Case Presentation

Horacio M. Tous, M.D. PG-Y III Department of Ophthalmology University of Puerto Rico Case Presentation

Chief complaint • Painless, progressive growth of a brownish mass in the left eye since almost 1 year ago.

History of present illness • 60 y/o female with hypertension, no allergies, who referred painless, progressive growth of a brownish mass in the temporal aspect of the left eye since almost 1 year ago. Denies any prior ocular surgeries or trauma in that eye.

Review of systems

Eye physical exam

Left eye

Conjunctival pigmented lesions • Diferential diagnosis: • Benign pigmented lesions • Bening acquired melanosis • Ocular melanocytosis • Nevus • Preinvasive pigmented lesions • Primary acquired melanosis • Malignant pigmented lesions • Melanoma

Benign acquired melanosis • Characterized by light brown pigmentation of the perilimbal and interpapebral bulbar conjunctiva of both eyes and is commonly seen in individuals with dark skin. • Streaks and whorls called striate melanokratosis can extend into the peripheral cornea

Ocular melanocytosis • Congenital melanocytosis of the episclera is more common in the black, Hispanic and Asians populations • Consists of focal proliferation of subepithelialmelanocytes • Patches of episclera pigmentation appears slate gray through the normal conjunctiva and are nonmobile • Malignant transformation is possible but rare and seems to occur only in white patients.

Ocular melanocytosis • Can present with ipsilateral dermal melanocytosis (nevus of Ota), a proliferation of dermal melanocytes in the periocular skin of the 1st and 2nd dermatome of CN V. • The combined ocular and cutaneous pigmentations are referred to as oculodermal melanocytosis. • Secondary glaucoma occurs in the affected eye in 10% of patients.

Nevus • Nevocellular nevi of the conjunctiva are hamartia that arise during childhood and adolescence • Nevi may become enlarged and can be affected by hormonal changes such as in puberty or pregnancy. • Pigmentation is variable, they may be light tan in color or amelanotic.

Nevus • Small epithelial inclusion cysts occur within about half of all conjunctival nevi. • Secretion of mucin by globlet cells in the cyst can cause a nevus to enlarge, producing a false impression of malignant change • Nevi, rarely become malignant • Excisional biopsy should be performed for suspicious appearing lesions, other than prolong observation or sequential photography

Primary acquired melanosis • Unilateral flat brown patches of noncystic pigmentation appearing over the superficial conjunctiva • Typically develops in middle-aged or elderly white patients. • Changes in size may be associated with inflammation or hormonal influences.

Primary acquired melanosis • Malignant transformation should be suspected when a lesion shows nodularity, enlargement or increased vascularity • Excisional biopsy should be performed for large, progressive or dark lesions • All palpebral conjuctival lesions should be excised • Regional lymph nodes should be checked regularly

Primary acquired melanosis Primary acquired melanosis of the conjunctiva: risks for progression to melanoma in 311 eyes. Shields JA, Shields CL, Mashavekhi A, Marr BP, Benavides R, Thangappan A, Phan L, Eagle RC Jr. Ophthalmology. 2008 Mar;115(3):511-519.e2. • Primary acquired melanosis without atypia or with mild atypia shows 0% progression to melanoma, whereas PAM with severe atypia shows progression to melanoma in 13%

Melanoma • Malignant melanoma of the conjunctiva presents as a raised, pigmented or nonpigmented lesion that appears most commonly in white patients in their early 50s • May arise from acquired nevi (25%), from PAM (50-75%), or from clinically normal conjunctiva (25%) • Accounts for only 2% of all ocular malignancies.

Melanoma • Is uncommon but potentially lethal. • The overall tumor-related mortality rate is 25%. This rate increases to 40-44% if the tumor arose from PAM with an intraepithelial pagetoid growth pattern. • Although it can metastasize, it has better prognosis than cutaneous melanoma • In addition to spread by lymphatics and the bloodstream, direct extension to the eyeball and orbit occurs. • This tumor tends to spread first to the parotid or submandibular nodes. • The most frequent site of metastasis is the lung, followed by the liver, brain, and bone.

