Journal of Pathology and Translational Medicine

Original Article

Deep learning for computer-assisted diagnosis of hereditary diffuse gastric cancer: Sean A. Rasmussen, Thomas Arnason, Weei-Yuarn Huang; J Pathol Transl Med. 2021;55(2):118-124. Published online January 22, 2021; DOI: https://doi.org/10.4132/jptm.2020.12.22

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Background
Patients with hereditary diffuse gastric cancer often undergo prophylactic gastrectomy to minimize cancer risk. Because intramucosal poorly cohesive carcinomas in this setting are typically not grossly visible, many pathologists assess the entire gastrectomy specimen microscopically. With 150 or more slides per case, this is a major time burden for pathologists. This study utilizes deep learning methods to analyze digitized slides and detect regions of carcinoma.
Methods
Prophylactic gastrectomy specimens from seven patients with germline CDH1 mutations were analyzed (five for training/validation and two for testing, with a total of 133 tumor foci). All hematoxylin and eosin slides containing cancer foci were digitally scanned, and patches of size 256×256 pixels were randomly extracted from regions of cancer as well as from regions of normal background tissue, resulting in 15,851 images for training/validation and 970 images for testing. A model with DenseNet-169 architecture was trained for 150 epochs, then evaluated on images from the test set. External validation was conducted on 814 images scanned at an outside institution.
Results
On individual patches, the trained model achieved a receiver operating characteristic (ROC) area under the curve (AUC) of 0.9986. This enabled it to maintain a sensitivity of 90% with a false-positive rate of less than 0.1%. On the external validation dataset, the model achieved a similar ROC AUC of 0.9984. On whole slide images, the network detected 100% of tumor foci and correctly eliminated an average of 99.9% of the non-cancer slide area from consideration.
Conclusions
Overall, our model shows encouraging progress towards computer-assisted diagnosis of hereditary diffuse gastric cancer.

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Review

Introduction to digital pathology and computer-aided pathology: Soojeong Nam, Yosep Chong, Chan Kwon Jung, Tae-Yeong Kwak, Ji Youl Lee, Jihwan Park, Mi Jung Rho, Heounjeong Go; J Pathol Transl Med. 2020;54(2):125-134. Published online February 13, 2020; DOI: https://doi.org/10.4132/jptm.2019.12.31

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Abstract PDF

Digital pathology (DP) is no longer an unfamiliar term for pathologists, but it is still difficult for many pathologists to understand the engineering and mathematics concepts involved in DP. Computer-aided pathology (CAP) aids pathologists in diagnosis. However, some consider CAP a threat to the existence of pathologists and are skeptical of its clinical utility. Implementation of DP is very burdensome for pathologists because technical factors, impact on workflow, and information technology infrastructure must be considered. In this paper, various terms related to DP and computer-aided pathologic diagnosis are defined, current applications of DP are discussed, and various issues related to implementation of DP are outlined. The development of computer-aided pathologic diagnostic tools and their limitations are also discussed.

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Original Articles

Difference of the Nuclear Green Light Intensity between Papillary Carcinoma Cells Showing Clear Nuclei and Non-neoplastic Follicular Epithelia in Papillary Thyroid Carcinoma: Hyekyung Lee, Tae Hwa Baek, Meeja Park, Seung Yun Lee, Hyun Jin Son, Dong Wook Kang, Joo Heon Kim, Soo Young Kim; J Pathol Transl Med. 2016;50(5):355-360. Published online August 22, 2016; DOI: https://doi.org/10.4132/jptm.2016.05.19

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Abstract PDF: Background
There is subjective disagreement regarding nuclear clearing in papillary thyroid carcinoma. In this study, using digital instruments, we were able to quantify many ambiguous pathologic features and use numeric data to express our findings.
Methods
We examined 30 papillary thyroid carcinomas. For each case, we selected representative cancer cells showing clear nuclei and surrounding non-neoplastic follicular epithelial cells and evaluated objective values of green light intensity (GLI) for quantitative analysis of nuclear clearing in papillary thyroid carcinoma.
Results
From 16,274 GLI values from 600 cancer cell nuclei and 13,752 GLI values from 596 non-neoplastic follicular epithelial nuclei, we found a high correlation of 94.9% between GLI and clear nuclei. GLI between the cancer group showing clear nuclei and non-neoplastic follicular epithelia was statistically significant. The overall average level of GLI in the cancer group was over two times higher than the non-neoplastic group despite a wide range of GLI. On a polygonal line graph, there was a fluctuating unique difference between both the cancer and non-neoplastic groups in each patient, which was comparable to the microscopic findings.
Conclusions
Nuclear GLI could be a useful factor for discriminating between carcinoma cells showing clear nuclei and non-neoplastic follicular epithelia in papillary thyroid carcinoma.

