Chapter 1- Methods in Ocular Cytopathology

CHAPTER 1

Methods in Ocular Cytology

In this chapter, methods for processing ocular cytology specimens are described. Most of the routine eye cytology specimens can be prepared by simple fixation and staining methods; although, occasionally more elaborate techniques, such as electron microscopy and immunocytochemistry, are helpful.

FIXATION AND STAINING METHODS

Each fixative and stain has advantages and disadvantages. In general, slides are either rapidly air dried or rapidly fixed in 95% ethanol. Air drying artificially expands the cells while ethanol artificially shrinks the cells. If air dried, a modified Wright or Giemsa stain should be used. (1) May-Grünwald Giemsa demonstrates excellent cytologic differentiation and is especially good for cells of hematopoietic origin. The Papanicolaou stain is excellent for squamous lesions. Hematoxylin and eosin recapitulates standard histopathology and is often preferred by those adept at surgical pathology, while Papanicolaou is preferred by those expert in exfoliative cytology. A combination of stains is helpful. The method of fixation and staining is determined by the clinical question to be answered. If allergic conjunctivitis is to be differentiated from infectious conjunctivitis, then air-dried, Giemsa-stained preparations are appropriate to differentiate eosinophils and neutrophils. If squamous dysplasia or carcinoma is suspected, then ethanol-fixed material reacted with direct fluorescent antibody is very sensitive. (2) Giemsa-stained, air-dried smears can be done as an adjunctive procedure. Example protocols for staining by May-Grünwald Giemsa, Papanicolaou, and hematoxylin and eosin are shown in Tables 1-1, 1-2, and 1-3.
References:
1. Reich C. Modified Wright stain. Am J Clin Pathol 1954:24:881.
2. Bell TA et al. Pediatrics 1984;74:224-228.

CT Scan 2.

CT Scans of Orbit continued. This cut is taken at the level of the inferior orbit just above the nasolacrimal duct opening in the lacrimal fossa and includes the inferior orbital fissure.

ANATOMY OF THE ORBIT- CT SCANS

Click on Picture for Enlarged View

CT scan below the orbits includes a section through the auditory canal and nose to show:
1. Maxillary sinus with the nasolacrimal duct just medial.
2. Temporalis fossa with the zygomatic arch at the arrow. Note the absence of bone on the opposite site.
3. Nasal septum.






Click on picture for enlarged view.

CT scan above the opening for the nasolacrimal duct in the lacrimal fossa and includes the inferior orbital fissure.
4. zygoma
5. inferior orbital fissure (note that the fissure is oriented medially and narrows slightly posteriorly).
6. greater wing of the sphenoid
7. nasolacrimal duct
8. inferior rectus muscle


click on picture for enlarged view.

Number 7 here demonstrates the superior orbital fissure. The most common mistake is to indicate that this is the optic canal. However, note that this opening is oriented laterally from the midline plane not medially. This is a key clue to the correct identification. Compare to the image of the CT scan that captures the optic canal below.



Click to enlarge photo

Here we see the optic canal (12 in the figure)which is of course medial to the tip superior orbital fissure and which we just capture more laterally.








Click to enlarge the photo.

In this CT image we are at the top of the orbit so that the lacrimal gland if evident (17). The real challenge here is number 15. This requires a great deal of knowledge. The structure starts lateral in the posterior orbit and moves medially. The immediate guess is that 15 is the superior oblique muscle. However, the origin for the superior oblique is medial to the optic canal, not lateral (see extraocular muscle origins). Therefore this is a critical but forgotten structure the superior ophthalmic vein which is descending to exit the superior orbital fissure in a lower plane (see venous drainage of the orbit). Correct identification of the dilated superior ophthalmic vein is key for the diagnosis of carotid-cavernous sinus fistulas.



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ANATOMY OF THE EYE FOR CYTOLOGY

CHAPTER 2 Normal Anatomic and Cytologic Features
Accurate cytologic interpretation of ocular specimens requires a fundamental knowledge of normal ocular histology. A general overview is presented here with emphasis on those areas relevant to cytology specimens. There are numerous treatises available for more complete study of ocular anatomy (1-4). The average adult eye measures about 25 mm horizontally, 23 mm vertically, and 21 to 26 mm anterior-posteriorly (Figures 2-1 and 2-2) (5). The eye has an external approximate volume of 7.6 milliliters (ml), the aqueous has a volume of about 200 microliters, and the vitreous a volume of 4.0 ml. The eye is contained in the pear-shaped orbit that has dimensions of about 35 mm vertically, 45 mm horizontally, and 40-45 mm anteroposteriorly (6). The lacrimal gland is located superolaterally in the orbit and is divided by the orbital septum.

CONJUNCTIVA
The conjunctiva covers the posterior surface of the eyelids (palpebral conjunctiva), curves anteriorly at the fornix to reflect onto the anterior surface of the eye as the bulbar conjunctiva (Figures 2-3 and 2-4). There are subtle histologic differences in the conjunctiva of the lid margins, tarsus, fornix, and bulbar conjunctivae (3). The conjunctiva covering the lid margin and bulbar conjunctiva is a modified nonkeratinized, stratified Squamous epithelium. The tarsal and fornix conjunctiva is covered by stratified cuboidal to columnar epithelium of varying thickness (Figures 2-5). This epithelium is unusual because it retains some squamoid features, such as numerous desmosomes, yet has a microvillus surface architecture (7,8). Goblet cells are abundant over the tarsus, fornix, and specialized areas such as the plica semilunaris. Goblet cells are scarce near the lid margin and adjacent to the cornea at the limbus. Most swabs of the conjunctiva are taken from the inferior fornix and show clusters and single epithelial cells with abundant cytoplasm, eccentric nuclei, and occasional single nucleoli . Goblet cells exhibit clear vacuoles filled with mucin. The presence of keratinized epithelium in the conjunctival smear is distinctly abnormal unless the sample is taken from the caruncle or accidentally from the eyelid.

CORNEA
The cornea is covered by five to six layers of a modified stratified Squamous epithelium (Figures 2-7) (9). The basal cells are smaller and have a higher nuclear-to-cytoplasmic ratio than the other epithelial cells in the cornea. There are two to three layers of wing cells with interdigitating cytoplasmic processes connected by desmosomes to other wing cells. These attachments may explain why corneal epithelium tends to be removed in sheets. The two top layers are flattened, superficial cells with small, round nuclei and inconspicuous nucleoli. The superficial epithelial cells are normally uniform in size and shape and have many microvilli that form a microplical complex on the external surface of the cornea (10). Epithelial cells are attached to a basement membrane, beneath which lies Bowman’s layer, a specialized layer of collagen that does not regenerate after injury. The stroma is composed of lamellar sheets of collagen arranged perpendicularly. The posterior surface of the cornea is covered by Descemet’s membrane, and endothelial cells line its posterior surface (Figure 2-7). Cytologic surface smears from the normal cornea will demonstrate cohesive sheets of non-keratinized Squamous epithelium. Individual cells exhibit intermediate-size, round nuclei with bland and uniform chromatin (Figure 2-8). The presence of keratinized cells in smears from the cornea is abnormal.

