Publications by authors named "Chang Gok Woo"

37 Publications

Spontaneous heterotopic mesenteric ossification around the pancreas causing duodenal stenosis: A case report with literature review.

Int J Surg Case Rep 2021 Apr 6;81:105702. Epub 2021 Mar 6.

Department of Internal Medicine, Chungbuk National University Hospital, Cheongju, Republic of Korea. Electronic address:

Introduction And Importance: Heterotopic mesenteric ossification (HMO) is a rare condition that can be hereditary or nonhereditary. It can lead to small bowel obstruction, which may require corrective surgery. Most affected patients have a history of abdominal surgery or trauma. Spontaneously occurring HMO is even rarer, with only 7 cases reported till date. There has been no previous report of spontaneous peripancreatic HMO.

Case Presentation: A 60-year-old man presented with complaints of recurrent nausea and vomiting for 2 months. Esophagogastroduodenoscopy revealed luminal stenosis and edematous changes involving the second and third parts of the duodenum but not its complete obstruction. Abdominopelvic computed tomography showed faintly enhanced thickening of the involved duodenal walls along with mild dilatation of the common bile duct. Considering the possibility of periampullary cancer, we performed a pylorus-preserving pancreaticoduodenectomy. Histopathological examination confirmed the diagnosis of HMO with extensive fibrosis involving the peripancreatic soft tissue.

Clinical Discussion: The peripancreatic HMO with severe fibrosis can occur duodenal stenosis, and it is mimicking periampullary cancer. However, the preoperative diagnosis of spontaneous HMO is difficult, and a diagnosis confirmed after surgery.

Conclusion: Herein, we described our experience of managing a rare case of duodenal stenosis due to spontaneous HMO involving peripancreatic tissue.
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http://dx.doi.org/10.1016/j.ijscr.2021.105702DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8073193PMC
April 2021

Brain metastasis with subtype conversion in a patient with male breast cancer: A case report.

Medicine (Baltimore) 2021 Mar;100(11):e24373

Department of Neuroscience, Graduate School, College of Medicine, Chungbuk National University, Cheongju, Republic of Korea.

Rationale: Brain metastasis of male breast cancer is extremely rare, and the pathological changes between the primary tumor and the metastatic brain tumor have not been reported. Herein, we report for the first time a case of male breast cancer with metastasis to the parietal lobe with subtype conversion after metastasis.

Patient Concerns: we describe a 45-year-old male patient admitted for an incidentally found brain tumor after a motorcycle accident. The patient had been treated for breast cancer 5 years previously. The primary tumor was an invasive ductal carcinoma classified as pT1N1M0 with hormone receptor positivity (estrogen receptor ++, progesterone receptor +++, human epidermal growth factor receptor-type2 (HER2) +) and was treated with surgery, adjuvant chemotherapy, radiation therapy and endocrine therapy (tamoxifen).

Diagnoses: Magnetic resonance imaging revealed a well enhanced focal solid tumor in the right parietal lobe (5.0 × 4.2 cm in size), Immunohistochemical staining revealed cerebral metastases of breast cancer with HER2 subtype conversion (estrogen receptor +++, progesterone receptor +++, HER2 -).

Interventions: The patient was successfully treated with surgery and whole brain irradiation (3 Gy × 10 fractions).

Outcomes: There was no additional complication after the surgery and the patient transferred to oncology department for chemotherapy. 2 years later, he had gamma knife radiosurgery due to the recurred brain lesion and after that he discontinued the treatment and opted for hospice care.

Lessons: Male breast cancer with metastasis to the brain is an extremely rare condition. Although a few similar cases have been reported, subtype conversion in similar cases has not been reported. Therefore, we report this case of a male patient with brain metastasis of invasive ductal carcinoma with HER2 status conversion after metastasis.
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http://dx.doi.org/10.1097/MD.0000000000024373DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7982243PMC
March 2021

Radioprotective effects of Cryptosporidium parvum lysates on normal cells.

Int J Biol Macromol 2021 May 23;178:121-135. Epub 2021 Feb 23.

Department of Radiation Oncology, Chungbuk National University Hospital, Chungbuk National University College of Medicine, Cheongju 28644, Republic of Korea. Electronic address:

Two fractions, small and big (CpL-S, CpL-B), from Cryptosporidium parvum lysate (CpL) were prepared and its radioprotective activity was evaluated on normal cells. Both fractions improved cell viability of normal cells in a dose-dependent manner. 20 μg CpL-S and CpL-B improved cell viability of 10 Gy irradiated COS-7 cells by 38% and 34% respectively, while in HaCat cells 16% and 18% improved cell viability was observed, respectively. CpL-S scavenged IR-induced ROS more effectively compared to the CpL-B, 50% more in COS-7 cells and 15% more in HaCat cells. There was a significant reduction of γH2AX, Rad51, and pDNA-PKcs foci in CpL-S treated cells compared to control or CpL-B group at an early time point as well as late time point. In 3D skin tissue, CpL-S reduced the number of γH2AX positive cells by 31%, compared to control, while CpL-B reduced by 9% (p < 0.005) at 1 h post 10 Gy irradiation and 22% vs 6% at 24 h post-IR (p < 0.005). Taken together, CpL-S significantly improved cell viability and prevented radiation-induced DNA damage in normal cells as well as 3D skin tissues by effectively scavenging ROS generated by ionizing radiation. CpL-S can be a candidate for radioprotector development.
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http://dx.doi.org/10.1016/j.ijbiomac.2021.02.151DOI Listing
May 2021

Primary Pancreatic Candidiasis Mimicking Pancreatic Cancer in an Immunocompetent Patient.

Korean J Gastroenterol 2021 01;77(1):45-49

Department of Internal Medicine, Chungbuk National University Hospital, Cheongju, Korea.