Nuclear Image Analysis Study of Neuroendocrine Tumors: Meeja Park, Taehwa Baek, Jongho Baek, Hyunjin Son, Dongwook Kang, Jooheon Kim, Hyekyung Lee; Korean J Pathol. 2012;46(1):38-41. Published online February 23, 2012; DOI: https://doi.org/10.4132/KoreanJPathol.2012.46.1.38

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Abstract PDF

Background

There is a subjective disagreement about nuclear chromatin in the field of pathology. Objective values of red, green, and blue (RGB) light intensities for nuclear chromatin can be obtained through a quantitative analysis using digital images.

Methods

We examined 10 cases of well differentiated neuroendocrine tumors of the rectum, small cell lung carcinomas, and moderately differentiated squamous cell lung carcinomas respectively. For each case, we selected 30 representative cells and captured typical microscopic findings. Using an image analyzer, we determined the longest nuclear line profiles and obtained graph files and Excel data on RGB light intensities. We assessed the meaningful differences in graph files and Excel data among the three different tumors.

Results

The nucleus of hematoxylin and eosin-stained tumor cells was expressed as a combination of RGB light sources. The highest intensity was from blue, whereas the lowest intensity was from green. According to the graph files, green showed the most noticeable change in the light intensity, which is consistent with the difference in standard deviations.

Conclusions

The change in the light intensity for green has an important implication for differentiating between tumors. Specific features of the nucleus can be expressed in specific values of RGB light intensities.

Citations

Citations to this article as recorded by

Difference of the Nuclear Green Light Intensity between Papillary Carcinoma Cells Showing Clear Nuclei and Non-neoplastic Follicular Epithelia in Papillary Thyroid Carcinoma
Hyekyung Lee, Tae Hwa Baek, Meeja Park, Seung Yun Lee, Hyun Jin Son, Dong Wook Kang, Joo Heon Kim, Soo Young Kim
Journal of Pathology and Translational Medicine.2016; 50(5): 355. CrossRef
Comparison of diagnostic accuracy between CellprepPlus® and ThinPrep® liquid‐based preparations in effusion cytology
Yong‐Moon Lee, Ji‐Yong Hwang, Seung‐Myoung Son, Song‐Yi Choi, Ho‐Chang Lee, Eun‐Joong Kim, Hye‐Suk Han, Jin young An, Joung‐Ho Han, Ok‐Jun Lee
Diagnostic Cytopathology.2014; 42(5): 384. CrossRef

Computerization of Surgical Pathology Reporting and Data Storage by Automatic Coding System using Personal Computer.: Woo Ho Kim, Jeong Wook Seo, Yong Il Kim; Korean J Pathol. 1989;23(4):410-415.

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Abstract PDF: The authors developed a computer program for use in report printing as well as data storage and retrieval system at the surgical pathology and its efficacy was evaluated at the Department of Pathology, Seoul National University Hospital. This program used IBM PC XT and was written in DBASE III plus language. The main features of the program included an automatic coding and decoding of the diagnosis, automatic searching of the previous biopsy during gross dictation, powerful word processing function and flexibility of the program. The data storage was carried out during the typewriting of the report, so that the typist's workload became markedly reduced. Two kinds of data files wer stored in the hard disk ; the temporary file contained full informations and the permanent file contained the core data only. Searching of a specific case was performed by pathology accession number, chart number, patient's name or by SNOMED code within a second. All the cases were arranged by copied to the diskette during the daily service automatically, with which data were easily restored in case of hard disk failure. The advantages of this program using a persosnal computer were discussed with comparison to those of larger computer system. Based on the experience of 8 months usage in Seoul National University, we assume that this program gives a sufficient solution to the surgical pathology service of many institutes where a large computer system with well designed software is not available yet.

Image Analysis of Glomerular Changes in Patients with Post-transplant IgA Nephropathy.: Kye Won Kwon, Hyeon Joo Jeong; Korean J Pathol. 2001;35(3):206-211.

