Jpn J Clin Oncol 2014;44(11)1052 – 1057 doi:10.1093/jjco/hyu138 Advance Access Publication 23 October 2014
Diagnosis and Surgical Treatment of Cavernous Sinus Angioleiomyoma: A Report of Four Cases Kangmin He†, Liang Chen†, Wei Zhu, Haixia Cheng, Yin Wang and Ying Mao* Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai 200040, China
Received March 7, 2014; accepted August 18, 2014
Objective: The aims of the study were to retrospectively evaluate the imaging characteristics of cavernous sinus angioleiomyoma and explore appropriate surgical approaches. Methods: A total of four cases admitted to our hospital for repeated episodes of headache were enrolled. The common clinical manifestations included decreased vision, diplopia, blepharoptosis and facial numbness. The first three patients were misdiagnosed with cavernous sinus hemangioma, meningioma and chordoma, respectively. The fourth case was suspected to be angioleiomyoma. Imaging examination showed an oval-shaped tumor occupying the cavernous sinus. The tumor was hypointense on T1-weighted magnetic resonance imaging and extremely hyperintense on T2-weighted scan, which was similar to the cerebrospinal fluid, and was progressively enhanced from one side after gadolinium injection, pushing the internal carotid artery toward the inner side. Results: Surgical resection was performed via an epidural approach for these four cases. Clinical symptoms were improved after surgery and no recurrence was observed during followup visits (average, 47.5 months). Conclusions: The initial symptom of cavernous sinus angioleiomyoma was repeated headache. The tumor seems extremely hyperintense on a T2-weighted image and expansive growth is pushing away the internal carotid artery rather than encasing it. It was progressively enhanced from one side after gadolinium injection. Surgical treatment based on an epidural approach had an excellent outcome in tumor resection and nerve protection. Key words: cavernous sinus angioleiomyoma – neurological – surgery – tumor – nerve protection
INTRODUCTION Angioleiomyoma (also known as angiomyoma, vascular leiomyoma or dermal angioma 1), one subtype of leiomyomas, is a relatively rare benign soft tissue tumor that consists of a mixture of well-differentiated smooth muscle cells and small thick-walled vessels (2). Recently, angioleiomyoma, commonly located in the extremities of middle-aged individuals (3), has been described in other locations, including uterus (4), larynx (5) and rectum (6). This tumor presents as hoarseness or pain and the therapy of choice is complete surgical excision (7,8). An accurate intracranial site for this tumor is exceedingly rare and four relevant cases have been
reported so far. Only two of these case reports have discussed angioleiomyoma involved in the cavernous sinus (9,10). Although the surgical anatomy of the cavernous sinus has been studied by a number of investigators, cavernous sinus exposure remains a difficult task because of the complicated neural and vascular relationships in this area (11), and the pre-operative misdiagnosis rate is very high (12). In this article, we present four cases of cavernous sinus angioleiomyoma (CSA) along with a concise review of clinical, pathological, radiological and surgical features for the purpose of identifying clinical characteristics and exploring suitable surgical treatments.
# The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: [email protected]
Downloaded from http://jjco.oxfordjournals.org/ at University of North Carolina at Chapel Hill on November 3, 2014
*For reprints and all correspondence: Ying Mao, Department of Neurosurgery, Huashan Hospital, No.12 Wulumuqi Middle Road, Shanghai 200040, China. E-mail:[email protected] † Kangmin He and Liang Chen contributed equally to this paper as co-first authors.
Jpn J Clin Oncol 2014;44(11)
PATIENTS AND METHODS
misdiagnosed with cavernous sinus hemangioma (CSH), meningioma and chordoma, respectively. The fourth case was suspected to be angioleiomyoma. The results of MRI of the fourth case are shown in Figure 1a – e. Computed tomography (CT) scan of head revealed a hyperintense lesion; MRI revealed a round or oval mass lesion occupying the cavernous sinus. The tumor seems hypointense on a T1-weighted MRI scan and was abnormally hyperintense on a T2-weighted scan, which was similar to the cerebrospinal fluid (CSF) and was progressively enhanced from one side after gadolinium injection. In addition, the internal carotid artery (ICA) was pushed toward the inner side.
CLINICAL MANIFESTATION
SURGICAL TREATMENT
The most common clinical manifestations of the four cases are listed in Table 1.
The surgical procedure was performed by using the middle fossa extradural approach through pterional incision, for which the patients were given general anesthesia using tracheal cannula. A lumbar drainage was used to drain CSF during the operation to control intracranial pressure. The dura mater was separated from the lateral orbital wall until the turning point. In addition, the lateral bone of the superior orbital fissure was drilled off. After opening the dura, the tumor was visible and then it was completely removed. The cranial nerves were preserved carefully during the normal anatomical procedure. If the subdural water-filling was normal, the dural wall was sutured closely. At the end of the operation, the operated area of the cavernous sinus was obturated with a gelatin sponge when the efficacy of hemostasis was satisfactory. Meanwhile, the surrounding dura was suspended and the bone flap was repositioned.
† Case 1: A 46-year-old woman had a 1-year history of headache and 4 months of blepharoptosis in the right eye. Physical examination revealed right oculomotor nerve palsy and decreased visual acuity. In addition, strength of the right masseter muscle was poor. † Case 2: A 57-year-old man having a more than 10-year history of headache and 3-month history of progressive right vision loss accompanied by diplopia. Physical examination revealed that an abduction defect had occurred in his right eye. † Case 3: A 48-year-old woman presented with 7-year history of headache and 1-year history of right severe ptosis. The physical examination disclosed central visual field defects of the right eye and right oculomotor nerve paresis. † Case 4: A 35-year-old woman with 1-year history of headache and 1-week history of decreased left vision accompanied with diplopia. Physical examination revealed that the bilateral vision field was normal. Although movement of her left eye was limited, optical acuity was normal. IMAGING EXAMINATION All patients were evaluated pre-operatively using magnetic resonance imaging (MRI). The first three patients were
PATHOLOGICAL FINDINGS The lesions of all the cases were similar with the typical appearance of angioleiomyoma composed of numerous thickwalled vessels without vascular elastic lamina and intermingled with intersecting fascicles of spindle-shaped smooth muscle cells. The distribution of vessels displayed cracks or spongy expansion. The spindle-shaped cells with blunt-ended nuclei and vacuolar cytoplasm were irregularly arranged surrounding the vessels. The cell nuclei were well differentiated
Table 1. Clinical manifestation of cavernous sinus angioleiomyoma Case
Sex/age (years)
Tumor diameter (cm)
Duration of headache (years)
Vision Right
Left
Diplopia
Blepharoptosis
Oculomotor nerve palsy
Abduction limitation
1
F/46
2
1
0.1
0.8
–
Right
Right
–
2
M/57
3
10
0.1
0.6
Right
–
–
Right
3
F/48
3
7
–
–
–
Right
Right
–
4
F/35
2
1
0.8
0.8
Left
–
–
Left
– Stands for normal.
