Expression of female sex hormone receptors and its relation to clinicopathological characteristics and prognosis of lung adenocarcinoma

Background@#Adenocarcinoma (ADC) of the lung exhibits different clinicopathological characteristics in men and women. Recent studies have suggested that these differences originate from the expression of female sex hormone receptors in tumor cells. The aim of the present study was to evaluate the immunohistochemical expression of female sex hormone receptors in lung ADC and determine the expression patterns in patients with different clinicopathological characteristics. @*Methods@#A total of 84 patients with lung ADC who underwent surgical resection and/or core biopsy were recruited for the present study. Immunohistochemical staining was performed for estrogen receptor α (ERα), estrogen receptor β (ERβ), progesterone receptor (PR), epidermal growth factor receptor (EGFR), EGFR E746- A750 del, and EGFR L858R using tissue microarray. @*Results@#A total of 39 (46.4%) ERα-positive, 71 (84.5%) ERβ-positive, and 46 (54.8%) PR-positive lung ADCs were identified. In addition, there were 81 (96.4%) EGFR-positive, 14 (16.7%) EGFR E746-A750 del–positive, and 34 (40.5%) EGFR L858R–positive cases. The expression of female sex hormone receptors was not significantly different in clinicopathologically different subsets of lung ADC. @*Conclusions@#Expression of female sex hormone receptors is not associated with the prognosis and clinicopathological characteristics of patients with lung ADC.

Current Cytology Practices in Korea: A Nationwide Survey by the Korean Society for Cytopathology

BACKGROUND: Limited data are available on the current status of cytology practices in Korea. This nationwide study presents Korean cytology statistics from 2015. METHODS: A nationwide survey was conducted in 2016 as a part of the mandatory quality-control program by the Korean Society for Cytopathology. The questionnaire was sent to 208 medical institutions performing cytopathologic examinations in Korea. Individual institutions were asked to submit their annual cytology statistical reports and gynecologic cytology-histology correlation data for 2015. RESULTS: Responses were obtained from 206 medical institutions including 83 university hospitals, 87 general hospitals, and 36 commercial laboratories. A total of 8,284,952 cytologic examinations were performed in 2015, primarily in commercial laboratories (74.9%). The most common cytology specimens were gynecologic samples (81.3%). Conventional smears and liquid-based cytology were performed in 6,190,526 (74.7%) and 2,094,426 (25.3%) cases, respectively. The overall diagnostic concordance rate between cytologic and histologic diagnoses of uterine cervical samples was 70.5%. Discordant cases were classified into three categories: category A (minimal clinical impact, 17.4%), category B (moderate clinical impact, 10.2%), and category C (major clinical impact, 1.9%). The ratio of atypical squamous cells of undetermined significance to squamous intraepithelial lesion was 1.6 in university hospitals, 2.9 in general hospitals, and 4.9 in commercial laboratories. CONCLUSIONS: This survey reveals the current status and trend of cytology practices in Korea. The results of this study can serve as basic data for the establishment of nationwide cytopathology policies and quality improvement guidelines in Korean medical institutions.

A Rare Case of Recurrent Metastatic Solid Pseudopapillary Neoplasm of the Pancreas

A 61-year-old woman visited our hospital for bilateral multiple lung nodules and a mass in her thorax. She had a long history of multiple metastatic recurrences of solid pseudopapillary neoplasm (SPN); 24 years previously, the patient had undergone pylorus-preserving pancreaticoduodenectomy for a 9.9 × 8.6 cm mass in the pancreatic head. The tumor was diagnosed as an SPN. Nine years later, metastatic nodules were found on computed tomography in the patient's liver and peritoneum and were excised. She subsequently underwent an additional eight metastatectomy procedures in diverse organs. For the presented event, the lung nodules were removed. The prevalence of malignant SPN in the general population is 5%–15%. However, multiple metastatic recurrence of malignant SPN is rare; the lung is a particularly rare site of metastasis, found in only three cases in the literature. Here, we describe this exceptional case and provide a literature review.

Pulmonary graft-versus-host disease after autologous hematopoietic stem cell transplantation

No abstract available.

