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11 "Sang Yun Ha"
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Original Articles
Analysis of Histologic Features Suspecting Anaplastic Lymphoma Kinase (ALK)-Expressing Pulmonary Adenocarcinoma
In Ho Choi, Dong Won Kim, Sang Yun Ha, Yoon-La Choi, Hee Jeong Lee, Joungho Han
J Pathol Transl Med. 2015;49(4):310-317.   Published online June 22, 2015
DOI: https://doi.org/10.4132/jptm.2015.05.13
  • 9,418 View
  • 86 Download
  • 18 Web of Science
  • 19 Crossref
AbstractAbstract PDF
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.

Citations

Citations to this article as recorded by  
  • Clinicopathological significances of cribriform pattern in lung adenocarcinoma
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  • Clinicopathological features and prognostic significance of pulmonary adenocarcinoma with signet ring cell components: meta-analysis and SEER analysis
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    World Journal of Surgical Oncology.2021;[Epub]     CrossRef
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    Yang Qu, Haifeng Lin, Chen Zhang, Kun Li, Haiqing Zhang
    Pathology - Research and Practice.2019; 215(2): 347.     CrossRef
  • Incidence of brain metastasis in lung adenocarcinoma at initial diagnosis on the basis of stage and genetic alterations
    Bumhee Yang, Hyun Lee, Sang-Won Um, Kyunga Kim, Jae Il Zo, Young Mog Shim, O Jung Kwon, Kyung Soo Lee, Myung-Ju Ahn, Hojoong Kim
    Lung Cancer.2019; 129: 28.     CrossRef
  • Qualitative and quantitative cytomorphological features of primary anaplastic lymphoma kinase‐positive lung cancer
    Ryuko Tsukamoto, Hiroyuki Ohsaki, Sho Hosokawa, Yasunori Tokuhara, Shingo Kamoshida, Toshiko Sakuma, Tomoo Itoh, Chiho Ohbayashi
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    Clinical Lung Cancer.2018; 19(1): 35.     CrossRef
  • Update on the potential significance of psammoma bodies in lung adenocarcinoma from a modern perspective
    Akio Miyake, Koji Okudela, Mai Matsumura, Mitsui Hideaki, Hiromasa Arai, Shigeaki Umeda, Shoji Yamanaka, Yoshihiro Ishikawa, Michihiko Tajiri, Kenichi Ohashi
    Histopathology.2018; 72(4): 609.     CrossRef
  • Integrin β3 Inhibition Enhances the Antitumor Activity of ALK Inhibitor in ALK-Rearranged NSCLC
    Ka-Won Noh, Insuk Sohn, Ji-Young Song, Hyun-Tae Shin, Yu-Jin Kim, Kyungsoo Jung, Minjung Sung, Mingi Kim, Sungbin An, Joungho Han, Se-Hoon Lee, Mi-Sook Lee, Yoon-La Choi
    Clinical Cancer Research.2018; 24(17): 4162.     CrossRef
  • An anaplastic lymphoma kinase-positive lung cancer microlesion: A case report
    Tetsuo Kon, Youichiro Baba, Ichiro Fukai, Gen Watanabe, Tomoko Uchiyama, Tetsuya Murata
    Human Pathology: Case Reports.2017; 7: 11.     CrossRef
  • The prevalence of ALK rearrangement in pulmonary adenocarcinomas in an unselected Caucasian population from a defined catchment area: impact of smoking
    Birgit G Skov, Paul Clementsen, Klaus R Larsen, Jens B Sørensen, Anders Mellemgaard
    Histopathology.2017; 70(6): 889.     CrossRef
  • Ciliated muconodular papillary tumor of the lung harboring ALK gene rearrangement: Case report and review of the literature
    Yan Jin, Xuxia Shen, Lei Shen, Yihua Sun, Haiquan Chen, Yuan Li
    Pathology International.2017; 67(3): 171.     CrossRef
  • Molecular breakdown: a comprehensive view of anaplastic lymphoma kinase (ALK)‐rearranged non‐small cell lung cancer
