Background Since 2007 when anaplastic lymphoma kinase (ALK) rearrangements were discovered in non-small cell lung cancer, the ALK gene has received attention due to ALK-targeted therapy, and a notable treatment advantage has been observed in patients harboring the EML4/ALK translocation. However, using ALK-fluorescence in situ hybridization (FISH) as the standard method has demerits such as high cost, a time-consuming process, dependency on interpretation skill, and tissue preparation. We analyzed the histologic findings which could complement the limitation of ALK-FISH test for pulmonary adenocarcinoma. Methods: Two hundred five cases of ALK-positive and 101 of ALK-negative pulmonary adenocarcinoma from January 2007 to May 2013 were enrolled in this study. The histologic findings and ALK immunohistochemistry results were reviewed and compared with the results of ALK-FISH and EGFR/KRAS mutation status. Results: Acinar, cribriform, and solid growth patterns, extracellular and intracellular mucin production, and presence of signet-ring-cell element, and psammoma body were significantly more often present in ALK-positive cancer. In addition, the presence of goblet cell-like cells and presence of nuclear inclusion and groove resembling papillary thyroid carcinoma were common in the ALK-positive group. Conclusions: The above histologic parameters can be helpful in predicting ALK rearranged pulmonary adenocarcinoma, leading to rapid FISH analysis and timely treatment.
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BACKGROUND This study investigated whether human papillomavirus (HPV) genotype is related to koilocytic changes in cervical cytology and histology, and what factors cause discrepancies among cytology, HPV DNA chip tests, and biopsies. METHODS We examined 174 of 949 cases histologically confirmed by both cytology and HPV DNA chip testing. We analyzed koilocytic changes in cytology and biopsies according to HPV genotype. RESULTS HPV-16 significantly coincided with nuclear size variation and hyperchromasia, although the cytomorphologic features correlated with other HPV genotypes were not statistically significant. By analyzing 68 cases in which there were discrepancies between the HPV DNA chip test and histological results, we confirmed that artifacts or glycogen acanthosis resulted in the over-diagnoses of four HPV-negative cases with normal cytology. Four diagnostic errors and four sampling errors were present in eight HPV-positive cases. The degree of nuclear size variation significantly influenced the cytologically under-diagnosed cases (p=0.006). CONCLUSIONS Other than HPV-16, HPV genotype exhibited no cytological or histological differences. The discrepancy between the results of HPV DNA chip test and histology was created by glycogen acanthosis, immature squamous metaplasia, artifacts, and sampling errors.
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Koilocytic changes are not elicited by human papillomavirus genotypes with higher oncogenic potential Mitsuaki Okodo, Kaori Okayama, Koji Teruya, Hirokazu Kimura, Natsumi Noji, Yasuyoshi Ishii, Masahiko Fujii, Mizue Oda, Toshiyuki Sasagawa Journal of Medical Virology.2020; 92(12): 3766. CrossRef
Analysis of Sequence Variation and Risk Association of Human Papillomavirus 52 Variants Circulating in Korea Youn Jin Choi, Eun Young Ki, Chuqing Zhang, Wendy C. S. Ho, Sung-Jong Lee, Min Jin Jeong, Paul K. S. Chan, Jong Sup Park, Xuefeng Liu PLOS ONE.2016; 11(12): e0168178. CrossRef
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
Distribution of Human Papillomavirus 52 and 58 Genotypes, and Their Expression of p16 and p53 in Cervical Neoplasia Tae Eun Kim, Hwal Woong Kim, Kyung Eun Lee Korean Journal of Pathology.2014; 48(1): 24. CrossRef
Sung Ran Hong, In Sun Kim, Dong Won Kim, Mi Jin Kim, Ae Ree Kim, Young Ok Kim, Hye Sun Kim, Seo Hee Rha, Gyeong Sin Park, Yong Koo Park, Yong Wook Park, Ho Sung Park, Kwang Sun Suh, Jin Hee Sohn, Mi Kyung Shin, Hoon Kyu Oh, Ki Jung Yun, Hye Kyoung Yoon, Shi Nae Lee, Ah Won Lee, Hyo Jin Lee, Hyun Yee Cho, Chan Choi, Woon Won Jung
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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BACKGROUND Cervicovaginal cytology is a screening test of uterine cervical cancer. The sensitivity of cervicovaginal cytology is less than 50%, but studies of cytologic/histologic correlation are limited. We analyzed the diagnostic accuracy of cervicovaginal cytology in the detection of the squamous epithelial lesions of the uterine cervix and investigate the cause of diagnostic discordance.
