Background The Korean Society for Cytopathology introduced a digital proficiency test (PT) in 2021. However, many doubtful opinions remain on whether digitally scanned images can satisfactorily present subtle differences in the nuclear features and chromatin patterns of cytological samples.
Methods We prepared 30 whole-slide images (WSIs) from the conventional PT archive by a selection process for digital PT. Digital and conventional PT were performed in parallel for volunteer institutes, and the results were compared using feedback. To assess the quality of cytological assessment WSIs, 12 slides were collected and scanned using five different scanners, with four cytopathologists evaluating image quality through a questionnaire.
Results Among the 215 institutes, 108 and 107 participated in glass and digital PT, respectively. No significant difference was noted in category C (major discordance), although the number of discordant cases was slightly higher in the digital PT group. Leica, 3DHistech Pannoramic 250 Flash, and Hamamatsu NanoZoomer 360 systems showed comparable results in terms of image quality, feature presentation, and error rates for most cytological samples. Overall satisfaction was observed with the general convenience and image quality of digital PT.
Conclusions As three-dimensional clusters are common and nuclear/chromatin features are critical for cytological interpretation, careful selection of scanners and optimal conditions are mandatory for the successful establishment of digital quality assurance programs in cytology.
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Sensitivity, Specificity, and Cost–Benefit Effect Between Primary Human Papillomavirus Testing, Primary Liquid‐Based Cytology, and Co‐Testing Algorithms for Cervical Lesions Chang Gok Woo, Seung‐Myoung Son, Hye‐Kyung Hwang, Jung‐Sil Bae, Ok‐Jun Lee, Ho‐Chang Lee Diagnostic Cytopathology.2024;[Epub] CrossRef
Background The Korean Society for Cytopathology has conducted the Continuous Quality Improvement program for cytopathology laboratories in Korea since 1995. In 2018 as part of the program, an annual survey of cytologic data was administered to determine the current status of cytopathology practices in Korea. Methods: A questionnaire was administered to 211 cytopathology laboratories. Individual laboratories submitted their annual statistics regarding cytopathology practices, diagnoses of gynecologic samples, inadequacy rates, and gynecologic cytology-histology correlation review (CHCR) data for 2018. In addition, proficiency tests and sample adequacy assessments were conducted using five consequent gynecologic slides. Results: Over 10 million cytologic exams were performed in 2018, and this number has almost tripled since this survey was first conducted in 2004 (compounded annual growth rate of 7.2%). The number of non-gynecologic samples has increased gradually over time and comprised 24% of all exams. The overall unsatisfactory rate was 0.14%. The ratio of the cases with atypical squamous cells to squamous intraepithelial lesions accounted for up to 4.24. The major discrepancy rate of the CHCR in gynecologic samples was 0.52%. In the proficiency test, the major discrepancy rate was approximately 1%. In the sample adequacy assessment, a discrepancy was observed in 0.1% of cases. Conclusions: This study represents the current status of cytopathology practices in Korea, illustrating the importance of the Continuous Quality Improvement program for increasing the accuracy and credibility of cytopathologic exams as well as developing national cancer exam guidelines and government projects on the prevention and treatment of cancer.
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Diagnostic proficiency test using digital cytopathology and comparative assessment of whole slide images of cytologic samples for quality assurance program in Korea Yosep Chong, Soon Auck Hong, Hoon Kyu Oh, Soo Jin Jung, Bo-Sung Kim, Ji Yun Jeong, Ho-Chang Lee, Gyungyub Gong Journal of Pathology and Translational Medicine.2023; 57(5): 251. CrossRef
Recent Application of Artificial Intelligence in Non-Gynecological Cancer Cytopathology: A Systematic Review Nishant Thakur, Mohammad Rizwan Alam, Jamshid Abdul-Ghafar, Yosep Chong Cancers.2022; 14(14): 3529. CrossRef
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Background Intratumoral fibrosis (ITF) is a frequent histologic finding in solid organ tumors. Renal cell carcinoma (RCC) is a highly vascularized tumor with different shapes and degrees of ITF and inflammation. ITF is a poor prognostic factor, especially in breast cancer, and is related to intratumoral necrosis (ITN) and intratumoral inflammation (ITI). However, the significance of ITF in RCC has not been fully studied. In this study, we evaluate the relationships between ITF and other clinicopathologic parameters associated with RCC prognosis.
Methods ITF was evaluated in 204 clear cell renal cell carcinoma (CCRCC) specimens according to presence and grade of fibrosis, degree of ITI, and presence of ITN. Lysyl oxidase (LOX) expression in tumor cells was also evaluated with clinicopathologic parameters.
