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Primary adenocarcinoma of pigmented ciliary epithelium in a phthisical eye
Accepted Manuscript Primary Adenocarcinoma of Pigmented Ciliary Epithelium in a Phthisical Eye Jaya B. Kumar, MD, Alan D. Proia, MD, PhD, Prithvi Mruthyunjaya, MD, Sumit Sharma, MD PII:
S0039-6257(15)30036-9
DOI:
10.1016/j.survophthal.2015.11.001
Reference:
SOP 6598
To appear in:
Survey of Ophthalmology
Received Date: 13 August 2015 Revised Date:
1 November 2015
Accepted Date: 6 November 2015
Please cite this article as: Kumar JB, Proia AD, Mruthyunjaya P, Sharma S, Primary Adenocarcinoma of Pigmented Ciliary Epithelium in a Phthisical Eye, Survey of Ophthalmology (2015), doi: 10.1016/ j.survophthal.2015.11.001. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT
Primary Adenocarcinoma of Pigmented Ciliary Epithelium in a Phthisical Eye Jaya B Kumar, MD1, Alan D. Proia, MD, PhD2, Prithvi Mruthyunjaya, MD1, Sumit Sharma, MD1
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2 Department of Pathology, Duke University, Durham, NC
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1 Department of Ophthalmology, Duke Eye Center, Duke University, Durham, NC
ACCEPTED MANUSCRIPT
Abstract We report a case of adenocarcinoma of the pigmented ciliary epithelium arising in a phthisical eye. A 92year-old man initially presented with severe ocular pain had calcification extending from the posterior
RI PT
pole to ciliary body on B-scan ultrasonography to a degree not previously reported. We highlight the importance of screening for intraocular neoplasms in adults with a longstanding phthisical eye. Clinical Presentation
A 92-year-old Caucasian man presented with acute onset of right eye pain. His ocular history was
SC
significant for a metallic foreign body injury to the right eye over 50 years ago leaving him with no light perception vision. Slit lamp examination revealed 360 degrees of neovascularization of the iris, 30% hyphema, diffuse anterior chamber cell and flare, brunescent cataract with no view to the posterior pole
M AN U
(Figure 1). B-scan ultrasonography showed a possible mass with diffuse calcification and hyperechogenicity extending from the posterior pole anteriorly to the ciliary body with retinal detachment (Figure 2 A and B). The anterior segment changes were attributed to chronic phthisis bulbi or an intraocular mass of unclear etiology. The patient was placed on prednisolone drops every 2 hours and atropine every 12 hours, buthis symptoms and exam were unchanged 6 weeks later.
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Imaging
A review was made of ultrasound imaging from 9 months prior, and the questionable hyperechogenic mass appeared to have grown (Figure 2C). Computed axial tomography scans of the head, chest, abdomen, and pelvis were negative for metastatic disease, but showed a circular compact
EP
heterogeneous hyperdense lesion in the globe (Figure 2 D). MRI could not be obtained because of the history of a metallic object in the orbit. Given the concern for malignancy and lack of clinical
AC C
improvement, a decision was made to enucleate the right eye. Pathology
Gross examination revealed a 2.0 x 1.5 x 0.1 cm tan-brown mass with areas of hemorrhage in the posterior half of the globe that microscopically was composed of organizing hemorrhage, gliotic retina, and choroidal ossification. Inferiorly, there was a tumor centered in the region of the ciliary body with invasion posteriorly into the choroid. The maximum anterior-posterior dimension of the tumor in histological sections was 8 mm and the maximum thickness was 3 mm.
ACCEPTED MANUSCRIPT
The tumor was composed of cells with moderate amounts of cytoplasm having variable melanin pigmentation and round to oval nuclei with stippled chromatin. The tumor cells formed sheets, cords, and glands with an eosinophilic basement membrane. Basement membrane was occasionally prominent and was highlighted using periodic acid-Schiff (PAS) stain (figure 3 A-D). Small foci of
RI PT
ossification were in the tumor. Choroidal invasion of the tumor cells provided the key in differentiating adenoma from adenocarcinoma (Figure 4). A diagnosis of adenocarcinoma arising from the pigmented CE was made based on the cytological features of the tumor cells, invasion of the choroid, and the presence of a basement membrane surrounding tumor cells5,9. The metastatic workup has been
SC
negative, and he has otherwise been clinically stable.
