- Email: [email protected]
Mesectodermal leiomyoma of the ciliary body: Report of a case and review of the literature
ARTICLE IN PRESS
Pathology – Research and Practice 205 (2009) 125–130 www.elsevier.de/prp
TEACHING CASES
Mesectodermal leiomyoma of the ciliary body: Report of a case and review of the literature Triantafyllia Koletsaa, Georgia Karayannopouloua,, Dimitrios Dereklisb, Ippokratis Vasileiadisb, Constantine S. Papadimitrioua, Prodromos Hytirogloua a
Department of Pathology, Aristotle University Medical School, 540 06 Thessaloniki, Greece Department of Opthalmology, Aristotle University Medical School, Thessaloniki, Greece
b
Received 30 January 2008; accepted 6 June 2008
Abstract Mesectodermal leiomyoma of the ciliary body is a rare benign tumor with double (muscular and neural) differentiation. This neoplasm is considered to originate from the ciliary body smooth muscle, a neural crest derivative. We report a case of mesectodermal leiomyoma of the right eye occurring in a 53-year-old woman, who presented with significant decrease of visual acuity. A malignant melanoma was highly suspected on clinical evaluation, and the globe was enucleated. The tumor measured 1.2 cm in greatest dimension, and consisted of spindle and ovoid cells with abundant fibrillary cytoplasmic processes. Immunohistochemical stains revealed positivity for smooth muscle actin, caldesmon, neuron-specific enolase, and CD56 antigen. A review of the 23 cases thus far reported in the literature shows a striking predilection for women, as well as significant difficulties in differentiating this tumor from malignant melanoma on clinical grounds. r 2008 Elsevier GmbH. All rights reserved. Keywords: Mesectodermal leiomyoma; Ciliary body; Neoplasm
Introduction Mesectodermal leiomyoma of the ciliary body is a rare tumor that is considered to originate from the ciliary body smooth muscle, a neural crest derivative [7,9,13]. This neoplasm exhibits features of both neural and muscular differentiation on histologic and ultrastructural examination. Thus far, immunohistochemical studies have confirmed the smooth muscle aspect of tumor cell differentiation, but have not provided sufficient support for the
neural aspect, with the exception of two recently reported cases with CD56 positivity [12,15]. This rare tumor has important clinical implications, because it may mimick malignant melanoma on ophthalmologic and radiologic examination, resulting in ocular enucleation. We report a case of mesectodermal leiomyoma of the ciliary body with extensive immunohistochemical stains, providing further evidence of double differentiation of the neoplastic cells.
Clinical history Corresponding author. Tel.: +302310 999 234; fax: +302310 999229. E-mail address: [email protected] (G. Karayannopoulou).
0344-0338/$ - see front matter r 2008 Elsevier GmbH. All rights reserved. doi:10.1016/j.prp.2008.06.004
A 53-year-old woman presented with progressive decrease in visual acuity of two-year duration. Two
ARTICLE IN PRESS 126
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months prior to admission, her visual acuity had worsened significantly. On examination, a tumor was found extending from 7 to 10 h, from the pars plana of
the ciliary body to the temporal aspect of the macula. The lesion had distorted the lens, and had involved the visual axis. Visual acuity was 20/400. The mass was dark gray-brown in color, with an appearance suggestive of malignant melanoma. The left eye showed no abnormalities. The findings of ultrasonography, computed tomography (CT), and magnetic resonance imaging (MRI) were thought to be compatible with malignant melanoma of the right eye (Fig. 1). Therefore, the right globe was enucleated and was sent for pathologic examination.
Materials and methods
Fig. 1. Radiographic findings: post-contrast T1-weighted magnetic resonance image showing a space-occupying lesion at the anterior temporal wall of the right eye. It has a broad base, without signs of wall infiltration or increased uptake.
Table 1.
The globe was fixed in 10% formalin, and sections were embedded in paraffin blocks. Four micron-thick paraffin sections were stained with hematoxylin and eosin. Unstained paraffin sections were used for immunohistochemical stains. A standard streptavidin– biotin method was used for immunohistochemistry. The antibody panel and pertinent information are shown in Table 1.