Sclerosing Perivascular Epithelioid Cell Tumor of the Lung: A Case Report with Cytologic Findings

Benign perivascular epithelioid cell tumor (PEComa) of the lung is a rare benign neoplasm, a sclerosing variant of which is even rarer. We present a case of 51-year-old man who was diagnosed with benign sclerosing PEComa by percutaneous fine needle aspiration cytology and biopsy. The aspirate revealed a few cell clusters composed of bland-looking polygonal or spindle cells with fine granular or clear cytoplasm. Occasional fine vessel-like structures with surrounding hyalinized materials were seen. The patient later underwent wedge resection of the lung. The histopathological study of the resected specimen revealed sheets of polygonal cells with clear vacuolated cytoplasm, variably sized thin blood vessels, and densely hyalinized stroma. In immunohistochemical studies, reactivity of tumor cells for human melanoma black 45 and Melan-A further supported the diagnosis of benign sclerosing PEComa. To the best of our knowledge, this is the first case of benign sclerosing PEComa described in lung.

Analysis of Mutations in Epidermal Growth Factor Receptor Gene in Korean Patients with Non-small Cell Lung Cancer: Summary of a Nationwide Survey

BACKGROUND: Analysis of mutations in the epidermal growth factor receptor gene (EGFR) is important for predicting response to EGFR tyrosine kinase inhibitors. The overall rate of EGFR mutations in Korean patients is variable. To obtain comprehensive data on the status of EGFR mutations in Korean patients with lung cancer, the Cardiopulmonary Pathology Study Group of the Korean Society of Pathologists initiated a nationwide survey. METHODS: We obtained 1,753 reports on EGFR mutations in patients with lung cancer from 15 hospitals between January and December 2009. We compared EGFR mutations with patient age, sex, history of smoking, histologic diagnosis, specimen type, procurement site, tumor cell dissection, and laboratory status. RESULTS: The overall EGFR mutation rate was 34.3% in patients with non-small cell lung cancer (NSCLC) and 43.3% in patients with adenocarcinoma. EGFR mutation rate was significantly higher in women, never smokers, patients with adenocarcinoma, and patients who had undergone excisional biopsy. EGFR mutation rates did not differ with respect to patient age or procurement site among patients with NSCLC. CONCLUSIONS: EGFR mutation rates and statuses were similar to those in published data from other East Asian countries.

Tumor Sprouting in Papillary Thyroid Carcinoma Is Correlated with Lymph Node Metastasis and Recurrence

BACKGROUND: Identification of poor prognostic factors in papillary thyroid carcinoma (PTC) patients is important for the patients' care and follow-up. We can sometimes see small tumor clusters without desmoplasia and no evidence of lymphatic emboli around the main tumor mass of PTC. We termed this form of tumor clustering, 'tumor sprouting,' and determined whether these tumors correlate with lymphovascular invasion, lymph node metastasis, and recurrence. METHODS: We analyzed a total of 204 cases of papillary thyroid macrocarcinoma. Number, size and distance from the main tumor of the tumor sprouting were observed and analyzed with clinicopathologic characteristics. RESULTS: Tumor sprouting was observed in 101 patients. Presence of tumor sprouting was significantly associated with positive resection margin (p=.002), lymphovascular invasion (p=.001), lymph node metastasis (p<.001), and recurrence (p=.004). Univariate analysis of recurrence-free survival revealed that tumor multiplicity (p=.037), positive resection margin (p=.007), lymphovascular invasion (p=.004), lymph node metastasis (p<.001), and tumor sprouting (p=.004) were poor prognostic factors. In multivariate analysis, positive resection margin was an independent poor prognostic factor of recurrence. CONCLUSIONS: In conclusion, tumor sprouting is significantly correlated with lymph node metastasis and recurrence. Evaluation of tumor sprouting in PTC patients could be helpful in predicting tumor recurrence or lymph node metastasis.

