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BRST5:Adenoid Cystic Carcinoma (view source)
Revision as of 17:27, 9 November 2023
, 17:27, 9 November 2023→Morphologic Features
==Morphologic Features==
==Morphologic Features==
Tubular, cribriform, and solid patterns are observed.
The classic subtype contains epithelial and myoepithelial cells with spaces called pseudolamina that contain stromal matrix with stromal cells (endothelial cells, fibroblasts) and basement membrane material (stains positive for collagen IV and laminin). Two cell populations are observed: an epithelial component that stains with low molecular weight cytokeratins (CK7, CK8), EMA, and sometimes CK5/6, and a myoepithelial component that stains with high molecular weight cytokeratins (CK14, CK5/6, p63) and typically also with myoepithelial markers (heavy-chain myosin, calponin, S100, CD10).
The solid basaloid subtype contains solid nests of basaloid cells with high grade nuclear features (marked nuclear atypia, high mitotic count, and necrosis).
Rare cases of adenoid cystic carcinoma can undergo high-grade transformation.
[[File:10x AdCC HE stain.tif|none|thumb|844x844px|H&E stained section of an adenoid cystic carcinoma of the left breast in an 81 year old female. Stromal elements surround and infiltrate into the nests of neoplastic cells, forming pseudolumina (bottom left). Image captured at 10x magnification by light microscopy.]]
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==Immunophenotype==
==Immunophenotype==
|Promotes cellular proliferation
|Promotes cellular proliferation
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A study of adenoid cystic carcinoma of salivary glands by Drier and others delineates the mechanism of MYB gene pathway upregulation via rearrangements that increase MYB expression. ''MYB'' rearrangements typically juxtapose ''MYB'' with strong enhancers in regions downstream of ''NFIB, TGFBR3'' and ''RAD51B.'' Gene fusions most often occur on the 3' side of ''MYB'', a subset of gene fusions occur on the 5' side, and all serve to bring the ''MYB'' gene locus close to strong enhancer elements, thus upregulating MYB expression. The authors note that TP63 signaling is active in the myoepithelial component of low grade adenoid cystic carcinomas, while Notch signaling is active in luminal epithelial components. Furthermore, the authors suggest that Notch pathway mutations may underlie the switch to solid histology and the more aggressive clinical course of these tumors.<ref>{{Cite journal|last=Drier|first=Yotam|last2=Cotton|first2=Matthew J.|last3=Williamson|first3=Kaylyn E.|last4=Gillespie|first4=Shawn M.|last5=Ryan|first5=Russell J. H.|last6=Kluk|first6=Michael J.|last7=Carey|first7=Christopher D.|last8=Rodig|first8=Scott J.|last9=Sholl|first9=Lynette M.|date=2016-03|title=An oncogenic MYB feedback loop drives alternate cell fates in adenoid cystic carcinoma|url=https://pubmed.ncbi.nlm.nih.gov/26829750|journal=Nature Genetics|volume=48|issue=3|pages=265–272|doi=10.1038/ng.3502|issn=1546-1718|pmc=4767593|pmid=26829750}}</ref>
A study of adenoid cystic carcinoma of salivary glands by Drier and others delineates the mechanism of ''MYB'' gene pathway upregulation via rearrangements that increase MYB expression. ''MYB'' rearrangements typically juxtapose ''MYB'' with strong enhancers in regions downstream of ''NFIB, TGFBR3'' and ''RAD51B.'' Gene fusions most often occur on the 3' side of ''MYB'', a subset of gene fusions occur on the 5' side, and all serve to bring the ''MYB'' gene locus close to strong enhancer elements, thus upregulating MYB expression. The authors note that TP63 signaling is active in the myoepithelial component of low grade adenoid cystic carcinomas, while Notch signaling is active in luminal epithelial components. Furthermore, the authors suggest that Notch pathway mutations may underlie the switch to solid histology and the more aggressive clinical course of these tumors.<ref>{{Cite journal|last=Drier|first=Yotam|last2=Cotton|first2=Matthew J.|last3=Williamson|first3=Kaylyn E.|last4=Gillespie|first4=Shawn M.|last5=Ryan|first5=Russell J. H.|last6=Kluk|first6=Michael J.|last7=Carey|first7=Christopher D.|last8=Rodig|first8=Scott J.|last9=Sholl|first9=Lynette M.|date=2016-03|title=An oncogenic MYB feedback loop drives alternate cell fates in adenoid cystic carcinoma|url=https://pubmed.ncbi.nlm.nih.gov/26829750|journal=Nature Genetics|volume=48|issue=3|pages=265–272|doi=10.1038/ng.3502|issn=1546-1718|pmc=4767593|pmid=26829750}}</ref>
==Genetic Diagnostic Testing Methods==
==Genetic Diagnostic Testing Methods==
FISH for MYB rearrangement; RT-PCR for MYB-NFIB fusion transcript; RNA-based sequencing (whole transcriptome or targeted)
FISH for MYB rearrangement; RT-PCR for MYB-NFIB fusion transcript; RNA-based sequencing (whole transcriptome or targeted)
[[File:MYB FISH break-apart probe.png|none|thumb|FISH with a break-apart probe targeting the 5' (red) and 3' (green) ''MYB'' gene region. Juxtaposed red and green signals indicate alleles with an intact ''MYB'' gene locus, and split / separated red and green signals indicate alleles with ''MYB'' rearrangement. The separation in this case is small, suggesting an inversion (i.e., intrachromosomal rearrangement).]]
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==Familial Forms==
==Familial Forms==