5 aminolevulinic acid fluorescence guided resection of spinal tumor

Multiple studies have attempted to evaluate the utility of 5-ALA-aided resection of spinal neoplasms.

Wainwright et al., from the Westchester Medical CenterTohoku University Hospital, reviewed the existing literature on the use of 5-ALA and PpIXfluorescence as an aid to resection of primary and secondary spinal neoplasms by searching the PUBMED and EMBASE database for records up to March 2018. Data was abstracted from all studies describing spinal neurosurgical uses in the English language.

In the reviewed studies, the most useful fluorescence was observed in meningiomas, ependymomas, drop metastases from cerebral gliomas, and spinal hemangiopericytoma, which is consistent with applications in cerebral neoplasms.

The available literature is significantly limited by a lack of standardized methods for measurement and quantification of 5-ALA fluorescence. The results of the reviewed studies should guide future development of rational trial protocols for the use of 5-ALA guided resection in spinal neoplasms1).


Three hours before the induction of anesthesia, 5-ALA was administered to patients with different intra- and extradural spinal tumors. In all patients a neurosurgical resection or biopsy of the spinal tumor was performed under conventional white-light microscopy. During each surgery, the presence of Protoporphyrin IX fluorescence was additionally assessed using a modified neurosurgical microscope. At the end of an assumed gross-total resection (GTR) under white-light microscopy, a final inspection of the surgical cavity of fluorescing intramedullary tumors was performed to look for any remaining fluorescing foci. Histopathological tumor diagnosis was established according to the current WHO classification.

Fifty-two patients with 55 spinal tumors were included in this study. Resection was performed in 50 of 55 cases, whereas 5 of 55 cases underwent biopsy. Gross-total resection was achieved in 37 cases, STR in 5, and partial resection in 8 cases. Protoporphyrin IX fluorescence was visible in 30 (55%) of 55 cases, but not in 25 (45%) of 55 cases. Positive PpIX fluorescence was mainly detected in ependymomas (12 of 12), meningiomas (12 of 12), hemangiopericytomas (3 of 3), and in drop metastases of primary CNS tumors (2 of 2). In contrast, none of the neurinomas (8 of 8), carcinoma metastases (5 of 5), and primary spinal gliomas (3 of 3; 1 pilocytic astrocytoma, 1 WHO Grade II astrocytoma, 1 WHO Grade III anaplastic oligoastrocytoma) revealed PpIX fluorescence. It is notable that residual fluorescing tumor foci were detected and subsequently resected in 4 of 8 intramedullary ependymomas despite assumed GTR under white-light microscopy.

In this study, 5-ALA-PpIX fluorescence was observed in spinal tumors, especially ependymomas, meningiomas, hemangiopericytomas, and drop metastases of primary CNS tumors. In cases of intramedullary tumors, 5-ALA-induced PpIX fluorescence is a useful tool for the detection of potential residual tumor foci 2).


A study included 10 patients who underwent surgical resection of an intramedullary ependymoma. Nine patients were orally administered 5-ALA (20 mg/kg) 2 hours before the induction of anesthesia. 5-ALA fluorescence was visualized with an operating microscope. Tumors were removed in a standardized manner with electrophysiological monitoring. The extent of resection was evaluated on the basis of intraoperative findings and postoperative magnetic resonance imaging. Histopathological diagnosis was established according to World Health Organization 2007 criteria. Cell proliferation was assessed by Ki-67 labeling index.

5-ALA fluorescence was positive in 7 patients (6 grade II and 1 grade III) and negative in 2 patients (grade II). Intraoperative findings were dichotomized: Tumors covered by the cyst were easily separated from the normal parenchyma, whereas tumors without the cyst appeared to be continuous to the spinal cord. In these cases, 5-ALA fluorescence was especially valuable in delineating the ventral and cranial and caudal margins. Ki-67 labeling index was significantly higher in 5-ALA-positive cases compared with 5-ALA-negative cases. All patients improved neurologically or stabilized after surgery.

5-ALA fluorescence was useful for detecting tumor margins during surgery for intramedullary ependymoma. When combined with electrophysiological monitoring, fluorescence-guided resection could help to achieve maximum tumor resection safely 3).

References

1)

Wainwright JV, Endo T, Cooper JB, Tominaga T, Schmidt MH. The role of 5-aminolevulinic acid in spinal tumor surgery: a review. J Neurooncol. 2018 Dec 29. doi: 10.1007/s11060-018-03080-0. [Epub ahead of print] Review. PubMed PMID: 30594965.
2)

Millesi M, Kiesel B, Woehrer A, Hainfellner JA, Novak K, Martínez-Moreno M, Wolfsberger S, Knosp E, Widhalm G. Analysis of 5-aminolevulinic acid-induced fluorescence in 55 different spinal tumors. Neurosurg Focus. 2014 Feb;36(2):E11. doi: 10.3171/2013.12.FOCUS13485. PubMed PMID: 24484249.
3)

Inoue T, Endo T, Nagamatsu K, Watanabe M, Tominaga T. 5-aminolevulinic acid fluorescence-guided resection of intramedullary ependymoma: report of 9 cases. Neurosurgery. 2013 Jun;72(2 Suppl Operative):ons159-68; discussion ons168. doi: 10.1227/NEU.0b013e31827bc7a3. PubMed PMID: 23149963.

Spinal primitive neuroectodermal tumor

Epidemiology

Primary spinal primitive neuroectodermal tumor (PNET) of the central nervous system has a low incidence. The intraspinal case is very rare. Around 30 cases have been reported so far 1).

Outcome

Spinal PNETs, like their cranial counterparts, are aggressive tumors and patients with these tumors typically have short survival times despite maximal surgery, chemotherapy, and radiation. Because no standard management guidelines exist for treating these tumors, a multitude of therapeutic strategies have been employed with varying success 2)

Case series

Ma et al. from the Beijing Tiantan Hospital summarized the cases of primary spinal PNET available in the database of the institute, either intramedullary or extramedullary cases. Then they did literature review of the same disease.

