bluuebunny/crossref_metadata_2025 huggingface dataset:
Increasing the Efficiency of Autopsy Reporting
Authors: Siebert Joseph R.
Published: February 2021

Context.—When autopsy reports are delayed, clinicians and families do not receive information in a timely fashion.

Objective.—Using lean principles derived from the Toyota Production System, we set out to streamline our autopsy reporting process.

Design.—In a formal workshop setting, we identified the steps involved in producing an autopsy report, then sought to eliminate, abbreviate, or reschedule them into a more efficient format. We established intermediate deadlines for each case, taking care to make them visible; we initiated a weekly quality assurance review, giving attention to both scientific issues and approaching deadlines.

Results.—By adopting a more standardized approach, eliminating redundancy, and improving the visibility of tasks, we improved the mean completion time of autopsy reports from 53 days (N = 47 cases) to 25 days (N = 47 cases). Previously, 17% of reports were completed by 30 days and 71% by 60 days; in the 15 months following initiation of the program, 72% of reports were completed by 30 days and 100% by 60 days. A follow-up survey of attending physicians revealed continuing appreciation for the autopsy and timely communication, with no perceived diminution in the quality of reports.

Conclusions.—This approach was of great benefit in our laboratory and may assist others in reducing the turnaround time of their autopsy reports. It may also benefit other areas of the laboratory.
Gastrointestinal Basidiobolomycosis: An Unusual Fungal Infection Mimicking Colon Cancer
Authors: Nemenqani Dalal , Yaqoob Nausheen , Khoja Hatem , Al Saif Osama , Amra Nasir K. , Amr Samir S.
Published: February 2021

Context.—Basidiobolomycosis is a rare disease caused by the fungus Basidiobolus ranarum, an environmental saprophyte found worldwide. Patients with B ranarum infection may present with subcutaneous, gastrointestinal, or systemic lesions. Gastrointestinal basidiobolomycosis poses diagnostic difficulties, as its clinical presentation is nonspecific, with no identifiable risk factors.

Objective.—To discuss and compare the clinical features and histopathologic findings and other ancillary techniques that could be helpful in identifying gastrointestinal basidiobolomycosis.

Design.—We report 3 cases of gastrointestinal basidiobolomycosis and describe the clinical and morphologic findings while emphasizing the importance of identifying this unusual entity on endoscopic biopsies, thus avoiding unnecessary major surgeries. Fungal cultures were also performed, which are of diagnostic significance. Our first patient was lost to follow-up; however, patients 2 and 3 were followed up for 4 and 2 years, respectively.

Results.—In all 3 cases, patients presented with a clinical profile suggestive of malignancy. None of the patients gave any specific history. There was widespread abdominal disease with peritoneal involvement and colonic masses. Colonoscopic biopsy specimens showed nonspecific inflammation in 1 case; however, they showed only granulomatous inflammation in a second case and granulomas associated with fungal hyphae in a third. Typical morphology included hyphae, irregularly branched, thin-walled, occasionally septated and surrounded by a thick eosinophilic cuff (Splendore-Hoeppli phenomenon).

Conclusion.—Gastrointestinal basidiobolomycosis can be detected on small endoscopic biopsy. The unequivocal diagnosis requires microbiologic cultivation of the fungus obtained from tissues. The prognosis for this disease is usually favorable as seen in 3 of our cases; however, cases with fatal outcome are on record.
Strategies for Improving the Collection of 24-Hour Urine for Analysis in the Clinical Laboratory: Redesigned Instructions, Opinion Surveys, and Application of Reference Change Value to Micturition
Authors: Tormo Consuelo , Lumbreras Blanca , Santos Ana , Romero Luis , Conca Minerva
Published: February 2021

Context.—The preanalytic phase of 24-hour urine collection, before clinical analysis, requires the active participation of patients and usually takes place outside the laboratory.

