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Melanocytic Lesions of the Conjunctiva

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Melanocytic Lesions of the Conjunctiva Melanocytic Lesions of the Conjunctiva Artur Zembowicz, MD, PhD; Rajni V. Mandal, MD; Pitipol Choopong, MD N Context.—Melanocytic proliferations are among the most Data Sources.—Review of the literature and personal common neoplasms of the conjunctiva. They often represent experience of the authors. challenging lesions for pathologists unfamiliar with unique Conclusions.—Classification, state of the art, and prac- histologic features of melanocytic proliferations in this tical aspects of pathology of melanocytic proliferations of location and with nomenclature used by ophthalmologists. the conjunctiva are discussed. Objective.—To comprehensively review clinical aspects, (Arch Pathol Lab Med. 2010;134:1785–1792) pathologic features, and management of melanocytic proliferations of the conjunctiva. elanocytic proliferations are the most common ic proliferations. In contrast, the concept of conjunctival M tumors of the conjunctiva, accounting for up to melanosis and the restricted use of the term melanoma to 53% of all conjunctival neoplasms.1,2 These lesions can be a invasive tumors are unique to the conjunctiva. One of the challenging diagnosis for general pathologists, as both peculiar aspects of this classification scheme is absence of benign and malignant melanocytic proliferations occur- the formal concept of melanoma in situ. All clinically ring in the anatomic context of the conjunctiva produce macular intraepithelial melanocytic proliferations that are unique histologic patterns that are often different from not nevi are included in a broad category of conjunctival those in the skin. Therefore, applying directly the melanosis. Melanosis can be primary or secondary (such histologic criteria developed for cutaneous melanocytic as in Addison disease), and congenital (such as complex- proliferations to these lesions may result in erroneous ion-associated melanosis) or acquired. The most common diagnoses. Moreover, proper communication with clini- form of melanosis is primary and acquired. It is further cians requires an understanding of the terminology for subdivided into primary acquired melanosis (PAM) conjunctival melanocytic proliferations used by ophthal- without atypia and PAM with atypia. The concept of mologists. PAM with atypia is controversial, as it includes a This review aims to provide an update on the classifi- spectrum of lesions showing only mild cytologic atypia cation of melanocytic lesions of the conjunctiva for to severely atypical lesions frequently associated with practicing general pathologists and dermatopathologists. invasive melanoma.8 Even though a strong argument can be made for using the term melanoma in situ for PAM with CLASSIFICATION OF CONJUNCTIVAL severe atypia, ophthalmic oncologists generally believe MELANOCYTIC PROLIFERATIONS that ‘‘the term melanoma in situ could unnecessarily Classification of conjunctival melanocytic prolifera- alarm both clinician and patients, particularly since many tions, as used by ophthalmologists, is unique to this PAM lesions have little propensity to evolve into anatomic location and has been a subject of ongoing melanoma.’’ 9 Historically, this attitude emerged as a debate and critique.3–5 The 1980 World Health Organiza- reaction to overly aggressive management of cases that tion classification is based on the ideas introduced by were diagnosed as melanoma in the past. Zimmerman at the Armed Forces Institue of Pathology6,7 and includes 3 categories: melanocytic nevus, conjunctival Conjunctival Nevus melanosis, and invasive melanoma. Conjunctival melano- Clinical Features.—Melanocytic nevi are the most com- cytic nevi are similar to those occurring in the skin and are mon tumors of the conjunctiva, accounting for 28% of all benign, acquired or congenital, circumscribed melanocyt- tumors.1,2 These lesions most commonly arise in the bulbar conjunctiva, caruncle, or plica semilunaris.10 They are Accepted for publication December 8, 2009. most common in young white individuals, with a mean From the Department of Pathology, Lahey Clinic, Burlington, age at presentation of about 32 years. The nevi present Massachusetts, and www.DermatopathologyConsultations.com, Bos- ton, Massachusetts (Dr Zembowicz); the Division of Dermatopathology, clinically as circumscribed, flat to slightly raised macules New York University Langone Medical Center, New York, New York or papules. Nevi in children often lack pigmentation, but (Dr Mandal); and the Department of Ophthalmology, Siriraj Hospital, usually acquire pigmentation after puberty. However, up Mahidol University, Bangkok, Thailand (Dr Choopong). to 30% of nevi remain amelanotic.11 Nevi on the bulbar The authors have no relevant financial interest in the products or conjunctiva move freely over the sclera and appear well companies described in this article. 