Pineal region tumors

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1 Case Series Pineal region tumors Meena Patil, Manjiri Karandikar Abstract The pineal gland is located near the center of the brain, between two hemispheres in between the two thalamic bodies. It is activated by light and controls the various bio-rhythms of the body. It also secretes melatonin a potent regulator of gonadotrophic and other endocrine hormonal activity. It is made of cells, called pineocytes and tumors arise from these cells as also from other cells in the pineal region. Pineal tumors account for 1% of all brain tumors. Tumors of pineal parenchymal lineage include germ cell tumors, embryonal pineoblastoma, the mature pineocytoma, and lesions exhibiting mixed histology or intermediate degree of differentiation. During the period January 2008 to December 2011, we encountered three cases of pineal tumors. A brief summary of these cases is given in this case report. Keywords: Papillary tumor of pineal region, pineal gland, pineoblastoma, pineocytoma Introduction Pineal region tumors are derived from cells located in and around the pineal gland. The principle cell of the pineal gland is the pineal parenchymal cell or pineocyte. This cell is a specialized neuron related to retinal rods and cones. These pineocytes are surrounded by a stroma of fibrillary astrocytes, which interact with adjoining blood vessels to form part of the blood - pial barrier. The cells of the pineal gland are unique in that they are not related to the support cells of the brain (astrocytes, etc.) or to the brain neurons, rather they develop on their own. Therefore, the true pineal cell tumors are quite different from other brain tumors. [1] Pineal region tumors make up % of intracranial tumours in adults and % of brain tumors in children. Most children are aged years at Quick Response Code: Access this article online Website: DOI: / presentation with average age at presentation being 13 years. Adults typically are older than 30 years at presentation. [1] Tumors of the pineal region have a varied histology that can generally be divided into germ cell and non-germ cell derivatives. Most tumors are a result of displaced embryonic tissue, malignant transformation of pineal parenchymal cells, or transformation of surrounding astrocytes. [1] During the period January 2008 to December 2011, three cases of pineal tumors got operated at Bharati Hospital. A brief summary of these cases is given below. Case Report 1 An 8 year female child presented with headache, vomiting, neck pain for 1 month, and diminished vision for 15 days. History of midbrain glioma operated 2 years back was reported. MRI brain showed a well-defined lobulated lesion in posterior third ventricular region beneath the splenium Department of Pathology, Bharati Vidyapeeth Deemed University Medical College, Pune, Maharashtra, India Address for correspondence: Asst. Prof. Meena Patil, Flat no. 8, Surya Appt., Kohinoor colony, Sahakarnagar no. 2, Pune , Maharashtra, India. meenipatil@yahoo.co.in

2 101 and corpus callosum and posteriorly upto midbrain. Lesion was causing compression of distal third ventricle with obstructive hydrocephalus. Differential diagnoses of pineal germinoma and midbrain glioma were offered. Tissue was sent for frozen section. Smears from crush cytology and frozen sections showed predominantly uniform round tumour cells with central prominent nuclei and clumped chromatin. Occasional mitotic figures were noted. Tumor was excised from posterior cranial fossa and sent for histopathology. b a c d e Figure 1: H and E 100 Papillary tumor of pineal region, (a) PTPR Vimentin positive, (b) PTPR S-100 Protein positive, (c) PTPR p53 focal positive, (d) PTPR Low MIB 1 index Histopathology showed a cellular tumor comprised very primitive cells with dense, hyperchromatic and some angulated nuclei with very scanty cytoplasm. The tumor cells show perivascular arrangement. A small component of more differentiated cells forming pineocytomatous rosettes was also seen. Areas of necrosis were also noted. Histopathological diagnosis of Pineal parenchymal tumor of intermediate differentiation with mixed embryonal pineoblastoma and pineocytoma [Figure 3]. Case Report 2 A 25 year female presented with headache, nausea, vomiting for one year, watery discharge from both eyes and intermittent giddiness. Figure 2: Frozen section Toludine blue-pineal parenchymal tumor of intermediate differentiation (PPTID) Sagittal and coronal (T1 weighted magnetic resonance) T1W MR images revealed well defined irregular heterogeneously enhancing lesion in the region of the pineal gland effacing the posterior aspect of the third ventricle and compressing the quadrigeminal plate, without causing hydrocephalus. MRI brain was suggestive of pineal gland tumor or germinoma. Crush cytology smears and frozen sections showed round to oval cells showing monomorphism and absence of mitotic activity. Diagnosis of pineocytoma was offered. The tumor from posterior fossa was removed and sent for histopathology [Figure 2]. March 2015 Vol 20 Issue 1 Figure 3: H and E Pineal parenchymal tumor of intermediate differentiation (PPTID) Histopathology showed a tumor composed of small round cells with central hyperchromatic nuclei and scanty eosinophilic cytoplasm, arranged in sheets Journal of Mahatma Gandhi Institute of Medical Sciences

