- Email: [email protected]
Orbital leiomyoma: Report of a case and review of the literature
SURVEY OF OPHTHALMOLOGY
VOLUME 49 • NUMBER 2 • MARCH–APRIL 2004
CLINICAL PATHOLOGIC REVIEWS MILTON BONIUK AND STEFAN SEREGARD, EDITORS
Orbital Leiomyoma: Report of a Case and Review of the Literature Kaan Gu¨ndu¨z, MD,1 Ilhan Gu¨nalp, MD,1 Esra Erden, MD,2 and Selim Erekul, MD2 1
Ocular Oncology Service, Department of Ophthalmology, and 2Department of Pathology, Ankara University Faculty of Medicine, Ankara, Turkey
Abstract. A 10-year-old female presented with slowly progressive proptosis of 1 year’s duration. Orbital MRI revealed an extraconal oval mass occupying the lateral half of the mid and posterior orbit. The tumor was isointense to the extraocular muscle and cerebral gray matter on T1-weighted images and hyperintense on T2-weighted images. The patient underwent superolateral orbitotomy, and it was felt that the tumor was totally excised in a piecemeal fashion. Histopathologic examination showed that the tumor was composed of spindle cells arranged in a fibrous stroma rich in dilated sinusoidal capillaries. The nuclei of tumor cells were oval with blunted ends. There were no mitotic figures. Immunohistochemically, the tumor stained positive with smooth muscle actin, desmin, and vimentin. Based on the histopathologic and immunohistochemical staining results, a diagnosis of orbital leiomyoma was made. At 34 months follow-up, the patient continues to have 20/20 vision and is free of tumor recurrence clinically. Orbital leiomyoma is an uncommon tumor. Search of the English literature showed only 15 previous cases of orbital leiomyoma that have been published since 1963. (Surv Ophthalmol 49:237–242, 2004. 쑖 2004 Elsevier Inc. All rights reserved.) Key words. Computed tomography • immunohistochemistry resonance imaging • orbit • pathology
Leiomyoma is a benign tumor that is most commonly encountered in the uterus and gastrointestinal tract. However, it can also occur in the uveal tract and orbit. Uveal leiomyoma is an uncommon intraocular tumor, which usually occurs in the iris and ciliary body.3 Rarely, it can also occur in the posterior choroid.23 Uveal leiomyoma usually presents an an amelanotic mass, causing diagnostic confusion with amelanotic melanoma.9 Similar to uveal leiomyoma, orbital leiomyoma is an uncommon tumor. We report herein a case of orbital leiomyoma and review previously published cases. Our case is interesting because of the anatomic
•
leiomyoma
•
magnetic
location of the tumor which has not been reported before. Further, it illustrates the immunohistochemical staining and magnetic resonance imaging (MRI) features of orbital leiomyoma, which have not been well illustrated in other publications.
Case Report A 10-year-old girl presented with a 1-year history of progressive proptosis in the left eye. She had 7 mm proptosis in the left eye (Fig. 1), which was pushed medially and inferiorly. The motility of the left eye 237
쑖 2004 by Elsevier Inc. All rights reserved.
0039-6257/04/$–see front matter doi:10.1016/j.survophthal.2003.12.010
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Surv Ophthalmol 49 (2) March–April 2004
Fig. 1. Preoperative facial photograph shows the 10-yearold child with proptosis of the left eye.
was restricted in all positions of gaze, especially superiorly and temporally. Visual acuity in the left eye was 20/20. Slit-lamp biomicroscopy revealed normal findings. On funduscopy, an elevated choroidal mass in the superotemporal quadrant arising from compression of the globe by the orbital tumor was noted. The right eye was normal. Orbital MRI demonstrated a well-circumscribed oval mass filling the middle and posterior left orbit, producing scleral indentation of the left globe. On MRI, the tumor was isointense with respect to the extraocular muscle and cerebral gray matter on T1weighted images and hyperintense on T2-weighted images (Fig. 2). The tumor showed moderate contrast enhancement. The patient underwent a superolateral orbitotomy with an eyelid crease approach (KG) and it was felt that the tumor was totally excised in a piecemeal
Fig. 2. Preoperative orbital MRI demonstrates a well-circumscribed oval mass occupying the lateral half of the mid and posterior orbit, producing scleral indentation of the left globe. The tumor is isointense to the extraocular muscle and cerebral gray matter on T1-weighted images (top) and hyperintense on T2-weighted images (bottom).
fashion. Grossly, the tumor had a solid lobulated redtan appearance (Fig. 3). Histopathologic findings disclosed that the tumor was composed of bundles of spindle cells embedded in a fibrous stroma rich in dilated sinusoidal capillaries. The nuclei of tumor cells had an oval shape with blunted ends and some had prominent nucleoli (Fig. 4). There were no mitotic figures. The tumor cells displayed intense fuchsinophilia on Masson trichrome stain. Immunohistochemically, the tumor stained positive with smooth muscle actin (SMA) (Fig. 5), desmin, and vimentin. The tumor cells showed negative immunoreactivity for myoglobulin, neuron specific enolase (NSE), CD-34, Leu-7, S-100, and HMB-45. The histopathologic findings and pattern of immunoreactivity were found to be consistent with orbital leiomyoma. At 38 months follow-up, left eye visual acuity remained at 20/20 and there was no clinical or MRI evidence of a recurrent tumor (Fig. 6).
