bluuebunny/crossref_metadata_2025_split huggingface dataset:
Immunohistochemical Expression of Estrogen and Progesterone Receptors in Primary Pulmonary Neuroendocrine Tumors
Authors: Sica Gabriel , Wagner Patrick L. , Altorki Nassar , Port Jeffrey , Lee Paul C. , Vazquez Madeline F. , Saqi Anjali 
Published: February 2021

Abstract
Context.—Lung and breast carcinomas are among the most prevalent cancers. Advances in cancer therapies can provide survival benefit and be potentially curative, even in metastatic disease. Due to the high prevalence of these carcinomas, it is not unusual to encounter lung nodule(s) in a patient with breast carcinoma, and distinguishing between primary and metastatic disease is critical for management/treatment. Occasionally neuroendocrine differentiation is present in breast carcinoma, making its distinction from pulmonary/nonpulmonary neuroendocrine tumors in the lung difficult.
Objective.—To assess estrogen and progesterone receptor expression in the entire spectrum of pulmonary neuroendocrine tumors.
Design.—Seventy-one neuroendocrine neoplasms including typical carcinoids (42), atypical carcinoids (7), small cell carcinomas (14), large cell neuroendocrine carcinomas (2), and combined small cell carcinomas (6) were evaluated for estrogen and progesterone receptors. Mammary and non–small cell lung carcinomas were also stained for comparison.
Results.—The entire spectrum of neuroendocrine neoplasms demonstrated focal to diffuse estrogen (typical carcinoid, 23; atypical carcinoid, 6; small cell carcinoma, 8; large cell neuroendocrine carcinoma, 2; combined small cell carcinoma, 4) and progesterone (typical carcinoid, 11; atypical carcinoid, 2; small cell carcinoma, 7; large cell neuroendocrine carcinoma, 0; combined small cell carcinoma, 2) expression. There was no correlation between sex and estrogen/progesterone status. Estrogen and progesterone staining were also noted in endothelial cells. Relative to neuroendocrine carcinomas, mammary carcinomas expressed estrogen and progesterone more frequently. Non–small cell carcinomas had greater and similar immunoreactivity for estrogen and progesterone, respectively.
Conclusions.—Although estrogen and progesterone receptor staining is frequently associated with breast and gynecologic primaries, it can also be observed in “nontarget” organs. Therefore, presence of estrogen and/or progesterone expression in neuroendocrine tumors involving the lung should not exclude a primary pulmonary neoplasm.
The Role of KRAS Mutation Testing in the Management of Patients With Metastatic Colorectal Cancer
Authors: Monzon Federico A. , Ogino Shuji , Hammond M. Elizabeth H. , Halling Kevin C. , Bloom Kenneth J. , Nikiforova Marina N. 
Published: February 2021

Abstract
Context.—KRAS mutations can be detected in approximately 30% to 40% of all patients with colorectal cancer. Several recent studies have shown that patients with KRAS mutations in codons 12 or 13 in metastatic tumors do not benefit from anti–epidermal growth factor receptor therapy with cetuximab or panitumumab.
Objective.—To review the literature on the role of KRAS mutation testing for management of patients with metastatic colorectal cancer and to discuss testing strategies.
Data Sources.—This review is based on published, peer-reviewed literature; available information from medical organizations (eg, National Comprehensive Cancer Network, American Society of Clinical Oncology, College of American Pathologists); and information from clinical laboratories conducting KRAS mutation analysis.
Conclusions.—Multiple methods for detecting KRAS mutations in colorectal tumors are available, and all methods in current clinical use appear to have adequate clinical sensitivity for predicting a lack of response to cetuximab and panitumumab. Pathologist expertise is essential to quality KRAS testing and to determining effective treatment for patients with metastatic colorectal cancer.
Update on Selected Salivary Gland Neoplasms
Authors: McHugh Jonathan B. , Visscher Daniel W. , Barnes E. Leon 
Published: February 2021

