bluuebunny/crossref_metadata_2025_split huggingface dataset:
Adequacy of Surgical Pathology Reporting of Cancer: A College of American Pathologists Q-Probes Study of 86 Institutions
Authors: Idowu Michael O. , Bekeris Leonas G. , Raab Stephen , Ruby Stephen G. , Nakhleh Raouf E. 
Published: February 2021

Abstract
Context.—Inclusion of all scientifically validated elements in surgical pathology cancer reports is needed for optimal patient care.
Objective.—To evaluate the frequency with which surgical pathology cancer reports contain all the scientifically validated elements required by the American College of Surgery (ACS) Commission on Cancer (CoC), the extent to which checklists are used, and the effects that the use of checklists have on the completeness of cancer reports.
Design.—Participants in the College of American Pathologists voluntary Q-Probes program reviewed 25 consecutive surgical pathology reports to include cancer reports from breast, colon, rectum, and prostate cancer specimens. For each report, the type and total number of missing required elements, deemed essential by the ACS CoC, was recorded.
Results.—A total of 2125 cancer reports were reviewed in 86 institutions; 68.8% of all surgical pathology cancer reports included all the required elements. Institutions in which checklists were routinely used reported all required elements at a higher rate than those that did not use checklists (88% versus 34%), and institutions that had a system in place to track errors also reported all required elements at a higher rate when compared to those that did not have such a system in place (88% versus 68%). The missing mandated elements, common to cancer reports of all tumor types, were extent of invasion and status of the resection margin.
Conclusions.—This study demonstrates that about 30% of cancer reports do not have all the scientifically validated elements required by the ACS CoC. Pathology departments in which checklists are not routinely used have a substantially lower rate of reports that include all the required elements.
Hypomethylation of the DNMT3L Promoter in Ocular Surface Squamous Neoplasia
Authors: Manderwad Guru Prasad , Gokul Gopinathan , Kannabiran Chitra , Honavar Santosh G. , Khosla Sanjeev , Vemuganti Geeta K. 
Published: February 2021

Abstract
Context.—Cancer is known to have epigenetic inputs, with events like genomewide hypomethylation and gene-specific hypermethylation of DNA. The DNA methyltransferase enzymes act as effectors of this reprogramming. A previous study revealed that hypomethylation at the DNA methyltransferase 3-like (DNMT3L) promoter could be a potential biomarker in cervical tumors. Because the pathobiology of ocular surface squamous neoplasia (OSSN) is similar to that of cervical tumors, we wanted to determine whether similar changes occur in the methylation pattern at the DNMT3L promoter in OSSN.
Objective.—To evaluate the methylation status of the DNMT3L promoter in OSSN compared with healthy conjunctiva.
Design.—We evaluated DNA methylation at the DNMT3L promoter in the tumor tissues of 6 patients with histologically proven OSSN and in healthy conjunctiva tissue from 7 individuals for controls using the sodium bisulfite–assisted conversion of genomic DNA. Extracted genomic DNA was treated with sodium bisulfite and amplified with specific primers for the DNMT3L promoter region. The specific polymerase chain reaction products were cloned and sequenced.
Results.—The mean age of these patients was 50.2 years (range, 35–65 years). Histologically, 4 OSSN cases were invasive; 2 were intraepithelial. Healthy conjunctival tissues exhibited a methylated promoter region, whereas a variable loss of methylation was observed in all 6 OSSN cases.
Conclusions.—We have, for the first time to our knowledge, identified loss of methylation at the DNMT3L promoter in OSSN cases, but its physiologic significance is yet to be understood. Further studies are warranted to substantiate our results.
Intraluminal Polypoid Metastasis of Renal Cell Carcinoma in Gallbladder Mimicking Gallbladder Polyp
Authors: Fang Xueping , Gupta Nilesh , Shen Steven S. , Tamboli Pheroze , Charnsangavej Chusilp , Rashid Asif , Wang Huamin 
Published: February 2021

