bluuebunny/crossref_metadata_2025_split huggingface dataset:
Diagnosing Nonneoplastic Lesions in Nephrectomy Specimens
Authors: Truong Luan D. , Shen Steven S. , Park Moon-Hyang , Krishnan Bhuvaneswari 
Published: February 2021

AbstractContext.—Nonneoplastic changes are often identified in nephrectomy specimens removed for renal neoplasms. Although they may be of prognostic or therapeutic importance, they are often overlooked. Nephrectomy is also performed for nonneoplastic lesions, the most frequent of which are urinary obstruction and end-stage renal disease, but the tissue diagnosis of these conditions and the implicated clinicopathologic correlation may not be well appreciated.Objective.—To outline these nonneoplastic lesions with special attention to important diagnostic caveats and clinicopathologic correlations.Data Sources.—The presented information was derived from literature, personal experience, and review of case materials at the authors' institutions.Results.—Nonneoplastic lesions are seen in most (90%) nephrectomy specimens removed for renal neoplasms. Although these lesions span the spectrum of “medical” kidney diseases, the most frequent of them are hypertensive nephrosclerosis and diabetic nephropathy. Recognition of these diseases is important because they are often first diagnosed and later confirmed clinically. Furthermore, the severity of these lesions may predicate both short- and long-term renal function and thus help guide treatment. Among conditions that necessitate nephrectomy, advanced urinary obstruction, end-stage renal disease, and end-stage renal disease with acquired cystic changes are probably the most frequent. These conditions have characteristic morphologic features, but they may be associated with superimposing lesions previously not well described. These superimposing lesions may create diagnostic confusion; yet, some of them are the reason for nephrectomy. Thus, acute bacterial infection, urine polyp, granulomatous pyelitis, papillary necrosis, massive bleeding, and renal dysplasia can develop against the background of obstructive nephropathy. Renal neoplasms may develop from the background of end-stage renal disease without cystic changes. A renal neoplasm or massive bleeding with or without neoplasm is usually the reason for nephrectomy in kidney with acquired cystic kidney diseases. Thus, while nonneoplastic changes are frequent in nephrectomy specimens, they are often unrecognized. Awareness of these conditions and a familiarity with their diagnostic features as well as the implicated clinicopathologic correlation should help obviate this diagnostic problem.
Focal Segmental Glomerulosclerosis: A Morphologic Diagnosis in Evolution
Authors: Thomas David B. 
Published: February 2021

Abstract
Context.—The diagnosis of focal segmental glomerulosclerosis (FSGS) is a descriptive pathologic diagnosis that in certain clinical situations (ie, primary or idiopathic) becomes its own disease. The clinical diversity, varied histology, and nonspecific morphologic features of FSGS all contribute to the complexity and problematic nature in making a pathologic diagnosis of FSGS. The definitions of the disease and of the morphologic features have evolved during the last century.
Objective.—To review historic and morphologic features of FSGS in order to demonstrate a practical approach in achieving a pathologic diagnosis of FSGS on kidney tissue.
Data Sources.—In 2004 a working proposal on the pathologic (morphologic) classification of FSGS was published in an attempt to unify the complexity of diagnosing FSGS, and it has shown to be both reproducible and with unique clinical implications for each defined FSGS variant.
Conclusions.—An accurate diagnosis of FSGS can be challenging. During the last few decades, numerous new scientific discoveries have enriched our knowledge of pathogenetic mechanisms of nephrotic syndrome. Thus, it is expected there will be a need for a further modification to a morphologic classification and that the pathologist's role in diagnosing FSGS will remain in evolution. This review recapitulates the history of the pathologic diagnosis of FSGS and a current morphologic classification, hopefully opening up a discussion for further modifications that reflect the status of knowledge evolving in the 21st century.
The Pathology and Genetics of Metastatic Pancreatic Cancer
Authors: Yachida Shinichi , Iacobuzio-Donahue Christine A. 
Published: February 2021

