial area, usually in the frontal and temporal lobes, and are closely related to the ventricles. Most PGNTs are located in the paraventricular white matter, and some of PGNTs may involve the ventricle. Sometimes, it occurs in the ventricles, but there are also reported cases in other locations, such as the cerebellum, pineal region, or brain stem [2, 8]. In our cohort, one tumor was located in the infratentorial brain stem, and 35 were found in the supratentorial region, including 11 in the frontal lobe, 7 in the temporal lobe, most of which were close to or involved the ventricles, 6 in the ventricle, and 1 in the pineal region. At present, the pathogenesis of PGNT is still unclear. Because of the close relationship between the tumor and ventricles, some studies have suggested that PGNT may originate from the germinal zone of the subependymal plate and that more superficial PGNT may arise from the secondary germinal layer [9]. The expression of stem cell markers within the tumor suggests a possible origin from neuroepithelial stem cells with biphenotypic differentiation [10].

PGNT imaging can be divided into four categories [11]: mixed cystic and solid mass, cystic mass with mural nodule, pure cystic mass, and pure solid mass. In this group, 66.7% (24/36) of the tumors were mixed cystic and solid mass, 11.1% (4/36) were cystic mass with mural nodule, 11.1% (4/36) were pure cystic mass, and 11.1% (4/36) were pure solid mass, most tumors did not have edema or had only mild peritumoral edema. In comparison, Park [11] summarized 76 cases of PGNT and found that cystic masses with mural nodules were the most common type. As that was a summary of multiple studies, there may be differences in tumor classification criteria, and further retrospective analysis with a large sample size is needed. Secondly, the number of tumors in this group was relatively small, and cystic mass with mural nodule is a type of mixed cystic and solid lesion.

PGNT may present with hemosiderin, calcification, septation, and superficial siderosis; the mass effect is mild, and mild perilesional edema is rare [6]. Only nine of the 36 lesions in our cohort were accompanied by edema. Septation was observed in 25 lesions, of which only one mixed cystic and solid lesion was not septated, which may be related to the obvious pseudopapillary structure of PGNT. The presence of prominent septations within the cystic component formed by long pseudopapillae traversing the cyst is a distinctive imaging feature [12]. Tavallaii et al. [2] mentioned that calcification can be seen in PGNT. Internal bleeding is an extremely rare radiological manifestation of these tumors; a hemorrhage in the form of chronic micro-bleeding leading to hemosiderosis has rarely been reported. Tan et al. [13] suggested that calcification is a common sign of mixed cystic and solid PGNT. Although only half of the patients in this cohort underwent CT or SWI examination simultaneously. Two patients had diffuse superficial siderosis, nine had mixed cystic and solid lesions, as well as a hemorrhage. Moreover, nine had calcification. Therefore, calcification and hemorrhage may be common signs of mixed cystic and solid PGNT. The pathogenesis of brain tumor-related hemorrhage mainly includes endothelial proliferation with subsequent obliteration of the lumen, thin-walled or poorly formed vessels, perivascular necrosis with subsequent loss of vessel support, and the presence of intratumoral arteriovenous fistulae [14]. Benzagmout et al. [15] described two cases of PGNT with hemorrhage at different periods. They believed that the pathogenesis of tumor hemorrhage included thin-walled blood vessels in the solid part or abnormally transparent blood vessels in the nipple area, so that PGNT could be accompanied by hemorrhage.

PGNT is a low-grade biphasic neoplasm with astrocyte and neuronal differentiation, with a prominent pseudopapillary architecture, composed of hyalinized vessels, and covered by single layer of small cuboidal glial cells [2, 7]. GFAP was positive in 34 patients in this group, and no GFAP results were found in 2 patients. Tanaka et al. [16] found another cellular component of PGNT, characterized by Olig-2 positivity, indicating a phenotype of oligodendrocytes. In this group, 33 patients were Olig-2 positive, 7 of which showed focal or sporadic positivity, and the Olig-2 results were not found in the other 3 patients. The average Ki-67 index of PGNT was 3.6%, with a Ki-67 < 5% in most cases, indicating low proliferative activity, absence, or low mitotic activity [4]. Most patients with PGNT have a good prognosis, and there are literature reports following patients for up to 26 years. Total tumor resection is the preferred treatment for PGNT, and although recurrence can sometimes occur after resection, in most cases the prognosis is good even if complete resection is not performed [8]. A Ki-67 ≤ 5% and maximum surgical resection are positive prognostic factors [17]. In our cohort, 27 patients with a Ki-67 < 5%, nine with a Ki-67 ≥ 5%. Four PGNT presented as pure cystic lesions, all of which were small, they exhibited a “T2-FLAIR mismatch” sign, and a Ki-67 < 5%. In 36 cases of PGNT, except for 1 case where the brain stem mass was mostly removed and 1 case where biopsy was performed, all others were total resection. However, patients with brain stem masses were not followed up. No recurrence was found among the nine patients who underwent postoperative review (the minimum postoperative review time was 6 months, and the longest was 24 months). Although PGNT is considered an indolent lesion, this tumor can be highly proliferative, which may indicate the possibility of transformation of PGNT to a more aggressive form [7]. The low frequency of PGNT and the description of only a few atypical cases may mask its occasional malignant potential [18]. Goethe et al. [19] found that a patient with PGNT had a Ki-67 index of 6–7%, and the tumor recurred 7 months after surgery with an increased Ki-67 index; the tumor recurred again 2 years after reoperation. Yadava et al. [20] reported a case of PGNT recurrence 9 years after surgery that was characterized by solid partial hyperperfusion, elevated Cho, intratumoral hemorrhage, and superficial siderosis. Carangelo et al. [21] reported their experience with a patient with PGNT with a Ki-67 index < 1% who relapsed 2 months after surgery. One of our patients had extensive flocculent lesions on the ventricle wall. A biopsy was performed, and a fistula was made at the bottom of the third ventricle. The biopsy indicated that the Ki-67 index was 2–5%. Multiple metastatic lesions in the brain were found 1 year and 4 months after the ostomy. Similarly, Bourekas et al. [18] reported a case of PGNT with anaplastic histological features that recurred three times after surgery and underwent resection. The patient developed multiple systemic metastases approximately 4.5 years later. These findings suggest that a high histological grade is more associated with central nervous system tumor metastasis, which may occur through vascular damage from surgery or radiation and via ventriculoperitoneal shunts. One of our patients developed metastasis, which may be related to surgical ostomy and the growth site.

This study has several limitations. First, the sample size was relatively small, mainly because of the low incidence of PGNT. Second, as this is a retrospective study, only some patients underwent CT or SWI examinations, which resulted in the inaccurate evaluation of the incidence of internal bleeding and calcification within the lesion. Third, the postoperative follow-up time was short; some patients did not undergo imaging follow-up examination after surgery. In conclusion, our results show that PGNTs mostly manifest as cystic mass with mural nodule or mixed cystic and solid mass in the white matter around the supratentorial ventricle and rarely occurs under the tentorium. Pure cystic lesions may exhibit the sign of “T2-FLAIR mismatch”. PGNT is seldom accompanied by edema and can be accompanied by calcification and hemorrhage. Pathological morphology and immunohistochemistry can help make a definite diagnosis.