bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clear Cell Adenocarcinoma of the Urinary Bladder: A Short Review
Authors: Adeniran Adebowale J. , Tamboli Pheroze 
Published: February 2021

Abstract
In this short review, we discuss clear cell adenocarcinoma of the urinary bladder, a rare tumor that primarily affects women. The histogenesis of this neoplasm is uncertain; in some tumors the clinicopathologic and histologic features are suggestive of a müllerian origin. Clear cell adenocarcinoma consists of cells with abundant clear cytoplasm, arranged in solid, glandular, or tubulocystic patterns. These tumors are positive for pancytokeratin, cytokeratin 7, and CA 125 immunohistochemical stains. Patients typically present with gross hematuria, dysuria, and discharge. The natural history is poorly understood and patient outcomes remain unclear. Currently, surgery is the treatment of choice. Nephrogenic adenoma is the most important differential diagnostic consideration, followed by metastatic clear cell carcinoma.
Nonneoplastic Kidney Diseases in Adult Tumor Nephrectomy and Nephroureterectomy Specimens: Common, Harmful, Yet Underappreciated
Authors: Henriksen Kammi J. , Meehan Shane M. , Chang Anthony 
Published: February 2021

AbstractContext.—Nonneoplastic kidney diseases, such as arterionephrosclerosis and/or diabetic nephropathy, are commonly encountered in tumor nephrectomy and nephroureterectomy specimens. Although any nonneoplastic kidney disease may be encountered in these resection specimens by chance, additional diseases that may be related to the underlying neoplasm or its treatment regimen include thrombotic microangiopathy, Amyloid A amyloidosis, membranous nephropathy, immunoglobulin A nephropathy, membranoproliferative glomerulonephritis, pauci-immune crescentic glomerulonephritis, focal segmental glomerulosclerosis, minimal-change disease, acute interstitial nephritis, and xanthogranulomatous pyelonephritis. Given the morbidity of chronic kidney disease and the relatively favorable 5-year survival rates for urothelial and renal cell carcinomas, accurate evaluation of the nonneoplastic kidney parenchyma is important.Objectives.—We will discuss our approach for evaluating the nonneoplastic kidney parenchyma in tumor nephrectomy and nephroureterectomy specimens. The pathologic features of the aforementioned kidney diseases as well as pertinent references will be reviewed. The identification of glomerular abnormalities, including mesangial sclerosis or hypercellularity, segmental sclerosis, crescent formation, glomerulitis, or glomerular basement membrane alterations, should lead to additional immunofluorescence and electron microscopic studies. Safeguards to ensure that the nonneoplastic parenchyma is not overlooked include adding this important parameter to synoptic reports and obtaining periodic acid–Schiff and/or Jones methenamine silver stains prior to microscopic evaluation of the neoplasm.Data Sources.—Relevant literature and University of Chicago Medical Center pathology archives.Conclusions.—The practicing surgical pathologist should be aware of the importance of both correctly classifying the resected renal or urothelial neoplasm and the concomitant nonneoplastic kidney disease that may be present in these specimens.
Molecular Biology Underlying the Clinical Heterogeneity of Prostate Cancer: An Update
Authors: Mackinnon A. Craig , Yan Benjamin C. , Joseph Loren J. , Al-Ahmadie Hikmat A. 
Published: February 2021

