Neurology India, Vol. 59, No. 3, May-June, 2011, pp. 455-460
Papillary tumor of pineal region: Report of three cases and review of literature
Sridhar Epari1, Reeta Bashyal1, Suman Malick2, Tejpal Gupta2, Aliasgar Moyadi3, SV Kane1, Munita Bal1, Rakesh Jalali2
1 Department of Pathology, Tata Memorial Centre, Mumbai, India
Correspondence Address: Sridhar Epari Department of Pathology, Dr. Ernest Borges Road, Tata Memorial Hospital, Mumbai - 400 012 India firstname.lastname@example.org
Date of Submission: 13-Mar-2011
Code Number: ni11130
AbstractPapillary tumors of the pineal region (PTPRs) are rare and are recognized as a distinct entity in the recent 2007 World Health Organization (WHO) classification of tumors of nervous system. Till date, only 55 cases have been reported. We report another three patients of PTPRs with characteristic radiological features. Histologically, all the three patients exhibited remarkable uniform histology of epithelioid morphology with variable presence of single to multilayered papillary architecture. Consistent absence of fibrillary matrix was noted in all the three cases. None of the cases showed aggressive histology. A large multicenter study is essential for upfront characterizing the biological behavior, as frequency of these tumors is very low.
Keywords: Fibrillary matrix, papillary architecture, papillary tumors of the pineal region
Papillary tumors of the pineal region (PTPRs) are rare and are recognized as a distinct entity in the recent 2007 World Health Organization (WHO) classification of tumors of nervous system.  These tumors occur both in children and adults with a mean age of 32 years and can be relatively large pineal lesions with size ranging from 2.5 to 4 cm in the greatest dimension. On magnetic resonance imaging (MRI), PTPRs are hypointense in T1-weighted (T1W) sequence and hyperintense in T2-weighted (T2W) sequence and enhance with contrast. Based on the immunophenotypic and ultrastructural findings, it has been postulated that PTPRs arise from the specialized ependymocytes of the subcommissural organ located in the lining of the posterior commissure and show ependymal differentiation.  Histologic features and immunohistochemical staining distinguish this type of papillary tumor from other papillary-like tumors that occur in this region. ,,,,, Biologically, most of the lesions can be categorized as WHO grade II; however, a few cases may have aggressive behavior (WHO grade III). Because of limited number of reported cases with aggressive behavior, precise histological grading criteria remain yet to be defined. To date, a total of only 55 cases have been reported in the English literature and we report an additional three cases.
A 39-year-old male presented with giddiness, heaviness of eye movement and headache of 3 months duration. Magnetic resonance imaging (MRI) revealed solid and cystic pineal gland lesion measuring 1.1 x 0.8 x 0.8 cm with associated obstructive hydrocephalus. It was hypointense in T1W and T2W images and showed contrast enhancement [Figure - 1]a. A gross total resection was performed. Histological examination revealed a tumor composed of papillae of heterogeneous appearance, composed of single to multilayers lined by relative monomorphous population of polygonal tumor cells with moderate amount of clear and esoinophilic cytoplasm [Figure - 1]b-e. Mitotic activity and necrosis were not seen. No fibrillary matrix was seen. The tumor was immunoreactive [Table - 1] for vimentin [Figure - 1]f, p53 [Figure - 1]i, Bcl-2 [Figure - 1]j, S-100 protein [Figure - 1]k, focally for cytokeratin (CK) [Figure - 1]g and glial fibrillary acidic protein (GFAP) [Figure - 1]l, while it was negative for epithelial membrane antigen (EMA) [Figure - 1]n, neuron specific enolase (NSE) [Figure - 1]h and synaptophysin [Figure - 1]m. MIB-1 labeling index (LI) was 2-4% [Figure - 1]o in the highest proliferating areas. Three months post-surgery MRI revealed no residual tumor and resolution of the hydrocephalus. At that point of time, due to lack of much literature on this entity and an intermediate MIB-1 LI, a decision was taken to irradiate. Subsequently, local radiation of 54 Gy in 30 fractions was given and the patient is on regular follow-up with periodic imaging for the last 4.5 years, with no recurrences.
A 37-year-old female presented with repeated recurrent convulsions, headache and diplopia of 2 months duration. MRI revealed a solid cystic pineal gland space-occupying lesion measuring 3.2 x 2.7 x 2.5 cm with associated obstructive hydrocephalus. It was hypointense in T1W and T2W images and showed contrast enhancement [Figure - 2]a. Gross total resection was performed. Histologically, the tumor was composed of polygonal cells (epithelioid morphology) arranged in solid sheets interspersed with tubular and single to multilayered papillary architecture. The predominant population of tumor cells showed esoinophilic cytoplasm and few cells were clear with the presence of distinct cytoplasmic membrane [Figure - 2]b-e. Mitotic activity and necrosis were not seen. No fibrillary matrix was seen. The tumor cells were immunoreactive [Table - 2] for vimentin [Figure - 2]f, p53-moderate intensity [Figure - 2]i, Bcl-2 [Figure - 2]j, S-100 protein [Figure - 2]k and focally for CK [Figure - 2]g, while they were negative for EMA [Figure - 2]n, NSE [Figure - 2]h, synaptophysin [Figure - 2]m and GFAP [Figure - 2]l. MIB-1 LI was 1-2% in the highest proliferating areas [Figure - 2]o. Postoperative MRI revealed no residual tumor and hydrocephalus and a decision to observe was taken in the joint neurooncology group meeting. The patient has been on regular follow-up with periodic imaging since then, i.e. 2.5 years, with uneventful course. No recurrences have been noted.
