Why moles and early melanomas are hard to diagnose, what research shows about pathologist agreement, and how a slide review works.
A pathology report reads like a lab value, but a diagnosis of a mole or melanoma is a judgment made by a physician looking at cells. Most of the time that judgment is clear-cut. For a group of lesions in the middle, skilled pathologists can look at the same slide and reach different conclusions.
Melanocytic lesions, the growths made of pigment cells, run along a spectrum. At one end sit ordinary moles. At the other sit obvious invasive melanomas. Between them lie atypical (dysplastic) moles, Spitz tumors, melanoma in situ, and very thin invasive melanomas, and the features that separate one from the next are matters of degree.
The pathologist weighs symmetry, how cells mature as they go deeper, how many cells are dividing, and many other clues. No single stain turns one color for benign and another for malignant. The sample can add its own limits, since a partial biopsy shows only part of the architecture.
The best-known research on this question is the M-Path study (Elmore and colleagues, BMJ, 2017). In it, 187 pathologists from 10 US states each interpreted a set of skin biopsy slides drawn from 240 cases, then read the same slides again at least 8 months later. Their answers were compared with a consensus diagnosis from 3 experienced dermatopathologists.
Agreement was strong at the 2 ends of the spectrum. Accuracy against the reference was 92% for ordinary moles and mildly atypical moles, and 72% for invasive melanomas staged T1b or higher. In the middle categories it fell sharply: 25% for moderately atypical moles, 40% for severely atypical moles and melanoma in situ, and 43% for the thinnest invasive melanomas.
The authors then estimated what this means across all the skin biopsies of this kind done in the United States, where ordinary moles far outnumber difficult cases. About 83% of diagnoses would be confirmed by an expert panel. Roughly 8% would be rated as more serious than the panel judged, and about 9% as less serious.
Study conditions differ from daily practice. Each participant had 1 slide per case and couldn't order more sections or special stains, or walk down the hall to ask a colleague, all of which pathologists do routinely with difficult cases. The findings still make a fair point: the middle of the spectrum is where a second set of eyes adds the most.
The same research group tested that directly (Piepkorn and colleagues, JAMA Network Open, 2019). Using the M-Path data, they modeled 10 different second-opinion strategies. Misclassification was lowest when every case received a second opinion and the reviewers had subspecialty training in dermatopathology.
The paper reported 2 details that stand out. The pathologists themselves said they would want a second opinion on 43% of their interpretations, which shows how normal consultation is within the field. And no strategy removed disagreement entirely, especially for melanoma in situ and thin invasive melanoma.
Many difficult cases get a second look before the report is ever signed. Pathologists show slides to partners, present them at group conferences, and send them to outside experts when needed. If this happened, the report's comment section usually says so and may name the consultant.
Cancer centers add another layer. When a patient is referred for melanoma treatment, the center's own pathologists commonly review the outside slides before surgery or drug treatment begins.
Shipping, review, and reporting often add 1 to 2 weeks, and longer if the consultant orders new stains or molecular tests. For most lesions in the uncertain middle of the spectrum, that delay doesn't change the outcome. If your doctor believes treatment shouldn't wait, the review and the surgical planning can often run in parallel.
Disagreement between careful pathologists usually means the lesion sits in a gray zone. The 2 pathologists often talk directly, and the treating doctor may ask for additional tests, such as immunostains or molecular studies, or for a third opinion.
When doubt remains, doctors commonly plan treatment around the more serious of the reasonable diagnoses. For a small skin lesion that usually means a somewhat wider excision, a modest price for covering the uncertainty.
Pathologists have worked to make uncertain results easier to act on. A classification system called MPATH-Dx, revised in 2023 by an international group of dermatopathologists, sorts the many diagnostic terms for melanocytic lesions into 4 classes, each tied to a suggested management step. A report that includes an MPATH-Dx class tells the treating doctor what the pathologist thinks should happen next, even when the name of the lesion is debated.
