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Artificial Intelligence in Pathology
Hye Yoon Chang, Chan Kwon Jung, Junwoo Isaac Woo, Sanghun Lee, Joonyoung Cho, Sun Woo Kim, Tae-Yeong Kwak
J Pathol Transl Med. 2019;53(1):1-12.   Published online December 28, 2018
DOI: https://doi.org/10.4132/jptm.2018.12.16
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AbstractAbstract PDF
As in other domains, artificial intelligence is becoming increasingly important in medicine. In particular,deep learning-based pattern recognition methods can advance the field of pathology byincorporating clinical, radiologic, and genomic data to accurately diagnose diseases and predictpatient prognoses. In this review, we present an overview of artificial intelligence, the brief historyof artificial intelligence in the medical domain, recent advances in artificial intelligence applied topathology, and future prospects of pathology driven by artificial intelligence.

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Original Articles
Interobserver Variability in Diagnosing High-Grade Neuroendocrine Carcinoma of the Lung and Comparing It with the Morphometric Analysis
Seung Yeon Ha, Joungho Han, Wan-Seop Kim, Byung Seong Suh, Mee Sook Roh
Korean J Pathol. 2012;46(1):42-47.   Published online February 23, 2012
DOI: https://doi.org/10.4132/KoreanJPathol.2012.46.1.42
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AbstractAbstract PDF
Background

Distinguishing small cell lung carcinoma (SCLC) and large cell neuroendocrine carcinoma (LCNEC) of the lung is difficult with little information about interobserver variability.

Methods

One hundred twenty-nine cases of resected SCLC and LCNEC were independently evaluated by four pathologists and classified according to the 2004 World Health Organization criteria. Agreement was regarded as "unanimous" if all four pathologists agreed on the classification. The kappa statistic was calculated to measure the degree of agreement between pathologists. We also measured cell size using image analysis, and receiver-operating-characteristic curve analysis was performed to evaluate cell size in predicting the diagnosis of high-grade neuroendocrine (NE) carcinomas in 66 cases.

Results

Unanimous agreement was achieved in 55.0% of 129 cases. The kappa values ranged from 0.35 to 0.81. Morphometric analysis reaffirmed that there was a continuous spectrum of cell size from SCLC to LCNEC and showed that tumors with cells falling in the middle size range were difficult to categorize and lacked unanimous agreement.

Conclusions

Our results provide an objective explanation for considerable interobserver variability in the diagnosis of high-grade pulmonary NE carcinomas. Further studies would need to define more stringent and objective definitions of cytologic and architectural characteristics to reliably distinguish between SCLC and LCNEC.

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    Youcai Zhu, Feng Zhang, Dong Yu, Fang Wang, Manxiang Yin, Liangye Chen, Chun Xiao, Yueyan Huang, Feng Ding
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Morphometric Analysis for Pulmonary Small Cell Carcinoma Using Image Analysis.
Sun Min Jeong, Seung Yeon Ha, Jungsuk An, Hyun Yee Cho, Dong Hae Chung, Na Rae Kim, Sanghui Park
Korean J Pathol. 2011;45(1):87-91.
DOI: https://doi.org/10.4132/KoreanJPathol.2011.45.1.87
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AbstractAbstract PDF
BACKGROUND
There are few studies of how to diagnose small cell lung cancer in cytological tests through morphometric analysis. We tried to measure and analyze characteristics of small cell carcinoma in lung by image analysis.
METHODS
We studied three types of cytologic specimens from 89 patients who were diagnosed with small cell lung cancer by immunohistochemistry. We measured area, perimeter, maximal length and maximal width of cells from small cell carcinoma using image analysis.
RESULTS
In lung aspirates, the nuclear mean area, perimeter, maximal length and maximal width of small cell lung cancer were 218.69 microm2, 55 microm, 18.48 microm and 14.65 microm. In bronchial washings, nuclear measurements were 194.66 microm2, 50.07 microm, 16.27 microm and 14.1 microm. In pleural fluid, values were 177.85 microm2, 48.09 microm, 15.7 microm and 13.37 microm.
CONCLUSIONS
Nuclear size of small cell lung carcinoma is variable and depends on the cytology method. Nuclei are spindle-shaped and larger in small cell carcinoma from lung aspirates than in bronchial washings or pleural fluid. The cytoplasms of the cells in bronchial washings and pleural fluid were swollen. Therefore, one should consider morphologic changes when trying to diagnose small cell lung cancer through cytological tests.

