Pub Date : 2024-03-04DOI: 10.5858/arpa.2023-0367-OA
Fateme Khalatbari, Miremad Moafi-Madani, Ali Amin
Context.—: Low-grade urothelial carcinoma (LGUC) and high-grade urothelial carcinoma (HGUC) are distinguished based on architectural and cytological features, with the anticipation that HGUC exhibits more aggressive behavior and a worse prognosis compared to LGUC. The current World Health Organization classification recognizes mixed-grade urothelial carcinoma (MGUC, for the purposes of this study) as a separate category that behaves like LGUC if the high-grade component is <5% and states that any tumor with ≥5% high-grade component should be graded as HGUC.
Objective.—: To evaluate the risk of tumor recurrence, grade, and stage progression of MGUC compared to LGUC and HGUC.
Design.—: A total of 150 de novo noninvasive polypoid urothelial carcinomas (41 cases of MGUC, 59 of LGUC, and 50 of HGUC) were included. Tumor recurrence, grade, and stage progression were compared among the MGUC, LGUC, and HGUC cases.
Results.—: Tumor recurrence was observed in 14 of 41 (34.2%) of MGUC, 33 of 59 (55.9%) of LGUC, and 28 of 50 (56%) of HGUC. Grade progression occurred in 5 of 41 (12.2%) of MGUC cases and 5 of 59 (8.5%) of LGUC cases. No stage progression was observed in LGUC or MGUC cases, while 7 of 50 (14%) of HGUC cases showed stage progression. MGUC was associated with lower odds and hazard of recurrence compared to LGUC. The rate of grade progression was higher in MGUC and occurred after a shorter interval compared to LGUC.
Conclusions.—: MGUC showed a prognosis closer to LGUC. Our study supports the current recommendation to classify tumors with <5% high-grade component as MGUC, as these tumors display clinical characteristics and outcomes close to that of pure LGUC.
{"title":"Mixed-Grade Urothelial Carcinoma: Insights Into Clinical Behavior and Prognostic Implications Compared to Pure Low-Grade and High-Grade Urothelial Carcinomas.","authors":"Fateme Khalatbari, Miremad Moafi-Madani, Ali Amin","doi":"10.5858/arpa.2023-0367-OA","DOIUrl":"https://doi.org/10.5858/arpa.2023-0367-OA","url":null,"abstract":"<p><strong>Context.—: </strong>Low-grade urothelial carcinoma (LGUC) and high-grade urothelial carcinoma (HGUC) are distinguished based on architectural and cytological features, with the anticipation that HGUC exhibits more aggressive behavior and a worse prognosis compared to LGUC. The current World Health Organization classification recognizes mixed-grade urothelial carcinoma (MGUC, for the purposes of this study) as a separate category that behaves like LGUC if the high-grade component is <5% and states that any tumor with ≥5% high-grade component should be graded as HGUC.</p><p><strong>Objective.—: </strong>To evaluate the risk of tumor recurrence, grade, and stage progression of MGUC compared to LGUC and HGUC.</p><p><strong>Design.—: </strong>A total of 150 de novo noninvasive polypoid urothelial carcinomas (41 cases of MGUC, 59 of LGUC, and 50 of HGUC) were included. Tumor recurrence, grade, and stage progression were compared among the MGUC, LGUC, and HGUC cases.</p><p><strong>Results.—: </strong>Tumor recurrence was observed in 14 of 41 (34.2%) of MGUC, 33 of 59 (55.9%) of LGUC, and 28 of 50 (56%) of HGUC. Grade progression occurred in 5 of 41 (12.2%) of MGUC cases and 5 of 59 (8.5%) of LGUC cases. No stage progression was observed in LGUC or MGUC cases, while 7 of 50 (14%) of HGUC cases showed stage progression. MGUC was associated with lower odds and hazard of recurrence compared to LGUC. The rate of grade progression was higher in MGUC and occurred after a shorter interval compared to LGUC.</p><p><strong>Conclusions.—: </strong>MGUC showed a prognosis closer to LGUC. Our study supports the current recommendation to classify tumors with <5% high-grade component as MGUC, as these tumors display clinical characteristics and outcomes close to that of pure LGUC.</p>","PeriodicalId":93883,"journal":{"name":"Archives of pathology & laboratory medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140023675","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-03-01DOI: 10.5858/arpa.2023-0363-OA
Yue Zhao, Imran Siddiqi, Tyler J Wildes, Derald Charles, Kristen Deak, Endi Wang
Context.—: BCR::ABL-negative myeloproliferative neoplasm (MPN) has a prolonged clinical course, and some cases eventually undergo transformation to blast phase; its pathogenesis remains to be elucidated.
Objective.—: To evaluate the clinicopathologic characteristics of MPN in blast phase.
Design.—: The study aimed to retrospectively analyze the clinical and laboratory data of 24 cases.
Results.—: Median latency to blast phase was 48 months (range, 7-384 months). Complex karyotypes were seen in 12 of the 24 cases (50%). Overall, 16 cases (66.7%) exhibited high allele burdens of MPN driver mutations along with increased blasts, consistent with linear clonal evolution, whereas the remainder (8; 33.3%) showed loss or partial loss of the driver mutation suggestive of a parallel evolution. Additional mutations were noted in 23 cases (100%), including TP53 mutations in 10 of 24 cases (41.7%). Following chemotherapy, 15 of the 24 patients (62.5%) reverted to a second chronic phase while retaining or regaining MPN driver mutations and losing blast-related mutations, although 9 of the 15 patients (60%) later died of disease progression. Median overall survival was 10 months (CI, 4.6-15.4), with those harboring complex karyotypes demonstrating decreased survival (6 versus 29 months; P = .004).