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All four subjects enrolled in the study gave informed consent and the study protocol was approved by the Hua Shan Hospital’s committee on human research. The primary antibodies for the immumohistochemical staining were as follows: mouse anti-human CD34 antibodies (clone 581, BD PharMingen); mouse anti-human smooth muscle actin (SMA) antibodies (clone 1A4, Sigma); mouse anti-human S100 antibodies (clone 19/S100B, BD Transduction Laboratories); mouse anti-human monoclonal Ki-67 (MIB-1) antibodies (clone B56, BD PharMingen).
1053
1054
Characteristics identification of CSA
without atypia and mitotic activity was rarely found. The lesion areas showed mucoid degeneration, glassy degeneration and lipoid degeneration (Fig. 1f). Immunohistochemical analysis demonstrated that the spindle-shaped cells were positive for SMA (Fig. 1h). The endothelial cells in the tumor vessel wall expressed high levels of CD34 (Fig. 1g). The small nerve fibers from the lesion capsule and stroma were positive for S100 (Fig. 1i), and the MIB-1 proliferation index ranged from 1 to 2% (Fig. 1j).
Table 2. The follow-up studies of four patients Case Discharge Follow-up study (days after operation) Months Vision
Diplopia Blepharoptosis Abduction limitation
Right Left 1
7
60
0.6
–
–
Improved
–
2
10
45
0.6
–
–
Improved
Improved
FOLLOW-UP STUDY
3
11
35
–
–
–
Improved
Improved
These four patients with CSA were not treated with radiation therapy post-operatively. A follow-up MRI examination was made available and the average follow-up period was 47.5 months. The follow-up examinations demonstrated no residual tumor and no recurrence. The Modified Rankin Scale (mRS) of all was 2. The details are given in Table 2.
4
14
2
–
–
–
–
–
CASE 1
CASE 3
The patient was discharged from the hospital 1 week after the operation. The right vision was improved, but other symptoms were not improved on discharge compared with that during admission. The follow-up visit of 72 months showed that the clinical symptoms improved well and right visual acuity returned to 0.6.
After the surgery, the patient was discharged 11 days later with dysfunction of her right eye, including blepharoptosis, limited movement, pupilla of 3 mm and the absence of optical acuity. Compared with the clinical conditions at the time of discharge, the follow-up outcome (47 months) showed that clinical symptoms were improved.
CASE 2
CASE 4
The body temperature rose post-operatively and was eased via conservative treatments. Although the right eye showed
The patient was discharged 2 weeks after surgery without any obvious change. The clinical and radiological follow-up visits
blepharoptosis and moved disorderly, the right vision was improved. A follow-up visit at 57 months showed that his right visual acuity returned to 0.6 and dysfunctions were recovered to different degrees.
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Figure 1. Results of MRI of the fourth case. (a) An oval-shaped lesion occupying the right cavernous sinus; (b) T1-weighted images showed hyperintense tumor (approach to cerebrospinal fluid) with a blunt round shape (white arrow); (c) tumor with progressive enhancement after contrast medium injection (white arrow); (d) CT angiography (CTA) indicated that the right intracavernous internal carotid artery (ICICA) was pressed toward the inner side; (e) the follow-up outcome showed that the tumor was completely removed with no residual tumor and no recurrence; (f ) microscopic images show that the tumor comprised welldifferentiated smooth muscle bundles and thick-walled blood sinuses, including hyaline degeneration (indicated as a triangle) (hematoxylin and eosin staining; 100); (g) endothelial cells showing positivity for CD34 (immunohistochemistry; 100); (h) smooth muscle cells showing strong positivity for smooth muscle actin (SMA) (immunohistochemistry; 100); (i) small nerve fibers from the lesion capsule and stroma showing strong positivity for S100, depicted by a black arrow (immunohistochemistry; 100); ( j) the MIB-1 proliferation index was 2% (immunohistochemistry; 200).
Jpn J Clin Oncol 2014;44(11)
(14 months) demonstrated that diplopia disappeared and others were not improved.
