Ординатура / Офтальмология / Английские материалы / Orbital Tumors Diagnosis and Treatment_Karcioglu_2005

5.Howard G, Nerad J, Carter K et al. Clinical characteristics associated with orbital invasion of cutaneous basal cell and squamous cell tumours of the eyelid. Am J Ophthalmol 1992; 113:123–133.

6.Gorlin RJ, Goltz RW. Multiple nevoid basal cell epithelioma, jaw cysts and bifid rib: a syndrome. N Engl J Med 1960;262: 908.

7.Anderson T, Best P. Linear basal cell nevus. Br J Dermatol 1962;74:20.

8.Basex A, Dope A, Christol B. Atrophodermie folliculaire, proliferationes basocellulaires et hypotrichoses. Ann Dermatol Syph 1966;93:241.

9.Wiggs E. Morphea-form basal cell carcinomas of the canthi.

Trans Am Acad Ophthal Otolaryngol 1975;79:649–653.

10.Wiggs E. Basal cell carcinoma of the medial canthus—its orbital implications. Mod Probl Ophthalmol 1975;14:549–552.

11.Glover A, Grove A. Orbital invasion by eyelid tumours. Ophthalmic Plast Reconstr Surg 1989;5:1–12.

12.Hornblass A, Stephano J. Pigmented basal cell carcinoma of the eyelids. Am J Ophthalmol 1988;92:193–197.

13.Rahbari H, Mehregan A. Basal cell carcinoma in children and teenagers. Cancer 1982;49:350–353.

14.de Potter P, Shields J, Shields C. Secondary orbital tumours. In: eds. MRI of the Eye and Orbit. Philadelphia: JB Lippincott; 1995:255–268.

15.Veness M, Biakin S. Perineural spread leading to orbital invasion from skin cancer. Australas Radiol 2000;44:296–302.

16.Yanoff M, Fine B. Ocular Pathology: A Text and Atlas. 3rd ed. Philadelphia: JB Lippincott; 1989:192–202.

17.Putterman A. Orbital exenteration with spontaneous granulation. Arch Ophthalmol 1986;104:139–140.

18.Bartley G, Garrity J, Waller R, et al. Orbital exenteration at the Mayo clinic 1967–1986. Ophthalmology 1989;96:468–474.

19.Günalp I, Gündüz K, Duruk K. Orbital exenteration: a review of 429 cases. Int Ophthalmol 1996;19:177–184.

20.Rathbun J, Beard C, Quickert M. Evaluation of 48 cases of orbital exenteration. Am J Ophthalmol 1971;72:191–199.

21.Hanke C, Wolf R, Hochman S et al. Perineural spread of basal cell carcinoma. J Dermatol Surg Oncol 1983;9:742–747.

22.Reifler D, Hornblass A. Surgical management of squamous cell carcinoma of the lid. Ophthalmic Plast Reconstr Surg

1986;2:75–82.

23.Reifler D, Hornblass A. Squamous cell carcinoma of the eyelid. Surv Ophthalmol 1986;6:349–365.

24.Duke Elder S. The ocular adnexae. In: Duke-Elder S, ed. System of Ophthalmology. Vol 8. St Louis: CV Mosby; 1974:423.

25.Csaky K, Custer P. Perineural invasion of the orbit by squamous cell carcinoma. Ophthalmic Surg 1990;21:218–220.

26.Caya J, Hidayat A, Weiner J. A clinicopathologic study of 21 cases of adenoid squamous cell carcinoma of the eyelid and periorbital region. Am J Ophthalmol 1985;99:291–297.

27.Mohs F, Lathrop T. Modes of spread of cancer of the skin. Arch Dermatol 1952;66:427–439.

28.Reese A. Tumours of the Eye. 3rd ed. Hagerstown, MD: Harper & Row; 1976:3.

29.Aurora A, Blodi F. Lesions of the eyelids: a clinicopathologic study. Surv Ophthalmol 1970;15:94–104.

30.Ferry A. The biological behavior and pathological features of carcinoma metastatic to the eye and orbit. Trans Am Ophthalmol Soc 1973;71:373—425.

31.Trobe J, Hood C, Parsons J, et al. Intracranial spread of squamous cell carcinoma along the trigeminal nerve. Arch Ophthalmol 1982;100:608–611.

