Jerry A. Shields
BASICS
DESCRIPTION
• Primary acquired melanosis (PAM) is an acquired flat pigmentation of the conjunctiva.
• Slowly progressive
• Generally without excessive vascularity
• Can affect the limbus, bulbar, forniceal, plical, caruncular, and tarsal conjunctiva
• Unilateral and nonhereditary
• Risk for development of conjunctival melanoma
ALERT
Any patient with a new onset flat pigmented conjunctival lesion should be examined to evaluate for primary acquired melanosis, a known precursor to melanoma.
Geriatric Considerations
Generally a disease of middle aged or older individuals.
Pediatric Considerations
This condition is rarely found in children.
Pregnancy Considerations
This condition is rarely seen during pregnancy.
RISK FACTORS
None clearly identified but patients at highest risk are those of:
• Caucasian race
• Older age
• Excessive sunlight exposure
GENERAL PREVENTION
Avoid excess sunlight exposure.
PATHOPHYSIOLOGY
• Begins as a flat area of pigmentation on the conjunctival surface. Histopathology shows it arising in the basal epithelial layers. As it progresses, the atypical cells involve the mid portion and then superficial portion of the conjunctival epithelium. With time, the anaplastic cells can grow through the basement membrane into the stroma and be classified then as microscopically invasive melanoma.
• Slowly and progressively enlarging pigmented conjunctival tumor
COMMONLY ASSOCIATED CONDITIONS
Lentigo maligna of eyelid skin that carries a 20% risk for cutaneous melanoma.
DIAGNOSIS
HISTORY
• Most patients note an area of pigmentation that slowly evolves and grows over time.
• Based on an analysis of 311 eyes with PAM by Shields and associates, the patient demographics include:
– Female in 44%, male in 38%
– Caucasian in 96%, African American in 1%, Hispanic in 2%, and Asian in <1%
– Unilateral in 87%, bilateral in 13%
– Eye color brown in 58%, blue in 35%, green in 5%
– Mean patient age 56 years (range 15–90)
• Patient symptoms include:
– Spot stable on eye in 29%
– Spot growing on eye in 16%
– Ocular redness in 1%
– No symptom in 55%
PHYSICAL EXAM
• Ocular examination, based on analysis of 311 eyes shows:
• Number (mean) of PAM per eye 2 (1–7)
• Quadrant location superior in 37%, temporal in 57%, inferior in 45%, nasal in 42%
• Anatomic location of PAM in cornea in 23%, limbal conjunctiva in 55%, fornix in 13%, palpebra in 12%, caruncle in 11%
• Extent (mean) of PAM in clock hours of 3
DIAGNOSTIC TESTS & INTERPRETATION
Lab
Initial lab tests
• None other than ocular exam
• If there is associated melanoma then the patient should have lymph node evaluation and chest x-ray.
Follow-up & special considerations
Careful follow-up is warranted for evolution of PAM into melanoma. Based on clinical studies, untreated PAM evolves into melanoma in 0% of those with minimal or no atypia and 13% of those with severe atypia. Based on pathology studies, PAM evolves into melanoma in 0% of those with no atypia, 46% if any atypia, and 75–90% of those with severe atypia.
Imaging
Initial approach
For PAM alone, anterior segment optical coherence tomography might be beneficial to demonstrate the lack of deep involvement.
Follow-up & special considerations
If there is conversion to melanoma then imaging with MRI is warranted.
Diagnostic Procedures/Other
• Some authorities prefer no manipulation of the conjunctiva prior to surgical treatment in the operating room.
• Other authorities wish to have superficial scraping of the conjunctival for cytologic documentation.
Pathological Findings
• Pathology reveals 2 basic types of PAM, those without atypia and those with atypia.
• PAM without atypia is defined as pigmentation of the conjunctival epithelium, usually the basal layer, with benign melanocytic hyperplasia.
• PAM with atypia is defined as the presence of atypical melanocytic hyperplasia in a mild, moderate, or severe form with gradually extension from the basal portion of the epithelium to the more superficial portion in a pagetoid fashion.
