title: Conjunctival Primary Acquired Melanosis: Is It Time for a New Terminology?
abstract: OBJECTIVE
  To review the diagnostic categories of a group of conditions referred to as "primary acquired melanosis."
  
  
  METHODS
  Literature review on the subject and proposal of an alternative diagnostic schema with histopathologic and immunohistochemical illustrations.
  
  
  METHODS
  Standard hematoxylin-eosin-stained sections and immunohistochemical stains for MART-1, HMB-45, microphthalmia-associated transcription factor (MiTF), and Ki-67 for calculating the proliferation index are illustrated.
  
  
  RESULTS
  "Melanosis" is an inadequate and misleading term because it does not distinguish between conjunctival intraepithelial melanin overproduction ("hyperpigmentation") and intraepithelial melanocytic proliferation. It is recommended that "intraepithelial melanocytic proliferation" be adopted for histopathologic diagnosis. Atypical proliferations are characterized either by bloated dendritic melanocytes with enlarged cell components (dendrites, cell bodies, and nuclei) or by epithelioid melanocytes without dendrites. Atypical polygonal or epithelioid pagetoid cells may reach higher levels of the epithelium beyond the basal layer. Immunohistochemistry defines the degree of melanocytic proliferation or the cellular shape (dendritic or nondendritic) (MART-1, HMB-45) or identifies the melanocytic nuclei (MiTF). Intraepithelial melanocytic proliferation without atypia represents increased numbers of normal-appearing dendritic melanocytes (hyperplasia or early neoplasia) that generally remain confined to the basal/basement membrane region. Intraepithelial nonproliferative melanocytic pigmentation signifies the usually small number of conjunctival basal dendritic melanocytes that synthesize increased amounts of melanin that is transferred to surrounding keratinocytes.
  
  
  CONCLUSIONS
  All pre- and postoperative biopsies of flat conjunctival melanocytic disorders should be evaluated immunohistochemically if there is any question regarding atypicality. This should lead to a clearer microscopic descriptive diagnosis that is predicated on an analysis of the participating cell types and their architectural patterns. This approach is conducive to a better appreciation of features indicating when to intervene therapeutically. An accurate early diagnosis should forestall unnecessary later surgery.
authors.affiliation: David G. Cogan Laboratory of Ophthalmic Pathology, Massachusetts Eye and Ear Infirmary and the Department of Ophthalmology, Massachusetts Eye and Ear Infirmary and Harvard Medical School, Boston, Massachusetts. Electronic address: Fred_Jakobiec@meei.harvard.edu.
authors.forename: Frederick A
authors.initials: FA
authors.lastname: Jakobiec
mesh_terms: D015415:Biomarkers / Q000378:metabolism; D003229:Conjunctival Diseases / Q000145:classification / Q000175:diagnosis* / Q000378:metabolism; D003230:Conjunctival Neoplasms / Q000145:classification / Q000175:diagnosis / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000378:metabolism; D058965:MART-1 Antigen / Q000378:metabolism; D058950:Melanoma-Specific Antigens / Q000378:metabolism; D008548:Melanosis / Q000145:classification / Q000175:diagnosis* / Q000378:metabolism; D051739:Microphthalmia-Associated Transcription Factor / Q000378:metabolism; D009508:Nevus, Pigmented / Q000145:classification / Q000175:diagnosis / Q000378:metabolism; D009626:Terminology as Topic; D058951:gp100 Melanoma Antigen
chemical_list: D015415:Biomarkers; D019394:Ki-67 Antigen; D058965:MART-1 Antigen; C497234:MITF protein, human; C548667:MLANA protein, human; D058950:Melanoma-Specific Antigens; D051739:Microphthalmia-Associated Transcription Factor; C548637:PMEL protein, human; D058951:gp100 Melanoma Antigen