There were eight cases of primary spinal PNET available in there database, with one intramedullary case and seven extramedullary cases. Surgical resection was performed. The histology diagnosis was PNET. Peri-operative image examinations of the whole central nervous system (CNS) were performed to exclude tumors other than spinal cord origin. Then during literature review, 33 reports of the disease were included. The pre-operative diagnosis rate was low. The disease had a high recurrence rate and poor prognosis given available treatment 3).

Case reports

A 14-year-old teenage girl had suffered from progressive left upper back pain with bilateral lower legs weakness and numbness for 1 year. After treatment, left neck mass was noted 3 years later.

Initially, magnetic resonance imaging (MRI) showed neurogenic tumor involving intradural extramedullary space of T5-T10. Pathology report showed PNET (World Health Organization grade IV) featuring lobules of neoplastic cells with round regular nuclei, high nucleus-to-cytoplasm ratio, and fibrillary cytoplasm. At the time of tumor recurrence, chest MRI then showed recurrent tumor at T2-T3 level of the epidural space with right neural foramina invasion. Brain MRI showed extensive bilateral calvarial metastases and leptomeningeal metastases in the right frontoparietal regions. Bone scan showed multiple bone metastases.

T-spine tumor removal and adjuvant radiotherapy (RT) to T-spine tumor bed were performed in the initial treatment. After clinical tumor recurrence, tumor removal was done again. She then received chemotherapy followed by whole brain irradiation with hippocampal sparing with 35 gray in 20 fractions.

After treatment, follow-up images showed that the disease was under control. There was no neurological sequela. She has survived more than 7 years from diagnosis and more than 4 years from recurrence to date 4).


A 5-year-old Moroccan boy, who presented with torticollis for 1 month. Computed tomography scan and Magnetic resonance imaging of the cervical spine revealed an extradural, dumbbell-shaped mass with extra-spinal extension at the left C1-C6 level. Multiple biopsy specimens were obtained. Histological examination revealed a highly cellular neoplasm composed of diffuse sheets of tumor cells having monomorphic, round to oval, finely vesicular nuclei. Immunohistochemical findings confirmed the diagnosis of intraspinal peripheral primitive neuroectodermal tumor.

After this illustrative case, they reviewed the literature on clinicopathological and therapeutic aspects. In practice, it is important to consider the diagnosis of peripheral primitive neuroectodermal tumor in children and adolescents with an apparent soft-tissue mass located in the spine 5).


A 60-year-old female, which presented clinically as an intraspinal tumor, causing symptoms of lower back pain, numbness and pain in the right lower extremity. The patient underwent tumorectomy. Following primary therapy, the symptoms of spinal cord compression were relieved. The patient underwent several courses of radiotherapy following surgery but refused to continue with chemotherapy. After a further four months, the tumors recurred and the patient succumbed to the disease 6).


A two years old female child presented with weakness both lower limbs. Preoperative MRI of the spine and paravertebral regionIso – hyper intense posterior placed extradural lesion, non contrast enhancing from D11-L2 levels with cord compression D9 to L3 laminectomy done. Granulation tissue found from D11 to L2. with cord compression. The granulation tissue removed in toto. The pathological findings were consistent with PNET. Post operative neurological improvement was minimal. Cranial screening ruled out any intracranialtumour. Hence a diagnosis of primary spinal PNET was made. A review of the literature shows that only 19 cases of primary intraspinal PNETs have been reported to date and the present case extradural in location. Primary intraspinal PNETs are rare tumors and carry a poor prognosis 7).


Multimodal therapy of an intramedullary cervical primitive neuroectodermal tumor in an adult. 8).


A 22-year-old woman with history of severe progressive neck pain, without radiation, associated with paresthesia in the right arm, and palpable right posterior cervical mass. Neurological examination showed increased reflexes in all four limbs, bilateral Hoffman’s sign, right Babinski’s sign, and right hemi-hypoesthesia. Neuroimaging revealed a right posterior cervical lesion with heterogeneous contrast enhancement extending to the neural foramina of the atlas and axis. Patient underwent microsurgical removal of the lesion, and histopathological and immunohistochemical analysis confirmed the diagnosis of peripheral primitive PNET (pPNET). The patient had adjuvant treatment with radiotherapy and chemotherapy. After twelve months, neuroimaging showed no signs of tumor regrowth and the patient had no neurological deficits. However, three months later, the patient developed hydrocephalus and cerebrospinal fluid (CSF) was positive for neoplastic cells. No other treatment was administered and the patient died.

pPNET is a rare malignant tumor with poor prognosis, although promising results with multimodal treatment-surgery, radiotherapy, and chemotherapy. Diagnosis requires immunohistochemical analysis, with identification of neuronal differentiation markers 9).


A 18-year-old female with conus intramedullary tumor diagnosed to be primary spinal primitive neuroectodermal tumor following histopathological examination after surgery 10).


A female who presented at age 21 with diffuse involvement of the lower spinal cord. After biopsy and successful treatment with radiation and chemotherapy, she recurred 10 years later with disease in her cerebellum. She was reinduced with chemotherapy and subsequently received high-dose chemotherapy with autologous stem cell support. She is alive and free of disease 11 years after her initial presentation. This represents the longest survival ever documented for a primary spinal PNET 11).


A 15-year-old girl who presented with gradual onset, over 1 month, of upper back pain and bilateral lower leg weakness. A thoracic spine MRI showed a dumbbell-shaped epidural mass at T2-4 with right paraspinal and posterior mediastinal extension. Surgical resection of the epidural tumor for decompression was performed. The pathologic examination revealed a PNET. Primary spinal PNETs typically have a poor prognosis and optimal therapy has not yet been defined. Surgical resection, with the combination of chemo-radiotherapy or radiotherapy, leads to better outcomes. However, primary epidural PNETs may be classified as a subtype of spinal PNETs because they are free from intrathecal invasion. For these patients, surgery alone and surgery combined with radiotherapy or chemo-radiotherapy remain controversial. Our patient received surgery alone and, 1y ear later, has experienced no local recurrence within the epidural space but the mediastinal part of the tumor has enlarged 12).


