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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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Case 24 was a variably, partly heavily pigmented lesion consisting of spindle to pleomorphic cells (a, c) (×200), showing infiltrative growth in a ganglion at the lumbar spinal region with dispersed incorporated ganglion cells (arrow) (b) (×400). The nuclei showed marked atypia with conspicuous nucleoli (c) (×200). In the reticulin stain, both a pericellular (d) and nested staining pattern were seen (e) (Laguesse, ×100). We, therefore, favored the diagnosis of a melanotic schwannoma with atypical features suggestive of aggressive behavior. Molecular analysis of this case did not reveal mutations in the GNAQ gene
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Fig3: Case 24 was a variably, partly heavily pigmented lesion consisting of spindle to pleomorphic cells (a, c) (×200), showing infiltrative growth in a ganglion at the lumbar spinal region with dispersed incorporated ganglion cells (arrow) (b) (×400). The nuclei showed marked atypia with conspicuous nucleoli (c) (×200). In the reticulin stain, both a pericellular (d) and nested staining pattern were seen (e) (Laguesse, ×100). We, therefore, favored the diagnosis of a melanotic schwannoma with atypical features suggestive of aggressive behavior. Molecular analysis of this case did not reveal mutations in the GNAQ gene

Mentions: Finally, two lesions could not be classified with certainty into melanotic schwannoma or melanocytoma (cases 24 and 25). Case 24 was a variably, partly heavily pigmented lesion consisting of spindle to pleiomorphic cells (Fig. 3a, c). The lesion showed infiltrative growth in or from a ganglion at the lumbar spinal region (Fig. 3b). The nuclei showed moderate to strong atypia with conspicuous nucleoli (Fig. 3c). MIB-1 staining was less than 10%. Psammoma bodies were absent. S-100, Melan-A and HMB-45 stains were diffusely positive. The reticulin, Collagen type IV and Laminin stains showed a biphasic pattern (Fig. 3d, e). Based on these histological features, we favored the diagnosis of melanotic schwannoma with atypical features suggestive of aggressive behavior. For case 25, only limited biopsy material was available which impaired unequivocal histological assessment. It concerned a heavily pigmented lesion located at the cerebellopontine angle consisting of spindle cells with mild cytonuclear atypia and small nucleoli. S-100 was focally positive, while the Melan-A and HMB-45 stains were diffusely positive. A nested/perilobulated staining pattern was present in the reticulin, Collagen type IV and Laminin stains. In this case, we favored the diagnosis of melanocytoma.Fig. 2


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)

Case 24 was a variably, partly heavily pigmented lesion consisting of spindle to pleomorphic cells (a, c) (×200), showing infiltrative growth in a ganglion at the lumbar spinal region with dispersed incorporated ganglion cells (arrow) (b) (×400). The nuclei showed marked atypia with conspicuous nucleoli (c) (×200). In the reticulin stain, both a pericellular (d) and nested staining pattern were seen (e) (Laguesse, ×100). We, therefore, favored the diagnosis of a melanotic schwannoma with atypical features suggestive of aggressive behavior. Molecular analysis of this case did not reveal mutations in the GNAQ gene
© Copyright Policy
Related In: Results  -  Collection

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

Fig3: Case 24 was a variably, partly heavily pigmented lesion consisting of spindle to pleomorphic cells (a, c) (×200), showing infiltrative growth in a ganglion at the lumbar spinal region with dispersed incorporated ganglion cells (arrow) (b) (×400). The nuclei showed marked atypia with conspicuous nucleoli (c) (×200). In the reticulin stain, both a pericellular (d) and nested staining pattern were seen (e) (Laguesse, ×100). We, therefore, favored the diagnosis of a melanotic schwannoma with atypical features suggestive of aggressive behavior. Molecular analysis of this case did not reveal mutations in the GNAQ gene
Mentions: Finally, two lesions could not be classified with certainty into melanotic schwannoma or melanocytoma (cases 24 and 25). Case 24 was a variably, partly heavily pigmented lesion consisting of spindle to pleiomorphic cells (Fig. 3a, c). The lesion showed infiltrative growth in or from a ganglion at the lumbar spinal region (Fig. 3b). The nuclei showed moderate to strong atypia with conspicuous nucleoli (Fig. 3c). MIB-1 staining was less than 10%. Psammoma bodies were absent. S-100, Melan-A and HMB-45 stains were diffusely positive. The reticulin, Collagen type IV and Laminin stains showed a biphasic pattern (Fig. 3d, e). Based on these histological features, we favored the diagnosis of melanotic schwannoma with atypical features suggestive of aggressive behavior. For case 25, only limited biopsy material was available which impaired unequivocal histological assessment. It concerned a heavily pigmented lesion located at the cerebellopontine angle consisting of spindle cells with mild cytonuclear atypia and small nucleoli. S-100 was focally positive, while the Melan-A and HMB-45 stains were diffusely positive. A nested/perilobulated staining pattern was present in the reticulin, Collagen type IV and Laminin stains. In this case, we favored the diagnosis of melanocytoma.Fig. 2

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