References:
1. Jakobiec FA. Ocular anatomy, embryology, and teratology. Philadelphia: Harper & Row, 1982.
2. Hogan MJ, Alvarado JA, Weddell JE. Histology of the human eye. Philadelphia: W.B. Saunders, 1971.
3. Last RJ. Eugene Wolff's anatomy of the eye and orbit. Philadelphia: W.B. Saunders, 1961.
4. Fine BS, Yanoff M. Ocular histology, a text and atlas. New York: Harper & Row, 1972.
5. Stenstrom S. Untersuchungen uber die variation unk kovariation der optishen elemente des menshlickhen auges. Acta Ophthalmol 1946;26:1.
6. Duke-Elder WS. The anatomy of the visual system. In: System of ophthalmology. St Louis: CV Mosby, 1961;2:410-413.
7. Greiner JV, Covington HI, Allansmith MR. Surface morphology of the human upper tarsal conjunctiva. Am J Ophthalmol 1977;83:892-905.
8. Dark AJ, Durrant TE, McGinty F, Shortland JR, et al. Tarsal conjunctiva of the upper eyelid. Am J Ophthalmol 1974;77:555-564.
9. Hogan MJ, Alvarado JA, Weddell JE. Histology of the human eye. Philadelphia: W.B. Saunders, 1971.
10. Blumcke S, Morgenroth K Jr. The stereo ultrastructure of the external and internal surface of the cornea. J Ultrastruct Res 1967;18:502.

