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Improved discrimination of melanotic schwannoma from melanocytic lesions by combined morphological and GNAQ mutational analysis.

Küsters-Vandevelde HV, van Engen-van Grunsven IA, Küsters B, van Dijk MR, Groenen PJ, Wesseling P, Blokx WA - Acta Neuropathol. (2010)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, Canisius Wilhelmina Hospital, Nijmegen, The Netherlands. h.vandevelde@pathol.umcn.nl

ABSTRACT
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.

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Intermediate-grade melanocytoma (case 20) with invasion of neuroglial tissue; note the Rosenthal fibers (arrow) in the surrounding neuropil (a) (×200). Epithelioid cell morphology with bland nuclei and small nucleoli in a melanocytoma (case 22) (b) (×400). Focal positivity for S-100 in the same lesion (case 22) (c) (×200). Diffuse positivity for HMB-45 and Melan-A, respectively, in the same lesion (d, e) and a nested staining pattern in the reticulin stain (f) (case 22) (Laguesse stain, ×200)
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Fig2: Intermediate-grade melanocytoma (case 20) with invasion of neuroglial tissue; note the Rosenthal fibers (arrow) in the surrounding neuropil (a) (×200). Epithelioid cell morphology with bland nuclei and small nucleoli in a melanocytoma (case 22) (b) (×400). Focal positivity for S-100 in the same lesion (case 22) (c) (×200). Diffuse positivity for HMB-45 and Melan-A, respectively, in the same lesion (d, e) and a nested staining pattern in the reticulin stain (f) (case 22) (Laguesse stain, ×200)

Mentions: Nine lesions initially diagnosed elsewhere as melanotic schwannoma were reclassified as conventional schwannomas. These lesions showed the typical histological features of schwannomas with frequent Antoni A and B areas, nuclear palisading, blood vessel hyalinization and wavy nuclei. We did not classify them as melanotic schwannoma, because positivity for both Melan-A and HMB-45 was lacking. They all contained focally some fine intracytoplasmic grayish pigment in tumor cells (Schmorl positive). Furthermore, extensive areas with deposition of basement membrane material around individual tumor cells in the basement membrane stains were present. Based on the criteria described by Brat et al. [1, 2], four lesions located around the spinal cord were reclassified as melanocytomas. Three of them showed an infiltrative growth pattern in the neuroglial tissues and were classified as intermediate-grade melanocytomas (Fig. 2a). All lesions consisted of fascicles and nests of spindle and/or epithelioid cells with variable melanin pigment. Nuclei were round to oval and uniform in size, with mostly small nucleoli (Fig. 2b). Prominent nuclear atypia was absent. In contrast to the melanotic and conventional schwannomas, S-100 was only focally positive (Fig. 2c), while Melan-A and HMB-45 were more diffusely positive (Fig. 2d, e). MIB-1 staining was less than 1% in all cases. Reticulin, Collagen type IV and Laminin stains showed deposition of basement membrane material around vascular structures and nests of tumor cells (nested/perilobular), but not around individual tumor cells (Fig. 2f).


Improved discrimination of melanotic schwannoma from melanocytic lesions by combined morphological and GNAQ mutational analysis.

Küsters-Vandevelde HV, van Engen-van Grunsven IA, Küsters B, van Dijk MR, Groenen PJ, Wesseling P, Blokx WA - Acta Neuropathol. (2010)

Intermediate-grade melanocytoma (case 20) with invasion of neuroglial tissue; note the Rosenthal fibers (arrow) in the surrounding neuropil (a) (×200). Epithelioid cell morphology with bland nuclei and small nucleoli in a melanocytoma (case 22) (b) (×400). Focal positivity for S-100 in the same lesion (case 22) (c) (×200). Diffuse positivity for HMB-45 and Melan-A, respectively, in the same lesion (d, e) and a nested staining pattern in the reticulin stain (f) (case 22) (Laguesse stain, ×200)
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2991233&req=5

Fig2: Intermediate-grade melanocytoma (case 20) with invasion of neuroglial tissue; note the Rosenthal fibers (arrow) in the surrounding neuropil (a) (×200). Epithelioid cell morphology with bland nuclei and small nucleoli in a melanocytoma (case 22) (b) (×400). Focal positivity for S-100 in the same lesion (case 22) (c) (×200). Diffuse positivity for HMB-45 and Melan-A, respectively, in the same lesion (d, e) and a nested staining pattern in the reticulin stain (f) (case 22) (Laguesse stain, ×200)
Mentions: Nine lesions initially diagnosed elsewhere as melanotic schwannoma were reclassified as conventional schwannomas. These lesions showed the typical histological features of schwannomas with frequent Antoni A and B areas, nuclear palisading, blood vessel hyalinization and wavy nuclei. We did not classify them as melanotic schwannoma, because positivity for both Melan-A and HMB-45 was lacking. They all contained focally some fine intracytoplasmic grayish pigment in tumor cells (Schmorl positive). Furthermore, extensive areas with deposition of basement membrane material around individual tumor cells in the basement membrane stains were present. Based on the criteria described by Brat et al. [1, 2], four lesions located around the spinal cord were reclassified as melanocytomas. Three of them showed an infiltrative growth pattern in the neuroglial tissues and were classified as intermediate-grade melanocytomas (Fig. 2a). All lesions consisted of fascicles and nests of spindle and/or epithelioid cells with variable melanin pigment. Nuclei were round to oval and uniform in size, with mostly small nucleoli (Fig. 2b). Prominent nuclear atypia was absent. In contrast to the melanotic and conventional schwannomas, S-100 was only focally positive (Fig. 2c), while Melan-A and HMB-45 were more diffusely positive (Fig. 2d, e). MIB-1 staining was less than 1% in all cases. Reticulin, Collagen type IV and Laminin stains showed deposition of basement membrane material around vascular structures and nests of tumor cells (nested/perilobular), but not around individual tumor cells (Fig. 2f).

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, Canisius Wilhelmina Hospital, Nijmegen, The Netherlands. h.vandevelde@pathol.umcn.nl

ABSTRACT
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.

Show MeSH
Related in: MedlinePlus