Daniel J. Denis, Karim Elayoubi, Alexander G. Weil, France Berthelet, Michel W. Bojanowski
  1. Department of Surgery, Division of Neurosurgery, Centre Hospitalier de l’Université de Montréal, Hôpital Notre-Dame, Montreal, QC, Canada
  2. Department of Pathology, Division of Neurosurgery, Centre Hospitalier de l’Université de Montréal, Hôpital Notre-Dame, Montreal, QC, Canada

Correspondence Address:
Michel W. Bojanowski
Department of Surgery, Division of Neurosurgery, Centre Hospitalier de l’Université de Montréal, Hôpital Notre-Dame, Montreal, QC, Canada


Copyright: © 2013 Denis DJ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

How to cite this article: Denis DJ, Elayoubi K, Weil AG, Berthelet F, Bojanowski MW. Inflammatory myofibroblastic tumors of the central nervous system that express anaplastic lymphoma kinase have a high recurrence rate. Surg Neurol Int 28-May-2013;4:70

How to cite this URL: Denis DJ, Elayoubi K, Weil AG, Berthelet F, Bojanowski MW. Inflammatory myofibroblastic tumors of the central nervous system that express anaplastic lymphoma kinase have a high recurrence rate. Surg Neurol Int 28-May-2013;4:70. Available from:

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Background:Inflammatory myofibroblastic tumors (IMTs) of the central nervous system (CNS) are rare entities with diverse histopathological features and varying propensities to recur.

Case Description:A 26 year-old male with an IMT of the CNS of the left tentorium had tumor progression 2 months after partial surgical resection. Histopathological studies confirmed expression of ALK. Macroscopic total resection was performed followed by radiotherapy. A recurrence occurred 20 months after the second surgery that necessitate reoperation. Including the present case, we identified 30 cases of IMT of the CNS corresponding to our search criteria in the literature. The extent of resection was reported in 26 of these cases. Gross total resection was done in 75% of ALK-positive and in 61% of ALK-negative cases. Recurrence rate after gross total resection for ALK-positive and ALK-negative cases was 33% and 9%, respectively. Every recurrence in ALK-positive patients occurred within 2 years after surgery.

Conclusion:IMT of the CNS are a heterogeneous group of tumors and the treatment of choice is complete surgical resection. Because of the high recurrence rate reported for IMT of the CNS expressing ALK, a closed follow-up is recommended. When faced with an early recurrence, a surgical resection followed by radiotherapy may be advised.

Keywords: Anaplastic lymphoma kinase, fibrohistiocytic, inflammatory myofibroblastic tumor, pseudotumor, plasma cell granuloma, recurrence


Inflammatory myofibroblastic tumor (IMT) is a rare neoplasm composed of myofibroblastic spindle cells, accompanied by an inflammatory infiltrate of plasma cells, lymphocytes, and eosinophils.[ 5 ] This tumor is usually found in the lung or abdomen of children and young adults.[ 8 ] Its occurrence in the central nervous system (CNS) is rare. Here, we report a case of IMT of the CNS expressing anaplastic lymphoma kinase (ALK) with an aggressive pattern of recurrence despite macroscopic total resection and radiotherapy. We performed a literature review to determine features of IMTs of the CNS that may be associated with tumor progression.


History and examination

A 26-year-old right-handed male presented with a 3-month history of mild headaches and blurred vision. He had a 10-year history of tobacco use. There were no other neurological symptoms. Neurological exam was normal except for right homonymous hemianopia. A contrast-enhanced computed tomography (CT) scan revealed an enhancing left temporal mass. Magnetic resonance imaging (MRI) showed a gadolinium enhancing extra-axial tumor, originating from the left tentorial incisure. The lesion had a supratentorial extension with significant mass effect and peri-lesional edema in the left temporal lobe [ Figure 1 ]. Cerebral angiography demonstrated a poorly vascularized tumor. The preliminary diagnosis was that of a tentorial meningioma.