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REFERENCES FINE NEEDLE ASPIRATION OF THE ORBIT

REFERENCES- FINE NEEDLE ASPIRATION OF ORBITAL LESIONS
1. Krohel GB, Tobin D, Chavis RM. Inaccuracy of orbital fine needle aspiration biopsy. Ophthalmology 1984[Suppl.];91:83.
2. Czerniak B, Woyke S, Daniel B, Krzysztolik Z, Koss LG. Diagnosis of orbital tumors by aspiration biopsy guided by computerized tomography. Cancer 1984;54:2385-2389.
3. Glasgow BJ, Layfield LJ. Fine needle aspiration biopsy of orbital and periorbital masses. Diagn Cytopathol 1991;7:132-141.
4. Frayer WC, Enterline HT. embryonal rhabdomyosarcoma of the orbit in children and young adults. Arch Ophthalmol 1959;62:203-210.
5. Kirk RC, Zimmerman LE. Rhabdomyosarcoma of the orbit. Arch Ophthalmol 1969;81:559-564.
6. Yanoff M, Fine BS. Ocular pathology. A text and atlas. Philadelphia: J.B. Lippincott, 1989:532-534.
7. Knowles DM, Jakobiec FA, Potter G, Jones IS. Ophthalmic striated muscle neoplasms. A clinico-pathologic review. Surv Ophthalmol 1976;21:219-261.
8. Kennerdell JS, Slamovits TL, Dekker A, Johnson BL. Orbital fine-needle aspiration biopsy. Am J Ophthalmol 1985;99:547-551.
9. Zajdela A, Vielh P, Schlienger P, Haye C. Fine-needle aspiration cytology of 292 palpable orbital and eyelid tumors. Am J Clin Pathol 1990:93:100-104.
10. de Jong ASH, van Kessel-van Vark M, van Heerde P. Fine needle aspiration biopsy diagnosis of rhabdomyosarcoma. Acta Cytol 1987;31:573-577.
11. Wharam M, Beltangady M, Hays D, Heyn R, Ragab A. et al. Localized orbital rhabdomyosarcoma. An interim report of the intergroup rhabdomyosarcoma study committee. Ophthalmology 1987;94:251-254.
12. Jakobiec FA, McLean I, Font R. Clinicopathologic characteristics of orbital lymphoid hyperplasia. Ophthalmology 1979;86:948-966.
13. Knowles DM II, Jakobiec FA. Orbital lymphoid neoplasms, a clinicopathologic study of 60 patients. Cancer 1980;46:576-589.
14. McNally L, Jakobiec FA, Knowles DM II. Clinical, morphologic, immunophenotypic, and molecular genetic analysis of bilateral ocular adnexal lymphoid neoplasms in 17 patients. Am J Ophthalmol 1987;103:555-568.
15. Chen P, Liu JH, Lin SH, Hsu WM, Kao SC. Rearrangements of immunoglobulin gene and oncogenes in ocular adnexal pseudolymphoma. Current Eye Res 1991;10:493-500.
16. Southern EM. Detection of specific sequences among DNA fragments separated by gel electrophoresis. J Mol Biol 1975;98:503-517.
17. Wahl GM, Stern M, Stark GR. Efficient transfer of large DNA fragments from agarose gels to diazobenzyloxmethyl-paper and rapid hybridization by using dextran sufate. Proc Natl Acad Sci USA 1979;76:3683-3687.
18. Rigby RW, Dieckman M, Rhodes C, Berg P. Labeling deoxyribonucleic acid to high specific activity in vitro by nick translation with DNA polymerase I. J Mol Biol 1977;113:237-251.
19. Yanagi Y, Yoshikai Y, Leggett K, Clark SP, Aleksander I, et al. A human T cell-specific cDNA clone encodes a protein having extensive homology to immunoglobulin chains. Nature 1984;308:145-149.
20. Flug F, Pelicci PG, Bonetti F, et al. T-cell receptor gene rearrangement as markers of lineage and clonality in T-cell neoplasia. Proc Natl Acad Sci USA, 1985;82:3460-3464.
21. Knowles DM, Athan E, Ubriaco A, McNally L, Inghirami G, et al. extranodal noncutaneous lymphoid hyperplasia represent a continuous spectrum of B-cell neoplasia: demonstration by molecular genetic analysis. Blood 1989; 73:1635-1645.
22. Levitt S, Cheng L, duPuis MH, Layfield LJ. Fine needle aspiration diagnosis of malignant lymphoma with confirmation by immunoperoxidase staining. Acta Cytol 1985;29:895-902.
23. Knowles DM II, Jakobiec FA. Cell marker analysis of extranodal lympoid infiltrates: to what extent does the determination of mono- or polyclonality resolve the diagnostic dilemma of malignant lymphoma v pseudolymphoma in an extranodal site? Semin Diagn Pathol 1985;2:163-168.
24. Nikaido H, Mishima H, Kiuchi Y, Nanba K. Primary orbital malignant lymphoma: a clinicopathologic study of 17 cases. Albrecht von Grafes Arch Klin Exp Ophthalmol 1991;229:206-209.
25. Jakobiec FA, Jones IS. Introduction to ultrastructure, inflammation, and neoplasia. In: Jones IS, Jakobiec FA, eds. Diseases of the orbit. Hagerstown, MD: Harper and Row, 1979:145-179.
26. Goldberg L, Tao A, Romano P. Severe exophthalmos secondary to orbital myopathy not due to Grave’s disease. Br. J Ophthalmol 1982;66:392-395.
27. Kennerdell JS, Dresner SC. The nonspecific orbital inflammatory syndromes. Surv Ophthalmol 1984;29:93-103.
28. Font RL, Gamel JW. Epithelial tumors of the lacrimal gland: an analysis of 265 cases. In: Jakobiec FA, ed. Ocular and adnexal tumors. Birmingham, AL: Aesculapius Publishing, 1978:787-805.
29. Ni C, Cheng SC, Dryja TP, Cheng TY. Lacrimal gland tumors. A clinico-pathological analysis of 160 cases. Int Ophthalmol Clin 1982;22:99-120.
30. Ashton N. Epithelial tumors of the lacrimal gland. Mod Probl Ophthalmol 1975;14:306-311.
31. Zimmerman LE, Sanders TE, Ackerman LV. Epithelial tumors of the lacrimal gland: prognostic and therapeutic significance of histologic types. Int Ophthalmol Clin 1962;2:337-367.
32. Glasgow BJ, Brown HH, Zaragoza AM, Foos RY. Quantitation of tumor seeding from fine needle aspiration of ocular melanomas. Am J Ophthalmol 1988;105:528-546.
33. Layfield LJ, Tan P, Glasgow BJ. Fine needle aspiration cytology of primary salivary gland lesions. Arch Pathol Lab Med 1987;111:346-353.
34. Font RL, Gamel JW. Adenoid cystic carcinoma of the lacrimal gland. A clinicopathologic study of 79 cases. In:Nicholson DH, ed. Ocular pathology update. New York: Masson Publishing USA, 1980:277-283.
35. Perzin K, Gullane P, Clairmont A. Adenoid cystic carcinoma arising in salivary glands: a correlation of histologic features and clinical course. Cancer 1978;42:265-275.
36. Lloyd GAS. Lacrimal gland tumours: the role of CT and conventional radiology. Br J Radiol 1981;54:1034-1038.
37. Gamel JW, Font RL. Adenoid cystic carcinoma of the lacrimal gland: the clinical significance of a basaloid histologic pattern. Hum Pathol 1982;13:219-225.
38. Lee DA, Campbell RJ, Waller RR, IIstrup DM. A clinicopathologic study of primary adenoid cystic carcinoma of the lacrimal gland. Ophthalmology 1985;92:128-134.
39. Henderson JW, Nealt RW. En bloc removal of intrinsic neoplasms of the lacrimal gland. Am J Ophthalmol 1976;82:905-909.
40. Marsh JL, Wise DM, Smith M, Schwartz H. Lacrimal gland adenoid cystic carcinoma: intracarcinial and extracarcanial en bloc resection. Plast Reconst Surg. 1981;68:577-585.
41. Layfield LJ, Glasgow BJ, DuPuis MH. Fine needle aspiration of lymphadenopathy of suspected infectious etiology. Arch Pathol Lab Med 1985;109:810-812.
42. Font RL. Eyelids and lacrimal drainage system. In: Spencer WH, ed. Ophthalmic pathology, an atlas and textbook. Philadelphia: W.B. Saunders, 1986;3:2266-2268.
43. Arora R, Rewari R, Betheria SM. Fine needle aspiration cytology of eyelid lesions. Acta cytol 1990;34:227-232.
44. Henderson JW. Orbital tumors, 2nd ed. New York: Brian C. Decker (Thieme-Stratton), 1980.
45. Rootman J, Lapointe JS. Structural lesions. In Rootman J, ed. Diseases of the orbit. Philadelphia: J.B. Lippincott, 1988: 481-488.
46. Westman-Naeser S., et al. Tumours of the orbit diagnosed by fine-needle biopsy. Acta Othalmol,1978; 56:969-976.
47. Kennerdell JS, et al. Fine needle aspiration biopsy: its use in orbital tumors. Arch Opthalmol, 1979.

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CYSTIC AND VASCULAR LESIONS

CYSTIC AND VASCULAR LESIONS
Cavernous Hemangioma
Cavernous hemangiomas are well-encapsulated tumors found behind the eye within the boundaries of the rectus muscles (intraconal) and composed of very large vascular channels. The vessel walls contain smooth muscles and there is fibrous tissue in the trabeculae that separates the vessels. Cavernous hemangiomas produce slowly progressive proptosis and indentation of the posterior portion of the globe (Figure 10-47). Radiologic studies show a rounded mass with smooth contours (Figure 10-48). Echography shows a lesion with characteristic high internal reflectivity (highly echogenic). One would prefer not to aspirate this lesion because of the risk of orbital hemorrhage. However, at least four fine needle biopsies of cavernous hemangiomas have been performed without complications. [3, 8, 69] In every one of these cases, the fine needle revealed only the blood harbored in the large cavernous spaces (Figure 10-49).

Hemangiopericytoma
Hemangiopericytoma is a highly vascular tumor, presumably arising from pericytes, with a characteristic staghorn appearance of vessels. It occurs at a median age of 42, with twice the frequency in men as woman. [70] The presenting findings of the tumor include proptosis, palpable mass, pain, and diplopia of about three years’ duration. Fine needle aspiration reveals spindle and oval cells with occasional branched vessels (Figure 10-50).

Mucocele
Mucoceles are tumors composed of mucous debris and which are caused by obstruction of the ostia of the sinuses. Mucus is secreted by entrapped epithelium and enlarges the sinuses. The frontal sinus is the most common site of origin for orbital mucoceles, but they may also occur in the ethmoid, sphenoid, and maxillary sinuses. [71, 72, 73, 74, 75] Radiologically, the mucocele is recognizable as a lucent mass with smooth scalloped borders expanding the sinus and destroying sinus septae around the orbit. Fine needle aspiration reveals a large amount of mucoid material with occasional vacuolted macrophages (mucophages) (Figure 10-51). In general, fine needle aspiration is done when an underlying neoplasm is suspected.