A 45-year-old man with a peripheral primitive neuroectodermal tumour arising in the cervical spine. Alexander et al., believed this to be the first report of this type of tumour in the cervical spine 13).


A 25-year-old male patient presented with an extremely rare primary spinal peripheral primitive neuroectodermal tumor (pPNET) manifesting as acutely progressive paraparesis and back pain. Neuroimaging and intraoperative examination showed that the tumor was confined to the epidural space of the thoracic spine. The patient was treated successfully by gross total resection of the tumor followed by chemotherapy and local radiotherapy. The present case illustrates the unexpected occurrence and important differential diagnosis of primary epidural pPNET of the thoracic spine in young patients presenting with progressive paraparesis and back pain 14).


A 29-year-old male with a dumbbell-shaped pPNET at the T9-10 spine level, including details of his examination, surgical procedures applied, histological and genetic findings, and his subsequent treatment. They discussed the clinical course, the pathology and treatment for this disease, the surgical approach to thoracic dumbbell tumors and reviewed the literature. This is the first report of a case of a dumbbell-shaped intradural and spinal peripheral PNET 15).


A 54-year-old woman who presented with quadriplegia and bladder and bowel dysfunction. The patient had suffered symptoms of neck pain for 1 month and left shoulder weakness for 10 days. Magnetic resonance imaging of the cervical spine revealed an intramedullary mass extending from C-2 to C-5 with an exophytic component in the adjacent left subarachnoid space. Multiple biopsy specimens were obtained, and a partial excision was performed. Histological examination revealed nodular growth and neuronal differentiation, with a striking resemblance to desmoplastic medulloblastoma. A positron emission tomography scan did not reveal uptake at any site. These findings confirmed the diagnosis of a primary intramedullary PNET. Postoperatively, the patient was given craniospinal radiotherapy with a radiation boost to the tumor bed 16).

References

1) , 3)

Ma J, Ma S, Yang J, Jia G, Jia W. Primary spinal primitive neuroectodermal tumor: A single center series with literature review. J Spinal Cord Med. 2018 Dec 18:1-9. doi: 10.1080/10790268.2018.1547862. [Epub ahead of print] PubMed PMID: 30561250.
2)

Ellis JA, Rothrock RJ, Moise G, McCormick PC 2nd, Tanji K, Canoll P, Kaiser MG, McCormick PC. Primitive neuroectodermal tumors of the spine: a comprehensive review with illustrative clinical cases. Neurosurg Focus. 2011 Jan;30(1):E1. doi: 10.3171/2010.10.FOCUS10217. Review. PubMed PMID: 21194274.
4)

Chen F, Chiou SS, Lin SF, Lieu AS, Chen YT, Huang CJ. Recurrent spinal primitive neuroectodermal tumor with brain and bone metastases: A case report. Medicine (Baltimore). 2017 Nov;96(46):e8658. doi: 10.1097/MD.0000000000008658. PubMed PMID: 29145292; PubMed Central PMCID: PMC5704837.
5)

Khmou M, Malihy A, Lamalmi N, Rouas L, Alhamany Z. Peripheral primitive neuroectodermal tumors of the spine: a case report and review of the literature. BMC Res Notes. 2016 Sep 9;9(1):438. doi: 10.1186/s13104-016-2246-5. Review. PubMed PMID: 27613377; PubMed Central PMCID: PMC5016941.
6)

Meng XT, He SS. Primitive neuroectodermal tumor in the spinal canal: A case report. Oncol Lett. 2015 Apr;9(4):1934-1936. Epub 2015 Jan 27. PubMed PMID: 25789071; PubMed Central PMCID: PMC4356409.
7)

Venkataraman S, Pandian C, Kumar SA. Primary spinal primitive neuroectodermal tumour – a case report. Ann Neurosci. 2013 Apr;20(2):80-2. doi: 10.5214/ans.0972.7531.200211. PubMed PMID: 25206019; PubMed Central PMCID: PMC4117112.
8)

Coumans JV, Walcott BP, Nahed BV, Oh KS, Chi AS. Multimodal therapy of an intramedullary cervical primitive neuroectodermal tumor in an adult. J Clin Oncol. 2012 Jan 10;30(2):e15-8. doi: 10.1200/JCO.2011.38.6474. Epub 2011 Dec 5. PubMed PMID: 22147740.
9)

Cabral GA, Nunes CF, Melo JO Jr, Guimarães RD, Gonçalves MB, Rodrigues RS, Correa JL, Teixeira OM Jr, Klescoski J Jr, Lapenta MA, Landeiro JA. Peripheral primitive neuroectodermal tumor of the cervical spine. Surg Neurol Int. 2012;3:91. doi: 10.4103/2152-7806.99938. Epub 2012 Aug 21. PubMed PMID: 23050205; PubMed Central PMCID: PMC3463148.
10)

Harbhajanka A, Jain M, Kapoor SK. Primary spinal intramedullary primitive neuroectodermal tumor. J Pediatr Neurosci. 2012 Jan;7(1):67-9. doi: 10.4103/1817-1745.97631. PubMed PMID: 22837786; PubMed Central PMCID: PMC3401662.
11)

Gollard RP, Rosen L, Anson J, Mason J, Khoury J. Intramedullary PNET of the spine: long-term survival after combined modality therapy and subsequent relapse. J Pediatr Hematol Oncol. 2011 Mar;33(2):107-12. doi: 10.1097/MPH.0b013e3181f84b7f. PubMed PMID: 21228722.
12)

Chang SI, Tsai MC, Tsai MD. An unusual primitive neuroectodermal tumor in the thoracic epidural space. J Clin Neurosci. 2010 Feb;17(2):261-3. doi: 10.1016/j.jocn.2009.05.018. Epub 2009 Dec 29. PubMed PMID: 20036552.
13)

Alexander HS, Koleda C, Hunn MK. Peripheral Primitive Neuroectodermal Tumour (pPNET) in the cervical spine. J Clin Neurosci. 2010 Feb;17(2):259-61. doi: 10.1016/j.jocn.2009.05.020. Epub 2009 Dec 29. PubMed PMID: 20036553.
14)