32.Ballantyne A, McCarten A, Ibanez M. The extension of cancer of the head and neck through peripheral nerves. Am J Surg 1963;106:651–667.

33.Cottel W. Perineural invasion by squamous cell carcinoma. J Dermatol Surg Oncol 1982;8:589–600.

34.McNab A, Francis I, Benger R, et al. Perineural spread of cutaneous squamous cell carcinoma via the orbit: clinical features and outcome in 21 cases. Ophthalmology 1997;104: 1457–1462.

35.Kass L, Hornblass A. Sebaceous carcinoma of the ocular adnexa. Surv Ophthalmol 1989;33:477–490.

36.Straatsma B. Meibomian gland tumours. Arch Ophthalmol 1958;56:71–93.

37.Honavor S, Shields C, Maus M, et al. Primary intraepithelial sebaceous gland carcinoma of the palpebral conjunctiva. Arch Ophthalmol 2001;119:764–767.

38.Boniuk M, Zimmerman L. Sebaceous carcinoma of the eyelid, eyebrow, caruncle and orbit. Trans Am Acad Ophthalmol Otolaryngol 1968;72:619–641.

39.Rao N, McLean I, Zimmerman L. Sebaceous carcinoma of eyelids and caruncle: correlation of clinicopathologic features with prognosis. In: Jakobiec F, ed. Ocular and Adnexal Tumours. Birmingham, Alabama: Aesculapius Publishing; 1978:461–476.

40.Martin P, Rogers P. Adenocarcinoma of the meibomian gland.

Aust J Ophthalmol 1982;10:63–67.

41.Ginsberg J. Present status of meibomian gland carcinoma. Arch Ophthalmol 1965;73:271–277.

42.Collin J, Garner A, Allen L, et al. Malignant melanoma of the eyelid and conjunctiva. Aust N Z J Ophthalmol 1986;14: 29–34.

43.Naidoff M, Bernardino V, Clark W. Melanocytic lesions of eyelid skin. Am J Ophthalmol 1976;82:371–382.

44.Clark W, Mihm M. Lentigo maligna and lentigo-maligna melanoma. Am J Pathol 1969;55:39–46.

45.McGovern V. The classification of melanoma and its relationship with prognosis. Pathology 1970;2:85–98.

46.Wick M. Prognostic factors for cutaneous melanoma. Am J Clin Pathol 1998;110:713–718.

47.Resnick K, Sadun A, Albert D. Basal cell epithelioma: an unusual case. Ophthalmology 1981;88:1182–1185.

48.Sutula F, Dortzbach R, Bolles J. Desmoplastic malignant melanoma of the upper eyelid. Ann Ophthalmol 1982;14:141– 143.

49.Esmaeli B. Sentinel lymph node mapping for patients with cutaneous and conjunctival malignant melanoma. Ophthalmic Plast Reconstr Surg 2000;16:170–172.

50.Grossniklaus H, McLean I. Cutaneous melanoma of the eyelid: clinicopathologic features. Ophthalmology 1991;98:1867– 1873.

51.Bernardino E, et al. Histogenesis and biologic behaviour of primary human malignant melanoma of the skin. Cancer Res 1969;29:705–727.

52.Rodriguez-Sains R, Jakobiec F, Iwamoto T. Lentigo maligna of the lateral canthal skin. Ophthalmology 1981;88:1186– 1192.

53.Pitman G, Kopf A, Bart R, et al. Treatment of lentigo maligna and lentigo maligna melanoma. J Dermatol Surg Oncol 1977; 9:727–737.

54.Breslow A. Thickness, cross-sectioned areas and depth of invasion in the prognosis of cutaneous melanoma. Ann Surg 1970;172:902–908.

55.Cook B, Bartley G. Epidemiologic characteristics and clinical course of patients with malignant eyelid tumours in an incidence cohort in Olmsted County, Minnesota. Ophthalmology 1999;106:746–750.

56.Tahery D, Goldberg R, Moy R. Malignant melanoma of the eyelid: a report of eight cases and a review of the literature. J Am Acad Dermatol 1992;27:17–21.

Although the conjunctiva can harbor many primary and secondary neoplasms (Table 21.1), the two most significant tumors that may ex-

tend into the orbit are squamous cell carcinoma (SCC) and melanoma.1 Therefore, only these tumors are discussed in detail in this chapter.