SIRT1 Expression Is Associated with Good Prognosis in Colorectal Cancer

BACKGROUND: Silent mating type information regulation 2 homolog 1 (SIRT1), an NAD+-dependent deacetylase, might act as a tumor promoter by inhibiting p53, but may also as a tumor suppressor by inhibiting several oncogenes such as beta-catenin and survivin. Deleted in breast cancer 1 (DBC1) is known as a negative regulator of SIRT1. METHODS: Immunohistochemical expressions of SIRT1, DBC1, beta-catenin, surviving, and p53 were evaluated using 2 mm tumor cores from 349 colorectal cancer patients for tissue microarray. RESULTS: Overexpression of SIRT1, DBC1, survivin, and p53 was seen in 235 (67%), 183 (52%), 193 (55%), and 190 (54%) patients, respectively. Altered expression of beta-catenin was identified in 246 (70%) patients. On univariate analysis, overexpression of SIRT1 (p=0.029) and altered expression of beta-catenin (p=0.008) were significantly associated with longer overall survival. Expression of SIRT1 was significantly related to DBC1 (p=0.001), beta-catenin (p=0.001), and survivin (p=0.002), but not with p53. On multivariate analysis, age, tumor stage, differentiation, and expression of SIRT1 were independent prognostic factors significantly associated with overall survival. CONCLUSIONS: SIRT1 overexpression is a good prognostic factor for colorectal cancer, and SIRT1 may interact with beta-catenin and survivin rather than p53.

Prognostic Significance of Heat Shock Protein 70 Expression in Early Gastric Carcinoma

BACKGROUND: Overexpression of heat shock protein 70 (HSP70) has been observed in many types of cancer including gastric adenocarcinomas, although the exact role of HSP70 in carcinogenesis remains unclear. METHODS: The study analyzed a total of 458 radical gastrectomy specimens which were immunohistochemically stained with HSP70, p53, and Ki-67 antibodies. RESULTS: The study determined that the expression of HSP70 was significantly increased in early gastric cancer (EGC) compared to advanced gastric cancer (p<0.001). The HSP70 expression was correlated with well-differentiated tumor type, intestinal type of Lauren classification and the lower pT and pN stage. Negative expression of Ki-67 and p53 expression was associated with poor prognosis. The study did not find any correlation between HSP70 and p53 expression. The study determined that HSP70 expression in the EGC subgroup was associated with a poor prognosis (p=0.009), as well as negative Ki-67 expression (p=0.006), but was not associated with p53. Based on multivariate analysis, HSP70 expression (p=0.024), negative expression of Ki-67, invasion depth and lymph node metastasis were determined to be independent prognostic markers. CONCLUSIONS: HSP70 is expressed in the early stages of gastric adenocarcinoma. In EGC, HSP70 is a poor independent prognostic marker and is correlated with a low proliferation index.

Expression of Cyclin A, B1, D1, D3, and E in Non-Small Lung Cancers

PURPOSE: Cyclins, and their associated cyclin dependent kinases, regulate progression of the cell cycle through the G1 phase and into the S-phase during the DNA replication process. Cyclin E regulation is an important event in cell proliferation. Despite its importance, abnormalities of these genes and their protein products have yet to be found in lits asoociation with lung cancer. MATERIALS AND METHODS: The relationships between expression of cyclin A, cyclin B1, cyclin D1, cyclin D3, and cyclin E and clinicopathologic factors were investigated in 103 cases with non-small cell carcinomas, using immunohistochemical analysis. RESULTS: The positive immunoreactivity was observed in 51 cases (50%) for cyclin A, 33 cases (32%) for cyclin B1, 83 cases (81%) for cyclin D1, 19 cases (18%) for cyclin D3, and 11 cases (11%) for cyclin E. Expression of cyclin E was significant for lymph node metastasis (p=0.004, Chi-square test). There was no relationship between cyclin A, B1, D1, and E and histological typing, tumor size, lymph node metastasis, or pathological tumor, node and metastasis staging. CONCLUSION: These findings suggest that the expression of cyclin E played a role, to some degree, in the lymph node metastasis.

Vascular Endothelial Growth Factor Bioactivity and Its Receptors in Patients with Acute Respiratory Distress Syndrome

BACKGROUND: Pathogenesis of acute respiratory distress syndrome (ARDS) is a controversial issue. Few studies have analyzed the possible role of vascular endothelial growth factor (VEGF) and its receptors in this lesion. METHODS: We compared the immunohistochemical expression of VEGF, its receptors (VEGFR1, VEGFR2) and CD68, in normal lungs and lungs with ARDS. Fifty necropsy cases and 12 lung biopsies with ARDS were analyzed. In total, eight cases were in the early stage and 54 cases were in late stage of ARDS. In addition, the serum level of VEGF165 was also determined. RESULTS: In normal lungs, all antibodies marked the endothelial cells (EC) and pneumocytes (PC), except for CD68, which was expressed in the alveolar macrophages. In early ARDS, the intensity of VEGF165 and VEGFR2 decreased in both EC and PC. VEGF121 was absent in PC but its expression increased in bronchial epithelium. VEGFR1 was expressed in the integral PC. In late ARDS, VEGF165 down-regulation was more significant in PC and EC but its intensity increased in hyaline membranes (HM). In some cases, HM were CD68 positive. The serum level of VEGF165 was up-regulated, while VEGF165 intensity in PC decreased and the HM appeared in alveolar spaces. CONCLUSIONS: Sporadic positivity of HM for CD68 and decreasing of VEGF165 expression in EC proved that VEGF165 is produced by PC, destroyed macrophages, and extravasated serum.