Objective.—We verify whether distribution of adequate information to health care personnel and patients will result in fewer preanalytic incidents. We also determine the intraindividual biologic variability associated with micturition and the corresponding reference change value (RCV).

Design.—The intervention provided training for 24-hour urine collection to the health care personnel of the 20th health district of the Valencian community in Spain. The preanalytic incidents related to 24-hour micturition were estimated before and after the intervention. An opinion survey on the problems involved in urine collection was also conducted among patients. The Harris formula was used to calculate the RCV.

Results.—Before the intervention, 130 preanalytic incidents were recorded (11.5%) and after the intervention, 76 (8.6%) (P = .04) were recorded. Of the 130 incidents recorded before the intervention, 63 (48.5%) involved omission to indicate the urine volume, and of the 76 incidents recorded after the intervention, only 1 (1.3%) (P < .001) involved this omission. Forty of 302 patients (13.2%) surveyed reported problems and more than half (175; 57.9%) had to collect various urine samples sequentially. The RCV determined was 54.5% for a percentage of variation in volume of 24-hour urine (PVVI) of 19.0 ± 16.5%. Therefore, micturition associated with a PVVI >±54.5% suggests that 24-hour urine collection by the patient was incomplete. The results obtained when applying the RCV after the intervention showed that 6.3% of the 24-hour urine samples should be rejected.

Conclusions.—The percentage of preanalytic incidents was reduced by providing health care personnel with information and training. The percentage of variation in volume of 24-hour urine can be used to evaluate the variation in patients' micturition. Reference change value was shown to be useful when determining whether 24-hour urine was properly collected.
The Renal Biopsy
Authors: Walker Patrick D.
Published: February 2021

Context.—The first renal biopsy was carried out more than a century ago, but its widespread introduction into clinical use, beginning in the 1950s, helped develop nephrology into the powerful subspecialty of internal medicine that it is today. In the past 25 years, the use of the spring-loaded biopsy gun, in combination with newer visualization techniques, including ultrasound and computed axial tomography scanning, has led to greater tissue yield and to a much lower risk of complication. During this same time, our understanding of renal pathology has increased many fold. Correct fixation and processing of renal biopsy tissue is critical, and the laboratory must be skilled with renal biopsy light microscopy, immunohistochemistry, and transmission electron microscopy preparation.

Objectives.—To provide an overview of the renal biopsy, including the techniques and its complications, and to summarize proper laboratory methods for processing renal biopsy tissue.

Data Sources.—This article is based on a review of the literature and on the experience of the author.

Conclusions.—The experienced nephropathologist, knowledgeable in both renal medicine and pathology and thus able to correlate subtle tissue-derived information with appropriate clinical data, remains the most important key to the development of an accurate clinicopathologic diagnosis.
The Spectrum of Eosinophilic Cystitis in Males: Case Series and Literature Review
Authors: Popescu Oana-Eugenia , Landas Steve K. , Haas Gabriel P.
Published: February 2021

Context.—Eosinophilic cystitis (EC) is an inflammatory condition of the bladder that has been linked to food allergens, infectious agents, drugs, and other genitourinary conditions. Like interstitial cystitis, EC has a strong female predominance. It is characterized by an intense eosinophilic infiltrate in the acute phase and fibrosis in the chronic phase.

Objectives.—To document and focus on specific features of EC in males and highlight the relationship between clinical and histopathologic findings.

Design.—The bladder biopsies of male patients were reviewed. Eight cases of EC were selected.

Results.—Several known associations were noted as well as unreported features and associations such as Charcot-Leyden crystals, celiac disease, lupus anticoagulant, and additional viral and bacterial agents.