DISCUSSION
PATHOLOGY The CSA comprises sharply demarcated nodules of smooth muscle tissue and thick-walled vessels with various sizes (16). The smooth muscle cells are mature and well differentiated. Microscopically, lesions with mucoid, fat or hyaline degeneration can be observed, as well as hemorrhage and calcification. These tumor cells usually lack nuclear atypia and mitotic activity (the MIB-1 proliferation index was merely 1.5% in four cases). Histologically, Morimoto et al. (17) have studied 241 cases of angioleiomyoma and classified them into solid, venous and cavernous types. Smooth muscle bundles are closely compacted in solid tumors and intersect with each other. Vascular channels are usually multiple and small-sized. In venous-type tumors, smooth muscle bundles are not closely compacted and have venous-type vascular channels with thin muscular walls. Dilated vascular channels can be seen in the cavernous type and muscular walls of these vessels are hardly to be distinguished from intervening smooth muscle bundles. In this study, all cases showed dilated vascular channels with thin muscular walls, which belonged to the cavernous type. Duhig and Ayer have suggested that angioleiomyomas are not true tumors but instances of vascular malformations (18). Moreover, the smooth muscle proliferation within a hemangioma produces a vascular leiomyoma and further leads to a simple leiomyoma (18). Combined with previous study, we proposed typical differences here between CSA and CSH. CSH is derived from cavernous sinus vasculature, consisting of irregularly sized vessel cavities or sinuses (19,20). The main characteristics are as follows: the sinus walls are formed by a single-layer intima; a few connective tissues are visible and no neural tissue is found among the vessels; less smooth muscle cells are found and distributed around the vessel wall from the immunostaining of SMA. In contrast, angioleiomyoma is derived from vascular smooth muscle (21). The main characteristics include thick-walled vessels and well-differentiated smooth muscle bundles within the lumens. Immunostaining of SMA indicates
that smooth muscles are generally localized in the stroma. Hasegawa et al. (1,10) have found that small nerve fibers (immunoreactive for S-100 protein and PGP 9.5) could be identified within the stroma of 69% of painful tumors in the clinicopathological and immunohistochemical studies of angioleiomyoma, suggesting that the painful tumors may be mediated by the nerve fibers located in the tumor parenchyma. The results of our study were consistent with those of previous studies. CLINICAL PRESENTATION Specific pain is the typical clinical symptom of angioleiomyoma and may be mediated by nerve fibers in the solid part of the tumor (22). According to the statistics of World Health Organization, non-intracranial angioleiomyomas are usually manifested as separated slowly growing subcutaneous nodules (diameter ,2 cm) and pain can be induced when exposed to cold wind (23). Meanwhile, pain is the most striking clinical feature of intracranial angioleiomyoma (24). Long repeated headache prior to the onset of the eye symptoms has been reported in two previous cases, which is also found in our studies, indicating that headache is the early characteristic symptom. The different pain of CSH is due to capsular tension, while the pain of angioleiomyoma may be induced by mechanical compression of vascular smooth muscle cells toward nerve fibers in the stroma. As a result, the pain of angioleiomyoma is stronger than that of CSH. In our study, it was interesting that all the four patients were middle-aged individuals, which might be related to the growth rate of CSA. Generally, these tumors occur insidiously and progress slowly, which leads to the missed diagnosis of CSA at the early stage. During admission, the diameters of lesions were .2 cm; the cranial nerves (II, III, IV, V and VI) showed dysfunction and compression symptoms that occurred in the cavernous sinus. RADIOLOGICAL FINDINGS Pre-operative diagnosis of CSA was performed to distinguish angioleiomyomas from meningiomas, neurinomas, chordomas and cavernous hemangiomas based on CT and MRI examination. In the two previous reports (9,10), CT revealed a well-defined or slightly hyperdense tumor with homogeneous enhancement after contrast medium injection. T 1-weighted MR images showed a hypointense tumor, while T2-weighted and T 2 /FLAIR MR images showed a hyperintense tumor (similar to CSF). These lesions were enhanced progressively after injection of contrast medium. The four cases in our study displayed similar MRI results. According to the varying levels of hyperintensity of the T2-weighted MRI and enhancement following the injection of contrast medium, it was easy to distinguish CSA from meningioma, neurilemmoma and chordoma. However, it was difficult to differentiate CSA from cavernous hemangiomas because of their similar characteristics on MRI. In this study,
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Angioleiomyoma is a benign soft tissue tumor arising from the muscle layer of blood vessels (13) and occurs frequently in the extremities of middle-aged individuals with a predominance in women (1,3). Head and neck locations have been described (14), but the case of angioleiomyoma arising within the cavernous sinus is extremely rare and only two reports concerning CSA have been reported (9,10). It has been reported that some etiologic factors may contribute to angioleiomyoma, such as hormonal changes (principally associated with estrogen), previous trauma and venous stasis (15). To date, the clinical features and surgical treatments of CSA have not been explicitly explained.
1055
1056
Characteristics identification of CSA
SURGICAL TREATMENT † Surgical indications: because of the insidious onset of CSA, radiation therapy was not planned and surgery seemed to be the best option for CSA patients. † Surgical approaches: the intradural approach (9), an acceptable procedure for tumors near the parasella, can cause significant atrophy of the temporal lobe after the resection of the CSA. In our study, we resected lesions of CSA via an epidural approach. During the surgical process, intracranial nerves and vessels were exposed adequately, the middle meningeal artery was blocked earlier to choke off blood supply, and the subarachnoid space was prevented from the contamination of hemorrhage. Meanwhile, the reflux venous of temporal lobe was normal. During the operation, the tumor was visible after stripping the outer layer of the cavernous sinus. The tumors were segregated carefully from cranial nerves III, IV and V along with the pseudocapsule of the tumors. The huge lesion was progressively dissociated by induction of whole-body decompression or bipolar coagulation. If shrinking of the huge tumor is not effective, puncture of the tumor should be performed to avoid misdiagnosis of CSH after the border tissue is separated out as much as possible. Cut-off of the capsule and piecemeal removal of the tumor was then performed under the condition of puncture position without hemorrhage. The follow-up visit after surgery showed recovered or improved cranial nerves and no recurrence. † Radiosurgery: the outcome of radiosurgical treatment was not clear and a malignant potential for the lesion was reported in previous study (27,28). Given the benign progress after resection of the CSA, complete resection was
verified by MRI and post-operative radiosurgical treatment was unnecessary.
CONCLUSION CSA is a rare benign tumor arising from the interlayer between the dura mater and the lateral wall of the cavernous sinus. Patients with CSA could present with recurrent headache of long duration prior to clinical symptoms of intracranial neurological dysfunctions and space-occupying oppressive symptoms of the cavernous sinus. The location of the ICA, tumor shape and the enhancement on MRI image could provide a possible basis for the diagnosis of CSA. The excision via an epidural approach is usually curative and the prognosis is good.
Funding This study was supported by the National Natural Science Foundation of China 2011 to Chen Liang.
Conflict of interest statement None declared.