Results Among 204 CCRCC cases, 167 (81.7%) showed ITF, 71 (34.8%) showed ITI, 35 (17.2%) showed ITN, and 111 (54.4%) showed LOX expression. ITF correlated with Fuhrman nuclear grade (p = .046), lymphovascular invasion (LVI) (p = .027), and ITN (p = .036). Patients with ITF had a poor five-year overall survival rate (p = .104).
Conclusions ITF is related to other poor prognostic factors in CCRCC, such as Fuhrman nuclear grade, ITN, and LVI, but ITF itself had no significant correlation with prognosis of CCRCC.
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BACKGROUND The cytokine-induced activation of hepatic stellate cells (HSC) plays a major role in liver fibrosis.
Quiescent HSCs undergo phenotypic transformation called "transdifferentiation" in response to viral, chemical or immune insults to the liver. The cytokine TGF-beta1 plays a key role in progressive liver fibrosis. Since small interfering RNA (siRNA) is a powerful tool for silencing gene expression post-transcriptionally, the present study aimed to determine whether synthetic TGF-beta1 siRNA down-regulates the expression of the TGF-beta1 gene in immortalized and activated rat HSCs (HSC-T6s). The study examined whether synthetic TGF-beta1 siRNA prevents rat HSCs activation and extracellular matrix (ECM) production. METHODS TGF-beta1 siRNA or a control (pU6) siRNA was added to HSC-T6 culture media. We then performed RT-PCR and western blot analyses for TGF-beta1 and ECM components (fibronectin, type-I collagen, and TIMP-1). RESULTS: TGF-beta1 siRNA significantly down-regulated expression of TGF-beta1 mRNA and protein and attenuated mRNA and protein expressions of type-I collagen, fibronectin, and TIMP-1, as compared to the control. CONCLUSIONS: TGF-beta1 siRNA can effectively down-regulate the expression of TGF-beta1 in rat HSC, resulting in significant inhibition of HSC activation and of ECM production. These data indicate that synthetic TGF-beta1 siRNA can be a useful treatment modality to prevent liver fibrosis.
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Background DNA prevalence and type distribution of human papillomavirus (HPV) varies geographically. We investigated HPV prevalence and type distribution in Korean women using the MyHPV DNA chip testing. Methods: A total of 2,368 women from five regions of the country underwent Pap smear examination and MyHPV chip testing. Results: Overall HPV positivity was 15.8% and 78.4% in women with normal and abnormal cytology, respectively. High-risk HPV infection was strongly correlated with cytological atypia. In women with abnormal cytology, the five most common HPV types were 16, 58, 18, 52, and 56/53, and HPV16 was significantly the most common type in most geographical regions. After HPV16, HPV58, and 52 were the next most frequently detected types.
Women with normal cytology, in contrast, showed heterogeneity in HPV type distribution. High-grade intraepithelial lesions infected with HPV16, 18, 31 or 45 are more likely to progress to carcinoma. Conclusions: The HPV chip test can provide useful data regarding HPV positivity and type. The most common HPV type in Korean women with abnormal cytology is HPV16, with HPV58 and 52 being frequently present. Our data may have important implications for vaccination programs and the development of cervical screening.
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Uncommon and Rare Human Papillomavirus Genotypes Relating to Cervical Carcinomas Na Rae Kim, Myunghee Kang, Soon Pyo Lee, Hyunchul Kim, Jungsuk An, Dong Hae Chung, Seung Yeon Ha, Hyun Yee Cho Korean Journal of Pathology.2014; 48(1): 43. CrossRef
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Sebaceous carcinoma is a rare malignant epithelial tumor and has diverse clinical presentations as well as a variety of histologic patterns. Although the overwhelming majority of sebaceous carcinomas occur on the eyelid, they may also arise where sebaceous gland and hair are found together, but they favor the head and neck. We report a case of sebaceous carcinoma of the umbilicus in a 68-year-old man who had suffered from a long standing recurrent Bowen's disease of 23 years. The recurrent Bowen's disease in this patient appeared to be closely related to multiple arsenic medication 49 years and 39 years earlier. The excised specimen of umbilicus revealed a well demarcated, 1.5x1 cm sized tumor with grey-yellow hue. The tumor was identified as sebaceous carcinoma, which was characterized by lobular and comedo-carcinoma patterns. The tumor cells showed cytoplasmic foamy vacuolation, nuclear pleomorphism, and high mitotic activity. On an Oil-Red-O stain, the tumor cells were found to contain fine lipid droplets. The intracytoplasmic lipid vacuoles were demonstrated by an electron microscopic examination.