MATERIALS AND METHODS: We collected a total of 481 sets of cervicovaginal cytology and biopsies over 5 years. The cytologic diagnoses were categorized based on The Bethesda System and the histologic diagnoses were classified as negative, flat condyloma, cervical intraepithelial neoplasia (CIN) I, CIN II, CIN III, or squamous cell carcinoma.
Cytohistologic discrepancies were reviewed. RESULTS The concordance rate between the cytological and the histological diagnosis was 79.0%. The sensitivity and specificity of cervicovaginal cytology were 80.6% and 92.6%, respectively. Its positive predictive value and negative predictive value were 93.7% and 77.7%, respectively. The false negative rate was 19.4%. Among 54 false negative cytology cases, they were confirmed by histology as 50 flat condylomas, 2 CIN I, 1 CIN III, and 1 squamous cell carcinoma. The causes of false negative cytology were sampling errors in 75.6% and interpretation errors in 24.4%.
The false positive rate was 7.4%. Among 15 false positive cytology cases, they were confirmed by histology as 12 atypical squamous cells of undetermined significance (ASCUS) and 3 low grade squamous intraepithelial lesions (LSIL). The cause of error was interpretation error in all cases. The overall diagnostic accuracy of cervicovaginal cytology was 85.7%. CONCLUSIONS Cervicovaginal cytology shows high overall diagnostic accuracy and is a useful primary screen of uterine cervical cancer.
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Overall accuracy of cervical cytology and clinicopathological significance of LSIL cells in ASC‐H cytology S. H. Kim, J. M. Lee, H. G. Yun, U. S. Park, S. U. Hwang, J.‐S. Pyo, J. H. Sohn Cytopathology.2017; 28(1): 16. CrossRef
Correlation Analysis Between Cervicovaginal Cytologic and Histopathologic Diagnoses in Cervical Squamous Cell Neoplasm Kyoung Bun Lee, Woon Sun Park, Jin Hee Sohn, Min Kyung Kim, Dong Hoon Kim, Hee Sung Kim, Seoung Wan Chae, Sung Hee Kang, Young Hye Cho, Hee Dae Pak, Sun Hee Kim The Korean Journal of Pathology.2009; 43(2): 157. CrossRef
Adenoid basal carcinoma of the uterine cervix is a rare neoplasm that accounts for less than 1% of cervical adenocarcinomas. Though it has been confused with adenoid cystic carcinoma, it is now distinctly recognized by better prognosis and different histologic and immunohistochemical findings. We have experienced a case of adenoid basal carcinoma associated with invasive squamous cell carcinoma of the uterine cervix in a 52-year-old woman. The tumor was composed of small, round to oval nests of basaloid cells with peripheral palisading. Some of the nests showed central cystic spaces, or cribriform pattern, and central squamous differentiation with cytological atypia. Invasive squamous cell carcinoma was located adjacent to the adenoid basal carcinoma without any transition between these two lesions.
Immunohistochemically, the tumor cells disclosed positive staining for cytokeratin, but negative reaction for CEA, EMA, and S-100 protein.
Pneumocystis carinii is the most common cause of diffuse pulmonary infiltrates in the immunocompromised patients.
Microscopically, Pneumocystis carinii pneumonia(PCP) shows characteristic frothy intraalveolar exudate and interstitial lymphocytic and plasma cell infiltrate. However, sometimes the only histologic finding of PCP on routine hematoxylin-eosin stain is that of diffuse alveolar damage(DAD), when we can miss the diagnosis without aid of special stains. We report a case of Pneumocystis carinii pneumonia presenting as DAD in a 50-year old man after chemotherapy due to malignant lymphoma. Open lung biopsy specimen reveals the early stage of DAD without any characteristic findings, such as foamy exudate. However many cysts of Pneumocystis carinii were found on Gomori's methenamine silver(GMS) stain. Therefore, GMS stain should be routinely performed on all biopsy specimens obtained from immunocompromised patients.
Despite its fall in incidence, gastric adenocarcinoma remains a common disease with dismal prognosis worldwide. A better understanding of its tumorigenesis and biologic properties of tumor cells related to invasion and metastasis is crucial to improving diagnosis and treatment. Conflicting results concerning the relationships between overexpression of PAI-1, c-erbB2, and p53 protein and biologic behavior of gastric carcinoma have been noted. The aim of this study was to evaluate the value of overexpression of PAI-1, c-erbB2, and p53 protein as prognostic factors in gastric adenocarcinoma. Overexpression of PAI-1, c-erbB2, and p53 protein by immunohistochemistry was correlated with variable clinicopathological parameters and patients' survival in 80 cases of gastric adenocarcinoma.