2 Cases of a Benign Pulmonary Metastasizing Leiomyoma / 결핵및호흡기질환

A benign pulmonary metastasizing leiomyoma is a recognized clinical entity that has been infrequently reported in the medical literature. We report two cases of a benign pulmonary metastasizing leiomyoma. A 35-year-old woman who underwent myomectomy and a cesarean section approximately 6 years earlier visited our hospital for further evaluation of incidentally revealed multiple lung nodules. A diagnostic percutaneuous biopsy was performed. Finally she was diagnosed with a benign metastasizing leiomyoma. The patient then received LH-RH and has been followed up since. The other 44-year-old woman presented after an initial radiology evaluation revealed the presence of multiple, small-sized lung nodules. She underwent a right middle lung wedge resection to confirm the diagnosis. Finally she diagnosed with a benign metastasizing leiomyoma. The multiple lung nodules have been followed up closely.

Development and Evaluation of a School-based Anger Management Program (SAMP) for Adolescents

PURPOSE: This study was done to develop a school-based anger management program (SAMP) of 4 sessions and examine its effects on the anger, anger expression, psychosomatic responses, psychosocial responses, and immunologic responses in adolescents. METHODS: A quasi-experimental study using a nonequivalent control group, pre-post design with repeated measures was used. Chi-square test, t-test, paired t-test, and Fisher's exact test were used to analyze the data. RESULTS: There were no differences between the experimental and control groups in outcome variables except for lymphocytes. However, following additional analyses, statistically significant differences by time point were observed for pain sensitivity, T cell, Helper T (Th) cell, Suppressor (Ts) cell and Natural Killer (NK) cell post-treatment, entrapment and psychosomatic symptoms at the 4-week follow-up, and resilience at the 10-week follow-up for the experimental group. CONCLUSION: Although some modifications in contents and administration will be required to increase the effectiveness of the program for anger management, SAMP can be used to promote anger management ability in adolescents.

Malignant Glomus Tumors of the Stomach: A Report of 2 Cases with Multiple Metastases

Glomus tumors are mesenchymal neoplasms usually developing in the dermis or subcutis of the extremities. The majority of glomus tumors are entirely benign, and malignant glomus tumors are very rare, especially those arising in the visceral organs. Here, we are presenting two cases of malignant glomus tumor, initially diagnosed in the stomach by endoscopic biopsy. Case 1 was found in the stomach, right kidney, brain and humerus of a 65-year-old woman, and Case 2 in the stomach and liver of a 63-year-old man. Histologically, the tumor was composed of solid sheets and nests of round and short-spindle shaped tumor cells with vesicular nucleus and prominent nucleolus. The tumor cells were closely admixed with blood vessels of varying size. Immunohistochemically, the tumor cells showed diffuse and strong positive staining for smooth muscle actin and paranuclear, dot-like staining for synaptophysin, but negative for desmin, c-kit, CD34 and S-100 protein. These two are rare cases of a malignant glomus tumor with widespread metastases.

Detecting Malignant Urothelial Cells by Morphometric Analysis of ThinPrep(R) Liquid-based Urine Cytology Specimens / 대한세포병리학회지

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.

Experimental Pulmonary Fat Embolism: Computed Tomography and Pathologic Findings of the Sequential Changes

