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Most-download articles are from the articles published in 2020 during the last three month.

Newsletter
What’s new in kidney tumor pathology 2022: WHO 5th edition updates
Maria Tretiakova
J Pathol Transl Med. 2022;56(6):383-384.   Published online September 8, 2022
DOI: https://doi.org/10.4132/jptm.2022.08.16
  • 892 View
  • 213 Download
AbstractAbstract PDF
The 5th edition WHO Classification of Urinary and Male Genital Tumours (2022) introduces significant changes relevant to daily practice, especially in the completely restructured renal cell tumor chapters. Herein we highlight the most important diagnostic updates of known kidney tumor types, new and molecularly defined entities and emerging/provisional entities.
Review
Noninvasive follicular thyroid neoplasm with papillary-like nuclear features: its updated diagnostic criteria, preoperative cytologic diagnoses and impact on the risk of malignancy
Hee Young Na, So Yeon Park
J Pathol Transl Med. 2022;56(6):319-325.   Published online November 9, 2022
DOI: https://doi.org/10.4132/jptm.2022.09.29
  • 451 View
  • 48 Download
AbstractAbstract PDF
Due to the extremely indolent behavior, a subset of noninvasive encapsulated follicular variant papillary thyroid carcinomas has been classified as “noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP)” since 2016 and is no longer considered carcinoma. Since the introduction of this new terminology, changes and refinements have been made in diagnostic criteria. Initially, the incidence of NIFTP was estimated substantial. However, the reported incidence of NIFTP varies greatly among studies and regions, with higher incidence in North American and European countries than in Asian countries. Thus, the changes in the risk of malignancy (ROM) in the Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) differ inevitably among regions. Because more conservative surgery is recommended for NIFTPs, distinguishing NIFTPs from papillary thyroid carcinomas in preoperative fine-needle aspiration cytology became one of the major concerns. This review will provide comprehensive overview of updates on diagnostic criteria, actual incidence and preoperative cytologic diagnoses of NIFTP, and its impact on the ROM in TBSRTC.
Original Articles
A clinicopathologic and immunohistochemical study of primary and secondary breast angiosarcoma
Evi Abada, Hyejeong Jang, Seongho Kim, Rouba Ali-Fehmi, Sudeshna Bandyopadhyay
J Pathol Transl Med. 2022;56(6):342-353.   Published online October 27, 2022
DOI: https://doi.org/10.4132/jptm.2022.08.31
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AbstractAbstract PDFSupplementary Material
Background
We aimed to study the clinicopathologic and immunohistochemical (IHC) (CD117, c-Myc, and p53) characteristics, and overall survival of primary and secondary breast angiosarcoma (BAS).
Methods
This was a retrospective study of BAS cases diagnosed between 1997 and 2020 at our institution. Hematoxylin and eosin-stained slides were reviewed for tumor morphology, margin status, and lymph node metastasis. CD117, p53, D2-40, CD31, and c-Myc IHC stains were performed on 11 viable tissue blocks. Additional clinical information was obtained from the electronic medical records.
Results
Seventeen patients with BAS were identified. Of these, five (29%) were primary and 12 (71%) were secondary BAS, respectively. The median age at diagnosis for primary BAS was 36 years. The median age at diagnosis for secondary BAS was 67 years. The median time to secondary BAS development following radiotherapy was 6.5 years (range, 2 to 12 years). There was no significant difference between primary and secondary BAS in several histopathologic parameters examined, including histologic grade, necrosis, mitotic count, lymph node metastasis, and positive tumor margins. There was also no difference in CD117, p53, D2-40, CD31, and c-Myc expression by IHC between primary and secondary BAS. During a median followup of 21 months, primary BAS had two (40%) reported deaths and secondary BAS had three (25%) reported deaths. However, this difference in survival between both groups was not statistically significant (hazard ratio, 0.51; 95% confidence interval, 0.09 to 3.28; p = .450).
Conclusions
BAS is a rare and aggressive disease. No histologic, IHC (CD117, c-Myc, and p53), or survival differences were identified between primary and secondary BAS in this study.