Overall PAI-1 expression rate was 63.7% (51/80) and higher in advanced cancer (p=0.0003) and nodal metastasis (p=0.003) groups. Overall c-erbB2 expression rate was 43.8% (35/80) and higher in antral (p=0.03), differentiated (p=0.001), intestinal (p=0.0007), and expanding (0.03) groups.
The p53 protein overexpression was 37.5% (30/80) and higher in early cancer (p=0.02), differentiated (p=0.006) and intestinal groups (p=0.009).
Patients with PAI-1, c-erbB2, and p53 protein positive tumors tended to have poorer survival rates than patients with PAI-1, c-erbB2, and p53 protein negative tumors, but the difference was not statistically significant (p=0.25, 0.37, 0.52). Our data indicated that PAI-1 overexpression is one of the poor prognostic factors in gastric adenocarcinoma and c-erbB2 and p53 protein seem to be involved in the early stage of carcinogenesis of intestinal type-gastric adenocarcinoma.
BACKGROUND There have been a few studies concerning the differential diagnosis between follicular adenomas and minimally invasive follicular carcinomas, but it is difficult to exclude the possibility of minute capsular and/or vascular invasion throughout the capsular areas as a whole. METHODS We examined the diagnostic usefulness of Ki-67 labelling index and bax expression for the differential diagnosis of follicular adenomas and minimally invasive follicular carcinomas. RESULTS The result of immunohistochemical staining with Ki-67 and bax antibodies were analyzed in 58 cases of follicular neoplasms from 1996 to 1999. Of 58 cases, 35 were follicular adenomas and 23 were minimally invasive follicular carcinomas. The Ki-67 labelling index was significantly higher in minimally invasive follicular carcinoma of the thyroid (Ki-67 labelling index, 1.62+/-0.35%) than follicular adenoma (0.46+/-0.21%) (P<0.05). Of the follicular adenomas, Ki-67 labelling index of the tumor with 5 cm or more in diameter was 0.38+/-0.13%, while that of the tumor with less than 5 cm was 0.51+/-0.24%. Of the minimally invasive follicular carcinoma, Ki-67 labelling index of the tumor with 5 cm more was 1.30+/-0.07%, while that of the tumor with less than 5 cm was 1.65+/-0.37%. Diffuse bax expression was seen in 27 of 35 cases of follicular adenomas and 2 of 23 cases of minimally invasive follicular carcinoma (P<0.05). CONCLUSIONS Our findings suggest Ki-67 labelling index and the degree of bax expression are useful markers for the differential diagnosis between the follicular adenoma and the minimally invasive follicular carcinoma of the thyroid.
BACKGROUND Glioblastomas are one of the most common and aggressive malignant glial tumors occuring in the central nervous system. This study analyzed the status of p15INK4b, p14ARF, p16INK4a, MTAP, IFNA, and IFNB genes in 36 primary glioblastomas to investigate whether the inactivation of these genes participate in primary glioblastoma tumorigenesis. METHODS We used polymerase chain reaction, polymerase chain reaction/single strand conformational polymorphism (PCR/SSCP) analysis, and methylation-specific PCR. RESULTS Homozygous deletions at the p16INK4a gene were detected in 11 cases (30.5%) of 36 primary glioblastomas, and the promoter hypermethylation was found in 3 cases (8.3%) of 36 primary glioblastomas. In mutational analysis for the p16INK4a gene by PCR/SSCP, there was no abnormal mobility-shifted band in 36 cases of primary glioblastomas.
The overall frequency of p16INK4a alterations including homozygous deletion and promoter hypermethylation in 36 primary glioblastomas was 38.8% (14 of 36). Deletions of p15INK4b were noted in 4 cases (11.1%), whereas deletions of the p14ARF and MTAP genes were detected in 1 case of 36 cases of primary glioblastomas. But deletions of the INFA and B genes were not found. CONCLUSIONS These results suggest that alterations of the p16INK4a gene can be important mechanisms of the tumorigenesis of primary glioblastomas, and the p16INK4a gene is inactivated by mechanisms including homozygous deletion and promoter hypermethylation.