Abstract
Context.—Malignancies of the salivary gland are uncommon and account for 0.3% of all malignancies. In addition to their rarity, diagnosing these tumors can be challenging given the histologic overlap among various subtypes, their morphologic heterogeneity, and the recent recognition of new entities.
Objective.—To provide an overview of 4 salivary gland malignancies that we often see in consultation, with a focus on essential diagnostic features and the importance of reporting pertinent diagnostic information to ensure appropriate clinical management.
Data Sources.—Review of the literature, supplemented by the personal experience of the authors, which is based on their respective institutional experiences and consultation services.
Conclusions.—When diagnosing carcinoma ex pleomorphic adenoma, pathologists must report several important pieces of information to allow for optimal clinical management. In addition to histologic subtype, the degree of differentiation as well as the degree of invasion, if any, must be reported because all have prognostic relevance. Polymorphous low-grade adenocarcinoma can be a challenging diagnosis on biopsy specimens. Evaluation of the tumor periphery and nuclear features should lead to the correct diagnosis in most cases. Salivary duct carcinoma is an aggressive malignancy characterized by histologic resemblance to breast carcinoma, high-grade cytologic features, and expression of androgen receptor. Benign and malignant myoepithelial neoplasms have a broad morphologic spectrum, and immunohistochemistry is important in reaching the correct diagnosis.
Changes in Participant Performance in the “Test-Taking” Environment: Observations From the 2006 College of American Pathologists Gynecologic Cytology Proficiency Testing Program
Authors: Hughes Jonathan H. , Bentz Joel S. , Fatheree Lisa , Souers Rhona J. , Wilbur David C. 
Published: February 2021

Abstract
Context.—Because the consequences of making an interpretive error on a proficiency test are more severe than those made on an educational challenge, the same slide may exhibit different performance characteristics in the 2 different settings.
Objective.—The results of the 2006 College of American Pathologists Gynecologic Cytology Proficiency Testing Program (PAP PT) provide the opportunity to compare the performance characteristics of the field-validated slides in the PAP PT environment with those of the same graded slides in the College of American Pathologists Educational Program (formerly known as the PAP Program).
Design.—All participant responses for negative (category B) and positive (categories C and D) validated slides in the 2006 PAP PT were used to determine the error rates of participants. These data were compared with the historical error rates observed on the same validated slides in the graded PAP Program.
Results.—The performance characteristics of the slides in the PAP PT environment were statistically different from those in the Educational PAP Program. In proficiency testing both cytotechnologists (P &lt; .001) and pathologists (P = .002) were more likely to interpret validated category B slides as category C or D and less likely to interpret category C slides as category B (P &lt; .001). These differences were more pronounced among cytotechnologists than among pathologists.
Conclusions.—In the test-taking environment, both cytotechnologists and pathologists appear to use a defensive strategy that results in “upgrading” of category B slides. This trend is more pronounced among cytotechnologists.
Pancreatic Intraepithelial Neoplasia and Pancreatic Tumorigenesis: Of Mice and Men
Authors: Ottenhof Niki A. , Milne Anya N. A. , Morsink Folkert H. M. , Drillenburg Paul , ten Kate Fiebo J. W. , Maitra Anirban , Offerhaus G. Johan 
Published: February 2021

AbstractContext.—Pancreatic cancer has a poor prognosis with a 5-year survival of less than 5%. Early detection is at present the only way to improve this outlook. This review focuses on the recent advances in our understanding of pancreatic carcinogenesis, the scientific evidence for a multistaged tumor progression, and the role genetically engineered mouse models can play in recapitulating the natural course and biology of human disease.Objectives.—To illustrate the stepwise tumor progression of pancreatic cancer and genetic alterations within the different stages of progression and to review the findings made with genetically engineered mouse models concerning pancreatic carcinogenesis.Data Sources.—A review of recent literature on pancreatic tumorigenesis and genetically engineered mouse models.Conclusions.—Pancreatic cancer develops through stepwise tumor progression in which preinvasive stages, called pancreatic intraepithelial neoplasia, precede invasive pancreatic cancer. Genetic alterations in oncogenes and tumor suppressor genes underlying pancreatic cancer are also found in pancreatic intraepithelial neoplasia. These mutations accumulate during progression through the consecutive stages of pancreatic intraepithelial neoplasia lesions. Also in genetically engineered mouse models of pancreatic ductal adenocarcinoma, tumorigenesis occurs through stepwise progression via consecutive mouse pancreatic intraepithelial neoplasia, and these models provide important tools for clinical applications. Nevertheless differences between mice and men still remain.
Current Concepts in Cervical Pathology
Authors: Park Kay J. , Soslow Robert A. 
Published: February 2021

