Aditi Rathi, Ayushi Sahay, Tanuja M Shet, Asawari Patil, Sangeeta B Desai
{"title":"Validation of Dual-Color Dual In Situ Hybridization for HER2/neu Gene in Breast Cancer.","authors":"Aditi Rathi, Ayushi Sahay, Tanuja M Shet, Asawari Patil, Sangeeta B Desai","doi":"10.5858/arpa.2022-0543-OA","DOIUrl":"10.5858/arpa.2022-0543-OA","url":null,"abstract":"<p><strong>Context.—: </strong>Human epidermal growth factor (HER2/neu) gene amplification, a poor prognostic factor in invasive breast cancer, has shown substantial utility as a predictive marker, with significantly improved survival following anti-HER2 therapies like trastuzumab. Dual-color dual in situ hybridization (D-DISH), a recently introduced fully automated assay for HER2/neu evaluation on light microscopy, has several advantages over fluorescence in situ hybridization (FISH).</p><p><strong>Objective.—: </strong>To standardize and validate the D-DISH assay using FISH as the gold standard and assess interobserver reproducibility in interpreting the D-DISH assay.</p><p><strong>Design.—: </strong>D-DISH was performed using the latest HER2 Dual ISH DNA Probe Cocktail assay (Ventana Medical Systems Inc, Tucson, Arizona) in 148 cases of invasive breast cancer. The same block was used for performing immunohistochemistry by Ventana PATHWAY anti-HER2/neu (4B5) antibody and FISH assay by ZytoLight SPEC ERBB2/CEN17 Dual Color Probe. D-DISH was separately interpreted by 4 pathologists blinded to FISH results.</p><p><strong>Results.—: </strong>Concordance of 98.65% and a Cohen κ value of 0.97 were observed between FISH and D-DISH. Intraclass correlation coefficient (0.93-0.97) and κ values (0.98-1.0) for interobserver reproducibility showed almost perfect agreement by D-DISH. Interobserver reproducibility was also evaluated for genomic heterogeneity, HER2 group categorization, and polysomy (κ values 0.42-0.74, 0.89-0.93, and 0.98-1.0, respectively).</p><p><strong>Conclusions.—: </strong>We successfully validated the latest version of D-DISH assay as a substitute for FISH in predicting HER2 gene status with significant interobserver reproducibility, concluding that this D-DISH assay may be introduced in routine diagnostic services as a reflex test to ascertain HER2 gene status.</p>","PeriodicalId":8305,"journal":{"name":"Archives of pathology & laboratory medicine","volume":" ","pages":"453-460"},"PeriodicalIF":3.2,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9870876","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Lydia Marie DeWitt and Mary Butler Kirkbride: Prototypical Circa-Early-1900s Women of Pathology and an Analysis of Their Contributions to the Discovery of Insulin.","authors":"James R Wright","doi":"10.5858/arpa.2023-0060-HP","DOIUrl":"10.5858/arpa.2023-0060-HP","url":null,"abstract":"<p><strong>Context.—: </strong>The year 2023 marks the centenary of the Nobel Prize honoring the discovery of insulin. Little-known experimental pathologists Lydia DeWitt, MD, at the University of Michigan and Mary Kirkbride, DSc [Hon], at Columbia University, both just beginning their academic careers, made independent contributions to the discovery that have never been critically examined. This happened at a time when it was exceedingly rare for women to work in pathology.</p><p><strong>Objective.—: </strong>To explore the facilitative roles of DeWitt and Kirkbride in the discovery of insulin and to examine their trail-breaking careers in academic pathology.</p><p><strong>Design.—: </strong>Available primary and secondary historical resources were reviewed.</p><p><strong>Results.—: </strong>DeWitt made and tested pancreatic extracts from duct-ligated atrophic pancreas (ie, Frederick Banting's great idea to prevent digestion of its hypothetical internal secretion) 15 years before Banting; Banting was unaware of her work. His idea came from reading a paper by pathologist Moses Barron. Prior duct-ligation studies had sometimes been viewed with skepticism because histologic identification of islets in atrophic duct-ligated pancreata was imperfect; Kirkbride addressed this with histochemical staining, convincing Barron and, therefore, indirectly influencing and motivating Banting. The lives and convoluted careers of these 2 early-20th-century women are explored and compared with those of other contemporary women in pathology. A unifying pattern becomes clear: careers in experimental pathology and bacteriology were accepted but performing clinical work in anatomic pathology was not.