References

69. Meyer E, et al. Fine-needle aspiration of orbital lesions. Ann Ophthalmol. 1983 Jul;15(7):635-8.
70. Croxatto JO, et al. Hemangiopericytoma of the orbit: a clinicopathologic study of 30 cases. Hum Pathol. 1982 Mar;13(3):210-8.
71. Montgomery WW. MUCOCELE OF THE MAXILLARY SINUS CAUSING ENOPHTHALMOS. Eye Ear Nose Throat Mon. 1964 May;43:41-4.
72. Alberti PW, et al. Fronto-ethmoidal mucocoele as a cause of unilateral proptosis. Br J Ophthalmol. 1968 Nov;52(11):833-8.
73. Guerry R, Smith J, Paranasal sinus carcinoma causing orbital muscocele. Am J Opthalmol 1975;80:943-946.
74. Johnson LN, et al. Sphenoid sinus mucocele (anterior clinoid variant) mimicking diabetic ophthalmoplegia and retrobulbar neuritis. Am J Ophthalmol. 1986 Jul 15;102(1):111-5.
75. Stanton MB. Sphenoid sinus mucocele. Am J Ophthalmol. 1970 Dec;70(6):991-4.

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SCHWANNOMA, MENINGIOMA OF THE ORBIT

PERINEURAL LESIONS
Schwannoma (Neurilemmoma)

Schwannomas are tumors of peripheral nerves that presumably arise from Schwann cells. They occur between the ages of 20 and 50 years and are associated with neurofibromatosis. [61]Clinically, patients frequently exhibit proptosis, lid swelling, diplopia, and indentation of the posterior sclera (Figure 10-39). [62] CT scan reveals that neurilemomas have round smooth borders and expand cortical bone (Figure 10-40). Fine needle aspiration of schwannoma is usually not diagnostic because scant material is obtained. However, myxoid areas associated with spindle cells and bent nuclei are suggestive of a neural lesion (Figure 10-41). Schwannomas are encapsulated and have a firm consistency (Figure 10-42). The tightly packed spindle cells form characteristic Antoni A and B areas that are difficult to discern in fine needle aspiration specimens (Figure 10-43). The cohesive architecture of the schwannoma accounts for the inadequate specimens previously reported. [8]

Meningioma

Meningiomas in the orbit presumably arise from the arachnoid tissue of the optic nerve and the meninges adjacent to the sphenoid and nearby intracranial structures. Clinical presentation is determined by location. Optic canal meningiomas compress the optic nerve and lead to early and profound visual deficits. [63] Radiologic findings may show well-defined soft-tissue lesions with hyperostosis when bone is involved. The optic nerve may show fusiform swelling, diffuse thickening, or globular enlargement. [64] Fine needle aspiration has been reported to effectively diagnose orbital meningiomas in 10 cases. [3, 8, 65, 66, 67, 68] Aspiration biopsy is appropriate for unresectable meningiomas if a tissue diagnosis is required for radiation therapy. Aspiration under CT guidance is helpful to place the needle in orbital apex and posterior meningiomas (Figures 10-44 and 10-45). Smears show oval and round cells organized in tight clusters and occasional whorls. The nuclei may have intranuclear inclusion (Figure 10-46). Rarely psammoma bodies are seen.

References

61. Izumi AK, et al. Von Recklinghausen's disease associated with multiple neurolemomas. Arch Dermatol. 1971 Aug;104(2):172-6.
62. Rootman J, Robertson WD. Tumors In: Rootman J, ed. Diseases of the orbit. Philadelphia: J.B. Lippincott, 1988:293-305.
63. Wilson WB. Meningiomas of the anterior visual system. Surv Ophthalmol. 1981 Nov-Dec;26(3):109-27.
64. Rootman J, Robertson WD. Tumors In: Rootman J, ed. Diseases of the orbit. Philadelphia: J.B. Lippincott, 1988:293-305.
65. Meyer E., et al. Fine-needle aspiration of orbital lesions. Ann Ophthalmol. 1983 Jul;15(7):635-8
66. Czerniak B., et al. Diagnosis of orbital tumors by aspiration biopsy guided by computerized tomography. Cancer, 1984 Dec 1;54(11):2385-9.
67. Zajdela A, et al. Cytologic diagnosis of orbital and periorbital palpable tumors using fine-needle sampling without aspiration. Diagn Cytopathol. 1986 Jan-Mar;2(1):17-20.
68. Cristallini EG, Fine needle aspiration biopsy of orbital meningioma. Report of a case. Acta Cytol. 1990 Mar-Apr;34(2):236-8.

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SQUAMOUS, SEBACEOUS AND BASAL CELL CARCINOMAS

EPITHELIAL LESIONS
Squamous Carcinoma
Squamous carcinoma is the most common paranasal sinus tumor to invade the orbit. [52] The maxillary sinus is the original site of the carcinoma in the majority of cases. The patients with this tumor may present predominantly with orbital signs. In these cases, destruction of the orbital floor is usually seen on CT scan (Figure 10-31).
Fine needle aspiration reveals abundant malignant cells. The key to the diagnosis is the discovery of squamous differentiation. Frequently, the tumors will have a spindle-cell appearance (Figure 10-32). Some of these tumors may arise from inverted papillomas (Figure 10-33). Patients with squamous carcinoma from a sinus involving the orbit in general, have a poor prognosis.

Sebaceous Carcinoma
Sebaceous carcinoma originates from meibomian glands and glands of Zeis in the eyelid. It may present clinically in different forms, a small yellow nodule, a diffuse thickening of the eyelid, or a mass in the lacrimal fossa. [53] As a small yellow nodule, it is frequently misdiagnosed as a chalazion. As a diffuse thickening of the eyelid, it may be misdiagnosed as blepharitis (Figure 10-34). As an orbital mass, it may be misdiagnosed as a primary lacrimal gland tumor (Figure 10-35). [54]
Fine needle aspiration of sebaceous carcinoma has been reported in numerous cases for eyelid tumors. [43, 55] Fine needle aspiration is generally done when an orbital mass is the predominant presenting feature or if the abnormalities of conjunctiva and eyelid are overlooked. Fine needle aspiration shows abundant material with large cells and numerous lipid vacuoles (Figure 10-36). As a result of fine needle aspiration, the surgeon may plan to do multiple eyelid and conjunctiva biopsies to determine the extent of the tumor because independent foci of sebaceous carcinoma in the eyelid have been noted in up to 10% cases (Figure 10-37). [56, 57]

Basal-cell Carcinoma
Basal-cell carcinoma is the most common malignant epithelial tumor if the eyelid. [58] Fine needle aspiration is unnecessary to diagnose most primary lesions because skin biopsy is so easily performed. Occasionally, recurrent deep orbital lesions present as orbital masses. Fine needle aspiration of basal-cell carcinoma shows tight clusters of small epithelial cells with atypical nuclei and occasional palisading (Figure 10-38). There is a high rate of negative and insufficient biopsies with basal cell carcinoma.