Abstract
Context.—The correct diagnosis and reporting of cervical in situ and invasive carcinoma are essential for the appropriate clinical management of patients with human papillomavirus–associated disease.
Objectives.—To review common mistakes made in the diagnosis of cervical dysplasia and invasive carcinoma, describe variants and benign mimics of high-grade squamous intraepithelial lesion and adenocarcinoma in situ, and discuss available ancillary studies that can be useful in making the distinctions as well as to review important factors related to prognosis that should be included in the pathology report.
Data Sources.—Review of current literature.
Conclusions.—There are many mimics and variants of cervical squamous and glandular lesions that can be resolved with ancillary studies and careful histologic examination. Prognostically important features, such as tumor size, presence of vascular invasion, and margin status, should always be included in the pathology report.
Histopathologic Features and Clinical Outcomes in 71 Cases of Bladder Diverticula
Authors: Tamas Ecaterina F. , Stephenson Andrew J. , Campbell Steven C. , Montague Drogo K. , Trusty; Dante C. , Hansel Donna E. 
Published: February 2021

Abstract
Context.—Bladder diverticula often come to clinical attention when complications or malignancy occur, although limited information is available regarding histopathologic features and clinical outcomes.
Objective.—To identify the morphologic findings, neoplastic subtypes, and clinical outcomes by reviewing all bladder diverticula that underwent pathologic sampling for primary diverticular processes at the Cleveland Clinic.
Design.—Hematoxylin-eosin slides from 71 cases of bladder diverticula were reviewed. Clinicopathologic features and patient outcomes were obtained from a retrospective review of patient records.
Results.—Patient ages ranged from 1 to 81 years (mean, 55 years), and the ratio of males to females was 68:3. Diverticular size ranged from 1 to 18 cm (mean, 5.3 cm) and often involved the lateral walls (38/71; 54%). Neoplastic changes were present in half of cases (36/71; 51%), including both noninvasive (16/36; 44%) and invasive (20/ 36; 56%) carcinoma. Of the invasive carcinomas, less-common subtypes included small cell carcinoma (n = 3), squamous cell carcinoma (n = 2), and adenocarcinoma (n = 1); 9 cases were pT1 (45%) and 11 cases were pT3 (55%). Follow-up for patients with benign findings demonstrated no subsequent neoplastic bladder disease. Patient follow-up for neoplastic diverticula (median, 27 months) demonstrated 4 cases of local recurrence and 3 cases of subsequent metastases. Of 9 patients with pT1 disease, only 1 patient (11%) developed subsequent metastases, whereas patients with pT3 disease demonstrated a higher rate of both local recurrence (3/11; 27%) and subsequent metastases (2/11; 18%).
Conclusions.—Patients with invasive carcinoma in diverticula have an increased frequency of less-common bladder cancer subtypes, and those with pT3 disease are at increased risk for subsequent progression.
Papillary Neoplasms of the Breast: A Review
Authors: Ueng Shir-Hwa , Mezzetti Thomas , Tavassoli Fattaneh A. 
Published: February 2021

Abstract
Context.—Interpretation of papillary lesions of the breast remains a challenging task because of the wide morphologic spectrum encountered in the benign, atypical, and malignant subtypes. Data on clinical significance and outcome of papillary lesions, with superimposed atypia or areas similar to ductal carcinoma in situ partially replacing the benign elements, are sparse. Furthermore, complete excision of even a fully developed papillary carcinoma confined to a dilated or cystic duct is associated with an excellent prognosis, whereas a complex papilloma extending into multiple branches of a duct may ultimately recur as a carcinoma because of incomplete excision of microscopic foci. This makes an outcome-based classification difficult.
Objective.—An arbitrary yet practical approach to classification is outlined, with discussion of methods to circumvent the various diagnostic difficulties. The limitations in precise diagnosis of papillary lesions in aspirates are addressed, and the implications of finding papillary lesions in core biopsies are discussed. Although the focus is on intraductal lesions, associated invasive carcinomas and invasive micropapillary carcinoma are also presented.
Data Sources.—The literature on papillary lesions and invasive micropapillary carcinoma is reviewed.
Conclusions.—It would be prudent to completely excise any papillary lesion that has not been entirely removed by the initial core biopsy. The optimal management of localized papillary lesions is complete excision with a small rim of uninvolved breast tissue without any prior needle instrumentation if and when the papillary nature can be determined by imaging. Thus managed, most of these lesions behave indolently, and outcome is usually excellent.
Laboratory-Guided Detection of Disease Outbreaks: Three Generations of Surveillance Systems
Authors: Sintchenko Vitali , Gallego Blanca 
Published: February 2021

