408 OPHTHALMOLOGY SECRETS IN COLOR
Figure 51-11. Teratoid medulloepithelioma with focus of cartilage.
They are associated with mutations in the Dicer 1 gene on 14q31. Like teratoid medulloepitheliomas, pleuropulmonary blastomas may contain cartilage.55
References
1.Nelson CC, Hertzberg BS, Klintworth GK: A histopathologic study of 716 unselected eyes in patients with cancer at the time of death, Am J Ophthalmol 95:788–793, 1983.
2.Kivelä T: The epidemiological challenge of the most frequent eye cancer: retinoblastoma, an issue of birth and death, Brit J Ophthalmol 93:1129–1131, 2009.
3.Shields JA, Shields CL, Brown GC, Eagle RC Jr: Mushroom-shaped choroidal metastasis simulating a choroidal melanoma, Retina 22:810–813, 2002.
4.Spraul CW, Kim D, Fineberg E, Grossniklaus HE: Mushroom-shaped choroidal hemangioma, Am J Ophthalmol 122:434–436, 1996.
5.You JY, Finger PT, Iacob C, et al.: Intraocular schwannoma, Surv Ophthalmol 58:77–85, 2013.
6.De la Cruz PO Jr, Specht CS, McLean IW: Lymphocytic infiltration in uveal malignant melanoma, Cancer 65:112–115, 1990.
7.Folberg R, Mehaffey M, Gardner LM, et al.: The microcirculation of choroidal and ciliary body melanomas, Eye 11:227–238, 1997.
8.McLean IW, Foster WD, Zimmerman LE: Uveal melanoma: location, size, cell type, and enucleation as risk factors in metastasis, Hum Pathol 13:123–132, 1982.
9.Edge SB, Byrd DR, Compton CC, et al.: editor: ed 7, ed 6. American joint commission on cancer. Cancer staging manual.
10.Callender G: Malignant melanotic tumors of the eye: a study of histologic types in 111 cases, Trans Am Acad Ophthalmol Otolaryngol 36:131–142, 1931.
11.McLean IW, Foster WD, Zimmerman LE, Gamel JW: Modifications of Callender’s classification of uveal melanoma at the Armed forces institute of pathology, Am J Ophthalmol 96:502–509, 1983.
12.McLean IW: Uveal nevi and malignant melanomas. In Spencer WH, editor: Ophthalmic pathology: an atlas and textbook, vol 3. Philadelphia, 1996, W.B. Saunders, pp 2121–2217.
13.Sisley K, Rennie IG, Parsons MA, et al.: Abnormalities of chromosomes 3 and 8 in posterior uveal melanoma correlate with prognosis, Genes Chromosomes Cancer 19:22–28, 1997.
14.White VA, Chambers JD, Courtright PD, et al.: Correlation of cytogenetic abnormalities with the outcome of patients with uveal melanoma, Cancer 83:354–359, 1998.
15.Onken MD, Worley LA, Ehlers JP, Harbour JW: Gene expression profiling in uveal melanoma reveals two molecular
classes and predicts metastatic death, Cancer Res 64:7205–7209, 2004.
16. COMS: Assessment of metastatic disease status at death in 435 patients with large choroidal melanoma in the collaborative ocular melanoma study (COMS). COMS report no. 15, Arch Ophthalmol 119:670–676, 2001.
17. COMS: Design and methods of a clinical trial for a rare condition: the collaborative ocular melanoma study. COMS report no. 3, Control Clin Trials 14:362–391, 1993.
18.Diener-West M, Earl JD, Fine SL, et al.: The COMS randomized trial of iodine 125 brachytherapy for choroidal melanoma. III: initial mortality findings. COMS report no. 18, Arch Ophthalmol 119:969–982, 2001.
19.Hawkins BS: The collaborative ocular melanoma study (COMS) randomized trial of pre-enucleation radiation of large choroidal melanoma. IV: ten-year mortality findings and prognostic factors. COMS report no. 24, Am J Ophthalmol 138:936–951, 2004.
20.Shields CL, Shields JA: Recent developments in the management of choroidal melanoma, Curr Opin Ophthalmol 15:244–251, 2004.