AbstractContext.—Metastatic disease is the most critical determinant of resectability of pancreatic cancer and accounts for the poor outcome of patients with this disease. Thus, a better understanding of metastatic pancreatic cancer will afford new opportunities for therapeutic intervention.Objective.—To summarize and discuss the current understanding of the clinical and molecular features of metastatic pancreatic cancer.Data Sources.—Published literature on advanced stage pancreatic cancer, pancreatic cancer metastasis, and autopsy findings in patients with pancreatic cancer.Conclusions.—In the clinical setting, it can be difficult to distinguish a metastatic pancreatic carcinoma from primary neoplasms in the liver, lung, or ovary. However, immunolabeling for DPC4 protein as part of a diagnostic panel is useful for making this distinction. Emerging data from a variety of investigators now indicate that overexpression of EphA2, loss of DPC4 and MKK4, and aberrant activation of the Hedgehog signaling pathway are associated with metastatic propensity of pancreatic cancers, providing novel therapeutic targets for the most lethal stage of this disease.
Morphologic Features of Adenocarcinoma of the Lung Predictive of Response to the Epidermal Growth Factor Receptor Kinase Inhibitors Erlotinib and Gefitinib
Authors: Zakowski Maureen F. , Hussain Sanaa , Pao William , Ladanyi Marc , Ginsberg Michelle S. , Heelan Robert , Miller Vincent A. , Rusch Valerie W. , Kris Mark G. 
Published: February 2021

AbstractContext.—A subset of lung adenocarcinomas appears preferentially sensitive to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). EGFR-activating mutations and never smoking are associated with response to TKIs.Objectives.—To describe the morphology of adenocarcinomas responsive to TKIs, compare it to tumors in nonresponding patients, and correlate findings with EGFR mutations, gene copy number, and protein expression.Design.—Material from 52 EGFR TKI-treated patients was studied: 29 responders and 23 nonresponders. Adenocarcinoma subtypes and morphologic features were defined in histologic and cytologic material. EGFR mutations were detected by sequencing, copy number by chromogenic in situ hybridization, and expression by immunohistochemistry.Results.—Tumors from TKI responders tended to be better-differentiated adenocarcinomas with bronchioloalveolar carcinoma components. Nonresponders showed more heterogeneous morphology, higher grade, and more subtypes, and were more likely to show solid growth. In nonresponders, the only pure bronchioloalveolar carcinoma was mucinous, a subtype known to be negative for EGFR mutations. Using World Health Organization criteria, all tumors in both groups other than pure bronchioloalveolar carcinomas would be classified as adenocarcinomas, mixed subtype, thereby obscuring some of these distinctions. EGFR mutations were significantly more common in responders (22/29 vs 0/23; P &lt; .001). Immunohistochemistry and chromogenic in situ hybridization results were not significantly correlated with EGFR mutations or response to TKIs in this study.Conclusions.—Overall, histologic differences exist between tumors that respond to TKIs and those that do not, although sampling affects classification, and there is significant histologic overlap between the 2 groups. Response is strongly associated with EGFR mutations.
College of American Pathologists Considerations for the Delineation of Pathology Clinical Privileges
Authors: Catalano Jr Edward W. , Ruby Stephen Gerard , Talbert Michael L. , Knapman Douglas G. 
Published: February 2021

Abstract
Context.—The Joint Commission (JC) established new medical staff privileging requirements effective January 2008. The new requirements include the development of ongoing professional practice evaluation (OPPE) and focused professional practice evaluation (FPPE) processes and incorporate the general competencies of patient care, medical knowledge, practice-based learning and improvement, interpersonal and communication skills, professionalism and systems-based practice jointly developed by the Accreditation Council for Graduate Medical Education (ACGME) and the American Board of Medical Specialties (ABMS). The College of American Pathologists makes resources available to assist members and their facilities in implementing the new requirements and improving patient care.
Objectives.—To review the general requirements for privileging and identify how they may apply to pathologists, to identify currently available activities and metrics that may be useful in addressing these requirements, and to present identified concepts, activities, and metrics for consideration by pathologists and hospitals for their adaptation into the policies and procedures that address the new JC physician privileging requirements.
Design.—Review available pathology privileging documentation that addressed the previous JC requirements, review the new requirements, and search for and review available and applicable resources, activities, and metrics.
Results.—Common pathology activities and metrics can be incorporated into the privileging processes. Current and new activities and metrics can be incorporated or developed to address the 6 ACGME/ABMS “General Competencies.”
Conclusion.—Each hospital has unique privileging and physician evaluation requirements. Providing concepts, activities, and metrics for pathologists and hospitals to consider in pathology privileging will help implement the OPPE and FPPE processes and meet medical staff privileging requirements.
Undifferentiated Malignant Neoplasms of the Sinonasal Tract
Authors: Wenig Bruce M. 
Published: February 2021

