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|NI FEATURE: PATHOLOGY PANORAMA - CASE REPORT
|Year : 2015 | Volume
| Issue : 4 | Page : 567-570
Papillary tumor of the pineal region-report of three cases with literature review
Debajyoti Chatterjee1, Kirti Gupta1, Narendra Kumar2, Rajesh Chhabra3, Bishan Dass Radotra1
1 Department of Histopathology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
2 Department of Radiotherapy, Postgraduate Institute of Medical Education and Research, Chandigarh, India
3 Department of Neurosurgery, Postgraduate Institute of Medical Education and Research, Chandigarh, India
|Date of Web Publication||4-Aug-2015|
Bishan Dass Radotra
Department of Histopathology, Postgraduate Institute of Medical Education and Research, Chandigarh
Source of Support: None, Conflict of Interest: None
Papillary tumor of the pineal region (PTPR) is a rare tumor of the pineal region. Not much is known about the pathogenesis, prognosis, and treatment protocol of this uncommon entity. We present three cases of PTPR with follow-up from 8 months to 98 months. All patients presented with headache and visual disturbance. One patient also had amenorrhea. Radiology revealed an heterogeneously enhancing mass arising from the pineal region with associated hydrocephalus. Histopathologically, all cases showed the papillary architecture, strong pan cytokeratin and cytokeratin 18 positivity, and faint positivity for synaptophysin and neuron-specific enolase. All cases received postoperative radiotherapy. One case showed tumor recurrence after 7 years. Other two cases did not show any recurrence till the last follow-up.
Keywords: Cytokeratin; papillary tumor of the pineal region; pineal gland
|How to cite this article:|
Chatterjee D, Gupta K, Kumar N, Chhabra R, Radotra BD. Papillary tumor of the pineal region-report of three cases with literature review. Neurol India 2015;63:567-70
| » Introduction|| |
Papillary tumor of the pineal region (PTPR) is a relatively uncommon tumor of the pineal gland, and less than 70 cases have been reported in literature so far. This entity was initially described by Jouvet et al., in 2003.  PTPR was introduced in World Health Organization (WHO) classification of brain tumors in 2007 following which it is being diagnosed more frequently as its awareness among pathologists has increased.  The exact behavior of this tumor is not well-known due to the limited information available and the rarity of the entity. Here, we present three more cases of PTPR with a clinical follow-up to add more information to the existing knowledge about this uncommon condition.
| » Case report|| |
An 18-year-old female patient presented with headache, blurring of vision, and amenorrhea for 2 months. There was no other sensory or motor disturbance. Magnetic resonance imaging (MRI) of the brain showed a hypointense 15 mm × 15 mm, solid tumor in the pineal region without contrast enhancement. The tumor was biopsied and diagnosed as a pineocytoma. The patient was given 45 Gy radiation in 25 fractions and remained asymptomatic for 2 years but then was lost to follow-up. She again presented with headache and visual disturbance 7 years after the initial surgery. Repeat MRI brain showed a solid 34 mm × 24 mm mass in the pineal region with similar radiological features [Figure 1]a and b. A repeat biopsy revealed a moderately cellular tumor arranged in prominent perivascular and papillary arrangement [Figure 1]c. The tumor cells were oval to elongated, showing moderate nuclear pleomorphism [Figure 1]d with small foci of necrosis and frequent mitotic activity (7-8 per 10 high power fields). There was no pineocytomatous rosettes or neuropil in the background. The tumor cells showed strong cytoplasmic positivity for pan cytokeratin (CK) [Figure 1]e and CK18, and faint cytoplasmic positivity for vimentin, synaptophysin, neuron-specific enolase (NSE), and nuclear positivity for S-100. The tumor cells did not express glial fibrillary acidic protein (GFAP), epithelial membrane antigen (EMA), thyroid transcription factor-1 (TTF-1), and chromogranin A. The histological diagnosis was PTPR, as per the WHO, 2007 criteria. The previous biopsy was reviewed which showed similar features. The patient received radiotherapy again using the same dosage schedule. At 14 months of follow-up after the second surgery, the patient has shown improvement of vision, and there is no new recurrence.
