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Subspecialties Basic & Translational Research, Comprehensive

Reclassifying Ocular Pathology

Eye Pathologists: Ralph C. Eagle Jr., one of the most critically important ocular pathologists in the world, and Tatyana Milman, who joined the Wills Eye Faculty.

The accurate classification and interpretation of pathology has important prognostic implications. Though some pigmented blemishes of the conjunctiva are benign and do not require close follow-up or treatment, others progress to conjunctival melanoma, a malignant tumor with a high potential for recurrence on (up to 50 percent) and a distant metastasis and death (20-30 percent at five years). An ideal classification system needs to be highly accurate, easy for pathologists and ophthalmologists to use, and have excellent inter-observer reproducibility.

Tatyana Milman, Ocular Pathologist at Wills Eye, says, “We are in the midst of re-appraising the two most commonly used classification systems: the primary acquired melanosis (PAM) system, and validating the recently developed WHO 4th edition of Eye Tumours classification system.”

We reviewed the histologic slides for adequacy, then scanned [them] to create digital slides, which were then scored by 12 international ophthalmic pathology experts.

Identifying and designing the ideal classification system is not without its challenges. Milman’s team identified five key barriers: difficulty in finding cases of primary conjunctival epithelial pigmentations that were not previously operated on (as this influences outcome); cases with long-term follow-up (progression to melanoma occurs on average 2.5 years after initial surgery); finding cases that were operated on with the same technique (as this also influences outcome); having identical material reviewed by a large panel of international experts; and, finally, available gold standards in interpretation.

“We selected 83 cases of pigmented conjunctival epithelial lesions that fulfilled our inclusion criteria – primary surgeries, handled uniformly by oncology service, with at least three years of follow-up information from the records of our oncology service,” Milman notes. “We reviewed the histologic slides for adequacy, then scanned the slides with virtual scanning technology to create digital slides, which were then displayed on a shared portal on the internet and scored by 12 international ophthalmic pathology experts." 

"These experts included Robert Folberg, the originator of the PAM classification system, Sarah Coupland, the originator of the C-MIN classification system, and members of the panel that developed the recent WHO classification – Charles Eberhart, Hans Grossniklaus, Steffen Heegaard, Sarah Coupland, Hardeep Mudhar and Ralph Eagle.”

The accuracy of each system for predicting recurrence and progression to melanoma and the agreement between the observers have been analyzed.  The time required for scoring with each classification system also has been assessed. Milman and her team now look forward to the final results.

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