Distinguishing malignant from benign microscopic skin lesions using desorption electrospray ionization mass spectrometry imaging

Katherine Margulis, Albert S. Chiou, Sumaira Z. Aasi, Robert J. Tibshirani, Jean Y. Tang, Richard N. Zare*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

63 Scopus citations


Detection of microscopic skin lesions presents a considerable challenge in diagnosing early-stage malignancies as well as in residual tumor interrogation after surgical intervention. In this study, we established the capability of desorption electrospray ionization mass spectrometry imaging (DESI-MSI) to distinguish between micrometer-sized tumor aggregates of basal cell carcinoma (BCC), a common skin cancer, and normal human skin. We analyzed 86 human specimens collected during Mohs micrographic surgery for BCC to cross-examine spatial distributions of numerous lipids and metabolites in BCC aggregates versus adjacent skin. Statistical analysis using the least absolute shrinkage and selection operation (Lasso) was employed to categorize each 200-μm-diameter picture element (pixel) of investigated skin tissue map as BCC or normal. Lasso identified 24 molecular ion signals, which are significant for pixel classification. These ion signals included lipids observed at m/z 200-1,200 and Krebs cycle metabolites observed at m/z < 200. Based on these features, Lasso yielded an overall 94.1% diagnostic accuracy pixel by pixel of the skin map compared with histopathological evaluation. We suggest that DESI-MSI/Lasso analysis can be employed as a complementary technique for delineation of microscopic skin tumors.

Original languageAmerican English
Pages (from-to)6347-6352
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number25
StatePublished - 19 Jun 2018
Externally publishedYes

Bibliographical note

Funding Information:
ACKNOWLEDGMENTS. We thank Jamaica Jensen, lead Mohs technician, and Samantha Rodriguez, Mohs technician, for their assistance in preparing specimens for this study. K.M. is grateful to the Stanford Center of Molecular Analysis and Design for supporting her fellowship. This work was supported by Air Force Office of Scientific Research Grant FA9550-16-1-0113.

Publisher Copyright:
© 2018 National Academy of Sciences.All Rights Reserved.


  • Basal cell carcinoma
  • Desorption electrospray ionization
  • Mass spectrometry imaging
  • Microscopic tumors
  • Mohs surgery


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