Figure 1

Preoperative axial (a), coronal (b) and sagittal (c) T1-weighted MRI studies showing a gadolinium enhancing extra-axial mass of the left tentorial incisure. Temporal lobe edema is seen on the axial T2-weighted MRI studies (d)



In order to prevent retraction of the temporal lobe and stretching the vein of Labbe, a supracerebellar transtentorial approach in the park-bench position was performed. Incision of the thickened posteromedial part of the left tentorium revealed a yellowish and fibrous tumor. The tumor was resected using standard microsurgical technique including intracapsular debulking and extracapsular dissection.

Postoperative course

No new neurological deficit was found after the surgery. Immediate postoperative CT showed a 2.0 × 1.5 × 1.0 cm tumor remnant involving the lateral border of the tentorium [ Figure 2 ]. The patient was discharged without steroids 1 week after the operation.

Figure 2

Postoperative axial CT-scan with contrast after a partial resection of the tumor through a supracerebellar-transtentorial approach


Pathological findings

Histopathological examination showed a predominance of spindled myofibroblasts arranged into fascicles surrounded by a diffuse inflammatory infiltrate of lymphocytes and plasmocytes [ Figure 3 ]. This confirmed the diagnosis of IMT. Mitotic activity was evident and the proliferative index was estimated to be 20%. ALK expression was strongly positive. Knowing that some of these lesions might recur after many years, we opted for a close follow up.

Figure 3

Histologic appearance of IMT of the CNS. (a) Fusiform cells organized in perpendicular oriented fascicules (arrow) (×100).(b) Diffuse lymphocytes and plasmocytes infiltrate (arrow) (×200). (c) Tumor cells have an oval shape nucleus, pale chromatin and a big purple nucleolus. Mitosis is seen (arrow) (×400). (d) ALK expression by tumor cells (×200)


Second operation and outcome

The patient presented 2 months later with a new episode of headache and transient aphasia. A second MRI [ Figure 4 ] showed significant local tumor progression. Gross total resection was achieved through a supratentorial approach for the lateral aspect of the tumor and through an infratentorial approach for its medial part. There was no neurological deterioration and a radiotherapy treatment of 60 Gy in 30 fractions was promptly started after discharge. MRI taken 3 [ Figure 5 ], 6, and 10 months after the second surgery showed no residual lesion.

Figure 4

Axial (a and b), coronal (c) and sagittal (d) postgadolinium T1-weighted MRI studies showing tumor progression 2-months following surgery


Figure 5

Axial (a and b) and coronal (c) post-gadolinium T1-weighted MRI studies performed 3 months after showing no recurrence after the second surgery and one cycle of radiotherapy


Third operation and outcome

Twenty months after his second surgery, the patient presented with aphasia, inappropriate laughter and increased aggressiveness. A head CT-scan with contrast showed a local recurrence with infra- and supratentorial extension [Figure 6a and b ]. The previous craniotomy was enlarged and a mastoidectomy was done to expose the transverse, sigmoid, and superior petrosal sinuses. The tumor was dissected from the temporo-occipital and cerebellar parenchyma and excised. Medial transverse sinus tumoral infiltration was macroscopically totally removed. Immediate and 2 months postoperative CT-scan with contrast showed no residual tumor. Pathological findings did not differ from the first surgery.

Figure 6

Axial head CT-scan with contrast showing tumor recurrence 20 months after the second surgery



To establish prognostic factors for IMT of the CNS aggressiveness, we searched the PubMed database using “myofibroblastic,” “pseudotumor,” “central nervous system,” “ALK,” and “recurrence” as search terms. We restricted our analysis to include only papers that investigated ALK expression by immunohistochemistry or fluorescence in situ hybridization (FISH). We based our review on articles that presented IMTs of the CNS cases investigated for ALK expression, since previous reports of extra-CNS IMTs have suggested that this gene could lead to a more aggressive course.[ 3 6 ]


Including our patient, we identified 30 cases of IMTs of the CNS investigated for ALK expression and followed for recurrence.[ 2 4 8 9 10 11 13 14 17 18 ] Six of the 30 cases (20%) presented with recurrence during a mean follow-up of 5.5 years [ Table 1 ]. The extent of resection was reported in 26 cases [ Table 2 ]. Most cases received gross total resection and nine cases received subtotal resection. The recurrence rate after gross total resection for ALK-positive and ALK-negative cases was 33% and 9%, respectively. No tumor progression was reported in six of the seven ALK-negative cases that had subtotal resection, whereas tumor progression was seen in every ALK-positive case that received subtotal resection.

