Malignant papillary glioneuronal tumor of the pineal gland: Case presentation and literature review of a distinct entity

Background

The authors present a most unusual case of a malignant papillary glioneuronal tumor of the pineal gland. This is only the second reported case of such a high grade glioneuronal tumor in the pineal gland, and the third overall papillary glioneuronal tumor of the pineal gland. We review the literature and discuss the epidemiology, natural history, pathologic diagnostic recommendations, and recommended treatment for this pathology.

Case Report

INTERVENTION:

He was taken to the operating room for supracerebellar-infratentorial approach for biopsy of the mass using neuro-navigation. Post-operatively he had continued hydrocephalus, and was taken to the operating room for a cerebral spinal fluid diversion procedure, an endoscopic third ventriculostomy. He had an uneventful hospitalization and was eventually discharge to home. Because of histological features, it was recommended that patient undergo chemotherapy and radiation; however he refused treatment. He died six months after his initial diagnosis due to an abdominal condition unrelated to his intracranial tumor.

PATHOLOGY:

Pathology demonstrated a rare high grade glioneuronal tumor (Figure 2A–K). Histology showed a mixture of neoplastic astrocytic and neuronal cells in roughly equal proportions. There was marked nuclear anaplasia, increased mitotic activity, and microvascular proliferation. No definitive necrosis was seen. Neoplastic astrocytes were strongly reactive for GFAP, while neuronal cells were immunoreactive for synaptophysin. No rosettes were seen. Papillary architecture was noted. Double label immunostaining with GFAP and Ki67 highlighted the proliferating astrocytes, and a similar double stain using MAP-2 and Ki67 showed proliferating neuronal cells. The Ki67 was found to be 20%. EGFR, CAM 5.2, and p53 markers were all negative. A diagnosis of malignant papillary glioneuronal tumor was made.

Discussion

Pineal tumors account for 0.5% of all intracranial tumors [1]. Pineal region pathology is diffuse but critical diagnosis of the exact pathology is important, as treatment options and prognosis are very different depending on the specific tumor type.

Papillary glioneuronal tumors (PGNT) were first described in 1998 by Komori et al. [2]. These tumors were noted to have a pseudopapillary pattern with mixed astrocytic, ganglionic and neurocytic differentiation [3]. Histologically these tumors show compact pseudopapillary appearance with hyalinized blood vessels covered by glial fibrillary acidic protein, suggesting astrocytic differentiation, along with areas that are synaptophysin positive, suggesting neuronal differentiation [3]. Ki67 positivity is reported to be low [3]. Classically these tumors are described in young patients, with rare cases affecting the elderly [2,4]. Since that time, WHO in 2007 has classified these distinct tumors in a group of their own [4] suggesting that these tumors low grade and exhibit benign pathophysiology.

Although most mixed papillary glioneuronal tumors have an indolent course, there are a few published cases of a more aggressive type. Newton et al. described a 19 year old woman with visual seizures and a aggressive papillary glioneuronal tumor in the occipital lobe with a ki67 of 26% [5]. Jahavery et al. described two cases of aggressively behaving papillary glioneuronal tumors. These tumors, one in the frontal lobe and the other along the lateral ventricle, recurred months after their initial resection and had a substantial increase in their KI67 compared to their initial pathology [6]. Ishizawa et al. reported a case of an aggressive papillary glioneuronal tumor in the parietal lobe with an increase in mini-gemistocytic cells up to 10% [7]. In our case, pathology demonstrated a similar combined glioneuronal tumor with aggressive features, of the pineal gland. As noted above, the tissue stained strongly for both GFAP and synaptophysin indicating a dual glioneuronal nature to this tumor. Necrosis was not identified. The proliferative index was 20%. We confirmed on histology that this tumor was neither metastatic in nature, nor a meningioma or intraparenchymal pineal tumor.

Aryan et al. reported the first case of papillary glioneuronal tumor of pineal gland in a 78-year-old man who presented with personality changes and gait disturbance [3]. Husain et al. recently reported a case involving a 4-year-old child with obstructive hydrocephalus with a tumor involving the pineal gland and the ventricular system (Table 1) [8] without anaplastic features or high vascularity. It seems that glioneuronal tumors in the pineal gland may occur in any group, with older patients having a greater predilection for anaplasic features (Table 2), however the number of cases is too small to postulate this trend.

The presentation common among these groups is obstructive hydrocephalus, as observed in all three patients illustrated in the table, caused by a mass approximately 2.0 cm or greater in size (Table 1). In all three cases, the pineal mass is heterogeneously enhancing, with hypointensity on T1 and hyperintensity on T2 MRI (Table 1). Both adult patients were managed with an endoscopic third ventriculostomy and biopsy (Table 1). One patient survived at least three months and the other six months (although he died from complications of diverticulitis). No data on the survival of the child was available. All cases exhibited strong GFAP and synaptophysin staining (Table 2). Two of the three cases (adult patients) exhibited high proliferative indices with anaplastic components (Table 2).

In review of other malignant tumors of the pineal gland, glioblastoma multiforme cases have been reported with similar presentation [1–15]. This case is clearly not a glioblastoma; necrosis was not seen, synaptophysin was strongly positive, and giant cells were not encountered on pathology. This is a glioneuronal tumor, recently classified entity is clinically and pathologically distinct from other tumors. Since 1998, mixed glioneuronal tumors arising from the cerebrum, cerebellum, ventricular wall have been reported, but the pineal gland are an extremely rare location and one with anaplastic features is even rarer, and it should be considered on the differential diagnosis for primary pineal gland tumors.

Conclusions

It may be surmised that glioneuronal tumor may arise from anywhere in the central nervous system and may showcase a wide spectrum of histological features. More cases and follow up data on these patients must be reported for a more accurate analysis of the natural history, population incidence, location predilection, histology, genetic features and most importantly treatment, of glioneuronal tumors of the pineal region.