- [Show abstract] [Hide abstract] ABSTRACT: GATA3 is a diagnostically useful immunohistochemical marker of breast cancer. Because of its strong association with ER expression, GATA3 has markedly reduced sensitivity in triple-negative breast cancer (TNBC). We constructed a tissue microarray using a large series of TNBCs and evaluated GATA3 expression by TNBC subtype as defined by surrogate immunohistochemical markers. A total of 205 TNBCs were classified into cancers of the molecular apocrine type (n=23, 11.2%), claudin-low type (n=21, 10.2%), basal-like type (n=91, 44.4%), mixed type (n=62, 30.2%), and null type (n=8, 3.9%). The GATA3 scores (staining intensity × proportion) were categorized as negative (0), focally positive (1-10), or positive (11-300). GATA3 staining was negative in 153 cancers (74.6%), focally positive in 11 (5.4%), and positive in 41 (20.0%). The rate of focal positivity or positivity for GATA3 was significantly higher in the molecular apocrine type (73.9%, 17/23) than in other types of TNBCs (P=.001). The mean GATA3 score of molecular apocrine type TNBC was significantly higher than that of the other types (P=.001) and differed significantly between AR- positive and -negative TNBCs (P<.001). In conclusion, GATA3 expression was correlated strongly with AR-positive, molecular apocrine type TNBCs. Co-expression of AR and GATA3 is a specific feature of molecular apocrine type TNBC, which may serve as a diagnostic aid for cancer of unknown primary.
Conference Paper: XXIV World Allergy Congress 2015: Seoul, Korea. 14-17 October 2015
- [Show abstract] [Hide abstract] ABSTRACT: Heterotopic bone formation is a very rare event in the gastrointestinal tract including in the appendix. Here we report three cases of heterotopic ossification in appendiceal mucinous neoplasms, one occurring in an appendiceal mucinous cystadenoma, another in a low-grade appendiceal mucinous neoplasm, and the third occurring in an appendiceal mucinous adenocarcinoma. The clinicopathologic characteristics of these three present cases and two previously reported cases are discussed in detail. The mechanism of heterotopic ossification in appendiceal mucinous neoplasm is still unclear, but mucin extravasation and subsequent calcification may be predisposing events. © 2006, Malaysian Society of Pathologists. All rights reserved.
- [Show abstract] [Hide abstract] ABSTRACT: A case of combined micropapillary and plasmacytoid urothelial carcinoma (UC) of the urinary bladder is presented for a 74-year-old male who was admitted to the hospital with gross hematuria and multifocal papillary bladder tumors. Abdominal computed tomography showed a large enhancing mass on the left lateral and anterior wall of the urinary bladder, which was highly suspicious for extravesicular extension and focal extension of the anterior lesion to the pubic bone. In voided urine, cancer cells were scattered as micropapillae or nests as well as single cells on the low power view. On a higher power view, micropapillae or nests were composed of pleomorphic, high grade tumor cells with an inverted nuclear arrangement and with acinar structures occasionally identified. Single cells were discohesive and large with a thick cytoplasm and eccentrically located nuclei. Histologically, the tumor from the resected bladder showed diffusely infiltrating micropapillae or nests with a surrounding halo and dense singly-scattered plasmacytoid cells. Immunohistochemically, the cancer cells were positive for cytokeratin-7 and cytokeratin-20 but negative for S-100, leukocyte common antigen, and vimentin. At the time of radical cystectomy, severe adhesions and peritoneal metastases were found and the surgery was discontinued. The patient received systemic chemotherapy, but died of bladder cancer 14 months after surgery. Diagn. Cytopathol. 2015. © 2015 Wiley Periodicals, Inc.
- [Show abstract] [Hide abstract] ABSTRACT: Viral oncogenes and host immunosenescence have been suggested as causes of Epstein-Barr virus-positive diffuse large B-cell lymphoma (EBV + DLBCL) of the elderly. To investigate the molecular genetic basis of immune evasion and tumor outgrowth, we analyzed copy number alterations (CNAs) and gene expression profiles in EBV + DLBCL samples compared with EBV - DLBCL. There were relatively few genomic alterations in EBV + DLBCL compared with those detected in EBV-negative DLBCL. The most frequent CNAs (>30%) in EBV + DLBCLs were gains at 1q23.2-23.3, 1q23.3, 1q32.1, 5p15.3, 8q22.3, 8q24.1-24.2, and 9p24.1; losses at 6q27, 7q11.2, and 7q36.2-36.3 were also recurrent. A gene expression profile analysis identified the host immune response as a key molecular signature in EBV + DLBCL. Antiviral response genes, proinflammatory cytokines, and chemokines associated with the innate immune response were overexpressed, indicating the presence of a virusinduced inflammatory microenvironment. Genes associated with the B-cell receptor signaling pathway were downregulated. An integrated analysis indicated that SLAMF1 and PDL2 were key targets of the gains detected at 1q23.2-23.3 and 9p24.1. The chromosomal gain at 9p24.1 was associated with poor overall survival. Taken together, our results led to the identification of recurrent copy number alterations and distinct gene expression associated with the host immune response in EBV + DLBCL. We suggest that the upregulation of PDL2 on 9p24.1 promotes immune evasion and is associated with poor prognosis in EBV + DLBCL. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.