Conclusions.—Eosinophilic cystitis represents a response to a variety of agents and may often be overlooked. The temporally biphasic morphologic features are the hallmark of this condition. Because clinical and imaging studies are not specific, a high index of clinical suspicion is often crucial to the correct diagnosis and proper management of EC.
Raymond's Paragraph System: An Alternative Format for the Organization of Gross Pathology Reports and Its Implementation in an Academic Teaching Hospital
Authors: Dayton Annette S. , Ro Jae Y. , Schwartz Mary R. , Ayala Alberto G. , Raymond A. Kevin
Published: February 2021

Context.—Traditionally organized gross pathology reports, which are widely used in pathology resident and pathologists' assistant training programs, may not offer the most efficient method of communicating pertinent information to treating physicians. Instructional materials for teaching gross pathology dictation are limited and the teaching methods used are inconsistent. Raymond's Paragraph System, a gross pathology report formatting system, was developed for use at a cancer center and has been implemented at The Methodist Hospital, Houston, Tex, an academic medical center. Unlike traditionally organized reports in which everything is normally dictated in 1 long paragraph, this system separates the dictation into multiple paragraphs creating an organized and comprehensible report. Recent literature regarding formatting of pathology reports focuses primarily on the organization of specimen diagnoses and overall report layout. However, little literature is available that highlights organization of the specimen gross descriptions.

Objective.—To provide instruction to pathologists, pathology residents and fellows, and pathologists' assistant students about an alternative method of organizing gross pathology reports.

Data Sources.—Review of pertinent literature relating to preparation of gross pathology reports, report formatting, and pathology laboratory credentialing requirements.

Conclusions.—The paragraph system offers a viable alternative to traditionally organized pathology reports. Primarily, it provides a working model for medical professionals-in-training. It helps create user-friendly pathology reports by giving precise and concise information in a standardized format. This article provides an overview of the system and discusses our experience in its implementation.
Subcutaneous Panniculitis-like T-Cell Lymphoma: Redefinition of Diagnostic Criteria in the Recent World Health Organization–European Organization for Research and Treatment of Cancer Classification for Cutaneous Lymphomas
Authors: Parveen Zahida , Thompson Karen
Published: February 2021

Subcutaneous panniculitis-like T-cell lymphoma is a primary T-cell lymphoma that preferentially involves the subcutaneous tissue. Although subcutaneous panniculitis-like T-cell lymphoma has been recognized as a distinctive entity in the category of peripheral T-cell lymphoma in the World Health Organization classification, its diagnostic criteria has been redefined by the recent World Health Organization–European Organization for Research and Treatment of Cancer classification for primary cutaneous lymphomas. Subcutaneous panniculitis-like T-cell lymphoma is now restricted to primary cutaneous T-cell lymphoma expressing αβ T-cell receptor phenotype. These lymphomas are usually CD3+, CD4−, CD8+, and CD56−, and usually have an indolent clinical course. The clinicopathologic features, differential diagnosis, immunophenotypic characteristics, and molecular features of subcutaneous panniculitis-like T-cell lymphoma are presented in light of the recent World Health Organization–European Organization for Research and Treatment of Cancer classification.
Endocrine Neoplasms of the Pancreas: Pathologic and Genetic Features
Authors: Capelli Paola , Martignoni Guido , Pedica Federica , Falconi Massimo , Antonello Davide , Malpeli Giorgio , Scarpa Aldo
Published: February 2021

Context.—Pancreatic endocrine neoplasms (PENs) are diagnostically challenging tumors whose natural history is largely unknown. Histopathology allows the distinction of 2 categories: poorly differentiated high-grade carcinomas and well-differentiated neoplasms. The latter include more than 90% of PENs whose clinical behavior varies from indolent to malignant and cannot be predicted by their morphology.

Objectives.—To review the literature and report on additional primary material about the clinicopathologic features, classification, staging, grading, and genetic features of PENs.

Data Sources.—Literature review of relevant articles indexed in PubMed (US National Library of Medicine) and primary material from the authors' institution.