Pancreatic candidiasis can develop in patients with acute pancreatitis, compromised immune responses, or iatrogenic intervention. This paper reports a case of pancreatic candidiasis presenting as a solid pancreatic mass in a patient without the risk factors. A previously healthy 37-year-old man visited the emergency department with left flank pain. Abdominal CT revealed a 5 cm, irregular heterogeneous enhancing mass accompanied by a left adrenal mass. Positron emission tomography-computed tomography and endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) could not discriminate pancreatic cancer from infectious disease. A laparoscopic exploration was performed for an accurate diagnosis. After distal pancreatectomy with splenectomy and left adrenalectomy, pancreatic candidiasis and adrenal cortical adenoma were diagnosed based on the pathology findings. His condition improved after the treatment with fluconazole. This paper reports a case of primary pancreatic candidiasis mimicking pancreatic cancer in an immunocompetent patient with a review of the relevant literature.
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http://dx.doi.org/10.4166/kjg.2020.155DOI Listing
January 2021

TOX-expressing terminally exhausted tumor-infiltrating CD8 T cells are reinvigorated by co-blockade of PD-1 and TIGIT in bladder cancer.

Cancer Lett 2021 02 27;499:137-147. Epub 2020 Nov 27.

Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea. Electronic address:

Exhausted T cells in the tumor microenvironment are major targets of immunotherapies. However, the exhaustion status of CD8 tumor-infiltrating lymphocytes (TILs) in bladder cancer has not been comprehensively evaluated. Herein, we examined distinct exhaustion status of CD8 TILs based on the level of programmed cell death-1 (PD-1) and thymocyte selection-associated high mobility group box protein (TOX) expression in urothelial bladder cancer. We also evaluated the reinvigoration of exhausted CD8 TILs upon ex vivo treatment with inhibitory checkpoint blockers. TOX-expressing PD-1CD8 TILs had the highest expression of immune checkpoint receptors (ICRs), the most terminally exhausted features, and the highest tumor antigen reactivity among PD-1CD8 TILs. Bladder cancer patients with a high percentage of PD-1TOXCD8 TILs had more progressed T-cell exhaustion features and higher programmed death-ligand 1 expression in tumor tissues. TIGIT was the most frequent co-expressed ICR on PD-1CD8 TILs, and TIGIT blockade enhanced the PD-1 blockade-mediated cytokine production by CD8 TILs from bladder cancer patients. Our findings provide an improved understanding of the heterogeneous exhaustion status of CD8 TILs and additional immunotherapy strategies to improve outcomes of bladder cancer patients.
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http://dx.doi.org/10.1016/j.canlet.2020.11.035DOI Listing
February 2021

Distinct tumor immune microenvironments in primary and metastatic lesions in gastric cancer patients.

Sci Rep 2020 08 31;10(1):14293. Epub 2020 Aug 31.

Department of Internal Medicine, Chungbuk National University Hospital, Cheongju, Republic of Korea.

This study compared the tumor immune microenvironments (TIMEs) of primary gastric cancer (PGC) and paired metastatic gastric cancer (MGC). CD4 and CD8 T-cell density and PD-L1 expression were evaluated by multiplex immunohistochemistry, DNA mismatch repair (MMR) by immunohistochemistry, and immune-related genes by RNA sequencing. Twenty-three patients who underwent surgical treatment for PGC and MGC were enrolled in this study. CD8 T-cell, PD-L1 cell, and PD-L1CK cell densities were significantly lower in MGC than PGC. PD-L1 positivity using a combined positive score (≥ 1%) and deficient MMR were observed in 52.2% and 8.7% of PGC samples, respectively, whereas both occurred in only 4.3% of MGC samples. The most frequent TIME types were inflamed (34.8%) and adaptive immune resistance (34.8%) in PGC, and immune desert (65.2%) and immunological ignorance (73.9%) in MGC. In transcriptome analysis, the expression of the T-cell inflamed gene set and co-stimulatory gene module was down-regulated in MGC compared to PGC. The total CD8 T-cell density was an independent prognostic marker in both PGC and MGC (univariate P = 0.002, multivariate P = 0.006). Our result suggest that the TIME of metastatic tumors was less immunologically active compared to that of primary tumors in gastric cancer patients.
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http://dx.doi.org/10.1038/s41598-020-71340-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7459099PMC
August 2020

Characterization and comparison of genomic profiles between primary cancer cell lines and parent atypical meningioma tumors.

Cancer Cell Int 2020 28;20:345. Epub 2020 Jul 28.

Laboratory of Veterinary Embryology and Biotechnology (VETEMBIO), Veterinary Medical Center and College of Veterinary Medicine, Chungbuk National University, 1 Chungdae-ro, Seowon-gu, Cheongju, 28644 Republic of Korea.

Background: Meningiomas are the second most common primary tumors of the central nervous system. However, there is a paucity of data on meningioma biology due to the lack of suitable preclinical in vitro and in vivo models. In this study, we report the establishment and characterization of patient-derived, spontaneously immortalized cancer cell lines derived from World Health Organization (WHO) grade I and atypical WHO grade II meningiomas.

Methods: We evaluated high-resolution 3T MRI neuroimaging findings in meningioma patients which were followed by histological analysis. RT-qPCR and immunostaining analyses were performed to determine the expression levels of meningioma-related factors. Additionally, flow cytometry and sorting assays were conducted to investigate and isolate the CD133 and CD44 positive cells from primary atypical meningioma cells. Further, we compared the gene expression profiles of meningiomas and cell lines derived from them by performing whole-exome sequencing of the blood and tumor samples from the patients, and the primary cancer cell lines established from the meningioma tumor.

