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Volume 50(3); May 2016
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Review
Pathologic Evaluation of Breast Cancer after Neoadjuvant Therapy
Cheol Keun Park, Woo-Hee Jung, Ja Seung Koo
J Pathol Transl Med. 2016;50(3):173-180.   Published online April 11, 2016
DOI: https://doi.org/10.4132/jptm.2016.02.02
  • 11,242 View
  • 357 Download
  • 22 Citations
AbstractAbstract PDF
Breast cancer, one of the most common cancers in women, has various treatment modalities. Neoadjuvant therapy (NAT) has been used in many clinical trials because it is easy to evaluate the treatment response to therapeutic agents in a short time period; consequently, NAT is currently a standard treatment modality for large-sized and locally advanced breast cancers, and its use in early-stage breast cancer is becoming more common. Thus, chances to encounter breast tissue from patients treated with NAT is increasing. However, systems for handling and evaluating such specimens have not been established. Several evaluation systems emphasize a multidisciplinary approach to increase the accuracy of breast cancer assessment. Thus, detailed and systematic evaluation of clinical, radiologic, and pathologic findings is important. In this review, we compare the major problems of each evaluation system and discuss important points for handling and evaluating NAT-treated breast specimens.
Original Articles
Nuclear Expression of Hepatitis B Virus X Protein Is Associated with Recurrence of Early-Stage Hepatocellular Carcinomas: Role of Viral Protein in Tumor Recurrence
Jing Jin, Hae Yoen Jung, KyuHo Lee, Nam-Joon Yi, Kyung-Suk Suh, Ja-June Jang, Kyoung-Bun Lee
J Pathol Transl Med. 2016;50(3):181-189.   Published online April 17, 2016
DOI: https://doi.org/10.4132/jptm.2016.03.18
  • 16,449 View
  • 92 Download
  • 4 Citations
AbstractAbstract PDF
Background
Hepatitis B virus (HBV) plays well-known roles in tumorigenesis of hepatocellular carcinoma (HCC) in infected patients. However, HBV-associated protein status in tumor tissues and the relevance to tumor behavior has not been reported. Our study aimed to examine the expression of HBV-associated proteins in HCC and adjacent nontumorous tissue and their clinicopathologic implication in HCC patients.
Methods
HBV surface antigen (HBsAg), HBV core antigen (HBcAg), and HBV X protein (HBx) were assessed in 328 HBV-associated HCCs and in 155 matched nontumorous tissues by immunohistochemistry staining.
Results
The positive rates of HBsAg and cytoplasmic HBx staining in tumor tissue were lower than those in nontumorous tissue (7.3% vs. 57.4%, p < .001; 43.4% vs. 81.3%, p < .001). Conversely, nuclear HBx was detected more frequently in tumors than in nontumorous tissue (52.1% vs. 30.3%, p < .001). HCCs expressing HBsAg, HBcAg, or cytoplasmic HBx had smaller size; lower Edmondson-Steiner (ES) nuclear grade, pT stage, and serum alpha-fetoprotein, and less angioinvasion than HCCs not expressing HBV-associated proteins. Exceptionally, nuclear HBx-positive HCCs showed higher ES nuclear grade and more frequent large-vessel invasion than did nuclear HBx-negative HCCs. In survival analysis, only nuclear HBx-positive HCCs had shorter disease-free survival than nuclear HBx-negative HCCs in pT1 and ES nuclear grade 1–2 HCC subgroup (median, 126 months vs. 35 months; p = .015).
Conclusions
Our data confirmed that expression of normal HBV-associated proteins generally decreases in tumor cells in comparison to nontumorous hepatocytes, with the exception of nuclear HBx, which suggests that nuclear HBx plays a role in recurrence of well-differentiated and early-stage HCCs.
Interobserver Agreement on Pathologic Features of Liver Biopsy Tissue in Patients with Nonalcoholic Fatty Liver Disease
Eun Sun Jung, Kyoungbun Lee, Eunsil Yu, Yun Kyung Kang, Mee-Yon Cho, Joon Mee Kim, Woo Sung Moon, Jin Sook Jeong, Cheol Keun Park, Jae-Bok Park, Dae Young Kang, Jin Hee Sohn, So-Young Jin
J Pathol Transl Med. 2016;50(3):190-196.   Published online April 18, 2016
DOI: https://doi.org/10.4132/jptm.2016.03.01
  • 8,668 View
  • 202 Download
  • 17 Citations
AbstractAbstract PDF
Background
The histomorphologic criteria for the pathological features of liver tissue from patients with non-alcoholic fatty liver disease (NAFLD) remain subjective, causing confusion among pathologists and clinicians. In this report, we studied interobserver agreement of NAFLD pathologic features and analyzed causes of disagreement.