Conclusions.—The diagnosis of PEN is generally easy, but unusual features may induce misdiagnosis. Immunohistochemistry solves the issue, provided that the possibility of a PEN has been considered. Morphology allows the distinction of poorly differentiated aggressive carcinomas from well-differentiated neoplasms. The World Health Organization classification criteria allow for the discernment of the latter into neoplasms and carcinomas with either benign or uncertain behavior. The recently proposed staging and grading systems hold great promise for permitting a stratification of carcinomas into clinically significant risk categories. To date, inactivation of the MEN1 gene remains the only ascertained genetic event involved in PEN genesis. It is inactivated in roughly one-third of PENs. The degree of genomic instability correlates with the aggressiveness of the neoplasm. Gene silencing by promoter methylation has been advocated, but a formal demonstration of the involvement of specific genes is still lacking. Expression profiling studies are furnishing valuable lists of mRNAs and noncoding RNAs that may advance further the research to discover novel markers and/or therapeutic targets.
Familial Pancreatic Cancer
Authors: Shi Chanjuan , Hruban Ralph H. , Klein Alison P.
Published: February 2021

Context.—Approximately 5% to 10% of individuals with pancreatic cancer report a history of pancreatic cancer in a close family member. In addition, several known genetic syndromes, such as familial breast cancer (BRCA2), the Peutz-Jeghers syndrome, and the familial atypical multiple mole melanoma syndrome, have been shown to be associated with an increased risk of pancreatic cancer. The known genes associated with these conditions can explain only a portion of the clustering of pancreatic cancer in families, and research to identify additional susceptibility genes is ongoing.

Objective.—To provide an understanding of familial pancreatic cancer and the pathology of familial exocrine pancreatic cancers.

Data Sources.—Published literature on familial aggregation of pancreatic cancer and familial exocrine pancreatic tumors.

Conclusions.—Even in the absence of predictive genetic testing, the collection of a careful, detailed family history is an important step in the management of all patients with pancreatic cancer. While most pancreatic cancers that arise in patients with a family history are ductal adenocarcinomas, certain subtypes of pancreatic cancer have been associated with familial syndromes. Therefore, the histologic appearance of the pancreatic cancer itself, and/or the presence and appearance of precancerous changes in the pancreas, may increase the clinical index of suspicion for a genetic syndrome.
Molecular Alterations in Exocrine Neoplasms of the Pancreas
Authors: Ranganathan Prathibha , Harsha H. C. , Pandey Akhilesh
Published: February 2021

Context.—Pancreatic cancer is one of the leading causes of cancer-related deaths. Most cases are diagnosed at an advanced stage when the disease is beyond surgical intervention. Molecular studies during the past decade have contributed greatly to our understanding of this disease. Various germ-line and somatic mutations associated with pancreatic cancers have been characterized, along with abnormal variations in the gene expression patterns. A thorough characterization of molecular alterations such as genetic and epigenetic changes, alterations in the expression of genes and changes in proteins, and posttranslational modifications in pancreatic cancer could lead to a better understanding of its pathogenesis.

Objective.—To provide an overview of the various molecular alterations in pancreatic cancer and the methodologies used to catalog such alterations.

Data Sources.—Published studies about various molecular alterations at the genomic, epigenetic, transcriptomic, and proteomic levels in pancreatic cancer.

Conclusions.—The available data from pancreatic cancer suggests that there are a large number of molecular alterations at genomic, epigenetic, transcriptomic, and proteomic levels. It is now possible to initiate a systems approach to studying pancreatic cancer especially in light of newer initiatives to dissect the pancreatic cancer genome.
Pancreatic Cysts: Pathologic Classification, Differential Diagnosis, and Clinical Implications
Authors: Basturk Olca , Coban Ipek , Adsay N. Volkan
Published: February 2021

Context.—Cystic lesions of the pancreas are being recognized with increasing frequency and have become a more common finding in clinical practice because of the widespread use of advanced imaging modalities and the sharp drop in the mortality rate of pancreatic surgery. Consequently, in the past 2 decades, the nature of many cystic tumors in this organ has been better characterized, and significant developments have taken place in the classification and in our understanding of pancreatic cystic lesions.