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Discussion
Tumors of the ciliary epithelium (CE) can be classified as benign from reactive hyperplasia, age-related hyperplasia (Fuchs adenoma), malignant--either congenital (medulloepithelioma) or acquired--or metastatic to the ciliary body6,8. True acquired neoplasms of the pigmented ciliary epithelium are rare, with few case reports10. Since these lesions may be clinically difficult to distinguish from ciliary body malignant melanoma, the diagnosis of adenoma or adenocarcinoma of the CE is often made
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pathologically after local resection or enucleation. These tumors have been mostly described in adults following trauma or inflammation as predisposing factors, though there has been a case report in a 7year-old child and one in a previously healthy adult eye7,9,10. Pigmented cells of the iris, ciliary body, and retina can undergo reactive proliferation and migration,
EP
seen as hyperplasia of the epithelium on histology5,9. Over time fibrotic changes and bone formation may develop5. Inflammation and trauma are thought to be predisposing factors for hyperplasia and
AC C
malignant transformation3; however, it is possible that the intraocular tumor is discovered because of more frequent examinations. These tumors are slow growing and usually do not portend malignancy until signs of neovascularization or orbital findings such as proptosis manifest. Therefore, inflammation may not play a role in malignant transformation. Another possibility is that the growing intraocular mass results in a phthisical eye.
At a more cellular level, defects in regulatory proteins may contribute to malignant conversion. Opticin is a small, leucine-rich repeat proteoglycan/protein produced throughout adult life by the nonpigmented ciliary body epithelium that is thought to be involved in both structural modulation of
ACCEPTED MANUSCRIPT
collagen fibrils, vitreoretinal adhesion, and the regulation of cellular activities including neoplastic cell proliferation. The loss of opticin expression may be associated with neoplastic transformation1. Clinical signs and symptoms that should raise suspicion for adenocarcinoma of CE in a patient with a
RI PT
longstanding phthisical eye include new onset of proptosis, ocular pain, intraocular calcification, hemorrhage, inflammation, secondary cataract formation, and/or subluxation of the lens. Other clinical symptoms include floaters, decreased vision, intractable pain, and/or elevated intraocular pressure4,7,10.
Imaging allows better characterization of the lesion and monitoring the size or response to treatment
SC
over time. B-scan ultrasonography of nonpigmented ciliary epithelial tumors reveals abrupt elevation, acoustic solidity, and high internal reflectivity8. CT images of nonpigmented ciliary epithelial tumors
M AN U
demonstrate circular, compact, heterogeneous, hyperdense lesions2,11. MRI may offer an additional clue to diagnosis, showing a low intensity lesion--lower than vitreous and gray matter but higher than white matter--on T2 weighted images10. Other imaging modalities such as OCT are not as helpful.
To our knowledge there are no previous reports describing the ultrasound findings associated with pigmented ciliary epithelial tumors. None of the previously published reports of non-pigmented ciliary
TE D
epithelial tumors describe the degree of calcification seen in our patient on both B-scan ultrasonography and CT scan. The onset of new symptoms and signs--including pain, hyphema, and neovascularization of the iris--and reevaluation of the B-scan images raised suspicion for malignancy. Although there are no published guidelines for evaluating long-standing blind eyes, our case reminds us that new onset of
EP
proptosis, ocular pain, intraocular calcification, hemorrhage, inflammation, secondary cataract formation and/or subluxation of the lens in a phthisical eye should not be ignored and should prompt
AC C
evaluation for possible intraocular malignancy with b-scan ultrasonography.
Diagnosis ultimately requires a combination of clinical findings, imaging studies (ultrasound and or MRI) and pathological confirmation. Treatment varies depending on the size of the lesion and severity of the symptoms. Plaque brachytherapy was used to treat a 5.5mm ciliary body lesion4. For painful phthisical eyes, enucleation is recommended for lesions confined to the globe or exenteration if there are signs of extraocular extension5.
ACCEPTED MANUSCRIPT
Given the rarity of the tumor, the prognosis is not well known. A localized ciliary body lesion treated with plaque brachytherapy was followed for 3 years without recurrence4. There are case reports of scleral invasion and secondary, fatal intracranial extension5; however without extrascleral extension,
RI PT
metastatic disease is rare5.
