Journal of Pathology and Translational Medicine

Volume 55(6); November 2021

Original Articles

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

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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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Myocardial Infarction Injury Is Exacerbated by Nicotine in Vape Aerosol Exposure
Clarissa Savko, Carolina Esquer, Claudia Molinaro, Sophie Rokaw, Abraham G. Shain, Faid Jaafar, Morgan K. Wright, Joy A. Phillips, Tyler Hopkins, Sama Mikhail, Abigail Rieder, Ariana Mardani, Barbara Bailey, Mark A. Sussman
Journal of the American Heart Association.2025;[Epub] CrossRef
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; 13(6): 510. CrossRef
Morin attenuates sepsis-induced acute kidney injury by regulating inflammatory responses, oxidative stress and tubular regeneration (morin and sepsis-induced acute kidney injury)
Aya M. Shehata, Nagui H. Fares, Basma H. Amin, Asmaa A. Mahmoud, Yomna I. Mahmoud
Environmental Toxicology and Pharmacology.2024; 111: 104543. CrossRef

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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Abstract PDF Supplementary Material

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

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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

Immunohistochemical expression of programmed death-ligand 1 and CD8 in glioblastomas: Dina Mohamed El Samman, Manal Mohamed El Mahdy, Hala Sobhy Cousha, Zeinab Abd El Rahman Kamar, Khaled Abdel Karim Mohamed, Hoda Hassan Abou Gabal; J Pathol Transl Med. 2021;55(6):388-397. Published online October 14, 2021; DOI: https://doi.org/10.4132/jptm.2021.08.04

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Abstract PDF

Background
Glioblastoma is the most aggressive primary malignant brain tumor in adults and is characterized by poor prognosis. Immune evasion occurs via programmed death-ligand 1 (PD-L1)/programmed death receptor 1 (PD-1) interaction. Some malignant tumors have responded to PD-L1/PD-1 blockade treatment strategies, and PD-L1 has been described as a potential predictive biomarker. This study discussed the expression of PD-L1 and CD8 in glioblastomas.
Methods
Thirty cases of glioblastoma were stained immunohistochemically for PD-L1 and CD8, where PD-L1 expression in glioblastoma tumor tissue above 1% is considered positive and CD-8 is expressed in tumor infiltrating lymphocytes. The expression of each marker was correlated with clinicopathologic parameters. Survival analysis was conducted to correlate progression-free survival (PFS) and overall survival (OS) with PD-L1 and CD8 expression.
Results
Diffuse/fibrillary PD-L1 was expressed in all cases (mean expression, 57.6%), whereas membranous PD-L1 was expressed in six of 30 cases. CD8-positive tumor-infiltrating lymphocytes (CD8⁺ TILs) had a median expression of 10%. PD-L1 and CD8 were positively correlated (p = .001). High PD-L1 expression was associated with worse PFS and OS (p = .026 and p = .001, respectively). Correlation of CD8⁺ TILs percentage with age, sex, tumor site, laterality, and outcomes were statistically insignificant. Multivariate analysis revealed that PD-L1 was the only independent factor that affected prognosis.
Conclusions
PD-L1 expression in patients with glioblastoma is robust; higher PD-L1 expression is associated with lower CD8+ TIL expression and worse prognosis.

