Malignant Melanoma Arising from Unusual Conjunctival Blue Nevus

CLINICOPATHOLOGIC REPORT

SECTION EDITOR: W. RICHARD GREEN, MD Malignant Melanoma Arising From Unusual Conjunctival Blue Nevus

Hakan Demirci, MD; Carol L. Shields, MD; Jerry A. Shields, MD; Ralph C. Eagle, Jr, MD

ellular blue nevus is an uncommon pigmented tumor in the conjunctiva, where it generally appears as a deep, circumscribed, pigmented conjunctival mass. We report a case of conjunctival blue nevus that clinically resembled primary acquired melanosis and gave rise to conjunctival melanoma. A 41-year-old man developed a dif- fuseC pigmented mass in the inferior fornix of his left eye. Over a 20-year period, he noted slight progression of the pigment. Foci of epibulbar pigmentation were also present. The lesion resembled primary acquired melanosis. Excisional biopsy and adjuvant cryotherapy were performed. Histopathologic examination disclosed an intense infiltrate of heavily pigmented dendritic melanocytes with aggregates of less pigmented plump cells in the substantia propria. The conjunctival epithelium was normal. Malignant cellular features consistent with melanoma were observed in some foci. Cellular blue nevus of the conjunctiva can simulate primary acquired melanosis and can give rise to malignant melanoma. Arch Ophthalmol. 2000;118:1581-1584

Blue nevus is a relatively uncommon be- nant component. In a series of 150 con- nign pigmented lesion of the dermal me- secutive patients with conjunctival mela- lanocytes.1 Although blue nevus is classi- noma, we are not aware of any that arose cally considered to be a skin lesion, it has from blue nevus (personal observations). also been observed in the oral mucosa, va- We report the clinical and histopatho- gina, uterine cervix, axillary lymph nodes, logic findings of a patient with an un- and prostate.1-3 Blue nevus has the poten- usual cellular blue nevus of the conjunc- tial for malignant transformation into tiva that simulated primary acquired melanoma.2-4 melanosis (PAM) clinically and under- Blue nevus has rarely occurred in the went focal malignant transformation into conjunctiva, eyelids, orbit, episclera, and malignant melanoma. sclera.5-9 In a series of 2455 conjunctival lesions in adults, only 5 (1.5%) of 317 pigmented lesions were found to be blue ne- REPORT OF A CASE vus.10 Additionally, only 1 (1.6%) of 71 conjunctival melanocytic lesions in chil- A 41-year-old white man was referred to dren were blue nevi.11 Likewise, malig- the Oncology Service at Wills Eye Hospi- nant transformation of cutaneous blue ne- tal, Philadelphia, Pa, for evaluation of a vus into melanoma is very uncommon.5,12 patchy pigmented conjunctival lesion on To our knowledge, transformation of con- his left eye. The lesion was first detected junctival blue nevus into melanoma has when the patient was 21-years-old. Dur- not been reported.13 Crawford et al14 re- ing the subsequent 2 decades, the lesion cently reported that none of 30 cases progressed slightly and became more with combined blue nevi had a malig- confluent. Examination revealed a movable, dif- From the Oncology Service (Drs Demirci, C. Shields, and J. Shields) and the Pathology fuse, blue-black lesion that lined the en- Department (Dr Eagle), Wills Eye Hospital, Thomas Jefferson University, tire inferior fornix and inferior bulbar con- Philadelphia, Pa. junctiva. It appeared to be located deep