|Figure 1: (a and b) Magnetic resonance imaging brain of case 1 showing a heterogeneously contrast enhancing mass arising in the pineal region with associated hydrocephalus. (c) Photomicrograph showing a tumor with papillary pattern with a fibrovascular core (H and E, ×100); (d) higher magnification of the same area showing moderate nuclear pleomorphism and frequent mitotic activity [arrow], (H and E, ×400), (e) the tumor cells showing strong positivity for pan cytokeratin (IP, ×400)|
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A 30-year-old female patient presented with headache, gait disturbance, and difficulty in walking for 3 months. She also complained of visual disturbance for the last 2 months. MRI brain showed a solid 28 mm × 27 mm mass arising from the pineal gland. A subtotal excision was performed. On histology, the tumor showed a predominant perivascular and papillary arrangement with multilayering of tumor cells around the fibrovascular core [Figure 2]a. At places, the solid pattern was also present. The tumor cells were oval to elongated with monomorphic nuclei containing vesicular chromatin. Mitosis was <1 per 10 high power fields. There was no necrosis, but tumor cells infiltrated the adjacent brain parenchyma. The tumor cells were strongly and diffusely positive for pancytokeratin and CK18 [Figure 2]b, focally positive for vimentin, synaptophysin, NSE and S-100, and negative for GFAP and TTF-1. Ki-67 proliferative index was 2%. Following a diagnosis of PTPR, the patient received 45 Gy of radiotherapy in 25 fractions. The patient showed symptomatic improvement and there was no recurrence at a follow-up of 30 months.
|Figure 2: (a) Photomicrograph of case 2 showing a prominent papillary pattern with uniform nuclei (H and E, ×100); (b) The tumor cells show strong cytokeratin 18 positivity and multilayering around the fibrovascular core (IP, ×400); (c and d) T1W postcontrast image shows a heterogeneous enhancing lesion seen in the posterior third ventricle involving the pineal region abutting and compressing the tectal plate (case 3); (e) Photomicrograph of the same case showing a papillary tumor with hyalinized core and moderate nuclear atypia (H and E, ×200)|
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A 50-year-old man presented with headache and gait disturbance for a period of 2 months. There was no sensory deficit. MRI brain showed a 30 mm × 28 mm heterogeneously enhancing solid-cystic mass arising from the pineal region, which projected into the third ventricle [Figure 2]c and d. A ventriculoperitoneal shunt was performed, and a small biopsy was taken from the mass which showed a tumor with papillary configuration. The multilayered tumor cells around a fibrovascular core showed moderate nuclear atypia and occasional mitosis [Figure 2]e. The tumor cells focally expressed pancytokeratin, CK18, vimentin, S-100, and synaptophysin but were negative for GFAP, neurofilament protein (NFP), and NSE. A diagnosis of PTPR was made. The patient received radiotherapy in the same dose as mentioned above for the second patient. At follow-up after 8 months, the tumor had reduced in size and there was symptomatic improvement without recurrence.
| » Discussion|| |
Papillary tumor of the pineal region (PTPR) is a rare tumor with limited available information on it. PTPR is characterized by papillary configuration with multiple-layered neoplastic cells with pan CK (particularly keratin 18) and CAM5.2 expression. They may show variable positivity for synaptophysin, NSE, chromogranin, vimentin, transthyretin, and S-100.  Focal and faint GFAP and EMA positivity can be observed while they are negative for NFP. Other tumors in the third ventricular region with papillary configuration are papillary ependymoma and choroid plexus papilloma. An ependymoma shows the characteristic GFAP and dot like EMA positivity. A choroid plexus papilloma morphologically resembles the normal choroid plexus and shows a single layer of monomorphic cuboidal to columnar cells lining the fibrovascular core. Choroid plexus tumors show immunoreactivity for Kir7.1 and stanniocalcin-1 while PTPR is negative. These markers may be helpful to differentiate these two conditions. However, these could not be performed due to unavailability of the antibodies. A papillary meningioma may be another rare neoplasm in this location which shows pseudopapillae with EMA and vimentin expression by tumor cells but these cells are CK negative. The exact origin of PTPR remains doubtful. They probably do not arise from the pineal gland. Based on the ultrastructural analysis, it is proposed that the cells of origin are the specialized ependymal cells of the subcommissural organ.  Recently, Goschzik et al., have described PTEN mutation and activation of PI3K/Akt/M tor pathway in the pathogenesis of PTPR.  On imaging, PTPR appears as a heterogeneously enhancing mass arising in the pineal region. The lesion is usually solid, but may show a variable cystic component. Although there are no pathognomonic imaging features of PTPR, they usually show characteristic hyperintensity in T1W imaging.  It is difficult to distinguish PTPR from other pineal parenchymal tumors based on imaging findings, and hence a tissue diagnosis is essential.