Kiatsoontorn K, Takami T, Ichinose T, Chokyu I, Tsuyuguchi N, Ohsawa M, Ohata K. Primary epidural peripheral primitive neuroectodermal tumor of the thoracic spine. Neurol Med Chir (Tokyo). 2009 Nov;49(11):542-5. PubMed PMID: 19940407.
15)

Hrabálek L, Kalita O, Svebisova H, Ehrmann J Jr, Hajduch M, Trojanec R, Kala M. Dumbbell-shaped peripheral primitive neuroectodermal tumor of the spine–case report and review of the literature. J Neurooncol. 2009 Apr;92(2):211-7. doi: 10.1007/s11060-008-9744-9. Epub 2008 Dec 3. Review. PubMed PMID: 19050994.
16)

Jain A, Jalali R, Nadkarni TD, Sharma S. Primary intramedullary primitive neuroectodermal tumor of the cervical spinal cord. Case report. J Neurosurg Spine. 2006 Jun;4(6):497-502. PubMed PMID: 16776362.

AOSpine Advanced Seminar—Tumor, Infection, Metabolic and Inflammatory Disorders of the Thoracolumbar Spine

AOSpine Advanced Seminar—Tumor, Infection, Metabolic and Inflammatory Disorders of the Thoracolumbar Spine

November 2 — November 3

Vilnius, Lithuania

More Information

UpToDate: Pediatric intracranial tumor

Pediatric intracranial tumor

Epidemiology

Malignant brain tumors are not uncommon in infants as their occurrence before the age of three represents 20-25% of all malignant brain tumors in childhood.

The location of brain tumors in very young children differs from the posterior fossa predominance of older children. This is especially true in the first 6– 12 months of life, where supratentorial location is signicantly more common.

Approximately 20% of pediatric intracranial tumors arise from the thalamus or brainstem, with an incidence rate of 5% and 15%, respectively.

Medulloblastoma is the most common malignant pediatric intracranial tumor.

Diffuse intrinsic pontine glioma account for 10% to 25% of pediatric intracranial tumor.

Diagnosis

Bächli et al., from the Heidelberg University Hospital, Germany, report a single-institutional collection of pediatric brain tumor cases that underwent a refinement or a change of diagnosis after completion of molecular diagnostics that affected clinical decision-making including the application of molecularly informed targeted therapies. 13 pediatric central nervous system tumors were analyzed by conventional histology, immunohistochemistry, and molecular diagnostics including DNA methylation profiling in 12 cases, DNA sequencing in 8 cases and RNA sequencing in 3 cases. 3 tumors had a refinement of diagnosis upon molecular testing, and 6 tumors underwent a change of diagnosis. Targeted therapy was initiated in 5 cases. An underlying cancer predisposition syndrome was detected in 5 cases. Although this case series, retrospectiveand not population based, has its limitations, insight can be gained regarding precision of diagnosis and clinical management of the patients in selected cases. Accuracy of diagnosis was improved in the cases presented here by the addition of molecular diagnostics, impacting clinical management of affected patients, both in the first-line as well as in the follow-up setting. This additional information may support the clinical decision making in the treatment of challenging pediatric CNS tumors. Prospective testing of the clinical value of molecular diagnostics is currently underway 1).

Treatment

Malignant brain tumors represent a true therapeutic challenge in neurooncology. Before the era of modern imaging and modern neurosurgery these malignant brain tumors were misdiagnosed or could not benefit of the surgical procedures as well as older children because of increased risks in this age group.

The pediatric oncologists are more often confronted with very young children who need a complementary treatment. Before the development of specific approaches for this age group, these children received the same kind of treatment than the older children did, but their survival and quality of life were significantly worse. The reasons of these poor results were probably due in part to the fear of late effects induced by radiation therapy, leading to decrease the necessary doses of irradiation which increased treatment failures without avoiding treatment related complications.

At the end of the 80s, pilot studies were performed using postoperative chemotherapy in young medulloblastoma patients. Van Eys treated 12 selected children with medulloblastoma with MOPP regimen and without irradiation; 8 of them were reported to be long term survivors.

Subsequently, the pediatric oncology cooperative groups studies have designed therapeutic trials for very young children with malignant brain tumors.

Different approaches have been explored: * Prolonged postoperative chemotherapy and delayed irradiation as designed in the POG (Pediatric Oncology Group). * Postoperative chemotherapy without irradiation in the SFOP (Société Française d’Oncologie Pédiatrique) and in the GPO (German Pediatric Oncology) studies. *

The role of high-dose chemotherapy with autologous stem cells transplantation was explored in different ways: High-dose chemotherapy given in all patients as proposed in the Head Start protocol. High-dose chemotherapy given in relapsing patients as salvage treatment in the French strategy. In the earliest trials, the same therapy was applied to all histological types of malignant brain tumors and whatever the initial extension of the disease. This attitude was justified by the complexity of the classification of all brain tumors that has evolved over the past few decades leading to discrepancy between the diagnosis of different pathologists for a same tumor specimen. Furthermore, it has become increasingly obvious that the biology of brain tumors in very young children is different from that seen in older children. However, in the analysis of these trials an effort was made to give the results for each histological groups, according to the WHO classification and after a central review of the tumor specimens. All these collected data have brought to an increased knowledge of infantile malignant brain tumors in terms of diagnosis, prognostic factors and response to chemotherapy. Furthermore a large effort was made to study long term side effects as endocrinopathies, cognitive deficits, cosmetic alterations and finally quality of life in long term survivors. Prospective study of sequelae can bring information on the impact of the different factors as hydrocephalus, location of the tumor, surgical complications, chemotherapy toxicity and irradiation modalities. With these informations it is now possible to design therapeutic trials devoted to each histological types, adapted to pronostic factors and more accurate treatment to decrease long term sequelae 2).

