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Original Article
The spectrum of microvascular patterns in adult diffuse glioma and their correlation with tumor grade
Soni , Vaishali Walke, Deepti Joshi, Tanya Sharma, Adesh Shrivastava, Amit Agrawal
J Pathol Transl Med. 2024;58(3):127-133.   Published online May 14, 2024
DOI: https://doi.org/10.4132/jptm.2024.03.11
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AbstractAbstract PDF
Background
Primary brain tumors constitute the leading cause of cancer-related mortality. Among them, adult diffuse gliomas are the most common type, affecting the cerebral hemispheres and displaying a diffuse infiltrative pattern of growth in the surrounding neuropil that accounts for about 80% of all primary intracranial tumors. The hallmark feature of gliomas is blood vessel proliferation, which plays an important role in tumor growth, tumor biological behavior, and disease outcome. High-grade gliomas exhibit increased vascularity, the worst prognosis, and lower survival rates. Several angiogenic receptors and factors are upregulated in glioblastomas and stimulate angiogenesis signaling pathways by means of activating oncogenes and/or down-regulating tumor-suppressor genes. Existing literature has emphasized that different microvascular patterns (MVPs) are displayed in different subtypes of adult diffuse gliomas.
Methods
We examined the distribution and biological characteristics of different MVPs in 50 patients with adult diffuse gliomas. Haematoxylin and eosin staining results, along with periodic acid–Schiff and CD34 dual-stained sections, were examined to assess the vascular patterns and correlate with different grades of diffuse glioma.
Results
The present observational study on adult diffuse glioma evaluated tumor grade and MVPs. Microvascular sprouting was the most common pattern, while a bizarre pattern (type 2) was associated with the presence of a high-grade glioma. Vascular mimicry was observed in 6% of cases, all of which were grade 4 gliomas.
Conclusions
This study supplements the role of neo-angiogenesis and aberrant vasculature patterns in the grading and progression of adult diffuse gliomas, which can be future targets for planning treatment strategies.
Review
Clinical practice recommendations for the use of next-generation sequencing in patients with solid cancer: a joint report from KSMO and KSP
Miso Kim, Hyo Sup Shim, Sheehyun Kim, In Hee Lee, Jihun Kim, Shinkyo Yoon, Hyung-Don Kim, Inkeun Park, Jae Ho Jeong, Changhoon Yoo, Jaekyung Cheon, In-Ho Kim, Jieun Lee, Sook Hee Hong, Sehhoon Park, Hyun Ae Jung, Jin Won Kim, Han Jo Kim, Yongjun Cha, Sun Min Lim, Han Sang Kim, Choong-Kun Lee, Jee Hung Kim, Sang Hoon Chun, Jina Yun, So Yeon Park, Hye Seung Lee, Yong Mee Cho, Soo Jeong Nam, Kiyong Na, Sun Och Yoon, Ahwon Lee, Kee-Taek Jang, Hongseok Yun, Sungyoung Lee, Jee Hyun Kim, Wan-Seop Kim
Received September 15, 2023  Accepted November 1, 2023  Published online January 10, 2024  
DOI: https://doi.org/10.4132/jptm.2023.11.01    [Epub ahead of print]
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AbstractAbstract PDF
In recent years, next-generation sequencing (NGS)–based genetic testing has become crucial in cancer care. While its primary objective is to identify actionable genetic alterations to guide treatment decisions, its scope has broadened to encompass aiding in pathological diagnosis and exploring resistance mechanisms. With the ongoing expansion in NGS application and reliance, a compelling necessity arises for expert consensus on its application in solid cancers. To address this demand, the forthcoming recommendations not only provide pragmatic guidance for the clinical use of NGS but also systematically classify actionable genes based on specific cancer types. Additionally, these recommendations will incorporate expert perspectives on crucial biomarkers, ensuring informed decisions regarding circulating tumor DNA panel testing.
Original Article
BRCA-mutated gastric adenocarcinomas are associated with chromosomal instability and responsiveness to platinum-based chemotherapy
Ji Hyun Oh, Chang Ohk Sung, Hyung-Don Kim, Sung-Min Chun, Jihun Kim
J Pathol Transl Med. 2023;57(6):323-331.   Published online November 14, 2023