- [Show abstract] [Hide abstract] ABSTRACT: UTX is a histone demethylase gene located on the X chromosome and is a frequently mutated gene in urothelial bladder cancer (UBC). UTY is a paralog of UTX located on the Y chromosome. We performed target capture sequencing on 128 genes in 40 non-metastatic UBC patients. UTX was the most frequently mutated gene (30%, 12/40). Of the genetic alterations identified, 75% were truncating mutations. UTY copy number loss was detected in 8 male patients (22.8%, 8/35). Of the 9 male patients with UTX mutations, 6 also had copy number loss (66.7%). To evaluate the functional roles of UTX and UTY in tumor progression, we designed UTX and UTY single knockout and UTX-UTY double knockout experiments using a CRISPR/Cas9 lentiviral system, and compared the proliferative capacities of two UBC cell lines in vitro. Single UTX or UTY knockout increased cell proliferation as compared to UTX-UTY wild-type cells. UTX-UTY double knockout cells exhibited greater proliferation than single knockout cells. These findings suggest both UTX and UTY function as dose-dependent suppressors of UBC development. While UTX escapes X chromosome inactivation in females, UTY may function as a male homologue of UTX, which could compensate for dosage imbalances.
- [Show abstract] [Hide abstract] ABSTRACT: Background: One hundred forty nine stromal nodules (SNs) from transurethral resection of benign prostatic hyperplasia specimens in 39 patients (57-85 years with mean of 70.9) were investigated to characterize the SNs and to outline the etiopathogenesis of solitary fibrous tumors (SFTs) and gastrointestinal stromal tumors (GISTs) of prostate by immunohistochemistry performed on tissue microarray sections. Methods: Antibodies used included smooth muscle actin, desmin, vimentin, and S-100 protein for subtyping, vascular endothelial growth factor, insulin-like growth factor-1, fibroblast growth factor, and TGF-ß as growth factors; CD133, c-KIT, CD34, and CD44 as stem cell markers; and estrogen (ER), progesterone (PR), and androgen receptor (AR) as hormone receptors. Results: SNs were classified into four subtypes: (1) immature mesenchymal (n = 7, 4.7%); (2) fibroblastic (n = 74, 49.7%); (3) fibromuscular (n = 53, 35.6%); and (4) smooth muscular (n = 15, 10.1%) types. There were linear trends of the expression of all growth factors (VEGF, IGF-1, FGF, TGF-ß), but only CD44 stem cell marker and AR hormone receptor as maturation progressed from immature mesenchymal to smooth muscular type (Ptrend < 0.05). S-100, c-KIT, and ER were not expressed in any types of SNs. CD34 was positive in 55% of the SNs (82/149). Conclusions: The data suggest that AR and growth factors are important factors for maturation of SNs, but not influenced by the administration of 5-alpha reductase inhibitor (5ARI). Although the cells comprising the SNs seem to be not associated with the origin of prostatic GISTs, there is a possibility of a tentative link of SFTs arising from SNs of the prostate.
- [Show abstract] [Hide abstract] ABSTRACT: Objectives: Our study examines thyroid transcription factor 1 (TTF-1) expression in 40 primary adenoid cystic carcinomas (ACCs) arising in various sites and compares TTF-1 expression between primary and metastatic ACCs in 12 cases with distant metastases. Methods: Forty patients with ACCs, including 12 pairs of primary and metastatic ACCs, were evaluated for the immunohistochemical expression of TTF-1 (clone SPT24). In addition, 10 metastatic ACCs to the lung were tested on napsin A and a different TTF-1 antibody (clone 8G7G3) for further evaluation. Results: No primary ACCs showed TTF-1 immunoreactivity (clone SPT24). TTF-1 was positive in five (41.7%) of 12 metastatic ACCs; all five cases were found only in the lung and comprised five (50.0%) of 10 cases. In all positive cases, staining was focal and detected only in the cribriform histologic subtype. Staining patterns using both antibodies (both SPT24 and 8G7G3) were very similar, and TTF-1-positive tumor cells were also positive for napsin A. Extrapulmonary ACCs were all negative for TTF-1 regardless of origination and metastasis. Conclusions: TTF-1- and napsin A-positive ACCs in the lung should not be considered primary ACCs because TTF-1 and napsin A can be expressed in metastatic ACCs of the lung.