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©2000 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/23/2021 within the conjunctiva and had no Because of suspicion for PAM apparent nodularity, vascularity, or with conjunctival melanoma, we cysts (Figure 1). The caruncle, plica performed excisional biopsy with semilunaris, inferonasal bulbar con- no-touch technique and double- junctiva, and inferior and infero- freeze thaw cryotherapy to the sur- temporal limbal conjunctiva were all rounding conjunctiva.15 Multiple speckled with apparent intraepithe- map biopsies of the presumed nor- lial and superficial and deep subepi- mal conjunctival epithelium were thelial brown pigmentation. There performed. The conjunctiva was was corneal epithelial pigmenta- closed with bilimbal transposi- tion near the limbus inferiorly. Find- tional conjunctiva flaps. A sym- ings from the remainder of the ocu- blepharon ring was used to prevent Figure 1. Slitlamp biomicroscopy shows a lar examination were unremarkable. conjunctival adhesions with excel- movable, diffuse, blue-black lesion with no There was no preauricular or cervi- lent results. apparent vascularity, or cysts, that lined the cal lymphadenopathy and no cuta- Histopathologic examination entire fornix and inferior bulbar conjunctiva. neous blue nevi or dysplastic nevi. of the forniceal lesion revealed melanocytic proliferation in the substantia propria with no junc- tional or epithelial component (Figure 2). The cells showed a biphasic pattern with ovoid aggregates of less pigmented plump cells and intense infiltrate of heavily pigmented dendritic cells with bland nuclei (Figure 2 and Figure 3). The dendritic cells innocuously infiltrated the deep tissue sur- rounding the blood vessels and within the orbital fat. In one area, nuclear atypia indicative of malignant transformation into melanoma was present (Figure 4). Histo- pathologic examination of several limbal and bulbar conjunctival biopsies disclosed other smaller foci of pigmented cells consistent Figure 2. Conjunctival blue nevus. The substantia propria contains intense infiltrate of heavily pigmented with cellular blue nevus in the sub- dendritic melanocytes and several ovoid aggregates of less pigmented nevus cells. The conjunctival epithelium is normal without evidence of acquired melanosis (hematoxylin-eosin, original magnification stantia propria. The conjunctival ϫ10). epithelium contained no pigmentation or atypical hyperplasia. The patient has done well on 13 months of follow-up with no recurrence of melanoma or blue nevus.

COMMENT

Blue nevus cells are derived from melanocytes of neural crest origin that become arrested during the course of embryonic migration to the surface epithelium.13 When these pigmented dendritic melanocytes ag- gregate together as a distinct mass in the dermis, the lesion is called a blue nevus. The blue color of this cutaneous lesion is due to the Tyndall phenomenon, which is caused by ab- sorption of longer, less energetic A B wavelengths of visible light as they pass through the dermis.3 Figure 3. The blue nevus is composed of plump, heavily pigmented melanocytes with a spindled or dendriform configuration. Depigmentation (B) discloses bland nuclei in nevus cells (A, By convention, 2 well-defined hematoxylin-eosin; B, bleach; A and B, original magnification ϫ100). histopathologic variants of blue

