Journal of Pathology and Translational Medicine

Original Articles

A multicenter study of interobserver variability in pathologic diagnosis of papillary breast lesions on core needle biopsy with WHO classification: Hye Ju Kang, Sun Young Kwon, Ahrong Kim, Woo Gyeong Kim, Eun Kyung Kim, Ae Ree Kim, Chungyeul Kim, Soo Kee Min, So Young Park, Sun Hee Sung, Hye Kyoung Yoon, Ahwon Lee, Ji Shin Lee, Hyang Im Lee, Ho Chang Lee, Sung Chul Lim, Sun Young Jun, Min Jung Jung, Chang Won Jung, Soo Youn Cho, Eun Yoon Cho, Hye Jeong Choi, So Yeon Park, Jee Yeon Kim, In Ae Park, Youngmee Kwon; J Pathol Transl Med. 2021;55(6):380-387. Published online October 6, 2021; DOI: https://doi.org/10.4132/jptm.2021.07.29

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Background
Papillary breast lesions (PBLs) comprise diverse entities from benign and atypical lesions to malignant tumors. Although PBLs are characterized by a papillary growth pattern, it is challenging to achieve high diagnostic accuracy and reproducibility. Thus, we investigated the diagnostic reproducibility of PBLs in core needle biopsy (CNB) specimens with World Health Organization (WHO) classification.
Methods
Diagnostic reproducibility was assessed using interobserver variability (kappa value, κ) and agreement rate in the pathologic diagnosis of 60 PBL cases on CNB among 20 breast pathologists affiliated with 20 medical institutions in Korea. This analysis was performed using hematoxylin and eosin (H&E) staining and immunohistochemical (IHC) staining for cytokeratin 5 (CK5) and p63. The pathologic diagnosis of PBLs was based on WHO classification, which was used to establish simple classifications (4-tier, 3-tier, and 2-tier).
Results
On WHO classification, H&E staining exhibited ‘fair agreement’ (κ = 0.21) with a 47.0% agreement rate. Simple classifications presented improvement in interobserver variability and agreement rate. IHC staining increased the kappa value and agreement rate in all the classifications. Despite IHC staining, the encapsulated/solid papillary carcinoma (EPC/SPC) subgroup (κ = 0.16) exhibited lower agreement compared to the non-EPC/SPC subgroup (κ = 0.35) with WHO classification, which was similar to the results of any other classification systems.
Conclusions
Although the use of IHC staining for CK5 and p63 increased the diagnostic agreement of PBLs in CNB specimens, WHO classification exhibited a higher discordance rate compared to any other classifications. Therefore, this result warrants further intensive consensus studies to improve the diagnostic reproducibility of PBLs with WHO classification.

Citations

Citations to this article as recorded by

Invasive papillary carcinoma of the breast
Shijing Wang, Qingfu Zhang, Xiaoyun Mao
Frontiers in Oncology.2024;[Epub] CrossRef
Recommendations for Performance Evaluation of Machine Learning in Pathology: A Concept Paper From the College of American Pathologists
Matthew G. Hanna, Niels H. Olson, Mark Zarella, Rajesh C. Dash, Markus D. Herrmann, Larissa V. Furtado, Michelle N. Stram, Patricia M. Raciti, Lewis Hassell, Alex Mays, Liron Pantanowitz, Joseph S. Sirintrapun, Savitri Krishnamurthy, Anil Parwani, Giovann
Archives of Pathology & Laboratory Medicine.2024; 148(10): e335. CrossRef
Encapsulated papillary carcinoma of the breast: A single institution experience
Liang Xu, Qixin Mao, Qiuming Liu, Yufeng Gao, Lihua Luo, Chungen Guo, Wei Qu, Ningning Yan, Yali Cao
Oncology Letters.2023;[Epub] CrossRef
High-risk and selected benign breast lesions diagnosed on core needle biopsy: Evidence for and against immediate surgical excision
Aparna Harbhajanka, Hannah L. Gilmore, Benjamin C. Calhoun
Modern Pathology.2022; 35(11): 1500. CrossRef

The Analysis of Indeterminate Category in Thyroid Fine Needle Aspiration.: Soo Kee Min, Jinwon Seo, Sun Young Jun, Kwangseon Min, Hye Rim Park; Korean J Pathol. 2010;44(6):657-661.; DOI: https://doi.org/10.4132/KoreanJPathol.2010.44.6.657