21.Eskelin S, Pyrhonen S, Summanen P, et al.: Tumor doubling times in metastatic malignant melanoma of the uvea: tumor progression before and after treatment, Ophthalmology 107:1443–1449, 2000.
22.Shields CL, Furata M, Berman EL, et al.: Choroidal nevus transformation into melanomal analysis of 2514 consecutive cases, Arch Ophthalmol 127:981–987, 2009.
CHAPTER 51 OCULAR TUMORS 409
23.Harbour JW, Augsburger JJ, Eagle RC Jr: Initial management and follow-up of melanocytic iris tumors, Ophthalmology 102:1987–1993, 1995.
24.Jakobiec FA, Silbert G: Are most iris “melanomas” really nevi? A clinicopathologic study of 189 lesions, Arch Ophthalmol 99:2117–2132, 1981.
25.Shields CL, Shields JA, Gross NE, et al.: Survey of 520 eyes with uveal metastases, Ophthalmology 104:1265–1276, 1997.
26.Eagle RC Jr: Immunohistochemistry in diagnostic ophthalmic pathology: a review, Clin Experiment Ophthalmol 36:675–688, 2008.
27.Witschel H, Font RL: Hemangioma of the choroid. A clinicopathologic study of 71 cases and a review of the literature, Surv Ophthalmol 20:415–431, 1976.
28.Gunduz K: Transpupillary thermotherapy in the management of circumscribed choroidal hemangioma, Surv Ophthalmol 49:316–327, 2004.
29.Madreperla SA: Choroidal hemangioma treated with photodynamic therapy using verteporfin, Arch Ophthalmol 119:1606–1610, 2001.
30.McLean IW: Retinoblastomas, retinocytomas and pseudoretinoblastomas. In Spencer WH, editor: Ophthalmic pathology: an atlas and textbook, vol 3. Philadelphia, 1996, W.B. Saunders, pp 1332–1438.
31.Burnier MN, McLean IW, Zimmerman LE, Rosenberg SH: Retinoblastoma. The relationship of proliferating cells to blood vessels, Invest Ophthalmol Vis Sci 31:2037–2040, 1990.
32.Ts’o MO, Fine BS, Zimmerman LE: The Flexner-Wintersteiner rosettes in retinoblastoma, Arch Pathol 88:664–671, 1969.
33.Shields JA, Eagle RC Jr, Shields CL, Potter PD: Congenital neoplasms of the nonpigmented ciliary epithelium (medulloepithelioma), Ophthalmology 103:1998–2006, 1996.
34.Ts’o MO, Fine BS, Zimmerman LE: The nature of retinoblastoma. II. Photoreceptor differentiation: an electron microscopic study, Am J Ophthalmol 69:350–359, 1970.
35.Dimaras H, Khetan V, Halliday W, et al.: Loss of Rb1 induces non-proliferative retinoma: increasing genomic instability correlates with progression to retinoblastoma, Hum Mol Genet 15(17):1363–1372, 2008.
36.Eagle RC Jr, Shields JA, Donoso L, et al.: Malignant transformation of spontaneously regressed retinoblastoma, retinoma/retinocytoma variant, Ophthalmology 96:1389–1395, 1989.
37.Kopelman JE, McLean IW, Rosenberg SH: Multivariate analysis of risk factors for metastasis in retinoblastoma treated by enucleation, Ophthalmology 94:371–377, 1987.
38.Singh AD, Shields CL, Shields JA: Prognostic factors in retinoblastoma, J Pediatr Ophthalmol Strabismus 37:134–141, 2000. quiz, 168–169.
39.Eagle RC Jr: High-risk features and tumor differentiation in retinoblastoma: a retrospective histopathologic study, Arch Pathol Lab Med 133:1203–1209, 2009.
40.Sastre X, Chantada GL, Doz F, et al.: Proceedings of the consensus meetings from the International Retinoblastoma staging working group on the pathology guidelines for the examination of enucleated eyes and evaluation of prognostic risk factors in retinoblastoma, Arch Pathol Lab Med 133:1199–1202, 2009.
41.McLean IW: Retinoblastomas, retinocytomas and pseudoretinoblastomas, Philadelphia, 1996, W.B. Saunders.