SQUAMOUS CELL CARCINOMA

Clinical Features

The bulbar conjunctiva, particularly the limbus, is the frequent site for the occurrence of slow-growing, dyskeratotic epithelial proliferations. Similar to epithelial neoplasms elsewhere in the body, conjunctival tumors evolve through morphologic stages of dysplasia and carcinoma in situ to the invasive stage. Most of the conjunctival epitheliomas show histologic changes analogous to actinic solar keratosis of skin and follow a benign course early in their development. However, the degree of dysplasia in these lesions cannot be determined by clinical examination, therefore, it is absolutely necessary that biopsy samples be obtained and examined histopathologically. The incidence varies from 0.02 to 3.5 per 100,000 population depending on the geographic location.2,3 SCC of the conjunctiva is predominantly a disease of the elderly that occurs most commonly during the sixth and seventh decades of life. However, it is reported to occur at a much younger age in patients with xeroderma pigmentosum.4 Although the exact incidence of SCC in children is not known, it has been reported in individuals as young as 4 years old.5 It has been recently recognized that SCC of the conjunctiva not only occurs more frequently in individuals who are immunosuppressed, but also develops at a younger age and behaves more aggressively (see Chapter 3).6,7

SCC of the conjunctiva usually presents as an elevated pinkish-gray lesion with a pearly or gelatinous appearance and surrounding feeding vessels (Figure 21.1).8.9 The most common presenting symptoms of these interpalpebral/limbal lesions are redness and irritation of the eye with or without foreign body sensation. Although most lesions begin as a localized mass formation,3 atypical presentations of SCC as a

diffuse growth or a masquerade lesion mimicking scleral keratitis or scleromalacia have also been reported.10 Atypical cases may show extensive invasion because of delayed treatment.

Conjunctival and invasive SCC is considered to be a low-grade malignancy that is locally invasive but rarely presents with distant metastases. When the neoplasm breaks through the basement membrane of the conjunctival epithelium and invades the subepithelial tissues and episclera, it behaves in a locally aggressive fashion.11 Although these are slowly growing tumors, under certain conditions they are known to extend into the underlying structures, including the globe and the orbit.10–15

Although less frequently, SCC may originate from the tarsal conjunctiva as solitary or multifocal, slightly elevated, placoid tumors. These lesions clinically present as rough, irregular plaques with or without leukoplakic changes on the surface. Later, the lesions may grow into papillary masses or nodules. The SCC of the bulbar conjunctiva extends toward either eyelids, orbit, or into the globe (Figure 21.2). When the tarsal conjunctiva and the underlying lid layers are involved, the behavior of the tumors is similar to that of eyelid skin SCC involving the lymph and blood vessels and nerve sheaths (Figure 21.3) (see Chapter 20). These lesions may reach a significant size, and even in moderate sizes they develop easy access into the substance of the eyelid and into the orbit. Traditionally, SCC of the conjunctiva has been considered to be a low-grade malignancy accounted for about 5 to 7% of secondary orbital tumors.16 But recently higher incidences have been reported. Conjunctival SCC comprised approximately 25% of secondary orbital tumors in an extensive study.17 Although the initial site of tumor origin (bulbar vs tarsal conjunctiva) was not specified in this series, orbital invasion is considered to occur more often in tarsal tumors. The occurrence of orbital invasion has been approximately 10% in other series.18

SCC of the Lacrimal Drainage System

Malignant epithelial tumors of the lacrimal drainage system (LDS) outnumber the benign ones 3 to 1, and the majority of these tumors are SCCs.19 In the LDS, SCC extends into the orbit early because of the thin

TABLE 21.1. Primary and Secondary Tumors and Pseudotumors of the Conjunctiva.

FIGURE 21.1. A nodular squamous cell carcinoma of bulbar conjunctiva.

recurrent fashion. The name inverted stems from its histopathologic structure, which consists of epithelial papillary proliferations inverting into the underlying stroma instead of an exophytic proliferation, which is characteristic of papillomas in general. Another distinctive feature of this tumor is the presence of numerous, small mucin-containing cysts throughout the epithelial component of the tumor. This characteristic can be best demonstrated with mucicarmine stain.20

Although most of these tumors originating in the conjunctiva behave as benign proliferations, approximately 40% of LDS inverted papillomas are known to develop malignant transformation ranging from dysplasia to invasive SCC.21 Even the histopathologically benign inverted papillomas are known to recur fre-

walls of the lacrimal passages. Fortunately, SCC of the LDS is not common. If these tumors can be recognized early and excised with clear surgical margins, the prognosis is good. Because of early extension into the orbital soft tissues, however, the recurrence rate is high.19 A detailed discussion of these tumors is in Chapter 19.