Antibodies used for paraffin section immunohistochemistry
Antigen
Antibody
Source
Titer
Pretreatment
Vimentin SMA Caldesmon Desmin S-100 protein NSE CD56 CD57 Neurofilaments Peripherin Chromogranin Synaptophysin GFAP CD34 CD105 Human melanoma EGFR Pankeratin CD117/c-kit ER PR Ki-67 Fascin Calcitonin
V9 1A4 h-CD D33 polyclonal BBS/NC/VI_H14 1B6 NK1 2F11 PJM50 DAKA3 SY38 polyclonal QBEnd 10 4G11 HMB-45 31G7 AE1/AE3 polyclonal 6F11 16 mib-1 IM20 Ca13-F5
DakoCytomation, Glostrup, Denmark DakoCytomation, Glostrup, Denmark DakoCytomation, Glostrup, Denmark DakoCytomation, Glostrup, Denmark DakoCytomation, Glostrup, Denmark DakoCytomation, Glostrup, Denmark Novocastra, Newcastle upon Tyne, UK Novocastra, Newcastle upon Tyne, UK DakoCytomation, Glostrup, Denmark Novocastra, Newcastle upon Tyne, UK DakoCytomation, Glostrup, Denmark DakoCytomation, Glostrup, Denmark DakoCytomation, Glostrup, Denmark DakoCytomation, Glostrup, Denmark Novocastra, Newcastle upon Tyne, UK DakoCytomation, Glostrup, Denmark Zymed, San Francisco, Calif., USA DakoCytomation, Glostrup, Denmark Novocastra, Newcastle upon Tyne, UK Novocastra, Newcastle upon Tyne, UK Novocastra, Newcastle upon Tyne, UK DakoCytomation, Glostrup, Denmark Novocastra, Newcastle upon Tyne, UK DakoCytomation, Glostrup, Denmark
1/15 1/150 1/50 1/5 1/120 1/240 1/50 1/10 1/80 1/100 1/40 1/10 1/2000 1/20 1/40 1/50 1/50 1/50 1/30 1/50 1/10 1/50 1/100 1/30
MWO-CB MWO-CB MWO-CB MWO-CB Pronase MWO-CB MWO-CB Pronase MWO-CB MWO-CB MWO-CB MWO-D Pronase MWO-D MWO-CB MWO-CB MWO-CB MWO-CB MWO-EDTA MWO-CB MWO-CB MWO-CB MWO-CB Pronase
Abbreviations: MWO-CB: microwave oven in citrate buffer 0.01 M pH 6; SMA: smooth muscle actin; NSE: neuron-specific enolase; MWO-D: microwave-oven in target retrieval solution S1699 (DakoCytomation, Glostrup, Denmark); GFAP: glial fibrillary acidic protein; pronase: 0.1% pronase solution in TBS 0.01 M pH 7.4; EGFR: epidermal growth factor receptor protein; MWO-EDTA: microwave oven in EDTA 0.01 M pH 9; ER: estrogen receptor protein; PR: progesterone receptor protein.
ARTICLE IN PRESS T. Koletsa et al. / Pathology – Research and Practice 205 (2009) 125–130
127
Fig. 2. Histologic findings: (a) the neoplasm has moderate cellularity, and (b) The neoplastic cells are ovoid or spindle-shaped with fibrillary cytoplasm, without evidence of pleomorphism or mitotic activity (H&E; a: 100; b: 400).
Fig. 3. Immunohistochemical findings: the tumor cells are positive for smooth muscle actin (a), caldesmon (b), NSE (c), and CD56 antigen (d) (streptavidin–biotin, 400).
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Results On gross examination, a well demarcated, yellow-tan ciliary body tumor was found, measuring 12 9 7 mm3. The cut surface of the tumor showed a homogenous yellowish-white, solid appearance. On microscopic examination, the lesion was moderately cellular and consisted of spindle and ovoid cells with normochromatic, mostly roundish nuclei and abundant fibrillary cytoplasmic processes (Fig. 2a and b). The chromatin pattern was finely granular. There was no appreciable mitotic activity. The cells were arranged diffusely. Many small vessels were present throughout the tumor. The periphery of the lesion was circumscribed. On immunohistochemical stains, the neoplastic cells were positive for vimentin, smooth muscle actin
Table 2.
(Fig. 3a), caldesmon (Fig. 3b), neuron-specific enolase (NSE) (Fig. 3c), and CD56 antigen (Fig. 3d). Stains for desmin, cytokeratins AE1/AE3, chromogranin, synaptophysin, neurofilaments, CD57 antigen, S-100 protein, peripherin, GFAP, HMB45, CD34 antigen, CD117/ c-kit, CD105, calcitonin, epidermal growth factor receptor, estrogen receptor protein, progesterone receptor protein, and fascin were negative. On Ki-67/mib-1 stain, o1% of tumor cell nuclei were positive, a feature consistent with a very low proliferative activity.
Discussion Mesectodermal leiomyoma of the ciliary body is a rare tumor. Since 1977, when this neoplasm was defined as a distinct entity by Jakobiec et al. [9], only 23 cases
Review of all reported cases of ciliary body mesectodermal leiomyoma
Ref. no
Age
Sex
Location
[10]
1 2 1
37 20 28
F F F
[6] [16] [20] [3]
1 1 1 1
23 18 28 63
F F F F
OS/CB, superonasal left OS/CB, superotemporal right OD/CB, superotemporal right OS/CB, superonasal left OD/CB, inferotemporal right OS/CB, superior left OD/CB, inferotemporal
[8]
1
28
F
OD/CB, inferior right
8.5
[21]
1
38
M
OD/CB, inferior right
8
[22] [19]
1 1
8 80
M F
2 3 4 5 6
11 29 20 68 54
F F F M F
OS/CB, inferotemporal left OS/CBCh, superotemporal left OD/CBCh, superonasal right OD/CBCh, temporal right OD/CBCh, temporal right OD/CB, inferotemporal left OD/CB, superonasal left
14 7 16 15 9
7
24
M
OD/CBCh, superior left
13
[1] [4]
1 1
37 47
F F
[17] [12]
1 1
19 23
F F
OS/CB, left OD/CB, superotemporal, right OD/CB, anterolateral,right OS/CB, inferonasal left
[15]
1
21
M
OD/CB, inferior, right
2 1
54 53
F F
OD/CB, right OS/CB, anterotemporal right
[9]
Present case
Size/mm
Clinical impression
Treatment
Melanoma Melanoma Melanoma
Resection Enucleation Enucleation
Melanoma or cyst Malignant Malignant Malignant v.s benign lesion Malignant v.s benign lesion Malignant v.s benign lesion Cystic lesion Melanoma, leiomyoma
Iridocyclectomy Enucleation Enucleation Resection
Resection Resection Resection Enucleation Resection
15 22
Melanoma ‘‘Atypical staphyloma’’ Leiomyoma Melanoma Melanoma v.s leiomyoma vs neurilemmoma Melanoma v.s leiomyoma vs neurilemmoma Melanoma Melanoma
20 9.6
Melanoma v.s glioma Melanoma v.s benign
Enucleation Sclerotomy with tumor biopsy Iridocyclectomy
6 9 9 7 8 13 6
10 4
5 9 12
Inflammatory lesion v.s hemangioma Melanoma Melanoma
Abbreviations: OS: oculus sinister; CB: ciliary body; OD: oculus dexter; CBCh: ciliochoroidal area.