Conclusion
Pain, proptosis, and hyphema in conjunction with intraocular calcification raise suspicion for an
SC
intraocular mass. Our case highlights the importance of screening phthisical eyes for intraocular malignancy with b-scan ultrasonography.
M AN U
Method of Literature Search
Literature search was completed using PubMed. Search phrases included the following: adenocarcinoma of pigmented ciliary epithelium, adenocarcinoma of nonpigmented ciliary epithelium, and ciliary body
References
TE D
mass. Articles in English were included and spanned from 1984-2014.
1. Assheton DC, Guerin EP, Sheridan CM, Bishop PN, Hiscott PS. Neoplastic transformation of ciliary body epithelium is associated with loss of opticin expression. The British journal of ophthalmology. 2007;91(2):230-2.
EP
2. Chen ZQ, Fang XY. Adenoma of nonpigmented epithelium in ciliary body: literature review and case report. Journal of Zhejiang University Science B. 2007;8(9):612-5.
AC C
3. Grossniklaus HE, Zimmerman LE, Kachmer ML. Pleomorphic adenocarcinoma of the ciliary body. Immunohistochemical and electron microscopic features. Ophthalmology. 1990;97(6):763-8. 4. Finger PT, Reid JE, Iacob CE. Palladium-103 eye plaque brachytherapy for primary adenocarcinoma of the ciliary body epithelium. Brachytherapy. 2011;10(6):503-7. 5. Laver NM, Hidayat AA, Croxatto JO. Pleomorphic adenocarcinomas of the ciliary epithelium. Immunohistochemical and ultrastructural features of 12 cases. Ophthalmology. 1999;106(1):103-10. 6. Lee BJ, Lowder CY, Biscotti C, Schoenfield L, Singh AD. Ciliary body metastasis masquerading as scleritis. The British journal of ophthalmology. 2007;91(12):1582, 649. 7. Papale JJ, Akiwama K, Hirose T, Tsubota K, Hanaoka K, Albert DM. Adenocarcinoma of the ciliary body pigment epithelium in a child. Archives of ophthalmology. 1984;102(1):100-3.
ACCEPTED MANUSCRIPT
8. Shields JA, Eagle RC, Jr., Shields CL, De Potter P. Acquired neoplasms of the nonpigmented ciliary epithelium (adenoma and adenocarcinoma). Ophthalmology. 1996;103(12):2007-16.
RI PT
9. Shields JA, Shields CL, Gunduz K, Eagle RC, Jr. Adenoma of the ciliary body pigment epithelium: the 1998 Albert Ruedemann, Sr, memorial lecture, Part 1. Archives of ophthalmology. 1999;117(5):592-7. 10. Sukeda A, Mori T, Suzuki S, Ochiai A. Adenocarcinoma of the pigmented ciliary epithelium. BMJ case reports. 2014;2014.
SC
11. Takahashi Y, Takahashi E, Goto H, Kakizaki H. Adenoma of the nonpigmented ciliary epithelium in the phthisic eye. Orbit (Amsterdam, Netherlands). 2013;32(3):184-6.
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Figure 1: Slit lamp photo of right eye revealing diffuse corneal edema, corneal scars, 360 degrees of neovascularization of the iris, 30% hyphema, diffuse anterior chamber cell and flare, and brunescent cataract.
Figure 2: B-scan ultrasonographs showing diffuse calcification (green arrows) and homogenous hyperechogenic mass (yellow arrows) extending from posterior pole anteriorly to ciliary body (A,B) larger compared to 9 months prior (C). Sagittal (D) and coronal (E) CT sections showing corresponding hyperdense mass and posterior calcification.
ACCEPTED MANUSCRIPT
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M AN U
SC
RI PT
Figure 3. The ciliary body tumor was composed of a cells with moderate amounts of cytoplasm having variable melanin pigmentation and round to oval nuclei with stippled chromatin forming sheets (A), cords (B), and glands (C). Eosinophilic basement membrane among tumor cells was highlighted with periodic acid-Schiff stain (D). All images are at the same magnification (bar = 50 µm), except for the insert in A (magnification bar = 10 µm).
Figure 4: Choroidal invasion of the tumor cells (seen on right side of image), the key in differentiating adenocarcinoma from adenoma.