Results: Our results were consistent with earlier studies that reported mutations in , , and genes in atypical meningiomas, and we also observed mutations in , a gene that was recently discovered. Significantly, the genomic signature was consistent between the atypical meningioma cancer cell lines and the tumor and blood samples from the patient.

Conclusion: Our results lead us to conclude that established meningioma cell lines with a genomic signature identical to tumors might be a valuable tool for understanding meningioma tumor biology, and for screening therapeutic agents to treat recurrent meningiomas.
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http://dx.doi.org/10.1186/s12935-020-01438-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7388534PMC
July 2020

Degenerative joint disease in the temporomandibular joint with fibrous ankylosis in a rhesus macaque ().

Lab Anim Res 2020 2;36:19. Epub 2020 Jul 2.

Xenotransplantation Research Center, 103 Daehar-ro Jongno-gu, Seoul, 110-799 Korea.

Background: Ankylosis in the temporomandibular joint (TMJ) is known to have various etiologies in veterinary medicine. We observed a case of fibrous ankylosis of the TMJ in a newly imported rhesus monkey ().

Case Presentation: Moderate to severe attrition was found in the middle labial portion of the left maxillary canine. No tenderness around the jaw was detected in the physical examination. The WBC count, CRP level, rheumatoid factor level, and other parameters were normal. Irregularity in the joint surface was observed in both TMJs in the radiographic and computed tomographic examinations, but the left TMJ presented more severe irregularity. It was determined that the removal of the locked portion of the left canine would alleviate the case of lockjaw and allow intubation with an endotracheal tube. Canine tooth crown reduction was performed for both canine teeth. The mouth opening distance slightly (approximately 5 mm) increased up to 20 mm. We concluded that the attrition of canine teeth was not the reason for lockjaw and ankyloses originating from TMJ disease. Fibrotic synovial tissue and joint surface irregularity were observed by necropsy. The presence of fibrocartilage in most areas of the TMJ was confirmed by histology. The diagnosis was fibrous ankylosis of the TMJ associated with DJD.

Conclusions: To the best of our knowledge, this is the first report of degenerative joint disease of the TMJ in a rhesus monkey with fibrous ankylosis of the TMJ.
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http://dx.doi.org/10.1186/s42826-020-00052-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7333388PMC
July 2020

Analysis of EGFR mutation status in malignant pleural effusion and plasma from patients with advanced lung adenocarcinoma.

Clin Chem Lab Med 2020 08 25;58(9):1547-1555. Epub 2020 Mar 25.

Department of Pathology, Chungbuk National University Hospital, Cheongju, Republic of Korea.

Background: Cell-free DNA (cfDNA) is emerging as a surrogate sample type for mutation analyses. We investigated the suitability of malignant pleural effusion (MPE) and plasma as a biomaterial for analyzing epidermal growth factor receptor (EGFR) mutation by peptide nucleic acid (PNA) clamping-assisted fluorescence melting curve (PANAMutyper™) analysis.

Methods: Matched tissue, MPE cell block (MPE-CB), MPE supernatant, and plasma samples were collected from patients with advanced lung adenocarcinoma who had a MPE at the time of diagnosis. EGFR mutation was assessed by PANAMutyper™.

Results: Mutation analyses in matched tumor tissues, MPE-CB, MPE supernatant, and/or plasma samples were available for 67 patients. In comparison with tumor tissue and MPE-CB, MPE supernatant exhibited 84.4% sensitivity, 97.1% specificity, 96.4% positive predictive value (PPV), and 87.2% negative predictive value (NPV). In the same comparison, plasma exhibited 70.6% sensitivity, 100.0% specificity, 100.0% PPV, and 73.7% NPV. When sorted by mutation type, MPE supernatant had better sensitivity than plasma for the detection of two major EGFR mutations: 93.8% vs. 75.0% for exon 19 deletion and 73.3% vs. 60.0% for L858R.

Conclusions: In this cohort of patients with MPEs, MPE supernatant demonstrated superior diagnostic performance compared with plasma using a PNA-based real-time PCR method.
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http://dx.doi.org/10.1515/cclm-2019-1139DOI Listing
August 2020

EML4-ALK V3 oncogenic fusion proteins promote microtubule stabilization and accelerated migration through NEK9 and NEK7.

J Cell Sci 2020 05 11;133(9). Epub 2020 May 11.

Department of Molecular and Cell Biology, University of Leicester, Lancaster Road, Leicester LE1 9HN, UK

EML4-ALK is an oncogenic fusion present in ∼5% of non-small cell lung cancers. However, alternative breakpoints in the gene lead to distinct variants of EML4-ALK with different patient outcomes. Here, we show that, in cell models, EML4-ALK variant 3 (V3), which is linked to accelerated metastatic spread, causes microtubule stabilization, formation of extended cytoplasmic protrusions and increased cell migration. EML4-ALK V3 also recruits the NEK9 and NEK7 kinases to microtubules via the N-terminal EML4 microtubule-binding region. Overexpression of wild-type EML4, as well as constitutive activation of NEK9, also perturbs cell morphology and accelerates migration in a microtubule-dependent manner that requires the downstream kinase NEK7 but does not require ALK activity. Strikingly, elevated NEK9 expression is associated with reduced progression-free survival in EML4-ALK patients. Hence, we propose that EML4-ALK V3 promotes microtubule stabilization through NEK9 and NEK7, leading to increased cell migration. This represents a novel actionable pathway that could drive metastatic disease progression in EML4-ALK lung cancer.
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http://dx.doi.org/10.1242/jcs.241505DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7240300PMC
May 2020

Characteristics of Renal Cell Carcinoma Harboring Fusion.

Yonsei Med J 2020 Mar;61(3):262-266

Department of Pathology, Chungbuk National University Hospital, Cheongju, Korea.