Complications

Case series

1)

Bächli H, Ecker J, van Tilburg C, Sturm D, Selt F, Sahm F, Koelsche C, Grund K, Sutter C, Pietsch T, Witt H, Herold-Mende C, von Deimling A, Jones D, Pfister S, Witt O, Milde T. Molecular Diagnostics in Pediatric Brain Tumors: Impact on Diagnosis and Clinical Decision-Making – A Selected Case Series. Klin Padiatr. 2018 Jul 11. doi: 10.1055/a-0637-9653. [Epub ahead of print] PubMed PMID: 29996150.
2)

Kalifa C, Grill J. The therapy of infantile malignant brain tumors: current status? J Neurooncol. 2005 Dec;75(3):279-85. Review. PubMed PMID: 16195802.

Papillary tumor of the pineal region

Papillary tumor of the pineal region

The WHO 2007 definition of Papillary tumor of the pineal region (PTPR) is as follows: – “A rare neuroepithelial tumor of the pineal region in adults, characterized by papillary architecture and epithelial cytology, immunopositivity for cytokeratin and ultra structural features suggesting ependymal differentiation.“ 1).
First described by Jouvet et al., in 2003 who reported six cases and called it “Papillary Tumor of Pineal region.” The tumor’s clinicopathological characteristics as described and illustrated in that series were very similar to the description of some entities reported by neuropathologists from different parts of the world. Many more independent case reports were published after Jouvet et al.’s initial report 2).


Various other names, like papillary pineocytoma, pineal parenchymal tumor, choroid plexus tumor, ependymoma and papillary meningioma have been given to these tumors in earlier reports 3).
They arise from specialized ependymocytes in the subcommissural organ, which is located in the pineal region. Characterized by papillary architecture and epithelial cytology, immunopositivity for cytokeratin and ependymal differentiation. It is considered grade II-III by the World Health Organization.
A review of the literature was performed to collect all the cases published with gross total resection and no complementary treatment. In conclusion, there is still much to be learned about the pathogenesisprognosis and management of this tumor. 4).

Epidemiology

Papillary tumor of pineal region (PTPR) arises exclusively in the pineal region and occurs most commonly in adults with slight preponderance in females.
Till 2008, about 64 cases of PTPR have been reported 5)

Clinical

The clinical behavior is often aggressive. Headache of short duration is the common presenting symptom. This occurs due to increased intracranial tension as a result of compression of the aqueduct.

Diagnosis

They may also have a cystic component. CT imaging shows their hypodense nature and enhancement with contrast. MRI demonstrates hypointensity in T1-weighted (T1W) sequence and hyperintensity in T2-weighted (T2W) sequence and enhance with contrast 6).

Treatment

Limited reports suggest surgical resection is the mainstay of treatment
The findings suggest that radiotherapy provides durable local control, particularly when administered in the adjuvant setting after GTR 7).

Case series

Little is known about the prognostic markers that might aid to identify patients at increased risk for recurrence. Therefore, the prognostic value of histopathologic and clinical features was examined in a series of 21 patients. Median age of the 12 male and 9 female patients was 35 years (range, 10 to 56 y). On histopathologic examination, all tumors were characterized by loose papillary structures and tumor cells forming broad perivascular pseudorosettes showing cytokeratin expression. In addition, tumors showed increased cellularity (n=4; 19%), nuclear pleomorphism (n=4; 19%), solid growth (n=11; 52%), necrosis (n=8; 38%), increased mitotic activity (≥3 mitoses per 10 high-power fields [n=10; 48%]), and increased proliferation (Ki67/MIB1 index ≥10% [n=8/20; 40%]). Gross total resection could be achieved in 13/21 patients (62%). Postoperatively, 13 patients received radiotherapy and 4 patients chemotherapy. Median recurrence-free survival was 66 months in 19 patients, for whom detailed follow-up information was available. Twelve patients (63%) experienced tumor progression. Three patients (16%) died of disease. Among the clinical and histopathologic features examined, only increased mitotic activity (52 [8 to 96] vs. 68 [66 to 70] mo [median [95% confidence interval]]) and proliferative activity (29 [0 to 64] vs. 67 [44 to 90] mo) were significantly associated with recurrence (P<0.05). Tumors of the 3 patients who had succumbed to disease showed increased mitotic and proliferative activity.
Increased mitotic and proliferative activities are associated with worse prognosis in papillary tumors of the pineal region 8).

Case reports

A 34-year-old male with headaches, blurred vision and normal examination. Radiological study showed a nodulocystic lesion in the pineal region compatible with pineocytoma. Surgery was performed using an infratentorial supracerebellar approach, finding a cystic tumor in the quadrigeminal cistern which was completely resected. Histopathology reported a papillary tumor of the pineal region. The patient made good progress without adjuvant therapy, and after 57 months of follow-up he remained asymptomatic and free of recurrence 9).
1)

Kleihues P, Cavenee WK. Pathology and Genetics of Tumours of Nervous System, No. 21. Geneva: World health Organization; 1979. World Health Organization Classification of Tumors. Lyon: IARC Press; 2000.
2)

Jouvet A, Fauchon F, Liberski P, Saint-Pierre G, Didier-Bazes M, Heitzmann A, Delisle MB, Biassette HA, Vincent S, Mikol J, Streichenberger N, Ahboucha S, Brisson C, Belin MF, Fèvre-Montange M. Papillary tumor of the pineal region. Am J Surg Pathol. 2003 Apr;27(4):505-12. PubMed PMID: 12657936.
3)

Roncaroli F, Scheithauer BW. Papillary tumor of the pineal region and spindle cell oncocytoma of the pituitary: new tumor entities in the 2007 WHO Classification. Brain Pathol. 2007 Jul;17(3):314-8. PubMed PMID: 17598824.
4) , 9)

Cañizares Méndez MA, Amosa Delgado M, Álvarez Salgado JA, Villaseñor Ledezma JJ, Capilla Cabezuelo E, Díaz Crespo F. Papillary tumor of the pineal region: Case report and review of the literature. Neurocirugia (Astur). 2018 Apr 21. pii: S1130-1473(18)30029-0. doi: 10.1016/j.neucir.2018.03.003. [Epub ahead of print] English, Spanish. PubMed PMID: 29691144.
5)

Fuller GN. The increasing diversity of Pineal and Sellar region tumors, Americal Association Of Neuropathologists USCAP Companion Society Inaugral Meeting Denver, CO. 2008
6)