Citations

Citations to this article as recorded by  
  • Interobserver Variability in Diagnosing High-Grade Neuroendocrine Carcinoma of the Lung and Comparing It with the Morphometric Analysis
    Seung Yeon Ha, Joungho Han, Wan-Seop Kim, Byung Seong Suh, Mee Sook Roh
    Korean Journal of Pathology.2012; 46(1): 42.     CrossRef
Detecting Malignant Urothelial Cells by Morphometric Analysis of ThinPrep(R) Liquid-based Urine Cytology Specimens.
Bong Kyung Shin, Young Suk Lee, Hoiseon Jeong, Sang Ho Lee, Hyunchul Kim, Aree Kim, Insun Kim, Han Kyeom Kim
Korean J Cytopathol. 2008;19(2):136-143.
DOI: https://doi.org/10.3338/kjc.2008.19.2.136
  • 2,516 View
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  • 5 Crossref
AbstractAbstract PDF
Urothelial carcinoma accounts for 90% of all the cases of bladder cancer. Although many cases can be easily managed by local excision, urothelial carcinoma rather frequently recurs, tends to progress to muscle invasion, and requires regular follow-ups. Urine cytology is a main approach for the follow-up of bladder tumors. It is noninvasive, but it has low sensitivity of around 50% with using the conventional cytospin preparation. Liquid-based cytology (LBC) has been developed as a replacement for the conventional technique. We compared the cytomorphometric parameters of ThinPrep(R) and cytospin preparation urine cytology to see whether there are definite differences between the two methods and which technique allows malignant cells to be more effectively discriminated from benign cells. The nuclear-to-cytoplasmic ratio value, as measured by digital image analysis, was efficient for differentiating malignant and benign urothelial cells, and this was irrespective of the preparation method and the tumor grade. Neither the ThinPrep(R) nor the conventional preparation cytology was definitely superior for distinguishing malignant cells from benign cells by cytomorphometric analysis of the adequately preserved cells. However, the ThinPrep(R) preparation showed significant advantages when considering the better preservation and cellularity with a clear background.