</p><p><strong>Conclusions.—: </strong>Both DeWitt and Kirkbride are prototypical early-20th-century women in academic pathology whose careers were constrained by gender. However, Kirkbride made a unique and unrecognized contribution to the discovery of insulin.</p>","PeriodicalId":8305,"journal":{"name":"Archives of pathology & laboratory medicine","volume":" ","pages":"476-492"},"PeriodicalIF":3.2,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9778207","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Estimation of Numbers of Testing Personnel and Test Volume in the Clinical Laboratory Improvement Amendments of 1988 Certificate of Accreditation and Certificate of Compliance Laboratories in the United States.","authors":"Yang Xia, Thomas H Taylor, Jufu Chen, Jason Hsia","doi":"10.5858/arpa.2022-0345-OA","DOIUrl":"10.5858/arpa.2022-0345-OA","url":null,"abstract":"<p><strong>Context.—: </strong>Two major categories of laboratories performing nonwaived testing under the Clinical Laboratory Improvement Amendments of 1988 (CLIA) are the Certificate of Accreditation (CoA) and Certificate of Compliance (CoC) laboratories. Accreditation organizations collect more detailed laboratory personnel information than the Centers for Medicare & Medicaid Services (CMS) Quality Improvement and Evaluation System (QIES).</p><p><strong>Objective.—: </strong>To estimate total numbers of testing personnel and testing volumes in CoA and CoC laboratories, by laboratory type and state.</p><p><strong>Design.—: </strong>We developed a statistical inference method by using the respective correlations between testing personnel counts and test volume by laboratory type.</p><p><strong>Results.—: </strong>QIES reported 33 033 active CoA and CoC laboratories in July 2021. We estimated testing personnel to be 328 000 (95% CI, 309 000-348 000), which is supported by the count of 318 780 reported by the US Bureau of Labor Statistics. There were twice as many testing personnel in hospital laboratories as in independent laboratories (158 778 versus 74 904, P < .001). Independent laboratories had the highest test volume per person, which was twice as high as physician office laboratories (62 228 versus 30 102, P < .001). Hospital and independent laboratories comprised 34% of all CoA and CoC laboratories but performed the largest portion of testing (81%). Physician office laboratories, accounting for 44% of all CoA and CoC laboratories, performed a comparatively low proportion of total tests (9%).</p><p><strong>Conclusions.—: </strong>Numbers of testing personnel vary considerably by laboratory type and across states. These data can provide valuable insight when assessing laboratory workforce training needs and planning for public health emergencies.</p>","PeriodicalId":8305,"journal":{"name":"Archives of pathology & laboratory medicine","volume":" ","pages":"443-452"},"PeriodicalIF":3.2,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11024983/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9755123","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"An Updated Contextual Approach to Mesothelial Proliferations in Pleural Effusion Cytology Leveraging Morphology, Ancillary Studies, and Novel Biomarkers.","authors":"Lauren J Miller, Isabella M Holmes, Madelyn Lew","doi":"10.5858/arpa.2023-0049-RA","DOIUrl":"10.5858/arpa.2023-0049-RA","url":null,"abstract":"<p><strong>Context.—: </strong>Pleural effusions are common cytologic specimens that can be leveraged to make diagnoses of malignancy that drive appropriate patient management. However, the overlap in morphologic features of reactive mesothelial proliferations, mesotheliomas, and adenocarcinomas can create diagnostic pitfalls in the cytologic evaluation of pleural fluids.</p><p><strong>Objective.