42.Murphree AL: Molecular genetics of retinoblastoma, Ophthalmol Clin North Am 8:155–166, 1995.
43.Rushlow DE, Berber MM, Kennett JY, et al.: Characterisation of retinoblastomas without Rb1 mutations: genomic, gene expression, and clinical studies, Lancet Oncol 14:327–334, 2013.
44.Shields JA, Parsons HM, Shields CL, Shah P: Lesions simulating retinoblastoma, J Pediatr Ophthalmol Strabismus 28:338–340, 1991.
45.Shields JA, Shields CL: Intraocular tumors: a text and atlas, Philadelphia, 1992, W.B. Saunders.
46.Shields JA, Shields CL: Atlas of intraocular tumors, Philadelphia, 1999, Lippincott, Williams & Wilkins.
47.Shields JA, Shields CL, Parsons HM: Differential diagnosis of retinoblastoma, Retina 11:232–243, 1991.
48.Shields JA, Shields CL, Honavar SG, Demirci H: Clinical variations and complications of Coats’ disease in 150 cases: the 2000 Sanford Gifford memorial lecture, Am J Ophthalmol 131:561–571, 2001.
49.Shields JA, Shields CL, Honavar SG, et al.: Classification and management of Coats’ disease: the 2000 Proctor lecture, Am J Ophthalmol 131:572–583, 2001.
50.Goldberg MF: Persistent fetal vasculature (PFV): an integrated interpretation of signs and symptoms associated with persistent hyperplastic primary vitreous (PHPV). LIV Edward Jackson memorial lecture, Am J Ophthalmol 124:587– 626, 1997.
51.Broughton WL, Zimmerman LE: A clinicopathologic study of 56 cases of intraocular medulloepithelioma, Am J Ophthalmol 85:407–418, 1978.
52.Kaliki S, Shields CL, Eagle RC Jr, et al.: Ciliary body medulloepithelioma: analysis of 41 cases, Ophthalmology 120:2552–2559, 2013.
53.Green WR, Iliff WJ, Trotter RR: Malignant teratoid medulloepithelioma of the optic nerve, Arch Ophthalmol 91:451–454, 1974.
54.O’Keefe M, Fulcher T, Kelly P, et al.: Medulloepithelioma of the optic nerve head, Arch Ophthalmol 115:1325–1327, 1997.
55.Priest JR, Williams GM, Manera R, et al.: Ciliary body medullepithelioma: four cases associated with pleuropulmonary blastoma—a report from the international pleuropulmonary blastoma registry, Br J Ophthalmol 95:1001–1005, 2001.
ORBITAL TUMORS
Jurij R. Bilyk
1.Should all orbital capillary hemangiomas be excised?
No. Orbital capillary hemangioma (hemangioma of infancy) should be treated only if there is evidence of:
•Amblyopia caused by refractive error (induced myopia or astigmatism) or
•Ptosis causing visual obstruction or head tilt.
Treatment options include the following:
•The treatment of choice at present is the use of systemic β-blockers (propranolol). Systemic monitoring should be performed during induction to ensure cardiopulmonary stability. The use of topical therapy for more superficial lesions is under investigation, with positive initial results. However, the efficacy of topical therapy for deeper orbital lesions has not yet been proven.
•Corticosteroid injections or systemic therapy. Of note, corticosteroid suspensions (e.g., triamcinolone) may rarely case vascular occlusions and visual loss when injected into the orbit. Such medications now come with a black-box warning from the manufacturer warning against their use in the periocular region. The clinician should either obtain a clear consent from the parents or guardians or use a nonsuspension corticosteroid injection or systemic therapy.
•Excision is usually reserved for cases unresponsive to more conservative therapy.
•Interferon α-2 therapy, especially in large localized or systemic cases. This option is becoming more of a rarity with the advent of β-blocker therapy. Interferon α-2 therapy in children is also associated with a risk of spastic diplegia.1-4
2.What orbital tumors can mimic orbital cellulitis?
In both adults and children, the differential includes noninfectious inflammation (idiopathic orbital inflammatory syndrome (inflammatory orbital pseudotumor), sarcoidosis, thyroid eye disease (Graves’ orbitopathy), and granulomatosis with polyangiitis (Wegener granulomatosis)).