Citations

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  • Utility of Image Morphometry in the Atypical Urothelial Cells and High-Grade Urothelial Carcinoma Categories of the Paris System for Reporting Urinary Cytology
    K.C. Sharan, Manish Rohilla, Pranab Dey, Radhika Srinivasan, Nandita Kakkar, Ravimohan S. Mavuduru
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    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
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    Ji Yong Kim, Hyung Jin Kim
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    Indian Journal of Surgery.2014; 76(1): 26.     CrossRef
  • Evaluation of Urine Cytology in Urothelial Carcinoma Patients: A Comparison of CellprepPlus® Liquid-Based Cytology and Conventional Smear
    Seung-Myoung Son, Ji Hae Koo, Song-Yi Choi, Ho-Chang Lee, Yong-Moon Lee, Hyung Geun Song, Hae-Kyung Hwang, Hye-Suk Han, Seok-Joong Yun, Wun-Jae Kim, Eun-Joong Kim, Ok-Jun Lee
    Korean Journal of Pathology.2012; 46(1): 68.     CrossRef
The Effect of Ginseng Saponin on the Dopaminergic Neurons in the Parkinson's Disease Model in Mice.
Chang Ok Kim, Ki Sok Kim, Young Buhm Huh, Byeong Woo Ahn, Beom Seok Han, Kwang Sik Choi, Ki Yul Nam, Sang Woo Juhng
Korean J Pathol. 1997;31(9):805-814.
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AbstractAbstract PDF
Saponin has been known to be a major antioxidant component in panax ginseng. Recent experimental study suggests that some antioxidant materials prevent Parkinson's disease caused by 1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine (MPTP) in an animal model. The present study was performed to demonstrate the effect of ginseng saponins in the Parkinson's disease model induced by MPTP. To verify the effect of ginseng saponin on dopaminergic neurons in the mice brain, the tyrosine hydroxylase-immunoreactive (TH-ir) neurons were observed by immunohistochemical stain and immunoelectron microscopy (preembedding method). Also, in order to estimate the immunoreactivity of dopaminergic neuropils, they were quantified by image analysis. The number of TH-ir neurons of substantia nigra was significantly increased in the high-dose (0.46 mg/kg) ginseng saponin group compared with the MPTP injected group. The immunoreactivity of TH-ir neuropils in striatum was significantly increased in both high and low-dose (0.1 mg/kg) ginseng saponin groups compared with the MPTP injected group. In immunoelectron microscopic observation, TH-ir neurons of the control and both ginseng saponin injected group showed normal nuclei and well preserved cytoplasmic organelles. In the MPTP injected group, dying dopaminergic neurons showed destroyed nuclei and cytoplasmic organelles. These results suggest that ginseng saponin has a protective effect on the Parkinson's disease model induced by MPTP.
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.
  • 1,503 View
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AbstractAbstract
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.
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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AbstractAbstract 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.
DNA Ploidy in Anaplastic Carcinoma of the Thyroid Gland by Image Analysis.
Ji Shin Lee, Min Cheol Lee, Chang Soo Park, Sang Woo Juhng
Korean J Cytopathol. 1995;6(1):10-17.
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AbstractAbstract PDF
Anaplastic carcinoma of the thyroid gland is one of the most malignant tumors. Recently, DNA ploidy measured by flow cytometry and image analysis has been suggested as an additional useful indicator of tumor behavior. Studies on the occurrence and clinical significance of DNA aneuploidy in anaplastic carcinoma of the thyroid are rare. In this study, the pattern of DNA ploidy was measured by image analysis on Papanicolaou stained slides in four cases of anaplastic carcinoma and also measured by flow cytometry using paraffin blocks in two cases. In all cases of anaplastic carcinoma. DNA aneuploidy was found by image analaysis. By flow cytometry, one case had a diploid peak and the other case had an arieuploid peak. According to the above results, we conclude that anaplastic carcinoma of the thyroid glands have a high incidence of DNA aneuploidy and image analysis using Papanicolaou stained slides is a useful method in detecting DNA aneuploidy.
A study of Digital Image Analysis of Chromatin Texture for Discrimination of Thyroid Neoplastic Cells.
Sang Woo Juhng, Jae Hyuk Lee, Eun Kyung Bum, Chang Won Kim
Korean J Cytopathol. 1996;7(1):23-30.
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AbstractAbstract PDF