    Ka‐Won Noh, Mi‐Sook Lee, Seung Eun Lee, Ji‐Young Song, Hyun‐Tae Shin, Yu Jin Kim, Doo Yi Oh, Kyungsoo Jung, Minjung Sung, Mingi Kim, Sungbin An, Joungho Han, Young Mog Shim, Jae Ill Zo, Jhingook Kim, Woong‐Yang Park, Se‐Hoon Lee, Yoon‐La Choi
    The Journal of Pathology.2017; 243(3): 307.     CrossRef
  • Anaplastic lymphoma kinase immunohistochemistry in lung adenocarcinomas: Evaluation of performance of standard manual method using D5F3 antibody
    D Jain, K Jangra, PS Malik, S Arulselvi, K Madan, S Mathur, MC Sharma
    Indian Journal of Cancer.2017; 54(1): 209.     CrossRef
  • Clinicopathological Features and Therapeutic Responses of Chinese Patients with Advanced Lung Adenocarcinoma Harboring an Anaplastic Lymphoma Kinase Rearrangement
    Danxia Lin, De Zeng, Chen Chen, Xiao Wu, Miaojun Wang, Jiongyu Chen, Hui Lin, Xihui Qiu
    Oncology Research and Treatment.2017; 40(1-2): 27.     CrossRef
  • A Validation Study for the Use of ROS1 Immunohistochemical Staining in Screening for ROS1 Translocations in Lung Cancer
    Patrizia Viola, Manisha Maurya, James Croud, Jana Gazdova, Nadia Suleman, Eric Lim, Tom Newsom-Davis, Nick Plowman, Alexandra Rice, M. Angeles Montero, David Gonzalez de Castro, Sanjay Popat, Andrew G. Nicholson
    Journal of Thoracic Oncology.2016; 11(7): 1029.     CrossRef
  • Non-small Cell Lung Cancer with Concomitant EGFR, KRAS, and ALK Mutation: Clinicopathologic Features of 12 Cases
    Taebum Lee, Boram Lee, Yoon-La Choi, Joungho Han, Myung-Ju Ahn, Sang-Won Um
    Journal of Pathology and Translational Medicine.2016; 50(3): 197.     CrossRef
  • ALK gene rearranged lung adenocarcinomas: molecular genetics and morphology in cohort of patients from North India
    Amanjit Bal, Navneet Singh, Parimal Agarwal, Ashim Das, Digambar Behera
    APMIS.2016; 124(10): 832.     CrossRef
PHH3 as an Ancillary Mitotic Marker in Gastrointestinal Stromal Tumors
Yooju Shin, Jiyeon Hyeon, Boram Lee, Sang Yun Ha, Min Eui Hong, In Gu Do, Kyoung-Mee Kim
J Pathol Transl Med. 2015;49(1):23-29.   Published online January 15, 2015
DOI: https://doi.org/10.4132/jptm.2014.10.08
  • 8,563 View
  • 71 Download
  • 8 Web of Science
  • 8 Crossref
AbstractAbstract PDF
Background
Counting mitoses is subjective and time-consuming. The adjunctive diagnostic utility of a recently reported mitotic marker, phosphohistone H3 (PHH3), was investigated in gastrointestinal stromal tumors (GISTs). Methods: We reviewed 77 GISTs for several proliferative indices. These included the mitotic count per 50 high power fields (HPFs), the immunohistochemical Ki- 67 labeling index and the immunohistochemical PHH3 mitotic index (MI). For comparison, Spearman’s rank correlation and interclass correlation coefficient were used. Results: Mitotic counts ranged from 0–138 (mean, 7.57±2.34) and the PHH3 MI ranged from 0–126 per 50 HPFs (mean, 9.61±2.27). We found a positive correlation between mitotic counts and PHH3 MI (r=0.810, p<.001). The inter-observer correlation coefficient for three participants was 0.975 for mitotic counts and 0.940 for the PHH3 MI. When using the PHH3 MI instead of mitotic counts in the Armed Forces Institute of Pathology (AFIP) stratification criteria, 10 cases were reclassified. In one patient with a mitotic count of 2 and a PHH3 MI of 6 per 50 HPFs, distant metastasis occurred. Conclusions: In GISTs, the PHH3 MI correlated adequately with mitotic counts and can be used as a useful adjunctive to count mitotic figures efficiently.