Conclusions.—: MPN-blast phase resembles acute myeloid leukemia, myelodysplasia-related, in cytogenetic pattern, mutation profile, and clinical outcome. Two patterns of clonal evolution are inferred by dynamic analysis of mutation profiles: linear and parallel evolutions. Although overall survival was dismal, 62.5% of our cases achieved second chronic phase, and they showed better survival than those without second chronic phase.
{"title":"Blast Phase of Myeloproliferative Neoplasm Resembles Acute Myeloid Leukemia, Myelodysplasia-Related, in Clinical Presentation, Cytogenetic Pattern, and Genomic Profile, and Often Undergoes Reversion to Second Chronic Phase Status After Induction Chemotherapy.","authors":"Yue Zhao, Imran Siddiqi, Tyler J Wildes, Derald Charles, Kristen Deak, Endi Wang","doi":"10.5858/arpa.2023-0363-OA","DOIUrl":"https://doi.org/10.5858/arpa.2023-0363-OA","url":null,"abstract":"<p><strong>Context.—: </strong>BCR::ABL-negative myeloproliferative neoplasm (MPN) has a prolonged clinical course, and some cases eventually undergo transformation to blast phase; its pathogenesis remains to be elucidated.</p><p><strong>Objective.—: </strong>To evaluate the clinicopathologic characteristics of MPN in blast phase.</p><p><strong>Design.—: </strong>The study aimed to retrospectively analyze the clinical and laboratory data of 24 cases.</p><p><strong>Results.—: </strong>Median latency to blast phase was 48 months (range, 7-384 months). Complex karyotypes were seen in 12 of the 24 cases (50%). Overall, 16 cases (66.7%) exhibited high allele burdens of MPN driver mutations along with increased blasts, consistent with linear clonal evolution, whereas the remainder (8; 33.3%) showed loss or partial loss of the driver mutation suggestive of a parallel evolution. Additional mutations were noted in 23 cases (100%), including TP53 mutations in 10 of 24 cases (41.7%). Following chemotherapy, 15 of the 24 patients (62.5%) reverted to a second chronic phase while retaining or regaining MPN driver mutations and losing blast-related mutations, although 9 of the 15 patients (60%) later died of disease progression. Median overall survival was 10 months (CI, 4.6-15.4), with those harboring complex karyotypes demonstrating decreased survival (6 versus 29 months; P = .004).</p><p><strong>Conclusions.—: </strong>MPN-blast phase resembles acute myeloid leukemia, myelodysplasia-related, in cytogenetic pattern, mutation profile, and clinical outcome. Two patterns of clonal evolution are inferred by dynamic analysis of mutation profiles: linear and parallel evolutions. Although overall survival was dismal, 62.5% of our cases achieved second chronic phase, and they showed better survival than those without second chronic phase.</p>","PeriodicalId":93883,"journal":{"name":"Archives of pathology & laboratory medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139998542","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-02-27DOI: 10.5858/arpa.2023-0320-OA
Yaileen D Guzmán-Arocho, Timothy D Weber, Taylor St Jacques, James G Fujimoto, Seymour Rosen, Yue Sun
Context.—: Histology, the traditional method of examining surgical tissue under a microscope, is a time-consuming process involving the fixation of tissue in formalin, dehydration, embedding in paraffin, and cutting into thin sections for hematoxylin-eosin (H&E) staining. Frozen section analysis is a faster alternative used in surgery to quickly evaluate tissue, but it has limitations, such as the size of the specimens that can be analyzed and difficulties with fatty and bony tissues.
Objective.—: To rapidly examine nonprocessed kidney tumors using nonlinear microscopy (NLM), a fluorescence microscopy technique that can rapidly visualize fresh or fixed, rapidly stained, nonprocessed tissue resembling H&E histology. This technology eliminates the need for fixation, embedding, microtome sectioning, or slide preparation.
Design.—: In this study, a total of 190 tissue specimens were collected from 46 patients who underwent partial or radical nephrectomy.
Results.—: Two genitourinary pathologists confirmed that diagnostically important features present in the H&E images could also be identified in the NLM images.
Conclusions.—: The results of this study demonstrated that NLM had a high degree of correspondence with H&E staining for the classical variants of renal cell carcinoma. NLM offers several clinical benefits, such as facilitating rapid renal cell carcinoma diagnosis, assessment of targeted kidney biopsies for both tumor and medical kidney diseases, and collection of fresh renal cell carcinoma tissue for molecular studies.