DOI: https://doi.org/10.4132/jptm.2023.10.22
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  • 194 Download
AbstractAbstract PDFSupplementary Material
Background
Homologous recombination defect is an important biomarker of chemotherapy in certain tumor types, and the presence of pathogenic or likely pathogenic mutations involving BRCA1 or BRCA2 (p-BRCA) mutations is the most well-established marker for the homologous recombination defect. Gastric cancer, one of the most prevalent tumor types in Asia, also harbors p-BRCA mutations.
Methods
To investigate the clinical significance of p-BRCA mutations, we analyzed 366 gastric cancer cases through next-generation sequencing. We determined the zygosity of p-BRCA mutations based on the calculated tumor purity through variant allelic fraction patterns and investigated whether the presence of p-BRCA mutations is associated with platinum-based chemotherapy and a certain molecular subtype.
Results
Biallelic p-BRCA mutation was associated with better response to platinum-based chemotherapy than heterozygous p-BRCA mutation or wild type BRCA genes. The biallelic p-BRCA mutations was observed only in the chromosomal instability subtype, while all p-BRCA mutations were heterozygous in microsatellite instability subtype.
Conclusions
In conclusion, patients with gastric cancer harboring biallelic p-BRCA mutations were associated with a good initial response to platinum-based chemotherapy and those tumors were exclusively chromosomal instability subtype. Further investigation for potential association with homologous recombination defect is warranted.
Case Study
EWSR1 rearranged primary renal myoepithelial carcinoma: a diagnostic conundrum
Nilay Nishith, Zachariah Chowdhury
J Pathol Transl Med. 2023;57(5):284-288.   Published online September 15, 2023
DOI: https://doi.org/10.4132/jptm.2023.08.08
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  • 182 Download
AbstractAbstract PDF
Primary renal myoepithelial carcinoma is an exceedingly rare neoplasm with an aggressive phenotype and Ewing sarcoma breakpoint region 1 (EWSR1) rearrangement in a small fraction of cases. In addition to its rarity, the diagnosis can be challenging for the pathologist due to morphologic heterogeneity, particularly on the biopsy specimen. At times, immunohistochemistry may be indecisive; therefore, molecular studies should be undertaken for clinching the diagnosis. We aim to illustrate a case of primary myoepithelial carcinoma of the kidney with EWSR1-rearrangement in a 67-year-old male patient who presented with right supraclavicular mass, which was clinically diagnosed as carcinoma of an unknown primary. An elaborate immunohistochemical work-up aided by fluorescent in-situ hybridization allowed us to reach a conclusive diagnosis. This unusual case report advocates that one should be aware of the histological mimickers and begin with broad differential diagnoses alongside sporadic ones and then narrow them down with appropriate ancillary studies.
Reviews
Aneurysmal bone cyst: a review
Elham Nasri, John David Reith
J Pathol Transl Med. 2023;57(2):81-87.   Published online March 14, 2023
DOI: https://doi.org/10.4132/jptm.2023.02.23
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  • 368 Download
  • 6 Web of Science
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AbstractAbstract PDF
Aneurysmal bone cyst (ABC) is a benign locally destructive bone neoplasm composed of multi-loculated blood-filled cystic spaces. The most common sites of involvement are the meta-diaphysis of the long bones and posterior elements of the vertebrae. Secondary, ABC-like changes can complicate a variety of other benign and malignant primary bone neoplasms, including giant cell tumor, fibrous dysplasia, and osteosarcoma. About two-third of primary ABCs have a rearrangement of the USP6 gene, which is not present in the ABC-like changes that occur secondary to other primary bone tumors (i.e., secondary ABC). Primary ABC of bone carries a variable but generally high rate of local recurrence. This paper provides an overview of the pathophysiology, clinical presentation, radiographic and pathologic findings, treatment, and prognosis of ABC.