Focal segmental glomerulosclerosis (FSGS) is presented as not only one of the primary glomerular diseases but also as a secondary phenomenon for chronic irreversible renal diseases. The main pathological feature of FSGS is the accumulation of extracellular matrix in the glomeruli, for which overexpression of transforming growth factor-beta (TGF-beta) may be responsible for the accumulation of pathological matrix. A new animal model (FGS/NgaKist mouse) of renal failure by spontaneously generating glomerulosclerosis was developed. To elucidate the role of TGF-beta for FSGS, authors observed glomeruli of FGS/NgaKist mouse periodically. FGS/NgaKist mouse strain showed progression of proteinuria and focal glomerular sclerosis with the aging. The glomeruli showed anti IgG, IgA, IgM and complement complex deposits and extracellular matrix accumulation in the mesangium. TGF-beta mRNA and beta2antibody expressions were increased with the advance of glomerular sclerosis. The results suggest the following; FSGS of FGS/NgaKist strain is immune mediated disease and this stimuli on mesangial or endothelial cells may activate TGF-beta gene in their nuclei. This activation, in turn, can cause sclerosis by increasing TGF-beta mRNA transcription followed by secretion of TGF-beta and its action as cytokine for making collagen fibrils.
Almost all advanced glomerular diseases have glomerular sclerotic changes to varying degrees whatever causes their primary glomerular disease are. Pathogenesis of these sclerosis has been thought of as the hyperfiltration in the primary glomerulosclerosis due to development of glomerular hypertension in each insulted glomeruli. This background gave the theoretical bases for antihypertensive therapies for supporting chronic renal insufficient patients.
Angiotensin converting enzyme (ACE) inhibitor, one of the antihypertensive drugs, has received attention recently for its effectiveness. The aims of this study determined the effects and mechanism of the ACE inhibitor, enalapril, on the glomerulosclerosis in FGS/NgaKist mice, which was an animal model of chronic renal failure by generating spontaneously heavy proteinuria and progressive glomerulosclerosis. Five-week-old FGS/NgaKist mice (n=38) were assigned to four groups. Group 1a (n=6) and group 2a (n=8) fed with a vehicle, were sacrificed at the end of 10 weeks and 15 weeks, respectively. Group 1b (n=12) and 2b (n=12) received enalapril (100 mg/L) in drinking water for 5 weeks and 10 weeks from 6th week of age respectively, and were sacrified on the same day as the control groups. Doses of enanapril were maintained to 2 mg/kg/day by measuring the amount of water consumption. In enalapril groups 1b and 2b, systemic blood pressure (74.7 14.0 mm Hg, 74.3 15.9 mmHg) were significantly lower than control group 2a (116.1 4.6 mmHg, P<0.001). Similarly, degree of proteinuria lowered in enalapril group 2b versus control group 2a (0% and 50.0%, P<0.001). Glomerulosclerosis percentage significantly decreased (P<0.001) (group 1b and 2b; 1.9 6.5, 5.6 7.0 vs control 1a and 2a; 32.8 15.5, 31.4 13.8). Glomerulosclerosis score also decreased (P<0.001) (group 1b and 2b; 0.02 0.08 vs control 1a and 2a; 0.48 0.12, 0.30 0.14). The immunofluorescent staining of enalapril groups showed negative for mesangial deposition of IgG, IgA, IgM, and C3 which were positive in control groups. Immunohistochemical staining with TGF-beta1 was negative in enalapril groups and sclerotic glomeruli both enalapril groups and control groups. These results support that the ACE inhibitor has a renoprotective effect on glomerulosclerosis not only by decreasing the blood pressure but also by suppressing the immune deposits on glomeruli.
The association between occupational asbestos exposure and the subsequent development of malignant mesothelioma of pleura is well recognized. We analyzed an asbestos body by energy dispersive X-ray analyser in a case of malignant mesothelioma of pleura who had a history of asbestos exposure 30 years ago. In transmission electron microscope, the asbestos body was composed of a core of refractile thin asbestos fiber bundle and beaded masses of electron-dense iron and protein complex. The core fibers were analyzed as an amphibole type crocidolite fiber [(Na2Fe3Fe2(Si8O22)(OH)2] which composed of high content of silicon, iron and sodium.
A case of plasmacytoma of the ovary and breast, which developed in a patient with a solitary plasmacytoma in the lumbar vertebra for nine months, was diagnosed cytologically and histologically.
Enlargement of the right ovary and multiple palpable masses in the right and left breast were already present at six months after the diagnosis of vertebral solitary plasmacytoma. At eight months, plasma cell leukemia developed, and nine months the enlarged both ovaries, replaced by yellowish-gray solid tumors showed infiltration of immature plasma cells. The cytologic features of the ovarian tumors were same with those of the breast tumor. The tumor cells were of predominantly immature plasma cells with one or more nuclei. Some mature plasma cell had an eccentric nucleus with single nucleolus and peripherally clumped chromatin. Binucleated or multinucleated giant cells were often present.