Melanoma • Because heavy vascularization is common, these tumors may bleed easily • Bulbar conjunctival melanomas have a better prognosis than melanomas of the palpebral conjunctiva, fornix or caruncle • A melanoma can be distinguished from PAM by its tendency to become fixed to the underlying tissues

Melanoma • Excisional biopsy should be considered for any suspicious pigmented epibulbar lesions; biopsy seems not to increase the risk of metastasis • The recommended treatment comprises: • excision of conjunctiva 4mm beyond the clinically apparent margins of the tumor, • along with a thin lamellar scleral flap beneath the tumor, • treatment of the remaining sclera with absolute alcohol, and • cryotherapy applied to the conjunctival margins • Primary closure is performed when feasible, but conjunctival or amniotic membrane grafts are necessary for large excisions

Melanoma staging • Clinical staging: The assessment is based on inspection; slit lamp examination; palpation of the regional lymph nodes; and, when indicated, radiologic (including computed tomography) and ultrasonographic examination of the orbit, paranasal sinuses, and chest. • Pathologic staging: Complete resection of the primary site is indicated. Histologic study of the margins and the deep aspect of resected tissues is necessary. Resection or needle biopsy of enlarged regional lymph nodes or orbital masses is desirable.

Melanoma staging • Clinical classification (cTNM) • Primary tumor (T) • TX - Primary tumor cannot be assessed. • TO - No evidence of primary tumor • T1 – Tumor of bulbar conjunctiva • T2 – Tumor of bulbar conjunctiva with corneal extension • T3 – Tumor extending into the conjunctival fornix, palpebral or caruncle • T4 - Tumor invades eyelid, globe, orbit, sinuses or CNS • Regional lymph nodes (N) • NX - Regional lymph nodes cannot be assessed. • N0 - No regional lymph node metastasis • N1 - Regional lymph node metastasis • Distant metastasis (M) • MX - Distant metastasis cannot be assessed. • M0 - No distant metastasis • M1 - Distant metastasis

Melanoma staging • Pathologic classification (pTNM) • Primary tumor (pT) • pTX - Primary tumor cannot be assessed. • pT0 - No evidence of primary tumor • pT1 – Tumor of bulbar conjunctiva confined to the epithelium • pT2 – Tumor of bulbar conjunctiva (0.8mm in thickness with invasion of the substantiapropia) • pT3 – Tumor of the bulbar conjunctival > 0.8mm in thickness with invasion of the substantiapropia or tumors involving palpebral or caruncular conjunctiva • pT4 - Tumor invades eyelid, globe, orbit, sinuses or CNS • Regional lymph nodes (pN) • pNX - Regional lymph nodes cannot be assessed. • pN0 - No regional lymph node metastasis • pN1 - Regional lymph node metastasis • Distant metastasis • pMX - Distant metastasis cannot be assessed. • pM0 - No distant metastasis • pM1 - Distant metastasis

Conjunctival pigmentary lesions

Our patient • Initially came by ER consult: • Evaluated at our OPH ASEM clinics • Chest x ray ordered • CT scan Abdomen ordered • CBC, CMP, Coagulation panel, U/A • Evaluation by cornea specialist next day

Our patient • All labs results within normal limits • Chest x-ray and abdominal CT Scan, negative for metastasis • Scheduled for excisional biopsy: • Excisional biopsy, conjunctivoplasty and lamellar keratectomy

Pathology slide

Our patient: • Pathology report: • Malignant melanoma • Did not mention margin status • Immunostains • S-1OO: Positive (neuroectodermal origin) • HMB45: Positive focal (melanocytic lesions) • Melan A: Positive

Our patient • Good post op • No evidence of recurrence • No lymphadenopathy • Excellent best corrected visual acuity in both eyes 20/25 • Being followed also by primary MD

Questions? • Thank you

Case Presentation