Usefulness of BRAF VE1 immunohistochemistry in non–small cell lung cancers: a multi-institutional study by 15 pathologists in Korea
Sunhee Chang, Yoon-La Choi, Hyo Sup Shim, Geon Kook Lee, Seung Yeon Ha
J Pathol Transl Med. 2022;56(6):334-341.   Published online October 27, 2022
DOI: https://doi.org/10.4132/jptm.2022.08.22
  • 445 View
  • 45 Download
AbstractAbstract PDF
Background
Next-generation sequencing (NGS) is an approved test to select patients for BRAF V600E targeted therapy in Korea. However, the high cost, long turnaround times, and the need for sophisticated equipment and skilled personnel limit the use of NGS in daily practice. Immunohistochemistry (IHC) is a rapid and relatively inexpensive assay available in most laboratories. Therefore, in this study, we evaluate the usefulness of BRAF VE1 IHC in terms of predictive value and interobserver agreement in non–small cell lung cancers (NSCLCs).
Methods
A total of 30 cases with known BRAF mutation status were selected, including 20 cases of lung adenocarcinomas, six cases of colorectal adenocarcinomas, and four cases of papillary thyroid carcinomas. IHC for BRAF V600E was carried out using the VE1 antibody. Fifteen pathologists independently scored both the staining intensity and the percentage of tumor cell staining on whole slide images.
Results
In the lung adenocarcinoma subset, interobserver agreement for the percentage of tumor cell staining and staining intensity was good (percentage of tumor cell staining, intraclass correlation coefficient = 0.869; staining intensity, kappa = 0.849). The interobserver agreement for the interpretation using the cutoff of 40% was almost perfect in the entire study group and the lung adenocarcinoma subset (kappa = 0.815). Sensitivity, specificity, positive predictive value, and negative predictive value of BRAF VE1 IHC were 80.0%, 90.0%, 88.9%, and 81.8%, respectively.
Conclusions
BRAF VE1 IHC could be a screening test for the detection of BRAF V600E mutation in NSCLC. However, further studies are needed to optimize the protocol and to establish and validate interpretation criteria for BRAF VE1 IHC.
Newsletter
What’s new in breast pathology 2022: WHO 5th edition and biomarker updates
Kristen Muller, Julie M. Jorns, Gary Tozbikian
J Pathol Transl Med. 2022;56(3):170-171.   Published online May 15, 2022
DOI: https://doi.org/10.4132/jptm.2022.04.25
  • 3,364 View
  • 243 Download
AbstractAbstract PDF
The 5th edition WHO Classification of Breast Tumours (2019) has introduced changes to our practices. Highlights are presented below, with a focus on modifications to morphological subtype categorization. In addition, we summarize important updates to ER and PR testing made in the 2020 ASCO/CAP guidelines, and briefly discuss PD-L1 and Ki-67 testing in breast cancer.
Review
The application of high-throughput proteomics in cytopathology
Ilias P. Nikas, Han Suk Ryu
J Pathol Transl Med. 2022;56(6):309-318.   Published online November 9, 2022
DOI: https://doi.org/10.4132/jptm.2022.08.30
  • 498 View
  • 43 Download
AbstractAbstract PDF
High-throughput genomics and transcriptomics are often applied in routine pathology practice to facilitate cancer diagnosis, assess prognosis, and predict response to therapy. However, the proteins rather than nucleic acids are the functional molecules defining the cellular phenotype in health and disease, whereas genomic profiling cannot evaluate processes such as the RNA splicing or posttranslational modifications and gene expression does not necessarily correlate with protein expression. Proteomic applications have recently advanced, overcoming the issue of low depth, inconsistency, and suboptimal accuracy, also enabling the use of minimal patient-derived specimens. This review aims to present the recent evidence regarding the use of high-throughput proteomics in both exfoliative and fine-needle aspiration cytology. Most studies used mass spectrometry, as this is associated with high depth, sensitivity, and specificity, and aimed to complement the traditional cytomorphologic diagnosis, in addition to identify novel cancer biomarkers. Examples of diagnostic dilemmas subjected to proteomic analysis included the evaluation of indeterminate thyroid nodules or prediction of lymph node metastasis from thyroid cancer, also the differentiation between benign and malignant serous effusions, pancreatic cancer from autoimmune pancreatitis, non-neoplastic from malignant biliary strictures, and benign from malignant salivary gland tumors. A few cancer biomarkers—related to diverse cancers involving the breast, thyroid, bladder, lung, serous cavities, salivary glands, and bone marrow—were also discovered. Notably, residual liquid-based cytology samples were suitable for satisfactory and reproducible proteomic analysis. Proteomics could become another routine pathology platform in the near future, potentially by using validated multi-omics protocols.