{"title":"Rapid Examination of Nonprocessed Renal Cell Carcinoma Using Nonlinear Microscopy.","authors":"Yaileen D Guzmán-Arocho, Timothy D Weber, Taylor St Jacques, James G Fujimoto, Seymour Rosen, Yue Sun","doi":"10.5858/arpa.2023-0320-OA","DOIUrl":"10.5858/arpa.2023-0320-OA","url":null,"abstract":"<p><strong>Context.—: </strong>Histology, the traditional method of examining surgical tissue under a microscope, is a time-consuming process involving the fixation of tissue in formalin, dehydration, embedding in paraffin, and cutting into thin sections for hematoxylin-eosin (H&E) staining. Frozen section analysis is a faster alternative used in surgery to quickly evaluate tissue, but it has limitations, such as the size of the specimens that can be analyzed and difficulties with fatty and bony tissues.</p><p><strong>Objective.—: </strong>To rapidly examine nonprocessed kidney tumors using nonlinear microscopy (NLM), a fluorescence microscopy technique that can rapidly visualize fresh or fixed, rapidly stained, nonprocessed tissue resembling H&E histology. This technology eliminates the need for fixation, embedding, microtome sectioning, or slide preparation.</p><p><strong>Design.—: </strong>In this study, a total of 190 tissue specimens were collected from 46 patients who underwent partial or radical nephrectomy.</p><p><strong>Results.—: </strong>Two genitourinary pathologists confirmed that diagnostically important features present in the H&E images could also be identified in the NLM images.</p><p><strong>Conclusions.—: </strong>The results of this study demonstrated that NLM had a high degree of correspondence with H&E staining for the classical variants of renal cell carcinoma. NLM offers several clinical benefits, such as facilitating rapid renal cell carcinoma diagnosis, assessment of targeted kidney biopsies for both tumor and medical kidney diseases, and collection of fresh renal cell carcinoma tissue for molecular studies.</p>","PeriodicalId":93883,"journal":{"name":"Archives of pathology & laboratory medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11347715/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139974945","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-02-23DOI: 10.5858/arpa.2023-0406-OA
Makoto Abe, Fahdi Kanavati, Masayuki Tsuneki
Context.—: Squamous cell carcinoma (SCC) is a histologic type of cancer that exhibits various degrees of keratinization. Identifying lymph node metastasis in SCC is crucial for prognosis and treatment strategies. Although artificial intelligence (AI) has shown promise in cancer prediction, applications specifically targeting SCC are limited.
Objective.—: To design and validate a deep learning model tailored to predict metastatic SCC in radical lymph node dissection specimens, using whole slide images (WSIs).
Design.—: Using the EfficientNetB1 architecture, a model was trained on 6587 WSIs (2413 SCC and 4174 nonneoplastic) from several hospitals, encompassing esophagus, head and neck, lung, and skin specimens. The training exclusively relied on WSI-level labels without annotations. We evaluated the model on a test set consisting of 541 WSIs (41 SCC and 500 nonneoplastic) of radical lymph node dissection specimens.
Results.—: The model exhibited high performance, with receiver operating characteristic curve areas under the curve between 0.880 and 0.987 in detecting SCC metastases in lymph nodes. Although true positives and negatives were accurately identified, certain limitations were observed. These included false positives due to germinal centers, dust cell aggregations, and specimen-handling artifacts, as well as false negatives due to poor differentiation.
Conclusions.—: The developed artificial intelligence model presents significant potential in enhancing SCC lymph node detection, offering workload reduction for pathologists and increasing diagnostic efficiency. Continuous refinement is needed to overcome existing challenges, making the model more robust and clinically relevant.
{"title":"Evaluation of a Deep Learning Model for Metastatic Squamous Cell Carcinoma Prediction From Whole Slide Images.","authors":"Makoto Abe, Fahdi Kanavati, Masayuki Tsuneki","doi":"10.5858/arpa.2023-0406-OA","DOIUrl":"https://doi.org/10.5858/arpa.2023-0406-OA","url":null,"abstract":"<p><strong>Context.—: </strong>Squamous cell carcinoma (SCC) is a histologic type of cancer that exhibits various degrees of keratinization. Identifying lymph node metastasis in SCC is crucial for prognosis and treatment strategies. Although artificial intelligence (AI) has shown promise in cancer prediction, applications specifically targeting SCC are limited.</p><p><strong>Objective.—: </strong>To design and validate a deep learning model tailored to predict metastatic SCC in radical lymph node dissection specimens, using whole slide images (WSIs).</p><p><strong>Design.—: </strong>Using the EfficientNetB1 architecture, a model was trained on 6587 WSIs (2413 SCC and 4174 nonneoplastic) from several hospitals, encompassing esophagus, head and neck, lung, and skin specimens. The training exclusively relied on WSI-level labels without annotations. We evaluated the model on a test set consisting of 541 WSIs (41 SCC and 500 nonneoplastic) of radical lymph node dissection specimens.</p><p><strong>Results.—: </strong>The model exhibited high performance, with receiver operating characteristic curve areas under the curve between 0.880 and 0.987 in detecting SCC metastases in lymph nodes. Although true positives and negatives were accurately identified, certain limitations were observed. These included false positives due to germinal centers, dust cell aggregations, and specimen-handling artifacts, as well as false negatives due to poor differentiation.</p><p><strong>Conclusions.—: </strong>The developed artificial intelligence model presents significant potential in enhancing SCC lymph node detection, offering workload reduction for pathologists and increasing diagnostic efficiency. Continuous refinement is needed to overcome existing challenges, making the model more robust and clinically relevant.</p>","PeriodicalId":93883,"journal":{"name":"Archives of pathology & laboratory medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139934640","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-02-23DOI: 10.5858/arpa.2023-0426-RA
Claudio Luchini
Context.—: The examination of small pancreatic biopsies is a difficult task for pathologists. This is due to the scant and fragmented material often obtained from diagnostic procedures as well as the significant overlap between different neoplastic and nonneoplastic entities. In the upcoming neoadjuvant era, biopsies could become even more important, representing the only possibility to look at the real histomorphology of tumors before chemotherapy-induced modifications.
