© 2015 APMIS. Published by John Wiley & Sons Ltd. DOI 10.1111/apm.12384
APMIS 123: 540–545
Posterior choroidal leiomyoma: a rare case report and literature review WEI-YU CHIANG,1 JUI-WEI LIN,2 I-HUI YANG1 and HSI-KUNG KUO1 Departments of 1Ophthalmology and 2Pathology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
Chiang W-Y, Lin J-W, Yang I-H, Kuo H-K. Posterior choroidal leiomyoma: a rare case report and literature review. APMIS 2015; 123: 540–545. We report a literature review and detailed evaluation of a rare case of posterior choroidal leiomyoma to emphasize the importance of diﬀerentiating this from other choroidal tumors. A 30-year-old male presented with variable blurred vision in his right eye secondary to a choroidal tumor. Clinical examinations were performed including fundus photography, optical coherence tomography, B scans, ﬂuorescein and indocyanine green angiography, computed tomography, and magnetic resonance imaging. Preoperative examination revealed a suspected choroidal melanoma and enucleation was performed. However, a deﬁnitive diagnosis of choroidal leiomyoma was made following postoperative pathological light microscopy and immunohistochemical studies. Published case reports were collected and the common characteristics and distinctive features were compared with the current case. Posterior choroidal leiomyoma was summarized from the literature, and beneﬁcial information for diagnosis and treatment was obtained. In conclusion, posterior choroidal leiomyoma is rare and should be diﬀerentiated from amelanotic melanomas. Despite the benign nature, an explanation regarding the rare incidence and diﬃcult diagnosis of posterior choroidal leiomyoma must be provided to patients, prior to enucleation or detrimental treatment. Key words: Choroidal leiomyoma; choroidal tumor; smooth muscle tumor. Hsi-Kung Kuo, Department of Ophthalmology, No.123, Dapi Rd., Niaosong Dist., Kaohsiung City 83301, Taiwan. e-mail: [email protected]
An intraocular smooth muscle tumor, or leiomyoma, is rare and has been known to arise in the iris, ciliary body, or the choroid, but it tends to aﬀect the ciliary body and peripheral choroid rather than the posterior choroid. Consequently, leiomyoma of the posterior choroid is extremely rare (1, 2). Clinically, it is very diﬃcult to diﬀerentiate leiomyoma from melanoma. We report a case of posterior choroidal leiomyoma initially diagnosed as choroidal melanoma that later proved to be leiomyoma following enucleation and immunohistochemistry (IHC). Unusual diﬀerences were noted in this case after review, comparison, and summarization of clinical manifestations, diagnosis, and treatment of posterior choroidal leiomyoma in published case reports. Hence, we emphasize the importance of including choroidal leiomyoma in the diﬀerential diagnosis of choroidal tumors. Received 26 November 2014. Accepted 16 February 2015
CASE HISTORY A 30-year-old Asian man without underlying ocular disease presented with a 4-day history of variable blurred vision (oculus dexter, OD). Upon examination, the best-corrected visual acuity ﬂuctuated from hand motion to 0.6. The intraocular pressure, extraocular movement, and anterior segment were normal. However, fundus examination revealed a large, pigmented bulging choroidal tumor involving the superior temporal quadrant located about 2 disc diameters away from the optic disc. Peripheral exudative retinal detachment involving the macula was also observed (Fig. 1). A series of image surveys were performed to evaluate the manifestation of this lesion. B scan ultrasonography (Fig. 2A) showed medium-reﬂectivity anterior border and low to medium internal reﬂectivity. Fluorescein angiography (FA) (Fig. 2B) and indocyanine green angiography (ICGA) (Fig. 2C) indicated mild non-early hyperﬂuorescence and late mottled staining. High
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Fig. 1. Fundus photographs. A large dome-shaped choroidal tumor occupies the superotemporal quadrant with peripheral exudative retinal detachment involving the macula (A). The lesion is yellowish-white in color with some pigmentations (B).