One unique type of the LDS tumor is the inverted papilloma, which is in essence a benign papillary hyperplasia that may behave clinically in an aggressive,

FIGURE 21.2. Extension of squamous cell carcinoma of conjunctiva into the eyelid and orbital tissues.

A

B

FIGURE 21.3. (A) Perineural invasion leading to the extension of squamous cell carcinoma (CC) into the orbit (B) (arrow: nerve).

quently and have been reported to invade the orbit after several recurrences (Figure 21.4).22 These tumors are difficult to cure surgically because of their infiltrating mode of invasion and scarring.

Variations Based on Histology

Since all SCCs arise from the keratinocyte, they all display the same histopathologic appearance, whether originating in skin or other types of epithelium with squamous metaplasia potential such as the conjunctiva. In carcinoma in situ, the full thickness of the epithelium/epidermis is involved with disorderly proliferation of squamous cells (keratinocytes) with cytologic maturation. Instead, the SCC cells form sheaths of atypical, dyskeratotic groups with a scattered mitosis at all levels of the epithelium. Once the basement membrane has been violated and the tumor goes into the subepithelial/subepidermal layers, it is known as invasive SCC.23 Downward growth of the neoplasm consists of irregular nests of neoplastic cells extending into the underlying tissues. Invading tumor cells are composed in varying proportions of normalappearing and atypical squamous cells showing varying degrees of pleomorphism. The SCC may be well differentiated with keratinization horn pearls (characteristic structures composed of concentric layers of squamous cells showing gradually increasing keratinization toward the center), and intercellular bridges (desmosomes). As the tumor becomes less differentiated, these features are lost and atypical cells and mi-

totic figures increase. Poorly differentiated tumors exhibit minimal keratinization, and their keratocyte origin may be difficult to identify histopathologically. Immunohistochemistry for cytokeratin B is an invaluable technique to identify the cell of origin of these poorly differentiated tumors.24 Histopathologic types of conjunctival SCC, including spindle cell carcinoma,25 mucoepidermoid carcinoma,26,27 and adenoid squamous carcinoma (ASC),28 are the bestknown varieties. The histopathologic patterns of these tumors, which are composed of cells of different types, appear to influence the clinical course and the prognosis of the patient. Spindle cell carcinoma behaves in a rather aggressive fashion, with recurrences and invasion of the globe.25

Mucodepidermoid carcinoma is composed of a mixture of malignant keratinocytes and cells that secrete mucus containing acid mucopolysaccharides (Figure 21.5). These tumors behave in a more aggressive fashion than the conventional SCC, with a tendency to recur and invade ocular and orbital structures.27 Most of the mucoepidermoid carcinomas originate in the bulbar conjunctiva, close to the limbus, and appear to look flashier and less keratinized than the conventional SCC. Recurrent lesions have a tendency to extend into the globe and orbit and metastasize.

The ASC of the conjunctiva is made of islands of malignant keratinocytes, which present in a pseudoglandular pattern and show extracellular Alcian blue positivity. Studies with transmission electron microscopy documented that ASC of the conjunctiva is different from the mucoepidermoid type.29 ASC of the conjunctiva, like its cutaneous and oral counterparts, appears to have a worse prognosis than conventional SCC.30

Management and Prognosis

The management of superficial disease (carcinoma in situ and/or superficial invasive SCC) includes surgical excision of the lesion with lamellar scleral keratoconjunctivectomy and cryotherapy (Figure 21.6).31,32 Mauriello et al. also advocate the “microscopically controlled excision” technique of ASC; in this technique the lesion is resected with a no. 69 Beaver blade, and the margins of excision are treated with absolute alcohol to devitalize any residual tumor cells.29 If the possibility of the existence of tumor cells cannot be ruled out at the deep margin, cryotherapy with a freeze–thaw–refreeze technique is advised.