References 1. Ramesh P, Annapureddy SR, Khan F, Sutaria PD. Angioleiomyoma: a clinical, pathological and radiological review. Int J Clin Pract 2004;58:587– 91. 2. Willoughby AD, Schlussel AT, Freeman JH, Lin-Hurtubise K. Angioleiomyoma in a rare location: a case report. Hawaii J Med Public Health 2013;72:45– 8. 3. Hachisuga T, Hashimoto H, Enjoji M. Angioleiomyoma. A clinicopathologic reappraisal of 562 cases. Cancer 1984;54:126–30. 4. Jin CH, Yi KW, Kim YS, et al. Uterine angioleiomyoma: unusual appearance at laparoscopy. J Minim Invasive Gynecol 2013;20:149– 50. 5. Eyigor H, Suren D, Osma U, Sezer C, Yilmaz MD. A case of angiomyolipoma rarely located in the larynx. Case Rep Otolaryngol 2011;2011:427074. 6. Stanojevic GZ, Mihailovic DS, Nestorovic MD, et al. Case of rectal angioleiomyoma in a female patient. World J Gastroenterol 2013;19:2114– 7. 7. Choe KS, Sclafani AP, McCormick SA. Angioleiomyoma of the auricle: a rare tumor. Otolaryngol Head Neck Surg 2001;125:109– 10. 8. Brooks J, Ricalde P, Nikitakis N, Levy B. Angioleiomyoma of the tongue. Gen Dent 2004;52:52. 9. Colnat-Coulbois S, Schmitt E, Klein O, et al. Angioleiomyoma of the cavernous sinus: case report. Neurosurgery 2008;62:E257 – 258; discussion E258. 10. Figueiredo EG, Gomes M, Vellutini E, Rosemberg S, Marino R, Jr. Angioleiomyoma of the cavernous sinus: case report. Neurosurgery 2005;56:E411; discussion E411. 11. Dalgic A, Boyaci S, Aksoy K. Anatomical study of the cavernous sinus emphasizing operative approaches. Turk Neurosurg 2010;20: 186– 204. 12. Li D, Hao S-Y, Tang J, et al. Primary intracranial angioleiomyomas: diagnosis, treatment, and literature review. Brain Tumor Pathol 2013;31:1–7. 13. Freedman AM, Meland NB. Angioleiomyomas of the extremities: report of a case and review of the mayo clinic experience. Plast Reconstr Surg 1989;83:328–31. 14. Matsuyama A, Hisaoka M, Hashimoto H. Angioleiomyoma: a clinicopathologic and immunohistochemical reappraisal with special reference to the correlation with myopericytoma. Hum Pathology 2007;38:645– 51.
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there were some factors that might improve the diagnosis of angioleiomyoma. The CSH was derived from the venous plexus inside the cavernous sinus and then grew expansively (25). The tumor might encase the internal carotid arteries and grow along with the intercavernous sinus after the breaking through the thin medial wall of the cavernous sinus. Therefore, the image of CSH showed an irregular dumbbell or beak shape, whereas CSA showed a blunt circle shape. From the surgery it was observed that CSA seemed to be derived from the interlayer between the dura mater and the lateral wall of the cavernous sinus, which was supported by the radiographic regular blunt circle shape of the medial wall of the CSA and the compressed ICA. Moreover, the progressive enhancements of the two tumors were also different. The T1 enhancement of CSH manifested that the capsule was gradually diffused to the tumor after enhancement (26); however, CSA showed sponge-like diffusion from one side or pointed toward other parts of the tumor. More stroma and less blood sinus in CSA might cause slower diffusion of contrast agents than that in CSH. Clinically, MRI easily detected an early dispersoid of CSA and a late dispersoid of CSH; the imaging significance of which was needed to be confirmed in further tests.
Jpn J Clin Oncol 2014;44(11)
23. 24. 25. 26. 27. 28.
literature and magnetic resonance imaging findings of this rare entity. Oral Surg Oral Med Oral Pathol Oral Radiol 2012;114:e45– 9. Moon IH, Chin SS, Park MK. Preauricular angioleiomyoma. Korean J Audiol 2012;16:138–40. Song X-l, Sun X-y, Zhang G-l, Yu Y-w, Wang C-h. Myopericytoma presenting as multiple pulmonary nodules. Intern Med 2012;51: 639 – 42. Sohn CH, Kim SP, Kim IM, Lee JH, Lee HK. Characteristic mr imaging findings of cavernous hemangiomas in the cavernous sinus. Am J Neuroradiol 2003;24:1148–51. Goel A, Muzumdar D, Sharma P. Extradural approach for cavernous hemangioma of the cavernous sinus: Experience with 13 cases. Neurol Med Chir 2003;43:112–9. Coppa ND, Raper DM, Zhang Y, et al. Treatment of malignant tumors of the skull base with multi-session radiosurgery. J Hematol Oncol 2009;2:16. Nikolajek K, Kufeld M, Muacevic A, et al. Spinal radiosurgery—efficacy and safety after prior conventional radiotherapy. Radiat Oncol 2011;6:173.
