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Year : 2017  |  Volume : 60  |  Issue : 2  |  Page : 247-249
Primary leptomeningeal primitive neuroectodermal tumor: A difficult entity to diagnose

1 Department of Neurology, Medanta - The Medicity Hospital, Gurgaon, Haryana, India
2 Department of Neurology, The Institute of Neurological Sciences, Care Hospital, Hyderabad, Telangana, India
3 Department of Neurosurgery, The Institute of Neurological Sciences, Care Hospital, Hyderabad, Telangana, India
4 Department of Pathology, Nizam's Institute of Medical Sciences, Hyderabad, Telangana, India

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Date of Web Publication19-Jun-2017


A 25-year-old male presented with difficulty in walking, loss of vision, and seizures. A clinical possibility of craniospinal meningeal pathology was considered. On computed tomography (CT) scan and magnetic resonance imaging, there was an enhancement of leptomeninges with few ring-enhancing lesions in both frontal lobes and right frontoparietal region. He was evaluated for low backache and occipital headache 2½ years earlier and was found to have communicating hydrocephalus on CT scan. He underwent ventriculoperitoneal shunt and was followed up with CT scans. Meningeal biopsy was done in the present admission, and there was a diffusely infiltrating small round cell tumor. Immunohistochemistry was done, and the tumor cells were found to be negative for glial, mesenchymal, melanotic, and lymphoid markers. The cells were positive for neuron-specific enolase, chromogranin, and vimentin. A diagnosis of primitive neuroectodermal tumor involving the meninges was made. A possibility of primary leptomeningeal tumor extending to parenchyma was considered based on the clinical progression. Patient was treated with chemotherapy and radiotherapy. He improved partially and was stable at 3-year follow-up.

Keywords: Central nervous system, embryonal tumor, leptomeningeal tumor, primitive neuroectodermal tumor

How to cite this article:
Sehgal J, Jagarlapudi MM, Tenneti MV, Basha SA, Challa S. Primary leptomeningeal primitive neuroectodermal tumor: A difficult entity to diagnose. Indian J Pathol Microbiol 2017;60:247-9

How to cite this URL:
Sehgal J, Jagarlapudi MM, Tenneti MV, Basha SA, Challa S. Primary leptomeningeal primitive neuroectodermal tumor: A difficult entity to diagnose. Indian J Pathol Microbiol [serial online] 2017 [cited 2022 Aug 16];60:247-9. Available from: https://www.ijpmonline.org/text.asp?2017/60/2/247/208376

   Introduction Top

Primitive neuroectodermal tumors (PNETs) of central nervous system (CNS) are rare and occur predominantly in children and adolescents and characterized by early onset and aggressive clinical course. They may arise in the cerebral hemispheres, brainstem, and spinal cord.[1] Leptomeningeal dissemination of CNS PNETs is a common complication, but primary leptomeningeal PNET in the absence of parenchymal solid tumor is extremely rare [2],[3],[4],[5] and hence this report.

   Case Report Top

A 25-year-old male presented in our hospital with a past history of localized, nonradiating low backache and episodes of occipital headache for 2½ years. After 6 months of initial symptoms, he had developed visual obscuration which used to get relief following vomiting. He was brought to the emergency department, then for altered mental state of 1-day duration and computed tomography (CT) had shown communicating hydrocephalus. He underwent ventriculoperitoneal shunt. Cerebrospinal fluid (CSF) analysis, biochemistry, and cell count were essentially normal. During follow-up, with CT scans, he had needed repeated shunt revision. CSF analysis during the last admission for shunt revision showed twenty cells (all lymphocytes), proteins 35 mg/dl, sugar 45 mg/dl, and adenosine deaminase 3U/L (normal 0–6 U/L). Polymerase chain reaction (PCR) for tuberculosis (TB) was twice negative. For the next 2 years, he did well except for poor scholastic performance.

