Main histopathological difficulties in diagnosing atypical melanocytic proliferations using MPATH-Dx V2: impact on...

Diagnosing atypical melanocytic proliferations (AMPs) is histologically challenging, and hence, these cases are referred to expert dermatopathologists for second opinions. The impact of such diagnoses varies depending on the case. Our study retrospectively analysed 6006 AMPs referred for second opinions over 13 years (the largest series to date), classifying them into the four Melanocytic Pathology Assessment Tool and Hierarchy for Diagnosis version 2.0 (MPATH-Dx-V2.0) classes. MPATH-Dx-V2.0 does not supplant existing nomenclature/classifications but is a complementary tool (based on the probabilistic tumour-progression risk) enabling clinicians to better prioritise problems and assess their impact on patient management. We propose a step-by-step ​integrative methodology using the 5th World Health Organization and MPATH-Dx classifications. MPATH-Dx classes I and II (76.4%), which carry favourable prognoses, presented the most frequent diagnostic problems. Invasive thick melanoma mimicking a naevus accounted for 50% of class IV melanomas and was the predominant differential diagnosis for class II melanocytomas. Low- and high-grade dysplastic naevi and melanoma in situ were problematic in 24.5% and 25.6% of class I and II lesions, respectively. Atypical Spitz/spitzoid tumours were the second major diagnostic challenge, representing 50% of class II compared with 11% for other melanocytomas. Other frequently encountered difficult histopathological diagnoses included inflamed tumours, combined naevi, special-site atypical naevi, and melanoma regression. Our results identified the most common problems encountered by pathologists in routine practice through the application of the MPATH-Dx v2.0 classification. We propose a step-by-step integrative methodology to interpret AMPs, aiming to optimise patient management by enhancing non-pathologists' understanding of diagnostic terminology.