Abstract
Context.—Metastatic renal cell carcinoma (RCC) in gallbladder is rare with only 18 cases published in the English literature.
Objectives.—To review the clinicopathologic characteristics of metastatic RCC in gallbladder and to correlate the findings with clinical outcomes.
Design.—We report 4 additional cases of intraluminal polypoid metastasis of RCC in gallbladder and reviewed all reported cases, to our knowledge, of metastatic RCC in gallbladder in the English literature.
Results.—Most of the patients (19 of 22; 86%) were men. The ages at presentation ranged from 39 to 84 years with a median age of 61.5 years. All cases showed an intraluminal polypoid/pedunculated mucosal mass mimicking a gallbladder polyp. Histologically, all cases were clear cell RCC with most of the tumors either confined to gallbladder mucosa (67%) or involved both mucosa and muscular layer (27%). The longest interval between nephrectomy and the development of gallbladder metastasis was 27 years.
Conclusions.—Metastatic clear cell RCC should be considered in the differential diagnosis of polypoid lesion of the gallbladder with clear cell morphology. Solitary metastasis of RCC in gallbladder correlated with better survival, and simple cholecystectomy for solitary metastatic RCC may provide patients with favorable long-term survival.
Revisiting Chordoma With Brachyury, a “New Age” Marker: Analysis of a Validation Study on 51 Cases
Authors: Jambhekar Nirmala A. , Rekhi Bharat , Thorat Kiran , Dikshit Rajesh , Agrawal Manish , Puri Ajay 
Published: February 2021

Abstract
Context.—Chordoma is a rare, notochordal tumor with a characteristic histomorphology and immunohistochemical profile. At times, it presents a diagnostic challenge, especially in small biopsies. Brachyury, a nuclear transcription factor, is a recently described immunohistochemical marker for diagnosing chordomas.
Objective.—To study the sensitivity and specificity of brachyury in diagnosing chordomas by comparing its expression in axial chordomas with nonchordomatous tumors.
Design.—Fifty-one axial chordomas, accessioned during a 10-year period, and 58 nonchordomatous tumors were subjected to brachyury staining by immunohistochemistry.
Results.—The 51 chordomas occurred in 36 men and 15 women. Sitewise, 34 cases (66.7%) occurred in the sacrococcyx, 9 (17.6%) in the spine, and 8 (15.7%) in the skull base. Histologically, 34 cases (66.7%) were classical chordomas, 13 cases (25.5%) had a dominant chondroid component, and 2 cases each (3.9%) were chondroid chordomas and dedifferentiated chordomas, respectively. Brachyury staining was positive in 46 of the 51 chordomas (90.2%) and negative in all 58 nonchordomatous tumors. The dedifferentiated area in 2 chordomas was negative for brachyury staining. Fourteen of 15 chordomas with chondroid component showed positive brachyury staining. Immunohistochemical expression of other markers, included cytokeratin (positive in 23 of 23 cases; 100%), epithelial membrane antigen (positive in 22 of 22 cases; 100%) and S100 protein (positive in 18 of 21 cases; 85.7%).
Conclusion.—Exclusive brachyury expression in more than 90% of chordomas indicates its value as a unique, specific marker with other sensitive markers like cytokeratin, epithelial membrane antigen, and/or S100 protein in substantiating a diagnosis of chordoma, including on small biopsies.
Melanocytic Lesions of the Conjunctiva
Authors: Zembowicz Artur , Mandal Rajni V. , Choopong Pitipol 
Published: February 2021

Abstract
Context—Melanocytic proliferations are among the most common neoplasms of the conjunctiva. They often represent challenging lesions for pathologists unfamiliar with unique histologic features of melanocytic proliferations in this location and with nomenclature used by ophthalmologists.
Objective—To comprehensively review clinical aspects, pathologic features, and management of melanocytic proliferations of the conjunctiva.
Data Sources—Review of the literature and personal experience of the authors.
Conclusions—Classification, state of the art, and practical aspects of pathology of melanocytic proliferations of the conjunctiva are discussed.
Pulmonary Lymphangioleiomyomatosis
Authors: Zhang Xuchen , Travis William D. 
Published: February 2021

Abstract
Lymphangioleiomyomatosis is an uncommon lung disease primarily affecting women of childbearing age. It is characterized by the progressive proliferating and infiltrating smooth musclelike cells (lymphangioleiomyomatosis cells), which lead to the cystic destruction of the lung parenchyma; obstruction of airways, blood vessels, and lymphatics; and loss of pulmonary function. Lymphangioleiomyomatosis cells coexpress smooth muscle markers (such as smooth muscle actin and desmin) and melanocytic markers (such as HMB-45, Melan-A/MART-1, and microphthalmia transcription factor). Dyspnea on exertion and recurrent pneumothorax are the most common clinical features. Somatic or genetic mutations of tumor suppressor genes tuberous sclerosis complex (TSC) 1 or TSC2 are closely related to lymphangioleiomyomatosis. The TSC1/TSC2 protein-related signaling pathways are involved in the pathogenesis and may provide novel therapeutic targets for lymphangioleiomyomatosis and diseases associated with TSC1/TSC2 dysfunction.
Neuroendocrine Tumors of the Lung: An Update
Authors: Rekhtman Natasha 
Published: February 2021