He presented to our hospital with a history of progressive difficulty in walking for 6 months, loss of vision in both eyes for 2 months, recurrent tonic–clonic seizures for 15 days, and urinary retention for 3 days. He was empirically started on anti-TB treatment. On examination, he was emaciated, afebrile, and normotensive. Systemic examination revealed no lymphadenopathy or organomegaly. Neurologic examination revealed mini–Mental Status Examination 23/30 and impaired immediate recall, no perception of light in both eyes, bilateral optic atrophy, right ptosis, impaired left adduction, and downbeat nystagmus. Motor system examination revealed hypotonia of all four limbs, generalized wasting, motor power 4+/5 in both upper limbs and 2/5 in both lower limbs, elicitable deep tendon reflexes in both the upper limbs, and bilaterally upgoing plantar response. There was suspended sensory hyperesthesia over T2–T6 segments and impaired vibration sense below T6 segment. A diagnostic possibility of craniospinal meningeal pathology was considered.

Complete blood picture and blood biochemistry were normal. Erythrocyte sedimentation rate was 50 mm in 1st hour. Ultrasound examination of the abdomen was essentially normal with no organomegaly. Chest X-ray and two-dimensional echo were normal. Serum angiotensin-converting enzyme levels were normal. Serum venereal disease research laboratory test was nonreactive, and CSF TB-PCR was negative.

CT and magnetic resonance imaging (MRI) showed focal lesions in the right frontoparietal lobes. The lesions were iso- to hypo-intense on T1-weighted and hyperintense on T2-weighted (T2W) images with no restriction on diffusion-weighted image. Gadolinium contrast study showed enhancement of pachy meninges in the right frontoparietal region with small ring-enhancing lesion in the left frontal lobe. One of the lesions in the right parietal lobe showed solid component within. There was effacement of cortical sulci, perilesional edema, and compression of the right lateral ventricle. MRI dorsal spine revealed multiple focal hyperintense lesions on T2W in the spinal cord suggesting drop metastasis. Lumbar puncture was a dry tap.

Meningeal biopsy was done. Histopathology showed multiple fragments of densely fibrotic tissue diffusely infiltrated by small round cells with scant cytoplasm and vesicular nuclei [Figure 1]a-c]. The cells were diffusely infiltrating with no acini or rosettes. There were frequent mitoses and apoptotic bodies. Immunohistochemistry with antibodies (Dako, USA) for leukocyte common antigen, CD10, CD3, CD20, pan Cytokeratin, epithelial membrane antigen, CD99, synaptophysin, neurofilament, S100, glial fibrillary acidic protein, desmin, myogenin, and vimentin were negative. Neuron-specific enolase and chromogranin were strongly positive in the cytoplasm of the tumor cells. Ki-67 labeling index was 20% [Figure 1]d-i]. A diagnosis of supratentorial PNET (embryonal tumor), WHO grade IV, with diffuse leptomeningeal involvement and drop metastases was made. A possibility of primary leptomeningeal tumor extending to parenchyma was considered based on the clinical progression. Molecular studies for differentiating into central and peripheral types could not be performed. Patient received craniospinal radiotherapy and six cycles of chemotherapy with vincristine, cyclophosphamide, and carboplatin. Patient recovered partially, was able to walk, but vision did not improve. He was doing well at 3-year follow-up and subsequently was lost for follow-up.
Figure 1: (a) Meninges infiltrated by small round cells (H and E, ×10). (b) Sheets of undifferentiated small round cells with scant cytoplasm and hyperchromatic nuclei (H and E, ×40). (c) Atypical mitosis and karyorrhectic debris (H and E, ×40). Tumor cells are immunohistochemically negative for (d) GFAP (e) synaptophysin (f) CD99 (×100). Immunohistochemically positive for (g) NSE (h) chromogranin (i) Ki-67 labeling index 20% ×100

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   Discussion Top

Primary leptomeningeal PNETs show two patterns; diffuse involvement of the cranial and spinal leptomeninges in the absence of a primary intraparenchymal or meningeal tumor or a localized dural-based mass mimicking meningiomas.[6],[7] This patient had a diffuse involvement of cranial leptomeninges with drop metastases and no dural-based mass on CT and MRI at the time of diagnosis. There was no evidence of meningeal or parenchymal lesion at evaluation 2½ years earlier and during the follow-up with CT scans. Ebinger et al. opined that leptomeningeal enhancement in PNET was an early manifestation of the disease, and long-term identification of a tumor is possible on repeat scans, if the life expectancy of the patient allowed it.[3] Multiple investigations done initially in our patient were noncontributory, and the extensive desmoplasia resulting in dry lumbar tap led to delay in diagnosis. Similar difficulties in diagnosis were reported earlier.[8]