Table 1

Characteristics of six patients with recurrent IMT of CNS investigated for ALK positivity


Table 2

Characteristics for 26 cases of IMT of the CNS investigated for ALK positivity and tumor progression


Eight of the 16 cases with the fibrohistiocytic (FHC) variant (50%) were positive for ALK, but none of the cell granuloma-like (PCG-like) type cases showed this feature. All ALK-positive cases reported had a nodular morphology. Most ALK-positive tumors were supratentorial dural-based lesions, but one case was in the third ventricle near the pineal region[ 2 ] and one case was intradural and extramedullar in the thoracic spine.[ 13 ] All first recurrence in ALK-positive patients was noted early during the first 2 years after surgery. Recurrence of ALK-negative cases, by contrast, appeared between 7 and 12 years after initial surgery and at a different brain region.[ 10 ]


IMT is a rare tumor that can exceptionally be found in the CNS. This tumor's rarity, its various histopathological characteristics and its variable aggressive course render it difficult to diagnose and treat. Characteristics of tumor aggressiveness have not been systematically evaluated for IMT of the CNS. We sought to assess and further identify possible prognostic factors for tumor progression and recurrence through an analysis of previously published cases of IMT of the CNS.

Over the past 20 years, some 100 sporadic cases of IMTs of the CNS have been reported, sometimes with different nomenclature such as “inflammatory pseudotumor” (IP) or “plasma cell granuloma”.[ 5 8 ] Theses lesions are predominantly extra-axial, occurring as dural-based nodular or en plaque-like lesions, and have a predilection to involve the mastoid and the orbit.[ 10 ] Most are meningeal lesions that can invade the brain tissue, whereas some are purely intraparenchymal or intraventricular.[ 8 14 ] Intradural spinal lesions have been described with or without intramedullary involvement.[ 10 13 ] Clinical manifestation with multiple synchronous lesions involving different levels of the neuraxis is another possibility.[ 1 9 ] Based on radiology, the differential diagnosis for intracranial IMTs includes meningioma, plasmacytoma, lymphoma, and idiopathic hypertrophic pachymeningitis.[ 12 ]

IMTs of the CNS can be classified into two histopathological types: A form rich in spindle myofibroblasts mixed with few inflammatory cells, also called the FHC variant, and the PCG-like type composed mainly of plasma cells and lymphocytic infiltration.[ 10 14 18 ] Recent case series proposed that the two types are different in terms of tumor aggressiveness.[ 10 14 18 ] The FHC variant often contains clonal rearrangements in chromosome band 2p23, that constitutively activate the ALK gene.[ 7 ] ALK is a tyrosine kinase receptor that is normally expressed in the developing CNS.[ 19 ] In IMTs located outside of the CNS, investigators have reported several fusion genes that render ALK oncogenic.[ 20 ] In addition, ALK rearrangements with specific fusion genes have been reported in other types of cancer such as anaplastic large cell lymphoma, nonsmall cell lung cancer and renal medullary carcinoma.[ 15 ] To our knowledge, no ALK fusion gene has yet been identified in IMTs of the CNS.

From this review, we conclude that IMT of the CNS that express ALK can have an aggressive course despite gross total resection. The ALK expression in IMT of the CNS is specific to the FHC variant. Compared with IMT of the CNS that do not express ALK, the reported recurrence rate of ALK-positive tumors tend to be higher. The ALK-positive recurrences also seem to occur earlier. Our results are similar to those found for IMTs located outside the CNS, which tend to be associated with an earlier age of presentation and a higher rate of recurrence.[ 3 ] This study was limited by its retrospective nature and by the small number of IMT of the CNS cases that were investigated for ALK expression in the literature. Further research with longer follow up is needed to clarify the natural history of this rare tumor.


Total resection of ALK-positive IMTs should be achieved as theses tumors recurred often rapidly. Confirmation of the FHC variant by histopathology warrants searching for ALK expression. Such findings may lead to considering adjuvant therapy such as radiotherapy or novel ALK inhibitors.[ 16 ]


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