Citations

Citations to this article as recorded by  
  • Management of aggressive recurrent thoracic spine aneurysmal bone cyst in a 7-year-old male: A case report and review of the literature
    Pedram Jahangiri, Faramarz Roohollahi, Zohreh Habibi, Mohammad Hosein Mirbolouk, Mohsen Rostami
    Surgical Neurology International.2024; 15: 30.     CrossRef
  • Intraosseous hemangioma with aneurysmal bone cyst-like changes of the hyoid bone: Case report and literature review
    Jeonghyun Oh, Song Iy Han, Sung-Chul Lim
    Medicine.2024; 103(6): e37137.     CrossRef
  • Fibrous dysplasia with aneurysmal bone cyst-like change occurring in pediatric orbit: case report and literature review
    Xinyao Wang, Wenbin Guan, Haibo Zhang, Lei Bao, Xiaoqiang Wang
    Oral and Maxillofacial Surgery.2024; 28(2): 999.     CrossRef
  • Pathological Fractures in Aneurysmal Bone Cysts: A Systematic Review
    Doriana Di Costa, Elena Gabrielli, Mariagrazia Cerrone, Emidio Di Gialleonardo, Giulio Maccauro, Raffaele Vitiello
    Journal of Clinical Medicine.2024; 13(9): 2485.     CrossRef
  • Metastatic patellar bone tumor due to gastric cancer resembling a primary or secondary aneurysmal bone cyst: A case report
    T. Furuta, T. Sakuda, K. Yoshioka, K. Arihiro, N. Adachi
    International Journal of Surgery Case Reports.2023; 108: 108379.     CrossRef
  • Clear cell chondrosarcoma: a review of clinicopathologic characteristics, differential diagnoses, and patient management
    Borislav A. Alexiev, Erica R. Vormittag-Nocito, Terrance D. Peabody, Jonathan Samet, William B. Laskin
    Human Pathology.2023; 139: 126.     CrossRef
  • Malignant transformation of an aneurysmal bone cyst of the femoral neck: A case report
    Xiaoyang Song, Yongjie Qiao, Haoqiang Zhang, Lirong Sha, Jinpeng Lou, Xinyuan Yu, Hao Liu, Langfeng Zhu, Shenghu Zhou
    Experimental and Therapeutic Medicine.2023;[Epub]     CrossRef
Lymphoproliferative disorder involving body fluid: diagnostic approaches and roles of ancillary studies
Jiwon Koh, Sun Ah Shin, Ji Ae Lee, Yoon Kyung Jeon
J Pathol Transl Med. 2022;56(4):173-186.   Published online July 4, 2022
DOI: https://doi.org/10.4132/jptm.2022.05.16
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AbstractAbstract PDF
Lymphocyte-rich effusions represent benign reactive process or neoplastic condition. Involvement of lymphoproliferative disease in body cavity is not uncommon, and it often causes diagnostic challenge. In this review, we suggest a practical diagnostic approach toward lymphocyte-rich effusions, share representative cases, and discuss the utility of ancillary tests. Cytomorphologic features favoring neoplastic condition include high cellularity, cellular atypia/pleomorphism, monomorphic cell population, and frequent apoptosis, whereas lack of atypia, polymorphic cell population, and predominance of small T cells usually represent benign reactive process. Involvement of non-hematolymphoid malignant cells in body fluid should be ruled out first, followed by categorization of the samples into either small/medium-sized cell dominant or large-sized cell dominant fluid. Small/medium-sized cell dominant effusions require ancillary tests when either cellular atypia or history/clinical suspicion of lymphoproliferative disease is present. Large-sized cell dominant effusions usually suggest neoplastic condition, however, in the settings of initial presentation or low overall cellularity, ancillary studies are helpful for more clarification. Ancillary tests including immunocytochemistry, in situ hybridization, clonality test, and next-generation sequencing can be performed using cytologic preparations. Throughout the diagnostic process, proper review of clinical history, cytomorphologic examination, and application of adequate ancillary tests are key elements for successful diagnosis.

