Indian Journal of Pathology and Microbiology
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Year : 2019  |  Volume : 62  |  Issue : 3  |  Page : 445-447
Pigmented variant of pleomorphic xanthoastrocytoma - A rare long-term epilepsy associated neoplasm

1 Department of Neuropathology, NIMHANS, Bengaluru, Karnataka, India
2 Department of Neurosurgery, NIMHANS, Bengaluru, Karnataka, India
3 Department of Neuroimaging and Interventional Radiology, NIMHANS, Bengaluru, Karnataka, India

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Date of Web Publication26-Jul-2019


Pleomorphic xanthoastrocytoma (PXA) is an uncommon, long-term epilepsy associated tumor of young adults. Its pigmented variant is exceedingly rare, with only five previously reported cases on record. We report the sixth case of pigmented PXA in a 24-year-old lady presenting with long-standing seizures. The MRI revealed a solid cystic lesion located in the right medial temporal lobe. Histopathologically, the superficially located tumor showed typical features of PXA with melanin-laden astrocytic component and was negative for V600E-mutant BRAF. The histogenesis is discussed.

Keywords: Epilepsy, histopathology, melanin, pleomorphic xanthoastrocytoma, V600E-mutant BRAF

How to cite this article:
Poyuran R, Moudgil N, Arimappamagan A, Bharath RD, Mahadevan A. Pigmented variant of pleomorphic xanthoastrocytoma - A rare long-term epilepsy associated neoplasm. Indian J Pathol Microbiol 2019;62:445-7

How to cite this URL:
Poyuran R, Moudgil N, Arimappamagan A, Bharath RD, Mahadevan A. Pigmented variant of pleomorphic xanthoastrocytoma - A rare long-term epilepsy associated neoplasm. Indian J Pathol Microbiol [serial online] 2019 [cited 2021 Jul 25];62:445-7. Available from: https://www.ijpmonline.org/text.asp?2019/62/3/445/263501

   Introduction Top

Melanin pigment is well-documented in primary/metastatic central nervous system (CNS) melanotic neoplasms, but its presence in astrocytic neoplasms is uncommon. The reports of melanin-containing astrocytomas include a case of pilocytic astrocytoma[1] and 5 cases of pleomorphic xanthoastrocytoma (PXA).[2],[3],[4],[5],[6] A case of ganglioglioma has been reported in which the glial component was in the form of PXA that exhibited pigmentation.[7]

PXA is a WHO grade II neoplasm, typically seen in young individuals with long-standing epilepsy. It has a meningococcal pattern of involvement and is predominantly located in the supratentorial compartment. In spite of its pleomorphic microscopic appearance, mitotic activity is generally low and it has a good prognosis. Pigmented PXA is a rare morphological variant, and to the best of our knowledge, only five cases have been reported in the literature.

   Case History Top

A 24-year-old lady presented with a history of seizures of 12 years duration. The seizure was a complex partial type with secondary generalization. She was on three antiepileptic drugs. On examination, she did not have any neurological deficits. The MRI revealed a right medial temporal solid and cystic lesion with dilation of temporal horn. Clinical suspicion was that of dysembryoplastic neuroepithelial tumor or ganglioglioma. An anterior temporal lobectomy with amygdalohippocampectomy was performed. The temporal lobe on sectioning revealed a single, circumscribed, firm lesion measuring 0.5 cm. The lesion was black in color and superficial in location. The hippocampus measured 2 cm in length and appeared firm and mildly shrunken.