Objectives.—: To summarize and discuss the state-of-the-art diagnostic workflow for small pancreatic biopsies, including the most important morphologic and immunohistochemical features and molecular alterations. The main diagnostic pearls and pitfalls of this challenging scenario are also discussed. The most important topics of this review are represented by: (1) pancreatic ductal adenocarcinoma, along with its main differential diagnoses, including autoimmune pancreatitis; (2) solid hypercellular neoplasms, including neuroendocrine neoplasms, acinar cell carcinoma, pancreatoblastoma, and solid pseudopapillary neoplasms; and (3) cystic lesions. Real-world considerations will be also presented and discussed.
Data sources.—: Sources included a literature review of published studies and the author's own work.
Conclusions.—: The correct diagnosis of pancreatic lesions is a crucial step in the therapeutic journey of patients. It should be based on robust, standardized, and reliable hallmarks. As presented and discussed here, the integration of morphology with immunohistochemistry, and in selected cases, with molecular analysis, represents a decisive step in this complex scenario.
{"title":"Diagnostic Pearls and Pitfalls in the Evaluation of Biopsies of the Pancreas.","authors":"Claudio Luchini","doi":"10.5858/arpa.2023-0426-RA","DOIUrl":"https://doi.org/10.5858/arpa.2023-0426-RA","url":null,"abstract":"<p><strong>Context.—: </strong>The examination of small pancreatic biopsies is a difficult task for pathologists. This is due to the scant and fragmented material often obtained from diagnostic procedures as well as the significant overlap between different neoplastic and nonneoplastic entities. In the upcoming neoadjuvant era, biopsies could become even more important, representing the only possibility to look at the real histomorphology of tumors before chemotherapy-induced modifications.</p><p><strong>Objectives.—: </strong>To summarize and discuss the state-of-the-art diagnostic workflow for small pancreatic biopsies, including the most important morphologic and immunohistochemical features and molecular alterations. The main diagnostic pearls and pitfalls of this challenging scenario are also discussed. The most important topics of this review are represented by: (1) pancreatic ductal adenocarcinoma, along with its main differential diagnoses, including autoimmune pancreatitis; (2) solid hypercellular neoplasms, including neuroendocrine neoplasms, acinar cell carcinoma, pancreatoblastoma, and solid pseudopapillary neoplasms; and (3) cystic lesions. Real-world considerations will be also presented and discussed.</p><p><strong>Data sources.—: </strong>Sources included a literature review of published studies and the author's own work.</p><p><strong>Conclusions.—: </strong>The correct diagnosis of pancreatic lesions is a crucial step in the therapeutic journey of patients. It should be based on robust, standardized, and reliable hallmarks. As presented and discussed here, the integration of morphology with immunohistochemistry, and in selected cases, with molecular analysis, represents a decisive step in this complex scenario.</p>","PeriodicalId":93883,"journal":{"name":"Archives of pathology & laboratory medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139934638","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-02-23DOI: 10.5858/arpa.2023-0330-OA
Xiaoqun Yang, Yang Liu, Huafeng Wang, Yunze Xu, Huizhi Zhang, Ming Zhao, Xiaoqing Luo, Hongtao Jin, Ji Xiong, Lili Tao, Jiankun Xu, Luting Zhou, Xiangyun Li, Haimin Xu, Lei Dong, Chaofu Wang
Context.—: Fumarate hydratase (FH)-deficient renal cell carcinoma (RCC) rarely exhibits a predominant tubulocystic architecture with few other components. RCC with pure tubules and cysts lined by eosinophilic tumor cells with prominent nucleoli would raise the diagnosis of tubulocystic RCC. It is important to differentiate the 2 entities because they lead to different outcomes.
Objective.—: To address the concern, a multicenter study was implemented to explore useful clinicopathologic features in differentiation between tubulocystic FH-deficient RCC and tubulocystic RCC.
Design.—: Clinical factors included age, sex, tumor size, and outcome. Morphologic factors included cell morphology, presence or absence of a nontubulocystic component, and stromal findings. Immunohistochemistry, fluorescence in situ hybridization, and next-generation sequencing were performed to explore the protein expression and molecular profiles of the 2 entities.
Results.—: We evaluated 6 patients with tubulocystic RCC and 10 patients with tubulocystic FH-deficient RCC. Tubulocystic RCC exhibited a small size (<4.0 cm, pT1a), low Ki-67 index (<5%), retained FH, and negative 2SC expression. Tubulocystic FH-deficient RCC had a relatively large size and a high Ki-67 index. Perinucleolar haloes, loss of FH, and 2SC positivity were always observed. Pure tubulocystic architecture was not observed in FH-deficient RCC, because focal nontubulocystic components can always be seen.
Conclusions.—: We emphasized multiple sectioning to identify a nontubulocystic architecture to exclude tubulocystic RCC. Moreover, tumor size, FH/2SC staining, and the Ki-67 index can differentiate tubulocystic FH-deficient RCC from tubulocystic RCC. The diagnosis of tubulocystic RCC was not recommended in renal mass biopsy because of the limited tissues sampled.