The World Health Organization 2016 edition assigned anaplastic lymphoma kinase () rearrangement-associated renal cell carcinoma (ALK-RCC) as an emerging renal tumor entity. Identifying ALK-RCC is important because ALK inhibitors have been shown to be effective in treatment. Here, we report the case of a 14-year-old young man with ALK-RCC. Computed tomography revealed a well-demarcated 5.3-cm enhancing mass at the upper pole of the left kidney. There was no further history or symptoms of the sickle-cell trait. The patient underwent left radical nephrectomy. Pathologically, the mass was diagnosed as an unclassified RCC. Targeted next-generation sequencing identified a fusion gene. The present report and literature review demonstrate that TPM3-ALK RCC may be associated with distinct clinicopathological features. Microscopically, the tumors showed diffuse growth and tubulocystic changes with inflammatory cell infiltration. Tumor cells were dis-cohesive and epithelioid with abundant eosinophilic cytoplasm and cytoplasmic vacuoles. If morphological features and TFE3 expression are present in adolescent and young patients, molecular tests for translocation should be performed. This awareness is critically important, because rearrangement confers sensitivity to ALK inhibitors.
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http://dx.doi.org/10.3349/ymj.2020.61.3.262DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7044692PMC
March 2020

Factors affecting retrieval of 12 or more lymph nodes in pT1 colorectal cancers.

J Int Med Res 2019 Oct 9;47(10):4827-4840. Epub 2019 Sep 9.

Department of Pathology, Chungbuk National University Hospital, Cheongju, Republic of Korea.

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http://dx.doi.org/10.1177/0300060519862055DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6833376PMC
October 2019

Collision tumor comprising metastatic cholangiocarcinoma and seminoma in an undescended testis: a case report.

J Int Med Res 2019 Nov 9;47(11):5809-5816. Epub 2019 Sep 9.

Department of Pathology, Chungbuk National University Hospital, Cheongju, Republic of Korea.

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http://dx.doi.org/10.1177/0300060519869448DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6862903PMC
November 2019

Discordance in HER2 status between primary gastric adenocarcinoma tumors and cells from the corresponding malignant effusions.

BMC Cancer 2019 Sep 3;19(1):834. Epub 2019 Sep 3.

Department of Internal Medicine, Chungbuk National University Hospital, Chungdae-ro 1, Seowon-gu, Cheongju, 28644, South Korea.

Background: Metastasis of gastric cancer commonly manifests as a malignant effusion, which presents an alternative cell source for human epidermal growth factor receptor 2 (HER2) status identification. This study aimed to compare HER2 status in primary gastric adenocarcinoma tumors and corresponding cell blocks prepared from malignant effusions (CB-MEs).

Methods: HER2 status was retrospectively evaluated by immunohistochemistry (IHC) in primary gastric adenocarcinomas and paired pathologically confirmed CB-MEs of 45 patients. Silver in situ hybridization (SISH) was also performed in cases with IHC 2+ for primary gastric adenocarcinomas and above IHC 1+ for CB-MEs.

Results: HER2 positivity was observed in 4.4% (2/45) of primary gastric adenocarcinomas and 6.7% (3/45) of CB-MEs. The HER2 concordance rate between primary gastric adenocarcinomas and CB-MEs was 88.9% (40/45) (κ = - 0.056). All five patients with HER2 positivity in the primary tumor or a CB-ME had a negative result in the corresponding paired sample. Of the 15 patients with two or more serially sampled CB-MEs, HER2 expression determined by IHC differed between each CB-ME in six (40%) patients, and all three patients with HER2 positivity in CB-MEs exhibited HER2 positivity in one of the serially sampled CB-MEs.

Conclusions: The HER2 positivity rate was very low in gastric cancer patients with malignant effusions. Our results suggest that HER2 positivity was discordant between the primary gastric adenocarcinoma and corresponding CB-MEs and among serially sampled CB-MEs. The possibility of detecting HER2 positivity can be improved if the primary gastric adenocarcinoma tumor as well as all the available CB-MEs from each patient are analyzed.
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http://dx.doi.org/10.1186/s12885-019-6035-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6721206PMC
September 2019

Therapeutic Effect of pHLIP-mediated CEACAM6 Gene Silencing in Lung Adenocarcinoma.

Sci Rep 2019 09 2;9(1):11607. Epub 2019 Sep 2.

Department of Pathology, Chungbuk National University Hospital, 776, 1Sunhwan-ro, Seowon-gu, Cheongju, 28644, Republic of Korea.

Carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6) plays an important role in lung cancer progression. Here, we examined the therapeutic efficacy of CEACAM6 gene silencing using an siRNA delivery platform targeting the acidic tumour microenvironment in a lung adenocarcinoma xenograft mouse model. An siRNA delivery vector was constructed by tethering the peptide nucleic acid form of an siRNA targeting CEACAM6 (siCEACAM6) to a peptide with a low pH-induced transmembrane structure (pHLIP) to transport siRNAs across the plasma membrane. Specific binding of the pHLIP-siCEACAM6 conjugate to A549 lung adenocarcinoma cells at low pH was demonstrated by flow cytometry. A549 cells incubated with pHLIP-siCEACAM6 at an acidic pH showed downregulated expression of endogenous CEACAM6 protein and reduced cell viability. The in vivo tumour-suppressing effects of pHLIP-siCEACAM6 in lung adenocarcinoma were assessed in a xenograft model generated by injecting BALB/c nude mice with A549 cells. pHLIP-siCEACAM6 treatment alone resulted in tumour growth inhibition of up to 35.5%. When combined with cisplatin treatment, pHLIP-siCEACAM6 markedly enhanced tumour growth inhibition by up to 47%. In conclusion, the delivery of siCEACAM6 to lung adenocarcinoma using the pHLIP peptide has therapeutic potential as a unique cancer treatment approach.
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http://dx.doi.org/10.1038/s41598-019-48104-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6717735PMC
September 2019

Pseudoprogression presenting as intestinal perforation in non-small cell lung cancer treated with anti-PD-1: A case report.