Citations

Citations to this article as recorded by  
  • The urgency of Burkitt lymphoma diagnosis in fluid cytology—A tertiary care experience
    Soundarya Ravi, Anu K. Devi, Prabhu Manivannan, Debasis Gochhait, Rakhee Kar, Neelaiah Siddaraju
    Cytopathology.2024; 35(2): 275.     CrossRef
  • Immunocytochemistry on frozen-embedded cell block for the diagnosis of hematolymphoid cytology specimen: a straightforward alternative to the conventional cell block
    Youjeong Seo, Sanzida Alam Prome, Lucia Kim, Jee Young Han, Joon Mee Kim, Suk Jin Choi
    Journal of Hematopathology.2024; 17(1): 1.     CrossRef
  • Lymphoma presenting as the first finding in pleural fluid cytology: A rare cytologic presentation
    Kafil Akhtar, Gowthami Nagendhran, Anjum Ara, Masheera Akhtar
    IP Archives of Cytology and Histopathology Research.2024; 8(4): 250.     CrossRef
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
  • 8,255 View
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  • 8 Web of Science
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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

Citations to this article as recorded by  
  • The follicular lymphoma tumor microenvironment at single-cell and spatial resolution
    Andrea J. Radtke, Mark Roschewski
    Blood.2024; 143(12): 1069.     CrossRef
  • Chronic pancreatitis for the clinician: complications and special forms of the disease. Interdisciplinary position paper of the Catalan Society of Digestology (SCD) and the Catalan Pancreatic Society (SCPanc)
    Xavier MOLERO, Juan R. AYUSO, Joaquim BALSELLS, Jaume BOADAS, Juli BUSQUETS, Anna CASTERÀS, Mar CONCEPCIÓN, Míriam CUATRECASAS, Gloria FERNÀNDEZ ESPARRACH, Esther FORT, Francisco GARCIA BOROBIA, Àngels GINÈS, Lucas ILZARBE, Carme LORAS, Miquel MASACHS, Xa
    Minerva Gastroenterology.2024;[Epub]     CrossRef
  • Transformation of low-grade follicular lymphoma to a high-grade follicular lymphoma with the histopathological diagnosis from oral biopsy: a case report
    Gabriela Silveira de Araujo, Leandro Dorigan de Macedo, Alfredo Ribeiro-Silva, Hilton Marcos Alves Ricz, Lara Maria Alencar Ramos Innocentini
    Hematology, Transfusion and Cell Therapy.2023;[Epub]     CrossRef
  • Clinical features and prognostic factors in 49 patients with follicular lymphoma at a single center: A retrospective analysis
    Hao Wu, Hui-Cong Sun, Gui-Fang Ouyang
    World Journal of Clinical Cases.2023; 11(14): 3176.     CrossRef
  • A rare case of follicular lymphoma of the bladder
    Matthew DeSanto, Robert Strait, Jared Zopp, Kevin Brown, Samuel Deem
    Urology Case Reports.2023; 51: 102542.     CrossRef
  • Analysis of immunophenotypic features in hyaline vascular type Castleman disease
    Yu Chang, Yu Ma, Chen Chang, Wensheng Li
    Diagnostic Pathology.2023;[Epub]     CrossRef
  • A Review of the Totality of Evidence in the Development of ABP 798, A Rituximab Biosimilar
    Patrick Cobb, Dietger Niederwieser, Stanley Cohen, Caroline Hamm, Gerd Burmester, Neungseon Seo, Sonya G Lehto, Vladimir Hanes
    Immunotherapy.2022; 14(9): 727.     CrossRef
Case Study
An unusual case of microsatellite instability–high/deficient mismatch repair (MSI-H/dMMR) diffuse large B-cell lymphoma revealed by targeted gene sequencing
Bogyeong Han, Sehui Kim, Jiwon Koh, Jeong Mo Bae, Hongseok Yun, Yoon Kyung Jeon
J Pathol Transl Med. 2022;56(2):92-96.   Published online November 16, 2021
DOI: https://doi.org/10.4132/jptm.2021.10.15
  • 5,470 View
  • 242 Download
  • 2 Web of Science
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AbstractAbstract PDF
Microsatellite instability-high/deficient mismatch repair (MSI-H/dMMR) status has been approved as a tissue-agnostic biomarker for immune checkpoint inhibitor therapy in patients with solid tumors. We report the case of an MSI-H/dMMR diffuse large B-cell lymphoma (DLBCL) identified by targeted gene sequencing (TGS). A 90-year-old female who presented with vaginal bleeding and a large mass in the upper vagina was diagnosed with germinal center-B-cell-like DLBCL, which recurred at the uterine cervix at 9 months after chemotherapy. Based on TGS of 121 lymphoma-related genes and the LymphGen algorithm, the tumor was classified genetically as DLBCL of EZB subtype. Mutations in multiple genes, including frequent frameshift mutations, were detected by TGS and further suggested MSI. The MSI-H/dMMR and loss of MLH1 and PMS2 expression were determined in MSI-fragment analysis, MSI real-time polymerase chain reaction, and immunohistochemical tests. This case demonstrates the potential diagnostic and therapeutic utility of lymphoma panel sequencing for DLBCL with MSI-H/dMMR.

