Detection of malignant mesothelioma using nuclear structure of mesothelial cells in effusion cytology specimens

Mesothelioma is a form of cancer generally caused from previous exposure to asbestos. Although it was considered a rare neoplasm in the past, its incidence is increasing worldwide due to extensive use of asbestos. In the current practice of medicine, the gold standard for diagnosing mesothelioma is through a pleural biopsy with subsequent histologic examination of the tissue. The diagnostic tissue should demonstrate the invasion by the tumor and is obtained through thoracoscopy or open thoracotomy, both being highly invasive surgical operations. On the other hand, thoracocentesis, which is removal of effusion fluid from the pleural space, is a far less invasive procedure that can provide material for cytological examination. In this study, we aim at detecting and classifying malignant mesothelioma based on the nuclear chromatin distribution from digital images of mesothelial cells in effusion cytology specimens. Accordingly, a computerized method is developed to determine whether a set of nuclei belonging to a patient is benign or malignant. The quantification of chromatin distribution is performed by using the optimal transport‐based linear embedding for segmented nuclei in combination with the modified Fisher discriminant analysis. Classification is then performed through a k‐nearest neighborhood approach and a basic voting strategy. Our experiments on 34 different human cases result in 100% accurate predictions computed with blind cross validation. Experimental comparisons also show that the new method can significantly outperform standard numerical feature‐type methods in terms of agreement with the clinical diagnosis gold standard. According to our results, we conclude that nuclear structure of mesothelial cells alone may contain enough information to separate malignant mesothelioma from benign mesothelial proliferations. © 2015 International Society for Advancement of Cytometry

[1]  Robert M. Haralick,et al.  Textural Features for Image Classification , 1973, IEEE Trans. Syst. Man Cybern..

[2]  F M Muggia,et al.  Pleural mesothelioma: clinical features and therapeutic implications. , 1977, Annals of internal medicine.

[3]  J. Vegelius,et al.  Computerized nuclear morphometry as an objective method for characterizing human cancer cell populations. , 1978, Cancer research.

[4]  S. P. Lloyd,et al.  Least squares quantization in PCM , 1982, IEEE Trans. Inf. Theory.

[5]  R. Thurer,et al.  New strategies are needed in diffuse malignant mesothelioma , 1992, Cancer.

[6]  C. Cicala,et al.  SV40 induces mesotheliomas in hamsters. , 1993, The American journal of pathology.

[7]  F Rey,et al.  Thoracoscopy in pleural malignant mesothelioma: A prospective study of 188 consecutive patients. Part 1: Diagnosis , 1993, Cancer.

[8]  J Espinosa Arranz,et al.  [Malignant mesothelioma]. , 1994, Medicina clinica.

[9]  R. Hoda The Art and Science of Cytopathology , 1996 .

[10]  A. Thor,et al.  The art and science of cytopathology: Richard M. DeMay, MD. Chicago IL, ASCP Press, 1996, 2 vol set, 1,289 pages, $285 , 1996 .

[11]  Takeshi Nagashima,et al.  Morphometry in the cytologic evaluation of thyroid follicular lesions , 1998, Cancer.

[12]  F Levi,et al.  The European mesothelioma epidemic , 1999, British Journal of Cancer.

[13]  K R Abrams,et al.  Prognostic factors for malignant mesothelioma in 142 patients: validation of CALGB and EORTC prognostic scoring systems , 2000, Thorax.

[14]  A. Darnton,et al.  The quantitative risks of mesothelioma and lung cancer in relation to asbestos exposure. , 2000, The Annals of occupational hygiene.

[15]  Robert F. Murphy,et al.  A neural network classifier capable of recognizing the patterns of all major subcellular structures in fluorescence microscope images of HeLa cells , 2001, Bioinform..

[16]  M Nesti,et al.  Analysis of survival of mesothelioma cases in the Italian register (ReNaM). , 2003, European journal of cancer.

[17]  Bertram Price,et al.  Mesothelioma trends in the United States: an update based on Surveillance, Epidemiology, and End Results Program data for 1973 through 2003. , 2004, American journal of epidemiology.

[18]  E. van Marck Pathology of malignant mesothelioma. , 2004, Lung cancer.

[19]  J. Silverman,et al.  The value of epithelial membrane antigen expression in separating benign mesothelial proliferation from malignant mesothelioma: A comparative study , 2005, Diagnostic cytopathology.

[20]  Chunming Li,et al.  Level set evolution without re-initialization: a new variational formulation , 2005, 2005 IEEE Computer Society Conference on Computer Vision and Pattern Recognition (CVPR'05).

[21]  J. Silverman,et al.  The diagnostic utility of D2‐40 for malignant mesothelioma versus pulmonary carcinoma with pleural involvement , 2006, Diagnostic cytopathology.

[22]  A. Oshima,et al.  Incidence and survival of mesothelioma in Osaka, Japan. , 2006, Japanese journal of clinical oncology.

[23]  Yaoguo Wu,et al.  Application of hydrochemical signatures to delineating portable groundwater resources in Ordos Basin, China , 2006 .

[24]  Radford M. Neal Pattern Recognition and Machine Learning , 2007, Technometrics.

[25]  Robert F Murphy,et al.  Deformation‐based nuclear morphometry: Capturing nuclear shape variation in HeLa cells , 2008, Cytometry. Part A : the journal of the International Society for Analytical Cytology.

[26]  B. Addis,et al.  Problems in mesothelioma diagnosis , 2009, Histopathology.

[27]  Wei Wang,et al.  Detection and classification of thyroid follicular lesions based on nuclear structure from histopathology images , 2010, Cytometry. Part A : the journal of the International Society for Analytical Cytology.

[28]  Eun‐Kee Park,et al.  Global mesothelioma deaths reported to the World Health Organization between 1994 and 2008. , 2011, Bulletin of the World Health Organization.

[29]  Yilin Mo,et al.  Penalized Fisher discriminant analysis and its application to image-based morphometry , 2011, Pattern Recognit. Lett..

[30]  N. Cox,et al.  Germline BAP1 mutations predispose to malignant mesothelioma , 2011, Nature Genetics.

[31]  B. Jasani,et al.  Mesothelioma not associated with asbestos exposure. , 2012, Archives of pathology & laboratory medicine.

[32]  Gustavo K. Rohde,et al.  A Linear Optimal Transportation Framework for Quantifying and Visualizing Variations in Sets of Images , 2012, International Journal of Computer Vision.

[33]  F. Galateau-Sallé,et al.  The Separation of Benign and Malignant Mesothelial Proliferations , 2000, Archives of pathology & laboratory medicine.

[34]  Wei Wang,et al.  A flexible and robust approach for segmenting cell nuclei from 2D microscopy images using supervised learning and template matching , 2013, Cytometry. Part A : the journal of the International Society for Analytical Cytology.

[35]  Manxia Wu,et al.  Mesothelioma incidence in 50 states and the District of Columbia, United States, 2003–2008 , 2013, International journal of occupational and environmental health.

[36]  Jia Guo,et al.  Cancer diagnosis by nuclear morphometry using spatial information , 2014, Pattern Recognit. Lett..

[37]  Soheil Kolouri,et al.  Detecting and visualizing cell phenotype differences from microscopy images using transport-based morphometry , 2014, Proceedings of the National Academy of Sciences.