DIFFERENTIAL DIAGNOSIS
• Racial melanosis (also referred to as complexion related melanosis)
• Conjunctival nevus
• Conjunctival melanoma
• Secondary conjunctival pigmentation from medications (argyrosis), exposure, trauma (shrapnel injury)
TREATMENT
MEDICATION
First Line
• First line therapy for PAM requires biopsy proof of the condition. Our first choice is to biopsy and provide cryotherapy to all sites of pigmentation. If the PAM is completely resectable, then that would be our first choice. Closure of all wounds is advised following therapy.
• Regarding medications, Mitomycin C (MMC) 0.02% or 0.04% can be given 4 times daily for 1–2 weeks then 1–2 weeks of drop-free recovery. This can be repeated as need be. MMC can effectively reduce the pigmentation and can be used as a primary or adjuvant therapy.
• 5 Fluorouracil and interferon have been used to treat PAM.
Second Line
If there is extensive PAM with multiple recurrences, consideration for custom fit plaque radiotherapy in a conformer design can effectively treat the entire surface of the eye in a fairly homogeneous fashion.
ADDITIONAL TREATMENT
General Measures
Topical lubricants are given to help heal the ocular surface following surgery, cryotherapy, or topical chemotherapy.
Issues for Referral
All patients with PAM should be managed by consultants familiar with this condition as this precancerous disease carries a strong risk for life-threatening melanoma.
SURGERY/OTHER PROCEDURES
• Surgery is usually the main initial procedure for PAM. The treatment strategy depends on the extent of tumor and the presence or history of previous melanoma. Patients are discharged the same day following therapy.
• If PAM is <1 clock hour, its significance remains debatable and most would observe it.
• PAM is 4–5 clock hours or less, consideration is given for complete resection followed by cryotherapy of the remaining conjunctival margins and closure with absorbable sutures.
• If PAM is >5 clock hours then wide resection of the suspicious areas is performed with heavy double freeze thaw cryotherapy to all residual areas of pigmentation. This can be used for PAM involving the entire ocular surface, except the cornea.
• If cornea PAM, then epithelial removal following topical absolute alcohol with microscopic monitoring is performed.
• If recurrent extensive PAM, then topical MMC is considered.
• If there is a history of conjunctival or cutaneous melanoma, then complete treatment is encouraged to the point that the patient shows no conjunctival pigmentation at all.
ONGOING CARE
FOLLOW-UP RECOMMENDATIONS
Return visits initially every 3–4 months and after stability documented, then every 6 months for life.
Patient Monitoring
Monitor the ocular surface for PAM using slit-lamp biomicroscopy.
PATIENT EDUCATION
If the patient notices recurrent pigmentation, then return visit is justified.
PROGNOSIS
• Excellent if there is no transformation into melanoma
• Guarded if there is transformation into melanoma
COMPLICATIONS
• Dry eye
• Symblepharon
• Blepharoptosis
• Diplopia
• Limbal stem cell loss
• Conjunctival overgrowth onto cornea
• Chronic pain
• Loss of the eye
ADDITIONAL READING
• Shields JA, Shields CL, Mashayekhi A, et al. Primary acquired melanosis of the conjunctiva. Risks for progression to melanoma in 311 eyes. The 2006 Lorenz E. Zimmerman Lecture. Ophthalmology 2008;115(3):511–519.
• Shields CL, Shields JA. Conjunctival primary acquired melanosis and melanoma. Tales, fairy tales and facts. Ophthal Plast Reconstr Surg 2009;25:167–72.
• Folberg R, McLean IW, Primary acquired melanosis and melanoma of the conjunctiva: Terminology, classification, and biologic behavior. Hum Pathol 1986;76:307–8.
• Shields JA, Shields CL. Eyelid, Conjunctival and orbital tumors: An atlas and text, 2nd ed. Philadelphia: Lippincott, Williams and Wilkins, 2008.
See Also (Topic, Algorithm, Electronic Media Element)
CODES
ICD9
• 190.3 Malignant neoplasm of conjunctiva
• 372.55 Conjunctival pigmentations
CLINICAL PEARLS
• Any patient with PAM of more than 1 clock hour should have consultation by an experienced examiner.
• If a patient with previous skin or conjunctival melanoma shows evidence of PAM, then eradication of PAM is warranted.
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