AbstractContext.—Recent studies have uncovered a number of possible mechanisms by which prostate cancers can become resistant to systemic androgen deprivation, most involving androgen-independent reactivation of the androgen receptor. Genome-wide expression analysis with microarrays has identified a wide array of genes that are differentially expressed in metastatic prostate cancers compared to primary nonrecurrent tumors. Recently, recurrent gene fusions between TMPRSS2 and ETS family genes have been identified and extensively studied for their role in prostatic carcinoma.Objective.—To review the recent developments in the molecular biology of prostate cancer, including those pertaining to the androgen receptor and the newly identified TMPRSS2-related translocations.Data Sources.—Literature review and personal experience.Conclusions.—Prostatic adenocarcinoma is a heterogeneous group of neoplasms with a broad spectrum of pathologic and molecular characteristics and clinical behaviors. Numerous mechanisms contribute to the development of resistance to androgen ablation therapy, resulting in ligand-independent reactivation of the androgen receptor, including amplification, mutation, phosphorylation, and activation of coreceptors. Multiple translocations of members of the ETS oncogene family are present in approximately half of clinically localized prostate cancers. TMPRSS2:ERG gene rearrangement appears to be an early event in prostate cancer and is not observed in benign or hyperplastic prostatic epithelium. Duplication of TMPRSS2:ERG appears to predict a worse prognosis. The relationship between TMPRSS2:ERG gene rearrangement and other morphologic and prognostic parameters of prostate cancer is still unclear.
Recent Developments in Liver Pathology
Authors: Yan Benjamin C. , Hart John A. 
Published: February 2021

AbstractContext.—Hepatocellular carcinoma is the sixth most common malignancy and the third leading cause of cancer deaths worldwide, making pathologic identification of precursor lesions essential. Recent molecular genetic, pathologic, and clinical data have led to the stratification of hepatic adenomas into subgroups with unique molecular profiles and varying potential for malignant transformation, as well as to the reclassification of telangiectatic focal nodular hyperplasia as telangiectatic adenoma. Clinical, morphologic, and molecular genetic studies have also established juvenile hemochromatosis and pediatric nonalcoholic steatohepatitis as entities distinct from their adult counterparts.Objective.—To review the recent molecular genetic characterization of telangiectatic hepatic adenomas and juvenile hemochromatosis, as well as the recent clinicopathologic characterization of pediatric nonalcoholic steatohepatitis.Data Sources.—Literature review, personal experience, and material from the University of Chicago.Conclusions.—Basic science and translational research have led to the classification of many pathologic entities of the liver according to molecular genetic and protein expression profiles that correspond to traditional morphologic categories. Insights into signal transduction pathways that are activated in, and protein expression patterns unique to, an individual disease may lead to the development of new therapeutic agents and novel diagnostic biomarkers.
Proceedings of the Consensus Meetings From the International Retinoblastoma Staging Working Group on the Pathology Guidelines for the Examination of Enucleated Eyes and Evaluation of Prognostic Risk Factors in Retinoblastoma
Authors: Sastre Xavier , Chantada Guillermo L. , Doz François , Wilson Matthew W. , de Davila Maria T. G. , Rodríguez-Galindo Carlos , Chintagumpala Murali , Chévez-Barrios Patricia 
Published: February 2021

AbstractRetinoblastoma is the most common intraocular malignant childhood tumor in need of prospective clinical trials to address important unanswered questions about biology, treatment, and prognostic factors. Currently, there is controversy about the definitions for choroidal invasion and an inconsistency in the handling of eyes with retinoblastoma. The International Retinoblastoma Staging Working Group (IRSWG) composed of 58 participants from 24 countries on 4 continents had a series of Internet meetings to discuss the staging and tissue handling guidelines to reach consensus for adequate processing, establishing definitions of histopathologic risk factors, and reporting of enucleated eyes with retinoblastoma to serve as the basis for clinical trials and studies to validate the proposed criteria. The meetings were facilitated by the International Outreach Program of the St. Jude Children's Research Hospital through Cure4Kids. The retinoblastoma guidelines from the Children's Oncology Group, the French Society for Pediatric Cancers, the Association of Directors of Anatomic and Surgical Pathology, and some published data were the basis for this consensus document. Discussions of the feasibility, practicality, and efficacy of the guidelines and criteria resulted in this report. The consensus definitions reached included definition of massive choroidal invasion stated as a maximum diameter of invasive tumor focus of 3 mm or more that may reach the scleral tissue. Focal choroidal invasion is defined as a tumor focus of less than 3 mm and not reaching the sclera. Optic nerve invasion is classified as prelaminar, laminar, retrolaminar, or tumor at surgical margin, and the measurement of the depth of invasion should also be recorded. These guidelines also address handling of the enucleated eye with retinoblastoma in an efficient, practical, and feasible manner for a meaningful diagnosis. The consensus criteria reached by the IRSWG should be validated through prospective clinical trials and studies.
High-Risk Features and Tumor Differentiation in Retinoblastoma: A Retrospective Histopathologic Study
Authors: Eagle Jr Ralph C. 
Published: February 2021