—: </strong>To review the morphologic spectrum of benign and malignant mesothelial proliferations in pleural effusions, as well as relevant clinicoradiologic contexts and ancillary tests.</p><p><strong>Data sources.—: </strong>Existing scientific and clinical literature as of January 2023.</p><p><strong>Conclusions.—: </strong>We can leverage the knowledge of several overlapping morphologic features, clinicoradiologic scenarios, and immunohistochemical studies to enhance the diagnostic accuracy of pleural effusion cytology to appropriately delineate cases of adenocarcinoma, reactive mesothelial proliferation, and mesothelioma. Earlier diagnosis through cytology, particularly in cases of mesothelioma, may positively impact patient treatment options and prognosis.</p>","PeriodicalId":8305,"journal":{"name":"Archives of pathology & laboratory medicine","volume":" ","pages":"409-418"},"PeriodicalIF":3.2,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10423648","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ming Li, Shuling Zhou, Hong Lv, Mengyuan Cai, Xiaochun Wan, Hongfen Lu, Ruohong Shui, Wentao Yang
{"title":"FOXC1 and SOX10 in Estrogen Receptor-Low Positive/HER2-Negative Breast Cancer: Potential Biomarkers for the Basal-like Phenotype Prediction.","authors":"Ming Li, Shuling Zhou, Hong Lv, Mengyuan Cai, Xiaochun Wan, Hongfen Lu, Ruohong Shui, Wentao Yang","doi":"10.5858/arpa.2022-0370-OA","DOIUrl":"10.5858/arpa.2022-0370-OA","url":null,"abstract":"<p><strong>Context.—: </strong>Breast cancer with low (1%-10%) estrogen receptor (ER) expression (ER-low positive) constitutes a small portion of invasive breast cancers, and the treatment strategy for these tumors remains debatable.</p><p><strong>Objective.—: </strong>To characterize the features and outcomes of ER-low positive patients, and clarify the clinical significance of FOXC1 and SOX10 expression in ER-low positive/HER2-negative tumors.</p><p><strong>Design.—: </strong>Among 9082 patients diagnosed with primary invasive breast cancer, the clinicopathologic features of those with ER-low positive breast cancer were characterized. FOXC1 and SOX10 mRNA levels were analyzed in ER-low positive/HER2-negative cases from public data sets. The expression of FOXC1 and SOX10 in ER-low positive/HER2-negative tumors was evaluated by immunohistochemistry.</p><p><strong>Results.—: </strong>The clinicopathologic study of ER-low positive tumors indicated more aggressive characteristics compared with those tumors with ER >10%, while they had more overlapping features with ER-negative tumors irrespective of the HER2 status. The intrinsic molecular subtype of ER-low positive cases with high FOXC1 and SOX10 mRNA expression was more likely to be nonluminal. Among the ER-low positive/HER2-negative tumors, 56.67% (51 of 90) and 36.67% (33 of 90) were positive for FOXC1 and SOX10, respectively, which was significantly positively correlated with CK5/6 expression. In addition, the survival analysis demonstrated no significant difference between patients who received and who did not receive endocrine therapy.</p><p><strong>Conclusions.—: </strong>ER-low positive breast cancers biologically overlap more with ER-negative tumors. ER-low positive/HER2-negative cases demonstrate a high rate of FOXC1 or SOX10 expression, and these cases might be better categorized as a basal-like phenotype/subtype. FOXC1 and SOX10 testing may be used for the intrinsic phenotype prediction for ER-low positive/HER2-negative patients.</p>","PeriodicalId":8305,"journal":{"name":"Archives of pathology & laboratory medicine","volume":" ","pages":"461-470"},"PeriodicalIF":3.2,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9755125","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sharad Khurana, Michael G Heckman, Fiona E Craig, Jordan J Cochuyt, Patricia Greipp, Zaid Abdel Rahman, Lisa Z Sproat, Mark Litzow, James M Foran, Liuyan Jennifer Jiang