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©2000 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/23/2021 nevus are recognized, designated as “common” and “cellular” blue nevus.1,3 However, other new and related entities, including combined nevus, deep penetrating nevus, compound blue nevus, atypical blue nevus, and malignant blue nevus, have been reported recently.2,3,14 Differentiation of the blue nevus from these related but rare entities is usually based on histopathologic features.2,3 Craw- ford and associates14 recently reported that combined blue nevus can occur in the conjunctiva, but the other variants of blue nevus are extremely rare in the conjunctiva. A B Among these variants of blue nevus, the cellular blue nevus rarely Figure 4. Focus of malignant transformation. Cells comprising focus of malignant melanoma found within blue nevus (B) have large pleomorphic nuclei with prominent nucleoli. (A, hematoxylin-eosin, undergoes malignant transforma- original magnification ϫ10; B, hematoxylin-eosin, original magnification ϫ250). tion into melanoma.12 Several forms of blue nevi can affect the epibulbar and adnexal only 1 case of blue nevus (1.6%) in Patients with orbital cellular tissues, including ocular melanocy- 71 conjunctival melanocytic le- blue nevus have been found to be tosis, common blue nevus, and cel- sions in children. Other studies have at risk for malignant transforma- lular blue nevus.13 These condi- confirmed the rarity of conjuncti- tion of the nevus into melano- tions are usually diagnosed at birth val blue nevi.17,18 ma.5,22 Primary orbital melanoma or shortly thereafter. Congenital The differential diagnosis of likely develops from congenital ocular melanocytosis is character- conjunctival blue nevus includes rests of cellular blue nevus in the ized by flat, slate-gray pigmentation common congenital and acquired orbit.22 Tellado et al22 found that 19 of the sclera, generally without nevus, congenital ocular melanocy- (90%) of 21 patients with orbital conjunctival involvement. Al- tosis, PAM, and malignant mela- melanoma had blue nevus of the though uveal melanoma, primary noma. Clinically, unlike the com- orbit. orbital melanoma, and leptomen- mon nevus, the blue nevus lacks The prognosis of melanoma ingeal melanoma have been cystic inclusions of conjunctival epi- arising from cutaneous blue nevus reported in patients with ocular thelium.13 In contrast to the flat, is poor, with a high incidence of re- melanocytosis affecting these tis- slate-gray episcleral pigmentation of currence and metastasis.4,12 Con- sues, conjunctival melanoma has ocular melanocytosis and the dif- nelly and Smith4 reported that 10 not been identified.13 Conjunctival fuse, brown epithelial pigmenta- (83%) of 12 patients with mela- blue nevus appears as a noncystic tion of PAM, cellular blue nevus gen- noma arising from blue nevus in the brown or black-blue mass in the erally is well-circumscribed and skin developed metastases over a stroma.13,16 Common blue nevus is located deep within the conjuncti- mean period of 40 months. Our composed of a uniform population val stroma.13 In our case, the blue ne- group described 2 patients with ex- of pigmented dendritic cells. Cellu- vus was atypical because it was dif- tensive periocular cutaneous and lar blue nevus shows a biphasic fuse and resembled PAM clinically. orbital cellular blue nevus who de- cellular pattern with lightly pig- Conjunctival melanoma can veloped orbital melanoma and even- mented nodules consisting gener- originate from PAM, a preexisting tually died of intracranial mela- ally of uniform spindle cells sur- conjunctival nevus, or de novo.19,20 noma in both cases.5 The overall rounded by heavily pigmented Our group recently reviewed 150 survival for conjunctival mela- dendritic melanocytes. As observed cases of conjunctival melanoma noma is 69% to 87% at 10 years.23 in our case, malignant changes and found histopathologic evi- Since the focus of melanoma in our tend to occur in the central oval or dence of possible origin from pre- patient is relatively small, we are un- spindle cells, which are considered existing nevus in 4%, PAM in 57%, certain about the risk for meta- to be immature and have greater and de novo in 39%. There were no static disease. malignant potential.12 cases of conjunctival melanoma In summary, the unusual case Common blue nevus and cel- arising from cellular blue nevus.21 reported here documents a cellular lular blue nevus are extremely un- Folberg et al19 found the distribu- blue nevus, which simulated PAM common in the conjunctiva.13 tion of nevus in 20%, PAM in 75%, clinically, and eventually devel- Grossniklaus et al10 reported 5 cases and de novo in 5%. In the case pre- oped into malignant melanoma. of blue nevus (1.5%) in 317 pig- sented here, a focus of conjunctival We believe that patients with sus- mented conjunctival lesions in melanoma originated in the cellu- picious, pigmented conjunctival adults. McDonnell et al11 observed lar blue nevus. lesions should have wide exci-