Downloaded from http://jjco.oxfordjournals.org/ at University of North Carolina at Chapel Hill on November 3, 2014
15. Miranda LQ, Rehfeldt FV, Silva RS, Fonseca JC, Alves Mde F. Case for diagnosis. An Bras Dermatol 2012;87:322–3. 16. Figueiredo EG, Gomes M, Vellutini E, Rosemberg S, Marino Jr R. Angioleiomyoma of the cavernous sinus: case report. Neurosurgery 2005;56:E411. 17. Morimoto N. Angiomyoma (vascular leiomyoma): A clinicopathologic study. Med J Kagoshima Univ 1973;24:663–83. 18. Duhig JT, Ayer JP. Vascular leiomyoma. A study of sixtyone cases. Arch Pathol 1959;68:424– 30. 19. Zhou L-F, Mao Y, Chen L. Diagnosis and surgical treatment of cavernous sinus hemangiomas: an experience of 20 cases. Surg Neurol 2003;60: 31–6. 20. Diamantopoulou A, Kotziamani N, Tsitouridis I. Imaging findings of cavernous sinus hemangiomas. Neuroradiol J 2009;22:419– 25. 21. Hiromatsu S, Nata S, Tobinaga S, Aoyagi S. A case of angioleiomyoma presenting as a pulsatile tumor in the left ring finger. Ann Vasc Surg 2011;25:698. e699–698. e612. 22. Eley KA, Alroyayamina S, Golding SJ, Tiam RN, Watt-Smith SR. Angioleiomyoma of the hard palate: report of a case and review of the
1057
Diagnosis and Surgical Treatment of Cavernous Sinus Angioleiomyoma: A Report of Four Cases Kangmin He†, Liang Chen†, Wei Zhu, Haixia Cheng, Yin Wang and Ying Mao* Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai 200040, China
Received March 7, 2014; accepted August 18, 2014
Objective: The aims of the study were to retrospectively evaluate the imaging characteristics of cavernous sinus angioleiomyoma and explore appropriate surgical approaches. Methods: A total of four cases admitted to our hospital for repeated episodes of headache were enrolled. The common clinical manifestations included decreased vision, diplopia, blepharoptosis and facial numbness. The first three patients were misdiagnosed with cavernous sinus hemangioma, meningioma and chordoma, respectively. The fourth case was suspected to be angioleiomyoma. Imaging examination showed an oval-shaped tumor occupying the cavernous sinus. The tumor was hypointense on T1-weighted magnetic resonance imaging and extremely hyperintense on T2-weighted scan, which was similar to the cerebrospinal fluid, and was progressively enhanced from one side after gadolinium injection, pushing the internal carotid artery toward the inner side. Results: Surgical resection was performed via an epidural approach for these four cases. Clinical symptoms were improved after surgery and no recurrence was observed during followup visits (average, 47.5 months). Conclusions: The initial symptom of cavernous sinus angioleiomyoma was repeated headache. The tumor seems extremely hyperintense on a T2-weighted image and expansive growth is pushing away the internal carotid artery rather than encasing it. It was progressively enhanced from one side after gadolinium injection. Surgical treatment based on an epidural approach had an excellent outcome in tumor resection and nerve protection. Key words: cavernous sinus angioleiomyoma – neurological – surgery – tumor – nerve protection
INTRODUCTION Angioleiomyoma (also known as angiomyoma, vascular leiomyoma or dermal angioma 1), one subtype of leiomyomas, is a relatively rare benign soft tissue tumor that consists of a mixture of well-differentiated smooth muscle cells and small thick-walled vessels (2). Recently, angioleiomyoma, commonly located in the extremities of middle-aged individuals (3), has been described in other locations, including uterus (4), larynx (5) and rectum (6). This tumor presents as hoarseness or pain and the therapy of choice is complete surgical excision (7,8). An accurate intracranial site for this tumor is exceedingly rare and four relevant cases have been
reported so far. Only two of these case reports have discussed angioleiomyoma involved in the cavernous sinus (9,10). Although the surgical anatomy of the cavernous sinus has been studied by a number of investigators, cavernous sinus exposure remains a difficult task because of the complicated neural and vascular relationships in this area (11), and the pre-operative misdiagnosis rate is very high (12). In this article, we present four cases of cavernous sinus angioleiomyoma (CSA) along with a concise review of clinical, pathological, radiological and surgical features for the purpose of identifying clinical characteristics and exploring suitable surgical treatments.
# The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: [email protected]
Downloaded from http://jjco.oxfordjournals.org/ at University of North Carolina at Chapel Hill on November 3, 2014
*For reprints and all correspondence: Ying Mao, Department of Neurosurgery, Huashan Hospital, No.12 Wulumuqi Middle Road, Shanghai 200040, China. E-mail:[email protected] † Kangmin He and Liang Chen contributed equally to this paper as co-first authors.
Jpn J Clin Oncol 2014;44(11)
PATIENTS AND METHODS
misdiagnosed with cavernous sinus hemangioma (CSH), meningioma and chordoma, respectively. The fourth case was suspected to be angioleiomyoma. The results of MRI of the fourth case are shown in Figure 1a – e. Computed tomography (CT) scan of head revealed a hyperintense lesion; MRI revealed a round or oval mass lesion occupying the cavernous sinus. The tumor seems hypointense on a T1-weighted MRI scan and was abnormally hyperintense on a T2-weighted scan, which was similar to the cerebrospinal fluid (CSF) and was progressively enhanced from one side after gadolinium injection. In addition, the internal carotid artery (ICA) was pushed toward the inner side.
CLINICAL MANIFESTATION
SURGICAL TREATMENT
The most common clinical manifestations of the four cases are listed in Table 1.
The surgical procedure was performed by using the middle fossa extradural approach through pterional incision, for which the patients were given general anesthesia using tracheal cannula. A lumbar drainage was used to drain CSF during the operation to control intracranial pressure. The dura mater was separated from the lateral orbital wall until the turning point. In addition, the lateral bone of the superior orbital fissure was drilled off. After opening the dura, the tumor was visible and then it was completely removed. The cranial nerves were preserved carefully during the normal anatomical procedure. If the subdural water-filling was normal, the dural wall was sutured closely. At the end of the operation, the operated area of the cavernous sinus was obturated with a gelatin sponge when the efficacy of hemostasis was satisfactory. Meanwhile, the surrounding dura was suspended and the bone flap was repositioned.
† Case 1: A 46-year-old woman had a 1-year history of headache and 4 months of blepharoptosis in the right eye. Physical examination revealed right oculomotor nerve palsy and decreased visual acuity. In addition, strength of the right masseter muscle was poor. † Case 2: A 57-year-old man having a more than 10-year history of headache and 3-month history of progressive right vision loss accompanied by diplopia. Physical examination revealed that an abduction defect had occurred in his right eye. † Case 3: A 48-year-old woman presented with 7-year history of headache and 1-year history of right severe ptosis. The physical examination disclosed central visual field defects of the right eye and right oculomotor nerve paresis. † Case 4: A 35-year-old woman with 1-year history of headache and 1-week history of decreased left vision accompanied with diplopia. Physical examination revealed that the bilateral vision field was normal. Although movement of her left eye was limited, optical acuity was normal. IMAGING EXAMINATION All patients were evaluated pre-operatively using magnetic resonance imaging (MRI). The first three patients were
PATHOLOGICAL FINDINGS The lesions of all the cases were similar with the typical appearance of angioleiomyoma composed of numerous thickwalled vessels without vascular elastic lamina and intermingled with intersecting fascicles of spindle-shaped smooth muscle cells. The distribution of vessels displayed cracks or spongy expansion. The spindle-shaped cells with blunt-ended nuclei and vacuolar cytoplasm were irregularly arranged surrounding the vessels. The cell nuclei were well differentiated
Table 1. Clinical manifestation of cavernous sinus angioleiomyoma Case
Sex/age (years)
Tumor diameter (cm)
Duration of headache (years)
Vision Right
Left
Diplopia
Blepharoptosis
Oculomotor nerve palsy
Abduction limitation
1
F/46
2
1
0.1
0.8
–
Right
Right
–
2
M/57
3
10
0.1
0.6
Right
–
–
Right
3
F/48
3
7
–
–
–
Right
Right
–
4
F/35
2
1
0.8
0.8
Left
–
–
Left
– Stands for normal.