Abstract
Context.—The most commonly encountered malignant neoplasms of the sinonasal tract are the keratinizing and nonkeratinizing types of squamous cell carcinoma. However, this complex anatomic region may represent the site of aggressive, non–squamous cell epithelial and nonepithelial malignant neoplasms of varying histogenesis, which are grouped under the term undifferentiated malignant neoplasms. Frequently, these undifferentiated malignancies share clinical and light microscopic features, which makes differentiation of one from the other virtually impossible without the use of adjunct analyses (eg, immunohistochemistry, electron microscopy, or molecular biologic studies). These tumors often are clinically aggressive and usually fatal, despite all attempts at controlling disease. Nevertheless, differentiating these tumors has clinical import because advances in therapeutic intervention may increase survival with good quality of life, and in some instances may achieve a cure.
Objective.—To compare and contrast the clinical, light microscopic, and immunohistochemical features of sinonasal undifferentiated malignant neoplasms.
Data Sources.—Case-derived material and literature review.
Conclusions.—A variety of undifferentiated malignant neoplasms occur in the sinonasal tract with overlapping clinical and pathologic findings. In limited biopsy material, differentiation of these tumor types can be challenging. The pathologist plays a primary role in establishing the correct diagnosis, which often necessitates the use of adjunct studies that allow for differentiating among these neoplasms.
Pulmonary Site Bioprostheses: Morphologic Findings in 40 Cases
Authors: Soor Gursharan S. , Leong Shaun W. , Butany Jagdish , Shapero Jonathan L. , Williams William G. 
Published: February 2021

Abstract
Context.—From January 1995 to June 2003, there were 514 patients who underwent pulmonary valve replacements at either the Hospital for Sick Children or Toronto General Hospital. Fifty-four (10.5%) of these adults returned for replacement of their prostheses because of failure. Forty (74.1%) of the 54 explants were bioprostheses, and 14 (25.9%) were homografts.
Objective.—To present the morphologic findings from this consecutive series of 40 pulmonary-site bioprostheses.
Design.—Data were obtained by review of pathologic, clinical, and surgical records for all 40 patients with bioprosthetic pulmonary valves explanted from 1995 to June of 2003.
Results.—The mean duration of valve implantation was 14.3 ± 5.2 years (2–26 years). Median age at implantation was 16.7 ± 10.3 years (range, 3 months to 53 years). Structural valve deterioration was found in 39 (97.5%) of the valves. Morphologic evidence of stenosis was found in all valves, whereas incompetence was found in 28 (70.0%). Calcification was present in 32 (80.0%) of the valves and was severe and diffuse in 22 (55.0%). Host tissue overgrowth, or pannus, was present on 39 (97.5%) of the valves and was severe in 35 (87.5%). Tears were present in 19 (47.5%) of the valves.
Conclusions.—Explanted bioprostheses showed a high degree of calcification and pannus, which together led to stenosis. Cusp immobilization, involving all 3 cusps, was frequent and was more common in patients younger than 30 years of age at explantation (P &lt; .001). Host-tissue overgrowth is a significant problem with bioprostheses, and pulmonary-site bioprostheses are no exception.
Gene Expression–Based Prognostic and Predictive Markers for Breast Cancer: A Primer for Practicing Pathologists
Authors: Kim Chungyeul , Taniyama Yusuke , Paik Soonmyung 
Published: February 2021

Abstract
Context.—Gene expression–based prognostic assays for breast cancer are now available as commercial reference laboratory tests covered by insurance.
Objective.—To provide practicing pathologists with information about the nature of these assays, differences among them, and their use by clinical oncologists in the management of patients diagnosed with breast cancer.
Data Sources.—Review of literature and unpublished data from the National Surgical Adjuvant Breast and Bowel Project. This review focused on a general conceptual description of the technology behind these assays and differences among them to aid understanding by pathologists in practice.
Conclusions.—While these assays are clinically useful, they are still evolving. The future development of gene expression–based markers will need to be more clinical-context–specific to be clinically useful.
Pathology's Contributions to Disease Surveillance: Sending Our Data to Public Health Officials and Encouraging Our Clinical Colleagues to Do So
Authors: Aller Raymond D. 
Published: February 2021