This study was done to demonstrate the computed tomography (CT) and pathologic findings of the sequential changes for experimental pulmonary fat embolism (PFE), and to correlate the CT and pathologic findings of rabbit lung. PFE was induced by an intravenous injection of 0.2 mL linoleic acid in 24 rabbits. The rabbits were divided into 4 groups of 6 rabbits each. CT scans were obtained sequentially at 2 hr (n= 24), day 1 (n=18), day 3 (n=12) and day 7 (n=6) after fat embolization. The pathologic findings were analyzed and CT-pathologic correlation was done. CT scans showed bilateral ground-glass opacity (GGO), consolidation and nodule in all cases. The findings of PFE at 2 hr after fat embolization were areas of decreased attenuation, GGO, consolidation and nodule. These findings were aggravated on the follow- up CT after 1 day and 3 days. The follow-up CT revealed linear density in the subpleural lungs after 7 days. On CT-pathology correlation, wedge-shaped ischemic necrosis in the subpleural lungs correlated with nodule at 2 hr. GGO and consolidation at day 1 on CT correlated with congestion and edema, and these findings at day 3 were correlated with inflammation and hemorrhagic edema. The linear density in the subpleural lungs correlated with interstitial fibrosis and pleural contraction at day 7. In conclusion, PFE was caused by using linoleic acid which is kind of free fatty acid and this study served as one model of the occurrence of nontraumatic PFE. CT accurately depicted the natural evolution of PFE in the serial followup, and this correlated well with the pathologic findings.

Age Estimation of Mummies by Dental Attrition: Application of Three-dimensional CT Images

BACKGROUND: Because of the rarity of mummies in Korea and the difficulty in obtaining samples from mummies, studies to determine the ages of mummies are uncommon in Korea. This study was performed to determine the ages of mummies using the information obtained by nondestructive methods to minimize damages to the mummies. METHODS: Three mummies excavated between 2002 and 2004 were used. Three-dimensional reconstructed images of the total teeth were obtained by CT scanning. The age at death was determined according to the 'Age Estimation Table of Dental Attrition' as developed by Takei. Three teeth were extracted from each of three mummies and examined grossly and microscopically by serial sections using the Gustafson-Johanson method. RESULTS: The ages at death of the three mummies estimated by the Takei method were 23.57 years (Yoon mummy), 51.01 years (Bong mummy), and 64.45 years (Black mummy). These results were similar to the ages determined by the Gustafson method. CONCLUSION: Age determination method using a CT scan and three-dimensional reconstruction may be a valuable method because it minimizes the damages to valuable mummies and it gives reliable data similar to that obtained by other standard methods.

The Korean Journal of Pathology is Selected for Coverage in Science Citation Index Expanded and Journal Citation Reports by Thomson Reuters

No abstract available.

Genetic and Epigenetic Alterations of the Wnt/beta-catenin Signaling Pathway in Cancer of the Ampulla of Vater

BACKGROUND: Carcinoma of the ampulla of Vater is rare and its pathogenesis is unclear. The role of epigenetic changes in the APC or CDH1, in the Wnt pathway, has not been reported in ampullary carcinomas. METHODS: We performed immunohistochemistry on 73 sporadic ampullary carcinomas to identify Wnt-related molecules (APC, beta-catenin, E-cadherin, c-erbB2, cyclin D1) and examined mutations in the CTNNB1, loss of heterozygosity of 5q21, and the methylation status of the CpG island of APC and CDH1. RESULTS: Thirteen tumors (17.8%) showed abnormal nuclear localization of beta-catenin; this was more prominent in the intestinal type than in the pancreaticobiliary type (p=0.01). The loss of APC correlated with the loss of beta-catenin or c-erb B2 (p<0.01). The prognosis was worse in the group with APC loss than when APC was maintained (p<0.05). There was no mutation identified in CTNNB1. Six (24%) out of 25 informative cases had 5q21 allelic loss. CpG island methylation in APC and CDH1 was detected in 33 (45.2%) and 29 (31.5%) cases, respectively. CONCLUSIONS: The absence of mutations in CTNNB1 and the epigenetic alteration of APC and CDH1, might be characteristic changes in the Wnt/beta-catenin signaling pathway during the carcinogenesis of ampullary carcinomas.

Follicular Lymphoma with Monoclonal Plasma Cell Differentiation: A Case Report

We present a case of recurrent follicular lymphoma with an extensive plasma cell component involving infra-auricular lymph nodes in a 64 year-old woman. Immunohistochemical staining showed a strongly positive reaction of the follicles with CD20, bcl-2, bcl-6, CD10 and CD21 on the first biopsy specimen. The intrafollicular and interfollicular plasma cells showed monoclonality for IgG heavy chain and lambda light chain. The histological and immunohistochemical findings in the recurrent tumor were identical with those of the original. Discussion is focused on the importance of the differential diagnosis between reactive lymphoid hyperplasia and other lymphomas having plasmacytic differentiation.