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All four subjects enrolled in the study gave informed consent and the study protocol was approved by the Hua Shan Hospital’s committee on human research. The primary antibodies for the immumohistochemical staining were as follows: mouse anti-human CD34 antibodies (clone 581, BD PharMingen); mouse anti-human smooth muscle actin (SMA) antibodies (clone 1A4, Sigma); mouse anti-human S100 antibodies (clone 19/S100B, BD Transduction Laboratories); mouse anti-human monoclonal Ki-67 (MIB-1) antibodies (clone B56, BD PharMingen).
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without atypia and mitotic activity was rarely found. The lesion areas showed mucoid degeneration, glassy degeneration and lipoid degeneration (Fig. 1f). Immunohistochemical analysis demonstrated that the spindle-shaped cells were positive for SMA (Fig. 1h). The endothelial cells in the tumor vessel wall expressed high levels of CD34 (Fig. 1g). The small nerve fibers from the lesion capsule and stroma were positive for S100 (Fig. 1i), and the MIB-1 proliferation index ranged from 1 to 2% (Fig. 1j).
Table 2. The follow-up studies of four patients Case Discharge Follow-up study (days after operation) Months Vision
Diplopia Blepharoptosis Abduction limitation
Right Left 1
7
60
0.6
–
–
Improved
–
2
10
45
0.6
–
–
Improved
Improved
FOLLOW-UP STUDY
3
11
35
–
–
–
Improved
Improved
These four patients with CSA were not treated with radiation therapy post-operatively. A follow-up MRI examination was made available and the average follow-up period was 47.5 months. The follow-up examinations demonstrated no residual tumor and no recurrence. The Modified Rankin Scale (mRS) of all was 2. The details are given in Table 2.
4
14
2
–
–
–
–
–
CASE 1
CASE 3
The patient was discharged from the hospital 1 week after the operation. The right vision was improved, but other symptoms were not improved on discharge compared with that during admission. The follow-up visit of 72 months showed that the clinical symptoms improved well and right visual acuity returned to 0.6.
After the surgery, the patient was discharged 11 days later with dysfunction of her right eye, including blepharoptosis, limited movement, pupilla of 3 mm and the absence of optical acuity. Compared with the clinical conditions at the time of discharge, the follow-up outcome (47 months) showed that clinical symptoms were improved.
CASE 2
CASE 4
The body temperature rose post-operatively and was eased via conservative treatments. Although the right eye showed
The patient was discharged 2 weeks after surgery without any obvious change. The clinical and radiological follow-up visits
blepharoptosis and moved disorderly, the right vision was improved. A follow-up visit at 57 months showed that his right visual acuity returned to 0.6 and dysfunctions were recovered to different degrees.
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Figure 1. Results of MRI of the fourth case. (a) An oval-shaped lesion occupying the right cavernous sinus; (b) T1-weighted images showed hyperintense tumor (approach to cerebrospinal fluid) with a blunt round shape (white arrow); (c) tumor with progressive enhancement after contrast medium injection (white arrow); (d) CT angiography (CTA) indicated that the right intracavernous internal carotid artery (ICICA) was pressed toward the inner side; (e) the follow-up outcome showed that the tumor was completely removed with no residual tumor and no recurrence; (f ) microscopic images show that the tumor comprised welldifferentiated smooth muscle bundles and thick-walled blood sinuses, including hyaline degeneration (indicated as a triangle) (hematoxylin and eosin staining; 100); (g) endothelial cells showing positivity for CD34 (immunohistochemistry; 100); (h) smooth muscle cells showing strong positivity for smooth muscle actin (SMA) (immunohistochemistry; 100); (i) small nerve fibers from the lesion capsule and stroma showing strong positivity for S100, depicted by a black arrow (immunohistochemistry; 100); ( j) the MIB-1 proliferation index was 2% (immunohistochemistry; 200).
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(14 months) demonstrated that diplopia disappeared and others were not improved.