Discussion CLINICAL AND RADIOLOGICAL FEATURES
The first case of orbital leiomyoma was reported in 1896. Nath and Shukla18 in 1963 and Sanborn and associates21 in 1979 collectively recorded seven cases of orbital leiomyoma that had been diagnosed between 1896 and 1938. The data sources for these seven cases as cited in the two articles above are quoted in the references.5,6,16,17,24,25,29 The results of our English literature search showed that, starting with the case of Nath and Shukla in 1963,18 15 well-documented cases of orbital leiomyoma have been published over the past 40 years.1,2,4,10–12,14,15,18–21,26,27 The demographics, treatment methods, and follow-up in these 15 previously reported patients and our case reported herein are summarized in Table 1. The age of the patients ranged from 9 years to 57 years, the mean age being 30 years. Of the 16 patients with orbital leiomyoma, 11 were males, 4 were females, and the sex of the
Fig. 3. Gross photograph of the excised tumor showing the tan-red colored orbital leiomyoma.
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ORBITAL LEIOMYOMA
Fig. 4. Photomicrograph shows that the tumor is composed of spindle-shaped cells with blunt-ended nuclei embedded in a background of dilated sinusoidal capillaries (Hematoxylin-eosin × 400).
patient was not reported in one case. In contrast to uveal leiomyoma, orbital leiomyoma is more common in males. The reason for this male preponderance is not clear. Clinically, patients with orbital leiomyomas located deep in the orbit present with painless proptosis or displacement of the globe progressing slowly over several months or years. Our case had a similar clinical course spanning a 1-year period. Leiomyomas located in the anterior orbit and eyelids may present with progressive painless swelling of the eyelids.2,12,14,19 Orbital leiomyoma can occur as an intraconal or extraconal tumor. Review of the previously published cases (Table 1) showed that 6 of 16 orbital leiomyomas were intraconal, 7 occupied an extraconal location close to or infiltrating the eyelids, and 3 demonstrated orbital apex involvement. Two of three
Fig. 6. Postoperative facial photograph shows normal external findings and the skin scar from the orbitotomy incision on the left upper eyelid at one year follow-up.
cases of orbital leiomyoma with orbital apex involvement demonstrated intracranial involvement. The current case is unique in that the tumor occurred in a deep extraconal position in the orbit, unlike the previous extraconal leiomyomas that have been reported to occur in the anterior orbit.2,10,12,14,19,21 Computed tomography (CT) and MRI usually demonstrate a well-circumscribed orbital tumor. Compared to CT, MRI provides more detail on internal tissue characteristics of orbital leiomyoma. On MRI, orbital leiomyoma was isointense with respect to the extraocular muscle and cerebral gray matter on T1-weighted images and hyperintense on T2-weighted images. Orbital leiomyoma showed moderate contrast enhancement. Many orbital tumors demonstrate similar MRI signal characteristics on T1- and T2-weighted images.7 The differential diagnosis of orbital leiomyoma from other intraconal and extraconal tumors can be difficult with CT and MRI. Orbital leiomyoma can demonstrate intracranial extension12,15 which is best delineated on MRI. Other benign orbital tumors, such as schwannoma and neurofibroma, can also demonstrate intracranial extension through the superior orbital fissure.22 PATHOGENESIS
Fig. 5. Photomicrograph demonstrates that the tumor stains intensely with smooth muscle actin (SMA) (Smooth muscle actin × 400).
Orbital leiomyoma is believed to arise from the smooth muscle of orbital blood vessels, pericytes, Mu¨ller’s muscle, or capsulopalpebral muscle of Hessar.2,11,18 Tumors located in the anterior orbit close to the eyelids may develop from the capsulopalpebral muscle of Hessar.18 The pericyte is a possible cell of origin for orbital leiomyoma. Transmission electron microscopic studies have shown that the pericyte undergoes several evolutionary stages, ranging
240
The Demographics, Preoperative Tumor Features, Treatment Methods, and Follow-up in 16 Cases of Orbital Leiomyoma First Author
Year
Age/Sex
Location in the Orbit
Quadrant
Intracranial Extension
Nath18 Wolter27 Henderson10 Jakobiec11 Jakobiec12 Jakobiec12
1963 1965 1970 1973 1975 1975
18/F 41/M 9/F 17/NA 17/M 34/F
Intraconal Intraconal Anterior Apex Anterior Apex
– – Inferior – Medial –
No No No No No Yes
Excision Excision Excision Incision Excision Excision
N/A N/A N/A Residual tumor Stable Recurrent tumor
Neetens19 Sanborn21 Saga20 Vigstrup26
1979 1979 1982 1982
34/F 5/M 53/M 35/M
Anterior Anterior Intaconal Intraconal
Superior Medial – –
No No No No
N/A Stable Pseudo-tumor Stable
Betharia2 Carrier4 Jolly14 Badoza1 Kulkarni15
1991 1993 1995 1999 2000
39/M 57/M 42/M 56/M 9/M
Anterior Intraconal Anterior Intraconal Apex
Inferior – Inferior – –
No No No No Yes
Current case
2004
10/M
Extraconal
Excision Excision Incomplete excision Incomplete excision Excision Excision Excision Excision Subtotal excision via craniotomy Excision
a
Lateral
No
Initial Orbital Surgery
Orbital Status after Initial Surgery
N/A N/A Stable Stable Recurrent tumor Stable
Secondary Treatment
Follow-up
Patient Status
N/A N/A N/A Excision None EBRT(114 Gy), Exenteration N/A None Incision, steroids None
N/A N/A N/A 7 years 16 years 17 years N/A 28 monthsa 7 months 12 months
N/A N/A N/A Alive Alive Dead of sarcoma metastasis N/A Alive Alive Alive
N/A N/A None None Excision via craniotomy None
N/A N/A 15 months 1 month 5 years
N/A N/A Alive Alive Alive
38 months
Alive
Surv Ophthalmol 49 (2) March–April 2004
TABLE 1
After the submission of the report, the patient developed orbital recurrence treated by excision.