Methods
Thirty-one cases of clinicopathologically diagnosed NAFLD from 10 hospitals were selected. One hematoxylin and eosin and one Masson’s trichrome-stained virtual slide from each case were blindly reviewed with regard to 12 histological parameters by 13 pathologists in a gastrointestinal study group of the Korean Society of Pathologists. After the first review, we analyzed the causes of disagreement and defined detailed morphological criteria. The glass slides from each case were reviewed a second time after a consensus meeting. The degree of interobserver agreement was determined by multi-rater kappa statistics.
Results
Kappa values of the first review ranged from 0.0091–0.7618. Acidophilic bodies (k = 0.7618) and portal inflammation (k = 0.5914) showed high levels of agreement, whereas microgranuloma (k = 0.0984) and microvesicular fatty change (k = 0.0091) showed low levels of agreement. After the second review, the kappa values of the four major pathological features increased from 0.3830 to 0.5638 for steatosis grade, from 0.1398 to 0.2815 for lobular inflammation, from 0.1923 to 0.3362 for ballooning degeneration, and from 0.3303 to 0.4664 for fibrosis.
Conclusions
More detailed histomorphological criteria must be defined for correct diagnosis and high interobserver agreement of NAFLD.
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
J Pathol Transl Med. 2016;50(3):197-203.   Published online April 18, 2016
DOI: https://doi.org/10.4132/jptm.2016.03.09
  • 15,435 View
  • 261 Download
  • 49 Citations
AbstractAbstract PDF
Background
Although epidermal growth factor receptor (EGFR), v-Ki-ras2 Kirsten rat sarcoma viral oncogene (KRAS), and anaplastic lymphoma kinase (ALK) mutations in non-small cell lung cancer (NSCLC) were thought to be mutually exclusive, some tumors harbor concomitant mutations. Discovering a driver mutation on the basis of morphologic features and therapeutic responses with mutation analysis can be used to understand pathogenesis and predict resistance in targeted therapy.
Methods
In 6,637 patients with NSCLC, 12 patients who had concomitant mutations were selected and clinicopathologic features were reviewed. Clinical characteristics included sex, age, smoking history, previous treatment, and targeted therapy with response and disease-free survival. Histologic features included dominant patterns, nuclear and cytoplasmic features.
Results
All patients were diagnosed with adenocarcinoma and had an EGFR mutation. Six patients had concomitant KRAS mutations and the other six had ALK mutations. Five of six EGFR-KRAS mutation patients showed papillary and acinar histologic patterns with hobnail cells. Three of six received EGFR tyrosine kinase inhibitor (TKI) and showed partial response for 7–29 months. All six EGFR-ALK mutation patients showed solid or cribriform patterns and three had signet ring cells. Five of six EGFR-ALK mutation patients received EGFR TKI and/or ALK inhibitor and four showed partial response or stable disease, except for one patient who had acquired an EGFR mutation.
Conclusions
EGFR and ALK mutations play an important role as driver mutations in double mutated NSCLC, and morphologic analysis can be used to predict treatment response.
Analysis of Surgical Pathology Data in the HIRA Database: Emphasis on Current Status and Endoscopic Submucosal Dissection Specimens
Sun-ju Byeon, Woo Ho Kim
J Pathol Transl Med. 2016;50(3):204-210.   Published online April 4, 2016
DOI: https://doi.org/10.4132/jptm.2016.03.04
  • 6,776 View
  • 65 Download
  • 2 Citations
AbstractAbstract PDF
Background
In Korea, medical institutions make claims for insurance reimbursement to the Health Insurance Review and Assessment Service (HIRA). Thus, HIRA databases reflect the general medical services that are provided in Korea. We conducted two pathology-related studies using a HIRA national patient sample (NPS) data (selection probability, 0.03). First, we evaluated the current status of general pathologic examination in Korea. Second, we evaluated pathologic issues associated with endoscopic submucosal dissection (ESD).
Methods
The sample data used in this study was HIRA-NPS-2013-0094.
Results
In the NPS dataset, 163,372 pathologic examinations were performed in 103,528 patients during the year 2013. Considering sampling weight (33.3), it is estimated that 5,440,288 (163,372 × 33.3) pathologic examinations were performed. Internal medicine and general surgery were the most common departments requesting pathologic examinations. The region performing pathologic examinations were different according to type of medical institution. In total, 490 patients underwent ESD, and 43.4% (213/490) underwent ESD due to gastric carcinoma. The results of the ESD led to a change in disease code for 10.5% (29/277) of non-gastric carcinoma patients. In addition, 21 patients (4.3%) underwent surgery following the ESD. The average period between ESD and surgery was 44 days.
Conclusions
HIRA sample data provide the nation-wide landscape of specific procedure. However, in order to reduce the statistical error, further studies using entire HIRA data are needed.