Abstract
Context.—Certain histopathologic risk factors in enucleated eyes are important indicators for adjuvant chemotherapy in patients with retinoblastoma.
Objectives.—To determine the frequency of histopathologic risk factors in a large series of retinoblastomas treated by enucleation on file in the pathology laboratory of a large American eye hospital, assess the relationship between tumor differentiation and age at enucleation, and investigate the frequency of photoreceptor differentiation and the role of retinoma/retinocytoma as retinoblastoma precursor.
Design.—Retrospective histopathologic review of 387 eyes with retinoblastoma treated by enucleation including 297 with no prior treatment.
Results.—Fifty-five of 297 untreated eyes (18.5%) had high-risk features. Retrolaminar optic nerve invasion was present in 31 (10.4%), and 24 (8.1%) had massive uveal invasion (defined as &gt;3 mm in diameter). Of the high-risk eyes, 70.9% had iris neovascularization and 60% had neovascular glaucoma. There was a statistically significant inverse relationship between age at enucleation and the degree of tumor differentiation, evidenced by the presence of rosettes. Tumors in older children tended to be poorly differentiated, while rosettes were often numerous in the tumors of younger infants. In all, 20.4% of tumors contained foci of photoreceptor differentiation, which localized in the base of a predominantly endophytic tumor in about one-fourth. Lack of correlation between photoreceptor differentiation and age at enucleation is consistent with early or prenatal malignant transformation. Both preceding observations provide evidence for the hypothetical role of retinoma as a retinoblastoma precursor.
Conclusions.—Slightly less than 1 in 5 infants with retinoblastoma treated by enucleation at a large American eye hospital would require adjuvant chemotherapy on the basis of existing high-risk histopathologic features. Retinoblastomas become progressively less differentiated with time and may be spawned by precursor retinomas.
Primary Intraocular Lymphoma
Authors: Faia Lisa J. , Chan Chi-Chao 
Published: February 2021

Abstract
Primary intraocular lymphoma, recently suggested to be renamed primary retinal lymphoma, is a subset of primary central nervous system lymphoma and is usually an aggressive diffuse large B-cell lymphoma. Between 56% and 85% of patients who initially present with primary intraocular lymphoma alone will develop cerebral lesions. Patients typically complain of decreased vision and floaters, most likely secondary to the chronic vitritis and subretinal lesions. The diagnosis of primary intraocular lymphoma can be difficult to make and requires tissue for diagnosis. The atypical lymphoid cells are large and display a high nuclear to cytoplasmic ratio, prominent nucleoli, and basophilic cytoplasm. Flow cytometry, immunohistochemistry, cytokine analysis, and gene rearrangements also aid in the diagnosis. Local and systemic treatments, such as chemotherapy and radiation, are employed, although the relapse rate remains high.
Prognostic Value of E-Cadherin, β-Catenin, CD44v6, and HER2/neu in Metastatic Cutaneous Adenocarcinoma
Authors: Pozdnyakova Olga , Hoang Mai M. P. , Dresser Karen A. , Mahalingam Meera 
Published: February 2021