Original Articles
Current status of cytopathology practice in Korea: impact of the coronavirus pandemic on cytopathology practice
Soon Auck Hong, Haeyoen Jung, Sung Sun Kim, Min-Sun Jin, Jung-Soo Pyo, Ji Yun Jeong, Younghee Choi, Gyungyub Gong, Yosep Chong
J Pathol Transl Med. 2022;56(6):361-369.   Published online October 27, 2022
DOI: https://doi.org/10.4132/jptm.2022.09.21
  • 408 View
  • 39 Download
AbstractAbstract PDFSupplementary Material
Background
The Continuous Quality Improvement program for cytopathology in 2020 was completed during the coronavirus pandemic. In this study, we report the result of the quality improvement program.
Methods
Data related to cytopathology practice from each institute were collected and processed at the web-based portal. The proficiency test was conducted using glass slides and whole-slide images (WSIs). Evaluation of the adequacy of gynecology (GYN) slides from each institution and submission of case glass slides and WSIs for the next quality improvement program were performed.
Results
A total of 214 institutions participated in the annual cytopathology survey in 2020. The number of entire cytopathology specimens was 8,220,650, a reduction of 19.0% from the 10,111,755 specimens evaluated in 2019. Notably, the number of respiratory cytopathology specimens, including sputum and bronchial washing/ brushing significantly decreased by 86.9% from 2019, which could be attributed to the global pandemic of coronavirus disease. The ratio of cases with atypical squamous cells to squamous intraepithelial lesions was 4.10. All participating institutions passed the proficiency test and the evaluation of adequacy of GYN slides.
Conclusions
Through the Continuous Quality Improvement program, the effect of coronavirus disease 2019 pandemic, manifesting with a reduction in the number of cytologic examinations, especially in respiratory-related specimen has been identified. The Continuous Quality Improvement Program of the Korean Society for Cytopathology can serve as the gold standard to evaluate the current status of cytopathology practice in Korea.
Landscape of EGFR mutations in lung adenocarcinoma: a single institute experience with comparison of PANAMutyper testing and targeted next-generation sequencing
Jeonghyo Lee, Yeon Bi Han, Hyun Jung Kwon, Song Kook Lee, Hyojin Kim, Jin-Haeng Chung
J Pathol Transl Med. 2022;56(5):249-259.   Published online September 13, 2022
DOI: https://doi.org/10.4132/jptm.2022.06.11
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  • 52 Download
AbstractAbstract PDFSupplementary Material
Background
Activating mutations in the tyrosine kinase domain of epidermal growth factor receptor (EGFR) are predictive biomarkers for response to EGFR–tyrosine kinase inhibitor (TKI) therapy in lung adenocarcinoma (LUAD). Here, we characterized the clinicopathologic features associated with EGFR mutations via peptide nucleic acid clamping-assisted fluorescence melting curve analysis (PANAMutyper) and evaluated the feasibility of targeted deep sequencing for detecting the mutations.
Methods
We examined EGFR mutations in exons 18 through 21 for 2,088 LUADs from July 2017 to April 2020 using PANAMutyper. Of these, we performed targeted deep sequencing in 73 patients and evaluated EGFR-mutation status and TKI clinical response.
Results
EGFR mutation was identified in 55.7% of LUADs by PANAMutyper, with mutation rates higher in females (69.3%) and never smokers (67.1%) and highest in the age range of 50 to 59 years (64.9%). For the 73 patients evaluated using both methods, next-generation sequencing (NGS) identified EGFR mutation–positive results in 14 of 61 patients (23.0%) who were EGFR-negative according to PANAMutyper testing. Of the 10 patients reportedly harboring a sensitizing mutation according to NGS, seven received TKI treatment, with all showing partial response or stable disease. In the 12 PANAMutyper-positive cases, NGS identified two additional mutations in exon 18, whereas a discordant negative result was observed in two cases.