Epari S, Bashyal R, Malick S, Gupta T, Moyadi A, Kane SV, Bal M, Jalali R. Papillary tumor of pineal region: report of three cases and review of literature. Neurol India. 2011 May-Jun;59(3):455-60. doi: 10.4103/0028-3886.82773. PubMed PMID: 21743183.
7)

Edson MA, Fuller GN, Allen PK, Levine NB, Ghia AJ, Mahajan A, Brown PD, DeMonte F, Li J. Outcomes After Surgery and Radiotherapy for Papillary Tumor of the Pineal Region. World Neurosurg. 2015 Mar 5. pii: S1878-8750(15)00184-9. doi: 10.1016/j.wneu.2015.02.031. [Epub ahead of print] PubMed PMID: 25749579.
8)

Heim S, Beschorner R, Mittelbronn M, Keyvani K, Riemenschneider MJ, Vajtai I, Hartmann C, Acker T, Blümcke I, Paulus W, Hasselblatt M. Increased mitotic and proliferative activity are associated with worse prognosis in papillary tumors of the pineal region. Am J Surg Pathol. 2014 Jan;38(1):106-10. doi: 10.1097/PAS.0b013e31829e492d. PubMed PMID: 24121176.

Update: Multinodular and vacuolating neuronal tumor of the cerebrum

Multinodular and vacuolating neuronal tumor of the cerebrum

Multinodular and vacuolating neuronal tumors of the cerebrum (MVNT) are superficial neuronal tumors in adults that were first documented in 2013 1)
It is a new pattern of neuronal tumour included in the World Health Organization Classification of Tumors of the Central Nervous System 2016, as a unique cytoarchitectural pattern of gangliocytoma.
There are fifteen reports in the literature to date. They are typically associated with late onset epilepsy.
Clinical, pathological and genetic data could indicate that MVNT aligns more with a malformative lesion than a true neoplasm with origin from a progenitor neuro-glial cell type showing aberrant maturation 2).

Differential diagnosis

Dysembryoplastic neuroepithelial tumor – DNET can appear similar but usually is mostly cortical (rather than subcortical) often has bright FLAIR rim focal cortical dysplasia (Type II) high T2 signal deep to cortex is in the same location but is usually associated with a radial glial band (transmantle sign) and with thickened abnormal overlying cortex perivascular spaces location can be similar usually more elongated along vessel long axis fully attenuating on FLAIR 3).

Treatment

MVNTs appear to be benign tumours with very indolent biological behaviour which can, if asymptomatic, be followed with imaging alone. In symptomatic patients (epileptic) surgical resection often controls seizures, with no tumour regrowth reported 4) 5) 6) 7).

Case series

2017

Thom et al. present a series of ten cases and compare their pathological and genetic features to better characterised epilepsy associated malformations including focal cortical dysplasia type II (FCDII) and low-grade epilepsy associated tumours (LEAT). Clinical and neuroradiology data were reviewed and a broad immunohistochemistry panel was applied to explore neuronal and glial differentiation, interneuronal populations, mTOR pathway activation and neurodegenerative changes. Next generation sequencing was performed for targeted multi-gene analysis to identify mutations common to epilepsy lesions including FCDII and LEAT. All of the surgical cases in this series presented with seizures, and were located in the temporal lobe. There was a lack of any progressive changes on serial pre-operative MRI and a mean age at surgery of 45 years. The vacuolated cells of the lesion expressed mature neuronal markers (neurofilament/SMI32, MAP2, synaptophysin). Prominent labelling of the lesional cells for developmentally regulated proteins (OTX1, TBR1, SOX2, MAP1b, CD34, GFAPδ) and oligodendroglial lineage markers (OLIG2, SMI94) was observed. No mutations were detected in the mTOR pathway genes, BRAF, FGFR1 or MYB. Clinical, pathological and genetic data could indicate that MVNT aligns more with a malformative lesion than a true neoplasm with origin from a progenitor neuro-glial cell type showing aberrant maturation 8).


Nunes et al. report 33 cases of presumed multinodular and vacuolating neuronal tumor of the cerebrum that exhibit a remarkably similar pattern of imaging findings consisting of a subcortical cluster of nodular lesions located on the inner surface of an otherwise normal-appearing cortex, principally within the deep cortical ribbon and superficial subcortical white matter, which is hyperintense on FLAIR. Only 4 of the cases are biopsy-proven because most were asymptomatic and incidentally discovered. The remaining were followed for a minimum of 24 months (mean, 3 years) without interval change. They demonstrate that these are benign, nonaggressive lesions that do not require biopsy in asymptomatic patients and behave more like a malformative process than a true neoplasm 9).

2013

Huse et al. report 10 cases of a non-neurocytic, purely neuronal tumor affecting adults. Situated in the cerebral hemispheres, with 7 of 10 confined to the temporal lobes, most presented with seizures as their principal clinical manifestations. On magnetic resosnance imaging (MRI), the tumors generally appeared solid and non-contrast enhancing with minimal diffuse infiltration, edema, or mass effect. Six examples demonstrated internal nodularity. Microscopically, the tumor cells were largely distributed into discrete and coalescent nodules exhibiting varying degrees of matrix vacuolization, principally within the deep cortical ribbon and superficial subcortical white matter. Populating elements ranged from morphologically ambiguous to recognizably neuronal, with only two cases manifesting overt ganglion cell cytology. In all cases, tumor cells exhibited widespread nuclear immunolabeling for the HuC/HuD neuronal antigens, although expression of other neuronal markers, including synaptophysin, neurofilament and chromogranin was variable to absent. Tumor cells also failed to express GFAP, p53, IDH1 R132H, or CD34, although CD34-labeling ramified neural elements were present in the adjoining cortex of seven cases. Molecular analysis in a subset of cases failed to reveal DNA copy number abnormalities or BRAF V600E mutation. Follow-up data indicate that this unusual neuronal lesion behaves in benign, World Health Organization (WHO) grade I fashion and is amenable to surgical control 10).