Metastatic Carcinoma
A variety of metastatic carcinoma initially presents with orbital manifestations. [59] Metastatic breast, renal cell, transitional cell, and prostate carcinomas have all been specifically identified by orbital fine needle aspiration, but most are only identified as adenocarcinoma. Immunocytochemical studies may be helpful in specifying some sources of origin, such as prostate. [60]

References

52. Johnson LN, et al. Sinus tumors invading the orbit. Opthalmology, 1984.
53. Shield JA, Font RL, Meibomian gland carcinoma presenting as a lacrimal gland tumor. Arch Opthalmology 1974;92:304-306.
54. Shield JA, Font RL, Meibomian gland carcinoma presenting as a lacrimal gland tumor. Arch Opthalmology 1974;92:304-306.
55. Das KK, Das J, Natarajan R.m Chachra KL, Chacchra KL, et al. Meibomian gland carcinoma initially identified by cytology. Diagn Cytopathol 1986;2:154-156.
56. Boniuk M, et al. Sebaceous carcinoma of the eyelid, eyebrow, caruncle, and orbit. Trans Am Acad Ophthalmol Otolaryngol. 1968 Jul-Aug;72(4):619-42.
57. Rao NA, Sebaceous carcinomas of the ocular adnexa: A clinicopathologic study of 104 cases, with five-year follow-up data. Hum Pathol. 1982 Feb;13(2):113-22.
58. Aurora AL, Blodi FC. Lesions of the eyelids. A clinicopathologic study. Surv Opthalmol 1970;15:94-104.
59. Goldberg RA, et al. Clinical characteristics of metastatic orbital tumors. Ophthalmology. 1990 May;97(5):620-4.
60. Kopelman JE, et al. A case of prostatic carcinoma metastatic to the orbit diagnosed by fine needle aspiration and immunoperoxidase staining for prostatic specific antigen. Ophthalmic Surg. 1987 Aug;18(8):599-603.

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WEGENER'S GRANULOMATOSIS, SARCOID, LANGERHANS HISTIOCYTOSIS

Wegener’s Granulomatosis
Wegener’s granulomatosis is characterized by necrotizing vasculitis and granulomatous inflammation in the upper respiratory tract, lung, and kidneys. It occurs predominantly in males. Orbital involvement occurs in about 20% of the cases and is usually bilateral. [48] It is extremely difficult to make a specific diagnosis of Wegener’s granulomatosis or even a diagnosis of necrotizing vasculitis by fine needle aspiration. Usually, extremely scant material is obtained, but histiocytes and groups of necrotic cells can sometimes be identified (Figure 10-23). These lesions frequently have extensive fibrosis, and collection of adequate material by fine needle biopsy is very difficult (Figure 10-24).

Sarcoidosis
Sarcoidosis is a multisystem, granulomatous disease of unknown cause. It occurs more frequently in women and blacks. The lacrimal gland may be palpably enlarged in 7% of patients. Patients may be considered to have a lacrimal gland tumor (Figure 10-25). Fine needle biopsy demonstrates granulomatous inflammation without necrosis. Multinucleated giant cells are usually evident (Figure 10-26). When a fine needle aspirate reveals granulomatous inflammation on the first biopsy, another aspirate should be considered to obtain culture and special stains to rule out infectious causes. Sarcoidosis is a clinical diagnosis and cannot be made by cytologic or histologic findings alone.
Eosinophilic Granuloma
Eosinophilic granuloma is one of the spectrum of the diseases known as histiocytosis X, which includes Hand-Schüller-Christian disease, Letterer-Siwe disease, and eosinophilic granuloma. It is thought that proliferating Langerhans’ cells are responsible for the lesion. The orbit is most often involved by unifocal disease, eosinophilic granuloma. [49. 50] The disease usually occurs in children and teenagers and involves bone and adjacent soft tissue (Figure 10-27 and 10-28). It is common in the superotemporal portion of the orbit. The diagnosis can be readily made by fine needle aspiration provided sampling is adequate. [51] Langerhans’ cells are evident as histiocytes with grooved or indented nuclei. Multinucleated giant cells, eosinophils, and neutrophils are present (Figure 10-29). The diagnosis can be confirmed by electron microscopy of the aspiration specimen (Figure 10-30). Treatment usually includes curettage.

References

48. Straatsma BR, Ocular Manifestation of Wegner’s granulomatosis. Am J. Opthalmol, 1957.
49. Baghdassarian SA, et al. Eosinophilic granuloma of orbit. Ann Opthalmol 1977.
50. Jakobiec FA, et al. Localized eosinophilic granuloma (Langerhans' cell histiocytosis) of the orbital frontal bone. Arch Opthalmol, 1980.
51. Layfield LJ, et al. Fine-needle aspiration cytology of histiocytosis X: a case report. Diagn Cytopathol, 1988.

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GRANULOMATOUS LESIONS OF THE ORBIT

GRANULOMATOUS LESIONS
Some granulomatous lesions of the orbit may be differentiated from each other by fine needle aspiration cytology. Eosinophilic granuloma, ruptured dermoid cyst, and chalazion are so characteristic that the diagnosis can be suggested and usually made definitely with cytology alone. However, in certain cases, ancillary tests are helpful (e.g., electron microscopy for eosinophilic granuloma).

Foreign-body Granuloma
Foreign-body granuloma may present with a subconjunctival or orbital lesion. Frequently, patients will not be aware of a previous injury or implanted foreign material. Patients may present with a red eye and reduced eye movements. There may be a yellow infiltrate under the conjunctiva that mimics lymphoma. CT scan may reveal a mass (Figure 10-17).
Fine needle aspiration demonstrates a granuloma with foreign-body giant cells (Figure 10-18). Infectious causes of granulomatous inflammation should be excluded with culture and special stains. This can be accomplished by fine needle aspiration. [41] Biopsy is usually necessary to uncover the foreign body (Figure 10-19).