Resection Resection Enucleation Resection
Resection Enucleation Enucleation
Enucleation Enucleation
ARTICLE IN PRESS T. Koletsa et al. / Pathology – Research and Practice 205 (2009) 125–130
Table 3.
129
Immunohistochemical findings from previously reported cases
IHC stain/Ref. no SSSTAIN
3
8
Vimentin Actin Caldesmon Calponin Desmin S-100 NSE GFAP Myoglobin Factor VIII CK Chromogranin Synaptophysin CD56 CD57 Peripherin Neurofilaments HMB-45 CD34 EMA EGFR CD105 Fascin c-kit/CD117 Calcitonin ER PR Ki-67/mib-1
+ +
+
7
21
22
19
19
19
19
19
19
19
1
4
17
12
15
15
Our case
+
+
+
+
+
+
+
+
+
+ +
+ + + +
+ +
+ + + +
+ + +
+
+
+
o1
+f +f
+
+
+
o1%
Abbreviations: IHC: immunohistochemical; +: positive; : negative; +f: focally positive; NSE: neuron-specific enolase; GFAP: glial fibrillary acidic protein; CK: cytokeratin; EMA: epithelial membrane antigen; ER: estrogen receptor protein; PR: progesterone receptor protein.
[1,3,4,6,8–10,12,15–17,19–22] have been reported in the literature (Table 2). Six more cases were apparently reported as leiomyomas before 1977 [2]. This rare lesion has also been reported in the posterior chorioid [11,18]. Mesectodermal leiomyoma shows a striking predilection for women (only 5 out of the 23 cases thus far reported occurred in men). Most patients are in the second to fourth decades; however, the age range is wide (8–80 years). The majority of tumors do not exceed 1 cm in greatest dimension, but occasional examples measure up to 2.2 cm. Several cases were preoperatively considered to be malignant melanomas, because it is very difficult to differentiate this tumor from melanoma on clinical grounds [5]. The scientific interest in mesectodermal leiomyoma stems from the neural crest origin of the ciliary body smooth muscle, which explains the neural appearance of the spindle and ovoid cells on light microscopy. Ultrastructural studies have played an important role in confirming such origin since 1977 [4,9,14] by demonstrating evidence of both smooth muscle and neural differentiation. Characteristic neural features on
electron microscopy include concentric whorls of cellular processes, cytoplasmic membranous lamellar bodies within the cytoplasm, and intercellular skeinoid fibers. On the other hand, the presence of myofilaments with fusiform densities, dense attachments, external lamina, and pinocytotic vesicles are indicative of myoid differentiation. Since 1989, immunohistochemistry has been employed to further elucidate the nature of this tumor. To date, immunohistochemical analysis has been performed in 17 reported cases (Table 3). All cases were positive for smooth muscle actin, and occasional cases were positive for desmin. Stains for various neural markers including GFAP, neurofilaments, chromogranin, and synaptophysin have been consistently negative [12,17]. However, two cases of mesectodermal leiomyoma [12,15] were recently found to be positive for neural adhesion molecule (CD56), as well as for two previously unreported markers of smooth muscle differentiation, namely, caldesmon and calponin. Moreover, Odashiro et al. [15] also found focal positivity of the tumor cells in one case for NSE and S-100 protein.
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Our case confirms the findings of the previous studies [12,15] regarding positivity for CD56 antigen and caldesmon. Stain for calponin was unavailable in our study. However, stains for peripherin and fascin were performed for the first time in the literature, and were negative. Interestingly, NSE immunostaining was diffusely positive in our case, although it has been negative in four previously reported cases and only focally positive in another case. These findings suggest that some cases may have more advanced neural differentiation than others. Mesectodermal leiomyoma is a benign tumor. No metastases have been reported in the literature. Our immunohistochemical findings regarding Ki-67 antigen expression, together with those of Lai et al. [12], support the benign nature of this tumor. Although malignant melanoma is difficult to distinguish from mesectodermal leiomyoma on clinical grounds, histologic differential diagnosis is usually easy with the aid of immunohistochemistry. Immunohistochemical stains are also useful in the differential diagnosis from other histologically similar tumors such as neurofibromas, schwannomas, gliomas, or leiomyomas. In conclusion, mesectodermal leiomyoma is a rare tumor of the ciliary body with double (i.e., smooth muscle/neural) differentiation. The diagnosis relies on histopathologic examination, aided by immunohistochemistry and/or electron microscopy. Pathologists should be aware of this rare entity that often masquerades as malignant melanoma on clinical examination.