Conclusions
Although PANAMutyper identified high frequencies of EGFR mutations, targeted deep sequencing revealed additional uncommon EGFR mutations. These findings suggested that appropriate use of NGS may benefit LUAD patients with otherwise negative screening test results.
Inflammation and tissue remodeling contribute to fibrogenesis in stricturing Crohn’s disease: image processing and analysis study
Mustafa Erdem Arslan, Rupinder Brar, Lianna Goetz, Dipti Karamchandani, Michael W. Mikula, Kyle Hodge, Hua Li, Sangtae Ahn, Hwajeong Lee
J Pathol Transl Med. 2022;56(5):239-248.   Published online July 4, 2022
DOI: https://doi.org/10.4132/jptm.2022.05.18
  • 1,111 View
  • 91 Download
AbstractAbstract PDFSupplementary Material
Background
Inflammation and structural remodeling may contribute to fibrogenesis in Crohn’s disease (CD). We quantified the immunoexpression of calretinin, CD34, and calprotectin as a surrogate for mucosal innervation, telocytes (interstitial cells playing a role in networking), and inflammation, respectively, and correlated them with bowel alterations in stricturing CD.
Methods
Primary resection specimens for ileal CD (n = 44, 31 stricturing CD, 13 inflammatory CD) were identified. Left-sided ulcerative colitis and trauma cases were used as controls. Proximal and distal margin and middle (diseased) sections were stained for calretinin, CD34, and calprotectin. Microscopic images were captured from the mucosa (calretinin), submucosa (calprotectin), and myenteric plexus (CD34), and the immunostaining was quantified using image processing and analysis. Bowel thickness at the corresponding sections were measured and correlated with the amount of immunoexpression.
Results
A total of 2,037 images were analyzed. In stricturing CD, submucosal alteration/thickening at the stricture site correlated with calprotectin staining and inversely correlated with calretinin staining at the proximal margin. Muscularis propria alteration/thickening at the stricture site correlated with mucosal calretinin staining at the proximal margin. Submucosal alteration/thickening at the proximal margin correlated with calretinin and CD34 staining at the proximal margin and inversely correlated with CD34 staining at the stricture site. Calretinin immunostaining at the distal margin was significantly higher in stricturing CD than the controls.
Conclusions
Inflammation and tissue remodeling appear to contribute to fibrogenesis in stricturing CD. Increased mucosal calretinin immunostaining distal to the diseased segment could be helpful in diagnosing CD in the right clinical context.
Review
Biomarker testing of cytology specimens in personalized medicine for lung cancer patients
Hyojin Kim, Jin-Haeng Chung
J Pathol Transl Med. 2022;56(6):326-333.   Published online November 9, 2022
DOI: https://doi.org/10.4132/jptm.2022.10.17
  • 340 View
  • 36 Download
AbstractAbstract PDF
Every patient with advanced non–small cell lung cancer (NSCLC) should be tested for targetable driver mutations and gene arrangements that may open avenues for targeted therapy. As most patients with NSCLC in the advanced stage of the disease are not candidates for surgery, these tests have to be performed on small biopsies or cytology samples. A growing number of other genetic changes with targetable mutations may be treatable in the near future. To identify patients who might benefit from novel targeted therapy, relevant markers should be tested in an appropriate context. In addition, immunotherapy of lung cancer is guided by the status of programmed death-ligand 1 expression in tumor cells. The variety and versatility of cytological specimen preparations offer significant advantages for molecular testing; however, they frequently remain underused. Therefore, evaluating the utility and adequacy of cytologic specimens is important, not only from a lung cancer diagnosis, but also for the large number of ancillary studies that are necessary to provide appropriate clinical management. A large proportion of lung cancers is diagnosed by aspiration or exfoliative cytology specimens; thus, optimizing strategies to triage and best use the tissue for diagnosis and biomarker studies forms a critical component of lung cancer management. In this review, we discuss the opportunities and challenges of using cytologic specimens for biomarker testing of lung cancer and the role of cytopathology in the molecular era.
