"Spectral histopathology is based on the detection of changes in biochemical composition, rather than morphologic features, and is therefore more akin to methods such as matrix-assisted laser desorption ionization time-of-flight mass spectrometry imaging."

Ali Akalin, Ayşegül Ergin, Stanley Remiszewski, Xinying Mu, Dan Raz, and Max Diem (2018) Resolving Interobserver Discrepancies in Lung Cancer Diagnoses by Spectral Histopathology. Archives of Pathology & Laboratory Medicine In-Press.

Early Online Release

Resolving Interobserver Discrepancies in Lung Cancer Diagnoses by Spectral Histopathology

Ali Akalin, MD, PhD; Ayşegül Ergin, PhD; Stanley Remiszewski, ME; Xinying Mu, BA; Dan Raz, MD; Max Diem, PhD

From the Department of Pathology, University of Massachusetts Medical School, Worcester (Dr Akalin); CIRECA, LLC, Cambridge, Massachusetts (Drs Ergin and Diem, Mr Remiszewski, and Ms Mu); the Department of Mathematics and Statistics and Program in Bioinformatics, Boston University, Boston, Massachusetts (Ms Mu); the Division of Thoracic Surgery, City of Hope Medical Center, Duarte, California (Dr Raz); and the Department of Chemistry & Chemical Biology, Northeastern University, Boston, Massachusetts (Dr Diem).

Dr Ergin and Mr Remiszewski are employees of CIRECA, LLC. Dr Akalin, Ms Mu, and Dr Diem were paid consultants for CIRECA, LLC. Dr Raz was an unpaid consultant for CIRECA, LLC.

Corresponding author: Max Diem, PhD, CIRECA, LLC, 19 Blackstone St, Cambridge, MA 02139 (email: mdiem@cireca.com).

This paper reports the results of a collaborative lung cancer study between City of Hope Cancer Center (Duarte, California) and CIRECA, LLC (Cambridge, Massachusetts), comprising 328 samples from 249 patients, that used an optical technique known as spectral histopathology (SHP) for tissue classification. Because SHP is based on a physical measurement, it renders diagnoses on a more objective and reproducible basis than methods based on assessing cell morphology and tissue architecture. This report demonstrates that SHP provides distinction of adenocarcinomas from squamous cell carcinomas of the lung with an accuracy comparable to that of immunohistochemistry and highly reliable classification of adenosquamous carcinoma. Furthermore, this report shows that SHP can be used to resolve interobserver differences in lung pathology. Spectral histopathology is based on the detection of changes in biochemical composition, rather than morphologic features, and is therefore more akin to methods such as matrix-assisted laser desorption ionization time-of-flight mass spectrometry imaging. Both matrix-assisted laser desorption ionization time-of-flight mass spectrometry and SHP imaging modalities demonstrate that changes in tissue morphologic features observed in classical pathology are accompanied by, and may be correlated to, changes in the biochemical composition at the cellular level. Thus, these imaging methods provide novel insight into biochemical changes due to disease.