[8]
[9]
[10]
[11]
[12]
[13]
[14]
[15]
[16]
References [17] [1] C. Alenda, F.I. Aranda, A. Paya, C. Cordoba, Mesectodermal leiomyoma of ciliary body, Int. J. Surg. Pathol. 10 (2002) 309–312. [2] F.C. Blodi, Leiomyoma of the ciliary body, Am. J. Ophtalmol. 33 (1950) 939–942. [3] R.O. Burk, H.E. Volcker, W. Daus, I.A. Born, Mesectodermal leiomyoma of the ciliary body – clinical aspects, surgery and immunohistochemistry, Fortschr. Opthalmol. 86 (1989) 631–635. [4] R.J. Campbell, K.W. Min, J.P. Bolling, Skeinoid fibers in mesectodermal leiomyoma of the ciliary body, Ultrastruct. Pathol. 21 (1997) 559–567. [5] M. Chang, L.E. Zimmerman, I. Mclean, The persisting pseudomelanoma problem, Arch. Opthalmol. 102 (1984) 726–772. [6] J.O. Croxatto, E.S. Malbran, Unusual ciliary body tumor. Mesectodermal leiomyoma, Ophthalmology 89 (1982) 1208–1212. [7] R.L. Font, J.O. Croxatto, N.A. Rao, Tumors of the eye and ocular Adnexa, in: Atlas of Tumor Pathology,
[18]
[19]
[20]
[21]
[22]
4th series, Fascicle 5, AFIP, Washington, DC, 2006, pp. 65–66. H. Ishigooka, H. Yamabe, Y. Kobashi, M. Nagata, Clinical and pathological status of mesectodermal leiomyoma of the ciliary body. A case report and review of the literature, Graefes. Arch. Clin. Exp. Opthalmol. 227 (1989) 101–105. F.A. Jakobiek, R. Font, M. Tso, L. Zimmerman, Mesectodermal leiomyoma of the ciliary body. A tumor of presumed neural crest origin, Cancer 39 (1977) 2102–2173. F.A. Jakobiek, T. Iwamoto, Mesectodermal leiomyoma of the ciliary body associated with a nevus, Arch. Opthalmol. 96 (1978) 692–695. Y.K. Jeon, H.J. Cha, N.R. Kim, C.J. Kim, J.G. Chi, Leiomyoma in the posterior choroid: a case report, J. Korean Med. Sci. 17 (2002) 429–433. C.T. Lai, M.C. Tai, C.M. Liang, H.S. Lee, Unusual uveal tract tumor: mesectodermal leiomyoma of the ciliary body, Pathol. Int. 54 (2004) 337–342. I.W. McLean, M.N. Burnier, L.E. Zimmerman, F.A. Jakobiek, Tumors of the eye and ocular Adnexa, in: Atlas of Tumor Pathology, 3rd series, Fascicle 12, AFIP, Washington, DC, 1993, pp. 197–202. S.L. Meyer, B.S. Fine, R.L. Font, L.E. Zimmerman, Leiomyoma of the ciliary body: electron microscopic verification, Am. J. Opthalmol. 66 (1968) 1061–1068. A.N. Odashiro, B.F. Fernandes, A. Al Kandari, F.J. Gregoire, M.N. Burnier, Report of two cases of ciliary body mesectodermal leiomyoma-unique expression of neural markers, Ophthalmology 114 (2007) 157–161. J.G. Orsoni, B. Daicker, F. Cardillo Piccolino, Mesectodermal leiomyoma of the ciliary body extending into the anterior chamber, Opthalmologica 191 (1985) 127–129. S.H. Park, J.H. Lee, Y.S. Chae, C.H. Kim, Recurrent mesectodermal leiomyoma of the ciliary body: a case report, J. Korean Med. Sci. 18 (2003) 614–617. P. Perri, B. Paduano, C. Incorvaia, C. Costagliola, F. Parmeggiani, S. Rossi, G. Lamberti, I. Nenci, A. Sebastiani, Mesectodermal leiomyoma exclusively involving the posterior choroids, Am. J. Ophthalmol. 134 (2002) 451–454. J.A. Shields, C.L. Shields, R.C. Eagle, P. De Potter, Observations on seven cases of intraocular leiomyoma, Arch. Opthalmol. 112 (1994) 521–528. T. Tagaki, Y. Ueno, N. Matsuya, Mesectodermal leiomyoma of the ciliary body. An ultrastructural study, Arch. Ophthalmol. 103 (1985) 1711–1714. V. White, K. Stevenson, A. Garner, J. Hungerford, Mesectodermal leiomyoma of the ciliary body: case report, Br. J. Opthalmol. 73 (1989) 12–18. D.Y. Yu, S.B. Cohen, G. Peyman, M.O. Tso, Mesectodermal leiomyoma of the ciliary body: new evidence for neural crest origin, J. Pediatr. Opthalmol. Strabismus 27 (1990) 317–321.
