Application of fluorescence in situ hybridization as a diagnostic tool in melanocytic lesions, using paraffin wax-embedded tissues and imprint-cytology specimens.
BACKGROUND
Accurate histopathological diagnosis of certain melanocytic skin lesions as benign or malignant can be notoriously difficult. Recently, four-colour fluorescence in situ hybridization (FISH) has emerged as an important tool for classifying these lesions.


OBJECTIVE
To evaluate the sensitivity and specificity of a melanoma FISH probe kit for accurate diagnosis of melanocytic tumours, and to validate its use with imprint-cytology specimens from the cut surface of tumours.


METHODS
In total, 50 melanocytic skin lesions (31 malignant melanomas, 10 benign melanocytic naevi, and 9 histologically challenging benign melanocytic skin lesions) were evaluated. The samples comprise 47 tissue specimens embedded in paraffin wax, and three imprint-cytology specimens from the cut surface of melanomas. FISH was performed using four locus-specific identifier probes [Ras responsive element binding protein (RREB)1, myeloblastosis viral oncogene homologue (MYB), cyclin (CCN)D1 and centromere of chromosome (CEP)6], and results were compared with the clinical long-term follow-up and histopathological diagnosis data.


RESULTS
The melanoma FISH probe distinguished between naevi and melanomas with a sensitivity of 100% and a specificity of 94.1%. The most sensitive criterion was a gain in 6p25 (RREB1), seen in 100% of cases, followed by CEP6-related MYB loss (48.1%), CCND1 gain (37%) and MYB gain (22.2%). More than three-quarters (77.8%) of melanomas were positive for two or more criteria. Positive FISH results were also obtained for the imprint-cytology specimens.


CONCLUSIONS
FISH is a valuable diagnostic tool for differentiating between benign and malignant melanocytic lesions, providing a high degree of sensitivity and specificity. The probes displayed exceptional discriminative capacity in difficult or ambiguous lesions. To our knowledge, his is the first reported use of imprint-cytology specimens for FISH diagnosis.
Department of Pathology, Virgen Macarena University Hospital, Seville, Spain.
A
A
Abásolo
M T
MT
Vargas
J J
JJ
Ríos-Martín
I
I
Trigo
A
A
Arjona
R
R
González-Cámpora
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D002675:Child, Preschool; D003584:Cytological Techniques / Q000379:methods*; D015342:DNA Probes; D004268:DNA-Binding Proteins / Q000235:genetics; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence / Q000379:methods*; D008297:Male; D008875:Middle Aged; D009508:Nevus, Pigmented / Q000175:diagnosis*; D016612:Paraffin Embedding; D012680:Sensitivity and Specificity; D012878:Skin Neoplasms / Q000175:diagnosis*; D014157:Transcription Factors; D055815:Young Adult
D015342:DNA Probes; D004268:DNA-Binding Proteins; C101743:RREB1 protein, human; D014157:Transcription Factors