Citations

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  • A retrospective study on expression and clinical significance of PHH3, Ki67 and P53 in bladder exophytic papillary urothelial neoplasms
    Gaoxiu Qi, Jinmeng Liu, Shuqi Tao, Wenyuan Fan, Haoning Zheng, Meihong Wang, Hanchao Yang, Yongting Liu, Huancai Liu, Fenghua Zhou
    PeerJ.2023; 11: e15675.     CrossRef
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    Emilie E. Vomhof-DeKrey, Jack T. Lansing, Diane C. Darland, Josey Umthun, Allie D. Stover, Christopher Brown, Marc D. Basson
    American Journal of Physiology-Gastrointestinal and Liver Physiology.2021; 320(2): G136.     CrossRef
  • Phosphohistone H3 (PHH3) as a surrogate of mitotic figure count for grading in meningiomas: a comparison of PHH3 (S10) versus PHH3 (S28) antibodies
    Napaporn Puripat, Kongsak Loharamtaweethong
    Virchows Archiv.2019; 474(1): 87.     CrossRef
  • Gastrointestinal Stromal Tumors Risk Stratification Utilizing Phospho-Histone H3 Evaluated by Manual Counting and Computer-Assisted Image Analysis
    Cao Jin, Yan Huang, Mansoor Nasim, Yihe Yang, Lili Lee
    International Journal of Surgical Pathology.2019; 27(7): 706.     CrossRef
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    AymenM El-Saka, MohamedA Mlees, YomnaA Zamzam
    Egyptian Journal of Pathology.2019; 39(2): 402.     CrossRef
  • Identification of Phosphohistone H3 Cutoff Values Corresponding to Original WHO Grades but Distinguishable in Well-Differentiated Gastrointestinal Neuroendocrine Tumors
    Min Jeong Kim, Mi Jung Kwon, Ho Suk Kang, Kyung Chan Choi, Eun Sook Nam, Seong Jin Cho, Hye-Rim Park, Soo Kee Min, Jinwon Seo, Ji-Young Choe, Hyoung-Chul Park
    BioMed Research International.2018; 2018: 1.     CrossRef
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    Piotr Lewitowicz, Jaroslaw Matykiewicz, Magdalena Chrapek, Dorota Koziel, Agata Horecka-Lewitowicz, Martyna Gluszek-Osuch, Iwona Wawrzycka, Stanisław Gluszek
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  • The mitosis‐specific marker phosphohistone‐H3 (PHH3) is an independent prognosticator in uterine smooth muscle tumours: an outcome‐based study
    Kin‐Long Chow, Ka‐Yu Tse, Ching‐Lung Cheung, Ka‐Wing Wong, Annie N Y Cheung, Richard W C Wong, Alice N H Chan, Nancy W F Yuen, Hextan Y S Ngan, Philip P C Ip
    Histopathology.2017; 70(5): 746.     CrossRef
Extrapulmonary Lymphangioleiomyoma: Clinicopathological Analysis of 4 Cases
Dae Hyun Song, In Ho Choi, Sang Yun Ha, Kang Min Han, Jae Jun Lee, Min Eui Hong, Yoon-La Choi, Kee-Taek Jang, Sang Yong Song, Chin A Yi, Joungho Han
Korean J Pathol. 2014;48(3):188-192.   Published online June 26, 2014
DOI: https://doi.org/10.4132/KoreanJPathol.2014.48.3.188
  • 7,738 View
  • 58 Download
  • 9 Crossref
AbstractAbstract PDF
Background