{"title":"Fumarate Hydratase-Deficient Renal Cell Carcinoma With Predominant Tubulocystic Features Mimics Tubulocystic Renal Cell Carcinoma.","authors":"Xiaoqun Yang, Yang Liu, Huafeng Wang, Yunze Xu, Huizhi Zhang, Ming Zhao, Xiaoqing Luo, Hongtao Jin, Ji Xiong, Lili Tao, Jiankun Xu, Luting Zhou, Xiangyun Li, Haimin Xu, Lei Dong, Chaofu Wang","doi":"10.5858/arpa.2023-0330-OA","DOIUrl":"https://doi.org/10.5858/arpa.2023-0330-OA","url":null,"abstract":"<p><strong>Context.—: </strong>Fumarate hydratase (FH)-deficient renal cell carcinoma (RCC) rarely exhibits a predominant tubulocystic architecture with few other components. RCC with pure tubules and cysts lined by eosinophilic tumor cells with prominent nucleoli would raise the diagnosis of tubulocystic RCC. It is important to differentiate the 2 entities because they lead to different outcomes.</p><p><strong>Objective.—: </strong>To address the concern, a multicenter study was implemented to explore useful clinicopathologic features in differentiation between tubulocystic FH-deficient RCC and tubulocystic RCC.</p><p><strong>Design.—: </strong>Clinical factors included age, sex, tumor size, and outcome. Morphologic factors included cell morphology, presence or absence of a nontubulocystic component, and stromal findings. Immunohistochemistry, fluorescence in situ hybridization, and next-generation sequencing were performed to explore the protein expression and molecular profiles of the 2 entities.</p><p><strong>Results.—: </strong>We evaluated 6 patients with tubulocystic RCC and 10 patients with tubulocystic FH-deficient RCC. Tubulocystic RCC exhibited a small size (<4.0 cm, pT1a), low Ki-67 index (<5%), retained FH, and negative 2SC expression. Tubulocystic FH-deficient RCC had a relatively large size and a high Ki-67 index. Perinucleolar haloes, loss of FH, and 2SC positivity were always observed. Pure tubulocystic architecture was not observed in FH-deficient RCC, because focal nontubulocystic components can always be seen.</p><p><strong>Conclusions.—: </strong>We emphasized multiple sectioning to identify a nontubulocystic architecture to exclude tubulocystic RCC. Moreover, tumor size, FH/2SC staining, and the Ki-67 index can differentiate tubulocystic FH-deficient RCC from tubulocystic RCC. The diagnosis of tubulocystic RCC was not recommended in renal mass biopsy because of the limited tissues sampled.</p>","PeriodicalId":93883,"journal":{"name":"Archives of pathology & laboratory medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139934657","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-02-22DOI: 10.5858/arpa.2023-0284-OA
Mei Liu, Jin-Peng Liu, Pan Wang, Ya-Jing Fu, Min Zhao, Yong-Jun Jiang, Zi-Ning Zhang, Hong Shang
Context.—: Regulatory T-cell (Treg) detection in peripheral blood, based on flow cytometry, is invaluable for diagnosis and treatment of immune-mediated diseases. However, there is a lack of reliable methods to verify the performance, which is pivotal towards standardization of the Tregs assay.
Objective.—: To conduct standardization studies and verify the performance of 3 commercially available reagent sets for the Tregs assay based on flow cytometry and agreement analysis for Treg detection across the different reagent sets.
Design.—: The analytical performance of Tregs assay using reagent sets supplied by 3 manufacturers was evaluated after establishing the gating strategy and determining the optimal antibody concentration. Postcollection sample stability was evaluated, as well as the repeatability, reproducibility, reportable range, linearity, and assay carryover. Agreement between the different assays was assessed via Bland-Altman plots and linear regression analysis. The relationship between the frequency of CD4+CD25+CD127low/- Tregs and CD4+CD25+Foxp3+ Tregs was evaluated.
Results.—: The postcollection sample stability was set at 72 hours after collection at room temperature. The accuracy, repeatability, reproducibility, and accuracy all met the requirements for clinical analysis. Excellent linearity, with R2 ≥0.9 and no assay carryover, was observed. For reportable range, a minimum of 1000 events in the CD3+CD4+ gate was required for Tregs assay. Moreover, the results for Tregs labeled by antibodies from the 3 manufacturers were in good agreement. The percentage of CD4+CD25+CD127low/- Tregs was closely correlated with CD4+CD25+Foxp3+ Tregs.
Conclusions.—: This is the first study to evaluate systematically the measurement performance of Tregs in peripheral blood by flow cytometry, which provides a practical solution to verifying the performance of flow cytometry-based immune monitoring projects in clinical practice.