Chalazion
Chalazia are lipogranulomatous reactions that occur in the eyelid because of meibomian gland obstruction. They may be associated with infection or neoplasms, but are usually secondary to inspissated secretions. [42] Usually, the diagnosis is obvious clinically and no biopsy is necessary. In longstanding cases, the chalazion may present as a discrete mass. Fine needle biopsy may be done to rule out sebaceous carcinoma or abscess. [3, 43] Smears of the aspiration show numerous histiocytes with foamy cytoplasm and occasional granulation tissue (Figure 10-20). Treatment of this lesion may include observation or removal by curettage.

Ruptured Dermoid Cysts
Dermoid cysts are congenital lesions that represent arrested migration of ectoderm entrapped in orbital soft tissue or between sutures of orbital bone. [44] They are the most common orbital tumor in children. It is preferable not to aspirate a dermoid cyst to avoid spillage of its contents. However, deep dermoids are frequently difficult to diagnose clinically. This type of dermoid cyst presents in adulthood as a slowly growing mass in the supero-temporal orbit. There is often extension through bone sutures that can be confused with boney erosion of lacrimal gland tumors. [45] Seven fine needle aspiration biopsies of dermoid cysts have been reported and all presented as adults and at least two of them had bone involvement. In at least two of the cases, there was a history of a tumor since childhood and the diagnosis was easily made by fine needle aspiration. [46, 47] In others, malignancy was clinically suspected. In one case, the cytologic findings were even reported malignant (a false positive), but details are not enclose. Fine needle aspiration of an unruptured dermoid cyst contains anucleate squamous cells, keratin debris, and, occasionally, hair shafts. A ruptured dermoid cyst will also contain granulomatous inflammation with multinucleated giant cells (Figures 10-21 and 10-22). We have not seen adnexal structures of the cyst wall in the four dermoid cysts we have examined cytologically.

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PRIMARY LACRIMAL GLAND TUMORS

The most common primary tumors of the lacrimal gland are pleomorphic adenoma and adenoid cystic carcinoma. Malignant mixed tumor is much less common.

Pleomorphic Adenoma
Pleomorphic adenoma (benign mixed tumor) accounts for about 50% of all epithelial lacrimal gland tumors. [28, 29, 30] Benign mixed tumor may occur at any age (mean is 39 years). A painless mass in the lacrimal fossa is often observed. By CT scan, the tumors are globular in shape and may indent sclera and remodeled bone. It has been demonstrated that open biopsy of both major salivary and lacrimal gland benign mixed tumors may lead to seeding. [31] No cases of seeding have been documented following fine needle aspiration biopsy of these tumors from salivary glands. [32, 33] No cases of fine needle aspiration of lacrimal gland mixed tumor have been reported. Fine needle aspiration of mixed tumors shows tightly clustered benign epithelial cells and characteristic mucinous chondroid matrix (Figure 10-12).

Adenoid Cystic Carcinoma
Adenoid cystic carcinoma accounts for about 25% to 30% of all epithelial lacrimal gland tumors. [34, 35] Clinically, the patients usually have symptoms of pain and develop a mass in the lacrimal fossa (Figure 10-13). On CT scan, adenoid cystic carcinomas are globular tumors, but frequently have irregular destructive margins around orbital bones (Figure 10-14). [36] Fine needle aspiration shows numerous clusters and single cells. The cells form characteristic rosettes that surround magenta basement membrane material (Figure 10-15). This material does not stain with hematoxylin and eosin or Papanicolaou stain. Occasionally, mitotic figures and individual cell necrosis can be seen. This pattern correlates well with basement membrane material seen in the center of cribiform areas on histologic sections (Figure 10-16). The correlation of prognosis of adenoid cystic carcinoma with the histologic patterns is controversial. [37, 38]The treatment for these lesions is also controversial and ranges from excision of the tumor with radiation, en bloc excision with resection of contiguous bone, orbital exenteration, and radical orbitectomy. [39, 40] At present, there is not enough follow-up data to demonstrate that radical procedures result in cure.

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METASTATIC SMALL CELL CARCINOMA OF LUNG

Metastatic Small Cell Carcinoma

Small-cell carcinoma is the most common type of lung cancer that metastatizes to the orbit. It is important because orbital findings are sometimes the initial manifestations. The tumor may fill the orbit or be localized to an extraocular muscle (Figure 10-10). The cytologic findings may mimic another small-cell tumor such as lymphoma. Differentiating features include the presence of cell necrosis, nuclear crush artifact, and some variation in cell size. The nuclear crush artifact occurs even in tissue sections and is probably related to increased fragility (Figure 10-11). Electron microscopy of aspiration cytology is useful to demonstrate epithelial elements. Leukocyte markers are helpful to exclude lymphoma.

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MALIGNANT LYMPHOMA OF THE ORBIT

Malignant Lymphoma

Patients with orbital lymphomas are usually 50 to 60 years old and present insidiously with proptosis and, frequently, a rubbery fleshy mass under the bulbar conjunctiva or eyelids (Figure 10-5). CT scan may show that the tumor conforms to the contours of the eye (Figure 10-6). Fine needle aspiration reveals abundant cellular material with a relatively homogenous population of lymphocytes (Figure 10-7). Orbital lymphomas are similar to other extranodal non-Hodgkin lymphomas. They are usually diffuse and of B-cell lineage.
Although histologic patterns of the diffuse and nodular lymphoma cannot be discerned from aspiration smears, B- and T-cell marker studies can be done (Figure 10-8). [22] The prognosis of orbital lymphomas may be better determined by location and involvement of other sites than histologic classification and marker studies. [23, 24]

Idiopathic Orbital Inflammation (Sclerosing Orbititis)

Idiopathic orbital inflammation is also referred to as inflammatory pseudotumor. It may present acutely or in a chronic form. In the acute form, there is an abrupt onset of pain, injection, chemosis, and decreased ocular motility. The inflammation involves orbital soft tissues including fat, extraocular muscle, tendon, lacrimal gland, and blood vessels. [25, 26] Sclera may be inflamed in late cases. [27] In the chronic form, there is marked fibrosis that may envelop the structures of the orbit and mimic a malignant neoplasm. The diagnosis often can be made clinically, but occasionally a fine needle aspiration biopsy will be requested. It is extremely difficult to get adequate material to diagnose chronic sclerosing orbititis. Usually, scant aspirates with a few fibroblasts and lymphocytes will be identified (Figure 10-9).