Mol Clin Oncol 2019 Aug 31;11(2):132-134. Epub 2019 May 31.

Division of Hematology and Oncology, Chungbuk National University Hospital, Cheongju, North Chungcheong 28644, Republic of Korea.

Pseudoprogression is not frequently observed in patients with non-small cell lung cancer (NSCLC) who are treated with immune checkpoint inhibitors. We report on a case of pseudoprogression, which was presented as intestinal perforation after pembrolizumab immunotherapy for NSCLC. A-54-year-old man with stage IV NSCLC received pembrolizumab therapy. The patient was admitted to our hospital because of acute abdominal pain and the computed tomography scan revealed diffuse wall thickening of the small bowel with free intraperitoneal air. Intestinal perforation was suspected and surgical resection was performed. Histological evaluation of the resected specimen showed infiltrated lymphocytes positive for CD3, CD8 with necrotic tumor cells, suggestive of an immune reaction. Although intestinal perforation after treatment with immune checkpoint inhibitors is rare, it can be an unusual presentation of pseudoprogression and clinicians should be aware of this possibility.
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http://dx.doi.org/10.3892/mco.2019.1871DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6589934PMC
August 2019

Schwannoma originating from the common iliac artery: a case report.

J Int Med Res 2020 Feb 27;48(2):300060519849792. Epub 2019 May 27.

Department of Pathology, Chungbuk National University Hospital, Cheongju, Korea.

Schwannomas of the large blood vessels are extremely rare, and tumors adjacent to major vessels may not be considered to originate from the vessels. There have been no previous reports of schwannomas of the common iliac artery. We report on a 57-year-old woman who presented with a mass in the left retroperitoneum. Computed tomography showed a mass abutting and adhering to the left common iliac artery. A portion of the artery was resected together with the mass and vascular reconstruction was carried out. The histological diagnosis was a schwannoma arising in the left common iliac artery. Despite its rarity, a schwannoma of a large artery should be considered as a differential diagnosis in patients with a retroperitoneal mass adjacent to a major vessel. Awareness of this entity might avoid profuse bleeding and enable surgeons to prepare for vascular interposition.
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http://dx.doi.org/10.1177/0300060519849792DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7574367PMC
February 2020

Clinicopathological characteristics of costal hemangiomas: a case report and literature review.

J Int Med Res 2019 Feb 26;47(2):982-985. Epub 2018 Nov 26.

1 Department of Pathology, Chungbuk National University Hospital, Cheongju, Korea.

Bone hemangioma accounts for approximately 1% of all bone neoplasms and commonly occurs in the vertebral body and skull. However, costal hemangiomas are extremely rare. We herein present a case involving a 52-year-old woman with a hemangioma in the third rib and review 29 cases of rib hemangiomas available in the literature. Rib hemangioma mainly affects women in their 50s and has expansile osteolytic features in radiographs and a weak maximum standardized uptake value in F-fluorodeoxyglucose positron emission tomography images. When these findings are displayed, clinicians should include rib hemangioma as a differential diagnosis and consider avoidance of preoperative biopsy because of the risk of life-threatening bleeding.
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http://dx.doi.org/10.1177/0300060518809589DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6381469PMC
February 2019

Diagnostic benefits of the combined use of liquid-based cytology, cell block, and carcinoembryonic antigen immunocytochemistry in malignant pleural effusion.

J Thorac Dis 2018 Aug;10(8):4931-4939

Department of Pathology, Chungbuk National University Hospital, Cheongju, Korea.

Background: Malignant pleural effusion (MPE) is a common complication of cancer cell metastasis to the pleura. Discrimination between MPE and benign pleural effusion is necessary to design treatment strategies. Cytology is important for the diagnosis of MPE. Carcinoembryonic antigen (CEA) is an epithelial biomarker with a strong staining pattern in adenocarcinomas. Here, the diagnostic performances of liquid-based cytology (LBC), cell block (CB) preparation, and CEA immunostaining for the detection of malignancy in effusion cytology were compared in a large case series.

Methods: In a single institution, 1,014 cytology samples from 862 patients were retrospectively collected and reviewed between January 2013 and November 2015. Ethanol-fixed, paraffin embedded CB of pleural effusions was analyzed by CEA immunostaining. Diagnostic values were compared among LBC, CB, CEA immunostaining, and the combination of two methods.

Results: The sensitivity and specificity of the CB preparation were 94.3% and 98.7%, respectively, compared with 81.3% and 99.4% for LBC preparations, respectively. Combination of LBC and CB increased sensitivity by 98.3%. Although the accuracy of CEA staining itself was moderate (sensitivity, 89.8%), the combined use of CB and CEA tumor marker increased the detection rate of malignancy (sensitivity, 100%; specificity, 100%), compared with that of cytology (LBC or CB) alone.

Conclusions: The sensitivity and specificity for the diagnosis of MPE could be improved by integrating the CB and CEA staining into LBC in routine clinical practice to improve diagnostic accuracy.
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http://dx.doi.org/10.21037/jtd.2018.07.139DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6129876PMC
August 2018

Carcinosarcoma of the parotid gland with abdominal metastasis: a case report and review of literature.

World J Surg Oncol 2018 Jun 2;16(1):103. Epub 2018 Jun 2.

Department of Pathology, Chungbuk National University Hosipital, 776, 1Sunhwan-ro, Seowon-gu, Cheongju, 28644, South Korea.