- [Show abstract] [Hide abstract] ABSTRACT: We present the first case of peripheral T-cell lymphoma, not otherwise specified expressing follicular helper T-cell (TFH) markers with different histologic features simultaneously involving the common bile duct and pericholedochal lymph nodes in a 72-year-old female patient. Abdominal computed tomography revealed a localized wall-thickening in the common bile duct. With the impression of cholangiocarcinoma, pancreaticoduodenectomy was done. Microscopically, dense small lymphoid cells with only minimal cytologic atypia were observed with occasional lymphoepithelial-like lesions, while many atypical large cells infiltrated the pericholedochal lymph nodes. Immunohistochemically, the majority of small cells in the bile duct and the large atypical cells in the lymph nodes were all reactive for TFH markers including CD4, PD-1, and CXCL-13. BIOMED-2 based polymerase chain reaction using the DNA template from either the bile duct lesion or the lymph node revealed identical but different dominant clonal peaks, indicating these two lesions represent a spectrum of the same disease.
- [Show abstract] [Hide abstract] ABSTRACT: Forkhead box P3 (Foxp3) is known as the most specific marker for regulatory T lymphocytes, which play an important role in immune tolerance to disturb antitumor immunity. The present study aimed to investigate the prognostic significance of Foxp3 regulatory T lymphocyte (Foxp3 Treg) infiltration in breast cancer. Immunohistochemical studies with Foxp3, CD4, and CD8 were performed on representative full tissue sections from 143 patients with invasive ductal carcinoma, not otherwise specified. Foxp3 Treg infiltration and the ratios between Foxp3 Treg and CD4 or CD8 T cells were separately analyzed for the tumor bed and tumor periphery to evaluate their association with different clinicopathological parameters and patients' outcome. The tumor periphery was considerably more densely infiltrated by Foxp3 Treg, CD4, and CD8 T cells than the tumor bed. Unfavorable clinicopathological parameters (a Ki-67 labeling index of ≥14%, a worse histologic grade, a worse nuclear grade, hormone receptor negativity, human epidermal growth factor receptor 2 positivity, and tumor recurrence) were associated with increased Foxp3 Treg infiltration and a high ratio between Foxp3 Treg and CD4/CD8 T cells. In the tumor periphery, as Foxp3 Treg infiltration and the Foxp3 Treg/CD8 ratio increased, patients' 5-year disease-free survival rate decreased. The infiltration densities of Foxp3 Treg, CD4, and CD8 T cells were markedly different between the tumor bed and periphery. Besides the absolute count of Foxp3 Treg, the ratio between Foxp3 Treg and effector T cells was a significant prognostic factor in breast cancer.
Article: Peripheral T cell lymphoma in Asia[Show abstract] [Hide abstract] ABSTRACT: Peripheral T-cell lymphomas (PTCLs) comprise a heterogeneous group of mature T- and NK-cell neoplasms, the incidence of which is higher in Asian countries than in Western countries. Although its etiology is mainly unknown, several risk factors (such as genetic factors, abnormal immunity, environmental factors, and infectious causes) have been proposed. PTCL are classified based on a combination of several parameters, including morphology, site of presentation, viral status, immunophenotype, and specific genetic alterations. Their classification is ongoing, with the emergence of new entities and refinement of existing entities because of the development of diagnostic markers and new genetic alterations. This review presents epidemiologic data for PTCL in Asia, together with recent progress in the pathology of PTCL compared with the WHO 2008 classification.