Lymphangioleiomyomatosis (LAM) is a slowly progressive neoplastic disease that predominantly affects females. Usually, LAM affects the lung; it can also affect extrapulmonary sites, such as the mediastinum, the retroperitoneum, or the lymph nodes, although these locations are rare. A localized form of LAM can manifest as extrapulmonary lesions; this form is referred to as extrapulmonary lymphangioleiomyoma (E-LAM). Due to the rare occurrence of E-LAM and its variable, atypical location, E-LAM is often difficult to diagnose. Herein, we report the clinicopathological information from four E-LAM cases, and also review previous articles investigating this disease.

Methods

Four patients with E-LAM were identified at the Samsung Medical Center (Seoul, Korea) from 1995 to 2012. All E-LAM lesions underwent surgical excision.

Results

All patients were females within the age range of 43 to 47 years. Two patients had para-aortic retroperitoneal masses, while the other two patients had pelvic lesions; two out of the four patients also had accompanying pulmonary LAM. In addition, no patient displayed any evidence of tuberous sclerosis. Histologically, two patients exhibited nuclear atypism with cytologic degeneration.

Conclusions

E-LAM should be considered in the differential diagnosis of patients presenting with pelvic or para-aortic masses. We also conclude that further clinical and pathological evaluation is needed in patients with E-LAM and nuclear atypism.

Citations

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    Aiko Ogasawara, Shogo Yamaguchi, Hiroaki Inui, Mieko Hanaoka, Daisuke Shintani, Sho Sato, Masanori Yasuda, Akira Yabuno
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Usual Interstitial Pneumonia with Lung Cancer: Clinicopathological Analysis of 43 Cases
Dae Hyun Song, In Ho Choi, Sang Yun Ha, Kang Min Han, Jae Jun Lee, Min Eui Hong, Kyeongman Jeon, Man Pyo Chung, Jhingook Kim, Joungho Han
Korean J Pathol. 2014;48(1):10-16.   Published online February 25, 2014
DOI: https://doi.org/10.4132/KoreanJPathol.2014.48.1.10
  • 8,799 View
  • 71 Download
  • 15 Crossref
AbstractAbstract PDF
Background

Previous studies have suggested an association between usual interstitial pneumonia (UIP) and lung cancer (Ca). However, clinical and histological information is not enough to determine such an association, due to the low incidence and short survival time of patients with both conditions.

Methods

We retrospectively reviewed the clinical and histological records of Ca patients with UIP between January 1999 and August 2013 at the Samsung Medical Center, Seoul, Korea. We found 43 patients who had Ca with UIP (UIP-Ca). Previously reported data of eighty-four patients with UIP-only were included as a comparison group.

Results

Smoking is related to poor prognosis in patients with UIP-Ca, and the number of patients with a high smoking index of more than 30 pack-years significantly increased in UIP-Ca patients compared with UIP-only patients. There is no significant prognostic differentiation between UIP-Ca patients and UIP-only patients. Microscopically, UIP-Ca patients showed characteristically heterogeneous histological patterns and degrees of differentiation. There were many foci of squamous metaplasia or dysplasia at the peripheral area of squamous cell carcinomas.

Conclusions

We report 43 cases of UIP-Ca. Our results suggest that smoking is related to cancer occurrence in UIP patients and poor prognosis in UIP-Ca patients.

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Comparison of Three BRAF Mutation Tests in Formalin-Fixed Paraffin Embedded Clinical Samples
Soomin Ahn, Jeeyun Lee, Ji-Youn Sung, So Young Kang, Sang Yun Ha, Kee-Taek Jang, Yoon-La Choi, Jung-Sun Kim, Young Lyun Oh, Kyoung-Mee Kim
Korean J Pathol. 2013;47(4):348-354.   Published online August 26, 2013
DOI: https://doi.org/10.4132/KoreanJPathol.2013.47.4.348
  • 7,448 View
  • 54 Download
  • 9 Crossref
AbstractAbstract PDF
Background

Recently, BRAF inhibitors showed dramatic treatment outcomes in BRAF V600 mutant melanoma. Therefore, the accuracy of BRAF mutation test is critical.