Aberrant Blood Vessel Formation Connecting the Glomerular Capillary Tuft and the Interstitium Is a Characteristic Feature of Focal Segmental Glomerulosclerosis-like IgA Nephropathy
Beom Jin Lim, Min Ju Kim, Soon Won Hong, Hyeon Joo Jeong
J Pathol Transl Med. 2016;50(3):211-216.   Published online April 11, 2016
DOI: https://doi.org/10.4132/jptm.2016.02.01
  • 6,176 View
  • 61 Download
  • 1 Citations
AbstractAbstract PDF
Background
Segmental glomerulosclerosis without significant mesangial or endocapillary proliferation is rarely seen in IgA nephropathy (IgAN), which simulates idiopathic focal segmental glomerulosclerosis (FSGS). We recently recognized aberrant blood vessels running through the adhesion sites of sclerosed tufts and Bowman’s capsule in IgAN cases with mild glomerular histologic change.
Methods
To characterize aberrant blood vessels in relation to segmental sclerosis, we retrospectively reviewed the clinical and histologic features of 51 cases of FSGS-like IgAN and compared them with 51 age and gender-matched idiopathic FSGS cases.
Results
In FSGS-like IgAN, aberrant blood vessel formation was observed in 15.7% of cases, 1.0% of the total glomeruli, and 7.3% of the segmentally sclerosed glomeruli, significantly more frequently than in the idiopathic FSGS cases (p = .009). Aberrant blood vessels occasionally accompanied mild cellular proliferation surrounding penetrating neovessels. Clinically, all FSGS-like IgAN cases had hematuria; however, nephrotic range proteinuria was significantly less frequent than idiopathic FSGS.
Conclusions
Aberrant blood vessels in IgAN are related to glomerular capillary injury and may indicate abnormal repair processes in IgAN.
Core Needle Biopsy Is a More Conclusive Follow-up Method Than Repeat Fine Needle Aspiration for Thyroid Nodules with Initially Inconclusive Results: A Systematic Review and Meta-Analysis
Jung-Soo Pyo, Jin Hee Sohn, Guhyun Kang
J Pathol Transl Med. 2016;50(3):217-224.   Published online April 14, 2016
DOI: https://doi.org/10.4132/jptm.2016.02.15
  • 8,205 View
  • 97 Download
  • 17 Citations
AbstractAbstract PDF
Background
This study investigated the appropriate management of thyroid nodules with prior non-diagnostic or atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS) through a systematic review and meta-analysis.
Methods
This study included 4,235 thyroid nodules from 26 eligible studies. We investigated the conclusive rate of follow-up core needle biopsy (CNB) or repeat fine needle aspiration (rFNA) after initial fine needle aspiration (FNA) with non-diagnostic or AUS/FLUS results. A diagnostic test accuracy (DTA) review was performed to determine the diagnostic role of the follow-up CNB and to calculate the area under the curve (AUC) on the summary receiver operating characteristic (SROC) curve.
Results
The conclusive rates of follow-up CNB and rFNA after initial FNA were 0.879 (95% confidence interval [CI], 0.801 to 0.929) and 0.684 (95% CI, 0.627 to 0.736), respectively. In comparison of the odds ratios of CNB and rFNA, CNB had more frequent conclusive results than rFNA (odds ratio, 5.707; 95% CI, 2.530 to 12.875). Upon subgroup analysis, follow-up CNB showed a higher conclusive rate than rFNA in both initial non-diagnostic and AUS/FLUS subgroups. In DTA review of followup CNB, the pooled sensitivity and specificity were 0.94 (95% CI, 0.88 to 0.97) and 0.88 (95% CI, 0.84 to 0.91), respectively. The AUC for the SROC curve was 0.981, nearing 1.
Conclusions
Our results show that CNB has a higher conclusive rate than rFNA when the initial FNA produced inconclusive results. Further prospective studies with more detailed criteria are necessary before follow-up CNB can be applied in daily practice.
Investigation of the Roles of Cyclooxygenase-2 and Galectin-3 Expression in the Pathogenesis of Premenopausal Endometrial Polyps
Esin Kasap, Serap Karaarslan, Esra Bahar Gur, Mine Genc, Nur Sahin, Serkan Güclü
J Pathol Transl Med. 2016;50(3):225-230.   Published online April 16, 2016
DOI: https://doi.org/10.4132/jptm.2016.03.08
  • 6,077 View
  • 78 Download
  • 2 Citations
AbstractAbstract PDF
Background
The pathogenesis and etiology of endometrial polyps has not been elucidated. In this study, we aimed to examine the pathogenic mechanisms of endometrial polyp development using immunohistochemistry. We evaluated the expression of galectin-3 and cyclooxgenase-2 (COX-2) during the menstrual cycle in premenopausal women with endometrial polyps or normal endometrium.
