Table 3.

Clinicopathologic features of conjunctival blue nevi and differential diagnosis

Lesion	Location	Histological characteristics	Bleach	Sox 10/Melan A	CD68	Clinical characteristics
Blue nevus	Substantia propria	Dendritic, heavily pigmented spindle shaped melanocytes, morphologically benign, lack prominent nucleoli, have accompanying melanophages.	Bleaching shows cellular detail	Positive	Positive with surrounding melanophages	Congenital, may be discovered at later age. Usually dark, but may vary in shade and color.
Nevocellular nevus	Epithelium (Junctional nevus), Subepithelial, or both (Compound nevus)	Melanocytes with variable pigmentation that are present within the epithelium at a young age and migrate into the substantia propria over time. Epithelial cysts are common. Lack nucleoli and mitotic activity.	Bleaching shows cellular detail	Positive	Usually Negative	Congenital, cystic, may change in size with age and hormonal changes.
C-MIN/PAM without atypia	Epithelium	Acquired intraepithelial melanocytes with variable pigmentation in the basal epithelium. No atypia.	Bleaching shows cellular detail	Positive	Negative	Acquired, usually near limbus, can appear as light epithelial pigment dusting.
C-MIN/PAM with atypia	Epithelium	Melanocytes show signs of atypia including condensed nuclei with perinuclear clearing, prominent nucleoli, pleomorphism and migration into superficial epithelium.	Bleaching shows cellular detail	Positive	Negative	Acquired, usually near limbus, can appear as light epithelial pigmented dusting.
Melanoma in situ	Epithelium (full thickness)	Morphologically similar to PAM with atypia/C-MIN with full thickness involvement of the epithelium without extension into the substantia propria.	Bleaching shows cellular detail	Positive	Negative	Acquired, dark, irregular borders, and often history of prolonged sun exposure.
Invasive melanoma	Epithelium invading into substantia propria	Melanocytes with atypia including condensed nuclei with perinuclear clearing, prominent nucleoli, mitotic activity, pleomorphism, extension through the basement membrane into the underlying substantia propria.	Bleaching shows cellular detail	Positive	Negative within tumor, may be positive in surrounding macrophages	Acquired, dark, irregular borders, nodular and often history of prolonged sun exposure
Extraocular extension of uveal melanoma	Extending through sclera into substantia propria	Spindle and epithelioid cells with prominent nucleoli and mitotic figures. Typically, with no epithelial involvement. Often evidence of involvement at deep aspect of excised tissue and history of uveal melanoma.	Bleaching shows cellular detail	Positive	Negative within tumor, may be positive in surrounding macrophages	Acquired, dark, subconjunctival, immobile lesion with irregular borders. Extension confirmed with B-scan ultrasound.
Pigmented ocular surface squamous neoplasia	Epithelium +/− invasion into substantia propria	Atypical epithelial proliferation, may show pigmented dendritic melanocytes in epithelium which lack morphological atypia.	Bleaching shows cellular detail	Positive for dendritic melanocytes in epithelium	Negative	Opalescent lesions, can be pigmented in patients with tan/dark complexion.
Foreign body	Variable location	Variable appearance depending on foreign material/ink.	Does not typically bleach. Iron stain helpful for demonstrating hemosiderin.	Negative	Variably positive if macrophages engulfing foreign material	Variable presentation.

C-MIN: conjunctival melanocytic intraepithelial neoplasia; PAM: primary acquired melanosis