Accepted Manuscript A Rare Case of Brain Angiolipoma Imitating Arteriovenous Malformation: Differential Diagnosis, Surgical Treatment and Literature Review Oleg Shekhtman, MD. PhD, Vadim Gorozhanin, MD, Lyudmila Shishkina, MD, PhD PII: S1878-8750(18)30649-1 DOI: 10.1016/j.wneu.2018.03.167 Reference: WNEU 7779 To appear in: World Neurosurgery Received Date: 6 January 2018 Revised Date: 22 March 2018 Accepted Date: 23 March 2018 Please cite this article as: Shekhtman O, Gorozhanin V, Shishkina L, A Rare Case of Brain Angiolipoma Imitating Arteriovenous Malformation: Differential Diagnosis, Surgical Treatment and Literature Review, World Neurosurgery (2018), doi: 10.1016/j.wneu.2018.03.167. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. ACCEPTED MANUSCRIPT A rare case of brain angiolipoma imitating arteriovenous malformation: differential diagnosis, surgical treatment and literature review. Introduction. Angiolipomas (AL) are tumors of mesenchymal origin including abnormal vasculature and developed (mature) adipose tissue. Typically, they arise in subcutaneous tissue RI PT of the extremities. Usually, CNS angiolipomas are found in the extradural parts of the spine. There is only a dozen reports on intracranial angiolipomas published, all covering 1-2 patients experience [1-12]. Brain ALs are extremely rare and almost all presented observations describe tumors of the sellar region. On MRI study brain AL may be mistaken for pituitary adenoma or SC meningioma but fat saturation sequences and histological examination clear the diagnosis [2,6,10,12]. In those rare cases when AL is found in cerebral hemispheres, it is important to particularly profound bleeding. M AN U establish the diagnosis before surgery to plan correct treatment and avoid complications, A brain arteriovenous malformation (AVM) is a congenital malformation of cerebral vessels with annual incidence of 1-1.42 cases per 100,000 population. Estimated risk of hemorrhage demonstrated in meta-analysis by Gross et al. is 2.2% for unruptured and 4.5% per year for ruptured AVMs [13]. At 20 years mark after diagnosis was established an accumulated TE D risk of rupture is high comprising 42-67% [14,15]. AVM-related hemorrhages usually occur in young patients (mean age 28 years) and in most cases (58-81%) cause disabling neurological symptoms [15-17]. At onset, typical signs of the disease include parenchymatous hemorrhage EP (70%), seizures (15%) or neurologic symptoms (6%) due to steal syndrome caused by blood shunting [18]. Diagnosis of AVM is usually straight forward and based on brain CT, MRI and AC C digital subtraction angiography (DSA). Below we present a rare case of angiolipoma of the right frontal lobe, which manifested with AVM-like features, both clinically and on neuroimaging. The discrepancy with the primary diagnosis became evident during surgery and was confirmed later by the histological examination. Case report Patient A., female, 14 years old. The disease onset was reported at 8 months with focal seizures in the left hand, twitching of the left eyelid, sometimes with the head rotation to the left, without loss of consciousness. These episodes were rare, 1-3 times per year. At 5 years the pattern of seizures had gradually changed: during paroxysm, the girl could talk, sing songs, or ACCEPTED MANUSCRIPT scream, without cooperation; no apparent stereotypic movements were reported. Episodes were about 1 minute long and followed by sleep for 1-2 hours. At 9 years the first brain MRI was performed after recurrent generalized seizure and AVM of the right frontal lobe with a posthemorrhagic cyst in the right frontal lobe was diagnosed (Fig. 1). Radiosurgical treatment was recommended but not performed due to RI PT logistical issues. SC Fig. 1. Brain MRI (2012). In the right frontal lobe, a focal signal change is visualized, hyperintense on T1-weighted images, (A - axial, B - sagittal) and hypointensive on T2-weighted images (B) imitating an early subacute stage of hemorrhage. MR-angiography (D) revealed a M AN U pathological vascular net similar to