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EP
TE D
M AN U
SC
RI PT
ACCEPTED MANUSCRIPT
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M AN U
SC
RI PT
ACCEPTED MANUSCRIPT
S0039-6257(15)30036-9
DOI:
10.1016/j.survophthal.2015.11.001
Reference:
SOP 6598
To appear in:
Survey of Ophthalmology
Received Date: 13 August 2015 Revised Date:
1 November 2015
Accepted Date: 6 November 2015
Please cite this article as: Kumar JB, Proia AD, Mruthyunjaya P, Sharma S, Primary Adenocarcinoma of Pigmented Ciliary Epithelium in a Phthisical Eye, Survey of Ophthalmology (2015), doi: 10.1016/ j.survophthal.2015.11.001. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT
Primary Adenocarcinoma of Pigmented Ciliary Epithelium in a Phthisical Eye Jaya B Kumar, MD1, Alan D. Proia, MD, PhD2, Prithvi Mruthyunjaya, MD1, Sumit Sharma, MD1
AC C
EP
TE D
M AN U
SC
2 Department of Pathology, Duke University, Durham, NC
RI PT
1 Department of Ophthalmology, Duke Eye Center, Duke University, Durham, NC
ACCEPTED MANUSCRIPT
Abstract We report a case of adenocarcinoma of the pigmented ciliary epithelium arising in a phthisical eye. A 92year-old man initially presented with severe ocular pain had calcification extending from the posterior
RI PT
pole to ciliary body on B-scan ultrasonography to a degree not previously reported. We highlight the importance of screening for intraocular neoplasms in adults with a longstanding phthisical eye. Clinical Presentation
A 92-year-old Caucasian man presented with acute onset of right eye pain. His ocular history was
SC
significant for a metallic foreign body injury to the right eye over 50 years ago leaving him with no light perception vision. Slit lamp examination revealed 360 degrees of neovascularization of the iris, 30% hyphema, diffuse anterior chamber cell and flare, brunescent cataract with no view to the posterior pole
M AN U
(Figure 1). B-scan ultrasonography showed a possible mass with diffuse calcification and hyperechogenicity extending from the posterior pole anteriorly to the ciliary body with retinal detachment (Figure 2 A and B). The anterior segment changes were attributed to chronic phthisis bulbi or an intraocular mass of unclear etiology. The patient was placed on prednisolone drops every 2 hours and atropine every 12 hours, buthis symptoms and exam were unchanged 6 weeks later.
TE D
Imaging
A review was made of ultrasound imaging from 9 months prior, and the questionable hyperechogenic mass appeared to have grown (Figure 2C). Computed axial tomography scans of the head, chest, abdomen, and pelvis were negative for metastatic disease, but showed a circular compact
EP
heterogeneous hyperdense lesion in the globe (Figure 2 D). MRI could not be obtained because of the history of a metallic object in the orbit. Given the concern for malignancy and lack of clinical
AC C
improvement, a decision was made to enucleate the right eye. Pathology
Gross examination revealed a 2.0 x 1.5 x 0.1 cm tan-brown mass with areas of hemorrhage in the posterior half of the globe that microscopically was composed of organizing hemorrhage, gliotic retina, and choroidal ossification. Inferiorly, there was a tumor centered in the region of the ciliary body with invasion posteriorly into the choroid. The maximum anterior-posterior dimension of the tumor in histological sections was 8 mm and the maximum thickness was 3 mm.
ACCEPTED MANUSCRIPT
The tumor was composed of cells with moderate amounts of cytoplasm having variable melanin pigmentation and round to oval nuclei with stippled chromatin. The tumor cells formed sheets, cords, and glands with an eosinophilic basement membrane. Basement membrane was occasionally prominent and was highlighted using periodic acid-Schiff (PAS) stain (figure 3 A-D). Small foci of
RI PT
ossification were in the tumor. Choroidal invasion of the tumor cells provided the key in differentiating adenoma from adenocarcinoma (Figure 4). A diagnosis of adenocarcinoma arising from the pigmented CE was made based on the cytological features of the tumor cells, invasion of the choroid, and the presence of a basement membrane surrounding tumor cells5,9. The metastatic workup has been
SC
negative, and he has otherwise been clinically stable.
