Circumscribed sebaceous neoplasms: a morphological, immunohistochemical and molecular analysis.
Sebaceous neoplasms encompass a range of lesions, including benign entities such as sebaceous adenoma and sebaceoma, as well as sebaceous carcinoma. The distinction of sebaceous carcinoma from benign lesions relies on histological identification of architectural or cytological features of malignancy. In this study we have assessed the diagnostic discriminatory ability of mitotic rate and immunohistochemical markers (p53, bcl-2 and p16) in a selected group of well circumscribed sebaceous neoplasms, incorporating examples of sebaceous adenoma, sebaceoma and sebaceous carcinoma. We found that mitotic rate was significantly higher in malignant lesions as compared to benign lesions, but none of the immunohistochemical markers showed a discriminatory expression pattern. In addition, we performed a mutational analysis on the same group of lesions using next generation sequencing (NGS) technology. The most commonly mutated gene was TP53, although there was no correlation between the p53 immunohistochemical results and number or type of TP53 mutation detected. CDKN2A, EGFR, CTNNB1 and KRAS were also commonly mutated across all lesions. No particular gene, mutation profile or individual mutation could be identified which directly correlated with the consensus histological diagnosis. In conclusion, within this diagnostically challenging group of lesions, mitotic activity, but not immunohistochemical labelling for p16 or bcl-2, correlates with diagnostic category. While a number of genes potentially involved in the genesis of sebaceous neoplasia were uncovered, any molecular differences between the histological diagnostic categories remain unclear.
Department of Anatomical Pathology, PathWest Laboratory Medicine, QEII Medical Centre, Nedlands, WA, Australia; Translational Cancer Pathology Laboratory, School of Pathology and Laboratory Medicine, The University of Western Australia, Crawley, WA, Australia. Electronic address: nathan.harvey@health.wa.gov.au.
Nathan Tobias
NT
Harvey
Translational Cancer Pathology Laboratory, School of Pathology and Laboratory Medicine, The University of Western Australia, Crawley, WA, Australia.
Tania
T
Tabone
Translational Cancer Pathology Laboratory, School of Pathology and Laboratory Medicine, The University of Western Australia, Crawley, WA, Australia.
Wendy
W
Erber
Department of Anatomical Pathology, PathWest Laboratory Medicine, QEII Medical Centre, Nedlands, WA, Australia; Translational Cancer Pathology Laboratory, School of Pathology and Laboratory Medicine, The University of Western Australia, Crawley, WA, Australia.
Benjamin Andrew
BA
Wood
D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000032:analysis / Q000096:biosynthesis; D004252:DNA Mutational Analysis; D066246:ErbB Receptors / Q000235:genetics; D005260:Female; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis / Q000096:biosynthesis; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics; D012626:Sebaceous Gland Neoplasms / Q000175:diagnosis* / Q000235:genetics* / Q000473:pathology*; D016159:Tumor Suppressor Protein p53 / Q000032:analysis / Q000096:biosynthesis / Q000235:genetics; D051176:beta Catenin / Q000235:genetics
C000595707:BCL2 protein, human; D014408:Biomarkers, Tumor; C000614131:CDKN2A protein, human; C495270:CTNNB1 protein, human; D019941:Cyclin-Dependent Kinase Inhibitor p16; C117307:KRAS protein, human; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D051176:beta Catenin; C512478:EGFR protein, human; D066246:ErbB Receptors; D016283:Proto-Oncogene Proteins p21(ras)
Sebaceous neoplasms; next generation sequencing; sebaceoma; sebaceous adenoma; sebaceous carcinoma