¨ NDU ¨ Z ET AL GU
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ORBITAL LEIOMYOMA
from poorly differentiated mesenchymal cells of capillary walls to more highly differentiated smooth muscle cells of venular walls.11 Considering its anatomic location in the orbit, the tumor in our case probably developed from the smooth muscle of orbital blood vessels or pericytes. The term mesectodermal leiomyoma has been used to describe some of uveal tumors, because the uveal tissues are believed to arise from the neural crest embryologically.23 Similar terminology has also been suggested for orbital leiomyoma because of the origin of this tumor from smooth muscle cells or pericytes derived from the neural crest.13 MORPHOLOGICAL FEATURES
The results of histopathologic examination in our case disclosed that the tumor consists of bundles of spindle-shaped cells with oval nuclei arranged in a fibrous stroma with dilated sinusoidal capillaries (Fig. 4). Sometimes the leiomyoma can present as a predominantly solid smooth muscle tumor18 that does not feature a conspicuous vascular component. On the other hand, leiomyoma can present as a predominantly vascular tumor with smooth muscle cells interspersed in the interstitial spaces.10,27 Such tumors are described as hemangioleiomyomas. The pathologic differential diagnosis of orbital leiomyoma includes other benign spindle cell tumors of the orbit, including schwannoma, neurofibroma, fibrous histiocytoma, and solitary fibrous tumor of the orbit, as well as malignant spindle cell tumors, such as leiomyosarcoma, fibrosarcoma, and amelanotic spindle cell malignant melanoma. The nuclei of tumor cells in leiomyoma have blunted ends, as in our case (Fig. 4). This is an important feature of leiomyoma that is not usually seen with other benign spindle cell tumors.2,21 The differentiation of leiomyoma from malignant spindle cell tumors is made based on the absence of mitotic figures and cellular morphology.8,12,28 In the current case, absence of mitotic figures and cellular atypia ruled out a malignant spindle cell tumor. Among the special stains, masson trichrome and reticulin stain have been commonly used in the diagnosis of leiomyoma. Masson trichrome stain has been used to demonstrate the intracellular nonstriated filaments.12,14,18,21 The intracellular filaments stain red with Masson trichrome stain. Masson trichrome also stains the interstitial collagen interspersed among whorls of smooth muscle cells in some cases.11 The collagen stains blue with Masson trichrome stain. Reticulin stain shows an orderly deposition of small amounts of reticulin between the cells.11,12,14,19,20,26 The reticulin framework wraps around each individual tumor cell in leiomyoma, forming a spiral configuration.12,14
On transmission electron microscopy, leiomyoma has characteristic features, such as intracytoplasmic bundles of parallel filaments, cytoplasmic fusiform densities, and a rod- shaped nucleus.11,12,14,21,23 These features are useful in differentiating leiomyoma from other spindle cell tumors. However, transmission electron microscopy has largely been superseded by immunohistochemistry. Immunohistochemistry is faster, cheaper, and can be performed on formaldehyde-fixed and paraffin-embedded tissue. Immunohistochemically, orbital leiomyoma has been reported to demonstrate positive immunoreactivity with desmin, vimentin, muscle specific actin, and smooth muscle actin (SMA; Fig. 5).1,14 The tumor in the current case stained positive with SMA, desmin, and vimentin. Positive immunoreactivity with SMA provides important evidence for the diagnosis of leiomyoma because this marker is expressed only in smooth muscle tumors. Negative immunoreactivity for myoglobulin, NSE, Leu-7, CD-34, S-100, and HMB-45 equivocally rules out other spindle cell tumors that are considered in the differential diagnosis, as discussed above. TREATMENT AND PROGNOSIS
The best treatment of orbital leiomyoma is complete excision of the tumor. Jakobiec and associates pointed out the presence of satellite nodules around the tumor, which should be removed to prevent recurrence.12 If the tumor is fragmented during removal as in our case, all the fragments should be excised. Whenever complete excision is not possible especially for tumors near the orbital apex, the surgeon should consider leaving a small residual behind to avoid damage to the vital structures. Recurrence after incomplete excision has been observed,11,21 but spontaneous malignant transformation does not occur in a recurrent tumor. In the case reported by Jakobiec, it is possible that the high dose external beam radiotherapy (114 Gy) administered might have contributed to the development of sarcomatous transformation of the recurrent leiomyoma.12 This is the only case with a recorded death causally related to orbital leiomyoma. Usually, the life prognosis is excellent for completely excised and recurrent orbital leiomyomas (Table 1). The same is also true for orbital leiomyoma with intracranial extension.15 Orbital leiomyoma is not radiosensitive.11,12 External beam radiotherapy has no role in the treatment of the residual tumor after incomplete excision. If a subtotal tumor excision is made, the patient should be followed with serial neuroimaging studies for signs of tumor recurrence. In the case reported by Saga and associates, incomplete excision of the orbital leiomyoma was followed
242
Surv Ophthalmol 49 (2) March–April 2004
by idiopathic orbital inflammation which responded to an oral course of steroids.20 We have no explanation for the occurrence of idiopathic orbital inflammation after incomplete excision of the orbital leiomyoma. In other cases that were incompletely excised at initial surgery,11,12,21 orbital inflammation did not develop.
Summary and Conclusions Orbital leiomyoma is an uncommon tumor. The tumor affects males twice as frequently as females with a mean age of 30 years. Orbital leiomyoma has been reported to occur in the anterior orbit infiltrating the eyelids, in the intraconal orbit, and in the apical orbit. In the case reported herein, the tumor developed in the lateral half of the mid and posterior orbit. The tumor is indistinguishable from other orbital tumors on orbital CT and MRI. Immunohistochemical staining with smooth muscle actin is important in differentiating this tumor from other spindle cell tumors. Total tumor excision is the best treatment option. Recurrence after incomplete excision is possible but malignant transformation has not been reported in the absence of high dose external beam radiotherapy.