M AN U
Discussion
Tumors of the ciliary epithelium (CE) can be classified as benign from reactive hyperplasia, age-related hyperplasia (Fuchs adenoma), malignant--either congenital (medulloepithelioma) or acquired--or metastatic to the ciliary body6,8. True acquired neoplasms of the pigmented ciliary epithelium are rare, with few case reports10. Since these lesions may be clinically difficult to distinguish from ciliary body malignant melanoma, the diagnosis of adenoma or adenocarcinoma of the CE is often made
TE D
pathologically after local resection or enucleation. These tumors have been mostly described in adults following trauma or inflammation as predisposing factors, though there has been a case report in a 7year-old child and one in a previously healthy adult eye7,9,10. Pigmented cells of the iris, ciliary body, and retina can undergo reactive proliferation and migration,
EP
seen as hyperplasia of the epithelium on histology5,9. Over time fibrotic changes and bone formation may develop5. Inflammation and trauma are thought to be predisposing factors for hyperplasia and
AC C
malignant transformation3; however, it is possible that the intraocular tumor is discovered because of more frequent examinations. These tumors are slow growing and usually do not portend malignancy until signs of neovascularization or orbital findings such as proptosis manifest. Therefore, inflammation may not play a role in malignant transformation. Another possibility is that the growing intraocular mass results in a phthisical eye.
At a more cellular level, defects in regulatory proteins may contribute to malignant conversion. Opticin is a small, leucine-rich repeat proteoglycan/protein produced throughout adult life by the nonpigmented ciliary body epithelium that is thought to be involved in both structural modulation of
ACCEPTED MANUSCRIPT
collagen fibrils, vitreoretinal adhesion, and the regulation of cellular activities including neoplastic cell proliferation. The loss of opticin expression may be associated with neoplastic transformation1. Clinical signs and symptoms that should raise suspicion for adenocarcinoma of CE in a patient with a
RI PT
longstanding phthisical eye include new onset of proptosis, ocular pain, intraocular calcification, hemorrhage, inflammation, secondary cataract formation, and/or subluxation of the lens. Other clinical symptoms include floaters, decreased vision, intractable pain, and/or elevated intraocular pressure4,7,10.
Imaging allows better characterization of the lesion and monitoring the size or response to treatment
SC
over time. B-scan ultrasonography of nonpigmented ciliary epithelial tumors reveals abrupt elevation, acoustic solidity, and high internal reflectivity8. CT images of nonpigmented ciliary epithelial tumors
M AN U
demonstrate circular, compact, heterogeneous, hyperdense lesions2,11. MRI may offer an additional clue to diagnosis, showing a low intensity lesion--lower than vitreous and gray matter but higher than white matter--on T2 weighted images10. Other imaging modalities such as OCT are not as helpful.
To our knowledge there are no previous reports describing the ultrasound findings associated with pigmented ciliary epithelial tumors. None of the previously published reports of non-pigmented ciliary
TE D
epithelial tumors describe the degree of calcification seen in our patient on both B-scan ultrasonography and CT scan. The onset of new symptoms and signs--including pain, hyphema, and neovascularization of the iris--and reevaluation of the B-scan images raised suspicion for malignancy. Although there are no published guidelines for evaluating long-standing blind eyes, our case reminds us that new onset of
EP
proptosis, ocular pain, intraocular calcification, hemorrhage, inflammation, secondary cataract formation and/or subluxation of the lens in a phthisical eye should not be ignored and should prompt
AC C
evaluation for possible intraocular malignancy with b-scan ultrasonography.
Diagnosis ultimately requires a combination of clinical findings, imaging studies (ultrasound and or MRI) and pathological confirmation. Treatment varies depending on the size of the lesion and severity of the symptoms. Plaque brachytherapy was used to treat a 5.5mm ciliary body lesion4. For painful phthisical eyes, enucleation is recommended for lesions confined to the globe or exenteration if there are signs of extraocular extension5.
ACCEPTED MANUSCRIPT
Given the rarity of the tumor, the prognosis is not well known. A localized ciliary body lesion treated with plaque brachytherapy was followed for 3 years without recurrence4. There are case reports of scleral invasion and secondary, fatal intracranial extension5; however without extrascleral extension,
RI PT
metastatic disease is rare5.
Conclusion
Pain, proptosis, and hyphema in conjunction with intraocular calcification raise suspicion for an
SC
intraocular mass. Our case highlights the importance of screening phthisical eyes for intraocular malignancy with b-scan ultrasonography.