Microscopic examination revealed a superficially placed lesion in the subarachnoid space dipping into the depth of a sulcus and infiltrating the superficial cortical layers. The lesion centrally had a spindle cell component arranged in tight interlacing fascicles. Many of these cells were intensely pigmented with melanin. Admixed with them, cells exhibiting marked nuclear pleomorphism with several giant, multinucleated, and bizarre forms were present. Some of them showed abundant cytoplasm and prominent nucleoli resembling ganglion cells. Along the periphery were xanthomatous cells with abundant foamy cytoplasm. Intranuclear inclusions and eosinophilic granular bodies were present. A rich reticulin network enveloped individual tumor cells. Beneath the lesion, the cortex was thinned out with gliosis rich in Rosenthal fibers. The intracellular pigment in the neoplastic glial cells stained black with Masson-Fontana stain and was bleached by pre-treatment using potassium permanganate. It failed to stain with Perls' Prussian blue method and periodic acid-Schiff and was not acid-fast on Ziehl-Neelsen stain. Mitotic activity was absent. The tumor revealed strong and diffuse positivity of all the cell types with GFAP and S-100. Neuronal markers-synaptophysin and phosphorylated neurofilament were negative. Immunohistochemistry for V600E-mutant BRAF was negative. Ki-67 labeling was low [Figure 1]. NeuN stain revealed disorganization of the laminar architecture in the adjacent compressed cortex, without dysmorphic change. Sections from the hippocampus revealed maintained architecture of dentate gyrus and Ammon's horn without appreciable neuronal loss in the Ammon's horn.
Figure 1: A meningocortical pigmented neoplasm (*in a) composed of pleomorphic spindle cells and multinucleate tumor giant cells with intracytoplasmic brown pigment (b) that is positive with Masson-Fontana stain (c). The tumor has a rich reticulin fiber network (d). The cells are diffusely positive for GFAP with a very low MIB-1 labeling index (f). [a and b: Hematoxylin and Eosin, c: Masson-Fontana, d: Reticulin stain, e and f: Immunoperoxidase. Scale bar: a: 1 mm, b to f: 20 μm]

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A follow-up MRI after 1 year revealed no residual lesion. At 5 years of follow-up, the patient remained seizure free and had no neurological deficits.

   Discussion Top

PXA account for less than 1% of astrocytic neoplasms.[8] Although typically seen in children and young adults, they can be encountered in elderly too. The reported age of occurrence ranges from 5 to 82 years (mean age: 26 years).[9] Seizures are the most common presentation (71%), which are usually long standing. About 98% of PXA are supratentorial in location with a predilection for temporal lobe and involve the meninges and the cerebral cortex.[9]

Microscopically, PXA is composed of pleomorphic spindle cells arranged in fascicles admixed with large, bi, and multinucleate giant astrocytic and xanthomatous cells. Eosinophilic granular bodies are a constant feature, and intranuclear inclusions and lymphocytic infiltration are frequently seen. The characteristic feature is the presence of rich reticulin network that surrounds individual tumor cells. The mitotic activity is generally low.[8] Majority of PXA exhibit BRAFV600E mutation by immunohistochemistry and/or molecular genetics testing (65%) and are negative for R132H-mutant IDH1.[10] The tumor described here was, however, negative for BRAFV600E mutation by immunohistochemistry.

Our case had the typical clinical and pathological features of PXA with the unusual presence of pigment in the tumor cells. The pigment was characterized as melanin as it stained with Masson-Fontana stain, bleached by potassium permanganate pretreatment, and remained unlabelled with PAS and Perls' Prussian blue stains.

Five cases of pigmented PXA have been reported in the literature[2],[3],[4],[5],[6] and are summarized in [Table 1]. Three of them were localized in the temporal lobe[2],[3],[6] and one each in the suprasellar region[4] and brainstem.[5] All the cases in the temporal lobe presented with seizures.
Table 1: Comparison of the reported cases of pigmented pleomorphic xanthoastrocytoma

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Pigments encountered in the nervous system include melanin, neuromelanin, and lipofuscin. Neuromelanin, a product of auto-oxidation of catecholamine precursors, is seen in the neurons of substantia nigra and locus coeruleus. Lipofuscin, a “wear and tear” pigment derived from oxidation of lipids or lipoprotein, is found in the neurons in precentral gyrus, cranial nerves nuclei, red nucleus, thalamus, globus pallidus, inferior olivary, and dentate nucleus. Neuromelanin and lipofuscin are closely linked histochemically. Experimentally, they are found to be interconvertible, and neuromelanin is thought to be a melanized form of lipofuscin.[11]

Neural crest in the trunk region gives rise to melanocytes, neurons, and glia. The cells that leave the crest early migrate ventrally and become neurons and glia and those that leave late follow a dorsolateral pathway to become melanocytes.[12] Henion and Weston in their study demonstrated that neurogenic (forming neuron-glial or fate-restricted neuronal precursors) and melanogenic (forming glial-melanocyte or fate-restricted melanocyte precursors) sublineages separate almost immediately after the start of migration from the crest. The separation of melanocyte and glial fates occurs later.[13] In addition, Schwann cells have been shown to dedifferentiated to a glia/melanocyte precursor in vitro.[14] Hence, there is evidence that glial and melanocytic cells are developmentally interlinked and this could explain the presence of melanin pigments in glial neoplasms.