In children, also consider:
•Ruptured dermoid cyst. This causes a fulminant soft tissue inflammation.
•Rhabdomyosarcoma. Usually, this is painless.
•Lymphangioma, especially with rapid expansion from a blood-filled “chocolate cyst.”
•Neuroblastoma. This can present with a rapid onset of proptosis and ecchymosis. In adults, also consider:
•Ruptured dermoid cyst.
•Lymphangioma.
•Extrascleral spread and/or necrosis of an intraocular melanoma.
•Metastatic disease to the orbit.
3.What are the most common causes of childhood proptosis?
•Orbital cellulitis
•Capillary hemangioma (hemangioma of infancy)
•Idiopathic orbital inflammatory syndrome (inflammatory orbital pseudotumor)
•Dermoid cyst
•Rhabdomyosarcoma
•Lymphangioma
4.When and how does cavernous hemangioma usually present?
•Cavernous hemangioma is the most common vascular orbital tumor in adults and the most common benign orbital tumor.
•Typically presents in the 4th and 5th decades.
•Well-circumscribed on imaging (see question 16).
•It is not the adult equivalent of capillary hemangioma. Not only are the lesions distinct histopathologically, but cavernous hemangioma is a slowly proliferating entity.
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CHAPTER 52 ORBITAL TUMORS 411
•Because of its slow growth, it is usually a well-tolerated lesion, causing few symptoms. Visual loss, if any, is slow and limited to lesions of the orbital apex.
•Excision is curative.5-9
5.List some basic facts about fibrous histiocytoma and hemangiopericytoma.
•Fibrous histiocytoma, malignant fibrous histiocytoma, and hemangiopericytoma have been characterized as subtypes of solitary fibrous tumor. Because all of these entities are spindle-cell tumors, histopathologic diagnosis may be difficult.
Fibrous histiocytoma:
•Fibrous histiocytoma is the most common mesenchymal tumor of adults.
•Excision is curative.
•Malignant transformation is rare, but possible. Hemangiopericytoma:
•A tumor of pericytes.
•Histopathologic appearance has little correlation with clinical behavior. In other words, a histologically benign lesion may behave aggressively and recur after excision, whereas a tumor with aggressive features on microscopic examination may never recur.
•Patients need to be followed clinically even after excision for possible recurrence or aggressive behavior.10-16
6.What about orbital schwannoma?
•A tumor of the Schwann cells, which form the lining of peripheral nerves.
•Schwannomas typically arise from sensory nerves, although motor and parasympathetic nerve involvement within the orbit has also been reported.
•N.B. Schwannomas do not arise from the optic nerve sheath (the optic nerve is lined with meninges; a tumor arising from the optic nerve sheath is a meningioma, not a schwannoma.
•Within the orbit, most schwannomas arise from sensory nerve sheaths, which may explain their predilection for the superior orbit.
•The Antoni A and B patterns are the classic histologic findings in schwannoma. The A pattern is characterized by abundant, tightly packed spindle cells, whereas the B pattern exhibits fewer cells within a myxoid matrix.17,18
7.How does one order an orbital computed tomography (CT) scan?
•Order axial and coronal cuts in all cases. The newest multiscan CTs typically image in the axial plane only and are then reconstructed as coronal and parasagittal images without loss of resolution or need for patient repositioning.
•If direct coronals cannot be obtained, coronal reconstructions usually suffice, but this is really an issue only with older scanners.
•Always review both soft tissue and bone windows.
•Never order cuts greater than 3 mm.
•Intravenous contrast is helpful in cases of infection or inflammation. It is not necessary for trauma or thyroid eye disease.
•In deep orbital and skull base processes, consider ordering the scan with intraoperative guidance protocols. This will allow a more precise localization of anatomy if subsequent intraoperative image guidance is needed during surgery.19
8.How does one order an orbital magnetic resonance image (MRI)?
Very carefully.
The Rules of Orbital MRI
•NEVER order MRI as the first imaging modality in trauma, for unresponsive patients, or for poor historians. Occult metal within the magnetic field can move and cause severe soft tissue damage.
•Always order axial, coronal, and parasagittal views.
•Always include the cavernous sinus and paranasal sinuses.