Background: Carcinosarcoma of the salivary gland is a rare aggressive malignant tumor, composed of a mixture of carcinomatous and sarcomatous components. The most common metastatic sites include the lungs, bones, and central nervous system.

Case Presentation: This report describes a rare case of carcinosarcoma of the parotid gland with an osteosarcoma as sarcomatous component in a 72-year-old man who had a history of low anterior resection for rectal cancer. Six months after parotidectomy, he presented abdominal pain as a symptom of abdominal metastasis by the sarcomatous component. At that time, the possibility of abdominal metastasis was overlooked because of the history of abdominal surgery. After several days of conservative treatment, emergency laparotomy was done. However, he died of acute respiratory distress syndrome.

Conclusions: Awareness of the possibility of abdominal metastasis by salivary carcinosarcoma may help in managing patients with a history of abdominal surgery.
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http://dx.doi.org/10.1186/s12957-018-1406-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5985058PMC
June 2018

Extra-articular tenosynovial giant cell tumor of diffuse type in the temporal area with brain parenchymal invasion: a case report.

Br J Neurosurg 2018 Dec 15;32(6):688-690. Epub 2018 Jan 15.

a Departments of Pathology , Chungbuk National University Hospital , Cheongju , South Korea.

Tenosynovial giant cell tumor of diffuse type is a locally aggressive neoplasm that most commonly arises in the lower extremities. Herein, we report for the first time a case of an extra-articular tenosynovial giant cell tumor of diffuse type in the temporal region with brain parenchymal invasion. Imaging studies revealed an intracranial expansile mass in the temporal bone without involvement of the temporomandibular joint. The unusual location of the tumor without involvement of the joint and the presence of brain parenchymal invasion made this case challenging to diagnose.
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http://dx.doi.org/10.1080/02688697.2018.1426729DOI Listing
December 2018

Protein Phosphatase Magnesium-Dependent 1δ (PPM1D) Expression as a Prognostic Marker in Adult Supratentorial Diffuse Astrocytic and Oligodendroglial Tumors.

J Pathol Transl Med 2018 Mar 18;52(2):71-78. Epub 2017 Oct 18.

Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.

Background: Protein phosphatase magnesium-dependent 1δ (PPM1D) is a p53-induced serine/threonine phosphatase, which is overexpressed in various human cancers. A recent study reported that a mutation in the gene is associated with poor prognosis in brainstem gliomas. In this study, we evaluated the utility of PPM1D as a prognostic biomarker of adult supratentorial diffuse astrocytic and oligodendroglial tumors.

Methods: To investigate PPM1D protein expression, mRNA expression, and copy number changes, immunohistochemistry, RNAscope hybridization, and fluorescence hybridization were performed in 84 adult supratentorial diffuse gliomas. We further analyzed clinical characteristics and overall survival (OS) according to PPM1D protein expression, and examined its correlation with other glioma biomarkers such as isocitrate dehydrogenase () mutation, and p53 expression.

Results: Forty-six cases (54.8%) were PPM1D-positive. PPM1D expression levels were significantly correlated with PPM1D transcript levels (p= .035), but marginally with gene amplification (p=.079). Patients with high-grade gliomas showed a higher frequency of PPM1D expression than those with low-grade gliomas (p <.001). Multivariate analysis demonstrated that PPM1D expression (hazard ratio [HR], 2.58; p=.032), age over 60 years (HR, 2.55; p=.018), and mutation (HR, 0.18; p=.002) were significantly independent prognostic factors; p53 expression had no prognostic significance (p=.986). The patients with tumor expressing PPM1D showed a shorter OS (p=.003). Moreover, patients with tumor harboring wild-type and PPM1D expression had the worst OS (p<.001).

Conclusions: Our data suggest that a subset of gliomas express PPM1D; PPM1D expression is a significant marker of poor prognosis in adult supratentorial diffuse astrocytic and oligodendroglial tumors.
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http://dx.doi.org/10.4132/jptm.2017.10.21DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5859240PMC
March 2018

Primary merkel cell carcinoma of the oral mucosa: a case report with review of literature.

Int J Clin Exp Pathol 2017 1;10(10):10539-10543. Epub 2017 Oct 1.

Department of Pathology Cheongju, Seowon-Gu, Korea.

We present a case of primary Merkel cell carcinoma in the oral mucosa of a 60-year-old man. The patient underwent incisional biopsy of the tumor. Histologically, the tumor was composed of small monotonous cells in a solid sheet-like and single-cell row growth pattern. Immunohistochemically, tumor cells were positive for pan-cytokeratin, CD56, and synaptophysin, and negative for leukocyte common antigen, vimentin, S-100 protein, HMB-45, and thyroid transcription factor 1. Cytokeratin 20 staining showed a paranuclear dot-like pattern in tumor cells. Therefore, the diagnosis of Merkel cell carcinoma was made. The patient received chemotherapy with etoposide and cisplatin followed by 62 Gy radiation in 31 fractions over seven weeks. Follow-up brain CT scans after three and five months showed complete remission of the mass and enlarged lymph node. He is currently doing well with no evidence of recurrence. The present case is the first report of Merkel cell carcinoma arising in the buccal vestibule.The patient is currently doing well with no evidence of recurrence at six months.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6965778PMC
October 2017

EGFR Mutation Status in Lung Adenocarcinoma-Associated Malignant Pleural Effusion and Efficacy of EGFR Tyrosine Kinase Inhibitors.

Cancer Res Treat 2018 Jul 19;50(3):908-916. Epub 2017 Sep 19.

Department of Internal Medicine, Chungbuk National University Hospital, Cheongju, Korea.