Although other treatments, including brachytherapy, external beam radiation therapy (EBRT), and immunotherapy with dinitrochlorobenzene have been used, most of these methodologies do not offer a good prognosis. Currently, topical chemotherapy with mitomycin C and 5-fluorouracil has reportedly achieved good results in superficial cases.33,34 No matter what

FIGURE 21.5. Mucoepidermoid carcinoma of the limbus (A) that recurred 9 months after excision (B). Center: Histopathology reveals nests of invading malignant squamous cells intermixed with vacuolated tumor cells containing mucin material as depicted with mucicarmine stain (arrow).

other therapeutic modality is coemployed, an initial attempt should be made for complete surgical removal of the tumor with free margins. This is best accomplished under frozen or permanent section monitoring.35,36 Once the ocular and orbital extension of the SCC occurs, the treatment is enucleation and exenteration, respectively, with or without postoperative EBRT. Detailed preoperative imaging studies with CT and MRI are needed to determine the extent of tumor; both procedures should be performed under frozen section control to ensure tumor-free margins.

The biological behavior of SCC has been traditionally based on Broders’s histopathologic grading system, which divides the tumors into grades based on the proportion of differentiated cells within a given SCC.37 The premise of Broders’s classification is that the more poorly differentiated the tumor, the more likely it is to invade aggressively, metastasize, and recur locally following treatment.38 In reality, the prognosis of a given SCC is dependent on many other factors, including the site of origin and inciting cause (e.g., tumors originating from solar keratosis behave less aggressively than lesions that arise de novo).39 SCCs originating from tissues scarred by ionizing radiation, heat, and/or chemical burns behave more aggressively.40,41

Other histologic features related to poor prognosis are the size of a given tumor and depth of its invasion. These two parameters should be taken into account relative to where SCC is located and the type of epithelium that it originates from. For example, a tumor measuring 1 cm in diameter may not be considered to be very deep if it is originating from the skin; on the other hand, an SCC of the same size, having ready access to the underlying vascular channels and is located in the conjunctiva, may be considered to be deeply invasive.

As our knowledge of oncogenesis expands, other risk factors are added to the histopathologic parameters just listed. Hereditary syndromes of certain types, such as xeroderma pigmentosum, albinism, epidermodysplasia verruciformis, have been associated with an increased incidence of cutaneous and conjunctival SCC. Other risk factors, including ultraviolet radiation,42,43 oncogenes such as the gene for p53 (Figure 21.7),44–46 human papilloma virus (HPV),47,48 immunosuppression, and particularly acquired immunodeficiency syndrome (AIDS)49,50 should be taken into account when one manages these patients (see Chapter 3).

CONJUNCTIVAL MELANOMA

Clinical Features

Conjunctival melanoma is a rare but aggressive ocular tumor that originates from melanocytes.51–54 It is estimated that about 20% of conjunctival melanomas arise

FIGURE 21.7. Squamous cell carcinoma of the conjunctiva stained with anti-p53 antibody: (A) in situ (A) and (B) in the invasive state.

from preexisting nevi, another 70% develop from primary acquired melanosis, and the rest are considered to develop de novo with no evident preexisting melanocytic lesion.52 All three groups originate from dendritic melanocytes, the basal layer of the conjunctival epithelium.53 Conjunctival nevi are not uncommon in children; about 50% of all nevi are encountered by the age of 20. The melanomatous transformation in the pediatric age group, however, is very rare.55

Variations Based on Histopathology

MELANOSIS

Generally speaking, melanosis refers to excessive melanocytic pigmentation occurring either as an epithelial or subepithelial lesion.56 It is crucial to determine whether the melanosis has developed as a congenital or an acquired lesion.

Congenital melanosis typically presents at birth as grayish-blue subepithelial lesions that do not become malignant. Two main types exist: lesions in which only the globe is affected (ocular melanosis) and lesions in which ocular melanosis is accompanied by ipsilateral dermal melanosis of periorbital skin (oculodermal melanosis or nevus of Ota). Both forms appear clinically as slate-blue areas of episcleral pigmentation that may increase in size during the first few decades of life. By moving the conjunctiva over the pigmented area on slit lamp examination, one can best appreciate the depth of these lesions. In contrast, intraepithelial forms of melanosis are yellow-brown to brown-black. Oculodermal melanosis is more common in Asians and blacks, while ocular melanosis occurs more often in Caucasians.