Fig. 2. B scan ultrasonography, ﬂuorescein angiography (FA), and indocyanine green angiography (ICGA). This choroidal tumor has smooth border with medium-reﬂectivity anterior border and low to medium internal reﬂectivity in ultrasonography (A). FA (B) and ICGA (C) show mild non-early hyperﬂuorescence and late mottled staining.
density with contrast enhancement was noted in computed tomography (CT) (Fig. 3A). Magnetic resonance imaging (MRI) revealed faintly hyperintense to vitreous on T1-weighted images (T1-WI) (Fig. 3B), markedly hypointense on T2-WI (Fig. 3C) and intense enhancement (Fig. 3D). No abnormalities were detected in the other (left) eye. Based on the aforementioned information, a clinical diagnosis of suspected choroidal melanoma was made. After discussion of a treatment strategy with the ophthalmologist and radiation oncologist, the patient opted to undergo enucleation. However, the light microscopy (LM) and IHC pathology report unexpectedly revealed a smooth muscle tumor with uncertain malignant potential. The globe was cut as the pupil-optic nerve (PO) section and indicated that the intraocular lesion was located at superior temporal side of the vitreous cavity (Fig. 4A). Under LM, the tumor occupied the choroidal stroma beneath the retinal pigment epithelium (Fig. 4B), and was composed of proliferative spindle cells bearing eosinophilic cytoplasm, and arranged in interlacing bundles (Fig. 4C) with mildly increased mitotic ﬁgures © 2015 APMIS. Published by John Wiley & Sons Ltd
(Fig. 4D). IHC (Table 1) was positive for smooth muscle actin (SMA), desmin, and h-caldesmon (Fig. 5), but negative for melanocytic markers (HMB-45, S100, Melan A), which was consistent with a smooth muscle tumor. Although the optic nerve margin was free from tumor involvement, routine follow-up for potential local recurrence or distant metastasis was suggested owing to the uncertain malignany and potential hematological spread of the choroidal tumor. No recurrence or metastasis was noted 1 year after enucleation.
DISCUSSION Posterior choroidal leiomyoma is very rare and is diﬃcult to clinically diﬀerentiate from choroidal melanoma, especially amelanotic melanomas. During transillumination, leiomyomas usually readily transmit light, whereas most melanomas cast a shadow (1). In contrast with melanomas, which are located in the uveal stroma, leiomyomas are usually located in the supraciliary or suprachoroidal space (1). Posterior choroidal leiomyomas
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Fig. 3. Computed tomography (CT) and magnetic resonance imaging (MRI). CT with contrast enhancement indicates the lesion with high density (A). MRI reveals a 1.3cm-sized mass with faintly hyperintense to vitreous on T1-weighted images (T1-WI) (B), markedly hypointense on T2-WI (C) and intense enhancement (D). Compared with the brain, T1-WI and T2-WI indicate isointense to brain (B, C).
Fig. 4. Pathological specimen and Light microscopy (LM). In gross picture with pupil-optic nerve (PO) section, the tumor was located at superior temporal side of the vitreous cavity (A; scale unit: centimeter; arrow with T: tumor, ON: optic nerve). Under LM, the tumor arising from uveal stroma shows a well-circumscribed border occupying the whole choroidal stroma beneath the retinal pigment epithelium, with the accompaniment of subretinal ﬂuid and retinal degeneration (B; hematoxylin and eosin stain, 920; T: tumor, R: retina, C: choroid, S: sclera). The neoplasm is composed of proliferative spindle cells bearing eosinophilic cytoplasm, in arrangement of interlacing bundles (C; hematoxylin and eosin stain, 9100), with mildly increased mitotic ﬁgure of 2/10 high power ﬁelds (D; hematoxylin and eosin stain, 9400; arrow: mitosis).
© 2015 APMIS. Published by John Wiley & Sons Ltd
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Table 1. Results of immunohistochemical (IHC) stain Antibody Tumor Antibody Tumor HMB-45 Negative CD99 Positive S 100 Negative BCL2 Negative Melan A Negative SMA Positive AE1/AE3 Negative H-Caldesmon Positive Ki-67 1% positive Desmin Focally positive EMA Negative ALK Negative CD34 Negative Myogenin Negative IHC demonstrated positivity for smooth muscle actin (SMA), desmin, and h-caldesmon, but negativity for melanocytic markers (HMB-45, S100, Melan A), consistent with a smooth muscle tumor.
may appear as yellowish-white vascularized masses on color fundus photography, and usually exhibit a dome-shaped smooth lesion with low to medium internal reﬂectivity in B-scan ultrasonography (2– 4). The ﬁlling of intratumoral vessels in the early phase and intense hyperﬂuorescence in the late phase has been docemented by FA (2). Compared with the vitreous on MRI, choroidal leiomyomas present as mildly hyperintense on T1-weighted images (T1-WI) and hypointense on T2-weighted images (T2-WI; 2). A 3-case series indicated isointensity compared to the brain on T1- and T2-WI
Fig. 5. Immunohistochemical stain (IHC) for smooth muscle. The tumor cells show diﬀuse positivity for SMA (A; 9200), H-Caldesmon (B; 9200) and focal positivity for desmin (C; 9200), which are smooth muscle markers.