3 102 separated by thin fibrocollagenous stroma. At places perivascular arrangement was also seen. Few foci of necroinflammation and psammomatous calcification were noted. Histopathological diagnosis was pineal parenchymal tumor of intermediate differentiation (PPTID) [Figure 3]. After 3 years she presented with metastasis in thoracic and lumbosacral spine. Sagittal T1W MR image of thoracic spine and lumbosacral spine revealed multiple lesions of solid nature with cystic areas of varying sizes dispersed throughout the spinal cord, in the intramedullary and subdural space predominantly involving the thoracic spine [Figures 4 and 5]. Patient was managed with chemotherapy and radiotherapy. Case Report 3 A 60 year old female presented with headache and reduced vision for 2 months, urinary incontinence and giddiness for 1 month. History of pineal gland tumor excised 1 year back. MRI brain showed well demarcated mass in pineal region cm 2 with hydrocephalus and areas of hemorrhage and calcification. Ventricles were normal with a shunt in situ. Excised pineal gland tumor was sent for histopathology. perivascular pseudorosettes and distinctive papillary growth pattern. Blood vessels appeared to be covered by multiple layers of tumor cells. Histopathological diagnosis was Papillary tumor of pineal region [Figure 1a]. Immunohistochemistry (IHC) showed strong reactivity for vimentin, S 100 protein, focal positivity for p53, and low MIB 1 index. EMA, CK 8-18, and GFAP, synaptophysin were negative [Figure 1b]. Discussion Tumors of the pineal region (so called pinealomas ) include germ cell tumors, which are the most common lesions in this region, as well as tumors derived from the pineocytes or their precursors. They exhibit a spectrum of differentiation ranging from tumors consisting of primitive undifferentiated cells to those comprised of mature elements. [1] These neoplasms present as solid contrast-enhancing masses associated with manifestations of obstructive hydrocephalus owing to aqueductal compression. Disturbances of ocular motility resulting from pressure on the mesencephalic tectum is another common symptom. [1] Pineal Parenchymal tumor of Intermediate Differentiation [2] These neoplasms occupy a rather broad middle ground between the mature and embryonal extremes. Histopathology showed cellular neoplasm characterized by eosinophilic cells with indistinct cell borders, large pleomorphic nuclei with columnar and cuboidal morphology. They were arranged in Figure 4: Sagittal and coronal T1W MR images revealed well-defined irregular heterogeneously enhancing lesion in the region of the pineal gland effacing the posterior aspect of the third ventricle and compressing the quadrigeminal plate without causing hydrocephalus Figure 5: PPTID-Sagittal T1W MR image of thoracic spine and lumbosacral spine revealed multiple lesions of solid nature with cystic areas of varying sizes dispersed throughout the spinal cord, in the intramedullary and subdural space predominantly involving the thoracic spine

