The histological differential diagnosis between melanotic
schwannoma, primary leptomeningeal melanocytic lesions and
cellular blue nevus can be challenging. Correct diagnosis of melanotic
schwannoma is important to select patients who need clinical evaluation for possible association with
Carney complex. Recently, we described the presence of activating
codon 209 mutations in the GNAQ gene in primary leptomeningeal melanocytic lesions. Identical
codon 209 mutations have been described in
blue nevi. The aims of the present study were to (1) perform a histological review of a series of lesions (initially) diagnosed as melanotic
schwannoma and analyze them for GNAQ mutations, and (2) test the diagnostic value of GNAQ mutational analysis in the differential diagnosis with leptomeningeal melanocytic lesions. We retrieved 25 cases that were initially diagnosed as melanotic
schwannoma. All cases were reviewed using established criteria and analyzed for GNAQ
codon 209 mutations. After review, nine cases were classified as melanotic
schwannoma. GNAQ mutations were absent in these nine cases. The remaining cases were reclassified as conventional
schwannoma (n = 9), melanocytoma (n = 4),
blue nevus (n = 1) and lesions that could not be classified with certainty as melanotic
schwannoma or melanocytoma (n = 2). GNAQ
codon 209 mutations were present in 3/4 melanocytomas and the
blue nevus. Including results from our previous study in leptomeningeal melanocytic lesions, GNAQ mutations were highly specific (100%) for leptomeningeal melanocytic lesions compared to melanotic
schwannoma (sensitivity 43%). We conclude that a detailed analysis of morphology combined with GNAQ mutational analysis can aid in the differential diagnosis of melanotic
schwannoma with leptomeningeal melanocytic lesions.