Table 2. Comparison between uveal amelanotic melanoma and uveal leiomyoma Uveal amelanotic melanoma Appearance Little or none pigmentation Serous RD Transillumination Cast a shadow B scan High-amplitude anterior border Low internal reﬂectivity MRI Hyperintense in T1, hypointense in T2 Hyperintense in T1+Contrast FA Site LM
Early ﬁlling, late staining In uveal stroma Spindle cell Epithlioid Mixed-cell IHC HMB-45 (+) S100 (+) Melana (+) TEM Spindle cell: ﬂat with small nucleoplasmatic ratio, mature melanosome Epithelioid: round with high NPR, free ribosome, few immature melanosome Treatment Enucleation Brachytherapy Charged-particle radiation External-beam radiation RD, retinal detachment; MRI, magnetic resonance imaging; FA, ﬂuorescein IHC, immunohistochemistry; TEM, transmission electron microscopy. © 2015 APMIS. Published by John Wiley & Sons Ltd
Uveal leiomyoma Yellowish-white mass Serous RD Transmits light readily Low to medium internal reﬂectivity Hyperintense in T1, hypointense in T2 Isointense to brain in T1, T2 Hyperintense in T1+C Early ﬁlling, late staining In supraciliary or suprachoroidal space Interlacing bundles of spindle cells with blunt-ended oval nuclei Smooth muscle actin (+) Desmin (+) H-caldesmon (+) Cytoplasmic ﬁlaments Fusiform densities Micropinocytotic vesicles Observation Partial iridectomy or partial lamellar sclerouvectomy Enucleation angiography; LM, light microscopy;
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Table 3. Literature review of posterior choroidal leiomyoma with clinical manifestation Case report Jeon et al. (4) Perri et al. (3) Miyamoto et al. (2) Age/Gender 27-year-old male 23-year-old male 40-year-old female VA CF 30 cm 20/200 20/100 Yellowish white, Smooth-surfaced, Appearance Yellowish white, smooth-surfaced, dome-shaped, smooth-surfaced dome-shaped, serous circumscribed, serous vascularized, domeRD (+) RD (+) shaped, serous RD (+) B scan Medium~low internal Low internal Low internal reﬂectivity reﬂectivity reﬂectivity MRI – – T1-WI: mildly hyperintense T2-WI: hypointense FA
Early ﬁlling, late staining
Early ﬁlling, late staining
Spindle cells arranged in intersecting fascicles Oval to round nuclei Mitosis (+, 3/10HPF) SMA(+), desmin(+), vimentin (+)
Spindle cells arranged in intersecting fascicles
Spindle cells arranged in intersecting fascicles Oval to round nuclei
SMA (+), CD56 (+)
This case 30-year-old male 0.6 Yellowish white, pigmentation(+), smooth-surfaced, dome-shaped, serous RD (+) Medium~low internal reﬂectivity T1-WI: mildly hyperintense T2-WI: hypointense Hyperintense after enhancement Non-early hyperﬂuorescence, late staining Spindle cells arranged in intersecting fascicles Oval to round nuclei Mitosis (+,2/10HPF) SMA(+), desmin(+, focal), h-caldesmon (+) –
Smooth muscle nature – Smooth muscle cells characterized by intracytoplasmic ﬁlaments with focal densities, subplasmalemmal densities Treatment Enucleation – Enucleation Enucleation VA, visual acuity; CF, counting ﬁnger; RD, retinal detachment; MRI, magnetic resonance imaging; WI, weighted images; FA, ﬂuorescein angiography; LM, light microscopy; HPF, high power ﬁeld; IHC, immunohistochemistry; SMA, smooth muscle actin; TEM, transmission electron microscopy. TEM
images, and strongly enhanced homogeneity on Gadolinium-enhanced T1-WI images (5). In this case, some manifestations were in accord with previously reported characteristics including the appearance of yellowish-white vascularized masses (Fig. 1) and dome-shaped smooth surfaces with low to medium internal reﬂectivity in B-scan ultrasonography (Fig. 2A), as well as mild hyperintensity and hypointense on T1-WI (Fig. 3B) and T2-WI (Fig. 3C) images respectively. However, diﬀerences including origination arising from the uveal stroma (Fig. 4B), some pigmentation noted in appearance (Fig. 1), and non-early hyperﬂuorescence, and late mottled staining in FA and ICG (Fig. 2B and C) were noted in this case. Histopathologically, intraocular leiomyomas are composed of interlacing bundles of spindle cells with blunt-ended oval nuclei, moderate amounts of ﬁbrillary cytoplasm, and intercellular myoglial ﬁbrils (4). LM alone often cannot discriminate a leiomyoma from another spindle cell tumor, such as an amela544