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SMALL CELL TUMORS

SMALL-CELL TUMORS

Fine needle aspiration is an excellent way to categorize small-cell tumors. However, further specification requires more extensive immunocytochemical or electron microscopic evaluation.

Rhabdomyosarcoma
Orbital rhabdomyosarcoma is the most common primary malignant orbital neoplasm in children. [4, 5] It often presents as a rapidly expanding lesion in the orbit and occurs most commonly at about age 6 or 7 (Figure 10-1). [6, 7] Fine needle aspiration smears show a small-cell tumor with scant cytoplasm (Figure 10-2). Rhabdomyosarcoma of the orbit has been reported to be specifically diagnosed in at least six previous cases with fine needle aspiration biopsy. [3, 4, 5, 6, 7, 8, 9, 10] In two other cases, a cytologic diagnosis of malignancy could be made, but not further specified. [9] To maximize the diagnostic potential of orbital aspiration cytology, other techniques, such as immunocytochemistry for desmin, actin, and myosin, or electron microscopic demonstration of myofibrils, are often required (Figure 10-3). [10] If a specific diagnosis can be made, fine needle aspiration has the advantages of being rapid and avoiding open biopsy. Radiation and chemotherapy are successful in 90% of cases. [11]

Reactive Lymphoid Hyperplasia
If one excludes basal-cell carcinomas, lymphoid lesions are the most common tumors in series of orbital fine needle aspiration. [8, 9]
Benign reactive lymphoid hyperplasia is a pathologic diagnosis given to orbital and periorbital lymphoid infiltrates that demonstrate germinal centers with tangible body macrophages and a heterogenous population of cells, including small lymphocytes, reactive lymphocytes (immunoblasts), and plasma cells. This diagnosis is made by identification of the heterogenous lymphoid elements. Architecture (diffuse or nodular) cannot be discerned in fine needle aspirates (Figure 10-4). Five percent to 25% of patients with the histologic appearance of a reactive process will eventually develop systemic lymphoma. [12] Lesions intermediate between benign reactive lymphoid hyperplasia and lymphoma have been called atypical lymphoid hyperplasia. These lesions have irregular follicles, more atypical lymphocytes, and perhaps a slightly worse prognosis. [13] However, reactive lesions by morphologic and immunophenotypic criteria may harbor clones of proliferating B cells. [14, 15] These clones are identified on Southern blots as nongermline bands that have the same size DNA fragments when cleaved by restriction endonucleases and hybridized to radioactively labeled probes from specific sites on the immunoglobulin gene. [16, 17, 18, 19, 20] It is becoming evident that orbital lymphoid lesions are a spectrum of B-cell neoplasias. [21] Because no specific morphologic, immunophenotypic, or molecular criteria have yet been well correlated with eventual outcome, it is not clear what investigative procedures are required in order to manage patients with lymphoid lesions. If treatment is to be based on clinical criteria, then fine needle aspiration biopsy with or without phenotyptic markers will suffice. However, if the type of treatment is predicated on gene rearrangement studies, then at this time open biopsy with removal of adequate tissue is necessary.

References:
4. Frayer WC, Enterline HT. Arch Ophthalmol 1959;62:203-210.
5. Kirk RC, Zimmerman LE, Rhabdomyosarcoma of the orbit. ARch Ophthalmol 1969;81:559-564.
6. Yanoff M, Fine BS. Ocular pathology. Philadelphia: J.B. Lippincott, 1989:532-534.
7. Knowles DM, Jakobiec FA, Potter G, Jones IS. Surc Ophthalmol 1976;21:219-261.
8. Kennerdell JS, Slamovits TL, Dekker A, Johnson BL. Am J Ophthalmol 1985;99:547-551.
9. Zajdela A, Vielh P, Schlienger P, Haye C. Am J Clin Pathol, 1990;93:100-104.
10. de Jong ASH, can Kessel-van Vark M, van Heerde P. Acta Cytol 1987;31:573-577.
11. Wharam M, Beltangady M, Hays D, Heyn R, Ragab A, et al. Ophthalmology 1987;94:251-254.
12. Jakobiec FA, McLean I, Font R. Ophthalmology 1979;86:948-966.
13. Knowles DM II, Jakobiec FA. Cancer 1980;46:576-589.

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CHAPTER 10 FNA ORBITAL LESIONS

Fine Needle Aspiration of Orbital and Periorbital Lesions

In this chapter, cytologic findings in orbital fine needle aspiration are illustrated. The general pathologists and cytopathologists who are skilled in interpretation of extra-orbital fine needle aspirates will readily transfer that expertise to orbital aspirates because the tumors are similar. Accuracy in differentiating benign and malignant orbital lesions by aspiration cytology varies from 50% to 100% in previous series. [1, 2] The utility of fine needle aspiration is determined by how the results will affect patient management. If patient management is unaffected, then the procedure is not necessary. For example, certain orbital tumors are removed completely during the first operation (mixed tumor of lacrimal gland, schwannoma, dermoid cyst, and cavernous hemangioma). If the clinical diagnosis of these lesions is certain prior to the operation, then fine needle biopsy is not required. However, the clinical and radiologic diagnoses are frequently wrong (over 50% of cases in one series) and fine needle aspiration has been useful. [3] There are two general indications in which fine needle aspiration of the orbit has proven most useful. First, if the suspected tumor can be treated without surgical intervention (e.g., rhabdomyosarcoma, sarcoidosis, metastatic cancer, reactive lymphoid hyperplasia, lymphoma, sclerosing orbititis, and infections), an accurate fine needle biopsy may spare the patient any further procedure. Second, fine needle aspiration may help surgeon plan an operation. For example, a patient with the erroneous clinical or radiologic diagnosis of osteosarcoma might have a planned radial orbitectomy changed to an appropriate curettage if a fine needle aspiration biopsy reveals eosinophilic granuloma. In addition, the fine needle biopsy may radically change a medical evaluation for metastatic disease. The patient with a suspected lymphoma requires a different evaluation than the patient with granulomatous disease.

References:
1. Krohel GB, Tobin D, Chavis RM. Inaccuracy of orbital fine needle aspiration biopsy. Ophthalmology 1984[Suppl.];91:83.
2. Czerniak B, Woyke S, Daniel B, Krzysztolik Z, Koss LG. Cancer 1984;54:2385-2389.
3. Glasgow BJ, Layfield LJ. Daign Cytopathol 1991;7:132-141.