There are genuine difficulties in diagnosing a PTPR, even though the morphology is quite distinctive. It may be difficult to appreciate the papillary pattern especially in a small biopsy. Interestingly, a pineocytoma can also show perivascular arrangement and formation of pseudopapillae and therefore, it is mandatory to perform immunohistochemistry including pan-CK or CAM5.2 or CK18, synaptophysin, and NSE to distinguish between a pineocytoma and PTPR, as the prognosis of these two conditions varies. A strong synaptophysin, NFP and NSE expression, and negative CK staining favors a pineocytoma, whereas a strong positivity for pancytokeratin/CAM5.2 or CK18 with a variable expression of synaptophysin and NSE establishes a diagnosis of PTPR. In a stereotactic biopsy, the tissue may not be sufficient to perform a complete panel, so a judicious panel of immunostains including pancytokeratin, CK18/CAM5.2, synaptophysin, GFAP, and Kir7.1 can help in resolving the diagnostic dilemma in most cases. Two biopsies in our series (case 1 and 3) were stereotactic, with a limited tissue for evaluation; we could still perform a reasonably extensive panel of immunohistochemistry. In all of our cases, the tumor cells were positive for pancytokeratin and CK18, thus confirming them to be PTPR (CAM5.2 could not be performed as the antibody was not available). The lack of awareness about this relatively uncommon condition is also a reason for the under-diagnosis of PTPR. In our first case, the initial biopsy was performed before the WHO 2007 classification of brain tumors, and therefore, it was diagnosed as a pineocytoma.
According to the 2007 WHO classification, no grading has been assigned to PTPR. It behaves like a Grade II or Grade III tumor, although the exact histological criterion remains to be defined.  This tumor usually does not show a high mitotic activity (usually 0-10/10 HPF), and its relevance in the tumor grading or outcome has not yet been determined. A PTPR with a MIB index of 15-20% recurred within 6 months, whereas another PTPR with a MIB index of 13.1% did not show any recurrence at 2 years follow-up. , In our first patient, the tumor showed a high mitotic activity and recurred after 7 years. PTPR is characterized by frequent local recurrence despite surgery and radiation therapy.  In a large multicentric study, increased mitosis and MIB index were found to be the best predictors of tumor recurrence whereas pleomorphism was considered as a degenerative change. , An occasional case of metastatic PTPR is also reported in the literature.  A retrospective review of 31 cases of PTPR revealed the 5-year estimate of an overall and progression-free survival as 73% and 27%, respectively.  No standard therapeutic guideline for PTPR has been established as yet because of the small number of reported cases in literature. A combination of surgery and radiotherapy with or without chemotherapy is used. Radiotherapy has been described as an effective modality for the treatment for PTPR as surgical excision is often difficult due to the critical location of the tumor. A recent study has described that gross total excision of the tumor and a younger age are associated with a better overall survival (OS), whereas chemotherapy and radiotherapy have no significant effects on the OS. 
| » Conclusion|| |
Although PTPR is a rare tumor, it is being recognized more commonly because of an increased awareness among neuropathologists who now include it in the differential diagnoses of tumors of the pineal region. More information is required through larger series to determine the prognosis and standard treatment protocol of this rare entity.
| » References|| |
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[Figure 1], [Figure 2]
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