Citations

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Tumor-associated microenvironment, PD-L1 expression and their relationship with immunotherapy in glioblastoma, IDH-wild type: A comprehensive review with emphasis on the implications for neuropathologists
Giuseppe Broggi, Giuseppe Angelico, Jessica Farina, Giordana Tinnirello, Valeria Barresi, Magda Zanelli, Andrea Palicelli, Francesco Certo, Giuseppe Barbagallo, Gaetano Magro, Rosario Caltabiano
Pathology - Research and Practice.2024; 254: 155144. CrossRef
Immunophenotypic Profile of Adult Glioblastoma IDH-Wildtype Microenvironment: A Cohort Study
Sofia Asioli, Lidia Gatto, Uri Vardy, Claudio Agostinelli, Vincenzo Di Nunno, Simona Righi, Alicia Tosoni, Francesca Ambrosi, Stefania Bartolini, Caterina Giannini, Enrico Franceschi
Cancers.2024; 16(22): 3859. CrossRef
Pathological diagnosis of central nervous system tumours in adults: what's new?
Evert-Jan Kooi, Lukas Marcelis, Pieter Wesseling
Pathology.2024;[Epub] CrossRef
Analysis of PD-L1 and CD3 Expression in Glioblastoma Patients and Correlation with Outcome: A Single Center Report
Navid Sobhani, Victoria Bouchè, Giovanni Aldegheri, Andrea Rocca, Alberto D’Angelo, Fabiola Giudici, Cristina Bottin, Carmine Antonio Donofrio, Maurizio Pinamonti, Benvenuto Ferrari, Stefano Panni, Marika Cominetti, Jahard Aliaga, Marco Ungari, Antonio Fi
Biomedicines.2023; 11(2): 311. CrossRef
Immuno-PET Imaging of Tumour PD-L1 Expression in Glioblastoma
Gitanjali Sharma, Marta C. Braga, Chiara Da Pieve, Wojciech Szopa, Tatjana Starzetz, Karl H. Plate, Wojciech Kaspera, Gabriela Kramer-Marek
Cancers.2023; 15(12): 3131. CrossRef

Programmed death-ligand 1 expression and tumor-infiltrating lymphocytes in non-small cell lung cancer: association with clinicopathologic parameters: Gaurav Garg, Kuruswamy Thurai Prasad, Navneet Singh, Parul Gupta, Valliappan Muthu, Ashim Das, Amanjit Bal; J Pathol Transl Med. 2021;55(6):398-405. Published online October 6, 2021; DOI: https://doi.org/10.4132/jptm.2021.08.08

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Abstract PDF Supplementary Material

Background
Data on the prevalence of programmed death-ligand 1 (PD-L1) expression and tumor-infiltrating lymphocytes (TILs) in non–small cell lung cancer (NSCLC) and their clinical significance in Indian patients are limited.
Methods
Newly diagnosed NSCLC cases (adenocarcinoma or squamous cell carcinoma [SqCC] histology) were included in the present study. The TILs were evaluated based on morphology on hematoxylin and eosin–stained slides. PD-L1 expression in tumors was assessed using immunohistochemistry with rabbit monoclonal antibody (SP263) on the Ventana automated immunostainer. Tumors with PD-L1 expression > 50% on tumor cells were considered PD-L1–positive. Tumors in which TILs occupy > 25% of stroma were considered to have high TILs. The association of PD-L1 expression and TILs with various clinical parameters including overall survival (OS) was investigated.
Results
The present study included 128 cases of NSCLC (67 adenocarcinoma, 61 SqCC). PD-L1 positivity was observed in 17.2% of the patients with NSCLC. Baseline characteristics of PD-L1–positive subjects were similar to PD-L1–negative subjects except for a higher prevalence of liver metastasis (18.2% vs. 2.8%; p = .018) and a higher probability of diagnosis from extrapulmonary biopsies. High TILs were observed in 26.6% of the subjects. However, PD-L1 expression and high TIL did not affect OS.
Conclusions
PD-L1 positivity and high TILs were observed in 20% and 25% of the patients with NSCLC, respectively, however, neither were predictors of survival in SqCC.

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Multiplex plasma protein assays as a diagnostic tool for lung cancer
Mohammad Tanvir Ahamed, Jenny Forshed, Adrian Levitsky, Janne Lehtiö, Amanj Bajalan, Maria Pernemalm, Lars E. Eriksson, Björn Andersson
Cancer Science.2024; 115(10): 3439. CrossRef
Real-world prevalence of PD-L1 expression in non-small cell lung cancer: an Australia-wide multi-centre retrospective observational study
Prudence A. Russell, Alexandra L. Farrall, Sarita Prabhakaran, Khashayar Asadi, Wade Barrett, Caroline Cooper, Wendy Cooper, Samuel Cotton, Edwina Duhig, Matthew Egan, Stephen Fox, David Godbolt, Shilpa Gupta, Aniza Hassan, Connull Leslie, Trishe Leong, D
Pathology.2023; 55(7): 922. CrossRef

