Conjunctival Melanoma arising from Primary Acquired Melanosis (PAM):

61 year-old Caucasian female presenting for evaluation of corneal mass OS found on routine exam ~2 months previous

Jeffrey Maassen, M.D., Kenneth Goins, M.D.

February 21, 2005

Chief Complaint: 61 year-old Caucasian female presenting for evaluation of corneal mass OS found on routine exam ~2 months previous.

History of Present Illness: Patient was unaware of lesion when initially discovered. She denied pain or visual changes. Denied any growth of the lesion since discovery. She lives at a residential care facility.

PMH/FH/POH: schizophrenia, diabetes, and myopia. Medications: escitalopram oxalate, mupirocin, valproic acid, metformin, quetiapine fumarate, docusate, glipizide, lorazepam, and insulin.

EXAM

• Best corrected visual acuities: 20/20 OD and 20/50 OS.
• W: -4.25+1.25 X 081 OD, -4.75+1.25 X 166 OS
• mRx: -3.25+3.00 X 066 OS (20/20)
• Pupils: normal, no RAPD
• Confrontational VF: normal
• EOM: normal
• IOP: normal
• SLE: 3+ NS cataract OD, see below for OS.
• DFE: normal OU.
• ON: normal OU.

Figure 1

OS	OS
Pigmented, elevated, fleshy mass on conjunctiva and extending onto the cornea. There is a sentinel vessel feeding the lesion.	Magnified view of the lesion denoting elevation and vascularity.

Figure 2

Pathology of Lesion	PAM with atypia
Low powered view of lesion after excision from cornea and conjunctiva. There are areas of hypercellularity (blue cells) and inflammation.	Higher magnified view of the conjunctival epithelium denoting cellular atypia, discohesiveness, and nesting. These areas were Primary Acquired Melanosis (PAM) with atypia.

Figure 3

Pathology of Lesion	Nesting of Melanocytes
Invasive cells with abnormal, large nuclei. These cells tend to spread in a pagetoid pattern and nested into groups.	Atypical melanocytes with large nuclei and pigment forming nests.

Figure 4. MART (Melanoma Antigen Recognized by T-cells) - 1 Positive

Melanocytic cells were positive for MART-1.

Discussion

Conjunctival Melanoma

This conjunctival melanoma likely developed from primary acquired melanosis (PAM) with atypia and then grew onto the superficial surface of the cornea. In 1980, the WHO proposed the term PAM to describe this disorder. The term "primary" distinguished these lesions from complexion related, post-inflammatory, or systemic disease, and the term "acquired" distinguished these lesions from congenital. PAM has been suggested to be a precancerous melanosis, and lesions identified as PAM with atypia will have a 50% chance of progressing to a melanoma. PAM with atypia has a high recurrence rate if there is incomplete excision or corneal involvment.

Robert Folberg, M.D. described the following clinically significant histologic features of PAM: basilar hyperplasia (confined to basilar epithelium); basilar nests (anchored at basilar layer); intraepithelial nests (within epithelium, not anchored), pagetoid (individual melanocytes suprabasally); and in situ (full thickness). He also described cell types and atypia grade: small polyhedral (small round nuclei, scant cytoplasm - mild atypia); epithelioid (abundant cytoplasm - moderate atypia); spindle (large atypical cells perpendicular to the basement membrane - severe atypia); and, polymorphic (all of the above). In a study of 131 cases of conjunctival melanoma, 98 cases were associated with PAM and 33 cases were not associated with PAM. Of the 131 cases, 26% of the patients died from melanoma.

According to Dr. Folberg, risk factors for death from metastasis include:

• Pagetoid growth of the PAM component.
• Palpebral conjunctival/caruncular involvement.
• Rarity of polyhedral melanocytes.
• Moderate to severe atypia.
• Tumor thickness >0.8 mm.
• 90% with basilar hyperplasia leading to malignant melanoma.
• 75% with epithelioid features leading to malignant melanoma.

Corneally displaced malignant melanomas are extremely rare. There are only 4 reported cases in the Finnish Cancer Registry between 1967 and 2000.

Diagnosis: Conjunctival Melanoma

EPIDEMIOLOGY Rare. 206 newly diagnosed patients with conjunctival melanoma from 1973 to 1999 in the US. Fair skinned individuals are at higher risk.	SIGNS Pigmented lesion. May be non-pigmented in an amelanotic melanoma. Invasive. Growth. Irregular borders. Indistinct margins. Sentinel vessel feeding the lesion. May be associated with ocular melanosis.
SYMPTOMS May be asymptomatic. Change in refractive error if affecting the cornea. Beware of metastases to: pre-auricular and submandibular nodes, lymph nodes, skin, bone, viscera, lung, brain, and liver.	TREATMENT Incisional biopsy reasonable to determine type of tumor. Definitive therapy with excisional biopsy with wide margins. Cryotherapy to lesion after excision. Mitomycin C therapy to lesion after excision. Patient should get follow-up chest X-rays, blood tests for liver enzymes, and PET scan or MRI if indicated.

Differential Diagnoses

• Melanoma
• Nevus
• Squamous cell carcinoma