Pathology – Research and Practice 205 (2009) 125–130 www.elsevier.de/prp
TEACHING CASES
Mesectodermal leiomyoma of the ciliary body: Report of a case and review of the literature Triantafyllia Koletsaa, Georgia Karayannopouloua,, Dimitrios Dereklisb, Ippokratis Vasileiadisb, Constantine S. Papadimitrioua, Prodromos Hytirogloua a
Department of Pathology, Aristotle University Medical School, 540 06 Thessaloniki, Greece Department of Opthalmology, Aristotle University Medical School, Thessaloniki, Greece
b
Received 30 January 2008; accepted 6 June 2008
Abstract Mesectodermal leiomyoma of the ciliary body is a rare benign tumor with double (muscular and neural) differentiation. This neoplasm is considered to originate from the ciliary body smooth muscle, a neural crest derivative. We report a case of mesectodermal leiomyoma of the right eye occurring in a 53-year-old woman, who presented with significant decrease of visual acuity. A malignant melanoma was highly suspected on clinical evaluation, and the globe was enucleated. The tumor measured 1.2 cm in greatest dimension, and consisted of spindle and ovoid cells with abundant fibrillary cytoplasmic processes. Immunohistochemical stains revealed positivity for smooth muscle actin, caldesmon, neuron-specific enolase, and CD56 antigen. A review of the 23 cases thus far reported in the literature shows a striking predilection for women, as well as significant difficulties in differentiating this tumor from malignant melanoma on clinical grounds. r 2008 Elsevier GmbH. All rights reserved. Keywords: Mesectodermal leiomyoma; Ciliary body; Neoplasm
Introduction Mesectodermal leiomyoma of the ciliary body is a rare tumor that is considered to originate from the ciliary body smooth muscle, a neural crest derivative [7,9,13]. This neoplasm exhibits features of both neural and muscular differentiation on histologic and ultrastructural examination. Thus far, immunohistochemical studies have confirmed the smooth muscle aspect of tumor cell differentiation, but have not provided sufficient support for the
neural aspect, with the exception of two recently reported cases with CD56 positivity [12,15]. This rare tumor has important clinical implications, because it may mimick malignant melanoma on ophthalmologic and radiologic examination, resulting in ocular enucleation. We report a case of mesectodermal leiomyoma of the ciliary body with extensive immunohistochemical stains, providing further evidence of double differentiation of the neoplastic cells.
Clinical history Corresponding author. Tel.: +302310 999 234; fax: +302310 999229. E-mail address: [email protected] (G. Karayannopoulou).
0344-0338/$ - see front matter r 2008 Elsevier GmbH. All rights reserved. doi:10.1016/j.prp.2008.06.004
A 53-year-old woman presented with progressive decrease in visual acuity of two-year duration. Two
ARTICLE IN PRESS 126
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months prior to admission, her visual acuity had worsened significantly. On examination, a tumor was found extending from 7 to 10 h, from the pars plana of
the ciliary body to the temporal aspect of the macula. The lesion had distorted the lens, and had involved the visual axis. Visual acuity was 20/400. The mass was dark gray-brown in color, with an appearance suggestive of malignant melanoma. The left eye showed no abnormalities. The findings of ultrasonography, computed tomography (CT), and magnetic resonance imaging (MRI) were thought to be compatible with malignant melanoma of the right eye (Fig. 1). Therefore, the right globe was enucleated and was sent for pathologic examination.
Materials and methods
Fig. 1. Radiographic findings: post-contrast T1-weighted magnetic resonance image showing a space-occupying lesion at the anterior temporal wall of the right eye. It has a broad base, without signs of wall infiltration or increased uptake.
Table 1.
The globe was fixed in 10% formalin, and sections were embedded in paraffin blocks. Four micron-thick paraffin sections were stained with hematoxylin and eosin. Unstained paraffin sections were used for immunohistochemical stains. A standard streptavidin– biotin method was used for immunohistochemistry. The antibody panel and pertinent information are shown in Table 1.