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Abstract PDF

BACKGROUND
Descriptive diagnosis reports have been causing some problems in communication. Our institution decided to use the category diagnosis system since June, 2008. So we evaluated the effectiveness of this change.
METHODS
The category system is composed of unsatisfactory, suboptimal for diagnosis but suggestive of, most probably benign, indeterminate, suspicious for malignancy and malignancy. We evaluated 1,525 cases from June, 2008 to September, 2009. We analyzed 159 cases of the indeterminate category.
RESULTS
Among the 159 cases, 21 were re-aspirated and 63 underwent an operation. The diagnoses of the re-aspirated cases were 2 positive for malignancy, 5 indeterminate, 13 most probably benign, and 1 unsatisfactory. The surgical diagnoses were 39 malignancies, 2 follicular adenomas and 1 Hurthle cell adenoma, and 21 benign lesions. Re-aspiration for the indeterminate cases could help decide whether the lesions need to be operated or not at above 70%. The indeterminate category could predict the surgical diagnosis of the thyroid nodule with statistical significance when the subcategories were indicated (p < 0.001).
CONCLUSIONS
The category diagnosis is replacing the descriptive diagnosis for the thyroid fine needle aspiration. The indeterminate category is useful and effective for making the decision to operate and especially when the indeterminate subcategories are used.

Citations

Citations to this article as recorded by

Fine Needle Aspiration Cytology of Thyroid Follicular Neoplasm: Cytohistologic Correlation and Accuracy
Changyoung Yoo, Hyun Joo Choi, Soyoung Im, Ji Han Jung, Kiouk Min, Chang Suk Kang, Young-Jin Suh
Korean Journal of Pathology.2013; 47(1): 61. CrossRef

Case Reports

Complete Hydatidiform Mole in Early Gestation: A Clinicopathologic Study of 51 Cases.: Kyu Rae Kim, Seung Koo Lee, Sun Young Jun, So Young Park; Korean J Pathol. 2002;36(2):93-99.

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Abstract PDF: BACKGROUND
With the widespread use of high resolution ultrasound in early pergnancy periods, poorly formed diagnostic features of complete hydatidiform mole (CHM) (which mimics normal or nonmolar gestation) often lead to a confusion fo CHM with partial mole, hydropic abortion or nonmolar chromosomal abnormalities.
METHODS
We studied the clinicopathologic finnings in 51 early CHM, evacuated before 12 weeks of gestation to characterize the early histologic changes.
RESULTS
Conventional diagnostic features were not uniformly identified; extensive cavitation was identified in 51.0%, trophoblastic hyperplasia in 49.1%, and avascular villi in 13.7%. The characteristic histologic features of early CHM were cellular and basophilic stroma (82.4%), bulbous projection with linear intervening clefts (76.5%), and apoptotic stromal cells (84.3%). In 86.3%, vascularized chorionic villi showed either primitive vascular network or clearly visible vascular lumen. Nonmetastatic persistent trophoblastic neoplasia developed in 35.3% and all were cured with single-agent or combination chemotherapy. Choriocarcinoma did not develop in any cases. The extent of trophoblastic proliferation at initial curettage han no prognostic value for clinical progression to persistent hydatidiform mole.
CONCLUSIONS
The fact that the histologic features of CHM in early gestation are often not as distinctive as those in later gestation should always be kept in mind in the diagnosis of conceptual products in early gestation.

Uterine Low Grade Endometrial Stromal Sarcoma Presented as Extrauterine Masses: A Case Report.: Sun Young Jun, Hongil Ha, In Ae Park, Kyu Rae Kim; Korean J Pathol. 2002;36(4):262-265.