Method of Literature Search A search of the PubMed database 1966–2003 was conducted using various combinations of the key words computed tomography, immunohistochemistry, leiomyoma, magnetic resonance imaging, orbit, pathology. Articles in all languages were considered, provided that the English abstracts were included in non-English articles. Relevant articles that were cited in the reference lists of the retrieved articles were also included. All reports related to orbital leiomyoma were included. Selected reports on leiomyomas at other locations and reports of other types of tumors with similar features were included for purposes of comparison.
References 1. 2. 3.
4. 5.
6.
Badoza D, Weil D, Zarate J: Orbital leiomyoma: A case report. Ophthalmic Plast Reconstr Surg 15:460–2, 1999 Betharia SM, Arora R, Kishore K, Patil ND: Leiomyoma of the orbit. Ind J Ophthalmol 39:35–7, 1991 Biswas J, Kumar SK, Gopal L, Bhende MP: Leiomyoma of the ciliary body extending to the anterior chamber: clinicopathologic and ultrasound biomicroscopic correlation. Surv Ophthalmol 44:336–42, 2000 Carrier DA, Mawad ME, Kirkpatrick JB: MR appearance of an orbital leiomyoma. AJNR 14:473–4, 1993 Cattaneo L: Leiomioma e fibroleiomioma dell’orbita. Atti Cong Oftal Ital. 318, 1925 Cited by Sanborn GE, Valenzuela RE, Green WR: Leiomyoma of the orbit. Am J Ophthalmol 87:371–375, 1979 De Quervain F: Leiomyoma der Orbita. Schweiz med Wochenschr 1:628, 1920 Cited by Nath K, Shukla BR: Orbital leiomyoma and its origin. Br J Ophthalmol 47:369–71, 1963.
¨ NDU ¨ Z ET AL GU 7. De Potter P, Dolinskas C, Shields CL, Shields JA: Vascular tumors, in De Potter P, Shields CL, Shields JA (eds): MRI of the Eye and Orbit. Philadelphia: JB Lippincott, 1995, pp 159–81 8. Folberg R, Cleasby G, Flanagan JA, et al: Orbital leiomyosarcoma after radiation therapy for bilateral retinoblastoma. Arch Ophthalmol 101:1562–5, 1983 9. Foss AJ, Pecorella I, Alexander RA, et al: Are most intraocular “leiomyomas” really melanocytic lesions? Ophthalmology 101:919–24, 1994 10. Henderson JW, Harrison EG Jr: Vascular leiomyoma of the orbit: report of a case. Trans Am Acad Ophthalmol Otolaryngol 74:970–4, 1970 11. Jakobiec FA, Jones IS, Tannenbaum M: Leiomyoma: an unusual tumour of the orbit. Br J Ophthalmol 57:825–31, 1973 12. Jakobiec FA, Howard GM, Rosen M, Wolff M: Leiomyoma and leiomyosarcoma of the orbit. Am J Ophthalmol 80:1028– 42, 1975 13. Jakobiec FA, Tannenbaum M: Embryological perspectives on the fine structure of orbital tumors. Int Ophthalmol Clin 15:85–110, 1975 14. Jolly SS, Brownstein S, Jordan DR: Leiomyoma of the anterior orbit and eyelids. Can J Ophthalmol 30:366–70, 1995 15. Kulkarni V, Rajshekhar V, Chandi SM: Orbital apex leiomyoma with intracranial extension. Surg Neurol 54:327–30, 2000 16. Lewis PM: Leiomyoma of orbit, abstracted. Am J Ophthal 21:788, 1938 Cited by Nath K, Shukla BR: Orbital leiomyoma and its origin. Br J Ophthalmol 47:369–71, 1963 17. Lodato G: Fibro-mioma dell’orbita. Arch Ottal 4:120, 1896 Cited by Nath K, Shukla BR: Orbital leiomyoma and its origin. Br J Ophthalmol 47:369–71, 1963 18. Nath K, Shukla BR: Orbital leiomyoma and its origin. Br J Ophthalmol 47:369–71, 1963 19. Neetens A, Smet H: Orbital leiomyoma. Bull Soc Belge Ophthal 210:73–7, 1984 20. Saga T, Takeuchi T, Tagawa Y: Orbital leiomyoma accompanied by orbital pseudotumor. Jpn J Ophthalmol 26:175–82, 1982 21. Sanborn GE, Valenzuela RE, Green WR: Leiomyoma of the orbit. Am J Ophthalmol 87:371–5, 1979 22. Shields JA, Kapustiak J, Arbizo V, et al: Orbital neurilemoma with extension through the superior orbital fissure. Arch Ophthalmol 104:871–3, 1986 23. Shields JA, Shields CL, Eagle RC Jr, De Potter P: Observations on seven cases of intraocular leiomyoma. The 1993 Byron Demorest Lecture. Arch Ophthalmol 112:521–8, 1994 24. Shoda M: Tumoren der Orbita. Albrecht von Graefes Arch Klin Ophthal 116:327, 1925 Cited by Nath K, Shukla BR: Orbital leiomyoma and its origin. Br J Ophthalmol 47:369– 71, 1963 25. Siegrist: Klin Mbl Augenheilk 71:233, 1923 Cited by Nath K, Shukla BR: Orbital leiomyoma and its origin. Br J Ophthalmol 47:369–71, 1963 26. Vigstrup J, Glenthoj A: Leiomyoma of the orbit. Acta Ophthalmol 60:992–7, 1982 27. Wolter JR: Hemangio-leiomyoma of the orbit. Eye Ear Nose Throat Monthly 44:42–6, 1965 28. Wojno T, Tenzel RR, Nadji M: Orbital leiomyosarcoma. Arch Ophthalmol 101:1566–8, 1983 29. Wright RE: Selected pictures of extraocular affections from the Museum of the Government Ophthalmic Hospital, Madras, India. Government Press, 1938, p 10. Cited by Nath K, Shukla BR: Orbital leiomyoma and its origin. Br J Ophthalmol 47:369–71, 1963 Presented as a case report at the Xth International Congress of Ocular Oncology, Amsterdam, the Netherlands, 17–21 June 2001. The authors reported no proprietary or commercial interest in any product mentioned or concept discussed in this article. Reprint address: Kaan Gu¨ndu¨z, MD, Associate Professor of Ophthalmology, G.M.K.Bulvari116/3, Maltepe 06570, Ankara, Turkey.