Abstract
Pathology and clinical laboratories produce many types of data and information that are of relevance in protecting the health of the public. Electronic linkages between laboratory/pathology information systems and public health surveillance databases help ensure that these data reach the appropriate responder rapidly, completely, and accurately. Many efforts are underway to facilitate the flow of data from laboratory/pathology data sources to public health systems. Likewise, pathologists can encourage the contribution of clinical data from other parts of the health care enterprise. Chief complaint data from the emergency department and usage of over-the-counter medications from the retail pharmacy are useful for real-time population health surveillance. Having directly advocated transmission of data from our laboratories and facilitated other departments' participation in the public health surveillance network, we can also serve the public's health in other ways. Public health jurisdictions have a great need for staff with the skill sets of an experienced laboratorian. So, plan to contribute: data and talent.
Insights Into Selected Genetic Diseases Affecting the Female Reproductive Tract and Their Implication for Pathologic Evaluation of Gynecologic Specimens
Authors: Gwin Katja , Wilcox Rebecca , Montag Anthony 
Published: February 2021

Abstract
Context.—Recent advances in the understanding of genetic conditions involving the female genital tract and mechanisms of carcinogenesis in this setting affect patient management and thus necessitate appropriate pathologic evaluation of specimens. In the past, specimens from prophylactic surgery were a rarity; however, they are now more frequently encountered and often require a significant variation from routine processing methods. Pathologists also receive more specimens requiring prospective workup for possible underlying genetic conditions such as microsatellite instability.
Objective.—To summarize the current knowledge of important genetic and hereditary conditions affecting the female reproductive organs while highlighting the resulting practical significance for specimen handling, “grossing,” and microscopic evaluation in gynecologic pathology.
Data Sources.—This update is based on a review of recent peer-reviewed literature and the experience with cases at the parent institutions.
Conclusions.—Gynecologic specimens received from patients with certain genetic conditions require specific clinicopathologic knowledge for appropriate pathologic examination. The evaluation of prophylactic resection specimens focuses on the detection of cancer precursors and possible occult disease, which may require a more thorough and detailed examination than an obvious carcinoma. Standardized protocols for handling prophylactic gynecologic resection specimens are available for some, but not all, types of specimens. The prospective evaluation of a gynecologic pathology specimen for potential genetic conditions such as microsatellite instability is a very recent subject. Currently, well-established protocols are not available; however, as clinical and prognostic significance has become more clearly elucidated, familiarity with this evolving field is increasingly important to properly assess these pathologic specimens.
Lobular Neoplasia of the Breast: An Update
Authors: Contreras Alejandro , Sattar Husain 
Published: February 2021

AbstractContext.—Lobular neoplasias (LNs) of the breast include atypical lobular neoplasia and lobular carcinoma in situ. Recent evidence suggests that LN is not only a risk factor for invasive lobular carcinoma, but is also a nonobligate precursor. Pleomorphic lobular carcinoma in situ (PLCIS) is a subtype of LN that has high-grade nuclei and other features that may mimic high-grade ductal carcinoma in situ. The management and follow-up of patients diagnosed with LN on core biopsy is a current issue of debate. However, recent genomic and molecular studies have identified candidate genes that may be important in understanding the pathogenesis of atypical lobular neoplasia and lobular carcinoma in situ, and thus may lead to other therapeutic interventions.Objective.—To review the literature on LN of the breast and discuss current issues in the diagnosis and management of this entity, with particular attention to the relatively newly recognized lesion PLCIS. Because the management of PLCIS varies from the other LN lesions, the recognition of PLCIS by the pathologist is necessary. Current issues in the molecular pathogenesis of LN are also presented.Data Sources.—Extensive review of the literature. Hematoxylin-eosin–stained and immunohistochemical-stained tissue from the author's personal collection.Conclusions.—Although morphology and immunohistochemical stains, such as E-cadherin, are important in the diagnosis and understanding of LN, genomic and molecular studies may guide the way these lesions are handled in the future. Recognizing PLCIS is important both for patient management and for our future understanding of LN pathogenesis.
Anterior Diffuse Retinoblastoma: Mutational Analysis and Immunofluorescence Staining
Authors: Crosby Michelle B. , Hubbard G. Baker , Gallie Brenda L. , Grossniklaus Hans E. 
Published: February 2021