Antibodies used for paraffin section immunohistochemistry
Antigen
Antibody
Source
Titer
Pretreatment
Vimentin SMA Caldesmon Desmin S-100 protein NSE CD56 CD57 Neurofilaments Peripherin Chromogranin Synaptophysin GFAP CD34 CD105 Human melanoma EGFR Pankeratin CD117/c-kit ER PR Ki-67 Fascin Calcitonin
V9 1A4 h-CD D33 polyclonal BBS/NC/VI_H14 1B6 NK1 2F11 PJM50 DAKA3 SY38 polyclonal QBEnd 10 4G11 HMB-45 31G7 AE1/AE3 polyclonal 6F11 16 mib-1 IM20 Ca13-F5
DakoCytomation, Glostrup, Denmark DakoCytomation, Glostrup, Denmark DakoCytomation, Glostrup, Denmark DakoCytomation, Glostrup, Denmark DakoCytomation, Glostrup, Denmark DakoCytomation, Glostrup, Denmark Novocastra, Newcastle upon Tyne, UK Novocastra, Newcastle upon Tyne, UK DakoCytomation, Glostrup, Denmark Novocastra, Newcastle upon Tyne, UK DakoCytomation, Glostrup, Denmark DakoCytomation, Glostrup, Denmark DakoCytomation, Glostrup, Denmark DakoCytomation, Glostrup, Denmark Novocastra, Newcastle upon Tyne, UK DakoCytomation, Glostrup, Denmark Zymed, San Francisco, Calif., USA DakoCytomation, Glostrup, Denmark Novocastra, Newcastle upon Tyne, UK Novocastra, Newcastle upon Tyne, UK Novocastra, Newcastle upon Tyne, UK DakoCytomation, Glostrup, Denmark Novocastra, Newcastle upon Tyne, UK DakoCytomation, Glostrup, Denmark
1/15 1/150 1/50 1/5 1/120 1/240 1/50 1/10 1/80 1/100 1/40 1/10 1/2000 1/20 1/40 1/50 1/50 1/50 1/30 1/50 1/10 1/50 1/100 1/30
MWO-CB MWO-CB MWO-CB MWO-CB Pronase MWO-CB MWO-CB Pronase MWO-CB MWO-CB MWO-CB MWO-D Pronase MWO-D MWO-CB MWO-CB MWO-CB MWO-CB MWO-EDTA MWO-CB MWO-CB MWO-CB MWO-CB Pronase
Abbreviations: MWO-CB: microwave oven in citrate buffer 0.01 M pH 6; SMA: smooth muscle actin; NSE: neuron-specific enolase; MWO-D: microwave-oven in target retrieval solution S1699 (DakoCytomation, Glostrup, Denmark); GFAP: glial fibrillary acidic protein; pronase: 0.1% pronase solution in TBS 0.01 M pH 7.4; EGFR: epidermal growth factor receptor protein; MWO-EDTA: microwave oven in EDTA 0.01 M pH 9; ER: estrogen receptor protein; PR: progesterone receptor protein.
ARTICLE IN PRESS T. Koletsa et al. / Pathology – Research and Practice 205 (2009) 125–130
127
Fig. 2. Histologic findings: (a) the neoplasm has moderate cellularity, and (b) The neoplastic cells are ovoid or spindle-shaped with fibrillary cytoplasm, without evidence of pleomorphism or mitotic activity (H&E; a: 100; b: 400).
Fig. 3. Immunohistochemical findings: the tumor cells are positive for smooth muscle actin (a), caldesmon (b), NSE (c), and CD56 antigen (d) (streptavidin–biotin, 400).
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Results On gross examination, a well demarcated, yellow-tan ciliary body tumor was found, measuring 12 9 7 mm3. The cut surface of the tumor showed a homogenous yellowish-white, solid appearance. On microscopic examination, the lesion was moderately cellular and consisted of spindle and ovoid cells with normochromatic, mostly roundish nuclei and abundant fibrillary cytoplasmic processes (Fig. 2a and b). The chromatin pattern was finely granular. There was no appreciable mitotic activity. The cells were arranged diffusely. Many small vessels were present throughout the tumor. The periphery of the lesion was circumscribed. On immunohistochemical stains, the neoplastic cells were positive for vimentin, smooth muscle actin
Table 2.
(Fig. 3a), caldesmon (Fig. 3b), neuron-specific enolase (NSE) (Fig. 3c), and CD56 antigen (Fig. 3d). Stains for desmin, cytokeratins AE1/AE3, chromogranin, synaptophysin, neurofilaments, CD57 antigen, S-100 protein, peripherin, GFAP, HMB45, CD34 antigen, CD117/ c-kit, CD105, calcitonin, epidermal growth factor receptor, estrogen receptor protein, progesterone receptor protein, and fascin were negative. On Ki-67/mib-1 stain, o1% of tumor cell nuclei were positive, a feature consistent with a very low proliferative activity.
Discussion Mesectodermal leiomyoma of the ciliary body is a rare tumor. Since 1977, when this neoplasm was defined as a distinct entity by Jakobiec et al. [9], only 23 cases
Review of all reported cases of ciliary body mesectodermal leiomyoma
Ref. no
Age
Sex
Location
[10]
1 2 1
37 20 28
F F F
[6] [16] [20] [3]
1 1 1 1
23 18 28 63
F F F F
OS/CB, superonasal left OS/CB, superotemporal right OD/CB, superotemporal right OS/CB, superonasal left OD/CB, inferotemporal right OS/CB, superior left OD/CB, inferotemporal
[8]
1
28
F
OD/CB, inferior right
8.5
[21]
1
38
M
OD/CB, inferior right
8
[22] [19]
1 1
8 80
M F
2 3 4 5 6
11 29 20 68 54
F F F M F
OS/CB, inferotemporal left OS/CBCh, superotemporal left OD/CBCh, superonasal right OD/CBCh, temporal right OD/CBCh, temporal right OD/CB, inferotemporal left OD/CB, superonasal left
14 7 16 15 9
7
24
M
OD/CBCh, superior left
13
[1] [4]
1 1
37 47
F F
[17] [12]
1 1
19 23
F F
OS/CB, left OD/CB, superotemporal, right OD/CB, anterolateral,right OS/CB, inferonasal left
[15]
1
21
M
OD/CB, inferior, right
2 1
54 53
F F
OD/CB, right OS/CB, anterotemporal right
[9]
Present case
Size/mm
Clinical impression
Treatment
Melanoma Melanoma Melanoma
Resection Enucleation Enucleation
Melanoma or cyst Malignant Malignant Malignant v.s benign lesion Malignant v.s benign lesion Malignant v.s benign lesion Cystic lesion Melanoma, leiomyoma
Iridocyclectomy Enucleation Enucleation Resection
Resection Resection Resection Enucleation Resection
15 22
Melanoma ‘‘Atypical staphyloma’’ Leiomyoma Melanoma Melanoma v.s leiomyoma vs neurilemmoma Melanoma v.s leiomyoma vs neurilemmoma Melanoma Melanoma
20 9.6
Melanoma v.s glioma Melanoma v.s benign
Enucleation Sclerotomy with tumor biopsy Iridocyclectomy
6 9 9 7 8 13 6
10 4
5 9 12
Inflammatory lesion v.s hemangioma Melanoma Melanoma
Abbreviations: OS: oculus sinister; CB: ciliary body; OD: oculus dexter; CBCh: ciliochoroidal area.