Methods

BRAF mutations were tested by dual-priming oligonucleotide-polymerase chain reaction (DPO-PCR), direct sequencing and subsequently retested with a real-time PCR assay, cobas 4800 V600 mutation test. In total, 64 tumors including 34 malignant melanomas and 16 papillary thyroid carcinomas were analyzed. DNA was extracted from formalin-fixed paraffin embedded tissue samples and the results of cobas test were directly compared with those of DPO-PCR and direct sequencing.

Results

BRAF mutations were found in 23 of 64 (35.9%) tumors. There was 9.4% discordance among 3 methods. Out of 6 discordant cases, 4 cases were melanomas; 3 cases were BRAF V600E detected only by cobas test, but were not detected by DPO-PCR and direct sequencing. One melanoma patient with BRAF mutation detected only by cobas test has been on vemurafenib treatment for 6 months and showed a dramatic response to vemurafenib. DPO-PCR failed to detect V600K mutation in one case identified by both direct sequencing and cobas test.

Conclusions

In direct comparison of the currently available DPO-PCR, direct sequencing and real-time cobas test for BRAF mutation, real-time PCR assay is the most sensitive method.

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Case Study
Silent Colonic Malakoplakia in a Living-Donor Kidney Transplant Recipient Diagnosed during Annual Medical Examination
Go Eun Bae, Nara Yoon, Ha Young Park, Sang Yun Ha, Junhun Cho, Yunkyung Lee, Kyoung-Mee Kim, Cheol Keun Park
Korean J Pathol. 2013;47(2):163-166.   Published online April 24, 2013
DOI: https://doi.org/10.4132/KoreanJPathol.2013.47.2.163
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  • 56 Download
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AbstractAbstract PDF

Malakoplakia is a characteristic inflammatory condition, which is usually seen in the urogenital tract, and less frequently in the gastrointestinal tract. We present a case of colonic malakoplakia in an immunocompromised patient. A 55-year-old female visited the outpatient clinic for routine cancer surveillance. Her past medical history was significant for kidney transplantation 11 years ago, and she had been taking immunosuppressants. A colonoscopy revealed several depressed flat lesions and elevated polyps, which were 0.3 to 0.4 cm in size and accompanied by whitish exudates. A biopsy revealed an infiltration of histiocytes with ample granular eosinophilic cytoplasm, with some lymphocytes and plasma cells. Many histiocytes had the characteristic morphology, described as Michaelis-Gutmann bodies: one or several round basophilic structures of approximately 1 to 10 µm in size with some being laminated, some appearing homogeneous, and others having a dense central core with a targetoid appearance. These Michaelis-Gutmann bodies were positively stained on von Kossa stain, and were diagnostic for malakoplakia.

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Original Article
Clinicopathological Analysis of 21 Thymic Neuroendocrine Tumors
Soomin Ahn, Jae Jun Lee, Sang Yun Ha, Chang Ohk Sung, Jhingook Kim, Joungho Han
Korean J Pathol. 2012;46(3):221-225.   Published online June 22, 2012
DOI: https://doi.org/10.4132/KoreanJPathol.2012.46.3.221
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AbstractAbstract PDF
Background

Thymic neuroendocrine carcinomas (NECs) are uncommon, for which there is no established information available because of a limited number of epidemiological study in Asia.

Methods

We reviewed 21 cases of surgically resected thymic NECs, and evaluated their pathological and clinical features.

