Hrev_master [page 32] [Eye Reports 2011; 1:e10] Conjunctival blue nevus Joseph J. Chen, Seongmu Lee, Michael T. Yen Cullen Eye Institute, Department of Ophthalmology, Baylor College of Medicine, Houston, TX, USA Abstract The authors report a case of a conjunctival blue nevus and review the literature pertain- ing to these pigmented lesions in this location, describing clinical and histological report of a patient with a blue nevus of the palpebral con- junctiva with a literature review. A 64-year-old white female was evaluated for a darkening pigmented lesion of the left lower palpebral conjunctiva. Examination revealed a 3 mm x 6mm blue-black lesion with sharply demarcat- ed edges and an irregular border. Histopa - thology showed plump spindle-shaped, pig- mented melanocytic cells revealing a branch- ing network of dendritic processes with small, elongated, and hyperchromatic nuclei consis- tent with a common blue nevus. No recurrence was noted at 9-month follow-up. Blue nevi of the conjunctiva are lesions that have a low risk for malignant transformation but can appear clinically similar to primary acquired melanosis or melanoma. Blue nevi of the con- junctiva are rare and represent 0.5%-3.0% of pigmented conjunctival lesions. There was one reported case in a literature search of a malig- nant melanoma arising from a conjunctival cellular blue nevus. Treatment is complete wide excisional biopsy. Introduction Blue nevi are skin lesions containing melanocytic proliferations which can present in a variety of locations, most commonly in the dorsum of the hands and feet, the scalp, and the sacrococcygeal regions.1 Blue nevi also rarely present in mucosal membranes, such as the mouth, nose, uterus, vagina, endometri- um, prostate, bronchus, and esophagus.2 We present a case of a rare presentation of a com- mon blue nevus in the palpebral conjunctiva. Case Report A 64-year-old white female was referred for a darkening pigmented lesion noted on her left lower palpebral conjunctiva. The patient reported that the lesion had been present for more than 10 years and while she had not noticed any growth in the size of the lesion, it had become darker in appearance. She denied any family history of skin malignancies or ocu- lar lesions. She had no history of previous pig- mented lesions or history of malignancy, and review of systems was noncontributory. On slit lamp exam, a flat hyperpigmented lesion with irregular borders was noted in the inferior palpebral conjunctiva on the right eye measuring 3.1 mm vertically and 6.2 mm hori- zontally (Figure 1). The remainder of the ocu- lar exam was unremarkable. The lesion was fully excised and sent for histopathologic analysis. Histologically, there was mid to deep dermal proliferation of pigmented dermal melanocytes with no junctional component and no involve- ment of the epidermal layers (Figure 2). On higher magnification, there were pigmented spindle-shaped dendritic melanocytes reveal- ing a branching network of dendritic processes with small, elongated, and hyperchromatic nuclei (Figure 3). The dendritic cells did not display any cytologic atypia or mitotic figures. A diagnosis of common blue nevus was made. At 9 month follow-up, the patient displayed no evidence of recurrence. Discussion Blue nevi were first described by Jadassohn- Tieche in 1906 with a distinction made by Allen and Spitz in 1953 dividing blue nevi into the classically described categories of common blue nevus and cellular blue nevus.1-3 In cur- rent literature, the common blue nevus type has been further subtyped to include common blue nevus, combined blue nevus, sclerosing (desmoplastic) blue nevus, hypomelanotic/ amelanotic blue nevus, and epithelioid blue nevus of Carney Complex/pigmented epithe- lioid melanocytoma. The cellular blue nevus has been further subtyped into cellular blue nevus, amelanotic cellular blue nevus, atypical cellular blue nevus, and malignant blue nevus.2 Common blue nevi are distinguished histo- logically by characteristic variably pigmented spindle-shaped dendritic melanocytes in the mid to deep dermis which do not have a junc- tional component and which do not display any significant cytologic atypia. Cellular blue nevi are distinguished from common blue nevi in that they usually present as a pigmented biphasic tumor with a classic blue nevus com- ponent and a component of distinct cellular areas of spindled to oval melanocytes with clear cytoplasm. Both common and cellular blue nevi can present at any age, although typ- ically present in the third or fourth decade and most commonly are found in the sacrococ- cygeal region, scalp, face, and dorsal areas of the extremities.1 A subtype of cellular blue nevus has been described as malignant blue nevus, which has features of cellular blue nevus but can metastasize and result in death. Malignant blue nevi can arise from prior biop- sy or excision sites of blue nevi or can arise de novo.2 Histopa thologically, malignant blue nevi appear similar to cellular blue nevi with a biphasic architecture but have severely atypi- cal cytologic features.4 Malignant blue nevi have a poor prognosis, with a high rate of recurrence and metastasis. In a case series of 12 patients with melanoma arising from blue nevus in the skin, 10 of 12 (83%) patients developed metastases over a mean period of 40 months.5 Some studies have shown that immunohistochemistry may be of benefit, showing that malignant blue nevi show increased Ki-67 expression and may lose HMB- 45 labeling.6 Recently, Zembowicz et al. have suggested that the Gnaq and Gna11 proteins of the G-protein alpha subunits involved in sig- naling by G-protein coupled receptors are important for controlling early dermal melanoblast proliferation, citing that there is a permanent increase in dermal melanoblast numbers with activating mutations in Gnaq and Gna11, and also that somatic mutations in the GNAQ gene have