Magnifying glass on spiradenoma and cylindroma histogenesis and tumorigenesis using systematic transcriptome analysis.

Spiradenoma and cylindroma are related sweat gland tumors. To delineate their histogenesis, gene profiles, and their potential drivers, we performed a whole-transcriptome sequencing analysis of fourteen samples of spiradenoma/cylindroma in comparison to normal samples. A total of 12 spiradenomas, 5 cylindromas, 3 hybrid spiradenomas/cylindromas and 2 adnexal carcinomas were included in this study. 1335 characteristic genes and transcripts expressed over all 14 spiradenoma/cylindroma tumors were identified, and two groups of expression profiles were observed. Highest upregulated top 7 gene signatures characterized benign tumors with developmental and differentiation related genes, and carcinomas with top 7 genes mainly related to signaling, reorganization and metabolism of membranes. Immunohistochemistry of protein expressions validated 4 upregulated genes (ODAM, HOXB13, MYB and SOX10) considered important and as potential biomarkers for spiradenomas and cylindromas. We further compared the transcriptome of eccrine adnexal tumors with the transcriptome of adenoid cystic carcinoma (ACC) to identify the overlapping genes that may indicate histogenesis. There were 36 specific genes overlapping between adnexal carcinomas and the epithelial-dominant subtype of ACC, and 27 specific genes overlapping benign adnexal tumors with the myoepithelial-dominant subtype of ACC, At this point there is no known specific biomarker to aid in the diagnosis of eccrine spiradenoma and cylindroma in small samples or biopsies within the context of morphological overlap with ACC. In conclusion, spiradenomas and cylindromas are characterized by overexpressed developmental genes, where LHX2 and activated WNT signaling possibly drive associated carcinomas.