Histologically, sheets of poorly differentiated plasmacytoid tumor cells were separated by strands of hyaline fibrous tissue. On immunohistochemical stains, the tumor cells showed strong reactivity for lambda-light chain but no reaction for kappa-light chain, cytokeratin, or leukocyte common antigen.
Fine needle aspiration (FNA) cytological examination is an appropriate method for the evaluation of pulmonary nodules.
In major types of lung cancer, its diagnostic accuracy is quite high. However, it is sometimes difficult, using this technique, to differentiate between some unusual phenotypes including adenosquamous carcinoma, bronchioloalveolar carcinoma (BAC), neuroendocrine tumor, mucoepidermoid carcinoma, and sclerosing hemangioma. Here, we present a case involving extremely well differentiated adenosquamous carcinoma, mimicking benign lesions, such as pulmonary scar and adenomatoid malformation with squamous metaplasia. The patient was a 68-year-old man presenting with a solitary pulmonary nodule (1.6x1.6 cm), which was incidentally found at the periphery of the right lower lobe.
FNA revealed some clusters of glandular cells with minimal atypia, in addition to squamous cells at a nearly full maturational state. Histological examination verified the cytological diagnosis on a lobectomy specimen. The tumor exhibited a well differentiated adenocarcinoma component, mimicking the bronchioles in scarred lung tissue, and a well differentiated squamous cell carcinoma component, mimicking the squamous cell nests of adenoacanthoma, in the other organs. In the present case, the possibility of adenosquamous carcinoma should have been considered if squamous cells were seen in the FNA from the peripheral pulmonary nodule, even though they appeared to be benign.
Colorectal adenocarcinoma with rhabdoid features is extremely rare and only two cases have been previously reported. We report here on a case of colorectal adenocarcinoma with prominent rhabdoid features in a 69-year-old female. The specimen was an ulcerative mass from the sigmoid colon, and it measured 3.5x3 cm. Microscopic examination of the tumor showed mostly rhabdoid cells that had eccentrically located large nuclei and foci of glandular formation. A transitional area from the poorly differentiated adenocarcinoma to the rhabdoid tumor was also noted. Immunohistochemical studies showed strong reactivity of the glandular forming cells for pan-cytokeratin, and the cells were occasionally positive for vimentin. The cells with rhabdoid features were diffusely positive for vimentin and focally positive for pan-cytokeratin. These results suggested that the cells with rhabdoid features originated from dedifferentiated primary adenocarcinoma. Since colorectal adenocarcinoma with rhabdoid features is highly aggressive and unresponsive to conventional therapy, making the preoperative diagnosis is important to facilitate the treatment.
A case of prominent pseudoepitheliomatous hyperplasia (PEH), that was misdiagnosed as squamous cell carcinoma (SCC) on the frozen section occured in the nasal mucosa of a patient suffering with nasal type NK/T cell lymphoma. To prevent misdiagnosis of this lesion, pathologists should be aware that NK/T cell lymphoma may be associated with overlying mucosal PEH, and so the physician must adhere to strict diagnostic criteria for making the diagnosis of SCC. The pathogenesis of PEH associated with NK/T cell lymphoma is not still clear, but it may be related to the production of growth factors, especially epidermal growth factor and transforming growth factor, by the underlying tumors.
Heterotopic mesenteric ossification is a very rare reactive lesion in the small bowel mesentery, and it is related with trauma or surgical operation. It is pathologically characterized by well formed bone trabeculae and prominent osteoblastic rimming and is clinically related to rapid and recurrent bowel obstruction symptoms. This unusual reactive process shares many clinical and pathologic features with myositis ossificans. We report here on a rare case of heterotopic mesenteric ossification in 28-year-old man who underwent a delayed small bowel resection 15 days after trauma.
Herein, a case of nabothian cysts, extending into the deep cervical wall is reported. The radiologic and clinical examinations were suggestive of adenoma malignum. The cysts were incidentally found in a 42 year-old woman with abnormal uterine bleeding of about ten days duration. The patient underwent a total abdominal hysterectomy. A gross examination of the cervix revealed multiple mucin-filled cysts that extended almost to the serosa. On microscopic examination, the cysts were lined by columnar to flattened endocervical type cells, which are usually found in nabothian cysts. No atypical features or mitotic activity were noted. A deep nabothian cyst is a rare benign lesion of the cervix that should be distinguished from a cystically dilated adenoma malignum.