A 43-year-old male presented with giddiness and headache on and off of 3 months duration. In addition, he developed diminished vision and hearing on the right side. MRI revealed solid cystic pineal gland space-occupying lesion measuring 2.2 x 2.2 x 1.9 cm with associated obstructive hydrocephalus. The lesion was hypointense in T1W and T2W images and showed contrast enhancement [Figure - 3]a. Gross total resection was achieved. Histologically, the tumor was composed of polygonal shaped tumor cells arranged predominantly in nests, sheets and papillae. The tumor cells showed clear to eosinophilic cytoplasm. Areas of loose edematous stroma separating nests were noted [Figure - 3]b-e. Occasional mitosis was noted. Necrosis and microvascular proliferation were not seen. No fibrillary matrix was seen. Tumor cells were immunoreactive [Table - 3] for vimentin [Figure - 3]f, p53 (moderate intensity) [Figure - 3]i, Bcl-2 [Figure - 3]j, S-100 protein [Figure - 3]k and NSE [Figure - 3]h, while they were negative for EMA [Figure - 3]n, synaptophysin [Figure - 3]m, GFAP [Figure - 3]l and CK [Figure - 3]g. MIB-1 LI was 1-2% in the highest proliferating areas. Though no aggressive histological features were seen, in view of relative more areas of enhancement coupled with lack of known precise histological grading criteria for this entity at that time, Joint Neuro-oncology group (JNOG) decided to give radiation. The patient was subsequently treated with local radiation of 54 Gy in 30 fractions. Post surgery and radiation MRI on follow-up revealed no residual tumor and complete resolution of the hydrocephalus. Presently, the patient is on regular, 6 monthly follow-up and is recurrence free since the last 18 months.
Papillary tumors of the pineal region are a distinct entity, but rare. These tumors can occur across wide age range,  but mostly they occur from third to fifth decade. ,, There is remarkable histologic and radiological uniformity in all the reported patients, as seen in this series. ,,,,,, Characteristic radiological features include: Solid and cystic tumor, T1W and T2W hypointensity, contrast enhancement, and presence of associated hydrocephalus. Pathological features include the consistent presence (at least focally) of papillary architecture with epithelial-like or epithelioid morphology of tumor cells and lack of fibrillary matrix. The latter feature is distinct from pineal parenchymal tumors and ependymomas. PTPRs, like ependymomas, show epithelioid morphology and variable immunoreactivity for epithelial markers. In the present series, two cases showed focal positivity for cytokeratin (CK) and none showed reactivity for EMA. This inconsistent immunoreactivity for epithelial markers was also highlighted by Hasselblatt et al. Of the six cases studied, one showed typical dot-like positivity for EMA. All the six cases studied by Jouvet et al. showed very weak positivity for EMA. Thus, highlighting the fact that epithelial-like or epithelioid morphology coupled with immunoreactivity for at least one of the epithelial markers is more characteristic rather than depending on any one feature. Similar to the findings in the series by the Jouvet et al., the cases in the present series showed variable reactivity for S-100 protein and negativity for GFAP and synaptophysin. However, most of the cases reported in the literature ,,, showed reactivity for synaptophysin and variable reactivity for GFAP and S-100 protein. These variable observations emphasize the inconsistent glial and neuronal differentiation in these tumors. Occasional cases reported to show Bcl-2 expression associated with high MIB-1 LI (13%),  but all the three cases in the present series showed nuclear immunoreactivity for p53 protein and cytoplasmic reactivity for Bcl-2 without any association with significant higher levels of Mib-1 LI and adverse biological behavior, raising the possibility of the role of p53 protein and anti-apoptotic mechanisms in the tumorigenesis. Fevre-Montange et al. reported a series of 31 cases, wherein most cases showed local recurrences, while in the present series no recurrences were noted though the follow-up period was variable between 16 months and 4.5 years. Two of three patients who received radiation after surgery did not show any different course from the other patient who had not received any radiation, suggesting the inadvertent use of the same in the two cases, when there is no histological suggestion. The requirement of radiation after gross total resection in PTPRs with no aggressive histology needs to be addressed in a larger randomized study.
Dr. Atul Goel and his team of Kind Edwards Memorial Hospital, Mumbai for contributing the cases.
Copyright 2011 - Neurology India
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