Primary acquired melanosis (PAM) may be due to simple hyperplasia of melanocytes in the basal epithelial layer or to atypical melanocytic hyperplasia. The latter form is considered a precursor of malignant acquired melanosis. Clinically, these lesions are unilateral, tannish-brown or black, flat, localized or patchy tumors occurring in the later decades of life. Often, the pigmentation in one area of the conjunctiva disappears spontaneously and simultaneously with the development of new lesions in an adjacent zone. Clinical experience tells us that about one-third of these lesions may eventually become melanomas, but the process is slow, usually taking several decades.

Malignant acquired melanosis refers to development of melanoma within a preexisting PAM. These tumors appear as darkly pigmented, thickened areas arising within preexisting flat lesions, often with nodules and inflammation. Because the precursor lesions are multicentric, melanoma may appear in several areas at once, or it may develop stepwise. Thus, it is essential to examine the entire conjunctiva carefully, including upper and lower fornices. These lesions may remain superficially invasive for a long time, with or-

bital extension and metastasis to regional lymph nodes occurring only in the late stages.

NEVUS

The nevus is the most frequently encountered as a melanocytic growth of the conjunctiva; approximately 30% of these lesions are detected before puberty and 90% by age 30.56 Depending on the histopathologic location of melanocytic proliferation, nevi are classified as junctional (proliferation at the epithelial–subep- ithelial interface), subepithelial (proliferation with subepithelial tissues), or compound (both junctional and subepithelial proliferation). Most conjunctival nevi are compound or subepithelial.

Nevi are often located on the bulbar conjunctiva within the interpalpebral fissure. Those at the limbus tend to be flat and may extend onto the cornea, while those in the other zones of the bulbar conjunctiva, particularly on the plica and caruncle, appear more bulky and elevated. Approximately 30% of nevi are salmon colored rather than dark-brown–black; pigmentation may increase during pubery and pregnancy and with other hormonal stimuli.

On slit lamp examination, small cystic structures are seen within the subepithelial matrix of the lesion. These represent epithelial inclusion cysts lined with conjunctival epithelium and mucus-producing goblet cells (Figure 21.8). As these inclusions gather secretions and grow, they may give the impression of lesional transformation into malignancy. The nevus may also exhibit secondary inflammation with subsequent increase in size and vascularity. In many cases, these changes are accompanied by pigmentary alterations, which again may suggest malignant transformation. Although these changes are known to occur during hormonally active periods, it is advisable to perform a biopsy to sample the changing lesion. The follow-up of the nevi is best done with serial slit lamp photographs. It is advisable to see these patients every 3, 6, and 12 months initially; if the lesion proves to be stable, the patient may be seen once a year from there on.

MELANOMA

Conjunctival melanomas are uncommon ocular neoplasms with an estimated incidence of 5 cases per million persons.52 The incidence of melanoma in general is much lower in the nonwhite population.57 Conjunctival melanoma as well is seen extremely rarely in the black population. In the series of Grossniklaus et al., the black-to-white ratio was given as 1:13.6.58,59 Melanoma of the conjunctiva, like melanoma of the skin, has a predilection for non-sun-exposed areas (e.g., palms, soles of the feet, fornices in the conjunctiva).60

The rapid growth, high vascularity, spontaneous bleeding, and fixation to underlying tissues of mela-

nomas differentiates them clinically from nevi. Any long-standing conjunctival nevus that suddenly changes its size, color, or appearance should be excised for histopathologic examination, with margins of the excised specimen specifically marked for proper orientation. This can be very useful for surgical planning if involved margins necessitate the further removal of additional tissue.

Melanomas are said to arise de novo when there is no clinical or histologic evidence of a precursor lesion within the epithelium adjacent to the tumor. The terms nodular melanoma (borrowed from dermatologic literature) and de novo melanoma are often used synonymously.