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LEUKEMIA, CHOROIDAL MELANOMA, METASTATIC CARCINOMA

LEUKEMIA

Leukemia may involve the eye in some form in as many as 80% to 90% of cases. [30, 31, 32] Usually, it takes the form of focal infiltration of the choroids. [33]Iris involvement by leukemic cells can lead to a pseudohypopyon (Figure 9-7). [34] This may occur with acute lymphocytic leukemia, chronic lymphocytic leukemia, or acute myelogenous leukemia. [35, 36, 37, 38, 39] A simple aqueous aspirate with a small gauge needle is often sufficient for diagnosis (Figure 9-8).

CHOROIDAL MELANOMA

Choroidal melanoma accounts for about 80% to 87% of all ocular melanomas. [40] Patients most frequently present clinically with blurred vision and examination reveals a mass in the posterior globe (Figure 9-9). Malignant melanomas of the choroids differ from those of the skin. They have a more bland histologic appearance and they have a better prognosis (Figure 9-10). [41] Historically, choroidal melanomas are classified according to the presence of spindle or epithelioid cells. [42, 43, 44] However, it is apparent the other cytologic information may be important, including the standard deviation of the nucleolar area. [45, 46] Fine needle aspiration of uveal tumors has been an effective means of diagnosis. [47, 48, 49, 50, 51, 52] Criteria for cytologic diagnosis of malignant include clusters or single pigmented cells with enlarged nuclei and prominent nucleoli. Spindle cells retain their elongated shaper and have nuclear grooves (Figure 9-11). [29] Cells with dendritic cytoplasm are frequently present (Figure 9-12). Epithelioid cells have more abundant cytoplasm, larger round nuclei, and more prominent nucleoli (Figure 9-13). Occasionally, enlarged cells with vacuolated cytoplasm (balloon cells) are sampled (Figure 9-14). Invariably present in fine needle aspirate smears are macrophages that are stuffed with pigment (Figure 9-15).

METASTATIC CARCINOMA

One source of difficulty in the differential diagnosis of ocular tumors is metatstatic disease. The incidence of metastatic ocular cancer in autopsy studies varies from 0.06% to 2.3%. [53, 54] The most common site for metastasis in the eye is the choroids. [55, 56] The site of the primary lesion is most often is the breast (46% to 90%) followed by the lung (10% to 29%). [57] Because metastatic lesions may produce dome-shaped tumors in the choroids, fine needle aspiration may be necessary to differentiate a primary ocular amelanotic melanoma from a metastatic cancer (Figure 9-16). The cytologic findings of metastatic tumors correspond to those of the primary tumor and occasionally, the features may suggest a primary site (Figure 9-17).

References


30. Duke-Elder WS, ed. System of ophthalmology. St. Louis, C.V. Mosby, 1965;13:817-818.
31. Allen RA, et al. Arch Ophthalmol. 1961 Oct;66:490-508.
32. Rosenthal AR., Ophthalmology. 1983 Aug;90(8):899-905.
33. Kincaid MC, et al. Surv Ophthalmol. 1983 Jan-Feb;27(4):211-32.
34. Perry HD, et al. Am J Ophthalmol. 1979 Apr;87(4):530-2.
35. Martin B. Br J Ophthalmol. 1968 Oct;52(10):781-5.
36. Fonken HA, et al. Arch Ophthalmol. 1966 Jul;76(1):32-6.
37. Holbrook CT, J Pediatr. 1978 Oct;93(4):626-8.
38. Johnston SS, et al. Br J Ophthalmol. 1973 May;57(5):320-4.
39. Kincaid MC, et al. Am J Ophthalmol. 1979 May;87(5):698-702.
40. Reese AB. Tumors of the eye. 3d edition. Hagerstown, MD Harper & Row, 1976:229.
41. Zimmerman LE. Malignant melanoma of the uveal tract. In: Opthalmic pathology. Philadelphia: W.B. Saunders Co, 1986;2072-2139.
42. Callendar GR. Malignant melanomic tumors of the eye. A study of histologic types in 111 cases. Trans Am Acad Opthalmol Otolaryngol 1931;367:131.
43. McLean IW, et al. Am J Ophthalmol. 1983 Oct;96(4):502-9.
44. Paul EV, Parnell BL, Fraker M. Prognosis of malignant melanomas of the choroid and ciliary body. Int Opthalmol Clin 1962;2:387.
45. Gamel JW, McLean IW, Greenberg RA, Naids RM, Folberg R, et al. Lichtenstein SJ. Computerized histological assessment of malignant potential: a method for determining the prognosis of uveal melanomas. Human Pathol 1982;13:893-897.
46. Gamel JW, et al. Hum Pathol. 1985 Jul;16(7):689-92.
47. Jakobeic FA, et al. Ophthalmology. 1979 Sep;86(9):1662-81.
48. Augsberg JJ, Shields JA. Fine needle aspiration biopsy of solid intraocular tumors. Indications, instrumentaion, and techniques. Opthalmic Surg 1984;15:34-40.
49. Czerniak B, et al. Acta Cytol. 1983 Mar-Apr;27(2):157-65.
50. Midena E, et al. Surv Ophthalmol. 1985 May-Jun;29(6):410-22.
51. Davey CC, et al. Trans Ophthalmol Soc U K. 1986;105 ( Pt 1):78-83
52. Char DH, et al. Acta Cytol. 1989 Sep-Oct;33(5):599-605.
53. Gotfredson E, et al. On the frequency of secondary carcinomas in the choroid. Acta Cytol 1944;22;394-400.
54. Albert DM, et al. Am J Ophthalmol. 1967 Apr;63(4):723-6.
55. Block RS, Gartner S. The incidence of ocular metastatic carcinoma. Arch Opthalmol 1971;85:673-675.
56. Stephens RF, et al. Ophthalmology. 1979 Jul;86(7):1336-49.
57. Ferry AP, et al. Arch Ophthalmol. 1974 Oct;92(4):276-86.

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CHAPTER 9- MALIGNANT NEOPLASMS- LYMPHOMA, RETINOBLASTOMA,

In this chapter, malignant neoplasms of the eye are illustrated. Iris and ciliary body melanomas were presented in Chapter 5. Orbital and periorbital tumors are discussed in Chapter 10.
Only a few malignant tumors originate in the eye. Interpretation of aspirates from these tumors is not difficult if sampling is adequate and one is familiar with their specific criteria. Some primary ocular tumors have different criteria for diagnosis than analogous systemic neoplasms (e.g., melanoma). Diagnosis of other tumors is complicated by inherent difficulty in obtaining adequate material (e.g., lymphoma).

MALIGNANT LYMPHOMA

Intraocular lymphomas are rare and usually associated with involvement of the central nervous system. [1, 2, 3,