AbstractContext.—Traditional biothreat surveillance systems are vulnerable to incomplete and delayed reporting of public health threats.Objective.—To review current and emerging approaches to detection and monitoring of biothreats enabled by laboratory methods of diagnosis and to identify trends in the biosurveillance research.Data Sources.—PubMed (1995 to December 2007) was searched with the combined search terms “surveillance” and “infectious diseases.” Additional articles were identified by hand searching the bibliographies of selected papers. Additional search terms were “public health,” “disease monitoring,” “cluster,” “outbreak,” “laboratory notification,” “molecular,” “detection,” “evaluation,” “genomics,” “communicable diseases,” “geographic information systems,” “bioterrorism,” “genotyping,” and “informatics.” Publication language was restricted to English. The bibliographies of key references were later hand searched to identify articles missing in the database search. Three approaches to infectious disease surveillance that involve clinical laboratories are contrasted: (1) laboratory-initiated infectious disease notifications, (2) syndromic surveillance based on health indicators, and (3) genotyping based surveillance of biothreats. Advances in molecular diagnostics enable rapid genotyping of biothreats and investigations of genes that were not previously identifiable by traditional methods. There is a need for coordination between syndromic and laboratory-based surveillance. Insufficient and delayed decision support and inadequate integration of surveillance signals into action plans remain the 2 main barriers to efficient public health monitoring and response. Decision support for public health users of biosurveillance alerts is often lacking.Conclusions.—The merger of the 3 scientific fields of surveillance, genomics, and informatics offers an opportunity for the development of effective and rapid biosurveillance methods and tools.
Chromosomal 3 and 8 Status Within Hepatic Metastasis of Uveal Melanoma
Authors: Singh Arun D. , Tubbs Raymond , Biscotti Charles , Schoenfield Lynn , Trizzoi Pierre 
Published: February 2021

Abstract
Context.—Several studies have evaluated clinical, histopathologic, cytogenetic, and molecular prognostic variables in uveal melanoma. However, it is not known whether the primary tumor cells maintain these aggressive attributes at the metastatic sites.
Objective.—To determine the status of chromosomes 3 and 8q and c-myc amplification using fluorescence in situ hybridization on hepatic metastatic lesions of primary uveal melanoma.
Design.—Ten patients with uveal melanoma with needle core biopsy–confirmed hepatic metastasis. Representative paraffin blocks were selected based on review of hematoxylin-eosin–stained sections. Fluorescence in situ hybridization was performed for detection of monosomy 3 and amplification at the 8q24 MYC locus using standard methods. The tricolor chromosome enumeration probe 8 (CEP8)/ IGH/MYC and the Urovysion probe consisting of CEP3, CEP7, CEP17, and 9P21 probes were used. A total of 200 interphase cells were scored.
Results.—Hepatic metastasis was confirmed in each case by needle core biopsy. Fluorescence in situ hybridization analysis revealed chromosome 3 monosomy in 5 of the 8 cases that could be satisfactorily evaluated. Aneusomy of chromosome 8 was observed in 2 cases. MYC amplification was observed in 5 samples. In a single case where the primary tumor was treated by enucleation, the chromosomal monosomy 3 and aneusomy of chromosome 8 were present both in the primary tumor and its hepatic metastatic lesion.
Conclusions.—The presence of cytogenetic changes within the metastatic lesions confirms that chromosome 3 monosomy and aneusomy of chromosome 8 are not just markers of metastatic potential of the primary tumor but are also present within the hepatic metastatic lesions.
Idiopathic Fibroinflammatory Disease of the Face, Eyelids, and Periorbital Membrane With Immunoglobulin G4–Positive Plasma Cells
Authors: Mehta Manisha , Jakobiec Frederick , Fay Aaron 
Published: February 2021