{"title":"Evaluation of Novel Targets, Including CC-Chemokine Receptor 4, in Adult T-Cell Acute Lymphoblastic Leukemia/Lymphoma: A Mayo Clinic Clinical and Pathologic Study.","authors":"Sharad Khurana, Michael G Heckman, Fiona E Craig, Jordan J Cochuyt, Patricia Greipp, Zaid Abdel Rahman, Lisa Z Sproat, Mark Litzow, James M Foran, Liuyan Jennifer Jiang","doi":"10.5858/arpa.2022-0482-OA","DOIUrl":"10.5858/arpa.2022-0482-OA","url":null,"abstract":"<p><strong>Context.—: </strong>Unlike B-cell acute lymphoblastic leukemia/lymphoma (ALL/LBL), there have been few therapeutic advances in T-cell ALL (T-ALL)/LBL, an aggressive ALL/LBL subtype.</p><p><strong>Objective.—: </strong>To perform a focused tissue array study to elucidate tumor markers of therapeutic potential in T-ALL/LBL.</p><p><strong>Design.—: </strong>Using immunohistochemistry, we evaluated expression of leukemic antigens of interest, specifically CC-chemokine receptor 4 (CCR4), among others, on available remnant diagnostic material, including tumor tissue slides obtained from formalin-fixed, paraffin-embedded preserved tissues.</p><p><strong>Results.—: </strong>Our analysis identified, for the first time, expression of CCR4 in T-ALL/LBL in 11 of 27 cases (40.7%) and confirmed common expression of BCL2, CD38, and CD47, as reported previously. We also identified the expression of CD123 in 4 of 26 cases (15.4%), whereas BCL6 and PDL1 were expressed in a small number of T-ALL/LBL cases. The potential novel target CCR4 was significantly more common in the Pre/Pro-T immunophenotypic subtype, 6 of 9 (66.7%, P = .01). No additional differences in clinical and epidemiologic variables were noted among positive or negative CCR4 cases.</p><p><strong>Conclusions.—: </strong>These findings support preclinical and clinical testing of therapies targeting CCR4, CD47, BCL2, CD38, and CD123 in T-ALL/LBL, and may help guide the development of targeted clinical trials in T-ALL/LBL, a rare disease in urgent need of novel therapies.</p>","PeriodicalId":8305,"journal":{"name":"Archives of pathology & laboratory medicine","volume":" ","pages":"471-475"},"PeriodicalIF":3.2,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10256129","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Christoph Fraune, Henry D Tazelaar, Yasmeen M Butt, Maxwell L Smith, Brandon T Larsen, Katalin Kelemen
{"title":"Usefulness and Limitations of Current Diagnostic Strategies for Pulmonary Mucosa-Associated Lymphoid Tissue Lymphoma: Lessons Learned From a Large Cohort.","authors":"Christoph Fraune, Henry D Tazelaar, Yasmeen M Butt, Maxwell L Smith, Brandon T Larsen, Katalin Kelemen","doi":"10.5858/arpa.2022-0521-OA","DOIUrl":"10.5858/arpa.2022-0521-OA","url":null,"abstract":"<p><strong>Context.—: </strong>The pathologic diagnosis of pulmonary extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT) is challenging.</p><p><strong>Objective.—: </strong>To evaluate the diagnostic usefulness and limitations of current diagnostic strategies for pulmonary MALT lymphoma.</p><p><strong>Design.—: </strong>A retrospective review of 120 cases of pulmonary MALT lymphoma from 2014 through 2021 was performed.</p><p><strong>Results.—: </strong>Clinicoradiologic presentations overlapped with previous observations in patients with MALT lymphoma, such as a wide age range, female predominance, frequent association with autoimmune disease or immunodeficiency, and broad imaging findings. The histopathologic diagnosis was based on a combination of morphology, immunohistochemistry, and demonstration of B-cell lineage clonality. Two-thirds (76 of 113) of MALT lymphomas had lymphoplasmacytoid cytomorphology. Occasionally, MALT lymphomas were associated with granulomas/giant cells (29%, 35 of 120) or immunoglobulin deposition disease (21%, 25 of 120), including light chain/heavy chain deposition disease, amyloidosis, and/or crystal storing histiocytosis. While CD5, CD10, Bcl-2, and Bcl-6 rarely revealed aberrancies, aberrant CD43 expression either on B-cells or on plasma cells was detected in 42% (27 of 64) of cases, including cases for which proof of clonality could not be obtained. κ/λ in situ hybridization was particularly useful for tumors with lymphoplasmacytoid morphology but performed poorly in lymphomas having no plasmacytic differentiation. κ/λ immunohistochemistry showed no additional usefulness when applied together with κ/λ in situ hybridization. Immunoglobulin gene rearrangement studies by polymerase chain reaction achieved high detection rates of clonality in all cytomorphologic subgroups.