Original Article
Cytopathologic features of human papillomavirus–independent, gastric-type endocervical adenocarcinoma
Min-Kyung Yeo, Go Eun Bae, Dong-Hyun Kim, In-Ock Seong, Kwang-Sun Suh
J Pathol Transl Med. 2022;56(5):260-269.   Published online September 13, 2022
DOI: https://doi.org/10.4132/jptm.2022.07.05
  • 675 View
  • 59 Download
AbstractAbstract PDF
Background
Gastric-type endocervical adenocarcinoma (GEA) is unrelated to human papillomavirus (HPV) infection and is clinically aggressive compared with HPV-associated usual-type endocervical adenocarcinoma (UEA). The cytological diagnosis falls short of a definitive diagnosis of GEA and is often categorized as atypical glandular cells (AGCs). To improve cytologic recognition, cytological findings of HPV-independent GEA were analyzed and the results compared with HPV-associated UEA.
Methods
Cervical Papanicolaou (Pap) smears from eight patients with a histopathologic diagnosis of GEA and 12 control cases of UEA were reviewed. All slides were conventionally prepared and/or liquid-based prepared (ThinPrep) and stained following the Pap method. A mucinous background, architectural, nuclear, and cytoplasmic features were analyzed and compared with UEA.
Results
Preoperative cytologic diagnoses of the eight GEA cases were AGCs, favor neoplastic in three cases, adenocarcinoma in situ in one case, and adenocarcinoma in four cases. Cytologically, monolayered honeycomb-like sheets (p = .002) of atypical endocervical cells with vacuolar granular cytoplasm (p = .001) were extensive in GEA, and three-dimensional clusters (p = .010) were extensive in UEA. Although the differences were not statistically significant, background mucin (p = .058), vesicular nuclei (p = .057), and golden-brown intracytoplasmic mucin (p = .089) were also discriminatory findings for GEA versus UEA.
Conclusions
Although GEA is difficult to diagnose on cytologic screening, GEA can be recognized based on cytologic features of monolayered honeycomb sheets of atypical endocervical cells with abundant vacuolar cytoplasm and some golden-brown intracytoplasmic mucin. UEA cases are characterized by three-dimensional clusters.
Reviews
HER2 status in breast cancer: changes in guidelines and complicating factors for interpretation
Soomin Ahn, Ji Won Woo, Kyoungyul Lee, So Yeon Park
J Pathol Transl Med. 2020;54(1):34-44.   Published online November 6, 2019
DOI: https://doi.org/10.4132/jptm.2019.11.03
  • 13,958 View
  • 820 Download
  • 46 Citations
AbstractAbstract PDF
Human epidermal growth factor receptor 2 (HER2) protein overexpression and/or HER2 gene amplification is found in about 20% of invasive breast cancers. It is a sole predictive marker for treatment benefits from HER2 targeted therapy and thus, HER2 testing is a routine practice for newly diagnosed breast cancer in pathology. Currently, HER2 immunohistochemistry (IHC) is used for a screening test, and in situ hybridization is used as a confirmation test for HER2 IHC equivocal cases. Since the American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines on HER2 testing was first released in 2007, it has been updated to provide clear instructions for HER2 testing and accurate determination of HER2 status in breast cancer. During HER2 interpretation, some pitfalls such as intratumoral HER2 heterogeneity and increase in chromosome enumeration probe 17 signals may lead to inaccurate assessment of HER2 status. Moreover, HER2 status can be altered after neoadjuvant chemotherapy or during metastatic progression, due to biologic or methodologic issues. This review addresses recent updates of ASCO/CAP guidelines and factors complicating in the interpretation of HER2 status in breast cancers.