Chromatin texture, which partly reflects nuclear organization, is evolving as an important parameter indicating cell activation or transformation. In this study, chromatin pattern was evaluated by image analysis of the electron micrographs of follicular and papillary carcinoma cells of the thyroid gland and tested for discrimination of the two neoplasms. Digital grey images were converted from the electron micrographs; nuclear images, excluding nucleolus and intranuclear cytoplasmic inclusions, were obtained by segmentation; grey levels were standardized; and grey level histograms were generated. The histograms in follicular carcinoma showed Gaussian or near-Gaussian distribution and had a single peak, whereas those in papillary carcinoma had two peaks(bimodal), one at the black zone and the other at the white zone. In papillary carcinoma. the peak in the black zone represented an increased amount of heterochromatin particles and that at the white zone represented decreased electron density of euchromatin or nuclear matrix. These results indicate that the nuclei of follicular and papillary carcinoma cells differ intheir chromatin pattern and the difference may be due to decondensed chromatin and/or matrix substances.
Analysis of DNA Ploidy Patterns and Nuclear Morphometry in Diethylnitrosamine Induced Hepatocyte Nodules and Hepatocellular Carcinoma of Rats.
Chan Choi, Myung Kwan Kim, Kwan Mook Chae, Eun Cheol Kim, Hyung Bae Moon
Korean J Pathol. 1993;27(3):226-234.
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This study was designed to answer the question; (1) How does the DNA ploidy pattern change in hepatocarcinogenesis? (2) How does the nuclear morphology change in hepatocarcinogenesis? Diethylnitrosamine(DEN) (16.5 mg per kg) was subcutaneously injected to female Sprague-Dawley rats(150~200g) by weekly interval for 30 weeks. DNA ploidy and parameters of nuclear morphology were measured by image analyser(IBAS 200, Kontron, FRG). The DNA ploidy pattern was divided into three basic patterns(diploid, polyploid, and aneuploid modes). In 8 cases of saline-injected control rats, the DNA histograms showed all polyploid pattern. Inhepatocyte nodules(hyperplastic nodules), DNA diploidy was the most frequent pattern, being followed by polyploid and aneuploid DNA patterns, contrast to hepatocelular carcinomas in which polyploid DNA pattern was most frequently noted being followed by diploid and aneuploid DNA pattern. Although the nuclei of hepatocytes in hepatocyte nodules and hepatocellular carcinomas were larger and more pleomorphic than those of normal hepatocytes, they were as same as those of normal hepatocytes in regard to nuclear hyperchromasia. DNA content, which was increased in hepatocarcinogenesis, was significantly related to the nuclear area.
An Image Analytical Study on the Structural Spectrum of Intestinal Metaplasia-Dysplasia-Carcinoma of the Stomach.
Sang Woo Juhng, Dong Ha Park, Ji Shin Lee, Kyu Hyuk Cho
Korean J Pathol. 1993;27(1):50-57.
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Intestinal metaplasia and dysplasia of the stomach have been stressed as precursors of gastric carcinoma of the intestinal type, although their preneoplastic nature is still debated. In this study, the cytomorphometric and cytokinetic spectra of the suggested preneoplastic and neoplastic lesions of the stomach were investigated. From the resected stomachs of early gastric carcinoma of intestinal type, areas of normal, intestinal metaplasia, dysplasia, and carcinoma were selected. They were immunostained for proliferating cell nuclear antigen, counterstained with propidium iodide, and various nuclear parameters were measured by image analysis. Normal and intestinal metaplastic mucosae differed by the localization of proliferation zone, but not by nuclear profile area, circular shape factor, and proliferation index. In dysplasia, proliferation zone covered large parts of the dysplastic area. Nuclear profile area and proliferation index were larger whereas circular shape factor was smaller than in normal or intestinal metaplasia. Carcinomatous lesion had diffuse proliferation activity, the largest nuclear profile area and proliferating index, and circular shape factor in-between those of normal or intestinal metaplasia and dysplasia. The above results showed a structural spectrum among normal of intestinal metaplasia, dysplasia, and carcinoma of intestinal type in cytomorphometric and cytokinetic terms. The structural spectrum raises the possibility that dysplasia of the stomach is a preneoplastic lesion.
Evaluation of DNA Ploidy and Other Morphometric Parameters of Ovarian Mucinous Tumors.