</p><p><strong>Conclusions.—: </strong>Our study offers a practical evaluation of common diagnostic tests in pulmonary MALT lymphoma. We offer recommendations for a diagnostic workup that takes into consideration the usefulness and the specific limitations of the various diagnostic strategies.</p>","PeriodicalId":8305,"journal":{"name":"Archives of pathology & laboratory medicine","volume":" ","pages":"419-429"},"PeriodicalIF":3.2,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10381577","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chloe A Brady, Tihesia Riley, Gauri Batra, Ian Crocker, Alexander E P Heazell
{"title":"Characterizing Histopathologic Features in Pregnancies With Chronic Histiocytic Intervillositis Using Computerized Image Analysis.","authors":"Chloe A Brady, Tihesia Riley, Gauri Batra, Ian Crocker, Alexander E P Heazell","doi":"10.5858/arpa.2022-0494-OA","DOIUrl":"10.5858/arpa.2022-0494-OA","url":null,"abstract":"<p><strong>Context.—: </strong>Chronic histiocytic intervillositis (CHI) is a rare condition characterized by maternal immune cell infiltration into the human placenta. CHI is strongly associated with fetal growth restriction, miscarriage, and stillbirth, and knowledge of its etiology, and consequently effective treatment, is limited. Currently, diagnosis is largely subjective and varies between centers, making comparison between studies challenging.</p><p><strong>Objective.—: </strong>To objectively quantify and interrelate inflammatory cells and fibrin in placentas with CHI compared with controls and determine how pathology may be altered in subsequent pregnancies following diagnosis. Macrophage phenotype was also investigated in untreated cases of CHI.</p><p><strong>Design.—: </strong>Computerized analysis was applied to immunohistochemically stained untreated (index) cases of CHI, subsequent pregnancies, and controls. Index placentas were additionally stained by immunofluorescence for M1 (CD80 and CD86) and M2 macrophage markers (CD163 and CD206).</p><p><strong>Results.—: </strong>Quantification revealed a median 32-fold increase in macrophage infiltration in index cases versus controls, with CHI recurring in 2 of 11 (18.2%) subsequent pregnancies. A total of 4 of 14 placentas (28.6%) with a diagnosis of CHI did not exhibit infiltration above controls. Macrophages in index pregnancies strongly expressed CD163. There was no significant difference in fibrin deposition between index cases and controls, although subsequent pregnancies displayed a 2-fold decrease compared with index pregnancies. CD3+ T cells were significantly elevated in index pregnancies; however, they returned to normal levels in subsequent pregnancies.</p><p><strong>Conclusions.—: </strong>In CHI, intervillous macrophages expressed CD163, possibly representing an attempt to resolve inflammation. Computerized analysis of inflammation in CHI may be useful in determining how treatment affects recurrence, and alongside pathologist expertise in grading lesion severity.</p>","PeriodicalId":8305,"journal":{"name":"Archives of pathology & laboratory medicine","volume":" ","pages":"430-442"},"PeriodicalIF":3.2,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9870874","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Correlation of In Situ HER2 RNA Expression With HER2 Immunohistochemistry and Fluorescence In Situ Hybridization Categories in Breast Cancer.","authors":"Yu-Fen Tseng, Yu-Chia Li, Yi-Hsuan Lee, Hsiang-We Hu, Man-San Zhang, Tze-Chun Hung, Huang-Chun Lien","doi":"10.5858/arpa.2023-0129-OA","DOIUrl":"10.5858/arpa.2023-0129-OA","url":null,"abstract":"<p><strong>Context.—: </strong>RNA sequencing study has demonstrated that human epidermal growth factor receptor 2 (HER2) RNA levels influence anti-HER2 therapeutic efficacy. However, in situ HER2 RNA expression (isHRE), which evaluates HER2 RNA expression in tissue, has remained unclear in breast cancers (BCs) of various HER2 immunohistochemistry (IHC)/in situ hybridization (ISH) categories.