Abstract
Progressive sclerosing orbital pseudotumors are a subset of usually primary and localized idiopathic fibroinflammatory disorders. We report on a 66-year-old man who developed this condition along the facial tissue planes with extension into the orbit and preferential involvement of the periorbital membrane. Fibrocollagenous tissue with scattered lymphoid aggregates without follicle formation dominated the process. There was a light dispersion of B and T lymphocytes and histiocytes in the stroma. Immunoglobulin G4 (IgG4)–positive plasma cells (&gt;35 per high-power field) were identified mostly in the lymphoid clusters, as has been discovered in similar IgG4–related fibrosclerosing conditions of other nonorbital sites. No associated systemic disease emerged during a 20-year clinical course. Previously reported orbital cases of IgG4-positive disease have all involved the lacrimal gland, usually bilaterally, and more closely resembled hypercellular reactive lymphoid hyperplasias with moderate interlobular fibrosis, rather than representing an essentially sclerosing process from the beginning.
Diagnosis of Metastatic Neoplasms: A Clinicopathologic and Morphologic Approach
Authors: Marchevsky Alberto M. , Gupta Ruta , Balzer Bonnie 
Published: February 2021

AbstractContext.—The diagnosis of the site of origin of metastatic neoplasms often poses a challenge to practicing pathologists. A variety of immunohistochemical and molecular tests have been proposed for the identification of tumor site of origin, but these methods are no substitute for careful attention to the pathologic features of tumors and their correlation with imaging findings and other clinical data. The current trend in anatomic pathology is to overly rely on immunohistochemical and molecular tests to identify the site of origin of metastatic neoplasms, but this “shotgun approach” is often costly and can result in contradictory and even erroneous conclusions about the site of origin of a metastatic neoplasm.Objective.—To describe the use of a systematic approach to the evaluation of metastatic neoplasms.Data Sources.—Literature review and personal experience.Conclusions.—A systematic approach can frequently help to narrow down differential diagnoses for a patient to a few likely tumor sites of origin that can be confirmed or excluded with the use of selected immunohistochemistry and/or molecular tests. This approach involves the qualitative evaluation of the “pretest and posttest probabilities” of various diagnoses before the immunohistochemical and molecular tests are ordered. Pretest probabilities are qualitatively estimated for each individual by taking into consideration the patient's age, sex, clinical history, imaging findings, and location of the metastases. This estimate is further narrowed by qualitatively evaluating, through careful observation of a variety of gross pathology and histopathologic features, the posttest probabilities of the most likely tumor sites of origin. Multiple examples of the use of this systematic approach for the evaluation of metastatic lesions are discussed.
Kikuchi-Fujimoto Disease
Authors: Hutchinson Charles Blake , Wang Endi 
Published: February 2021

Abstract
Kikuchi-Fujimoto disease, or histiocytic necrotizing lymphadenitis, is a self-limited condition, characterized by benign lymphadenopathy with associated fevers and systemic symptoms. It most commonly affects adults younger than 40 years of age and of Asian descent. Involved lymph nodes demonstrate paracortical areas of apoptotic necrosis with abundant karyorrhectic debris and a proliferation of histiocytes, plasmacytoid dendritic cells, and CD8+ T cells in the absence of neutrophils. Kikuchi-Fujimoto disease is thought to have 3 evolving phases: proliferative, necrotizing, and xanthomatous. The etiology is unknown, although viruses and autoimmune mechanisms have been proposed. No specific laboratory tests contribute to the diagnosis. Diagnosis requires histopathologic examination and exclusion of other factors by ancillary studies. Non-Hodgkin lymphoma and systemic lupus erythematosus should be ruled out before diagnosis of Kikuchi-Fujimoto disease, given the overlapped clinical and histologic features as well as the different therapeutic approaches. Treatment involves supportive measures, and the symptoms usually resolve spontaneously within 4 months.
Selected Pseudoneoplastic Lesions of the Skin
Authors: Wick Mark R. , Patterson James W. 
Published: February 2021

Abstract
Context.—Pseudoneoplastic cutaneous lesions are diverse, not only morphologically but also with respect to their causes and cellular lineages. They include proliferations of epithelial, as well as mesenchymal, elements.
Objective.—This review aims to consider selected lesions in the aforementioned groups, contrasting them with histologically similar neoplasms of the skin in a differential diagnostic setting.
Data Sources.—Information used in assembling this discussion was drawn from the published literature on cutaneous pseudoneoplasms, using an Internet-based search engine. The authors' collective experience was also used in writing this review.
Conclusions.—Sufficient clinical and morphologic differences exist in virtually all instances to separate pseudoneoplastic cutaneous proliferations from the tumors that they imitate.