{"title":"Approaches for Performance Verification Toward Standardization of Peripheral Blood Regulatory T-Cell Detection by Flow Cytometry.","authors":"Mei Liu, Jin-Peng Liu, Pan Wang, Ya-Jing Fu, Min Zhao, Yong-Jun Jiang, Zi-Ning Zhang, Hong Shang","doi":"10.5858/arpa.2023-0284-OA","DOIUrl":"https://doi.org/10.5858/arpa.2023-0284-OA","url":null,"abstract":"<p><strong>Context.—: </strong>Regulatory T-cell (Treg) detection in peripheral blood, based on flow cytometry, is invaluable for diagnosis and treatment of immune-mediated diseases. However, there is a lack of reliable methods to verify the performance, which is pivotal towards standardization of the Tregs assay.</p><p><strong>Objective.—: </strong>To conduct standardization studies and verify the performance of 3 commercially available reagent sets for the Tregs assay based on flow cytometry and agreement analysis for Treg detection across the different reagent sets.</p><p><strong>Design.—: </strong>The analytical performance of Tregs assay using reagent sets supplied by 3 manufacturers was evaluated after establishing the gating strategy and determining the optimal antibody concentration. Postcollection sample stability was evaluated, as well as the repeatability, reproducibility, reportable range, linearity, and assay carryover. Agreement between the different assays was assessed via Bland-Altman plots and linear regression analysis. The relationship between the frequency of CD4+CD25+CD127low/- Tregs and CD4+CD25+Foxp3+ Tregs was evaluated.</p><p><strong>Results.—: </strong>The postcollection sample stability was set at 72 hours after collection at room temperature. The accuracy, repeatability, reproducibility, and accuracy all met the requirements for clinical analysis. Excellent linearity, with R2 ≥0.9 and no assay carryover, was observed. For reportable range, a minimum of 1000 events in the CD3+CD4+ gate was required for Tregs assay. Moreover, the results for Tregs labeled by antibodies from the 3 manufacturers were in good agreement. The percentage of CD4+CD25+CD127low/- Tregs was closely correlated with CD4+CD25+Foxp3+ Tregs.</p><p><strong>Conclusions.—: </strong>This is the first study to evaluate systematically the measurement performance of Tregs in peripheral blood by flow cytometry, which provides a practical solution to verifying the performance of flow cytometry-based immune monitoring projects in clinical practice.</p>","PeriodicalId":93883,"journal":{"name":"Archives of pathology & laboratory medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139934637","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-02-22DOI: 10.5858/arpa.2023-0214-OA
Mehrvash Haghighi, Clare Bryce, John D Paulsen, Shafinaz Hussein, Brandon Veremis, Christian Salib, Roshanak Alialy, Mega Lahori, Yansheng Hao, Yuanxin Liang, Arnold Szporn, William Westra
Context.—: The diagnosis of some infectious diseases requires their identification in tissue specimens. As institutions adopt digital pathology for primary diagnosis, the limits of microorganism detection from digital images must be delineated.
Objective.—: To assess the reliability of microorganism detection from digitized images of histochemical and immunohistochemical stains commonly used in pathology.
Design.—: Original glass slides from 620 surgical pathology cases evaluated for the presence of infectious microorganisms were digitized. Immunohistochemical stains included those for herpes simplex virus (n = 100), cytomegalovirus (n = 100), Helicobacter pylori (n = 100), and spirochetes (n = 80). Histochemical stains included mucicarmine for Cryptococcus spp (n = 20), Grocott methenamine silver for fungi (n = 100), Giemsa for H pylori (n = 100), and Ziehl-Neelsen for acid-fast bacilli (n = 20). The original diagnosis based on the glass slides was regarded as the reference standard. Six pathologists reviewed the digital images.
Results.—: Digital review was generally associated with high (ie, ≥90%) specificity and positive predictive value owing to a low percentage of false positive reads, whereas a high percentage of false negatives contributed to low sensitivity and negative predictive value for many stains. Fleiss κ showed substantial interobserver agreement in the interpretation of Grocott methenamine silver and immunostains for herpes simplex virus, H pylori, and cytomegalovirus; moderate agreement for spirochete, Ziehl-Neelsen, and mucicarmine; and poor agreement for Giemsa.
Conclusions.—: Digital immunohistochemistry generally outperforms histochemical stains for microorganism detection. Digital interpretation of Ziehl-Neelsen and mucicarmine stains is associated with low scores for interrater reliability, accuracy, sensitivity, and negative predictive value such that it should not substitute for conventional review of glass slides.