</p><p><strong>Objective.—: </strong>To correlate isHRE with all HER2 IHC/fluorescence ISH (FISH) categories in BC.</p><p><strong>Design.—: </strong>Formalin-fixed, paraffin-embedded tissue sections from 259 BCs, covering all IHC/FISH categories, were analyzed for isHRE by RNAscope.</p><p><strong>Results.—: </strong>We validated HER2 RNAscope scoring as a semiquantitative method to evaluate isHRE and demonstrated significantly higher RNAscope scores in IHC 3+ than in IHC 2+ cases, and in IHC 2+ than in IHC 0/1+ cases. Among the 5 IHC 2+/FISH groups, group 1 (G1) cases had the highest scores. The scores in G3 cases were higher than those in G2, but not significantly different from those in G4 and G5. G4 cases had significantly higher scores than those in G2. Higher HER2 copy numbers and HER2:CEP 17 (centromere 17) copy number ratios were significantly correlated with higher isHRE in G1 cases, but not in G2 to G5 cases. RNAscope scores were significantly lower in HER2-negative (IHC 0) than in HER2-low (IHC 2+/FISH- and IHC 1+) BCs but were not different between IHC 0 and 1+ BCs when analyzed separately.</p><p><strong>Conclusions.—: </strong>We demonstrate the HER2 RNA expression status among BCs of various HER2 IHC/FISH categories in tissue. Such information may be relevant for anti-HER2 treatment decisions considering the role of HER2 RNA expression in predicting anti-HER2 therapeutic efficacy.</p>","PeriodicalId":8305,"journal":{"name":"Archives of pathology & laboratory medicine","volume":" ","pages":"e48-e56"},"PeriodicalIF":3.2,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10483882","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Cholangiocarcinoma: Pathologic and Molecular Classification in the Era of Precision Medicine.","authors":"Purva Gopal, Marie E Robert, Xuchen Zhang","doi":"10.5858/arpa.2022-0537-RA","DOIUrl":"10.5858/arpa.2022-0537-RA","url":null,"abstract":"<p><strong>Context.—: </strong>Cholangiocarcinoma (CCA) is a heterogeneous cancer of the bile duct, and its diagnosis is often challenging.</p><p><strong>Objective.—: </strong>To provide insights into state-of-the-art approaches for the diagnosis of CCA.</p><p><strong>Data sources.—: </strong>Literature review via PubMed search and authors' experiences.</p><p><strong>Conclusions.—: </strong>CCA can be categorized as intrahepatic or extrahepatic. Intrahepatic CCA is further classified into small-duct-type and large-duct-type, whereas extrahepatic CCA is classified into distal and perihilar according to site of origin within the extrahepatic biliary tree. Tumor growth patterns include mass forming, periductal infiltrating, and intraductal tumors. The clinical diagnosis of CCA is challenging and usually occurs at an advanced tumor stage. Pathologic diagnosis is made difficult by tumor inaccessibility and challenges in distinguishing CCA from metastatic adenocarcinoma to the liver. Immunohistochemical stains can assist in differentiating CCA from other malignancies, such as hepatocellular carcinoma, but no distinctive CCA-specific immunohistochemical profile has been identified. Recent advances in next-generation sequencing-based high-throughput assays have identified distinct genomic profiles of CCA subtypes, including genomic alterations that are susceptible to targeted therapies or immune checkpoint inhibitors. Detailed histopathologic and molecular evaluations of CCA by pathologists are critical for correct diagnosis, subclassification, therapeutic decision-making, and prognostication. The first step toward achieving these goals is to acquire a detailed understanding of the histologic and genetic subtypes of this heterogeneous tumor group. Here, we review state-of-the-art approaches that should be applied to establish a diagnosis of CCA, including clinical presentation, histopathology, staging, and the practical use of genetic testing methodologies.</p>","PeriodicalId":8305,"journal":{"name":"Archives of pathology & laboratory medicine","volume":" ","pages":"359-370"},"PeriodicalIF":3.2,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9640846","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}