AbstractContext.—The 2004 World Health Organization (WHO) classification recognizes 4 major types of lung neuroendocrine tumors: typical carcinoid, atypical carcinoid, small cell lung cancer, and large cell neuroendocrine carcinoma. Markedly different prognostic implications and treatment paradigms for these tumors underscore the importance of accurate pathologic diagnosis.Objective.—To detail the clinical and pathologic features of lung neuroendocrine tumors, with emphasis on diagnostic criteria, differential diagnoses, and application of immunohistochemistry. The emerging evidence for the utility of Ki-67 (MIB1) in the diagnosis of lung neuroendocrine tumors, particularly in small biopsy and cytology, is emphasized.Data Sources.—The 2004 WHO classification, other published literature, and primary material from the author's institution.Conclusions.—The current WHO classification of neuroendocrine tumors is based on morphologic features in combination with precisely defined mitotic rate and absence or presence of necrosis. Ki-67 (MIB1) is emerging as a useful ancillary tool in the diagnosis of these tumors. Continued research efforts are needed to identify additional immunohistochemical and molecular biomarkers that can serve as ancillary diagnostic tools and as potential therapeutic targets for these diseases.
Significance of High-Risk Human Papillomavirus DNA Detection in Women 50 Years and Older With Squamous Cell Papanicolaou Test Abnormalities
Authors: Zhao Chengquan , Zhao Shuping , Heider Amer , Austin R. Marshall 
Published: February 2021

Abstract
Context.—Data on cytologic screening and follow-up disproportionately reflect findings from frequently screened younger women, and data from screened women 50 years and older using newer screening technologies remain limited.
Objective.—To better understand the utility of adjunctive high-risk human papillomavirus (hrHPV) testing for disease risk stratification in women 50 years and older with a range of liquid-based cytology, abnormal, squamous cell Papanicolaou test results.
Design.—Liquid-based cytology cases interpreted as high-grade squamous intraepithelial lesion (HSIL); low-grade squamous intraepithelial lesion (LSIL); atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion (ASC-H); and atypical squamous cells of undetermined significance (ASC-US) at Magee-Womens Hospital (Pittsburgh, Pennsylvania) were retrospectively identified for a 36-month period between July 1, 2005, and June 30, 2008, from women 50 years and older who also had hrHPV DNA test results. Histopathologic follow-up diagnoses were analyzed.
Results.—During the study period, 4855 women 50 years and older had HSIL, LSIL, ASC-H, or ASC-US Papanicolaou test results and hrHPV testing. In 89.3% of HSIL cases, 71.0% of LSIL cases, 38.9% of ASC-H cases, and 14.2% of ASC-US cases, hrHPV test results were positive. The positive predictive value of a positive hrHPV test for histopathologic cervical intraepithelial neoplasia 2/3+ detection was 90.5% with HSIL, 15% with ASC-H, 9.8% with LSIL, and 3.2% with ASC-US. A negative hrHPV test result had a 100% negative predictive value for histopathologic cervical intraepithelial neoplasia 2/3+ in both LSIL and ASC-H cases.
Conclusions.—In women 50 years and older, a positive hrHPV test result significantly increased the likelihood of follow-up histopathologic diagnoses of cervical intraepithelial neoplasia 2 /3+ in patients with HSIL, LSIL, and ASC-H Papanicolaou test results compared with women with negative hrHPV test results. No cervical intraepithelial neoplasia 2/3+ diagnoses were documented in women 50 years and older with LSIL or ASC-H Papanicolaou test results and negative hrHPV test results.
Prognostication in Thin Cutaneous Melanomas
Authors: Gimotty Phyllis A. , Guerry DuPont 
Published: February 2021