been identified in 83% of cases of blue nevi, 50% of malignant blue nevi, and 46% of uveal melanoma.2 The pathogenesis of blue nevi has not been well established, but most currently, the pre- vailing theory postulates that dermal melanocytes are arrested during embryologic migration from the neural crest to the epider- Eye Reports 2011; volume 1:e10 Correspondence: Michael T. Yen, Cullen Eye Institute, Department of Ophthalmology, Baylor College of Medicine, 6565 Fannin NC-205, Houston, TX 77030, USA. Tel: +1.713.798-3231 - Fax: +1.713.798.8739. E-mail: myen@bcm.tmc.edu Key words: conjunctiva, blue nevus, melanocytic proliferation. Acknowledgements: supported in part by an unre- stricted educational grant from Research to Prevent Blindness, Inc. (New York, NY). Conflict of interest: the authors report no con- flicts of interest. Received for publication: 29 June 2011. Accepted for publication: 11 September 2011. This work is licensed under a Creative Commons Attribution NonCommercial 3.0 License (CC BY- NC 3.0). ©Copyright J.J. Chen et al., 2011 Licensee PAGEPress, Italy Eye Reports 2011; 1:e10 doi:10.4081/eye.2011.e10 Non -co mmerc ial us e o nly [Eye Reports 2011; 1:e10] [page 33] mis.2 This theory is supported by the fact that melanocytes, after population of the dermis from 10 weeks of gestation, will disappear at the end of gestation except in the presacral area, head and neck area, and dorsal areas of the distal extremities, which are also the most common sites of presentation for blue nevi in the skin.1 Blue nevi rarely occur in the conjunctiva, with only 22 reported cases of conjunctival blue nevi in the literature to date. There have been four large case series of pigmented conjuncti- val lesions, which noted blue nevi. In the largest series of 418 conjunctival nevi, Shields, et al. reported that 4 of the cases conjunctival nevi were histologically confirmed as blue nevi. Of these 4 cases, 2 were located in the bulbar conjunctiva, one in the tarsal conjuncti- va, and one in the fornix. All were brown in color, none had cysts, none had feeder vessels, and one has intrinsic vessels. One of the cases of blue nevus developed malignant melanoma; this case was one of the only 3 patients out of 410 patients in the series who developed malignant melanoma.7 Grossniklaus, et al. reported five out of 317 (1.5%) pigmented con- junctival lesions to be blue nevi in adults.8 Out of a series of 71 pigmented conjunctival lesions in children reported by McDonnell, et al., only one (1.6%) was found to be a blue nevus.9 Of the conjunctival blue nevi which report histopathologic analysis, there were 6 common blue nevi, including the blue nevus in this report, and 5 cellular blue nevi.10-12 In addi- tion to the one case from the Shield, et al. series in which malignant melanoma devel- oped,7 there was only one case of malignant transformation of a blue nevus reported, which was described histologically as a cellular blue nevus that appeared on exam as primary acquired melanosis and reported no recur- rence after excision at 7 year follow-up.11 It is uncertain whether these two reports represent the same patient or two different patients, as the two reports are from the same institution and share some authors. In summary, blue nevi are distinct melanocytic neoplasms that are commonly found in the skin but rarely occur in mucosal membranes, including the conjunctiva. Conjunctival blue nevi, particularly the cellular blue nevus subtype, have a rare potential for malignant transformation and have the poten- tial to recur after excision. Because of this low potential for malignant transformation, treat- ment is wide local excisional biopsy with sur- veillance. References 1. Rodriguez HA, Ackerman LV. Cellular blue nevus: clinicopathologic study of forty-five cases. Cancer 1968;21:393-405. 2. Zembowicz A, Pushkar AD. Blue nevi and variants: an update. Arch Pathol Lab Med 2011;135:327-36. 3. Allen AC, Spitz S. Malignant melanoma; a clinicopathological analysis of the criteria for diagnosis and prognosis. Cancer 1953; 6:1-45. 4. Duteille F, Duport G, Larregue M, et al. Malignant blue nevus: three new cases and a review of the literature. Ann Plast Surg 1998;41:674-8. 5. Connelly J. Smith JL Jr. Malignant blue nevus. Cancer 1991;67:2653-7. 6. Prieto VG, Shea CR. Use of immunohisto- chemistry in melanocytic lesions. J Cutan Pathol 2008;35 Suppl 2:1-10. 7. Shields CL, Fasiuddin AF, Mashayekhi A, Shields JA. Conjunctival nevi: clinical fea- tures and natural course in 410 consecu- tive patients. Arch Ophthalmol 2004;122: 167-75. 8. Grossniklaus HE, Green WR, Luckenbach M, Chan CC. Conjunctival lesions in adults: a clinical and histopathologic review. Cornea 1987;6:78-116. 9. McDonnell JM, Carpenter JD, Jacobs P, et al. Conjunctival melanocytic lesions in children. Ophthalmology 1989;96:986-93. 10. Alkatan HM, Arfaj KM, Maktabi A. Conjunctival nevi: clinical and histopatho- logic features in a Saudi population. Ann Saudi Med 2010;30:306-12. 11. Demirci H, Shields CL, Shields JA, Eagle RC Jr. Malignant melanoma arising from unusual conjunctival blue nevus. Arch Ophthalmol 2000;118:1581-4. 12. Leopold JG, Richards DB. The interrela- tionship of blue and common naevi. J Pathol Bacteriol 1968;95:37-46. Case Report Figure 1. External photograph shows a flat, hyperpigmented blue-black lesion with irregular borders deep in the stroma with no apparent vascularity. Figure 2. Conjunctival blue nevus. Heavily pigmented dendritic melanocytes located in the substantia propria with normal con- junctival epithelium and no evidence of acquired melanosis (hematoxylin-eosin, original magnification x 40). Figure 3. Plump, heavily pigmented spin- dle-shaped melanocytes with no junctional activity and no involvement of the conjunc- tival epithelium with small, elongated, and hyperchromatic nuclei (hematoxylin-eosin, original magnification x 200). Non -co mmerc ial us e o nly