{"title":"Digital Pathology in the Detection of Infectious Microorganisms: An Evaluation of Its Strengths and Weaknesses Across a Panel of Immunohistochemical and Histochemical Stains Routinely Used in Diagnostic Surgical Pathology.","authors":"Mehrvash Haghighi, Clare Bryce, John D Paulsen, Shafinaz Hussein, Brandon Veremis, Christian Salib, Roshanak Alialy, Mega Lahori, Yansheng Hao, Yuanxin Liang, Arnold Szporn, William Westra","doi":"10.5858/arpa.2023-0214-OA","DOIUrl":"https://doi.org/10.5858/arpa.2023-0214-OA","url":null,"abstract":"<p><strong>Context.—: </strong>The diagnosis of some infectious diseases requires their identification in tissue specimens. As institutions adopt digital pathology for primary diagnosis, the limits of microorganism detection from digital images must be delineated.</p><p><strong>Objective.—: </strong>To assess the reliability of microorganism detection from digitized images of histochemical and immunohistochemical stains commonly used in pathology.</p><p><strong>Design.—: </strong>Original glass slides from 620 surgical pathology cases evaluated for the presence of infectious microorganisms were digitized. Immunohistochemical stains included those for herpes simplex virus (n = 100), cytomegalovirus (n = 100), Helicobacter pylori (n = 100), and spirochetes (n = 80). Histochemical stains included mucicarmine for Cryptococcus spp (n = 20), Grocott methenamine silver for fungi (n = 100), Giemsa for H pylori (n = 100), and Ziehl-Neelsen for acid-fast bacilli (n = 20). The original diagnosis based on the glass slides was regarded as the reference standard. Six pathologists reviewed the digital images.</p><p><strong>Results.—: </strong>Digital review was generally associated with high (ie, ≥90%) specificity and positive predictive value owing to a low percentage of false positive reads, whereas a high percentage of false negatives contributed to low sensitivity and negative predictive value for many stains. Fleiss κ showed substantial interobserver agreement in the interpretation of Grocott methenamine silver and immunostains for herpes simplex virus, H pylori, and cytomegalovirus; moderate agreement for spirochete, Ziehl-Neelsen, and mucicarmine; and poor agreement for Giemsa.</p><p><strong>Conclusions.—: </strong>Digital immunohistochemistry generally outperforms histochemical stains for microorganism detection. Digital interpretation of Ziehl-Neelsen and mucicarmine stains is associated with low scores for interrater reliability, accuracy, sensitivity, and negative predictive value such that it should not substitute for conventional review of glass slides.</p>","PeriodicalId":93883,"journal":{"name":"Archives of pathology & laboratory medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139934639","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-02-20DOI: 10.5858/arpa.2023-0453-RA
Francesco Marongiu, Maria Filomena Ruberto, Silvia Marongiu, Doris Barcellona
Context.—: Prothrombin time (PT) and activated partial thromboplastin time (aPTT) are coagulative screening tests used for the diagnosis of several pathologic conditions, such as liver failure, coagulation factor deficiencies, anti-phospholipid antibodies (lupus anticoagulant), and factor VIII inhibitors. A new test was developed several years ago to detect the amount of thrombin generated during plasma clotting, using low tissue factor concentrations and fluorogenic substrates, and it has since been used successfully in conditions ranging from hypocoagulable to hypercoagulable states. However, the test is expensive and difficult to perform in nonspecialized laboratories, and efforts have thus been made to find an economic and easily implementable test suitable for routine use, even in nonspecialist laboratories.
Objective.—: To evaluate clot waveform analysis (CWA) of PT and aPTT, aiming to show the dynamics of clot formation; that is, the "hidden" features of both tests. CWA can be implemented by using an automated coagulometer with dedicated software. The aim of this review was to evaluate whether CWA is able to detect both hypercoagulative and hypocoagulative states.
Data sources.—: Using MedLine, we searched and retrieved articles relating to CWA. We only considered articles published in English, but with no limits in terms of article type, publication year, or geography.
Conclusions.—: CWA was shown to be a reliable test in patients with both hypercoagulable and hypocoagulable states. It represents a simple and inexpensive global test that can easily provide information on the behavior of the coagulation system. Both the first and second derivatives are computed by using dedicated software implemented with an on-board algorithm in a routine automated coagulometer.
{"title":"Clot Waveform Analysis: From Hypercoagulability to Hypocoagulability - A Review.","authors":"Francesco Marongiu, Maria Filomena Ruberto, Silvia Marongiu, Doris Barcellona","doi":"10.5858/arpa.2023-0453-RA","DOIUrl":"https://doi.org/10.5858/arpa.2023-0453-RA","url":null,"abstract":"<p><strong>Context.—: </strong>Prothrombin time (PT) and activated partial thromboplastin time (aPTT) are coagulative screening tests used for the diagnosis of several pathologic conditions, such as liver failure, coagulation factor deficiencies, anti-phospholipid antibodies (lupus anticoagulant), and factor VIII inhibitors. A new test was developed several years ago to detect the amount of thrombin generated during plasma clotting, using low tissue factor concentrations and fluorogenic substrates, and it has since been used successfully in conditions ranging from hypocoagulable to hypercoagulable states. However, the test is expensive and difficult to perform in nonspecialized laboratories, and efforts have thus been made to find an economic and easily implementable test suitable for routine use, even in nonspecialist laboratories.</p><p><strong>Objective.—: </strong>To evaluate clot waveform analysis (CWA) of PT and aPTT, aiming to show the dynamics of clot formation; that is, the \"hidden\" features of both tests. CWA can be implemented by using an automated coagulometer with dedicated software. The aim of this review was to evaluate whether CWA is able to detect both hypercoagulative and hypocoagulative states.</p><p><strong>Data sources.—: </strong>Using MedLine, we searched and retrieved articles relating to CWA. We only considered articles published in English, but with no limits in terms of article type, publication year, or geography.</p><p><strong>Conclusions.—: </strong>CWA was shown to be a reliable test in patients with both hypercoagulable and hypocoagulable states. It represents a simple and inexpensive global test that can easily provide information on the behavior of the coagulation system. Both the first and second derivatives are computed by using dedicated software implemented with an on-board algorithm in a routine automated coagulometer.</p>","PeriodicalId":93883,"journal":{"name":"Archives of pathology & laboratory medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139907122","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-02-20DOI: 10.5858/arpa.2023-0235-CP
Brett Baskovich, Alexander Baras, Raja R Seethala, Patrick L Fitzgibbons, Frank Schneider, Brent T Harris, Joseph Khoury
Context.—: Biomarker reporting has increasingly become a key component of pathology reporting, providing diagnostic, prognostic, and actionable therapeutic data for patient care.