Abstract
Retinoblastoma is the most common primary intraocular tumor of childhood and may be heritable or occur sporadically. Anterior diffuse retinoblastoma is an uncommon variant that is thought to be sporadic. We describe a child with anterior diffuse retinoblastoma who presented with a pseudohypopyon. Genetic analysis showed a germline mutation of the RB1 allele that is potentially heritable. Immunofluorescence staining was positive for transforming growth factor β and for vascular endothelial growth factor and negative for inducible nitric oxide synthase and for hypoxia inducible factor α in the tumor seeds, indicating acquisition of nonischemia-mediated survival factors of the tumor seeds in the aqueous humor.
Pseudomyxoma Peritonei Associated With Primary Mucinous Borderline Tumor of the Renal Pelvicalyceal System
Authors: Rao Priya , Pinheiro Jr Nathanael , Franco Marcello , Ra Seong , Costa Henrique , Manzano João , Paner Gladell P. , Silva Elvio G. , Amin Mahul B. 
Published: February 2021

Abstract
Primary mucinous cystic neoplasms are extraordinarily rare tumors of the kidney. Herein, we present a case of a 52-year-old man who presented with painless hematuria and mucusuria. The nephrectomy showed a markedly enlarged kidney replaced by a large cystic mass filled with mucin and with almost complete destruction of the renal parenchyma. Histologically, the mass was lined primarily by simple mucinous epithelium and showed foci of adenomatous (borderline) change with focal areas exhibiting intraepithelial carcinoma. No invasion was documented after extensive sampling of the tumor. A pathologic diagnosis of intraepithelial carcinoma arising in a mucinous neoplasm of borderline malignancy was rendered. One year later, the patient presented with pseudomyxoma peritonei. This case illustrates that, in a patient with pseudomyxoma peritonei, the absence of an appendiceal, gastrointestinal, or ovarian primary tumor raises the possibility of a primary neoplasm at an unusual site such as the kidney.
Infiltrating Syringomatous Adenoma of the Nipple: Clinical Presentation and Literature Review
Authors: Oo Khine Z. , Xiao Philip Q. 
Published: February 2021

Abstract
Infiltrating syringomatous adenoma of the nipple is a rare neoplasm of the breast. Syringomatous adenoma of the nipple is often misdiagnosed because clinical examination and mammographic findings of syringomatous adenoma of the nipple mimic carcinoma. Despite its benign behavior, syringomatous adenoma of the nipple usually shows infiltrative expansile proliferation into adjacent tissue and underlying breast tissue. Up until now, to our knowledge, there has been no reported case of regional or distant metastasis. Histologically and clinically, syringomatous adenoma of the nipple is often confused with tubular carcinoma as well as low-grade adenosquamous carcinoma of the breast. Special attention given to this tumor by pathologists and clinicians can avoid misdiagnosis and unnecessary treatment.
Fatal Parasitic Meningoencephalomyelitis Caused ByHalicephalobus deletrix: A Case Report and Review of the Literature
Authors: Ondrejka Sarah L. , Procop Gary W. , Lai Keith K. , Prayson Richard A. 
Published: February 2021

AbstractInfection with the saprophagous nematode Halicephalobus species is uncommon but has been reported in horses worldwide. Only 3 human cases have been previously described, all of which have been fatal. We report a fourth fatal case, which occurred in a 39-year-old woman who presented with meningeal signs, altered mental status, and a prodromal pruritic rash. Diagnostic evaluation included an open brain biopsy, which was diagnosed as granulomatous vasculitis. The patient subsequently died after a course of steroids and cyclophosphamide. At autopsy, a robust perivascular mixed inflammatory infiltration of the brain parenchyma, meninges, and ventricular system was present with larval forms and mature nematodes morphologically consistent with Halicephalobus deletrix. Although extremely rare, this organism needs to be considered in the differential diagnosis of human helminthic infection of the central nervous system.