Abstract
Context.—Our recent experience with a patient developing cutaneous metastases within 3 months of diagnosis of esophageal adenocarcinoma suggests that altered expression of the cellular adhesion molecules, E-cadherin and CD44v6, may have had a role to play in the rapid onset of metastases.
Objective.—To corroborate these findings, we designed a cross-sectional study to investigate the expression of select molecules involved in the metastatic cascade.
Design.—E-cadherin, β-catenin, CD44v6, and HER2/neu immunohistochemical stains were performed on archival materials of metastatic adenocarcinoma to the skin from 27 patients and the available corresponding primary tumors in 10 patients. The primary sites included breast (n = 10; 37%), gastrointestinal tract (n = 10; 37%), ovary (n = 1; 4%), thyroid (n = 2; 7%), lung (n = 1; 4%), and unknown primary (n = 3; 11%).
Results.—Expression of all markers was noted with the most significant increases observed in β-catenin (26 of 27 cases; 96%), followed by CD44v6 (24 of 27 cases; 89%), E-cadherin (22 of 27 cases; 82%), and HER2/neu (11 of 27 cases; 41%). Contrasting expression of these molecules in the primary versus the metastatic tumors, enhanced expression of CD44v6 was observed in the cutaneous metastases relative to the primary in 6 of 10 (60%) cases. Of interest, 2 of these 6 cases (33%) also showed reduction in E-cadherin—a member of the cadherin family functioning as an invasion suppressor molecule.
Conclusions.—These findings reinforce the complexities of the metastatic cascade and imply that the variation in adhesive properties of tumor cells is, perhaps, a consequence of the difference in density of the molecules mediating this process.
Evaluation of Microbiologic and Hematologic Parameters and E-Selectin as Early Predictors for Outcome of Neonatal Sepsis
Authors: El Sayed Zaki Maysaa , El Sayed Hesham 
Published: February 2021

AbstractContext.—Early diagnosis of neonatal sepsis is mandatory. Various markers are used to diagnose the condition.Objective.—To evaluate the diagnostic value of various clinical data and hematologic parameters, such as total leukocyte count, absolute neutrophil count, immature to total neutrophil ratio, and soluble E-selectin (sE-selectin) in identification and outcome of neonatal sepsis.Design.—Newborn infants with a clinical diagnosis of sepsis in the neonatal intensive care unit at Mansoura University Children's Hospital during the period between July 2007 and December 2007 were eligible for study. In addition, 30 healthy neonates were included in the study. Complete hematologic and microbiologic laboratory investigations were performed, and serum E-selectin was measured.Results.—Plasma sE-selectin levels were significantly higher (P &lt; .001) in infected infants (mean [SD], 156.9 [77.0] ng/mL) than in noninfected (mean [SD], 88.8 [47.1] ng/mL) and healthy infants (mean [SD], 8.67 [3.74] ng/ mL). Infants with gram-negative sepsis had higher sE-selectin levels than did those with gram-positive sepsis (P = .04). C-reactive protein was the best laboratory test for diagnosis of neonatal sepsis, with an overall sensitivity and specificity of 86% and 97%, respectively. Performing sE-selectin with C-reactive protein or immature to total ratio tests increased the specificity, but reduced the sensitivity, of the tests for the determination of neonatal sepsis. Plasma sE-selectin levels were higher in nonsurvivors than in survivors (P = .01) and were higher in those with hemodynamic dysfunction than in those without hemodynamic dysfunction (P &lt; .001).Conclusions.—We conclude that plasma sE-selectin levels are elevated in neonatal sepsis. Significant elevation was associated with gram-negative sepsis. Plasma sE-selectin had low diagnostic value when used alone or in combination with other tests; however, it can be used as a prognostic indicator for the outcome of neonatal sepsis.
Arteriosclerosis: Rethinking the Current Classification
Authors: Fishbein Gregory A. , Fishbein Michael C. 
Published: February 2021

Abstract
Context.—Arteriosclerosis is the vascular disease that is the leading cause of mortality in industrialized countries. Currently, there are 3 lesions within the broader category of arteriosclerosis: atherosclerosis, Mönckeberg medial calcific sclerosis, and arteriolosclerosis.
Objective.—In this review, we discuss the history of the terminology and current classification of arteriosclerosis and problems with the current classification. We also discuss recently described new arterial lesions that are not in the current classification.
Data Sources.—In spite of the prevalence and importance of arteriosclerotic vascular disease, and the widespread use of the current terminology, there are major problems with the current classification: (1) the current classification has an inconsistent naming convention, (2) the classification fails to use terms that accurately describe the lesions, and (3) important arterial lesions are absent from the classification. In addition, although the terms arteriosclerosis and atherosclerosis describe different lesions, these terms are often used interchangeably.
Conclusion.—Consideration should be given for a new more inclusive and accurate classification of “arteriosclerotic” lesions that more accurately reflects the pathology of these important vascular lesions.
Pseudoangiomatous Stromal Hyperplasia of the Breast
Authors: AbdullGaffar Badr 
Published: February 2021