Case reports

2015

Fukushima et al. report a case of MNVT involving a 37-year-old man who presented with an epileptogenic, superficial solid lesion in the left parietal lobe. Histomorphology of the resected specimen was characterized by nodular lesions with vacuolation. Nodules comprised irregular proliferation of neuronal cells, which ranged from ganglion-like forms to those with indistinct lineage. Immunohistochemical analysis showed that the lesional cells stained positively for HuC/HuD, synaptophysin, and Olig2, and negatively for NeuN, neurofilament, chromogranin A, GFAP, CD34, IDH1(R132H), and BRAF(V600E). Eighteen months following surgery, the patient is well and without neurological deficits. MVNTs are distinctive tumors that should be differentiated from ganglion cell tumors, dysembryoplastic neuroepithelial tumors, and malformation of cortical development 11).

2014

Bodi et al. report the findings in two cases with similar features, a surgical resection and the other an autopsy specimen.Case 1, a 34-year-old female, underwent surgical resection for a multinodular non-enhancing frontal white matter lesion causing intractable epilepsy. Case 2, presented with motor neurone disease (MND) at the age of 71 and MRI scanning revealed extensive multinodular non-enhancing white matter lesions in the temporal lobe. There was no history of epilepsy and post mortem histology confirmed MND.Macroscopically multiple small grey well-formed, discrete and coalescent nodules were seen in the deep cortex and subcortical white matter. On histology, mature-looking neurons with large cytoplasmic vacuoles were distributed in a fibrillary background, where vacuoles were also noted. In the resected tumour scattered oligodendroglia-like cells were present. No ganglion cells were seen. The vacuolated cells exhibited immunopositivity for synaptophysin, HuC/HuD and p62 but were negative for NeuN, neurofilament, GFAP, IDH1, nestin and CD34. Electron microscopy showed non-membrane bound cytoplasmic vacuoles in the neurons and in some neuronal processes. The seizures recurred in Case 1.Some clinicopathological features of this lesion suggest a possible relationship with dysembryoplastic neuroepithelial tumour (DNT) although the morphological features are not typical of DNT. Case 2 demonstrates that MVNT may remain asymptomatic 12).

References

1) , 6) , 10)

Huse JT, Edgar M, Halliday J, Mikolaenko I, Lavi E, Rosenblum MK. Multinodular and vacuolating neuronal tumors of the cerebrum: 10 cases of a distinctive seizure-associated lesion. Brain Pathol. 2013 Sep;23(5):515-24. doi: 10.1111/bpa.12035. Epub 2013 Feb 1. PubMed PMID: 23324039.
2) , 8)

Thom M, Liu J, Bongaarts A, Reinten RJ, Paradiso B, Jäger HR, Reeves C, Somani A, An S, Marsdon D, McEvoy A, Miserocchi A, Thorne L, Newman F, Bucur S, Honavar M, Jacques T, Aronica E. MULTINODULAR AND VACUOLATING NEURONAL TUMOURS IN EPILEPSY: DYSPLASIA OR NEOPLASIA? Brain Pathol. 2017 Aug 19. doi: 10.1111/bpa.12555. [Epub ahead of print] PubMed PMID: 28833756.
4) , 12)

Bodi I, Curran O, Selway R, Elwes R, Burrone J, Laxton R, Al-Sarraj S, Honavar M. Two cases of multinodular and vacuolating neuronal tumour. Acta Neuropathol Commun. 2014 Jan 20;2:7. doi: 10.1186/2051-5960-2-7. PubMed PMID: 24444358; PubMed Central PMCID: PMC3899932.
5) , 11)

Fukushima S, Yoshida A, Narita Y, Arita H, Ohno M, Miyakita Y, Ichimura K, Shibui S. Multinodular and vacuolating neuronal tumor of the cerebrum. Brain Tumor Pathol. 2015 Apr;32(2):131-6. doi: 10.1007/s10014-014-0198-9. Epub 2014 Aug 22. PubMed PMID: 25146549.
7) , 9)

Nunes RH, Hsu CC, da Rocha AJ, do Amaral LLF, Godoy LFS, Watkins TW, Marussi VH, Warmuth-Metz M, Alves HC, Goncalves FG, Kleinschmidt-DeMasters BK, Osborn AG. Multinodular and Vacuolating Neuronal Tumor of the Cerebrum: A New “Leave Me Alone” Lesion with a Characteristic Imaging Pattern. AJNR Am J Neuroradiol. 2017 Jul 13. doi: 10.3174/ajnr.A5281. [Epub ahead of print] PubMed PMID: 28705817.

Video Atlas of Neurosurgery: Contemporary Tumor and Skull Base Surgery, 1e

Video Atlas of Neurosurgery: Contemporary Tumor and Skull Base Surgery, 1e

By Alfredo Quinones-Hinojosa MD FAANS FACS

Video Atlas of Neurosurgery: Contemporary Tumor and Skull Base Surgery, 1e

List Price: $299.99
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Video Atlas of Neurosurgery: Contemporary Tumor and Skull Base Surgery is a unique resource that consists of 40 procedural videos and a concise companion book to reinforce your understanding of the material. Dr. Alfredo Quiñones-Hinojosa brings together a group of outstanding faculty, residents, and fellows lead by Dr. Jordina Rincon-Torroella, who carefully designed, assembled, and edited each chapter. The videos are enhanced through the inclusion of intraoperative photos, anatomical dissections, outstanding anatomical drawings, and animations that detail key steps and provide the experience of viewing a real-time surgery. Whether consulted together or independently of each other, the video and print content deliver all of the expert knowledge you need for effectively planning and understanding tumor and skull base surgeries.

  • Step-by-step, state-of-the-art videos – 40 in total – are accessible through Expert Consult and narrated by Dr. Quiñones-Hinojosa.
  • Each video is around 10 minutes with a total running time of over 6 hours
  • Videos highlight key surgical anatomy, focusing special attention on the relationship between lesions and important landmarks.
  • Procedures are broken down step-by-step for easy overview and comprehension.
  • Covers advanced techniques such as: intraoperative brain mapping; intraoperative assessment of resection through iMRI; fluorescence imaging; brain stem mapping techniques; combined open-and-endoscopic approaches, cortical-subcortical stimulation in awake surgery; and more.
  • Dedicated neurosurgical artwork by Devon Stuart includes superb figures that depict the surgical neuroanatomy and approaches in a step-wise fashion.
  • Chapters are presented from the less complex, more common surgeries to the most complex and cutting-edge procedures that may require multidisciplinary approaches.
  • Expert Consult eBook version included with purchase. This enhanced eBook experience allows you to access all of the text, figures, videos, and references from the book on a variety of devices.