Results

It showed male predominance (male/female ratio, 15/6) with wide age range from 20 to 72 years (mean age, 49 years). All 21 cases were divided into two types according to the World Health Organization criteria: atypical carcinoid (n=18) and large cell NEC (n=3). Three cases of atypical carcinoid (AC) were associated with ectopic Cushing's syndrome. All the patients (3/3) with large cell NEC (3/3) and 16.7% (3/18) of those with AC died of tumor progression. Common sites of metastasis included lung, lymph node, brain, lumbar spine, mediastinum, bone, and liver.

Conclusions

In conclusion, thymic neuroendocrine tumors carry a poor prognosis. Regarding the tumor classification, our results showed that a vast majority of carcinoids in the thymus correspond to ACs. In addition, our results also indicate that typical carcinoid is a very rare entity. Some cases of AC exhibited a large size, solid pattern and they showed aggressive clinical behavior, which highlights the spectrum of histologic appearances of thymic NECs.

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Case Reports
Localized Primary Thymic Amyloidosis Presenting as a Mediastinal Mass: A Case Report.
Sang Yun Ha, Jae Jun Lee, Heejung Park, Joungho Han, Hong Kwan Kim, Kyung Soo Lee
Korean J Pathol. 2011;45:S41-S44.
DOI: https://doi.org/10.4132/KoreanJPathol.2011.45.S1.S41
  • 3,480 View
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AbstractAbstract PDF
We herein describe a case of a 55-year-old healthy woman with localized primary thymic amyloidosis presented as a mediastinal mass, found incidentally by chest radiography. Computed tomography revealed a 4.1 cm soft tissue lesion with nodular calcification in the left anterior mediastinum. The resected specimen was a well-defined lobulating mass with calcification. Microscopically, the mass was consisted of amorphous eosinophilc hyalinized substances involving the thymus and intrathymic lymph nodes. These eosinophilic substances showed apple-green bi-refringence under polarized light after staining with Congo red. In immunohistochemical study, they were positive for kappa and lambda light chains and negative for amyloid A. There was no evidence of systemic amyloidosis in clinical investigations. A final diagnosis of localized primary thymic amyloidosis was made.

Citations

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    Avnee Kumar, Barathi Sivasailam, Ellen Marciniak, Janaki Deepak
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  • Ocular Myasthenia Gravis Associated With Thymic Amyloidosis
    Kristin O. Chapman, Debra M. Beneck, Marc J. Dinkin
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  • Localized Thymic Amyloidosis Presenting with Myasthenia Gravis: Case Report
    Seung-Myoung Son, Yong-Moon Lee, Si Wook Kim, Ok-Jun Lee
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Diffuse Large B-Cell Lymphoma Associated with Chronic Inflammation Manifested as a Soft Tissue Mass: Incidental Discovery on Histological Examination.
Sang Yun Ha, Yoon La Choi, Sung Joo Kim, Young Hye Ko
Korean J Pathol. 2011;45(4):417-422.
DOI: https://doi.org/10.4132/KoreanJPathol.2011.45.4.417
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AbstractAbstract PDF
We report an extraordinary case of diffuse large B-cell lymphoma arising in a cystic necrotic mass in a 35-year-old man who presented with a soft tissue mass at the site of previous surgery. A benign mass was surgically removed 17 years ago, after which a cystic lesion gradually developed at the same site. The resected mass appeared as a thick-walled cyst filled with brown necrotic and hemorrhagic material. On microscopic examination, the cyst wall was primarily necrotic tissue with some aggregates of large atypical lymphoid cells. These atypical cells were diffusely positive for CD20 and showed a high proliferation index, Epstein-Barr virus positivity, and clonal rearrangement of the immunoglobulin gene. His present condition was diagnosed as Epstein-Barr virus-associated diffuse large B-cell lymphoma arising from chronic inflammation. It is important to be aware of the clinical manifestations and histological features of this rare disease in light of diagnosis and treatment.