Objective.—: To expand and improve the College of American Pathologists (CAP) biomarker protocols.
Design.—: We surveyed CAP members to better understand the limitations they experienced when reporting cancer biomarker results. A Biomarker Workgroup reviewed the survey results and developed a strategy to improve and standardize biomarker reporting. Drafts of new and revised biomarker protocols were reviewed in both print and electronic template formats during interactive webinars presented to the CAP House of Delegates. Feedback was collected, and appropriate revisions were made to finalize the protocols.
Results.—: The first phase of the CAP Biomarker Workgroup saw the development of (1) a new stand-alone general Immunohistochemistry Biomarker Protocol that includes reporting for ER (estrogen receptor), PR (progesterone receptor), Ki-67, HER2 (human epidermal growth factor receptor 2), PD-L1 (programmed death ligand-1), and mismatch repair; (2) a new Head and Neck Biomarker Protocol that updates the prior 2017 paper-only version into an electronic template, adding new diagnostic and theranostic markers; (3) a major revision to the Lung Biomarker Protocol to streamline it and add in pan-cancer markers; and (4) a revision to the Colon and Rectum Biomarker Protocol to add HER2 reporting.
Conclusions.—: We have taken a multipronged approach to improving biomarker reporting in the CAP cancer protocols. We continue to review current biomarker reporting protocols to reduce and eliminate unnecessary methodologic details and update with new markers as needed. The biomarker templates will serve as standardized modular units that can be inserted into cancer-reporting protocols.
背景生物标记物报告已日益成为病理报告的关键组成部分,为患者护理提供诊断、预后和可操作的治疗数据:扩展并改进美国病理学家学会(CAP)生物标记物协议:我们对 CAP 成员进行了调查,以更好地了解他们在报告癌症生物标记物结果时遇到的限制。一个生物标记物工作组对调查结果进行了审查,并制定了改进和规范生物标记物报告的策略。在提交给 CAP 代表大会的互动式网络研讨会上,以印刷和电子模板的形式对新的和修订的生物标记物协议草案进行了审查。收集了反馈意见,并进行了适当的修订,最终确定了协议:CAP 生物标志物工作组第一阶段的工作包括:(1)制定新的独立的普通免疫组化生物标志物方案,其中包括报告 ER(雌激素受体)、PR(孕酮受体)、Ki-67、HER2(人表皮生长因子受体 2)、PD-L1(程序性死亡配体-1)和错配修复;(2) 新的《头颈部生物标记物协议》将 2017 年之前的纸质版更新为电子模板,增加了新的诊断和治疗标记物;(3) 对《肺部生物标记物协议》进行了重大修订,以简化该协议并增加泛癌症标记物;(4) 修订了《结肠和直肠生物标记物协议》,增加了 HER2 报告。结论我们采取了多管齐下的方法来改进 CAP 癌症方案中的生物标记物报告。我们将继续审查当前的生物标记物报告规程,以减少和消除不必要的方法细节,并根据需要更新新的标记物。生物标记物模板将作为标准化模块单元,可插入癌症报告规程中。
{"title":"The Journey to Improve the College of American Pathologists Cancer Biomarker Reporting Protocols.","authors":"Brett Baskovich, Alexander Baras, Raja R Seethala, Patrick L Fitzgibbons, Frank Schneider, Brent T Harris, Joseph Khoury","doi":"10.5858/arpa.2023-0235-CP","DOIUrl":"https://doi.org/10.5858/arpa.2023-0235-CP","url":null,"abstract":"<p><strong>Context.—: </strong>Biomarker reporting has increasingly become a key component of pathology reporting, providing diagnostic, prognostic, and actionable therapeutic data for patient care.</p><p><strong>Objective.—: </strong>To expand and improve the College of American Pathologists (CAP) biomarker protocols.</p><p><strong>Design.—: </strong>We surveyed CAP members to better understand the limitations they experienced when reporting cancer biomarker results. A Biomarker Workgroup reviewed the survey results and developed a strategy to improve and standardize biomarker reporting. Drafts of new and revised biomarker protocols were reviewed in both print and electronic template formats during interactive webinars presented to the CAP House of Delegates. Feedback was collected, and appropriate revisions were made to finalize the protocols.</p><p><strong>Results.—: </strong>The first phase of the CAP Biomarker Workgroup saw the development of (1) a new stand-alone general Immunohistochemistry Biomarker Protocol that includes reporting for ER (estrogen receptor), PR (progesterone receptor), Ki-67, HER2 (human epidermal growth factor receptor 2), PD-L1 (programmed death ligand-1), and mismatch repair; (2) a new Head and Neck Biomarker Protocol that updates the prior 2017 paper-only version into an electronic template, adding new diagnostic and theranostic markers; (3) a major revision to the Lung Biomarker Protocol to streamline it and add in pan-cancer markers; and (4) a revision to the Colon and Rectum Biomarker Protocol to add HER2 reporting.</p><p><strong>Conclusions.—: </strong>We have taken a multipronged approach to improving biomarker reporting in the CAP cancer protocols. We continue to review current biomarker reporting protocols to reduce and eliminate unnecessary methodologic details and update with new markers as needed. The biomarker templates will serve as standardized modular units that can be inserted into cancer-reporting protocols.</p>","PeriodicalId":93883,"journal":{"name":"Archives of pathology & laboratory medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139907123","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}