In a six-year period (from May 1988 to April 1994), fine needle aspiration cytology (FNAC) of 322 pulmonary lesions from 296 patients were performed at Soonchunhyang University Hospital. Of these 322, malignancy was diagnosed cytologically in 139 (43.2%), suspicious malignancy in 7 (2.2%), negative in 164 (50.8%), and insufficient material in 12 (3.8%). Malignant lesion consisted of 54 cases of adenocarcinoma, 50 cases of squamous cell carcinoma, 18 cases of small cell carcinoma. They were verified by histologic confirmation in 70 cases. There were 2 (0.6%) false positive cases due to florid bronchoalveolar hyperplasia and atypical bronchial epithelial cells associated with granulomatous lesion. Overall accuracy rate was 90%, the sensitivity 84.3% and the specificity 94.7%.
Clinical lymphadenopathies are subjected to fine needle aspiration cytology(FNAC) for diagnosing not only benign lesions but also malignant ones, as the first diagnostic procedure. While the diagnostic reliability in metastatic carcinoma is high, it is difficult to differentiate malignant lymphoma from reactive conditions.
We evaluated the diagnostic reliability of FNAC in lymphadenopathy, and discuss the diagnostic limitation and its place in clinical practice in this study. Over 8 years from January 1988, FNAC of 1,216 lymphadenopathies were analyzed and among them 170 cases were compared with histopathology.
The results are as follows.
1. Of all the cases, 890 cases(73.2%) were diagnosed cytologically as benign, 312 cases(25.7%) as malignant, and 14 cases(1.1%) as unsatisfactory material.
Reactive hyperplasia was diagnosed in 585 cases(65.7%) of the benign lesions, and among the malignant diseases, metastatic carcinoma was diagnosed in 248 cases(79.5%), and malignant lymphoma in 62 cases(19.9%).
2. The overall diagnostic accuracy was 89.2%, and no false positive case and 9 false negative results were observed among 170 cases which were proven by histopathology. Six cases of sampling error of false negative diagnoses included 3 of metastatic carcinomas and 3 of malignant lymphomas. The causes were difference between aspiration and biopsy site, poor fixation, or scanty cellularity with bloody smear. All 3 cases of misinterpretation error were malignant lymphomas, one of mixed type on biopsy which was diagnosed as reactive hyperplasia cytologically.
In summary, FNAC technique is thought to be useful in the initial diagnosis of lymphadenopathies as well as in the follow-up of patients with known malignancy.
Although the results of malignant lymphoma was less accurate than other malignant lesions, the application of strict cytologic criteria or lymphoid marker studies of aspiration material will reduce the false negative rate.
PURPOSE: To investigate renal toxicity of high-dose intravenous immunoglobulin(IVIG) in children with Kawasaki disease and idiopathic thrombocytopenic purpura. METHODS: 23 children with Kawasaki disease and 7 children with idiopathic thrombocytopenic purpura who were treated with high-dose IVIG(2 g/kg) were evaluated for the change of urine output, blood urea nitrogen(BUN), serum creatinine(Scr), creatinine clearance(Ccr), tubular reabsorption of phosphorus(TRP), fractional excretion of sodium(FENa), 24hour urine b2-microg1obuin/creatinine(b2MG/cr) ratio and urine microalbumin/creatinine(MA/cr) ratio at post-IVIG 1 and 3 day. RESULTS: There was no significant change of urine output, BUN, Scr, Ccr, TRP, 24hour urine b2MG/cr and MA/cr ratio after high-dose IVIG treatment. Transient increase of FENa at post-IVIG 1 day was the only significant change. CONCLUSION There was no significant renal toxicity of high-dose IVIG in children with Kawasaki disease and idiopathic thrombocytopenic purpura who had normal renal function.
Matrix producing carcinoma of the breast is a variant of heterologous metaplastic carcinoma which is defined as "overt carcinoma with direct transition to a cartilagenous and/or osseous stromal matrix without an intervening spindle cell zone or osteoclastic cells". This tumor is very rare, occuring in less than 0.2% of total breast carcinoma, but the prognosis is better than other metaplastic carcinoma.
We experienced a case of fine needle aspiration(FNA) cytologic finding of matrix producing carcinoma of the breast. A 75-year old woman, who presented a right huge breast mass(9x8cm) during 10months, was examined.
Mammography reveals right lateral mass with even density without calcification.
Breast ultrasonography shows multifocal hypoechogenic cystic change in the huge mass, suggesting resolving hematoma or carcinoma or sarcoma with necrosis.
On cytologic finding of FNA, myxoid matrix was the dominant feature and the rest of the material was composed of scanty isolated atypical cells with large irregular nuclei. The histologic finding was moderately differentiated adenocarcinoma with abundant cartilagenous matrix and focal squamous metaplasia.