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Original Articles
Mucoepidermoid Carcinoma of Tracheobronchial Tree: Clinicopathological Study of 31 Cases.
Sang Yun Ha, Joungho Han, Jae Jun Lee, Young Eun Kim, Yoon La Choi, Hong Kwan Kim
Korean J Pathol. 2011;45(2):175-181.
DOI: https://doi.org/10.4132/KoreanJPathol.2011.45.2.175
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AbstractAbstract PDF
BACKGROUND
All aspects of mucoepidermoid carcinoma (MEC) of the lung including histologic grading, clinical behavior and its differentiation from adenosquamous cell carcinoma are still not fully understood.
METHODS
We reviewed the hematoxylin-eosin stained slides and medical records of 31 cases of MEC of the lungs. The cases were classified as low and high grade according to the quantitative grading system formulated for MEC. High grade tumors were tested for an epidermal growth factor receptor (EGFR) mutation.
RESULTS
Twenty eight cases were classified as low grade and 3 cases as high grade. Histologically, lower glandular component, cellular atypia, necrosis, mitoses >4/10 high power fields, and endolymphatic tumor emboli were typical characteristics of a high grade tumor. Although some tumors showed histologic features mimicking high grade tumors, they were classified as low grade tumors according to this quantitative grading system. Low grade tumors showed no recurrence or metastasis. However, among three patients with a high grade tumor, two had distant metastases and one died of disease. Additionally, an EGFR mutation was not detected.
CONCLUSIONS
A high grade MEC was consistently different from a low grade tumor with regard to malignant histologic features and poor prognosis. Therefore, correct histologic grading is important in predicting the prognosis to avoid unnecessary treatment.

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Prognostic Significance of Methylation Profiles in Urothelial Carcinomas of the Bladder.
Hee Jung Park, Eui Jin Lee, Sang Yun Ha, Ghee Young Kwon, Young Lyun Oh, Kyoung Mee Kim, Dae Shick Kim, Seongil Seo, Hyun Moo Lee, Han Yong Choi
Korean J Pathol. 2010;44(6):623-630.
DOI: https://doi.org/10.4132/KoreanJPathol.2010.44.6.623
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AbstractAbstract PDF
BACKGROUND
Study on epigenetics of urothelial carcinomas has expanded and allowed better understanding of their correlation with clinicopathologic features. The aim of this study was to determine reliable predictive epigenetic markers for patients with urothelial carcinoma of urinary bladder.
METHODS
In 64 urothelial carcinomas of the urinary bladder, methylationspecific polymerase chain reaction with RAS association domain family 1A (RASSF1A), adenomatous polyposis coli (APC), death-associated protein-kinase (DAPK), runt-related transcription factor 3 (RUNX3), p14, p16 and MGMT was performed and correlated the results with p53 mutations, DNA ploidy, clinicopathologic parameters and recurrences.
RESULTS
Hypermethyation of RASSF1A, APC, DAPK, RUNX3, p14, p16 and MGMT promoters was observed in 35 (54.7%), 29 (45.3%), 18 (28.1%), 18 (28.1%), 9 (14.1%), 2 (3.1%), and 6 (9.4%) cases, respectively. Hypermethylation of RUNX3 and APC was significantly associated with high histologic grades and aneuploidy. Methylation of DAPK was significantly associated with muscle invasion. Methylation of DAPK and RUNX3 genes was significantly associated with recurrence. In survival analyses, methylation of RUNX3 gene and methylation-high (methylation at two or more loci) phenotype was significantly associated with poor recurrence-free survival.
CONCLUSIONS
Methylation of RUNX3 gene and methylation-high phenotype are significant indicator of recurrence.

Citations

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  • DAPK Promoter Methylation and Bladder Cancer Risk: A Systematic Review and Meta-Analysis
    Lihe Dai, Chong Ma, Zhensheng Zhang, Shuxiong Zeng, Anwei Liu, Shijie Tang, Qian Ren, Yinghao Sun, Chuanliang Xu, Shengtao Zhou
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