VOLUME 49 • NUMBER 2 • MARCH–APRIL 2004
CLINICAL PATHOLOGIC REVIEWS MILTON BONIUK AND STEFAN SEREGARD, EDITORS
Orbital Leiomyoma: Report of a Case and Review of the Literature Kaan Gu¨ndu¨z, MD,1 Ilhan Gu¨nalp, MD,1 Esra Erden, MD,2 and Selim Erekul, MD2 1
Ocular Oncology Service, Department of Ophthalmology, and 2Department of Pathology, Ankara University Faculty of Medicine, Ankara, Turkey
Abstract. A 10-year-old female presented with slowly progressive proptosis of 1 year’s duration. Orbital MRI revealed an extraconal oval mass occupying the lateral half of the mid and posterior orbit. The tumor was isointense to the extraocular muscle and cerebral gray matter on T1-weighted images and hyperintense on T2-weighted images. The patient underwent superolateral orbitotomy, and it was felt that the tumor was totally excised in a piecemeal fashion. Histopathologic examination showed that the tumor was composed of spindle cells arranged in a fibrous stroma rich in dilated sinusoidal capillaries. The nuclei of tumor cells were oval with blunted ends. There were no mitotic figures. Immunohistochemically, the tumor stained positive with smooth muscle actin, desmin, and vimentin. Based on the histopathologic and immunohistochemical staining results, a diagnosis of orbital leiomyoma was made. At 34 months follow-up, the patient continues to have 20/20 vision and is free of tumor recurrence clinically. Orbital leiomyoma is an uncommon tumor. Search of the English literature showed only 15 previous cases of orbital leiomyoma that have been published since 1963. (Surv Ophthalmol 49:237–242, 2004. 쑖 2004 Elsevier Inc. All rights reserved.) Key words. Computed tomography • immunohistochemistry resonance imaging • orbit • pathology
Leiomyoma is a benign tumor that is most commonly encountered in the uterus and gastrointestinal tract. However, it can also occur in the uveal tract and orbit. Uveal leiomyoma is an uncommon intraocular tumor, which usually occurs in the iris and ciliary body.3 Rarely, it can also occur in the posterior choroid.23 Uveal leiomyoma usually presents an an amelanotic mass, causing diagnostic confusion with amelanotic melanoma.9 Similar to uveal leiomyoma, orbital leiomyoma is an uncommon tumor. We report herein a case of orbital leiomyoma and review previously published cases. Our case is interesting because of the anatomic
•
leiomyoma
•
magnetic
location of the tumor which has not been reported before. Further, it illustrates the immunohistochemical staining and magnetic resonance imaging (MRI) features of orbital leiomyoma, which have not been well illustrated in other publications.
Case Report A 10-year-old girl presented with a 1-year history of progressive proptosis in the left eye. She had 7 mm proptosis in the left eye (Fig. 1), which was pushed medially and inferiorly. The motility of the left eye 237
쑖 2004 by Elsevier Inc. All rights reserved.
0039-6257/04/$–see front matter doi:10.1016/j.survophthal.2003.12.010
238
¨ NDU ¨ Z ET AL GU
Surv Ophthalmol 49 (2) March–April 2004
Fig. 1. Preoperative facial photograph shows the 10-yearold child with proptosis of the left eye.
was restricted in all positions of gaze, especially superiorly and temporally. Visual acuity in the left eye was 20/20. Slit-lamp biomicroscopy revealed normal findings. On funduscopy, an elevated choroidal mass in the superotemporal quadrant arising from compression of the globe by the orbital tumor was noted. The right eye was normal. Orbital MRI demonstrated a well-circumscribed oval mass filling the middle and posterior left orbit, producing scleral indentation of the left globe. On MRI, the tumor was isointense with respect to the extraocular muscle and cerebral gray matter on T1weighted images and hyperintense on T2-weighted images (Fig. 2). The tumor showed moderate contrast enhancement. The patient underwent a superolateral orbitotomy with an eyelid crease approach (KG) and it was felt that the tumor was totally excised in a piecemeal
Fig. 2. Preoperative orbital MRI demonstrates a well-circumscribed oval mass occupying the lateral half of the mid and posterior orbit, producing scleral indentation of the left globe. The tumor is isointense to the extraocular muscle and cerebral gray matter on T1-weighted images (top) and hyperintense on T2-weighted images (bottom).
fashion. Grossly, the tumor had a solid lobulated redtan appearance (Fig. 3). Histopathologic findings disclosed that the tumor was composed of bundles of spindle cells embedded in a fibrous stroma rich in dilated sinusoidal capillaries. The nuclei of tumor cells had an oval shape with blunted ends and some had prominent nucleoli (Fig. 4). There were no mitotic figures. The tumor cells displayed intense fuchsinophilia on Masson trichrome stain. Immunohistochemically, the tumor stained positive with smooth muscle actin (SMA) (Fig. 5), desmin, and vimentin. The tumor cells showed negative immunoreactivity for myoglobulin, neuron specific enolase (NSE), CD-34, Leu-7, S-100, and HMB-45. The histopathologic findings and pattern of immunoreactivity were found to be consistent with orbital leiomyoma. At 38 months follow-up, left eye visual acuity remained at 20/20 and there was no clinical or MRI evidence of a recurrent tumor (Fig. 6).