Citations

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  • Chimeric and mutant CARD9 constructs enable analyses of conserved and diverged autoinhibition mechanisms in the CARD‐CC protein family
    Jens Staal, Yasmine Driege, Femke Van Gaever, Jill Steels, Rudi Beyaert
    The FEBS Journal.2024; 291(6): 1220.     CrossRef
  • PD-L1+diffuse large B-cell lymphoma with extremely high mutational burden and microsatellite instability due to acquiredPMS2mutation
    Andrew W. Allbee, James Gerson, Guang Yang, Adam Bagg
    Molecular Case Studies.2023; 9(4): a006318.     CrossRef
Original Articles
Association of PTTG1 expression with invasiveness of non-functioning pituitary adenomas
Su Jung Kum, Hye Won Lee, Soon Gu Kim, Hyungsik Park, Ilseon Hwang, Sang Pyo Kim
J Pathol Transl Med. 2022;56(1):22-31.   Published online October 15, 2021
DOI: https://doi.org/10.4132/jptm.2021.08.31
  • 3,434 View
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AbstractAbstract PDF
Background
Pituitary tumor transforming gene 1 (PTTG1), paired-like homeodomain 2 (PITX2), and galectin-3 have been widely studied as predictive biomarkers for various tumors and are involved in tumorigenesis and tumor progression. We evaluated the usefulness of PTTG1, PITX2, and galectin-3 as predictive biomarkers for invasive non-functioning pituitary adenomas (NFPAs) by determining the relationship between the expressions of these three proteins and the invasiveness of the NFPAs. We also investigated whether PTTG1, E-cadherin, and Ki-67, which are known to be related to each other, show a correlation with NFPA features.
Methods
A retrospective study was conducted on 87 patients with NPFAs who underwent surgical removal. The NFPAs were classified into three groups based on magnetic resonance imaging findings of suprasellar extension and cavernous sinus invasion. Immunohistochemical staining for PTTG1, PITX2, galectin-3, E-cadherin, and Ki-67 was performed on tissue microarrays.
Results
PTTG1 expression showed a statistically significant correlation with the invasiveness of NFPAs, whereas PITX2 and galectin-3 did not have a relationship with the invasiveness of NFPAs. Moreover, there was no association among PTTG1, E-cadherin, and Ki-67 expression.
Conclusions
PTTG1 has the potential to serve as a predictive biomarker for invasive NFPA. Furthermore, this study may serve as a reference for the development of PTTG1-targeted therapeutic agents.