Purpose: Malignant pleural effusions (MPEs) are often observed in lung cancer, particularly adenocarcinoma. The aim of this study was to investigate epidermal growth factor receptor (EGFR) mutation status in lung adenocarcinoma-associated MPEs (LA-MPEs) and its correlation with efficacy of EGFR tyrosine kinase inhibitor (TKI) therapy.

Materials And Methods: Samples comprised 40 cell blocks of pathologically-confirmed LA-MPEs collected before the start of EGFR TKI therapy. EGFR mutation status was re-evaluated by peptide nucleic acid clamping and the clinical outcomes of EGFR TKI‒treated patients were analyzed retrospectively.

Results: EGFR mutations were detected in 72.5% of LA-MPE cell blocks (29/40). The median progression-free survival for patients with EGFR mutations in LA-MPEs was better than that for patients with wild-type EGFR (7.33 months vs. 2.07 months; hazard ratio, 0.486; 95% confidence interval, 0.206 to 1.144; p=0.032). The objective response rate (ORR) of 26 patients with EGFR mutations in LA-MPEs among the 36 patients with measurable lesions was 80.8%, while the ORR of the 10 patients with wild-type EGFR in LA-MPEs was 10% (p < 0.001). Among the 26 patients with EGFR mutations in LA-MPEs, the ORR of target lesions and LA-MPEs were 88.5% and 61.5%, respectively (p=0.026).

Conclusion: EGFR mutation status in cell blocks of LA-MPEs confirmed by pathologic diagnosis is highly predictive of EGFR TKI efficacy. For patients with EGFR mutations in LA-MPEs, the response to EGFR TKIs seems to be worse for pleural effusions than for solid tumors.
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http://dx.doi.org/10.4143/crt.2017.378DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6056963PMC
July 2018

Gene copy number variation and protein overexpression of EGFR and HER2 in distal extrahepatic cholangiocarcinoma.

Pathology 2017 Oct 24;49(6):582-588. Epub 2017 Aug 24.

Department of Pathology, Soonchunhyang University Bucheon Hospital, Soonchunhyang University College of Medicine, Bucheon, Republic of Korea. Electronic address:

EGFR and HER2 are among the most promising therapeutic targets in solid cancers. The expression status of EGFR and HER2 are associated with the prognosis, and with a number of clinicopathological factors, in many cancers. However, few studies have examined this association in distal extrahepatic cholangiocarcinoma (EHCC). Therefore, we investigated EGFR and HER2 protein expression and gene copy number variation (CNV) in distal EHCC. We also studied the association of these factors with clinicopathological parameters and prognosis. Immunostaining, using antibodies against EGFR and HER2, was performed on 84 cases of distal EHCC. All positive (3+) and equivocal (2+) EGFR and HER2 expression cases, together with randomly selected negative (1+ and 0) cases, were evaluated for EGFR and HER2 CNV. Among distal EHCC samples, 6.0% (n=5) were positive (3+) for EGFR expression and 6.0% (n=5) were equivocal (2+). HER2 expression was positively identified in 2.4% of samples (n=2), and was equivocal in 1.2% of samples (n=1). All cases of positive EGFR expression showed amplification (n=1) or high polysomy (n=4) involving the EGFR gene; three cases (60%) of equivocal EGFR expression showed high polysomy of the EGFR gene. All cases of positive or equivocal HER2 expression (n=3, 3.6%) showed amplification of the HER2 gene. In univariate analysis, EGFR expression and CNV were associated with shorter cancer-specific overall survival (p=0.003 and p=0.018, respectively). Multivariate analysis also showed that EGFR CNV was a significant prognostic factor in distal EHCC (p=0.015). Although further study is warranted, our findings suggest that EGFR expression and CNV are factors associated with poor prognosis, and that anticancer therapeutics against EGFR and HER2 receptors may be promising therapeutic options for patients with distal EHCC.
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http://dx.doi.org/10.1016/j.pathol.2017.06.001DOI Listing
October 2017

Clear cell neuroendocrine tumor of the pancreas in von Hippel-Lindau disease: a case report and literature review.

Neuro Endocrinol Lett 2017 May;38(2):83-86

Department of Pathology, Soonchunhyang University Bucheon Hospital, Soonchunhyang University College of Medicine, Bucheon, Republic of Korea.

Clear cell neuroendocrine tumor (NET) of the pancreas is found in von Hippel-Lindau (VHL) disease, multiple endocrine neoplasia type I (MEN I), and sporadic form. Clear cell NETs are often misdiagnosed as metastatic renal cell carcinoma. A 47-year-old woman with VHL was found to have a mass in the pancreatic tail and two masses in the right kidney with two cysts. A distal pancreatectomy and right radical nephrectomy were performed. The pancreatic lesion was a well-circumscribed, golden-yellow solid mass, which was lobulated by septal fibrosis. Microscopically, the tumor consisted of entirely of clear cells with prominent nucleoli. The tumor cell nests were separated by collagen fibrosis. Immunohistochemical studies were positive for the neuroendocrine markers and vimentin. Synchronous kidney tumors were clear cell renal cell carcinoma and cystic renal cell carcinoma. Those with syndrome are younger than those without syndrome. Sporadic tumors have larger size and higher grade than those of VHL and MEN I. Stromal sclerosis is frequently observed in VHL, compared with the other two groups. In the absence of a documented genetic profile and family history, awareness of these features should help us to diagnose clear cell pancreatic NETs resembling metastatic renal cell carcinoma.
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May 2017

Clinicopathologic Features of the Non-CNS Primary Ewing Sarcoma Family of Tumors in the Head and Neck Region.

Appl Immunohistochem Mol Morphol 2018 10;26(9):632-639

Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.