CNS-PNETs are called central PNETs and differ from peripheral PNETs of Ewing's sarcoma/PNET group of tumors by characteristic immunohistochemical and molecular genetic features.[6],[9] Immunohistochemically, CD99 expression is considered highly sensitive though not specific for peripheral PNET, whereas central PNETs are negative for CD99.[9] The IHC pattern in our patient was in favor of neuroblastoma.[9] CNS PNETs showing only neuronal differentiation are termed CNS neuroblastoma.[1] Cytogenetic and molecular genetic studies could not be done in our patient. In the 2016 WHO classification of tumors of CNS, the term PNET was removed, and a category of CNS embryonal tumor, not otherwise specified, was created that includes tumors previously designated as CNS PNET.[10]

Leptomeningeal PNETs have an aggressive clinical course though long clinical course in up to 45%–60% in peripheral PNETs has been reported.[2],[5],[7] Long-term survival is reported to be uncommon in central PNETs.[2],[4] Characterization of leptomeningeal PNETs by molecular genetics in addition to IHC is recommended to optimize therapy.[4],[6] Our patient had delayed diagnosis after 2½ years, received radiotherapy and adjuvant chemotherapy, and recovered partially and doing well at 3-year follow-up.

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   References Top

McLendon RE, Judkins AR, Eberhart CG, Fuller GN, Sarkar C, Ng HK. Central nervous system primitive neuroectodermal tumours. In: Louis DN, Ohgaki H, Wiestler OD, Cavenee WK, editors. WHO Classification of Tumours of the Central Nervous System. 4th ed. Lyon: IARC; 2007. p. 141-6.  Back to cited text no. 1
Dirks PB, Harris L, Hoffman HJ, Humphreys RP, Drake JM, Rutka JT. Supratentorial primitive neuroectodermal tumors in children. J Neurooncol 1996;29:75-84.  Back to cited text no. 2
Ebinger F, Brühl K, Gutjahr P. Early diffuse leptomeningeal primitive neuroectodermal tumors can escape detection by magnetic resonance imaging. Childs Nerv Syst 2000;16:398-401.  Back to cited text no. 3
Kalidindi N, Torres CH, Michaud J, Zwicker JC. Primitive neuroectodermal tumor presenting with diffuse leptomeningeal involvement in a 55-year-old woman: A case report and brief summary of current diagnostic tests and treatment. Case Rep Oncol 2014;7:471-7.  Back to cited text no. 4
Maher OM, Sandberg DI, Kannan G, McGovern S, Ketonen L, Khatua S, et al. Primary leptomeningeal primitive neuroectodermaltumor. Neuro Oncol 2014;16 Suppl 5:VI30.  Back to cited text no. 5
Antunes NL, Lellouch-Tubiana A, Kalifa C, Delattre O, Pierre-Kahn A, Rosenblum MK. Intracranial Ewing sarcoma/'peripheral' primitive neuroectodermal tumor of dural origin with molecular genetic confirmation. J Neurooncol 2001;51:51-6.  Back to cited text no. 6
Dedeurwaerdere F, Giannini C, Sciot R, Rubin BP, Perilongo G, Borghi L, et al. Primary peripheral PNET/Ewing's sarcoma of the dura: A clinicopathologic entity distinct from central PNET. Mod Pathol 2002;15:673-8.  Back to cited text no. 7
Robertson PL, Muraszko KM, Blaivas M, Brunberg JA. Leptomeningeal fibrosis and the delayed diagnosis of a central nervous system neoplasm (primitive neuroectodermal tumor). Pediatr Neurol 1997;16:74-8.  Back to cited text no. 8
Bahrami A, Truong LD, Ro JY. Undifferentiated tumor: True identity by immunohistochemistry. Arch Pathol Lab Med 2008;132:326-48.  Back to cited text no. 9
Louis DN, Perry A, Reifenberger G, von Deimling A, Figarella-Branger D, Cavenee WK, et al. The 2016 World Health Organization classification of tumors of the central nervous system: A summary. Acta Neuropathol 2016;131:803-20.  Back to cited text no. 10

Correspondence Address:
Sundaram Challa
Department of Pathology, Nizam's Institute of Medical Sciences, Hyderabad - 500 082, Telangana
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0377-4929.208376

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