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©2000 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/23/2021 sional biopsy and adjuvant cryo- ential diagnostic review. Pathol Res Pract. 1994; nevi of the conjunctiva. Arch Ophthalmol. 1999; therapy. 190:627-635. 117:1121-1127. 3. Barnhill RL. Textbook of Dermatopathology. New 15. Shields JA, Shields CL, DePotter P. Surgical ap- York, NY: McGraw-Hill Inc; 1998:560-564 proach to conjunctival tumors: the 1994 Lynn B. Accepted for publication March 21, 4. Connelly J, Smith JL Jr. Malignant blue nevus. Can- McMahan Lecture. Arch Ophthalmol. 1997;115: 2000. cer. 1991;67:2653-2657. 808-815. Support for this study was pro- 5. Gunduz K, Shields JA, Shields CL, Eagle RC Jr. 16. Shields JA, Shields CL. Atlas of Eyelid and Con- Periorbital cellular blue nevus leading to orbito- junctival Tumors. Philadelphia, Pa: Lippincott Willi- vided by the International Award of palpebral and intracranial melanoma. Ophthal- ams & Wilkins; 1999:250-251. Merit in Retina Research, Houston, Tex mology. 1998;105:2046-2050. 17. Jay B. Naevi and melanomata of the conjunctiva. (Dr J. Shields), Lions Eye Bank, Phila- 6. Shields JA. Diagnosis and Management of Or- Br J Ophthalmol. 1965;49:169-204. delphia, Pa (Drs J. Shields and C. bital Tumors. Philadelphia, Pa: WB Saunders Co; 18. Jakobiec FA, Zuckerman BD, Berlin AJ, Odell P, 1989:275-287. MacRae DW, Tuthill RJ. Unusual melanocytic nevi Shields), Macula Foundation (Dr C. 7. Smith TR, Brockhurst RJ. Cellular blue nevus of of the conjunctiva. Am J Ophthalmol. 1985;100: Shields), and the Noel T. and Sara L. the sclera. Arch Ophthalmol. 1976;94:618-620. 100-113. Simmonds Endowment for Ophthal- 8. Blicker JA, Rootman J, White VA. Cellular blue ne- 19. Folberg R, McLean IW, Zimmerman LE. Primary mic Pathology, Wills Eye Hospital (Dr vus of the conjunctiva. Ophthalmology. 1992;99: acquired melanosis of the conjunctiva. Hum Pathol. Eagle), and the Eye Tumor Research 1714-1717. 1985;16:136-143. 9. Eller AW, Bernardino VB Jr. Blue nevi of the con- 20. Grossniklaus HE, Margo CE, Solomon AR. Foundation, Philadelphia, Pa. junctiva. Ophthalmology. 1983;90:1469-1471. Indetermine melanocytic proliferations of the Corresponding author: Carol L. 10. Grossniklaus HE, Green WR, Luckenbach M, conjunctiva. Arch Ophthalmol. 1999;117:1131- Shields, MD, Oncology Service, Wills Chan CC. Conjunctival lesions in adults: a clinical 1136. Eye Hospital, 900 Walnut St, Phila- and histopathologic review. Cornea. 1987;6:78- 21. Shields CL, Shields JA, Gunduz K, et al. Con- 116. junctival melanoma: risk factors for recurrence, delphia, PA 19107. 11. McDonnell JM, Carpenter JD, Jacobs P, Wan LW, exenteration, metastasis and death in 150 con- Gilmore JE. Conjunctival melanocytic lesions in secutive patients. Trans Am Ophthalmol Soc.In REFERENCES children. Ophthalmology. 1989;96:986-993. press. 12. Aloi F, Pich A, Pippione M. Malignant cellular blue 22. Tellado M, Specht CS, McLean IW, Grossniklaus nevus: a clinicopathological study of 6 cases. Der- HE, Zimmerman LE. Primary orbital melanomas. 1. Lever WF, Schaumburg-Lever G. Histopathology matology. 1996;192:36-40. Ophthalmology. 1996;103:929-932. of the Skin. Philadelphia, Pa: JB Lippincott; 1990: 13. Folberg R, Jakobiec FA, Bernardino VB, Iwamoto 23. Norregaard JC, Gerner N, Jensen OA, Prause JU. 776-796. T. Benign conjunctival melanocytic lesions: clini- Malignant melanoma of the conjunctiva: occur- 2. Gonzalez-Campora R, Galera-Davidson H, copathologic features. Ophthalmology. 1989; 96: rence and survival following surgery and radio- Vazquez-Ramirez FJ, Diaz-Cano S. Blue nevus: 436-461. therapy in a Danish population. Graefes Arch Clin classical types and new related entities: a differ- 14. Crawford JB, Howes EL Jr, Char DH. Combined Exp Ophthalmol. 1996;234:569-572.

From the Archives of the ARCHIVES

A look at the past. . .

u¨ ller reports from the Giessen clinic 80 cases of perforating injury of the ball treated with sutures. In 61 patients the ball was preserved; M in 17 it was enucleated later, six times for suppuration in the vitreous, and in the other cases for foreign bodies, rupture of the posterior pole, etc. Sutures prevent loss of vitreous and secondary infection, and secure a smooth union of the edges of the wound, thus shortening the healing process.

Reference: Arch Ophthalmol. 1898;27:575.

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