Ewing sarcoma family of tumor (ESFT) is a group of malignant neoplasms that affect children and young adults. Primary ESFT does not commonly arise from the head and neck region. This study aimed to elucidate the clinicopathologic characteristics of ESFT of the head and neck region except for central nervous system primitive neuroectodermal tumors. Among the 207 cases of ESFT of the bone and soft tissue, diagnosed at Asan Medical Center during a 20-year period, 25 (12.1%) involved the head and neck region. Of those, 21 were available for histologic, immunohistochemical, and molecular studies. EWSR1 rearrangement was detected in 19 cases by reverse transcriptase-polymerase chain reaction and/or fluorescence in situ hybridization. Primary sites included the cranial area (6 cases, 31.6%), sinonasal tract (6 cases, 31.6%), paraspinal space (4 cases, 21.0%), and other spaces (3 cases, 15.8%). The 5-year overall survival and disease-free survival rates for all cases were 69.7% and 33.6%, respectively. A large tumor size (>5 cm) correlated significantly with overall survival (P=0.009), but not with disease-free survival (P=0.210). Microscopically, 8 cases (42.1%) showed nested growth pattern. Clear and/or eosinophilic cytoplasm was observed in 68.4% cases. Immunopositivity for CD99, Friend leukaemia integration-1 (FLI-1), CD57, and caveloin-1 were detected in 100%, 88.9%, 83.3%, and 50% cases, respectively. ESFT in the head and neck region had a favorable prognosis and frequent atypical and epithelioid features. An awareness of these histologic and immunophenotypic characteristics will improve the diagnostic accuracy for head and neck round cell malignancies.
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http://dx.doi.org/10.1097/PAI.0000000000000501DOI Listing
October 2018

A potential pitfall in evaluating HER2 immunohistochemistry for gastric signet ring cell carcinomas.

Pathology 2017 Jan 5;49(1):38-43. Epub 2016 Dec 5.

Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.

Signet ring cell carcinoma (SRC) more commonly presents as metastatic disease and renders patients to be considered for chemotherapy. While treatment options are limited overall, trastuzumab has been shown to be effective for HER2 positive SRC cases. The current algorithm for HER2 evaluation heavily relies on positive membrane-specific staining by immunohistochemistry (IHC), but several anecdotal reports have suggested that SRCs may be susceptible to misinterpretation due to non-specific staining in the marginated cytoplasm with/without nucleus. Results of two FDA-approved IHC methods of HER2 evaluation, Pathway and HercepTest, along with silver in situ hybridisation were interpreted retrospectively and compared in 155 primary SRC cases. IHC results were discrepant between the two assays in SRC even at the strongest IHC scores. Discordance indeed occurred due to dark, non-specific staining obscured by the unique SRC morphology. True HER2 positive SRC was identified in three cases (3/155, 1.9%). In this study, we demonstrate the importance of recognising potential discrepancy in interpreting HER2 status depending on the assay used. Understanding this possible pitfall may prevent unnecessary trastuzumab in SRC patients.
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http://dx.doi.org/10.1016/j.pathol.2016.09.064DOI Listing
January 2017

Cauda equina lymphoma mimicking non-neoplastic hypertrophic neuropathy of the cauda equina: A case report.

Br J Neurosurg 2016 Dec 26;30(6):678-680. Epub 2015 Nov 26.

a Department of Neurological Surgery , Asan Medical Center, University of Ulsan College of Medicine , Seoul , Korea.

Spinal cauda equina lymphoma (CEL) is very rare, with only about 14 cases reported in the English medical literature. Magnetic resonance image findings and the gross appearance of CEL at surgery are similar to those of non-neoplastic hypertrophic neuropathy of the cauda equina (HNCE); however, their prognosis and treatment are very different. We report a case of CEL and discuss the differences from non-neoplastic HNCE.
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http://dx.doi.org/10.3109/02688697.2015.1111295DOI Listing
December 2016

Diagnostic Significance of Cellular Neuroglial Tissue in Ovarian Immature Teratoma.

J Pathol Transl Med 2017 Jan 14;51(1):49-55. Epub 2016 Oct 14.

Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.

Background: Immature teratoma (IT) is a tumor containing immature neuroectodermal tissue, primarily in the form of neuroepithelial tubules. However, the diagnosis of tumors containing only cellular neuroglial tissue (CNT) without distinct neuroepithelial tubules is often difficult, since the histological characteristics of immature neuroectodermal tissues remain unclear. Here, we examined the significance of CNT and tried to define immature neuroectodermal tissues by comparing the histological features of neuroglial tissues between mature teratoma (MT) and IT.

Methods: The histological features of neuroglial tissue, including the cellularity, border between the neuroglial and adjacent tissues, cellular composition, mitotic index, Ki-67 proliferation rate, presence or absence of tissue necrosis, vascularity, and endothelial hyperplasia, were compared between 91 MT and 35 IT cases.

Results: CNTs with a cellularity grade of ≥ 2 were observed in 96% of IT cases and 4% of MT cases (p < .001); however, CNT with a cellularity grade of 3 in MT cases was confined to the histologically distinct granular layer of mature cerebellar tissue. Moreover, CNT in IT exhibited significantly higher rates of Ki-67 proliferation, mitoses, and necrosis than those in MT (p < .001). Furthermore, an infiltrative border of neuroglial tissue and glomeruloid endothelial hyperplasia were significantly more frequent in IT cases than in MT cases (p < .001).

Conclusions: Our results suggest that if CNT with a cellularity grade of ≥ 2 is not a component of cerebellar tissue, such cases should be diagnosed as IT containing immature neuroectodermal tissue, particularly if they exhibit an infiltrative border, mitoses, necrosis, and increased Ki-67 proliferation.
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http://dx.doi.org/10.4132/jptm.2016.09.19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5267539PMC
January 2017
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