diffuse AVM nidus. Patient was lost for observation until 2017 when she came for re-evaluation visit as seizure frequency increased. Cerebral angiography identified an atypical vascular network consisting of small, tortuous arteries in the right anterior cerebral artery circulation draining blood into the superior sagittal sinus. Thus, angiographic pattern was evaluated as diffuse TE D arteriovenous malformation partly defragmented after the hemorrhage (Fig. 2). Surgical treatment of AVM was recommended. EP Fig. 2. Selective carotid angiography, lateral (A) and frontal (B) view. A bundle of tortuous AC C vessels in the right frontal lobe is visualized, with a vein draining into the superior sagittal sinus. Operative note. Arcuate skin incision 1 cm apart from hairline in right frontal region, standard osteoplastic craniotomy is performed. Dura mater is relaxed, it’s opened with X-shape incision. A slightly yellowish mass, visually clearly delineated from the brain was visualized on the cortex of the posterior middle and superior frontal gyrus. The size of the lesion - 6x3x3x cm. It had a relatively dense texture and moderately developed vasculature. Numerous small feeders came from anterior and middle cerebral arteries; all were excluded gradually during the excision. The efferent vein at the upper tumor pole carried a slightly arterialized blood and drained into anterior third of superior sagittal sinus. In step by step fashion the tumor was isolated and removed en bloc. After accurate hemostasis wound is closed in layers. ACCEPTED MANUSCRIPT Pathology report. Tumor node was presented by fragments of mature lobulated adipose tissue with proliferations of connective tissue fibers and a large number of thin-walled vessels of different diameters. In several areas, predominately subarachnoidal and subcapsular, relatively large vessels with undifferentiated walls and wide lumens were revealed (Fig. 3). In addition, there were small foci of fibrosis near the vascular cavities. What stands out is that the areas with morphological pattern corresponds to angiolipoma. Fig. 3. Histological preparation. Anigiolipoma: RI PT the clusters of the above vessels were similar to those seen in arteriovenous malformations. The SC A - mature adipose tissue with vessels of different diameters (1 - lipocytes, 2 - a large vessel with a thickened wall). M AN U B - conglomerate of vessels with undifferentiated walls separated by adipose and fibrous tissue (1 - lipocytes, 2 - intratumoral vessels, 3 - focus of fibrosis). The postoperative period went uneventful, neurological status remained unchanged. patient was discharged for further neurologist observation. Brain CT and cerebral angiography TE D confirmed complete tumor excision (Fig. 4). Fig. 4. Post-operative rt. carotid angiography, frontal projection (A), Brain CT (B, C): complete tumor excision. EP Six months after the surgery the patient feels well. She continues to take Depakine with seizures became less frequent (1 fit per 1 - 2 months). She is back to school and experiences no AC C limitations in daily activities. Discussion Brain ALs are very rare benign tumors with female predominance that typically present with pseudotumorous symptoms or seizures. The majority of intracranial angiolipomas are found in sellar-parasellar region what could be explained by close contact of 3 primitive layers here at pharyngeal cavity and cavernous sinus which may carry ectopic mesenchymal tissue. Sellar and parasellar ALs are slow growing, hormonally inactive tumors that are frequently taken for meningiomas or adenomas. Morphologists describe a non-infiltrating (encapsulated) and infiltration types of angiolipomas. The first are usually well delineated, rich vascularized lesions ACCEPTED MANUSCRIPT which require delicate, stepwise resection while infiltrating ALs are very difficult to remove totally and thus have tendency to recur [6,7,12]. Pubmed search by key words over the past 20 years revealed only 12 confirmed cases of intracranial angiolipomas. Spinal cord lesions are more common to see: in the largest literature review by Andaluz et al. 80 of 87 angiolipomas were identified in spinal cord [7]. Summary of RI PT recent reports of intracranial ALs is presented in Table 1 [1-12]. Table 1. Summary of brain angiolipomas clinical reports Pt. Manifestation Localization Treatment Takeuchi, 1981 1 subarachnoid hemorrhage sellar region partial removal Wilkins, 1987 1 seizures, headache, CN III palsy frontotemporal and suprasellar partial removal Lach, 1994 1 diplopia, CN III palsy sellar region partial removal Shuangshoti, 1995 1 retroorbital pain sellar region Prabu, 1995 2 seizures profuse bleeding death total removal well encapsulated improved frontal lobe total resection well delineated recovered right ptosis,diplopia, temporal hemianopsia sellar region partial removal bleeding from the red tumor improved yellowish, firm, vascular mass with multiple digitations into the normal parenchyma fibrous capsule recovered TE D M AN U improved EP 1 Outcomes profuse bleeding, a dense fibrous capsule, continuous with the dural covering of the cavernous sinus profuse bleeding AC C Pirotte, 1998 Surgical features SC Author, year Andaluz, 2000 1 seizures Frontal lobe total resection Pawar, 2003 1 inferior colliculus partial removal Vilela, 2005 1 ipsilateral hearing loss and upper limb ataxia subarachnoid hemorrhage Frontal lobe conservative -- Kolenc, 2008 2 headaches sellar region biopsy (transsphenoid al) + gammaknife profuse bleeding improved improved recovered, no rebleeding after 5 y. follow-up no change Francois, 2010 Rotondo, 2013 1 2 ACCEPTED MANUSCRIPT sellar + partial diplopia, headache, CN III palsy headache, diplopia cavernous sinus removal sellar region partial removal + gamma-knife profuse bleeding improved intraoperative hemorrhage improved RI PT We have found only 2 cases reported previously when AL have manifested with subarachnoid hemorrhage, in one case it was initially diagnosed as ruptured AVM [1,9]. As Pirotte et al. mentioned some areas of AVM may undergo lipomatous or angiolipomatous differentiation [6]. Immunohistochemical studies by Lach and Lesiuk have demonstrated a SC developmental association of all cell types forming vascular walls (smooth-muscle cells, pericytes, etc.) and adipose tissue which come from one precursor (primitive pluripotential mesenchymal cell). Thus an angiolipomas and angiomyolipomas is considered an intermediate M AN U forms in spectrum between hemangiomas and lipomas [3,12]. Most brain ALs present on CT scans as low-density, partially contrast-enhanced lesions. They are typically hyperintense on T1-weighted images and relatively homogenous; at T2 the signal may vary. Fat-suppression techniques (STIR, CHESS, etc.) are crucial for differential diagnosis helping to rule out a lipomatous tissue [19]. Other mass lesions with fat tissue such as TE D dermoids and lipomas do not enhance after contrast injection and this way could be distinguished from ALs. Because of low vascular flow and tiny vessel caliber ALs do not have typical to AVMs flow voids at MRI. However, diffuse (racemose) AVMs or partially destroyed malformations may resemble the same MRI pattern having no high flow vessels. Moreover, EP radiological presence of ALs as few authors report in large part depends on ratio between fat, stromal and vascular component. MRI presence of predominantly lipomatous AL is very close to AC C lipoma while densely vascularized tumor mimics meningioma or hemangioma. Unfortunately, our surgical decision was based on MRI study made at local hospital which had no fatsuppression sequence. Parenchymatous hemorrhage delivers a hyperintense MRI signal at T1 sequence in early subacute stage (2-7 days) what we incorrectly have attributed to AVMs rupture manifested with generalized seizure. Digital subtraction angiography remains a “gold standard” technique for brain AVM diagnostics. It is typically visualized as a packed mass of enlarged arteries (nidus), several feeding arteries and one or more dilated tortuous veins. On DSA both nidus and veins become contrasted in early arterial phase (shunting effect). Diagnosis of brain AVM in most instances is ACCEPTED MANUSCRIPT made without a doubt. In our case a DSA revealed a non-compact vessel net with draining vein visualized in arterial phase what was taken for a remnant of partially destroyed malformation. Seizures is a common symptom in low-grade gliomas which significantly decrease quality of life when uncontrolled. Tumors involving the frontal, temporal and parietal lobes are commonly associated with seizures, although intractable epilepsy is more typical for insular and RI PT mesiotemporal lesions. Our review has revealed only 3 cases of epilepsy as a main symptom of AL, obviously not enough to describe its natural history. Pathogenesis of tumor epilepsy is multifactorial and depends on tumor histology, location, size and other factors. Numerous studies have confirmed that gross total resection is the critical factor in seizure control and better results could be achieved when cortical mapping (ECoG) and awake surgery are applied [20,21]. In SC presented case total resection was achieved, however seizure control remained incomplete (Engel III) what we attribute to long history of the disease and irregular drug intake. M AN U Generally, surgical removal should be considered a first line treatment for most brain ALs, however total removal largely depends on a size, structure and above all - localization of the tumor. Sellar-parasellar ALs besides exofitic node growing to middle fossa often infiltrate walls of cavernous sinus and expand to sella turcica what makes surgery technically difficult and increases morbidity. Total removal rarely could be achieved. Overall, ALs are benign, slow TE D growing tumors and thus partial resection with irradiation or conservative treatment seem quite reasonable options. Recent reports suggest that radiosurgery (Gamma-knife, Cyber-knife) has become an effective yet less invasive treatment modality for highly vascularized or deep seated tumors (hemangiomas, glomus jugulare paraganglioma, etc.) and therefore could be a rational EP alternative to surgical excision of intracranial angiolipoma. Acknowledgement. Authors would like to thank Dr. Elena Okisheva, PhD for editing AC C and translation service. References 1. Takeuchi J, Handa H, Keyaki A, Haibara H, Ozaki S: Intracranial angiolipoma. Surg Neurol 15:110–113, 1981 2. Wilkins PR, Hoddinott C, Hourihan MD, Davies KG, Sebugwawo S, Weeks RD: Intracranial angiolipoma. J Neurol Neurosurg Psychiatry 50:1057–1059, 1987 3. Lach B, Lesiuk H: Intracranial suprasellar angiolipoma: ultrastructural and immunohistochemical features. Neurosurgery 34:163–167, 1994 ACCEPTED MANUSCRIPT 4. Shuangshoti S, Wangsuphachart S: Angiolipoma of suprasellar region. J Med Assoc Thai 78:631–634, 1995 5. Prabu SS, O’Donovan DG, Gurusinghe NT: Intracranial angiolipoma: report of two cases. Br J Neurosurg 9:793–797, 1995 6. Pirotte B, Krischek B, Levivier M, Bolyn S, Brucher JM, Brotchi J: Diagnostic and microsurgical presentation of intracranial angiolipomas. Case report and review of the RI PT literature. J Neurosurg 88:129–132, 1998 7. Andaluz N, Balko G, Bui H, Zuccarello M. Angiolipomas of the central nervous system. J Neurooncol 2000;49:219-30. 8. Pawar SJ, Sharma RR, Karapurkar AP, Tewari MK, Lad SD: Angiolipoma of the right SC inferior colliculus: a rare central cause of hearing loss and limb ataxia. J Clin Neurosci 10:346–348, 2003 M AN U 9. Vilela P, Saraiva P, Goulao A. Intracranial angiolipoma as cause of subarachnoid hemorrhage: case report and review of the literature. Neuroradiology 2005; 47:91–96 10. Kolenc D, Zarković K, Jednacak H, Ozretić D, Habek M. Sellar angiolipomas: two case reports and a review of the literature. J Neurooncol. 2008 Aug;89(1):109-12. 11. Francois P., Zemmoura I., Fouquet AM.B., Jan M., Velut S. Lateral sellar angiolipoma: a tumor illustrative of the extradural compartment of the neural axis. J Neurosurg TE D 113:1053–1058, 2010.