Methods
Thirty-one patients with endometrial polyps and 50 healthy control patients were included in this study. The levels of expression of COX-2 and galectin-3 were studied by immunohistochemistry.
Results
The percentage of COX-2–positive cells and the intensity of COX-2 staining in the endometrium did not vary during the menstrual cycle either in the control group or in patients with endometrial polyps. However, expression of galectin-3 was significantly lower in endometrial polyps and during the proliferative phase of the endometrium compared with the secretory phase.
Conclusions
Our data suggests that the pathogenesis of endometrial polyps does not involve expression of COX-2 or galectin-3.
Case Studies
Rare Case of Anal Canal Signet Ring Cell Carcinoma Associated with Perianal and Vulvar Pagetoid Spread
Na Rae Kim, Hyun Yee Cho, Jeong-Heum Baek, Juhyeon Jeong, Seung Yeon Ha, Jae Yeon Seok, Sung Won Park, Sun Jin Sym, Kyu Chan Lee, Dong Hae Chung
J Pathol Transl Med. 2016;50(3):231-237.   Published online October 8, 2015
DOI: https://doi.org/10.4132/jptm.2015.08.08
  • 9,747 View
  • 105 Download
  • 2 Citations
AbstractAbstract PDF
A 61-year-old woman was referred to surgery for incidentally found colonic polyps during a health examination. Physical examination revealed widespread eczematous skin lesion without pruritus in the perianal and vulvar area. Abdominopelvic computed tomography showed an approximately 4-cm-sized, soft tissue lesion in the right perianal area. Inguinal lymph node dissection and Mils’ operation extended to perianal and perivulvar skin was performed. Histologically, the anal canal lesion was composed of mucin-containing signet ring cells, which were similar to those found in Pagetoid skin lesions. It was diagnosed as an anal canal signet ring cell carcinoma (SRCC) with perianal and vulvar Pagetoid spread and bilateral inguinal lymph node metastasis. Anal canal SRCC is rare, and the current case is the third reported case in the English literature. Seven additional cases were retrieved from the world literature. Here, we describe this rare case of anal canal SRCC with perianal Pagetoid spread and provide a literature review.
Sclerosing Perivascular Epithelioid Cell Tumor of the Lung: A Case Report with Cytologic Findings
Ha Yeon Kim, Jin Hyuk Choi, Hye Seung Lee, Yoo Jin Choi, Aeree Kim, Han Kyeom Kim
J Pathol Transl Med. 2016;50(3):238-242.   Published online April 11, 2016
DOI: https://doi.org/10.4132/jptm.2016.02.19
  • 6,939 View
  • 90 Download
  • 5 Citations
AbstractAbstract PDF
Benign perivascular epithelioid cell tumor (PEComa) of the lung is a rare benign neoplasm, a sclerosing variant of which is even rarer. We present a case of 51-year-old man who was diagnosed with benign sclerosing PEComa by percutaneous fine needle aspiration cytology and biopsy. The aspirate revealed a few cell clusters composed of bland-looking polygonal or spindle cells with fine granular or clear cytoplasm. Occasional fine vessel-like structures with surrounding hyalinized materials were seen. The patient later underwent wedge resection of the lung. The histopathological study of the resected specimen revealed sheets of polygonal cells with clear vacuolated cytoplasm, variably sized thin blood vessels, and densely hyalinized stroma. In immunohistochemical studies, reactivity of tumor cells for human melanoma black 45 and Melan-A further supported the diagnosis of benign sclerosing PEComa. To the best of our knowledge, this is the first case of benign sclerosing PEComa described in lung.
Brief Case Reports
A Rare Case of Pulmonary Arteriovenous Hemangioma Presenting as a Peribronchial Mass
Soomin Ahn, Sejin Jung, Jong Ho Cho, Tae Sung Kim, Joungho Han
J Pathol Transl Med. 2016;50(3):243-245.   Published online November 17, 2015
DOI: https://doi.org/10.4132/jptm.2015.10.15
  • 6,815 View
  • 55 Download
  • 2 Citations
PDF
Soft Tissue Roasi-Dorfman Disease with Features of IgG4-Related Disease in a Patient with a History of Acute Myeloid Leukemia
Cheol Keun Park, Eun Kyung Kim, Ji-Ye Kim, Hayoung Woo, Mi Jang, Hyang Sook Jeong, Woo Ick Yang, Sang Kyum Kim
J Pathol Transl Med. 2016;50(3):246-249.   Published online November 17, 2015
DOI: https://doi.org/10.4132/jptm.2015.10.08
  • 6,363 View
  • 53 Download
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JPTM : Journal of Pathology and Translational Medicine