Citations

Citations to this article as recorded by  
  • Neoplasms and tumor-like lesions of the sellar region: imaging findings with correlation to pathology and 2021 WHO classification
    Lorenzo Ugga, Raduan Ahmed Franca, Alessandra Scaravilli, Domenico Solari, Sirio Cocozza, Fabio Tortora, Luigi Maria Cavallo, Marialaura Del Basso De Caro, Andrea Elefante
    Neuroradiology.2023; 65(4): 675.     CrossRef
  • A comprehensive characterisation of phaeochromocytoma and paraganglioma tumours through histone protein profiling, DNA methylation and transcriptomic analysis genome wide
    Prodromos Chatzikyriakou, Dimitria Brempou, Mark Quinn, Lauren Fishbein, Roberta Noberini, Ioannis N. Anastopoulos, Nicola Tufton, Eugenie S. Lim, Rupert Obholzer, Johnathan G. Hubbard, Mufaddal Moonim, Tiziana Bonaldi, Katherine L. Nathanson, Louise Izat
    Clinical Epigenetics.2023;[Epub]     CrossRef
  • Expression and clinical significance of Cathepsin K and MMPs in invasive non-functioning pituitary adenomas
    Hongyan Liu, Saichun Zhang, Ting Wu, Zhaohui Lv, Jianming Ba, Weijun Gu, Yiming Mu
    Frontiers in Oncology.2022;[Epub]     CrossRef
Post-mortem assessment of vimentin expression as a biomarker for renal tubular regeneration following acute kidney injury
Juan Carlos Alvarez Moreno, Hisham F. Bahmad, Christopher A. Febres-Aldana, Andrés Pirela, Andres Azuero, Ali Salami, Robert Poppiti
J Pathol Transl Med. 2021;55(6):369-379.   Published online October 14, 2021
DOI: https://doi.org/10.4132/jptm.2021.08.03
  • 3,602 View
  • 118 Download
  • 2 Web of Science
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AbstractAbstract PDF
Background
Acute kidney injury (AKI) is a common cause of morbidity and mortality. It mainly targets the renal tubular epithelium with pathological changes, referred to as acute tubular injury. The latter is followed by a regenerative response that is difficult to visualize on routine hematoxylin and eosin (H&E) stains. In this study, we examined the regenerative capacity of renal tubules by correlating vimentin (VIM) immunohistochemical (IHC) expression and pathological findings of AKI and renal tubular regeneration (RTR) on H&E.
Methods
We reviewed 23 autopsies performed in the clinical setting of AKI and RTR. VIM expression was scored in the renal cortical tubular epithelium using a statistical cutoff ≥ 3% for high expression and < 3% for low expression.
Results
Of the 23 kidney tissues examined, seven (30.4%) had low VIM expression, and 16 (69.6%) had high VIM expression. Kidney tissues with evidence of AKI and RTR had significantly higher VIM expression. Renal peritubular microenvironment features showing regenerative changes on H&E were associated with high VIM expression. In the univariate model, kidney tissues with RTR were 18-fold more likely to have high VIM expression.
Conclusions
In conclusion, our findings suggest that VIM could serve as an IHC marker for RTR following AKI. However, correlation with H&E findings remains critical to excluding chronic tubular damage. Collectively, our preliminary results pave the way for future studies including a larger sample size to validate the use of VIM as a reliable biomarker for RTR.

Citations

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  • Characterization of macrophages in ischemia–reperfusion injury-induced acute kidney injury based on single-cell RNA-Seq and bulk RNA-Seq analysis
    Qin Wang, Yuxing Liu, Yan Zhang, Siyuan Zhang, Meifang Zhao, Zhangzhe Peng, Hui Xu, Hao Huang
    International Immunopharmacology.2024; 130: 111754.     CrossRef
  • Renal tubular necrosis associated with anagrelide administration: a case report
    Atsushi Sawase, Mineaki Kitamura, Misato Morimoto, Haruka Fukuda, Tadashi Uramatsu, Eisuke Katafuchi, Hiroshi Yamashita, Toshiyuki Nakayama, Hiroshi Mukae, Tomoya Nishino
    CEN Case Reports.2024;[Epub]     CrossRef
Prognostic role of ALK-1 and h-TERT expression in glioblastoma multiforme: correlation with ALK gene alterations
Dalia Elsers, Doaa F. Temerik, Alia M. Attia, A. Hadia, Marwa T. Hussien
J Pathol Transl Med. 2021;55(3):212-224.   Published online May 11, 2021
DOI: https://doi.org/10.4132/jptm.2021.03.15
  • 3,480 View
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AbstractAbstract PDF
Background
Anaplastic lymphoma kinase (ALK) is a receptor tyrosine kinase that is expressed in the developing central and peripheral nervous systems during embryogenesis. Human telomerase reverse transcriptase (h-TERT) protein resumption is the main process of preservation of telomeres that maintains DNA integrity. The present study aims to evaluate the prognostic role of ALK-1 and h-TERT protein expression and their correlation with ALK gene alterations in glioblastoma multiforme (GBM).
Methods
The current study is a retrospective study on a cohort of patients with GBM (n = 53) that attempted to detect ALK gene alterations using fluorescence in situ hybridization. ALK-1 and h-TERT proteins were evaluated using immunohistochemistry.
Results
Score 3 ALK-1 expression was significantly associated with male sex, tumor multiplicity, Ki labeling index (Ki LI), and type of therapeutic modality. Score 3 h-TERT expression exhibited a significant association with Ki LI. ALK gene amplifications (ALK-A) were significantly associated with increased Ki LI and therapeutic modalities. Score 3 ALK-1 protein expression, score 3 h-TERT protein expression, and ALK-A were associated with poor overall survival (OS) and progression-free survival (PFS). Multivariate analysis for OS revealed that ALK gene alterations were an independent prognostic factor for OS and PFS.
Conclusions
High protein expression of both ALK-1 and h-TERT, as well as ALK-A had a poor impact on the prognosis of GBM. Further studies are needed to establish the underlying mechanisms.