DISCUSSION
PATHOLOGY The CSA comprises sharply demarcated nodules of smooth muscle tissue and thick-walled vessels with various sizes (16). The smooth muscle cells are mature and well differentiated. Microscopically, lesions with mucoid, fat or hyaline degeneration can be observed, as well as hemorrhage and calcification. These tumor cells usually lack nuclear atypia and mitotic activity (the MIB-1 proliferation index was merely 1.5% in four cases). Histologically, Morimoto et al. (17) have studied 241 cases of angioleiomyoma and classified them into solid, venous and cavernous types. Smooth muscle bundles are closely compacted in solid tumors and intersect with each other. Vascular channels are usually multiple and small-sized. In venous-type tumors, smooth muscle bundles are not closely compacted and have venous-type vascular channels with thin muscular walls. Dilated vascular channels can be seen in the cavernous type and muscular walls of these vessels are hardly to be distinguished from intervening smooth muscle bundles. In this study, all cases showed dilated vascular channels with thin muscular walls, which belonged to the cavernous type. Duhig and Ayer have suggested that angioleiomyomas are not true tumors but instances of vascular malformations (18). Moreover, the smooth muscle proliferation within a hemangioma produces a vascular leiomyoma and further leads to a simple leiomyoma (18). Combined with previous study, we proposed typical differences here between CSA and CSH. CSH is derived from cavernous sinus vasculature, consisting of irregularly sized vessel cavities or sinuses (19,20). The main characteristics are as follows: the sinus walls are formed by a single-layer intima; a few connective tissues are visible and no neural tissue is found among the vessels; less smooth muscle cells are found and distributed around the vessel wall from the immunostaining of SMA. In contrast, angioleiomyoma is derived from vascular smooth muscle (21). The main characteristics include thick-walled vessels and well-differentiated smooth muscle bundles within the lumens. Immunostaining of SMA indicates
that smooth muscles are generally localized in the stroma. Hasegawa et al. (1,10) have found that small nerve fibers (immunoreactive for S-100 protein and PGP 9.5) could be identified within the stroma of 69% of painful tumors in the clinicopathological and immunohistochemical studies of angioleiomyoma, suggesting that the painful tumors may be mediated by the nerve fibers located in the tumor parenchyma. The results of our study were consistent with those of previous studies. CLINICAL PRESENTATION Specific pain is the typical clinical symptom of angioleiomyoma and may be mediated by nerve fibers in the solid part of the tumor (22). According to the statistics of World Health Organization, non-intracranial angioleiomyomas are usually manifested as separated slowly growing subcutaneous nodules (diameter ,2 cm) and pain can be induced when exposed to cold wind (23). Meanwhile, pain is the most striking clinical feature of intracranial angioleiomyoma (24). Long repeated headache prior to the onset of the eye symptoms has been reported in two previous cases, which is also found in our studies, indicating that headache is the early characteristic symptom. The different pain of CSH is due to capsular tension, while the pain of angioleiomyoma may be induced by mechanical compression of vascular smooth muscle cells toward nerve fibers in the stroma. As a result, the pain of angioleiomyoma is stronger than that of CSH. In our study, it was interesting that all the four patients were middle-aged individuals, which might be related to the growth rate of CSA. Generally, these tumors occur insidiously and progress slowly, which leads to the missed diagnosis of CSA at the early stage. During admission, the diameters of lesions were .2 cm; the cranial nerves (II, III, IV, V and VI) showed dysfunction and compression symptoms that occurred in the cavernous sinus. RADIOLOGICAL FINDINGS Pre-operative diagnosis of CSA was performed to distinguish angioleiomyomas from meningiomas, neurinomas, chordomas and cavernous hemangiomas based on CT and MRI examination. In the two previous reports (9,10), CT revealed a well-defined or slightly hyperdense tumor with homogeneous enhancement after contrast medium injection. T 1-weighted MR images showed a hypointense tumor, while T2-weighted and T 2 /FLAIR MR images showed a hyperintense tumor (similar to CSF). These lesions were enhanced progressively after injection of contrast medium. The four cases in our study displayed similar MRI results. According to the varying levels of hyperintensity of the T2-weighted MRI and enhancement following the injection of contrast medium, it was easy to distinguish CSA from meningioma, neurilemmoma and chordoma. However, it was difficult to differentiate CSA from cavernous hemangiomas because of their similar characteristics on MRI. In this study,
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Angioleiomyoma is a benign soft tissue tumor arising from the muscle layer of blood vessels (13) and occurs frequently in the extremities of middle-aged individuals with a predominance in women (1,3). Head and neck locations have been described (14), but the case of angioleiomyoma arising within the cavernous sinus is extremely rare and only two reports concerning CSA have been reported (9,10). It has been reported that some etiologic factors may contribute to angioleiomyoma, such as hormonal changes (principally associated with estrogen), previous trauma and venous stasis (15). To date, the clinical features and surgical treatments of CSA have not been explicitly explained.
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SURGICAL TREATMENT † Surgical indications: because of the insidious onset of CSA, radiation therapy was not planned and surgery seemed to be the best option for CSA patients. † Surgical approaches: the intradural approach (9), an acceptable procedure for tumors near the parasella, can cause significant atrophy of the temporal lobe after the resection of the CSA. In our study, we resected lesions of CSA via an epidural approach. During the surgical process, intracranial nerves and vessels were exposed adequately, the middle meningeal artery was blocked earlier to choke off blood supply, and the subarachnoid space was prevented from the contamination of hemorrhage. Meanwhile, the reflux venous of temporal lobe was normal. During the operation, the tumor was visible after stripping the outer layer of the cavernous sinus. The tumors were segregated carefully from cranial nerves III, IV and V along with the pseudocapsule of the tumors. The huge lesion was progressively dissociated by induction of whole-body decompression or bipolar coagulation. If shrinking of the huge tumor is not effective, puncture of the tumor should be performed to avoid misdiagnosis of CSH after the border tissue is separated out as much as possible. Cut-off of the capsule and piecemeal removal of the tumor was then performed under the condition of puncture position without hemorrhage. The follow-up visit after surgery showed recovered or improved cranial nerves and no recurrence. † Radiosurgery: the outcome of radiosurgical treatment was not clear and a malignant potential for the lesion was reported in previous study (27,28). Given the benign progress after resection of the CSA, complete resection was
verified by MRI and post-operative radiosurgical treatment was unnecessary.
CONCLUSION CSA is a rare benign tumor arising from the interlayer between the dura mater and the lateral wall of the cavernous sinus. Patients with CSA could present with recurrent headache of long duration prior to clinical symptoms of intracranial neurological dysfunctions and space-occupying oppressive symptoms of the cavernous sinus. The location of the ICA, tumor shape and the enhancement on MRI image could provide a possible basis for the diagnosis of CSA. The excision via an epidural approach is usually curative and the prognosis is good.
Funding This study was supported by the National Natural Science Foundation of China 2011 to Chen Liang.
Conflict of interest statement None declared.
