Vanishing pineal mass in a young patient without therapy: Case report and review of the literature

Abstract

Spontaneous regression is defined as the decrease in size or disappearance of a primary tumour or metastatic disease without therapeutic intervention. Computed tomography and magnetic resonance imaging (MRI) of the brain was performed in a 14-year-old girl experiencing sudden-onset headaches. First diagnostic exams revealed a mass in the pineal region that disappeared at three-month MRI control. Three-year follow-up MRI studies were performed. No therapy was administered, but the pineal lesion had disappeared at three-year follow-up.

Introduction

Brain tumours in the pineal region are germ cell tumours, pineal parenchymal cell tumours, gliomas, meningioma, and metastases. Germ cell tumours in this region are predominantly found among young patients.¹ Spontaneous regression of malignant tumours is an extremely rare phenomenon that reportedly occurs in 1 out of 60,000–100,000 patients.²

Case report

A previously healthy 14-year-old girl experienced progressive photophobia and diplopia. After four months, she presented sudden-onset headaches, vomiting, dizziness and tinnitus, and was referred to our hospital. A neurological examination revealed binocular multi-directional diplopia, convergence-retraction nystagmus and mild photophobia. An eye examination showed normal focus range, fundus and Hess–Lancaster test. A computed tomography (CT) scan of the brain showed a well-circumscribed pineal region expansive process measuring 25 mm. It was well delineated, with spontaneous high density, and there was patchy calcification in the central part of the tumour, as well as mild hydrocephalus (Figure 1(a)).

Figure 1.

(a) Computed tomography (CT) shows the pineal region solid mass with calcifications (arrows). (b) Magnetic resonance imaging (MRI) T2-weighted images on the axial plane demonstrate a solid mass in the pineal region. (c) MRI T1-weighted images on the sagittal plane. After administration of contrast media, the lesion had homogeneous enhancement.

Electroencephalography (EEG) demonstrated mild abnormalities more prominent in the left posterior sites. Brainstem auditory evoked potentials (BAEP) evidenced impaired hearing on the left side. Motor evoked potentials were normal. Routine blood investigations were within normal limits. Magnetic resonance imaging (MRI) was performed using T1- and T2-weighted standard spin echo sequences, fluid attenuating inversion recovery and diffusion-weighted images/apparent diffusion coefficient sequences. Post-contrast T1-weighted images were also obtained on the axial, sagittal and coronal planes. MRI examination revealed a lesion in the pineal region which compressed the tectal plate and cerebral aqueduct. The mass appeared heterogeneously hypointense on the T1-weighted images. On T2-weighted images, the mass was heterogeneously iso- to hyperintense to the cortex (Figure 1(b)). A homogeneously enhanced mass was observed after administration of contrast medium (Figure 1(c)). On diffusion-weighted imaging, the mass was markedly hyperintense with hypointense signal on corresponding apparent diffusion coefficient maps. Proton magnetic resonance spectroscopy of the lesion identified a relatively decreased N-acetylaspartate (NAA) peak and an increased choline (CHO) peak. A slight increase of glutamate/glutamine (Glx) peak was also observed (Figure 2).

Figure 2.

(a) MRI perfusion map. There was no significant increase in perfusion inside the pineal lesion. (b) MRI single voxel spectroscopy reveals a relatively decreased N-acetylaspartate peak, an increased choline peak and an increased glutamate/glutamine peak.

Blood and cerebrospinal fluid markers of germinal tumours were negative. However, lymphoid elements (97% T CD3+, 3% B CD20+) were detected. Biopsy was scheduled, but clinical symptoms progressively disappeared in the meantime, without any therapy or treatment for hydrocephalus. A brain MRI performed three months later showed spontaneous regression of the tumour and resolution of the hydrocephalus (Figure 3(a)).

Figure 3.

(a) MRI T2-weighted sequences on the axial plane after three months show mass reduction. (b) Three-year MRI follow-up shows the normal appearance of the pineal region.

No evidence of recurrence was found on the annual follow-up MRI studies. The patient also remained asymptomatic at the three-year follow-up (Figure 3(b)). Informed consent was obtained to perform all exams.

Discussion and conclusion

The pineal gland or epiphysis is a small anatomical remnant of a dorsal third eye or an endocrine gland. The volume and structure of the epiphysis is subjected to size increasing from birth until 2 years of age and remains constant from ages 2 to 20 years. Calcification of the pineal gland is typical in adults, though its significance is still far from being completely understood. A vanishing tumour may be defined as a space-occupying lesion that shows radiological features consistent with a tumour but that unexpectedly disappears or shrinks down during the radiological follow-up, thereby behaving like a ‘ghost’. Only a few cases have been reported in the literature, although their incidence has been estimated to be approximately 1%. In the pineal region, the occurrence of apoplexy may play a pivotal role. Apoplexy, that is, an ischemia or haemorrhage into an organ, may explain this phenomenon. However, pineal apoplexy is a controversial issue, since only one case has been described in a normal gland occurring in the context of anticoagulation therapy.^3,4 On the other hand, almost all cases described so far are associated with a ‘lesion’.^5,6 In this context, pineal apoplexy can be related to haemorrhage into a pineal cyst, bleeding of a tumour or rupture of a vascular malformation. Sometimes apoplexy may follow an ischemic event in the context of a tumour.⁶ Indeed, large tumours may compress or outgrow the feeding vessels, especially those coming from the lateral pineal artery, which often provides monolateral vascularisation to the pineal gland. An ischemic mechanism can be hypothesised when neuroimaging exams do not show signs of haemorrhage, as happened in the present case. Multi-detector CT and MRI are very useful in diagnosis to demonstrate the presence of blood, ischemia or tumour.^7–11

According to Mattongo et al., the interference of raised intracranial pressure with cerebral blood perfusion may represent an alternative option. The mammalian pineal gland presents a remarkably rich vascularisation, which accounts for one of the higher local blood flow among endocrine glands.¹² Subsequently, the increased vascular resistance and vasoconstriction resulting from increased intracranial pressure may be complicated by an ischemic event, leading to the involution of the associated tumour. In the literature, pineal vanishing tumours do not show specific or recurrent histotypes, although, as expected, lymphomas are relatively frequently reported because of their trend to regress with corticosteroid therapy.^13,14 Furthermore, spontaneous regression of pediatric low grade astrocytomas, germinoma and pylocitic astrocytoma has also been reported.^12–15

Several hypotheses on the mechanism of spontaneous regression have been proposed, such as immunological responses, spontaneous apoptosis, hydration effects of cerebrospinal fluid drainage and effects of radiation by diagnostic X-ray, but they are still controversial.¹⁵

Interestingly, melatonin has showed oncostatic and immunomodulatory properties, which should be further investigated.¹⁶ Finally, the role of preoperative corticosteroid therapy has to be considered. In our case, steroids or other drugs were not administered. Ogiwara et al. found that the mean time for tumour regression in their series was 13.6 months, which led them to suggest that the mechanism involved ischemic necrosis and/or apoptosis.^17,18

Funding

This work received no grant from any funding agency in the public, commercial or not-for-profit sectors.

Conflict of Interest

The authors declared no potential conflicts of interest with respect to the research, authorship and/or publication of this article.