AbstractContext—While most patients diagnosed with thin cutaneous melanoma will have a good prognosis, nearly 5% will die of their disease. Thin melanomas are common and approximately one-quarter of all melanoma-related deaths result from thin primary tumors. Patients with thin melanoma commonly have sentinel lymph node biopsies that are uncommonly positive.Objective—To review the progress that has been made in the translation of prognostic and predictive biomarkers for patients with thin melanomas by focusing on the developments during the last 5 years in using measures of tumor proliferation. Given the paucity of biomarkers for patients with thin melanoma, we review some of the challenges in the development, validation, and translation of new biomarkers into clinical practice.Data Sources—Surveillance, Epidemiology and End Results registry data, cohort data from a cancer center's program in melanoma, and focused literature review.Conclusions—The presence of dermal mitoses improves prognostication and prediction. To optimize patient management, biomarkers reflecting biologic processes underlying tumor progression will need to be included in panels and risk models, validated, generalized, and ratified.
Differential Notch1 and Notch2 Expression and Frequent Activation of Notch Signaling in Gastric Cancers
Authors: Sun Yuan , Gao Xue , Liu Jia , Kong Qing-You , Wang Xiao-Wei , Chen Xiao-Yan , Wang Qian , Cheng Yi-Fan , Qu Xiao-Xia , Li Hong 
Published: February 2021

AbstractContext.—The biologic effects of Notch1 and Notch2 vary with cancer types and their potential role(s) in gastric cancers (GCs) remains largely unknown.Objectives.—This study aimed to address the previously mentioned issue by checking the expression of Notch1, Notch2, and Notch target gene Hes1 in GCs, premalignant gastric lesions, and noncancerous endoscopic gastric mucosa and by inhibiting Notch signal transduction in GC cells.Design.—The status of Notch1, Notch2, and Hes1 expression in 74 GC surgical specimens, 10 endoscopic samples, and 4 human GC cell lines was evaluated by tissue microarray–based immunohistochemical staining, Western blotting, and reverse transcription-polymerase chain reaction, and the importance of Notch signaling was elucidated by treating 2 GC cell lines with 2 γ-secretase inhibitors.Results.—Notch1 was undetectable in noncancerous gastric mucosa but was expressed with nuclear translocation in 16.7% (4 of 24) of chronic gastritis, 50.0% (9 of 18) of intestinal metaplasia, 54.2% (26 of 48) of intestinal GC, and 23.1% (6 of 26) of diffuse GC, showing distinct differences of Notch1 detection rates between either intestinal metaplasia and chronic gastritis or intestinal GCs and diffuse GCs (P  =  .03; P  =  .005, respectively). Notch2 nuclear translocation frequencies were 10.0% (1 of 10) in noncancerous endoscopic mucosa, 71.4% (30 of 42) in premalignant lesions, and 97.3% (72 of 74) in GC tissues, demonstrating a correlation of Notch2 expression with both intestinal GC and diffuse GC formation (P &lt; .001). The rates of nuclear-Hes1 labeling were 1 of 10 among noncancerous, 42.9% premalignant, and 81.1% cancer tissues, which were closely correlated with Notch2 (P &lt; .001) rather than Notch1 (P  =  .42) nuclear translocation. Only Notch2 was expressed accompanied with Hes1 nuclear labeling in the 4 GC cell lines established from diffuse GC cases. Inhibition of Notch signaling with γ-secretase inhibitors, L-685,458 and DAPT, prevented Hes1 nuclear translocation but neither suppressed growth nor induced cell death.Conclusions.—This study demonstrated a close correlation of Notch2 expression with GC formation and the potential link of Notch1 upregulation with intestinal-like phenotypes of gastric lesions. Although inhibition of Notch activity failed to achieve anti-GC effects, the activated Notch signaling may reflect a potential GC risk.
Comparison of Formalin-Free Tissue Fixatives: A Proteomic Study Testing Their Application for Routine Pathology and Research
Authors: Kothmaier Hannelore , Rohrer Daniela , Stacher Elvira , Quehenberger Franz , Becker Karl-Friedrich , Popper Helmut H. 
Published: February 2021