References 1. Ramesh P, Annapureddy SR, Khan F, Sutaria PD. Angioleiomyoma: a clinical, pathological and radiological review. Int J Clin Pract 2004;58:587– 91. 2. Willoughby AD, Schlussel AT, Freeman JH, Lin-Hurtubise K. Angioleiomyoma in a rare location: a case report. Hawaii J Med Public Health 2013;72:45– 8. 3. Hachisuga T, Hashimoto H, Enjoji M. Angioleiomyoma. A clinicopathologic reappraisal of 562 cases. Cancer 1984;54:126–30. 4. Jin CH, Yi KW, Kim YS, et al. Uterine angioleiomyoma: unusual appearance at laparoscopy. J Minim Invasive Gynecol 2013;20:149– 50. 5. Eyigor H, Suren D, Osma U, Sezer C, Yilmaz MD. A case of angiomyolipoma rarely located in the larynx. Case Rep Otolaryngol 2011;2011:427074. 6. Stanojevic GZ, Mihailovic DS, Nestorovic MD, et al. Case of rectal angioleiomyoma in a female patient. World J Gastroenterol 2013;19:2114– 7. 7. Choe KS, Sclafani AP, McCormick SA. Angioleiomyoma of the auricle: a rare tumor. Otolaryngol Head Neck Surg 2001;125:109– 10. 8. Brooks J, Ricalde P, Nikitakis N, Levy B. Angioleiomyoma of the tongue. Gen Dent 2004;52:52. 9. Colnat-Coulbois S, Schmitt E, Klein O, et al. Angioleiomyoma of the cavernous sinus: case report. Neurosurgery 2008;62:E257 – 258; discussion E258. 10. Figueiredo EG, Gomes M, Vellutini E, Rosemberg S, Marino R, Jr. Angioleiomyoma of the cavernous sinus: case report. Neurosurgery 2005;56:E411; discussion E411. 11. Dalgic A, Boyaci S, Aksoy K. Anatomical study of the cavernous sinus emphasizing operative approaches. Turk Neurosurg 2010;20: 186– 204. 12. Li D, Hao S-Y, Tang J, et al. Primary intracranial angioleiomyomas: diagnosis, treatment, and literature review. Brain Tumor Pathol 2013;31:1–7. 13. Freedman AM, Meland NB. Angioleiomyomas of the extremities: report of a case and review of the mayo clinic experience. Plast Reconstr Surg 1989;83:328–31. 14. Matsuyama A, Hisaoka M, Hashimoto H. Angioleiomyoma: a clinicopathologic and immunohistochemical reappraisal with special reference to the correlation with myopericytoma. Hum Pathology 2007;38:645– 51.
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there were some factors that might improve the diagnosis of angioleiomyoma. The CSH was derived from the venous plexus inside the cavernous sinus and then grew expansively (25). The tumor might encase the internal carotid arteries and grow along with the intercavernous sinus after the breaking through the thin medial wall of the cavernous sinus. Therefore, the image of CSH showed an irregular dumbbell or beak shape, whereas CSA showed a blunt circle shape. From the surgery it was observed that CSA seemed to be derived from the interlayer between the dura mater and the lateral wall of the cavernous sinus, which was supported by the radiographic regular blunt circle shape of the medial wall of the CSA and the compressed ICA. Moreover, the progressive enhancements of the two tumors were also different. The T1 enhancement of CSH manifested that the capsule was gradually diffused to the tumor after enhancement (26); however, CSA showed sponge-like diffusion from one side or pointed toward other parts of the tumor. More stroma and less blood sinus in CSA might cause slower diffusion of contrast agents than that in CSH. Clinically, MRI easily detected an early dispersoid of CSA and a late dispersoid of CSH; the imaging significance of which was needed to be confirmed in further tests.
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23. 24. 25. 26. 27. 28.
literature and magnetic resonance imaging findings of this rare entity. Oral Surg Oral Med Oral Pathol Oral Radiol 2012;114:e45– 9. Moon IH, Chin SS, Park MK. Preauricular angioleiomyoma. Korean J Audiol 2012;16:138–40. Song X-l, Sun X-y, Zhang G-l, Yu Y-w, Wang C-h. Myopericytoma presenting as multiple pulmonary nodules. Intern Med 2012;51: 639 – 42. Sohn CH, Kim SP, Kim IM, Lee JH, Lee HK. Characteristic mr imaging findings of cavernous hemangiomas in the cavernous sinus. Am J Neuroradiol 2003;24:1148–51. Goel A, Muzumdar D, Sharma P. Extradural approach for cavernous hemangioma of the cavernous sinus: Experience with 13 cases. Neurol Med Chir 2003;43:112–9. Coppa ND, Raper DM, Zhang Y, et al. Treatment of malignant tumors of the skull base with multi-session radiosurgery. J Hematol Oncol 2009;2:16. Nikolajek K, Kufeld M, Muacevic A, et al. Spinal radiosurgery—efficacy and safety after prior conventional radiotherapy. Radiat Oncol 2011;6:173.
Downloaded from http://jjco.oxfordjournals.org/ at University of North Carolina at Chapel Hill on November 3, 2014
15. Miranda LQ, Rehfeldt FV, Silva RS, Fonseca JC, Alves Mde F. Case for diagnosis. An Bras Dermatol 2012;87:322–3. 16. Figueiredo EG, Gomes M, Vellutini E, Rosemberg S, Marino Jr R. Angioleiomyoma of the cavernous sinus: case report. Neurosurgery 2005;56:E411. 17. Morimoto N. Angiomyoma (vascular leiomyoma): A clinicopathologic study. Med J Kagoshima Univ 1973;24:663–83. 18. Duhig JT, Ayer JP. Vascular leiomyoma. A study of sixtyone cases. Arch Pathol 1959;68:424– 30. 19. Zhou L-F, Mao Y, Chen L. Diagnosis and surgical treatment of cavernous sinus hemangiomas: an experience of 20 cases. Surg Neurol 2003;60: 31–6. 20. Diamantopoulou A, Kotziamani N, Tsitouridis I. Imaging findings of cavernous sinus hemangiomas. Neuroradiol J 2009;22:419– 25. 21. Hiromatsu S, Nata S, Tobinaga S, Aoyagi S. A case of angioleiomyoma presenting as a pulsatile tumor in the left ring finger. Ann Vasc Surg 2011;25:698. e699–698. e612. 22. Eley KA, Alroyayamina S, Golding SJ, Tiam RN, Watt-Smith SR. Angioleiomyoma of the hard palate: report of a case and review of the
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