Discussion CLINICAL AND RADIOLOGICAL FEATURES
The first case of orbital leiomyoma was reported in 1896. Nath and Shukla18 in 1963 and Sanborn and associates21 in 1979 collectively recorded seven cases of orbital leiomyoma that had been diagnosed between 1896 and 1938. The data sources for these seven cases as cited in the two articles above are quoted in the references.5,6,16,17,24,25,29 The results of our English literature search showed that, starting with the case of Nath and Shukla in 1963,18 15 well-documented cases of orbital leiomyoma have been published over the past 40 years.1,2,4,10–12,14,15,18–21,26,27 The demographics, treatment methods, and follow-up in these 15 previously reported patients and our case reported herein are summarized in Table 1. The age of the patients ranged from 9 years to 57 years, the mean age being 30 years. Of the 16 patients with orbital leiomyoma, 11 were males, 4 were females, and the sex of the
Fig. 3. Gross photograph of the excised tumor showing the tan-red colored orbital leiomyoma.
239
ORBITAL LEIOMYOMA
Fig. 4. Photomicrograph shows that the tumor is composed of spindle-shaped cells with blunt-ended nuclei embedded in a background of dilated sinusoidal capillaries (Hematoxylin-eosin × 400).
patient was not reported in one case. In contrast to uveal leiomyoma, orbital leiomyoma is more common in males. The reason for this male preponderance is not clear. Clinically, patients with orbital leiomyomas located deep in the orbit present with painless proptosis or displacement of the globe progressing slowly over several months or years. Our case had a similar clinical course spanning a 1-year period. Leiomyomas located in the anterior orbit and eyelids may present with progressive painless swelling of the eyelids.2,12,14,19 Orbital leiomyoma can occur as an intraconal or extraconal tumor. Review of the previously published cases (Table 1) showed that 6 of 16 orbital leiomyomas were intraconal, 7 occupied an extraconal location close to or infiltrating the eyelids, and 3 demonstrated orbital apex involvement. Two of three
Fig. 6. Postoperative facial photograph shows normal external findings and the skin scar from the orbitotomy incision on the left upper eyelid at one year follow-up.
cases of orbital leiomyoma with orbital apex involvement demonstrated intracranial involvement. The current case is unique in that the tumor occurred in a deep extraconal position in the orbit, unlike the previous extraconal leiomyomas that have been reported to occur in the anterior orbit.2,10,12,14,19,21 Computed tomography (CT) and MRI usually demonstrate a well-circumscribed orbital tumor. Compared to CT, MRI provides more detail on internal tissue characteristics of orbital leiomyoma. On MRI, orbital leiomyoma was isointense with respect to the extraocular muscle and cerebral gray matter on T1-weighted images and hyperintense on T2-weighted images. Orbital leiomyoma showed moderate contrast enhancement. Many orbital tumors demonstrate similar MRI signal characteristics on T1- and T2-weighted images.7 The differential diagnosis of orbital leiomyoma from other intraconal and extraconal tumors can be difficult with CT and MRI. Orbital leiomyoma can demonstrate intracranial extension12,15 which is best delineated on MRI. Other benign orbital tumors, such as schwannoma and neurofibroma, can also demonstrate intracranial extension through the superior orbital fissure.22 PATHOGENESIS
Fig. 5. Photomicrograph demonstrates that the tumor stains intensely with smooth muscle actin (SMA) (Smooth muscle actin × 400).
Orbital leiomyoma is believed to arise from the smooth muscle of orbital blood vessels, pericytes, Mu¨ller’s muscle, or capsulopalpebral muscle of Hessar.2,11,18 Tumors located in the anterior orbit close to the eyelids may develop from the capsulopalpebral muscle of Hessar.18 The pericyte is a possible cell of origin for orbital leiomyoma. Transmission electron microscopic studies have shown that the pericyte undergoes several evolutionary stages, ranging
240
The Demographics, Preoperative Tumor Features, Treatment Methods, and Follow-up in 16 Cases of Orbital Leiomyoma First Author
Year
Age/Sex
Location in the Orbit
Quadrant
Intracranial Extension
Nath18 Wolter27 Henderson10 Jakobiec11 Jakobiec12 Jakobiec12
1963 1965 1970 1973 1975 1975
18/F 41/M 9/F 17/NA 17/M 34/F
Intraconal Intraconal Anterior Apex Anterior Apex
– – Inferior – Medial –
No No No No No Yes
Excision Excision Excision Incision Excision Excision
N/A N/A N/A Residual tumor Stable Recurrent tumor
Neetens19 Sanborn21 Saga20 Vigstrup26
1979 1979 1982 1982
34/F 5/M 53/M 35/M
Anterior Anterior Intaconal Intraconal
Superior Medial – –
No No No No
N/A Stable Pseudo-tumor Stable
Betharia2 Carrier4 Jolly14 Badoza1 Kulkarni15
1991 1993 1995 1999 2000
39/M 57/M 42/M 56/M 9/M
Anterior Intraconal Anterior Intraconal Apex
Inferior – Inferior – –
No No No No Yes
Current case
2004
10/M
Extraconal
Excision Excision Incomplete excision Incomplete excision Excision Excision Excision Excision Subtotal excision via craniotomy Excision
a
Lateral
No
Initial Orbital Surgery
Orbital Status after Initial Surgery
N/A N/A Stable Stable Recurrent tumor Stable
Secondary Treatment
Follow-up
Patient Status
N/A N/A N/A Excision None EBRT(114 Gy), Exenteration N/A None Incision, steroids None
N/A N/A N/A 7 years 16 years 17 years N/A 28 monthsa 7 months 12 months
N/A N/A N/A Alive Alive Dead of sarcoma metastasis N/A Alive Alive Alive
N/A N/A None None Excision via craniotomy None
N/A N/A 15 months 1 month 5 years
N/A N/A Alive Alive Alive
38 months
Alive
Surv Ophthalmol 49 (2) March–April 2004
TABLE 1
After the submission of the report, the patient developed orbital recurrence treated by excision.