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Follicular lymphoma: updates for pathologists
Mahsa Khanlari, Jennifer R. Chapman
J Pathol Transl Med. 2022;56(1):1-15.   Published online December 27, 2021
DOI: https://doi.org/10.4132/jptm.2021.09.29
  • 3,585 View
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  • 1 Citations
AbstractAbstract PDF
Follicular lymphoma (FL) is the most common indolent B-cell lymphoma and originates from germinal center B-cells (centrocytes and centroblasts) of the lymphoid follicle. Tumorigenesis is believed to initiate early in precursor B-cells in the bone marrow (BM) that acquire the t(14;18)(q32;q21). These cells later migrate to lymph nodes to continue their maturation through the germinal center reaction, at which time they acquire additional genetic and epigeneticabnormalities that promote lymphomagenesis. FLs are heterogeneous in terms of their clinicopathologic features. Most FLs are indolent and clinically characterized by peripheral lymphadenopathy with involvement of the spleen, BM, and peripheral blood in a substantial subset of patients, sometimes accompanied by constitutional symptoms and laboratory abnormalities. Diagnosis is established by the histopathologic identification of a B-cell proliferation usually distributed in an at least partially follicular pattern, typically, but not always, in a lymph node biopsy. The B-cell proliferation is biologically of germinal center cell origin, thus shows an expression of germinal center-associated antigens as detected by immunophenotyping. Although many cases of FLs are typical and histopathologic features are straightforward, the biologic and histopathologic variability of FL is wide, and an accurate diagnosis of FL over this disease spectrum requires knowledge of morphologic variants that can mimic other lymphomas, and rarely non-hematologic malignancies, clinically unique variants, and pitfalls in the interpretation of ancillary studies. The overall survival for most patients is prolonged, but relapses are frequent. The treatment landscape in FL now includes the application of immunotherapy and targeted therapy in addition to chemotherapy.

Citations

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    Patrick Cobb, Dietger Niederwieser, Stanley Cohen, Caroline Hamm, Gerd Burmester, Neungseon Seo, Sonya G Lehto, Vladimir Hanes
    Immunotherapy.2022; 14(9): 727.     CrossRef
Standardization of the pathologic diagnosis of appendiceal mucinous neoplasms
Dong-Wook Kang, Baek-hui Kim, Joon Mee Kim, Jihun Kim, Hee Jin Chang, Mee Soo Chang, Jin-Hee Sohn, Mee-Yon Cho, So-Young Jin, Hee Kyung Chang, Hye Seung Han, Jung Yeon Kim, Hee Sung Kim, Do Youn Park, Ha Young Park, So Jeong Lee, Wonae Lee, Hye Seung Lee, Yoo Na Kang, Younghee Choi
J Pathol Transl Med. 2021;55(4):247-264.   Published online July 8, 2021
DOI: https://doi.org/10.4132/jptm.2021.05.28
  • 5,718 View
  • 459 Download
  • 2 Citations
AbstractAbstract PDFSupplementary Material
Although the understanding of appendiceal mucinous neoplasms (AMNs) and their relationship with disseminated peritoneal mucinous disease have advanced, the diagnosis, classification, and treatment of AMNs are still confusing for pathologists and clinicians. The Gastrointestinal Pathology Study Group of the Korean Society of Pathologists (GPSG-KSP) proposed a multicenter study and held a workshop for the “Standardization of the Pathologic Diagnosis of the Appendiceal Mucinous Neoplasm” to overcome the controversy and potential conflicts. The present article is focused on the diagnostic criteria, terminologies, tumor grading, pathologic staging, biologic behavior, treatment, and prognosis of AMNs and disseminated peritoneal mucinous disease. In addition, GPSG-KSP proposes a checklist of standard data elements of appendiceal epithelial neoplasms to standardize pathologic diagnosis. We hope the present article will provide pathologists with updated knowledge on how to handle and diagnose AMNs and disseminated peritoneal mucinous disease.

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    Madison Bowles, Jessica Y Ng, Hajir Nabi
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  • Unearthing novel fusions as therapeutic targets in solid tumors using targeted RNA sequencing
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Newsletter
What’s new in soft tissue and bone pathology 2022–updates from the WHO classification 5th edition
Erica Y. Kao, Jose G. Mantilla
J Pathol Transl Med. 2022;56(6):385-386.   Published online November 15, 2022
DOI: https://doi.org/10.4132/jptm.2022.10.18
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AbstractAbstract PDF
The 2020 release of the WHO Classification of Soft Tissue and Bone Tumors, 5th edition, contains several changes driven by new knowledge in the field. These include reclassification of some entities, refinement of risk classification systems, and the inclusion of novel disease processes, many of which are driven by recurrent gene fusions. The most notable changes are described here.

JPTM : Journal of Pathology and Translational Medicine