Abstract
Context.—Formalin-fixed, paraffin-embedded tissue is the routine processing method for diagnostics practiced in pathology departments worldwide.
Objective.—To determine the potential value of non–cross-linking, formalin-free tissue fixation for diagnostics in pathology and proteomic investigations.
Design.—We tested 3 commercially available, formalin-free tissue fixatives—FineFIX, RCL2, and HOPE—in lung cancer specimens from 10 patients. The fixatives were evaluated for their effects on tissue morphology, protein recovery, and immunoreactivity for a selected panel of proteins differently expressed in lung cancer, using immunohistochemistry and Western blotting.
Results.—Tumor-cell analysis with hematoxylin-eosin worked equally well for all tested fixatives when compared with the standard formalin-fixed, paraffin-embedded procedure. Movat pentachrome stains showed comparable results for the different matrices and cellular proteins analyzed. The RCL2 (P  =  .01) and HOPE fixatives (P  =  .03) improved protein recovery when compared with formalin-fixed, paraffin-embedded or frozen tissues. Our data clearly show that the fixatives evaluated influenced immunoreactivity to matched, formalin-fixed, paraffin-embedded lung cancer tissue. In particular, membrane-bound proteins, such as epidermal growth factor receptor EGFR, can be detected more efficiently by immunohistochemistry and Western blotting.
Conclusion.—We have demonstrated that formalin-free fixatives have the potential in routine pathology and research to replace formalin in histomorphology and protein preservation.
Immunohistochemistry of Melanocytic Proliferations
Authors: Prieto Victor G. , Shea Christopher R. 
Published: February 2021

Abstract
Context.—Histologic analysis allows accurate classification of most melanocytic lesions as benign or malignant. Only in a minority of lesions is it necessary to use other techniques as an aid in the diagnosis. Among them, most authors recommend immunohistochemistry.
Objective.—To describe how to apply immunohistochemistry to particular differential diagnoses and the potential pitfalls.
Data Sources.—Personal experience and review of literature.
Conclusions.—here is no single marker, or combination thereof, that establishes an unequivocal diagnosis of melanoma or nevus. Thus it is necessary to carefully analyze the pattern of expression (patchy versus diffuse) and localization (maturation) in the context of morphologic standard features.
UroVysion, Urine Cytology, and the College of American Pathologists: Where Should We Go From Here?
Authors: Renshaw Andrew A. 
Published: February 2021

Abstract
UroVysion (Abbott Molecular Inc, Des Plaines, Illinois) is a US Food and Drug Administration–approved test for the diagnosis of urothelial carcinoma. Although widely used, there are a variety of different ways to evaluate and interpret the test, and questions remain about the test's cost effectiveness and reproducibility in actual clinical practice. I suggest that the College of American Pathologists has a unique opportunity to create educational programs focusing on borderline or difficult urine cytology and UroVysion samples to provide data upon which to make evidence-based decisions concerning the best use of these tests.
Immunohistochemical Expression of Neurotrophic Tyrosine Kinase Receptors 1 and 2 in Lung Carcinoma: Potential Discriminators Between Squamous and Nonsquamous Subtypes
Authors: Terry Jefferson , De Luca Alessandro , Leung Samuel , Peacock Graeme , Wang Yuzhuo , Elliot W. Mark , Huntsman David 
Published: February 2021

Abstract
Context.—The neurotrophic tyrosine kinase receptors NTRK1 and NTRK2 have been implicated in the pathogenesis of lung carcinomas. NTRK receptor expression has been reported in lung carcinomas; however, the clinical utility of immunohistochemical expression of these receptors is unclear.
Objective.—To compare the immunohistochemical expression profiles of NTRK1 and NTRK2 in various histologic subtypes of lung carcinomas and correlate with patient outcome.
Design.—Six hundred eighty-six unique lung cancer cases (including squamous cell carcinoma, adenocarcinoma, large cell carcinoma, small cell carcinoma, and carcinoid tumor) with clinical outcome data in tissue microarray format were immunohistochemically stained for NTRK1 and NTRK2 using commercially available antibodies, automated immunostaining, and standard protocols.
Results.—Expression of both NTRK1 and NTRK2 correlates strongly with squamous histology. NTRK1 and NTRK2 are highly specific markers (1: 92.8%, 2: 96.4%) of squamous lung carcinoma when compared with the other carcinoma subtypes, including adenocarcinoma. Positive NTRK2 staining in squamous carcinoma correlates with improved disease-specific survival (P &lt; .001) and overall survival (P  =  .047).
Conclusions.—NTRK1 and NTRK2 are potentially useful immunohistochemical markers that may be particularly helpful in separating squamous cell carcinoma from adenocarcinoma.