- [Show abstract] [Hide abstract] ABSTRACT: Primary infection with Epstein-Barr virus (EBV) is usually asymptomatic and, in a normal host, EBV remains latent in B cells after primary infection for the remainder of life. Uncommonly, EBV can infect T or natural killer (NK) cells in a person with a defect in innate immunity, and EBV infection can cause unique systemic lymphoproliferative diseases (LPD) of childhood. Primary infection in young children can be complicated by hemophagocytic lymphohistiocytosis or fulminant systemic T-cell LPD of childhood. Uncommonly, patients can develop chronic active EBV (CAEBV) disease-type T/NK LPD, which includes CAEBV infection of the systemic form, hydroa vacciniforme-like T-cell LPD, and mosquito-bite hypersensitivity. The clinical course of CAEBV disease-type T/NK LPD can be smoldering, persistent or progressive, depending on the balance between viral factors and host immunity. Aggressive NK-cell leukemia, hydroa vacciniforme-like T-cell lymphoma, or uncommonly extranodal NK/T-cell lymphoma can develop in children and young adults with CAEBV disease-type T/NK-cell LPD. Extranodal T/NK-cell lymphoma is a disease of adults, and its incidence begins to increase in the third decade and comprises the major subtype of T/NK LPD throughout life. Aggressive NK-cell leukemia and nodal T/NK-cell lymphoma of the elderly are fulminant diseases, and immune senescence may be an important pathogenetic factor. This review describes the current progress in identifying different types of EBV-associated T/NK-cell LPD and includes a brief presentation of data from Korea.
- [Show abstract] [Hide abstract] ABSTRACT: Abstract This study aimed at evaluating the role of routine imaging versus symptom-directed unplanned early out-patient department (OPD) visits in patients with diffuse large B-cell lymphoma (DLBCL) in complete remission (CR) by analyzing the patterns and outcomes of OPD visits for disease monitoring. Patients with DLBCL in CR after treatment in the rituximab era with any OPD monitoring visit were analyzed. A total of 856 OPD visits were recorded: 501 visits were with routine imaging, 322 were without routine imaging, and 33 visits (3.9%) were unplanned early visits due to abnormal symptoms. Of the 106 analyzed patients, 15 experienced a relapse (median follow-up duration of 38.1 months). Routine imaging showed an unsatisfactory positive predictive value due to frequent false-positive visits, and a substantial number of patients with false-positive imaging underwent unnecessary biopsies or additional scans. Compared with planned OPD visits, unplanned early visits were highly related to relapse.
- [Show abstract] [Hide abstract] ABSTRACT: The aim of this study is to verify the status and the clinical significance of BRAF and NRAS mutations in patients of one of the university hospitals in Korea.
- [Show abstract] [Hide abstract] ABSTRACT: The incidence of renal cell neoplasms has been increased in worldwide as well as in Korea. Even though the World Health Organization (WHO) Classification of renal tumors (2004) is currently used, new entities require to be added in the updated classification because of recent modification with our understanding of the molecular biology and different clinical behavior of new renal tumors. In this review, recently described tumors and candidate entities will be discussed. It is of importance to know these new entities for the proper diagnosis, treatment, and their prognosis.
- [Show abstract] [Hide abstract] ABSTRACT: Background/aims: Baseline serum lactate dehydrogenase (LDH) level is a well-known prognostic factor in patients with non-Hodgkin's lymphoma; however, its role beyond initial diagnosis has not yet been defined. Methods: This study was conducted as a retrospective analysis of patients with diffuse large B cell lymphoma (DLBCL) treated with R-CHOP21, who had undergone regular checks for LDH during immunochemotherapy (n = 119) and during the posttreatment follow-up period after complete remission (CR; n = 100). The 119 patients were classified into 4 groups according to their baseline and change in LDH level during treatment, and an analysis of tumor response and survival was performed. The value of LDH as a predictor for relapse was evaluated among the patients with regular follow-up visits after achieving CR. Results: An increased LDH level during immunochemotherapy had no impact on tumor response or survival, and only the LDH status 'before' treatment was a prognostic marker. The sensitivity, specificity, positive predictive value and negative predictive value of serum LDH for detecting relapse after CR were 47.4, 86.5, 9.3 and 98.3%, respectively. Conclusion: The measurement of LDH level beyond initial diagnosis has no clear benefit in predicting disease progression or relapse in patients with DLBCL treated with R-CHOP21.
- [Show abstract] [Hide abstract] ABSTRACT: Methotrexate (MTX) has been established as a standard disease-modifying anti-rheumatic drug. If adequate disease control is achieved for a reasonable period of time, tapering the MTX dosage is recommended because the chronic use of MTX can result in opportunistic infection. We present here a case of a woman with rheumatoid arthritis taking MTX, and the woman developed actively caseating endobronchial Mycobacterium intracellulare disease with pulmonary infiltrations. After discontinuing the MTX, the patient was able to tolerate 18 months of antimycobacterial treatment without flare ups of rheumatoid arthritis, and she completely recovered from nontuberculous mycobacterial respiratory disease.