¨ NDU ¨ Z ET AL GU
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ORBITAL LEIOMYOMA
from poorly differentiated mesenchymal cells of capillary walls to more highly differentiated smooth muscle cells of venular walls.11 Considering its anatomic location in the orbit, the tumor in our case probably developed from the smooth muscle of orbital blood vessels or pericytes. The term mesectodermal leiomyoma has been used to describe some of uveal tumors, because the uveal tissues are believed to arise from the neural crest embryologically.23 Similar terminology has also been suggested for orbital leiomyoma because of the origin of this tumor from smooth muscle cells or pericytes derived from the neural crest.13 MORPHOLOGICAL FEATURES
The results of histopathologic examination in our case disclosed that the tumor consists of bundles of spindle-shaped cells with oval nuclei arranged in a fibrous stroma with dilated sinusoidal capillaries (Fig. 4). Sometimes the leiomyoma can present as a predominantly solid smooth muscle tumor18 that does not feature a conspicuous vascular component. On the other hand, leiomyoma can present as a predominantly vascular tumor with smooth muscle cells interspersed in the interstitial spaces.10,27 Such tumors are described as hemangioleiomyomas. The pathologic differential diagnosis of orbital leiomyoma includes other benign spindle cell tumors of the orbit, including schwannoma, neurofibroma, fibrous histiocytoma, and solitary fibrous tumor of the orbit, as well as malignant spindle cell tumors, such as leiomyosarcoma, fibrosarcoma, and amelanotic spindle cell malignant melanoma. The nuclei of tumor cells in leiomyoma have blunted ends, as in our case (Fig. 4). This is an important feature of leiomyoma that is not usually seen with other benign spindle cell tumors.2,21 The differentiation of leiomyoma from malignant spindle cell tumors is made based on the absence of mitotic figures and cellular morphology.8,12,28 In the current case, absence of mitotic figures and cellular atypia ruled out a malignant spindle cell tumor. Among the special stains, masson trichrome and reticulin stain have been commonly used in the diagnosis of leiomyoma. Masson trichrome stain has been used to demonstrate the intracellular nonstriated filaments.12,14,18,21 The intracellular filaments stain red with Masson trichrome stain. Masson trichrome also stains the interstitial collagen interspersed among whorls of smooth muscle cells in some cases.11 The collagen stains blue with Masson trichrome stain. Reticulin stain shows an orderly deposition of small amounts of reticulin between the cells.11,12,14,19,20,26 The reticulin framework wraps around each individual tumor cell in leiomyoma, forming a spiral configuration.12,14
On transmission electron microscopy, leiomyoma has characteristic features, such as intracytoplasmic bundles of parallel filaments, cytoplasmic fusiform densities, and a rod- shaped nucleus.11,12,14,21,23 These features are useful in differentiating leiomyoma from other spindle cell tumors. However, transmission electron microscopy has largely been superseded by immunohistochemistry. Immunohistochemistry is faster, cheaper, and can be performed on formaldehyde-fixed and paraffin-embedded tissue. Immunohistochemically, orbital leiomyoma has been reported to demonstrate positive immunoreactivity with desmin, vimentin, muscle specific actin, and smooth muscle actin (SMA; Fig. 5).1,14 The tumor in the current case stained positive with SMA, desmin, and vimentin. Positive immunoreactivity with SMA provides important evidence for the diagnosis of leiomyoma because this marker is expressed only in smooth muscle tumors. Negative immunoreactivity for myoglobulin, NSE, Leu-7, CD-34, S-100, and HMB-45 equivocally rules out other spindle cell tumors that are considered in the differential diagnosis, as discussed above. TREATMENT AND PROGNOSIS
The best treatment of orbital leiomyoma is complete excision of the tumor. Jakobiec and associates pointed out the presence of satellite nodules around the tumor, which should be removed to prevent recurrence.12 If the tumor is fragmented during removal as in our case, all the fragments should be excised. Whenever complete excision is not possible especially for tumors near the orbital apex, the surgeon should consider leaving a small residual behind to avoid damage to the vital structures. Recurrence after incomplete excision has been observed,11,21 but spontaneous malignant transformation does not occur in a recurrent tumor. In the case reported by Jakobiec, it is possible that the high dose external beam radiotherapy (114 Gy) administered might have contributed to the development of sarcomatous transformation of the recurrent leiomyoma.12 This is the only case with a recorded death causally related to orbital leiomyoma. Usually, the life prognosis is excellent for completely excised and recurrent orbital leiomyomas (Table 1). The same is also true for orbital leiomyoma with intracranial extension.15 Orbital leiomyoma is not radiosensitive.11,12 External beam radiotherapy has no role in the treatment of the residual tumor after incomplete excision. If a subtotal tumor excision is made, the patient should be followed with serial neuroimaging studies for signs of tumor recurrence. In the case reported by Saga and associates, incomplete excision of the orbital leiomyoma was followed
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by idiopathic orbital inflammation which responded to an oral course of steroids.20 We have no explanation for the occurrence of idiopathic orbital inflammation after incomplete excision of the orbital leiomyoma. In other cases that were incompletely excised at initial surgery,11,12,21 orbital inflammation did not develop.