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Abstract PDF: Endometrial stromal sarcoma (ESS) is a mesenchymal neoplasm that usually occurs as a primary tumor of the uterine corpus, but rarely arises in other sites, such as the ovary, the pelvic cavity, mesentery, omentum, and serosal or intramural portions of the large intestine. We present a case in which multiple nodules of ESS involving the taenia coli of the ascending colon were accompanied by grossly and radiologically unrecognized small, endometrial stromal lesions (less than 0.5 cm in the greatest dimension) with only focal marginal irregularities in the subsequent hysterectomy specimen. Whether this small sized endometrial stromal tumor is an incidentally associated endometrial stromal nodule (ESN) or a small sized, low grade ESS that was preceded by metastatic lesion is debatable. However, endometrial stromal tumors with tongue-like protrusions and associated fibroblastic stromal reaction around the tumor strongly favored these nodules being the small uterine ESS mimicking ESN. We propose that meticulous search for the detection of uterine ESS is mandatory before making a diagnosis of primary extrauterine ESS even in cases having a grossly or radiologically normal uterus and that the extent of focal irregularities of ESN should be more clearly defined for the correct diagnosis of ESS and ESN.

Primary Sclerosing Cholangitis: A Report of Two Liver Explants.: Sun Young Jun, Jung Sun Kim, Eun Sil Yu; Korean J Pathol. 2002;36(6):420-424.

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Abstract PDF: Primary sclerosing cholangitis (PSC) is usually progressive to the end stage liver disease and a common indication for liver transplantation (LT). We report two cases of liver explants with PSC. Case 1 was that of a 35-year-old male who was admitted for 4 weeks because he had jaundice. He had been treated several times without receiving a definite diagnosis during the last 7 years because he was excreting dark urine. Case 2 was that of a 30-year-old female who had taken a prednisolone for 6 years for treatment of ulcerative colitis. She also had stones and underwent a cholecystectomy and choledocholithotomy 2 years ago. She had complained of epigastric pain and febrile sensation for 2 months. In both cases, serum levels of aspartate aminotransferase, alanine aminotransferase, alkaline phospatase, gamma glutamyl transpeptidase, and direct builirubin were elevated. Autoantibodies were not detected. Computerized tomography scan and endoscopic retrograde cholangiopancreatography revealed hepato-splenomegaly, stricture of intra- and extra-hepatic bile ducts, and beaded dilatation of the intrahepatic bile ducts. Despite stent insertions and medication, another episode of jaundice occurred in case 1 and cirrhosis finally developed in case 2. The histopathologic features of liver needle biopsy specimens were nonspecific, while explant livers displayed periductal fibrosis, ductopenia, and/or ductular proliferation, which are characteristic features for PSC.

Original Articles

Methylation Patterns of Small Nuclear Ribonucleoprotein Polypeptide N (SNRPN) Related to the Germ Cell Differentiation of Human Germ Cell Tumors.: Sun Young Jun, Kyu Rae Kim, Jene Choi, Jae Y Ro; Korean J Pathol. 2007;41(1):21-29.

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Abstract PDF: BACKGROUND
The histogenesis and interrelationship of the various types of germ cell tumors (GCTs) have been proposed. Dysgerminoma/seminoma (D/S) is a primitive GCT that has not acquired the potential for further differentiation, whereas other types of GCTs are in a dynamic process of differentiation towards a somatic or extraembryonal direction. A primordial germ cell giving rise to a GCT undergoes a developmentally regulated erasure and resetting of imprinted genes, but changes in the imprinting pattern in GCTs as the tumor differentiates have not been well defined. We aimed to investigate the changes of the SNRPN methylation pattern between the germinomas and non-germinomatous GCTs, as compared with the somatic methylation pattern.
METHODS
We used formalin-fixed paraffin-embedded tissue sections of 97 GCTs (18 Ds, 21 Ss, 17 yolk sac tumors (YSTs), 19 immature teratomas, and 22 mature teratomas). DNA methylation was evaluated after bisulfite modification, PCR amplification, and restriction enzyme digestion.
RESULTS
The SNRPN methylation pattern was changed in 53/74 (71.6%) of GCTs as non-somatic patterns. There were significant differences in the methylation pattern between the germinomas and non-germinomatous GCTs, the GCTs being frequently hypo- methylated in Ds/Ss (73.3%), in contrast to the frequent hypermethylation seen in the YSTs and teratomas (47.7%, p<0.05).
CONCLUSIONS
The methylation status of an imprinting gene may be involved in the mechanism causing cellular differentiation and tumorigenesis of GCTs.

Second Opinion Diagnostic Discrepancy in Surgical Pathology: Asan Medical Center Experience.: Young Min Kim, Kyung Ja Cho, Sun Young Jun, Mi Sun Choe, Shin Kwang Khang, Jae Y Ro; Korean J Pathol. 2003;37(5):301-306.