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Abstract PDF: BACKGROUND
IgA nephropathy after renal transplantation (post-transplant IgAN) may recapitulate the IgAN of native kidneys, however, little has been reported about the histologic characteristics. The aim of this study is to apply glomerular morphometry using an image analyser to examine the histologic characteristics of post-transplant IgAN.
METHODS
The outer margin of the glomerulus (Bowman's area, BA) and glomerular tuft area (GA) were traced manually. The measured area were automatically calculated by KS300 image analysis system (Kontron, Munchen, Germany). The mesangial area (MA) was calculated with a summing each manually traced mesangial area. The total number of glomerular (GC) and mesangial cells (MC) were counted. Eight cases of renal section obtained by nephrectomy due to renal cell carcinoma (normal control: N-CTRL) and nineteen cases of renal section obtained from post-transplantation patients without IgAN (transplantation control: Tx-CTRL) served as controls.
RESULTS
A total of 35 biopsies were finally selected for measurement. BA and GA of post-transplant IgAN were 1.6 and 1.4 times larger than the N-CTRL, respectively, and were not significantly different from Tx-CTRL. MA was 1.4 times significantly larger than that of the Tx-CTRL. As compared to that of the N-CTRL, it was 1.2 times larger, but this difference was not statistically significant. The GC and MC of post-transplant IgAN and the Tx-CTRL were significantly lower than the N-CTRL. There were no significant correlations between glomerular hypertrophy and duration after renal transplantation, mesangial changes, segmental sclerosis, or degree of renal cortical interstitial fibrosis in post-transplant IgAN.
CONCLUSIONS
Prominent glomerular hypertrophy and mesangial expansion suggest a hyperfiltration injury in post-transplant IgAN and a possible way to glomerulosclerosis.

Development of the Pathology Laboratory Teaching Material Composed of Digital Pictures and Presentation over the Internet.: Sang Yeop Yi; Korean J Pathol. 2001;35(4):338-343.

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Abstract PDF: BACKGROUND
To maximize the efficiency of the pathology laboratory class, it has been realized that students should be given an environment with repeated learning situations. For this purpose, this study was designed to present the significance that pathologists need in order to publish teaching materials over the Internet.
METHODS
The pictures were captured as different magnified digital data from teaching glass slides. To modify the images, a graphics program was used, and these were transferred to the Microsoft PowerPoint software and developed as final teaching material. The final teaching material was then published on the Internet. This material can be browsed by searching through windows and by the indices of diagnosis. RESULTS: The comments from all users of the teaching material used in this study showed that it was user-friendly and appropriate for searching and reviewing. The users could assess information easily before and after the laboratory sessions. The quality of the images in this material was appropriate for printing. All users from our university were satisfied with the fact that all pictures were captured from their own teaching slides.
Conclusions
: Therefore, the teaching material used in this study is helpful for medical students studying pathology. Furthermore, this trial may induce others to develop pathology teaching materials over the Internet.

Computerization of Microscope Slide Labelling.: Dong Sug Kim, Dae Hong Suh; Korean J Pathol. 1997;31(7):628-634.

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Abstract PDF: The automation in surgical pathology, particularly in the reporting and encoding system using personal computers has been greatly improved in recent years, but the computerization of microscope slide labelling has not been improved. The authors have developed database program for slide labelling using FoxPro 2.5 and FoxBASE SCOUNIX 2.1.2: For I year during trial an effect has been put forward to simplify and organize the labelling work in routine surgical pathology. The program is now become easily applicable to the labelling work without disturbing the normal flow in a pathology laboratory. It is possible to get information concerning how many paraffin blocks and H&E slides have been made, as well as what kind of special stains have been requested for each case. The authors think that the computerization of labelling work in routine surgical pathology is a fairly easy task, and this should simplify the labelling work at a lower cost, diminish the workload of a typist or technician, and indirect information concerning the workload in a pathology laboratory can be calculated.

Computerization of 100,000 cases of Surgical Pathology Data at SNUH by Automatic Coding System using Personal Computer.: Woo Ho Kim, Ghee Young Choe, Jeong Wook Seo, Yong Il Kim; Korean J Pathol. 1990;24(4):509-512.

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Abstract PDF: A computer program using automatic coding of the diagnosis has been used for report printing as well as data storage and retrieval system at the Department of Pathology, Seoul National University Hospital. Previous surgical pathology files were also computerized by the automatic coding system using personal computer, and 100,000 cases of surgical pathology data during 7 years were computerized at present. The cpmputerized surgical files were counted and listed according to topograph and morphologic diagnosis. It is available to print out the list of a specific diagnosis or to copy the records to a floppy diskette. Collection of cases in surgical pathology files using cpmputerized automatic coding system becomes much convenient and accurate than using stored file cards or log books. In addition, previous biopsy records of the patient are automatically searched during the routine work so that understanding of a patient as a whole is possible through the informations about previous pathologic diagnosis. We confirm that automatic coding methods is the most practical and economic method for computerization of the surgical pathology records.

Korea University Laboratory Data Management and Communication System III-Pathology (KULAB III).: Kap N Lee, Seung Y Paik; Korean J Pathol. 1987;21(3):168-175.

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Abstract PDF: This pathology laboratory data management system is developed at the department of pathology and laboratory medicine, College of Medicine, Korea University, as an extension of Korea University laboratory Data managment and communication system. This is built in hospital computer for business, with the connection to the hospital business information system by software. The pathology department is only using terminals and printers, which enables us to maintain the lowest cost to maintain and operate the system. It has been written in COBO1 and utilized TOTAL Data Base and SNOMED (microglossary for surgical pathology). The input keys include patient hospital registration number, laboratory test code and SNOMED code or direct English written diagnostic words through dual masters of SNOMED.