Citations

Citations to this article as recorded by  
  • Association of human telomerase reverse transcriptase promoter mutation with unfavorable prognosis in glioma: A systematic review and meta-analysis
    Rongxuan Hua, Qiuxuan Li, Han Gao, Boya Wang, Chengwei He, Ying Wang, Sitian Zhang, Lei Gao, Hongwei Shang, Wen Wang, Jingdong Xu
    Journal of Research in Medical Sciences.2023; 28(1): 47.     CrossRef
  • Immunohistochemical surrogates for molecular alterations for the classification and grading of gliomas
    Viharkumar Patel, Sanda Alexandrescu
    Seminars in Diagnostic Pathology.2022; 39(1): 78.     CrossRef
  • Meme Kanseri Hastalarında hTERT Gen Ekspresyonunun Klinikopatolojik Önemi
    Ebubekir DİRİCAN, Burak KANKAYA, Zeynep TATAR
    Sağlık Bilimlerinde Değer.2022; 12(1): 22.     CrossRef
  • Prognostic and predictive markers in glioblastoma and ALK overexpression
    Jang-Hee Kim
    Journal of Pathology and Translational Medicine.2021; 55(3): 236.     CrossRef
Case Studies
A case of concomitant EGFR/ALK alteration against a mutated EGFR background in early-stage lung adenocarcinoma
Ki-Chang Lee, Jiwon Koh, Doo Hyun Chung, Yoon Kyung Jeon
J Pathol Transl Med. 2021;55(2):139-144.   Published online January 22, 2021
DOI: https://doi.org/10.4132/jptm.2020.12.16
  • 2,834 View
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AbstractAbstract PDF
Rare cases of lung adenocarcinoma (LUAD) with concomitant epidermal growth factor receptor (EGFR) mutation and anaplastic lymphoma kinase (ALK) translocation have been reported. However, their clonal and evolutional relationship remains unclear. We report a case of early-stage EGFR-mutated LUAD with a focal concomitant EGFR/ALK alteration. A 63-year-old male underwent lobectomy to remove a 1.9-cm-sized lung nodule, which was diagnosed with EGFR-mutated LUAD. ALK immunohistochemistry (IHC) showed focal positivity within the part of the tumor characterized by lepidic pattern, also confirmed by fluorescence in-situ hybridization (FISH). Targeted next-generation sequencing was performed separately on the ALK IHC/FISH-positive and -negative areas. EGFR L833V/L858R mutations were detected in both areas, whereas EML4 (echinoderm microtubule-associated protein-like 4)-ALK translocations was confirmed only in the ALK IHC/FISH-positive area, suggesting the divergence of an EGFR/ALK co-altered subclone from the original EGFR-mutant clone. Our study suggests that concurrent alterations of EGFR and ALK can arise via divergent tumor evolution, even in the relatively early phases of tumorigenesis.