Summary and Conclusions Orbital leiomyoma is an uncommon tumor. The tumor affects males twice as frequently as females with a mean age of 30 years. Orbital leiomyoma has been reported to occur in the anterior orbit infiltrating the eyelids, in the intraconal orbit, and in the apical orbit. In the case reported herein, the tumor developed in the lateral half of the mid and posterior orbit. The tumor is indistinguishable from other orbital tumors on orbital CT and MRI. Immunohistochemical staining with smooth muscle actin is important in differentiating this tumor from other spindle cell tumors. Total tumor excision is the best treatment option. Recurrence after incomplete excision is possible but malignant transformation has not been reported in the absence of high dose external beam radiotherapy.
Method of Literature Search A search of the PubMed database 1966–2003 was conducted using various combinations of the key words computed tomography, immunohistochemistry, leiomyoma, magnetic resonance imaging, orbit, pathology. Articles in all languages were considered, provided that the English abstracts were included in non-English articles. Relevant articles that were cited in the reference lists of the retrieved articles were also included. All reports related to orbital leiomyoma were included. Selected reports on leiomyomas at other locations and reports of other types of tumors with similar features were included for purposes of comparison.
References 1. 2. 3.
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¨ NDU ¨ Z ET AL GU 7. De Potter P, Dolinskas C, Shields CL, Shields JA: Vascular tumors, in De Potter P, Shields CL, Shields JA (eds): MRI of the Eye and Orbit. Philadelphia: JB Lippincott, 1995, pp 159–81 8. Folberg R, Cleasby G, Flanagan JA, et al: Orbital leiomyosarcoma after radiation therapy for bilateral retinoblastoma. Arch Ophthalmol 101:1562–5, 1983 9. Foss AJ, Pecorella I, Alexander RA, et al: Are most intraocular “leiomyomas” really melanocytic lesions? Ophthalmology 101:919–24, 1994 10. Henderson JW, Harrison EG Jr: Vascular leiomyoma of the orbit: report of a case. Trans Am Acad Ophthalmol Otolaryngol 74:970–4, 1970 11. Jakobiec FA, Jones IS, Tannenbaum M: Leiomyoma: an unusual tumour of the orbit. Br J Ophthalmol 57:825–31, 1973 12. Jakobiec FA, Howard GM, Rosen M, Wolff M: Leiomyoma and leiomyosarcoma of the orbit. Am J Ophthalmol 80:1028– 42, 1975 13. Jakobiec FA, Tannenbaum M: Embryological perspectives on the fine structure of orbital tumors. Int Ophthalmol Clin 15:85–110, 1975 14. Jolly SS, Brownstein S, Jordan DR: Leiomyoma of the anterior orbit and eyelids. Can J Ophthalmol 30:366–70, 1995 15. Kulkarni V, Rajshekhar V, Chandi SM: Orbital apex leiomyoma with intracranial extension. Surg Neurol 54:327–30, 2000 16. Lewis PM: Leiomyoma of orbit, abstracted. Am J Ophthal 21:788, 1938 Cited by Nath K, Shukla BR: Orbital leiomyoma and its origin. Br J Ophthalmol 47:369–71, 1963 17. Lodato G: Fibro-mioma dell’orbita. Arch Ottal 4:120, 1896 Cited by Nath K, Shukla BR: Orbital leiomyoma and its origin. Br J Ophthalmol 47:369–71, 1963 18. Nath K, Shukla BR: Orbital leiomyoma and its origin. Br J Ophthalmol 47:369–71, 1963 19. Neetens A, Smet H: Orbital leiomyoma. Bull Soc Belge Ophthal 210:73–7, 1984 20. Saga T, Takeuchi T, Tagawa Y: Orbital leiomyoma accompanied by orbital pseudotumor. Jpn J Ophthalmol 26:175–82, 1982 21. Sanborn GE, Valenzuela RE, Green WR: Leiomyoma of the orbit. Am J Ophthalmol 87:371–5, 1979 22. Shields JA, Kapustiak J, Arbizo V, et al: Orbital neurilemoma with extension through the superior orbital fissure. Arch Ophthalmol 104:871–3, 1986 23. Shields JA, Shields CL, Eagle RC Jr, De Potter P: Observations on seven cases of intraocular leiomyoma. The 1993 Byron Demorest Lecture. Arch Ophthalmol 112:521–8, 1994 24. Shoda M: Tumoren der Orbita. Albrecht von Graefes Arch Klin Ophthal 116:327, 1925 Cited by Nath K, Shukla BR: Orbital leiomyoma and its origin. Br J Ophthalmol 47:369– 71, 1963 25. Siegrist: Klin Mbl Augenheilk 71:233, 1923 Cited by Nath K, Shukla BR: Orbital leiomyoma and its origin. Br J Ophthalmol 47:369–71, 1963 26. Vigstrup J, Glenthoj A: Leiomyoma of the orbit. Acta Ophthalmol 60:992–7, 1982 27. Wolter JR: Hemangio-leiomyoma of the orbit. Eye Ear Nose Throat Monthly 44:42–6, 1965 28. Wojno T, Tenzel RR, Nadji M: Orbital leiomyosarcoma. Arch Ophthalmol 101:1566–8, 1983 29. Wright RE: Selected pictures of extraocular affections from the Museum of the Government Ophthalmic Hospital, Madras, India. Government Press, 1938, p 10. Cited by Nath K, Shukla BR: Orbital leiomyoma and its origin. Br J Ophthalmol 47:369–71, 1963 Presented as a case report at the Xth International Congress of Ocular Oncology, Amsterdam, the Netherlands, 17–21 June 2001. The authors reported no proprietary or commercial interest in any product mentioned or concept discussed in this article. Reprint address: Kaan Gu¨ndu¨z, MD, Associate Professor of Ophthalmology, G.M.K.Bulvari116/3, Maltepe 06570, Ankara, Turkey.