Resection Resection Enucleation Resection
Resection Enucleation Enucleation
Enucleation Enucleation
ARTICLE IN PRESS T. Koletsa et al. / Pathology – Research and Practice 205 (2009) 125–130
Table 3.
129
Immunohistochemical findings from previously reported cases
IHC stain/Ref. no SSSTAIN
3
8
Vimentin Actin Caldesmon Calponin Desmin S-100 NSE GFAP Myoglobin Factor VIII CK Chromogranin Synaptophysin CD56 CD57 Peripherin Neurofilaments HMB-45 CD34 EMA EGFR CD105 Fascin c-kit/CD117 Calcitonin ER PR Ki-67/mib-1
+ +
+
7
21
22
19
19
19
19
19
19
19
1
4
17
12
15
15
Our case
+
+
+
+
+
+
+
+
+
+ +
+ + + +
+ +
+ + + +
+ + +
+
+
+
o1
+f +f
+
+
+
o1%
Abbreviations: IHC: immunohistochemical; +: positive; : negative; +f: focally positive; NSE: neuron-specific enolase; GFAP: glial fibrillary acidic protein; CK: cytokeratin; EMA: epithelial membrane antigen; ER: estrogen receptor protein; PR: progesterone receptor protein.
[1,3,4,6,8–10,12,15–17,19–22] have been reported in the literature (Table 2). Six more cases were apparently reported as leiomyomas before 1977 [2]. This rare lesion has also been reported in the posterior chorioid [11,18]. Mesectodermal leiomyoma shows a striking predilection for women (only 5 out of the 23 cases thus far reported occurred in men). Most patients are in the second to fourth decades; however, the age range is wide (8–80 years). The majority of tumors do not exceed 1 cm in greatest dimension, but occasional examples measure up to 2.2 cm. Several cases were preoperatively considered to be malignant melanomas, because it is very difficult to differentiate this tumor from melanoma on clinical grounds [5]. The scientific interest in mesectodermal leiomyoma stems from the neural crest origin of the ciliary body smooth muscle, which explains the neural appearance of the spindle and ovoid cells on light microscopy. Ultrastructural studies have played an important role in confirming such origin since 1977 [4,9,14] by demonstrating evidence of both smooth muscle and neural differentiation. Characteristic neural features on
electron microscopy include concentric whorls of cellular processes, cytoplasmic membranous lamellar bodies within the cytoplasm, and intercellular skeinoid fibers. On the other hand, the presence of myofilaments with fusiform densities, dense attachments, external lamina, and pinocytotic vesicles are indicative of myoid differentiation. Since 1989, immunohistochemistry has been employed to further elucidate the nature of this tumor. To date, immunohistochemical analysis has been performed in 17 reported cases (Table 3). All cases were positive for smooth muscle actin, and occasional cases were positive for desmin. Stains for various neural markers including GFAP, neurofilaments, chromogranin, and synaptophysin have been consistently negative [12,17]. However, two cases of mesectodermal leiomyoma [12,15] were recently found to be positive for neural adhesion molecule (CD56), as well as for two previously unreported markers of smooth muscle differentiation, namely, caldesmon and calponin. Moreover, Odashiro et al. [15] also found focal positivity of the tumor cells in one case for NSE and S-100 protein.
ARTICLE IN PRESS 130
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Our case confirms the findings of the previous studies [12,15] regarding positivity for CD56 antigen and caldesmon. Stain for calponin was unavailable in our study. However, stains for peripherin and fascin were performed for the first time in the literature, and were negative. Interestingly, NSE immunostaining was diffusely positive in our case, although it has been negative in four previously reported cases and only focally positive in another case. These findings suggest that some cases may have more advanced neural differentiation than others. Mesectodermal leiomyoma is a benign tumor. No metastases have been reported in the literature. Our immunohistochemical findings regarding Ki-67 antigen expression, together with those of Lai et al. [12], support the benign nature of this tumor. Although malignant melanoma is difficult to distinguish from mesectodermal leiomyoma on clinical grounds, histologic differential diagnosis is usually easy with the aid of immunohistochemistry. Immunohistochemical stains are also useful in the differential diagnosis from other histologically similar tumors such as neurofibromas, schwannomas, gliomas, or leiomyomas. In conclusion, mesectodermal leiomyoma is a rare tumor of the ciliary body with double (i.e., smooth muscle/neural) differentiation. The diagnosis relies on histopathologic examination, aided by immunohistochemistry and/or electron microscopy. Pathologists should be aware of this rare entity that often masquerades as malignant melanoma on clinical examination.