•Always order gadolinium and fat suppression (Fig. 52-1). Be careful ordering gadolinium in patients with known or suspected renal disease, as this may result in nephrogenic systemic fibrosis.
•In T1, orbital fat is bright and vitreous is dark.
•In T2, vitreous is brighter than fat.
•The majority of orbital masses are dark in T1 before gadolinium administration. Exceptions to this rule are:
412 OPHTHALMOLOGY SECRETS IN COLOR
A
B
Figure 52-1. A and B, T1-weighted magnetic resonance images of the orbit with fat suppression.
1.Lesions containing melanin (e.g., melanoma);
2.Lesions containing fat (e.g., lipoma, liposarcoma);
3.Lesions containing mucus (mucocele, dermoid cyst);
4.Subacute blood (2 to 7 days old).20
9.Discuss the histologic classification of orbital rhabdomyosarcoma.
Orbital rhabdomyosarcoma (RMS) is histologically divided into three main groups (other schema are sometimes used, but this is the most basic):
1.Embryonal
2.Alveolar
3.Pleomorphic
The average age of onset is 9 years, but the span is broad. RMS is thought to arise from pleuripotential mesenchymal tissue within the orbit and not from extraocular muscle. Useful facts to remember about each group follow:
1.Embryonal
•Further subdivided into classic, botryoid, spindle cell, and anaplastic
•Most common histology in children
•The botryoid subtype is defined as an embryonal RMS abutting a mucosal surface (e.g., conjunctiva)
2.Alveolar
•Appears to affect the inferior orbit most frequently and carries the worst prognosis
•Fortunately, recent findings by the Intergroup Rhabdomyosarcoma Study (IRS) indicate that with more aggressive therapy, the prognosis for alveolar RMS approaches the prognosis for the embryonal form
3.Pleomorphic
•Occurs in older adults16
10.How is orbital RMS best treated? What is the prognosis?
•Much of what is known about the treatment of orbital rhabdomyosarcoma comes from the four IRSs.
•Treatment of orbital RMS consists of a combination of chemotherapy and radiation therapy.
•Radiation therapy in doses of 40 to 60 Gy definitely carries significant morbidity for the globe, but the IRS-III concluded that it is still necessary for adequate treatment. Lower doses of radiation are currently under study.
CHAPTER 52 ORBITAL TUMORS 413
Table 52-1. Clinical Characteristics of Lacrimal Gland Lesions
|
|
ADENOID CYSTIC |
|
PLEOMORPHIC ADENOMA |
CARCINOMA |
Duration |
>1 year |
<1 year |
Pain |
Rare |
Common |
Diplopia |
Uncommon |
Common |
CT findings |
No bony destruction. |
Bony destruction common. |
|
+/− fossa formation. |
|
Surgery |
Excisional biopsy. |
Incisional biopsy. |
When in Doubt, Perform Total Excision of the Mass |
|
Postsurgical therapy |
Clinical follow-up only. |
Controversial: Radiation, chemo- |
|
|
therapy (including intra-arterial |
|
|
therapy), radical excision. |
•Orbital and genitourinary RMS carry the best prognosis for unclear reasons.
•Local spread from the orbit into the paranasal sinuses or cranial vault decreases survival rates.21,22
11.With regard to lacrimal gland lesions, what is the “rule of 50s”?
The rule of 50s summarizes the incidence of lacrimal gland tumors in an orbital referral practice:
•50% of lacrimal gland lesions are nonepithelioid, consisting mostly of inflammatory and lymphoproliferative lesions, and 50% are of epithelial origin.
•50% of the epithelial tumors are benign pleomorphic adenomas (benign mixed tumor) and 50% are various malignant types.
•50% of the malignant tumors are adenoid cystic carcinomas.
•50% of the adenoid cystic carcinomas are of the basaloid variant. The final rule is important clinically, because a basaloid histopathology for adenoid cystic carcinoma carries the worst prognosis.
In a general ophthalmology practice the rule of 50s does not apply. The incidence of infectious and noninfectious inflammatory dacryoadenitis is several times higher than in an orbital referral practice.23,24
12.What factors help to distinguish benign and malignant epithelial lacrimal gland tumors?