Abstract
Pseudoangiomatous stromal hyperplasia is a relatively common lesion of the breast. In general, it is less commonly found as a clinically palpable mass and is more commonly found as incidental microscopic foci. It is a benign proliferative, probably neoplastic, hormonally driven process of the mammary stromal myofibroblasts. The clinical, radiologic, and cytologic findings can resemble those of fibroadenoma. Histologically, it can be confused with low-grade angiosarcoma. The exact etiology of pseudoangiomatous stromal hyperplasia is still controversial, but a neoplastic process of the stromal myofibroblasts, with a hormonal stimulus in its development and progression, is the favored theory. Most lesions can be cured by complete surgical excision, and patients undergoing the excision have a good prognosis.
Rare Nerve Lesions of Non–Nerve Sheath Origin: A 17-Year Retrospective Series
Authors: Strom Tobin , Kleinschmidt-DeMasters Bette K. , Donson Andrew , Foreman Nicholas K. , Lillehei Kevin O. 
Published: February 2021

AbstractContext.—Peripheral nerve masses are frequently encountered in surgical pathology practice. However, once a peripheral nerve mass is determined not to be a nerve sheath neoplasm, differential diagnostic considerations drop off sharply.Objective.—To review our experience with surgically resected nerve masses.Design.—Retrospective search of pathology database. Rare neoplasms were studied by cytogenetic analysis or gene microarray.Results.—Four hundred fifty-eight cases were identified. After elimination of common lesions (mostly nerve sheath tumors), 37 cases (8%) remained, almost all of which were of non–nerve sheath origin: for example, hemangioma, metastatic neuroendocrine pancreatic carcinoma, meningiomas invading nerve fascicles, and primary extrarenal rhabdoid tumor and Ewing sarcoma of nerve. The latter showed rearrangement of the EWSR1 locus (22q12). The gene expression pattern of an undifferentiated sarcoma, presenting as ropelike nerve enlargement, clustered with malignant peripheral nerve sheath neoplasms but not other sarcomas or neuroepithelial tumors.Conclusions.—Diverse benign and malignant conditions can affect peripheral nerve.
Crossword Puzzles: Active Learning in Undergraduate Pathology and Medical Education
Authors: Saxena Anurag , Nesbitt Raenelle , Pahwa Punam , Mills Sheryl 
Published: February 2021

AbstractContext.—Second-year medical students are introduced to many new terms and concepts in a short time frame in the hematology system and the neoplasia section of the undergraduate pathology course. It is a challenge to provide adequate practice and necessary repetition to reinforce key concepts.Objective.—To determine student perceptions of the usefulness of crosswords as a quick and effective way to reinforce essential concepts and vocabulary.Design.—Crosswords with ensured content validity built on a free Internet resource were completed by the students in collaborative and cooperative groups of 6 to 7 with a reward for the first group to successfully complete the puzzle. Student perceptions of the value of crosswords for their learning were examined in 2003 (39 students) with a survey of yes or no responses and in 2004 (41 students) with a survey using questions with a 5-point Likert scale.Results.—Many students (37 of 39 in 2003 and 24 of 41 in 2004) indicated that crosswords were useful and contributed to their learning. Specifically, crosswords were found to be useful for identifying key concepts and vocabulary and for their collaborative and competitive aspects. Written and informal comments indicated student enthusiasm for and a desire to participate in more of these exercises. Students have transferred this review strategy to other classes and the peer teachers have expressed an interest in it as an adjunct teaching tool.Conclusions.—The judicious use of crosswords was useful for near transfer content and provided an opportunity to discuss and recall essential concepts, think critically, and collaborate in small groups.