4 103 Clinical behavior of these tumors is variable. One variant is characterized by a neuroendocrine histologic profile in which small tumor cells are segregated into lobules surrounded by a delicate vasculature and a second by a more sheetlike proliferation of neoplastic elements in a scant fibrillary matrix. These pineocytic neoplasms can achieve relatively dense cellularity, occasional evidence of necrosis and may exhibit mitotic activity, but fall short of frank anaplasia and conspicuous proliferative activity that typifies pineoblastomas. Many behave in a relatively low-grade fashion but cerebrospinal fluid (CSF) born metastasis has been documented as an exceptional occurrence. [2] In one of our case metastasis from previous pineal tumor occurred in thoracic and lumbosacral spine after 3 years. Search for any other primary was done but no other primary lesion was found. Papillary Tumor of Pineal Region (PTPR) [3] Papillary tumor of pineal region is thought to arise from the specialized ependyma of the subcommissural organ. This assumption is based on of histomorphological and ultrastructural features, the characteristic anatomic localization in the posterior third ventricular region, and gene expression data. The sub commisural organ is a conserved brain gland present throughout the vertebrate phylum. It is an active secretory structure of brain in a 3-5 month old fetus. However it appears regressed in 9 month old fetus. This regression continues during childhood so that by 9 years of life, it is seen as few islets of cuboidal, nonsecretory ependyma. Papillary tumor of pineal region arises exclusively in the pineal region and occurs most commonly in adults with slight preponderance in females. Headache of short duration is the common presenting system. PTPR is a rare entity described in WHO 2007 classification of brain tumors and assigned a provisional code (ICD O code of 9395/3). In 2003, Jouvet and colleagues reported six cases under the title Papillary tumor of pineal region. These tumors typically present as relatively large, circumscribed mass lesions of the pineal region. Symptoms are typically related to obstructive hydrocephalus secondary to compression of cerebral aqueduct. Progression occurs in almost 75% of patients. Incomplete resection and increase mitotic activity indicate poor prognosis. PTPR is immunoreactive for broad spectrum of cytokeratins including KL1, AE1/AE3, CAM 5.2 and cytokeratin 18. PTPRs have also been reported to express vimentin, S 100 protein, MAP 2, N CAM and transthyretin. Reactivity for GFAP has been reported in approximately 12% of tumor, typically restricted to perivascular areas of tumor. No immunolabelling for neurofilament protein has been reported. Immunohistochemistry (IHC) of our case showed strong reactivity for vimentin, S 100 protein, focal positivity for p53, and low MIB 1 index. EMA, CK 8-18, and GFAP, synaptophysin were negative. The differential diagnosis of PTPR is broad and includes all pineal region lesions with papillary architecture. These include pineal parenchymal tumors, papillary ependymoma and metastases. Unlike PTPR, pineal parenchymal tumors show strong immunoexpression of neuronal markers. Distinction of PTPR from metastatic papillary carcinoma of unknown primary, is based on very low or absent expression of CK7/CK20 and low MIB 1 labelling indices that are characteristic of PTPR. Both PTPR and choroid plexus papilloma express cytokeratins and transthyretin; however most PTPRs show MAP 2 staining and do not express Kir 7.1, which is marker of choroid plexus tumor. Papillary meningioma can be usually excluded easily due to its CK negativity. Papillary tumors of pineal region are characterized by frequent local recurrence as in our case but spinal dissemination is rare Hence it is taken as a grade II/III tumor in WHO classification. [3] Conclusion Pineal gland once thought to be a vestigeal organ is the site of occurrence of a small percentage of intracranial space occupying lesions. Advanced radiologic techniques and stereotactic surgery definitely make the tumors of pineal region more accessible and amenable to treatment. Immunohistochemistry has been helpful in subclassification of pineal region tumors. March 2015 Vol 20 Issue 1 Journal of Mahatma Gandhi Institute of Medical Sciences

5 104 References 1. Bruce JN, Wyler AR. Pineal Tumors. Available from: workup. [Last accessed on 2013 Apr 17]. 2. Rosai J. Neuromuscular system- Central Nervous System: Primary tumors: Pineal parenchymal tumors. In: Rosai and Ackerman s Surgical Pathology- Vol II. 9 th ed. India; Mosby: p Louis DN, Ohgaki H, Wiestler OD, Cavenee WK, Burger PC, Jouvet A, et al. The 2007 WHO classification of tumours of the central nervous system. Acta Neuropathol 2007;114: How to cite this article: Patil M, Karandikar M. Pineal region tumors. J Mahatma Gandhi Inst Med Sci 2015;20: Source of Support: Nil, Conflict of Interest: None declared.

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