M AN U
Method of Literature Search
Literature search was completed using PubMed. Search phrases included the following: adenocarcinoma of pigmented ciliary epithelium, adenocarcinoma of nonpigmented ciliary epithelium, and ciliary body
References
TE D
mass. Articles in English were included and spanned from 1984-2014.
1. Assheton DC, Guerin EP, Sheridan CM, Bishop PN, Hiscott PS. Neoplastic transformation of ciliary body epithelium is associated with loss of opticin expression. The British journal of ophthalmology. 2007;91(2):230-2.
EP
2. Chen ZQ, Fang XY. Adenoma of nonpigmented epithelium in ciliary body: literature review and case report. Journal of Zhejiang University Science B. 2007;8(9):612-5.
AC C
3. Grossniklaus HE, Zimmerman LE, Kachmer ML. Pleomorphic adenocarcinoma of the ciliary body. Immunohistochemical and electron microscopic features. Ophthalmology. 1990;97(6):763-8. 4. Finger PT, Reid JE, Iacob CE. Palladium-103 eye plaque brachytherapy for primary adenocarcinoma of the ciliary body epithelium. Brachytherapy. 2011;10(6):503-7. 5. Laver NM, Hidayat AA, Croxatto JO. Pleomorphic adenocarcinomas of the ciliary epithelium. Immunohistochemical and ultrastructural features of 12 cases. Ophthalmology. 1999;106(1):103-10. 6. Lee BJ, Lowder CY, Biscotti C, Schoenfield L, Singh AD. Ciliary body metastasis masquerading as scleritis. The British journal of ophthalmology. 2007;91(12):1582, 649. 7. Papale JJ, Akiwama K, Hirose T, Tsubota K, Hanaoka K, Albert DM. Adenocarcinoma of the ciliary body pigment epithelium in a child. Archives of ophthalmology. 1984;102(1):100-3.
ACCEPTED MANUSCRIPT
8. Shields JA, Eagle RC, Jr., Shields CL, De Potter P. Acquired neoplasms of the nonpigmented ciliary epithelium (adenoma and adenocarcinoma). Ophthalmology. 1996;103(12):2007-16.
RI PT
9. Shields JA, Shields CL, Gunduz K, Eagle RC, Jr. Adenoma of the ciliary body pigment epithelium: the 1998 Albert Ruedemann, Sr, memorial lecture, Part 1. Archives of ophthalmology. 1999;117(5):592-7. 10. Sukeda A, Mori T, Suzuki S, Ochiai A. Adenocarcinoma of the pigmented ciliary epithelium. BMJ case reports. 2014;2014.
SC
11. Takahashi Y, Takahashi E, Goto H, Kakizaki H. Adenoma of the nonpigmented ciliary epithelium in the phthisic eye. Orbit (Amsterdam, Netherlands). 2013;32(3):184-6.
AC C
EP
TE D
M AN U
Figure 1: Slit lamp photo of right eye revealing diffuse corneal edema, corneal scars, 360 degrees of neovascularization of the iris, 30% hyphema, diffuse anterior chamber cell and flare, and brunescent cataract.
Figure 2: B-scan ultrasonographs showing diffuse calcification (green arrows) and homogenous hyperechogenic mass (yellow arrows) extending from posterior pole anteriorly to ciliary body (A,B) larger compared to 9 months prior (C). Sagittal (D) and coronal (E) CT sections showing corresponding hyperdense mass and posterior calcification.
ACCEPTED MANUSCRIPT
AC C
EP
TE D
M AN U
SC
RI PT
Figure 3. The ciliary body tumor was composed of a cells with moderate amounts of cytoplasm having variable melanin pigmentation and round to oval nuclei with stippled chromatin forming sheets (A), cords (B), and glands (C). Eosinophilic basement membrane among tumor cells was highlighted with periodic acid-Schiff stain (D). All images are at the same magnification (bar = 50 µm), except for the insert in A (magnification bar = 10 µm).
Figure 4: Choroidal invasion of the tumor cells (seen on right side of image), the key in differentiating adenocarcinoma from adenoma.
AC C
EP
TE D
M AN U
SC
RI PT
ACCEPTED MANUSCRIPT
AC C
EP
TE D
M AN U
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