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Abstract PDF: BACKGROUND
Review of the outside pathology material is an important practice that provides useful information on patient managements and improves the diagnostic quality in surgical pathology. We report our experience with the frequency and types of diagnostic discrepancies in patients referred to the Asan Medical Center for treatment or a second opinion.
METHODS
All referral pathology diagnoses (867 surgical cases) made from October 2001 to July 2002 at Asan Medical Center were compared with outside pathology diagnoses.
RESULTS
Of the 867 surgical cases reviewed, 231 (26.7%) cases had a diagnostic discrepancy, which included 49 (5.7%) major and 182 (21.0%) minor discrepancies. The contents of the major discrepancies were a change in the diagnosis (34 cases), a change in the type of malignancy including small cell carcinoma and non-small cell carcinoma of the lung (10), a diagnosis of a metastasis as the primary lesion (4), and errors in interpreting the invasiveness (1). The causes or reasons for the major discrepancy were a difference in interpretation (81.6%), the availability of special studies (10.2%), a failure to identify the lesions (4.1%), and a lack of clinical information (4.1%).
CONCLUSIONS
The major discrepancy rate (5.7%) was comparable to that of the other reports from western countries. Among the major discrepancies, a change in diagnosis was most commonly observed and difference in interpretation was the most common reason. A routine review of all the patients pathology material is recommended for all referral patients for an improvement in the pathologic diagnoses and to provide better medical care.

Case Reports

Pleomorphic Liposarcoma of the Kidney: A Case Report.: Mi Jung Kim, Hyun Lyoung Koo, Sun Young Jun, Jae Y Ro; Korean J Pathol. 2003;37(3):210-213.

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Abstract PDF: Although the liposarcoma is a common malignant mesenchymal tumor of the retroperitoneum, its occurrence in the kidney is very rare. A few cases involving only the renal parenchyma have been reported. The histologic features of these cases are not different from those of other body sites. We report a case of pleomorphic liposarcoma arising in the kidney of a 36-year-old man. He had been suffering from pain in the right flank for two weeks. A computed tomographic scan demonstrated a large mass in the right kidney. He underwent a radical nephrectomy under the clinical impression of renal cell carcinoma. There was a 11 cm-sized well demarcated solid mass in the lower pole of the right kidney. Microscopically, the tumor consisted of pleomorphic spindle and epithelioid cells with focal areas showing distinct adipocytic differentiation and geographic necrosis. A few diagnostic lipoblasts were present. Despite extensive search on samples, no carcinomatous component was found. Immunohistochemically, all of the tumor cells were negative for cytokeratin but positive for vimentin. Lipoblasts were positive for S-100 protein as well as for vimentin. When the kidney tumor is exclusively sarcomatous, a generous sampling with proper immunohistochemical staining is recommended to differentiate a primary sarcoma of the kidney from a sarcomatoid carcinoma.

Primary Primitive Neuroectodermal Tumor of the Kidney: Report of Two Cases.: Hyun Lyoung Koo, Sun Young Jun, Gene Choi, Jae Y Ro, Hanjong Ahn, Kyung Ja Cho; Korean J Pathol. 2003;37(2):145-149.

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Abstract PDF: Primitive neuroectodermal tumor (PNET) is a small round cell neoplasm that mainly develops in the central nervous system and soft tissue of children. Primary occurrence in the kidney is rare and the identification of immunopositivity for CD99 and t(11;22)(q24;q12) is essential in differential diagnoses. We report two cases of PNET developed in a 21-year-old woman and a 44-year-old man. Resected tumors were composed of sheets of round or ovoid cells with hyperchromatic nuclei and minimal eosinophilic cytoplasm. Rosette formations, more prominent in the first case, were observed. The tumor cells of both cases were diffusely positive for CD99, vimentin, and neuron specific enolase, while they were negative for cytokeratin, desmin, and chromogranin. Synaptophysin was focally expressed only in the first case. The EWS-FLI1 chimeric gene was identified by a reverse transcriptase-polymerase chain reaction in the first case. The first patient is alive with a recurrent tumor two years after the diagnosis, and has received combination chemotherapy. The second patient is alive with no evidence of recurrence or metastasis nineteen months after the diagnosis.

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