Citations

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  • Identification and validation of molecular subtype and prognostic signature for lung adenocarcinoma based on neutrophil extracellular traps
    Yanhua Zuo, Guangyi Leng, Ping Leng
    Pathology and Oncology Research.2023;[Epub]     CrossRef
  • Machine Learning-Based Integration Develops a Macrophage-Related Index for Predicting Prognosis and Immunotherapy Response in Lung Adenocarcinoma
    Zuwei Li, Minzhang Guo, Wanli Lin, Peiyuan Huang
    Archives of Medical Research.2023; 54(7): 102897.     CrossRef
  • Big data analysis identified a telomere-related signature predicting the prognosis and drug sensitivity in lung adenocarcinoma
    Weiyi Zhang
    Medicine.2023; 102(46): e35526.     CrossRef
Adenocarcinoma of the minor salivary gland with concurrent MAML2 and EWSR1 alterations
Sangjoon Choi, Junhun Cho, Seung Eun Lee, Chung-Hwan Baek, Yi-Kyung Kim, Hyung-Jin Kim, Young Hyeh Ko
J Pathol Transl Med. 2021;55(2):132-138.   Published online January 22, 2021
DOI: https://doi.org/10.4132/jptm.2020.12.11
  • 4,001 View
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  • 7 Crossref
AbstractAbstract PDF
Salivary gland tumors are histologically diverse, and each entity has distinctive histopathological and molecular features. We report two cases of salivary gland tumors with unique histological and molecular findings, which have not been documented previously. The tumors were located in the base of the tongue in both patients. Most tumor cells were arranged in cords and nests, giving a trabecularlike appearance. Focally, glandular structures with intraluminal mucin and perivascular pseudorosette-like configurations were identified. Tumor cells had eosinophilic to clear cytoplasm, and showed mild nuclear atypia. They were positive for pancytokeratin and negative for S-100, p63, c-KIT, androgen receptor, and neuroendocrine markers. Multiple foci of capsular or lymphovascular invasion were identified, but the Ki-67 labeling index was low (< 5%). Fluorescence in situ hybridization revealed concurrent alterations of MAML2 and EWSR1 gene. Further investigations with a larger number of cases with similar histological and molecular features will accurately classify this tumor.

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Reviews
DNA-protein biomarkers for immunotherapy in the era of precision oncology
Binnari Kim, So Young Kang, Kyoung-Mee Kim
J Pathol Transl Med. 2021;55(1):26-32.   Published online November 9, 2020
DOI: https://doi.org/10.4132/jptm.2020.09.23
  • 4,048 View
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  • 1 Web of Science
  • 1 Crossref
AbstractAbstract PDF
The use of biomarkers to guide patient and therapy selection has gained much attention to increase the scope and complexity of targeted therapy options and immunotherapy. Clinical trials provide a basis for discovery of biomarkers, which can then aid in development of new drugs. To that end, samples from cancer patients, including DNA, RNA, protein, and the metabolome isolated from cancer tissues and blood or urine, are analyzed in various ways to identify relevant biomarkers. In conjunction with nucleotide-based, high-throughput, next-generation sequencing techniques, therapy-guided biomarker assays relying on protein-based immunohistochemistry play a pivotal role in cancer care. In this review, we discuss the current knowledge regarding DNA and protein biomarkers for cancer immunotherapy

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  • Biomarkers for Predicting Response to Personalized Immunotherapy in Gastric Cancer
    Moonsik Kim, Ji Yun Jeong, An Na Seo
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Imaging features of breast cancer molecular subtypes: state of the art
Nariya Cho
J Pathol Transl Med. 2021;55(1):16-25.   Published online November 9, 2020
DOI: https://doi.org/10.4132/jptm.2020.09.03
  • 48,071 View
  • 302 Download
  • 8 Web of Science
  • 10 Crossref
AbstractAbstract PDF
Characterization of breast cancer molecular subtypes has been the standard of care for breast cancer management. We aimed to provide a review of imaging features of breast cancer molecular subtypes for the field of precision medicine. We also provide an update on the recent progress in precision medicine for breast cancer, implications for imaging, and recent observations in longitudinal functional imaging with radiomics.

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J Pathol Transl Med : Journal of Pathology and Translational Medicine