notic melanoma, nevus, neuroﬁbroma, neurilemmoma, hemangiopericytoma, and meningioma (6). Furthermore, it is almost impossible to distinguish leiomyomas from amelanotic melanomas without IHC or transmission electron microscopy (TEM). IHC reveals positive immunoreactivity for smooth muscle actin, desmin, h-caldesmon, and vimentin. TEM reveals smooth muscle cells features, including intracytoplasmic ﬁlaments with focal densities, subplasmalemmal densities, and suspicious pinocytic vesicles (4). The comparison of uveal amelanotic melanoma and uveal leiomyoma was summarized in Table 2. In our case, the pathology revealed similar characteristics, including proliferative spindle cells bearing eosinophilic cytoplasm with the arrangement of interlacing bundles in LM (Fig. 4C) and positivity for SMA and h-caldesmon and desmin in IHC (Table 1 and Fig. 5). However, some unique diﬀerences observed included mildly increased mitotic ﬁgures (2/10 high power ﬁelds) (Fig. 4D), and focal IHC positivity for desmin (Fig. 5C). © 2015 APMIS. Published by John Wiley & Sons Ltd
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Although cytologically intraocular leiomyomas are benign, leiomyomas may exhibit progressive growth and cause subluxation of the lens, as well as cataracts, retinal detachment, neovascular glaucoma, or visual loss (2). The degree of smooth muscle tumor malignancy in other organs has been questioned (7). Furthermore, the rarity of leiomyomas in the ciliary body and in the choroid has made it diﬃcult to characterize their biological behavior (7). A leiomyoma in the ciliary body that extended to the anterior chamber was removed by partial lamellar sclerouvectomy, but dialysis caused subsequent rhegmatogenous retinal detachment (7). The potential complications of partial lamellar sclerouvectomy include vitreous hemorrhage, cataracts, retinal detachment, and hemorrhagic choroidal detachment (7). Local resection is recommended when the ocular tumor is small and is located in the ciliary body or ciliochoroidal area; however, globe- and visionconserving treatment is diﬃcult when, as in our case, the tumor lies in the posterior choroid and the best treatment option in unknown (2). Due to the rare incidence of posterior choroidal leiomyoma, articles published from 2002 to 2014 and three case reports available in the literature were thoroughly reviewed (Table 3). Compared to previous case reports, the current case had several unique features including the appearance of pigmentation, failure to detect early ﬁlling by FA, and identiﬁcation of desmin focal positivity by IHC. When comparing the results of available reports with our case, the diversity in clinical presentations made it diﬃcult to characterize the speciﬁc features of posterior choroidal leiomyomas. Therefore, choroidal leiomyoma should be considered when making a diﬀerential diagnosis of choroidal tumors. In conclusion, posterior choroidal leiomyoma is extremely rare. A diagnosis based on clinical
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presentation is very diﬃcult, and a leiomyoma is often indistinguishable from amelanotic or melanotic melanomas. A deﬁnite diagnosis can be made by immunohistochemistry or transmission electron microscopy. It is crucial to include choroidal leiomyoma in the diﬀerential diagnosis of choroidal tumors, especially before performance of enucleation or a detrimental treatment. CONFLICT OF INTEREST None.
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