` 12. Rotondo M., D’Avanzo R., Natale M., Oliva G., Scuotto A. Lateral sellar angiolipomas: a therapeutic challenge. Our experience on two cases and review of the literature. British Journal of Neurosurgery, June 2013; 27(3): EP 359–363 13. Gross BA, Du R. Natural history of cerebral arteriovenous malformations: a meta-analysis. J AC C Neurosurg. 2013 Feb;118(2):437-43. 14. Fults D., Kelly D.L. Natural history of arteriovenous malformations of the brain: a clinical study. Neurosurgery 1984; 15: 658—662. 15. Graf C.J., Perret G.E., Torner J.C. Bleeding from cerebral arteriovenous malformations as part of their natural history. J Neurosurgery 1983; 58: 331— 337. 16. Perret G., Nishioka H. Report on the cooperative study of intracranial aneurysms and subarachnoidal hemorrhage. Section VI. Arteriovenous malformations. J Neurosurg 1966; 25: 467—490. 17. Stapf C, Mast H, Sciacca RR, Berenstein A, Nelson PK, Gobin YP, Pile-Spellman J, Mohr JP; New York Islands AVM Study Collaborators. The New York Islands AVM Study: design, study progress, and initial results. Stroke. 2003 May;34(5):e29-33. ACCEPTED MANUSCRIPT 18. Fults D., Kelly D.L. Natural history of arteriovenous malformations of the brain: a clinical study. Neurosurgery 1984; 15: 658—662. 19. Osborn AG, Salzman KL, Jhaveri MD, Barkovich AJ. Diagnostic Imaging: Brain, 3rd Edition. 2015, English. 20. Englot DJ, Berger MS, Barbaro NM, Chang EF. Predictors of seizure freedom after resection of supratentorial low-grade gliomas. A review. J Neurosurg. 2011 RI PT Aug;115(2):240-4. doi: 10.3171/2011.3.JNS1153. Epub 2011 Apr 2 Review. PubMed PMID: 21529134. 21. Rudà R, Bello L, Duffau H, Soffietti R. Seizures in low-grade gliomas: natural history, pathogenesis, and outcome after treatments. Neuro-Oncology. 2012;14(Suppl 4):iv55- AC C EP TE D M AN U SC iv64. ACCEPTED MANUSCRIPT Pt. Manifestation Localization Treatment Surgical features Outcomes Takeuchi, 1981 1 subarachnoid hemorrhage sellar region partial removal profuse bleeding death Wilkins, 1987 1 seizures, headache, CN III palsy frontotemporal and suprasellar partial removal improved Lach, 1994 1 diplopia, CN III palsy sellar region partial removal profuse bleeding, a dense fibrous capsule, continuous with the dural covering of the cavernous sinus profuse bleeding Shuangshoti, 1995 1 retroorbital pain sellar region total removal Prabu, 1995 2 seizures frontal lobe Pirotte, 1998 1 right ptosis,diplopia, temporal hemianopsia Andaluz, 2000 1 Pawar, 2003 1 Vivela, 2005 SC improved improved total resection well delineated recovered sellar region partial removal bleeding from the red tumor improved seizures Frontal lobe total resection recovered ipsilateral hearing loss and upper limb ataxia subarachnoid hemorrhage inferior colliculus partial removal yellowish, firm, vascular mass with multiple digitations into the normal parenchyma fibrous capsule Frontal lobe conservative -- biopsy (transsphenoid al) + gammaknife partial removal profuse bleeding Recovered, no rebleeding after 5 y. follow-up no change profuse bleeding improved partial removal + gamma-knife intraoperative hemorrhage improved TE D M AN U well encapsulated AC C 1 RI PT Author, year EP Table 1. Summary of brain angiolipomas clinical reports Kolenc, 2008 2 headaches sellar region Francois, 2010 1 Diplopia, headache, CN III palsy, sellar + cavernous sinus Rotondo, 2013 2 headache, diplopia sellar region improved AC C EP TE D M AN U SC RI PT ACCEPTED MANUSCRIPT AC C EP TE D M AN U SC RI PT ACCEPTED MANUSCRIPT AC C EP TE D M AN U SC RI PT ACCEPTED MANUSCRIPT AC C EP TE D M AN U SC RI PT ACCEPTED MANUSCRIPT ACCEPTED MANUSCRIPT Highlights Brain angiolipoma - rare mesenchymal supratentorial tumor Arteriovenous malformation diagnoses requires MRI, CT and angiography evaluation AC C EP TE D M AN U SC RI PT MRI fat-suppression sequences are highly effective in detection of adipose tissue ACCEPTED MANUSCRIPT Abbreviations AL - angiolipoma AVM – arteriovenous malformation CNS – central nervous system CT – computer tomography DSA – digital subtraction angiography SC ECoG - electrocorticography AC C EP TE D M AN U MRI – magnetic resonance imaging STIR – short tau inversion recovery RI PT CN – cranial nerve