Melanocytic tumors

Primary acquired melanosis

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Last staff update: 27 May 2022

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PubMed Search: Primary acquired melanosis

Deepali Jain, M.D.
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Cite this page: Jain D. Primary acquired melanosis. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/eyepamconj.html. Accessed September 21st, 2023.
Definition / general
  • See also benign melanosis
  • 11% of conjunctival melanocytic proliferations (Arch Pathol Lab Med 2010;134:1785)
  • Called melanoma in situ by some, although cases without atypia don't progress (Mod Pathol 1991;4:253)
  • Variable biologic behavior from benign to locally spreading to malignant
  • Usually ages 40+ years, whites
  • Presents as gradual appearance of golden brown pigmented lesion of bulbar conjunctiva
  • May be associated with Addison disease
  • May be contiguous with lentigo maligna (similar histology but with rete pegs) of adjacent eyelid skin
  • May involve pseudoglands of Henle in palpebral conjunctiva and resemble invasive melanoma
Conjunctival melanocytic intra-epithelial neoplasia (C-MIN)
  • Conjunctival melanosis now differentiated histologically into hypermelanosis and conjunctival melanocytic intra-epithelial neoplasia (C-MIN)
  • Cases formerly classified as PAM are now classified as C-MIN:
    • C-MIN score of 0 is melanosis only
    • C-MIN score of 1 is PAM with mild atypia
    • C-MIN score of 2 - 3 is PAM with moderate atypia
    • C-MIN score of 4 is PAM with severe atypia
    • C-MIN score of 5+ is Conjunctival melanoma in situ

  • Scoring of C-MIN based on pattern of horizontal epithelial involvement, vertical depth of melanocytic infiltration, degree of cellular atypia (Eye (Lond) 2013;27:142, Clin Experiment Ophthalmol 2008;36:786)
Clinical features
  • Unilateral, flat, acquired, brown pigmentation, rarely amelanotic, fair skinned individual
Prognostic factors
Case reports
Clinical images

AFIP images
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Flat diffuse pigmentation

Gross description
  • Diffuse granular conjunctival pigmentation, usually in bulbar conjunctiva, also cornea, palpebral conjunctiva, eyelid skin
Microscopic (histologic) description
  • See C-MIN scoring system above
  • Intraepithelial proliferation of abnormal melanocytes with variable atypia
  • Early: pigmentation of basilar epithelium only
  • Later:
    • Basilar melanocytic hyperplasia with nests, resembling Paget disease
    • Cells have retracted cytoplasm, larger nuclei than neighboring cells, clumped chromatin and prominent basophilic nucleoli
    • Cells may be small with scant cytoplasm and small round nuclei
  • Classification: with or without atypia
  • High risk of progression: atypia plus epithelioid features including abundant cytoplasm, vesicular nuclei, prominent nucleoli, may be mixed with low risk areas (almost all are associated with invasion, Am J Surg Pathol 2007;31:185)
  • Low risk of progression: atypia plus primarily single cell lentinginous growth, small / medium size, high N/C ratio, small / medium hyperchromatic nuclei, no nucleoli, 15% risk of invasion
  • Pitfalls: don't interpret melanophages as invasive tumor cells
  • Sine pigmento: melanocytes without pigment
  • Post-topical chemotherapy changes: epithelial atrophy, dyskeratosis, pyknosis, focal keratinization
Microscopic (histologic) images

AFIP images

Without atypia:
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Melanocytic hyperplasia is confined to basilar layer

With atypia:
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Minimal atypia

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Moderate atypia

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Severe atypia

Positive stains
Negative stains
Electron microscopy description
  • Grade 1: melanocytes with dendritic processes and transferred melanin in epithelial cells
  • Grade 2: melanocytes have short dendritic processes, incomplete melanin transfer and immature melanosomes, irregular nuclei with clumped chromatin and large nucleoli
  • Grade 3: epithelioid cells, no cytoplasmic processes, large irregular nuclei with large prominent nucleoli and abnormal melanin transfer
Differential diagnosis
  • Cystic benign melanosis:
    • Epithelial lined cysts in substantia propria, goblet cells and secondary pigmentation of basilar keratinocytes (Cornea 2012;31:1273)
  • Hypermelanosis:
    • Freckle or complexion melanosis
    • Bilateral, does not change over time
  • Junctional nevus:
    • Children, no irregular epithelial involvement, no melanocytic nests, no polygonal cells, no atypia
  • Melanoma:
    • Invasion
  • Secondary melanosis:
    • Due to Addison disease, pigmented squamous cell carcinoma
  • Subconjunctival pigmentation:
    • Congenital ocular melanocytosis
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