[8]
[9]
[10]
[11]
[12]
[13]
[14]
[15]
[16]
References [17] [1] C. Alenda, F.I. Aranda, A. Paya, C. Cordoba, Mesectodermal leiomyoma of ciliary body, Int. J. Surg. Pathol. 10 (2002) 309–312. [2] F.C. Blodi, Leiomyoma of the ciliary body, Am. J. Ophtalmol. 33 (1950) 939–942. [3] R.O. Burk, H.E. Volcker, W. Daus, I.A. Born, Mesectodermal leiomyoma of the ciliary body – clinical aspects, surgery and immunohistochemistry, Fortschr. Opthalmol. 86 (1989) 631–635. [4] R.J. Campbell, K.W. Min, J.P. Bolling, Skeinoid fibers in mesectodermal leiomyoma of the ciliary body, Ultrastruct. Pathol. 21 (1997) 559–567. [5] M. Chang, L.E. Zimmerman, I. Mclean, The persisting pseudomelanoma problem, Arch. Opthalmol. 102 (1984) 726–772. [6] J.O. Croxatto, E.S. Malbran, Unusual ciliary body tumor. Mesectodermal leiomyoma, Ophthalmology 89 (1982) 1208–1212. [7] R.L. Font, J.O. Croxatto, N.A. Rao, Tumors of the eye and ocular Adnexa, in: Atlas of Tumor Pathology,
[18]
[19]
[20]
[21]
[22]
4th series, Fascicle 5, AFIP, Washington, DC, 2006, pp. 65–66. H. Ishigooka, H. Yamabe, Y. Kobashi, M. Nagata, Clinical and pathological status of mesectodermal leiomyoma of the ciliary body. A case report and review of the literature, Graefes. Arch. Clin. Exp. Opthalmol. 227 (1989) 101–105. F.A. Jakobiek, R. Font, M. Tso, L. Zimmerman, Mesectodermal leiomyoma of the ciliary body. A tumor of presumed neural crest origin, Cancer 39 (1977) 2102–2173. F.A. Jakobiek, T. Iwamoto, Mesectodermal leiomyoma of the ciliary body associated with a nevus, Arch. Opthalmol. 96 (1978) 692–695. Y.K. Jeon, H.J. Cha, N.R. Kim, C.J. Kim, J.G. Chi, Leiomyoma in the posterior choroid: a case report, J. Korean Med. Sci. 17 (2002) 429–433. C.T. Lai, M.C. Tai, C.M. Liang, H.S. Lee, Unusual uveal tract tumor: mesectodermal leiomyoma of the ciliary body, Pathol. Int. 54 (2004) 337–342. I.W. McLean, M.N. Burnier, L.E. Zimmerman, F.A. Jakobiek, Tumors of the eye and ocular Adnexa, in: Atlas of Tumor Pathology, 3rd series, Fascicle 12, AFIP, Washington, DC, 1993, pp. 197–202. S.L. Meyer, B.S. Fine, R.L. Font, L.E. Zimmerman, Leiomyoma of the ciliary body: electron microscopic verification, Am. J. Opthalmol. 66 (1968) 1061–1068. A.N. Odashiro, B.F. Fernandes, A. Al Kandari, F.J. Gregoire, M.N. Burnier, Report of two cases of ciliary body mesectodermal leiomyoma-unique expression of neural markers, Ophthalmology 114 (2007) 157–161. J.G. Orsoni, B. Daicker, F. Cardillo Piccolino, Mesectodermal leiomyoma of the ciliary body extending into the anterior chamber, Opthalmologica 191 (1985) 127–129. S.H. Park, J.H. Lee, Y.S. Chae, C.H. Kim, Recurrent mesectodermal leiomyoma of the ciliary body: a case report, J. Korean Med. Sci. 18 (2003) 614–617. P. Perri, B. Paduano, C. Incorvaia, C. Costagliola, F. Parmeggiani, S. Rossi, G. Lamberti, I. Nenci, A. Sebastiani, Mesectodermal leiomyoma exclusively involving the posterior choroids, Am. J. Ophthalmol. 134 (2002) 451–454. J.A. Shields, C.L. Shields, R.C. Eagle, P. De Potter, Observations on seven cases of intraocular leiomyoma, Arch. Opthalmol. 112 (1994) 521–528. T. Tagaki, Y. Ueno, N. Matsuya, Mesectodermal leiomyoma of the ciliary body. An ultrastructural study, Arch. Ophthalmol. 103 (1985) 1711–1714. V. White, K. Stevenson, A. Garner, J. Hungerford, Mesectodermal leiomyoma of the ciliary body: case report, Br. J. Opthalmol. 73 (1989) 12–18. D.Y. Yu, S.B. Cohen, G. Peyman, M.O. Tso, Mesectodermal leiomyoma of the ciliary body: new evidence for neural crest origin, J. Pediatr. Opthalmol. Strabismus 27 (1990) 317–321.