Yun Mee Kim, Sang Woo Juhng, Joo Yong Yoo, Kyu Hyuk Cho
Korean J Pathol. 1991;25(5):397-406.
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AbstractAbstract
Biological behavior of malignant tumors has been assessed by morphological grading, clinical staging, and estimating other tumor markers. Recently DNA ploidy measured by flow cytometry and image analyser has been suggested as an additional useful indicator of the tumor behavior. In order to extract useful tumor cell-specific information in ovarian mucinous tumors, DNA contents and other morphologic parameters were measured by image analysis and DNA ploidy was also measured by flow cytometry. In all cases of cystadenoma, DNA diploidies were observed. In borderline malignancy, DNA diploidies were chiefly observed except one case of polyploidy. In true malignancy, DNA aneuploidies were observed except one case of polyploidy and two cases of diploidies by image analysis, and except four cases of diploides and one cas of polyploidy by flow cytometry. The statistical significance were observed in DNA ploidy pattern by image analysis. In nuclear areas, perimeters and major axis, statistical significance were not observed. These results suggest that DNA ploidy pattern are more or less independent parameter as an additional useful indicator of the histological grade of malignancy and that image analysis are better than flow cytometry in detecting DNA aneuploidy.
Morphometric Analysis of Cirrhotic Nodules in Hepatocellular Carcinoma-bearing Livers.
Gyeong Hoon Kang, Yong Il Kim
Korean J Pathol. 1991;25(4):338-345.
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It has been well known that liver cirrhosis, regardless of its etiology, is an important predisposing factor in hepatocarcinogenesis. However, the type of cirrhosis in hepatocellular carcinoma(HCC)-bearing liver varies not only by geographic areas but also with the cirteria applied for morphological classification of cirrhosis. To elucidate the relationship between the nodule size of HCC-bearing cirrhotic liver and clinicopathologic features, we measured cirrhotic nodule areas of 49 surgically resected HCC cases using image analyzer. The morphological type of cirrhosis was predominantly macronodular(49%), and followed by mixed(37%) and micronodular(14%). Seventy percent of the cases showed seropositivity for HBsAg. The average area of cirrhotic nodules was significantly larger in HBsAg-positive cases(mean: 6.14 mm2) than that of HBsAg-negative cases(mean: 2.5 mm2)(p<0.05), and their size was bigger in cases with grossly expansile pattern of HCC than those cases with infiltrative ones(p<0.05). Based on the above findings, we assume that seropositivity of HBsAg may influence on the regenerative activity of cirrhotic nodules and also subsequent increase of risk for further development of HCC. The presence of cirrhohsis and nodule size seem to be the important contributing factors to determine the growing patterns of HCC.
Evaluation of DNA Ploidy of Bronchogenic Carcinomas by Image Analysis.
Soo Sung Kim, Jae Hyuck Lee, Sang Woo Jung, Joo Yong Yoo
Korean J Pathol. 1991;25(3):238-244.
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In order to extract useful tumor cell-specific information. DNA contents and other morphological parameters were measured by image analysis. Single cell preparation was made from archived paraffin blocks of 14 cases of bronchogenic squamous cell carcinoma, poorly differentiated, by protease treatment. The cells were Feulgen stained, and DNA content, area, perimeter, and major axis of the tumor cell nuclei were measured. Inflammatory lymphocytes concurrent with the tumor cells were used as an internal standard. DNA ploidies of the lymphocytes and 2C tumor cells showed simple peaks with Gaussian distribution and mean coefficients of variation of 10% and 14% respectively. By the location and proportion of the tumor cells other than 2C cells, DNA ploidies could be classified into diploidy(1 case), polyploidy(2 cases), and aneuploidy(11 cases). The mean proportion of DNA aneuploidal tumor cells relative to the total tumor cells was 82.8%. In 8 cases, nuclear areas showed more or less overlapped distribution, whereas DNA contents showed discrete peaks. THes results suggest that many bronchogenic squamous cell carcinomas, poorly differentiated, have DNA aneuploidy and high proportion of aneuploidal cells, and that nuclear size and DNA content are more or less independent parameters.

J Pathol Transl Med : Journal of Pathology and Translational Medicine
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