10,12–14 Reprints: Artur Zembowicz, MD, PhD, www.DermatopathologyCon- circumscribed without extension into the cornea. A sultations.com, Department of Pathology, 6th Floor, 133 Brookline Ave, common and characteristic feature of conjunctival nevi is Boston, MA 02215 (e-mail: [email protected]). the presence of intralesional cysts.10,13 Arch Pathol Lab Med—Vol 134, December 2010 Conjunctival Melanocytic Proliferations—Zembowicz et al 1785 A biopsy is usually performed when a pigmented nevus of the junctional component (Figure 1, E and F). In shows clinical characteristics of possible malignancy such addition, a prominent inflammatory infiltrate may ob- as rapid growth, change in shape and/or color, recurrence scure the architecture of the nevus and foster misleading after prior biopsy, and unusual location such as the impression of cytologic atypia.17 palpebral conjunctiva or the fornix. Some lesions are Most variants of cutaneous nevi including combined removed for cosmetic reasons. Malignant melanoma will nevus, balloon cell nevus, Spitz nevus, pigmented spindle develop in less than 1% of conjunctival nevi.10,13 Clinical cell nevus, and blue nevus have been reported in the features particularly suggestive of evolving melanoma conjunctiva.18–25 Criteria for dysplastic or atypical nevi in include extension into the cornea, attachment to the sclera, the conjunctiva have not been established. It is not clear if and development of multiple ‘‘feeder vessels’’ seen by slit- patients with dysplastic nevus syndrome have higher lamp examination.10–14 There are no specific clinical signs incidence of conjunctival nevi. Earlier studies26 suggested that can accurately predict malignant transformation in a such a relationship, but a more recent case-control conjunctival nevus. population study27 has found no evidence for this claim. Pathologic Features.—Histologically, conjunctival mela- Treatment.—Conjunctival nevi do not require treatment nocytic nevi are classified similarly as in the skin, if clinically stable.2,10 Excision or rebiopsy is recommended including junctional, compound, and subepithelial nevi. in lesions that change in size or color, recur, or show other Nevomelanocytes can be organized into intraepithelial clinical features of possible malignancy, or for cosmetic nests of oval cells (type A), sheets of oval to cuboidal cells indications. There is no clinical benefit for reexcising (type B), and spindlelike cells in the subepithelium (type conjunctival nevi showing focal cytologic atypia. There- C) (Figure 1, A through D). About 5% of conjunctival nevi fore, pathologists should refrain from making recommen- are junctional, characterized by nested but sometimes also dation for reexcision in pathology reports without lentiginous proliferations of type A or type B cells understanding the clinical context of the lesion and the confined to the epithelium.10 They may show occasional risks of additional surgical intervention in this anatomi- mitotic activity.13 Junctional nevi with a prominent cally critical location. lentiginous growth pattern may be difficult to distinguish from PAM with atypia on a small biopsy specimen in the Primary Acquired Melanosis absence of clinical information.13 Most junctional nevi are Clinical Features.—Primary acquired melanosis (PAM) found in patients in the younger age groups. Therefore, comprises 11% of conjunctival melanocytic proliferations. they are believed to be at an early stage in the evolution of It is clinically defined as an acquired, usually unilateral, compound nevi. flat, pigmented lesion most commonly occurring on the Compound nevi are the most common type of conjunc- bulbar conjunctiva.2 Primary acquired melanosis is most 10 tival nevus, comprising about 70% to 78% of all nevi. In common in middle-aged or elderly white individuals. The adults, the intraepithelial component shows type A, or less melanosis can extend to the skin if the lesion involves the commonly, type B melanocytes. As in the skin, most palpebral conjunctiva. The pigmentation in PAM may conjunctival nevi arising in adults show ‘‘maturation’’ wax and wane and even disappear. A slit-lamp examina- with depth, that is, progressive evolution of the cell type tion may reveal subclinical melanosis around the clinically from A to B to neurotized spindle C cells, with depth of the visible lesion.2 Primary acquired melanosis may also be lesion into the superficial substantia propria.11,13 A very amelanotic, and thus clinically indistinct.12 By definition, characteristic and diagnostically useful feature of con- PAM does not have an inciting event, is not congenital, junctival nevi is induction of epithelial protrusions into and is not a secondary
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