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Primary Acquired Melanosis (PAM) with Atypia: Pathology and Clinical Correlations

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Title: Primary Acquired Melanosis (PAM) with Atypia: Pathology and Clinical Correlations

Author (s): Jack Li, BA


Date: 9/12/2016


Figure A: External photography of the eye in a patient with primary acquired melanosis. Diffuse melanosis of varying degrees of pigmentation noted.

Figure B: The same eye after surgical excision and cryotherapy. The melanotic lesions have been removed.

Figure C: Medium magnification H&E stain of the conjunctiva. Stratified squamous non-keratinized epithelium is observed. Melanin-laden cells are noted near the basement membrane. Atypical cells are appreciated clustered near the basement membrane.

Figure D: Mid-high magnification of H&E stain of the conjunctiva. Atypical cells can be appreciated mid-way through the epithelium. However, atypical cells have not invaded the entire depth of the epithelium.

Secondary CORE Category: Ophthalmic Pathology / Conjunctiva

Keywords/Main Subjects: Primary Acquired Melanosis, Melanocytic Lesions of Ocular

Diagnosis: Primary Acquired Melanosis with Atypia

Description of Images:

Primary acquired melanosis (PAM) of the conjunctiva is a pigmented lesion of the conjunctiva that is flat, painless and non-cystic. PAM typically occurs unilaterally, is more likely to occur in lightly pigmented individuals and is most likely to present in the 6th decade of life. PAM represents 11% of all conjunctival tumors and 21% of all conjunctival melanocytic lesions1. Figure A is the external photography of a 60-year-old female with approximately 13-year history of PAM of the conjunctiva. Features associated with PAM include unilaterality, waxing and waning of size and pigment over time and a mottled or dusted pigmented appearance. PAM most commonly occurs on the bulbar conjunctiva, limbal conjunctiva and cornea. The typical patient is a Caucasian adult presenting around 60 years of age. PAM is divided histopathologically into PAM with or without atypia. PAM with atypia has a high chance of progression into melanoma while PAM without atypia has little chance of progressing to melanoma2. Biopsy and histopathologic examination allow determination of the presence or absence of atypia. Because PAM with atypia has significant risk of progression into melanoma, a potentially lethal tumor, surgical and medical intervention is warranted. Figure B represents the same patient after excision of the lesion and cryotherapy.

PAM without atypia is defined as pigmentation of the conjunctival epithelium with or without benign melanocytic hyperplasia. PAM with atypia is characterized by the presence of atypical melanocytic hyperplasia. Mild atypia is defined as atypical melanocytes confined to the basal layer of the epithelium; severe atypia is defined as atypical melanocytes that extend into the superficial non-basal portion of the epithelium and may contain epitheloid cells1. Figure C and D are low and medium H&E photomicrographs of the specimen obtained from the patient where pigmentation along the basal layer of the epithelium can be appreciated. One can appreciate the extension of atypical melanocytes mid-way into the epithelium, qualifying this lesion to be PAM with severe atypia.

Atypia is determined by cytological features and growth patterns that are associated with malignant potential. Four types of atypical melanocytes include the small polyhedral cells, epitheloid cells, dendritic cells, and spindle cells. Polyhedral cells contain small, round nuclei with little cytoplasm. Epitheloid cells contain abundant eosinophilic cytoplasm. Spindle cells are aligned such that the long axis are parallel to the basement membrane. Dendritic cells are large cells with complex branching dendrites found along the basilar layer3.

The mainstay of treatment of PAM with atypia is wide excision of the lesion and cryotherapy of the borders of the lesions. Amniotic graft can be applied to the surgical site to facilitate healing. Topical chemotherapy, most commonly with mitomycin-c, can be used as adjuvant therapy in cases of diffuse lesion, positive surgical margins, large lesions that cannot be completely removed, or in cases of recurrent disease2. Interferon a-2b has shown promise as a medical management. A six-week trial showed that successive application of interferon a-2b resulted in shrinking of PAM4.


  1. Shields, J. A. et al. Primary acquired melanosis of the conjunctiva: experience with 311 eyes. Trans. Am. Ophthalmol. Soc. 105, 61-71–2 (2007).
  2. Oellers, P. & Karp, C. L. Management of pigmented conjunctival lesions. Ocul. Surf. 10, 251–263 (2012).
  3. Folberg, R., McLean, I. & Zimmerman, L. Primary acquired melanosis of the conjunctiva. Hum. Pathol. 16, 129–35 (1985).
  4. Garip, A. et al. Evaluation of a short-term topical interferon α-2b treatment for histologically proven melanoma and primary acquired melanosis with atypia. Orbit 35, 29–34 (2016).

Faculty Approval by: Amy Lin, MD; Griffin Jardine, MD

Identifier: Moran_CORE_23807

Disclosure (Financial or other): None

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