Development of a CD-ROM Titled 'Atlas of Pathology' for Medical Students.: Dong Sug Kim, Yong Jin Kim, Sun Woo Park; Korean J Pathol. 2000;34(5):374-380.

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Abstract PDF: The authors have made a CD-ROM titled 'Atlas of Pathology (AP)' for medical students to understand histopathologic findings with ease. We used a 35 mm film scanner to convert an existing file into digital images. A pathologist and two professional programmers collaborated to create the program 'AtlasMaster 1.0' based on (IBM) PC for organization of previously captured digital images. Minimum system requirement for the 'AP' was Pentium II 166 MHz, 32 MB RAM, Windows 95 or 98, 800 600 resolution, 16-bit color, 20 speed CD-ROM drive. The 'AP' was composed of a execution file (Pathology_Atlas.exe), a DB file (pathology.mdb), and reference files (*.bmp, *.jpg, *.txt). The DB file contained fields for chapter, section, disease entity, and information for location of reference files. About 1,000 color images for various kinds of gross and microscopic pictures were stored in the CD-ROM and those were classified according to the chapters, sections, and disease entities. The 'AP' was easy to manipulate, and had advantages of self-learning for students. It could be applied to other fields in which many images were dealt with, such as histology, radiology, endoscopy, dermatology, and plastic surgery. The 'AP' was handy and very useful for medical students to study pathology and it would be a powerful self-learning tool.

Image Standardization and Determination of Gray Level Threshold in the Assessment of the Myocardial Fibrosis by the Computerized Image Analysis.: Nam Young Lee, Young Sik Park, Jin Haeng Chung, Jeong Wook Seo; Korean J Pathol. 1998;32(7):494-503.

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Abstract: The computerized image analysis is a useful tool for the quantitative assessment of histopathologic findings. In contrast to the usual microscopic examination by pathologists, the computerization should be accompanied with the standardization process of the image. We developed an algorithm to standardize images and to determine the optimal gray level threshold, using a myocardial fibrosis model. Sirius red staining was more convenient for the image analysis than Masson's trichrome staining because of a better contrast with the surrounding structures. To get an optimal measurement, light intensity was standardized at each of the fibrosis, myocardium and background. In this study, the most promising method to determine the degree of fibrosis was that of revising the background without tissue to a gray level of 200, obtaining a green component of the color image, revising the myocardial fiber to 163, and defining a partial ratio as fibrosis index when the gray level threshold was 120. These threshold levels and parameters were determined after drawing the binarization index curves according to the change of the gray level threshold and by the morphological examination of the actual binarization figures overlaid to the original color image. Through these processes we could get a consistent result on the myocardial fibrosis and we expect a similar principle applies when we analyze color images in the histopathologic quantitation by computerized image analysis.

Pathologic Diagnoses Management System "Pathology Slide Bank" Using IBM-PC Microcomputer.: Yong Koo Park, Moon Ho Yang, Won Tae Lee, Joo Young Park; Korean J Pathol. 1988;22(3):285-288.

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Abstract PDF: A simple and convenient management system in coding and storage of the pathologic diagnoses was developed by generating the dBASE III with IBM-PC microcomputer. The program named "Pathology Slide Bank" can store about 3,600 data according to the SNOP coding in a standard 51/4 inch floppy disk and retrieve the data within two minutes.

Computerization of Surgical Pathology Reporting by Personal Computer.: Dong Sug Kim, Young Ran Shim, Mee Jin Kim, Hae Joo Nam, Won Hee Choi, Tae Sook Lee; Korean J Pathol. 1992;26(2):146-153.

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Abstract PDF: The authors have been developed a menu-driven FoxBASE system for surgical pathology reporting and automatic encoding in Systematized Nomenclature of Medicine. The system requires no prior knowledge of FoxBASE and is readily installed on any IBM or it's compatible personal computer. Working sheet generation is automatically accompanied by data from previous cases on the same patient. Important data which include patient name, age, sex, surgical number, hospital unit number and encoded diagnoses, are stored on the hard disk permanently; complete reports are saved on floppy diskettes. Cases can be retrieved by patient name, surgical number, hospital unit number and SNOMED codes within 0.1 second. Daily work lists and listings of incomplete cases are easily obtained. This FoxBASE system has been in use for 1 year and 6 months and resulted in increased efficiency of retrieval and gathering of basic information for specific study, cost effectiveness, markedly diminished workload of typist and very short wasting time during complete restoration of data file for hard disk failure.

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