Multiphoton microscopy: A potential "optical biopsy" tool for real-time evaluation of lung tumors without the need for exogenous contrast agents

Manu Jain, Navneet Narula, Amit Aggarwal, Brendon Stiles, Maria M. Shevchuk, Joshua Sterling, Bekheit Salamoon, Vishal Chandel, Watt W. Webb, Nasser K. Altorki, Sushmita Mukherjee

Research output: Contribution to journalArticlepeer-review

29 Scopus citations


Context.-Multiphoton microscopy (MPM) is an emerging, nonlinear, optical-biopsy technique, which can generate subcellular-resolution images from unprocessed and unstained tissue in real time. Objective.-To assess the potential of MPM for lung tumor diagnosis. Design.-Fresh sections from tumor and adjacent nonneoplastic lung were imaged with MPM and then compared with corresponding hematoxylin-eosin slides. Results.-Alveoli, bronchi, blood vessels, pleura, smokers' macrophages, and lymphocytes were readily identified with MPM in nonneoplastic tissue. Atypical adenomatous hyperplasia (a preinvasive lesion) was identified in tissue adjacent to the tumor in one case. Of the 25 tumor specimens used for blinded pathologic diagnosis, 23 were diagnosable with MPM. Of these 23 cases, all but one adenocarcinoma (15 of 16; 94%) was correctly diagnosed on MPM, along with their histologic patterns. For squamous cell carcinoma, 4 of 7 specimens (57%) were correctly diagnosed. For the remaining 3 squamous cell carcinoma specimens, the solid pattern was correctly diagnosed in 2 additional cases (29%), but it was not possible to distinguish the squamous cell carcinoma from adenocarcinoma. The other squamous cell carcinoma specimen (1 of 7; 14%) was misdiagnosed as adenocarcinoma because of pseudogland formation. Invasive adenocarcinomas with acinar and solid pattern showed statistically significant increases in collagen. Interobserver agreement for collagen quantification (among 3 observers) was 80%. Conclusions.-Our pilot study provides a proof of principle that MPM can differentiate neoplastic from nonneoplastic lung tissue and identify tumor subtypes. If confirmed in a future, larger study, we foresee real-time intraoperative applications of MPM, using miniaturized instruments for directing lung biopsies, assessing their adequacy for subsequent histopathologic analysis or banking, and evaluating surgical margins in limited lung resections.

Original languageEnglish (US)
Pages (from-to)1037-1047
Number of pages11
JournalArchives of Pathology and Laboratory Medicine
Issue number8
StatePublished - Aug 2014
Externally publishedYes

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Medical Laboratory Technology


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