Case Studies

Rosette-forming epithelioid osteosarcoma in the rib: a rare case of location and morphology: Sun-Ju Oh; J Pathol Transl Med. 2021;55(6):406-409. Published online August 3, 2021; DOI: https://doi.org/10.4132/jptm.2021.06.22

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Abstract PDF: The rib is an unusual location for osteosarcoma and is reported in only 2% of all cases. The major histological variants of osteosarcoma are osteoblastic, chondroblastic, and fibroblastic, with a few rare variants including one epithelioid type. This report describes a 44-year-old male with an osteolytic mass in the right seventh rib. Histological examination revealed osteosarcoma with unique features of epithelioid appearance and rosette structures. To the best of our knowledge, this is the first reported case of a rosette-forming osteosarcoma of the rib that showed epithelioid morphology. Despite successful surgery, the patient’s prognosis was poor because this malignancy had an unusual location within the axial skeleton and was a rare histological variant.

Primary testicular carcinoid tumor with marked lymphovascular invasion: Hyun Jung Lee, Joon Young Park, So Young Kim, Chung Su Hwang, Jung Hee Lee, Dong Hoon Shin, Jee Yeon Kim; J Pathol Transl Med. 2021;55(6):410-414. Published online October 20, 2021; DOI: https://doi.org/10.4132/jptm.2021.09.11

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Abstract PDF

Testicular carcinoid tumors are very rare, accounting for less than 1% of all testicular tumors. We report a rare case of a testicular carcinoid tumor with extensive lymphatic invasion. A 42-year-old man presented with a painless, enlarged right testicular mass. There was no history of injury or discomfort in this region. Right radical orchiectomy was performed, which showed a well-defined, non-encapsulated solid white mass with calcification (7.0 × 4.5 × 3.5 cm) and absence of cystic components. Microscopic examination using hematoxylin and eosin staining of the tumor sections identified organoid, trabecular, and solid patterns with rosette formation. Extensive multifocal lymphatic invasion was observed. Immunohistochemistry was positive for synaptophysin, chromogranin, and CD56. Testicular carcinoid tumors usually show good prognoses; however, there was extensive lymphovascular invasion in this case. Thus, in the case of unusual presentation of the disease, close follow-up is necessary.

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Testicular Primary Well-Differentiated Neuroendocrine Tumor: Clinicopathologic, Immunohistochemical, and Molecular Characterization of Two Patients
Liwei Jia, Bo Zhang, Daniel Shen, Prasad R. Koduru
International Journal of Surgical Pathology.2024; 32(8): 1574. CrossRef

Letters to the Editor

Fusobacterium nucleatum: caution with interpreting historical patient sample cohort: Kate L. F. Johnstone, Sinead Toomey, Stephen Madden, Brian D. P. O’Neill, Bryan T Hennessy; J Pathol Transl Med. 2021;55(6):415-418. Published online September 27, 2021; DOI: https://doi.org/10.4132/jptm.2021.08.27

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Comment on “Breast implant-associated anaplastic large cell lymphoma: the first South Korean case”: Il-Kug Kim, Tae Gon Kim; J Pathol Transl Med. 2021;55(6):419-420. Published online October 22, 2021; DOI: https://doi.org/10.4132/jptm.2021.09.21

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Breast Reconstruction after Breast Implant-Associated Anaplastic Large Cell Lymphoma Treatment: A Case Report and Literature Review
Won-Seob Lee, Tae-Gon Kim, Jun-Ho Lee, Il-Kug Kim
Journal of Clinical Medicine.2023; 12(5): 1885. CrossRef

Newsletter

What’s new in molecular genetic pathology 2021: solid tumors and NGS panel selection: Guoli Chen, Patricia C. Tsang; J Pathol Transl Med. 2021;55(6):421-422. Published online November 12, 2021; DOI: https://doi.org/10.4132/jptm.2021.09.01

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Abstract PDF: The linchpin of precision medicine is molecular genetic and genomic testing. Molecular biomarkers are important for establishing precise diagnoses and for predicting therapeutic responses that enable cancer patients to receive personalized and targeted treatment. Below are highlights of the current considerations in next generation sequencing (NGS) panel selection, and in molecular testing of solid tumors of the lung, digestive system, thyroid and soft tissue.

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