See Table 52-1.25-29
13.What are the most common tumors to metastasize to the orbital soft tissue in men and women?
•Men, lung; women, breast carcinoma (but the incidence of lung carcinoma is increasing).
•Note that the question asks specifically about orbital soft tissue. Otherwise, prostate carcinoma, which has a propensity for bony involvement, would be an acceptable alternative in men, depending on the clinical series.30-32
•N.B. Metastatic lesions are about 10 times more common to the uvea than the orbit on autopsy studies. This may be due to the high blood flow through the choroid, which may allow more facile metastatic seeding of uveal tissue.
14.What is the appropriate workup for orbital lymphoma and lymphoid hyperplasia?
Regardless of the histopathology, any lymphoproliferative lesion of the orbit or ocular adnexa requires a systemic workup:
•Complete blood count.
•Serum protein electrophoresis.
•Imaging of the neck, thorax, and abdomen, which should be repeated every 6 to 12 months for at least 2 years.
•Some specialists also perform bone marrow biopsy on initial presentation.33-35
15.What are the important facts about orbital lymphoproliferative lesions?
•Idiopathic orbital inflammatory syndrome (inflammatory orbital pseudotumor) is not a lymphoproliferative disorder, because histopathologically the reaction is not limited to lymphocytes. It is not a precursor for orbital lymphoma.
414 OPHTHALMOLOGY SECRETS IN COLOR
Table 52-2. Distribution of Lymphoma Subtypes Systemically and in the Ocular Adnexa
SYSTEMIC LYMPHOMA (WHO DATA)
Diffuse large B cell (30.6%)
Follicular cell (22.1%) EMZL/MALT (7.6%) CLL (6.7%)
Mantle cell (6.0%)
OCULAR ADNEXAL LYMPHOMA (OAL), N = 353
EMZL/MALT (52%) Follicular cell (23%)
Diffuse large B cell (8%) Mantle cell (5%)
CLL (4%)
Indolent subtypes are listed in normal text. Aggressive subtypes are italicized. EMZL/MALT = extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue; CLL = chronic lymphocytic leukemia.
Data modified from Ref. 36.
•The vast majority of orbital lymphomas are of B-cell origin, usually EMZL (extranodal marginal zone lymphoma), also frequently called MALT-oma (mucosa-associated lymphoid tissue lymphoma).
•Orbital B-cell lymphoma is mainly a disease of adults; it is exceedingly rare in children.
•The majority of lymphoid lesions, whether polyclonal (lymphoid hyperplasia) or monoclonal (lymphoma), are highly radiosensitive.
•The World Health Organization’s reclassification of lymphoma has markedly changed the diagnosis and management of orbital lymphoma. A brief review is warranted:
•The easiest classification schema is to simply divide ocular adnexal lymphoma (OAL) into indolent and aggressive rubrics (see Table 52-2).
•Unlike primary systemic lymphoma, of which about 1/3 are aggressive large cell types, 75 to 80% of OALs are indolent (see Table 52-2).
•When an aggressive subtype of OAL is encountered, it is either secondary from a different site or presents as stage III or IV disease (systemic involvement).
•In contrast, most indolent OALs presents as stage I disease.
•Management of OAL depends mainly on two factors: subtype of lymphoma and stage of disease. As an example, a stage I EMZL of the orbit is typically treated with 30 to 35 Gy of radiation, whereas a stage I diffuse large B-cell lymphoma would be managed with systemic chemotherapy because of its aggressive nature.
•The goal of treatment also depends on the subtype of disease. As a sweeping statement, aggressive OALs are treated to cure, whereas indolent subtypes are usually managed as a chronic disease.
•Transformation of an indolent OAL (e.g., EMZL/MALT) to a more aggressive type diffuse large B cell (DLBCL) can occur in a minority of patients.36-39
16.What is the differential diagnosis of a well-circumscribed orbital mass?
•Cavernous hemangioma
•Schwannoma
•Solitary fibrous tumor (fibrous histiocytoma)
•Neurofibroma
•Solitary fibrous tumor (hemangiopericytoma)
•Dermoid cyst
•+/− Lymphoma (about 50% of OALs will present as well circumscribed and the other half as infiltrating).