PXA has a good prognosis with a recurrence-free survival rate of 70.9% at 5 years and an overall survival rate of 90.4% at 5 years. Cases with BRAF V600E mutation have been found to have significantly longer overall survival than those without the mutation.[10] Presence of pigment does not seem to alter the clinical behavior as all the cases of pigmented PXA fared well on follow-up. Our case has remained asymptomatic and seizure free for 5 years after the surgery.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

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Conflicts of interest

There are no conflicts of interest.

   References Top

Vajtai I, Yonekawa Y, Schäuble B, Paulus W. Melanotic astrocytoma. Acta Neuropathol 1996;91:549-53.  Back to cited text no. 1
Kanzawa T, Takahashi H, Hayano M, Mori S, Shimbo Y, Kitazawa T. Melanotic cerebral astrocytoma: Case report and literature review. Acta Neuropathol 1997;93:200-4.  Back to cited text no. 2
Sharma MC, Arora R, Khanna N, Singh VP, Sarkar C. Pigmented pleomorphic xanthoastrocytoma. Report of a rare case with review of the literature. Arch Pathol Lab Med 2001;125:808-11.  Back to cited text no. 3
Krossnes BK, Mella O, Wester K, Mørk SJ. Pigmented astrocytoma with suprasellar location: Case report and literature review. Acta Neuropathol 2004;108:461-6.  Back to cited text no. 4
Chapman EM, Ranger A, Lee DH, Hammond RR. A 15 year old boy with a posterior fossa tumor. Brain Pathol 2009;19:349-52.  Back to cited text no. 5
Xiong J, Chu SG, Mao Y, Wang Y. Pigmented pleomorphic xanthoastrocytoma: A rare variant and literature review. Neuropathology 2011;31:88-92.  Back to cited text no. 6
Soffer D, Lach B, Constantini S. Melanotic cerebral ganglioglioma: Evidence for melanogenesis in neoplastic astrocytes. Acta Neuropathol 1992;83:315-23.  Back to cited text no. 7
Giannini C, Paulus W, Louis DN, Liberski P, Figarella-Branger D, Capper D. Pleomorphic xanthoastrocytoma. In: Louis DN, Ohgaki H, Wiestler OD, Cavenee WK, editors. WHO Classification of Tumors of the Central Nervous System. Revised 4th ed. Lyon: IARC Press; 2016. p. 94-7.  Back to cited text no. 8
Giannini C, Scheithauer BW, Burger PC, Brat DJ, Wollan PC, Lach B, et al. Pleomorphic xanthoastrocytoma. What Do We Really Know about It? Cancer 1999;85:2033-45.  Back to cited text no. 9
Ida CM, Rodriguez FJ, Burger PC, Caron AA, Jenkins SM, Spears GM, et al. Pleomorphic xanthoastrocytoma: Natural history and long-term follow-up. Brain Pathol 2015;25:575-86.  Back to cited text no. 10
Barden H. The histochemical relationship of neuromelanin and lipofuscin. J Neuropathol Exp Neurol 1969;28:419-41.  Back to cited text no. 11
Erickson CA, Goins TL. Avian neural crest cells can migrate in the dorsolateral path only if they are specified as melanocytes. Development 1995;121:915-24.  Back to cited text no. 12
Henion PD, Weston JA. Timing and pattern of cell fate restrictions in the neural crest lineage. Development 1997;124:4351-9.  Back to cited text no. 13
Dupin E, Real C, Glavieux-Pardanaud C, Vaigot P, Le Douarin NM. Reversal of developmental restrictions in neural crest lineages: Transition from Schwann cells to glial-melanocytic precursors in vitro. Proc Natl Acad Sci 2003;100:5229-33.  Back to cited text no. 14

Correspondence Address:
Anita Mahadevan
Department of Neuropathology, NIMHANS, Bangalore - 560 029, Karnataka
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/IJPM.IJPM_723_18

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