Product Details

  • Published on: 2016-12-02
  • Original language: English
  • Dimensions: 11.06″ h x 1.18″ w x 8.74″ l, .0 pounds
  • Binding: Hardcover
  • 316 pages

Editorial Reviews

Review
“One can only imagine the prodigious amount of work involved in producing this educational treasure chest. Credit is due to the authors and to the publishers for creating this appealing and useful Atlas.” Reviewed by: Edward R. Laws, Professor of Neurosurgery, Harvard Medical School, Oct 2015
“Useful, complete and visual are the words which best summarize the aim of this masterpiece. Really great job! Congratulations for this excellent Video-Book!!” Reviewed by: Dr. J. Gonzalez, Director of the Residency Program Hospital Clinic Barcelona, Oct 2015
About the Author
Alfredo Quinones-Hinojosa has edited several books including Schmidek and Sweet: Operative Neurosurgical Techniques, Controversies in Neuro-Oncology: Best Evidence Medicine for Brain Tumor Surgery, and Video Atlas of Neurosurgery: Contemporary Tumor and Skull Base Surgery, and Neural Stem Cells (An Issue of Neurosurgery Clinics). He has clinical expertise in Neuro-Oncology, tumor surgery, and is a world authority on these aspects of Neuro-Oncology.

Extirpan un tumor cerebral a un paciente mientras toca el saxofón en Málaga – España

Neurocirujanos, neurofisiólogos, neuropsicólogos, anestesiólogos y enfermeros del Hospital Regional Universitario de Málaga han realizado, por primera vez en Europa, una intervención en la que se le ha extirpado un tumor cerebral a un paciente mientras tocaba el saxofón en algunos momentos para evitar secuelas. En concreto, el equipo sanitario llevó a cabo un mapeo de la corteza cerebral del lenguaje musical a Carlos Aguilera, de 27 años, al que se mantuvo despierto –sin anestesia general– durante toda la intervención, incluida la fase de resección del tumor.
La intervención, con una duración de 12 horas, se desarrolló el pasado 15 de octubre y, en la misma, participaron 16 profesionales sanitarios del Hospital Regional; concretamente, tres neurocirujanos, dos neuropsicólogos, tres neurofisiólogos, un anestesista, cinco enfermeras, un auxiliar de enfermería y un celador. Tras permanecer dos semanas hospitalizado, Aguilera fue dado de alta y prosigue los cuidados en domicilio con una buena evolución, según el neurocirujano Guillermo Ibáñez.
De hecho, el paciente ha interpretado varias piezas musicales con el saxofón durante la rueda de prensa. Entre ellas, la balada de jazz ‘Misty’, que ya tocó durante la operación, y el arreglo de una de Johann Sebastian Bach. El paciente ha agradecido su trabajo a los profesionales del Hospital Regional y ha aplaudido que “tengamos la suerte de contar con ellos aquí”. “Hace dos meses estaba en una camilla y hoy he vuelto a nacer”, ha señalado.
Paciente ejemplar
Los profesionales emplearon monitorización neurofisiológica intraoperatoria, una técnica que permite garantizar la seguridad del acto quirúrgico, evitando secuelas derivadas del mismo, y para la que se contó con la colaboración del paciente, que es miembro de una orquesta y becario en la Banda Municipal de Málaga. Ibáñez ha valorado la actitud “valiente” del paciente, asegurando que “un 50 por ciento del éxito de la operación es suya”.
En los músicos profesionales el hemisferio cerebral izquierdo tiene una mayor implicación en la comprensión y ejecución del lenguaje musical, zona donde también se localiza el área motora, sensitiva y del lenguaje, y donde está también la masa tumoral. En el Hospital Regional se han intervenido hasta la fecha un total de 12 pacientes despiertos a los que se les ha realizado el mapeo cortical de las áreas del lenguaje, siendo ésta la primera vez que se realiza la monitorización de las áreas cerebrales relacionadas con el lenguaje musical.
Según han constatado los propios profesionales responsables de la operación, no existen otros precedentes en España o Europa, aunque sí en California (EEUU), con un caso similar realizado este pasado mes de junio. El neurocirujano del Hospital Regional ha explicado que la localización de regiones corticales funcionales durante la cirugía de tumores cerebrales ha adquirido una gran relevancia, ya que permite realizar una resección del tumor más extensa, y en consecuencia, disminuir la probabilidad de morbilidad asociada.
La anestesia
En la fase previa a la intervención quirúrgica es importante encontrar la colocación más confortable para el paciente, ya que durante la operación sólo va a estar sedado –de forma proporcional a las necesidades quirúrgicas de cada fase– y participando de forma activa en la misma.
El procedimiento anestésico se realiza en su totalidad con el paciente despierto, con sus funciones cerebrales intactas, ya que es imprescindible su colaboración para poder identificar las respuestas tanto en la fase de estimulación eléctrica para el mapeo cortical como en la de resección del tumor.
Por ello, no se somete al paciente a una anestesia general con intubación ni se utilizan relajantes musculares. Así, en una primera fase se aplica anestesia local –previa a la instalación del cabezal metálico que mantiene sujeto el cráneo– en la zona de la intervención, y se asocia una sedación profunda –con una perfusión continua intravenosa con fármacos que proporcionan la sedación y analgesia– durante la fase de incisión de la piel, craneotomía y cierre, una vez finalizada la extracción del tumor.
En palabras de Ibáñez, “la implicación y colaboración de todos los profesionales, y la del paciente, es vital para poder realizar una resección óptima considerando siempre los límites del tumor, y, por supuesto, las zonas elocuentes adyacentes identificadas debidamente”.

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