Clinically, the de novo melanoma develops as a tumor mass with increased pigmentation, surrounded by mild inflammation and prominent blood vessels. The growth rate of melanoma is quite variable. In early stages, these lesions are not deeply invasive into the underlying tissues, and surgical excision is easy (Figure 21.9). As they grow, however, they may become fixated to underlying structures and eventually invade the LDS, globe and/or orbit (Figures 21.10, 21.11, and 21.12). An extrascleral extension of a choroidal melanoma may take the form of an epibulbar pigmented tumor mass; this should not be confused with conjunctival melanoma (Figure 21.13). If there is any suspicion that a deeply located pigmented lesion represents an extrascleral extension of a ciliary body tumor, an echographic examination with A and B scans and/or MRI should be done immediately.

FIGURE 21.8. Nevi masquerading as melanoma because of clinical enlargement of the lesion. (A,B) Multicolored, dome-shaped bulbar nevus (N) appears to be enlarging because of the lymphangiectasis (L) with lymph/stasis developing under the lesion (B). (C,E) Enlargement of cystic nevus

(N) secondary to the distension of the cystic structures (C, D).

MANAGEMENT AND PROGNOSIS

The current management of early conjunctival melanoma is surgical excision under frozen section control followed by alcohol epitheliectomy and cryotherapy to the margins of excision. Cryotherapy, which is usually applied as a double freeze–thaw technique to the excision margins of the lesion, has proven value for local tumor control, but does not seem to change the incidence of metastatic disease.61 The cryotherapy should preferably be done to the excision margins of the conjunctiva; this application does not cause significant ad-

FIGURE 21.9. Melanocytic lesion at the caruncle. Although this tumor was a nongrowing nevus for many years, when the patient was about 45 years old, the lesion became thicker and darker. An excisional biopsy revealed a conjunctival melanoma, developing within a nevus. Caruncular melanoma is known to have a worse prognosis than melanoma originating from bulbar conjunctiva.

FIGURE 21.12. Exenteration specimen depicting a large, densely pigmented conjunctival melanoma extending into upper (UL) and lower (LL) eyelids and orbital soft tissues (arrow). (Courtesy of Dr. Jerry Shields, Philadelphia.)

gins is preserved; hence the importance of margin orientation. In large tumors, one can safely make an initial incisional biopsy to determine the nature of the lesion. Biopsies should be performed on the thickest, most irregular, and most pigmented parts of the melanoma, with particular care not to crush or cauterize the sample, especially if it is a small one.

In larger lesions, particularly those that are recurrent, the extent of surgical excision of the tumor is individualized. In general, the surgical approach should employ wider and deeper excision for melanomas on the surface of the eye. Enucleation or exenteration should be considered for tumors with ocular or orbital invasion.63 In patients with large tumors, the regional lymph nodes should be sampled for staging purposes (see Chapter 12).64

The management plan of conjunctival melanoma and the time of implementation of different treatment modalities depend on the clinical presentation and the recurrence pattern. Several histopathologic features observed in excisional and punch biopsies samples of conjunctival melanomas indicate the likelihood of recurrent and disseminated tumor (Figure 21.14). These features include invasive melanoma thickness more than 0.8 mm, lack of inflammatory cell response at

verse effects. However, it should be sparingly applied to the scleral base of the tumor because of the risk of damage to the underlying ocular components.52 It is believed that cryotherapy cures the clinically invisible extent of the tumor because patients who are treated with tumor excision alone have a higher recurrence rate than those who are treated with the combination of surgery and cryotherapy.31,61,62

Flat pigmented lesions that remain stable in size and appearance can usually be safely checked at 6- month intervals. Bulbar lesions are usually diagnosed earlier and monitored easily with sequential slit lamp examinations every 6 months. On the other hand, the tumors that originate from tarsal conjunctiva, caruncle, and fornices are usually recognized late and have a greater tendency to invade the orbit.63 If a tumor changes its size, shape, thickness, or pigmentation pattern, it should be subjected to biopsy or excised. If the lesion is small enough, it should be entirely removed, with generous margins (1–2 mm) as an excisional biopsy. This biopsy sample is placed flat on a piece of cardboard and its margins properly identified before it is sent to the pathology laboratory. If one margin shows tumor involvement and the others do not, additional tissue may be excised from the involved margin, while healthy conjunctival tissue in other mar-

FIGURE 21.13. (A) A ciliary body melanoma (CBM) that presented as an enlarging pigmented bulbar conjunctival lesion (arrowhead). (B) Histopathology shows the lesion (arrowheads) in relation to the CBM, the anterior chamber (AC), the conjunctiva (C), and the sclera (S).