Objective.—To provide an overview of the current concepts in classification, differential diagnosis, and clinical/biologic behavior of pancreatic cystic tumors.

Data Sources.—The authors' personal experience, based on institutional and consultation materials, combined with an analysis of the literature.

Conclusions.—In contrast to solid tumors, most of which are invasive ductal adenocarcinomas with dismal prognosis, cystic lesions of the pancreas are often either benign or low-grade indolent neoplasia. However, those that are mucinous, namely, intraductal papillary mucinous neoplasms and mucinous cystic neoplasms, constitute an important category because they have well-established malignant potential, representing an adenoma-carcinoma sequence. Those that are nonmucinous such as serous tumors, congenital cysts, lymphoepithelial cysts, and squamoid cyst of pancreatic ducts have no malignant potential. Only rare nonmucinous cystic tumors that occur as a result of degenerative/necrotic changes in otherwise solid neoplasia, such as cystic ductal adenocarcinomas, cystic pancreatic endocrine neoplasia, and solid-pseudopapillary neoplasm, are also malignant and have variable degrees of aggressiveness.
Nonneoplastic Mimickers of Pancreatic Neoplasms
Authors: Zamboni Giuseppe , Capelli Paola , Scarpa Aldo , Bogina Giuseppe , Pesci Anna , Brunello Eleonora , Klöppel Günter
Published: February 2021

Context.—A variety of nonneoplastic conditions may form pancreatic masses that mimic carcinoma. Approximately 5% to 10% of pancreatectomies performed with the clinical diagnosis of pancreatic cancer prove on microscopic evaluation to be pseudotumors.

Objectives.—To illustrate the clinical and pathologic characteristics of the 2 most frequent pseudotumoral inflammatory conditions, autoimmune pancreatitis and paraduodenal pancreatitis, and describe the criteria that may be useful in the differential diagnosis versus pancreatic carcinoma.

Data Sources.—Recent literature and the authors' experience with the clinical and pathologic characteristics of autoimmune pancreatitis and paraduodenal pancreatitis.

Conclusions.—The knowledge of the clinical, radiologic, and pathologic findings in both autoimmune pancreatitis and paraduodenal pancreatitis is crucial in making the correct preoperative diagnosis. Autoimmune pancreatitis, which occurs in isolated or syndromic forms, is characterized by a distinctive fibroinflammatory process that can either be limited to the pancreas or extend to the biliary tree. Its correct preoperative identification on biopsy material with ancillary immunohistochemical detection of dense immunoglobulin G4-positive plasma cell infiltration is possible and crucial to prevent major surgery and to treat these patients with steroid therapy. Paraduodenal pancreatitis is a special form of chronic pancreatitis that affects young males with a history of alcohol abuse and predominantly involves the duodenal wall in the region of the minor papilla. Pathogenetically, the anatomical and/or functional obstruction of the papilla minor, resulting from an incomplete involution of the intraduodenal dorsal pancreas, associated with alcohol abuse represents the key factor. Endoscopic drainage of the papilla minor, with decompression of the intraduodenal and dorsal pancreas, might be considered in these patients.
Recurrent Challenges in the Evaluation of Fibroepithelial Lesions
Authors: Giri Dilip
Published: February 2021

Context.—The morphologic spectrum of mammary fibroepithelial lesions ranges from fibroadenoma, a common benign neoplasm, to phyllodes tumor, an uncommon lesion that can sometimes recur and metastasize.

Objective.—To focus on problems encountered in the diagnostic evaluation of fibroepithelial tumors, highlighting the diagnostically relevant morphologic features and providing an update on the immunohistochemical profile and genetic alterations of these rare neoplasms.

Data Sources.—A PubMed search of the English-language literature identified published reports on fibroepithelial lesions, with a special focus on phyllodes tumor. The results and conclusions of these studies form the basis of this review.

Conclusions.—The distinction between fibroadenoma and phyllodes tumor is usually not problematic, especially in excision specimens. In some cases, however, the diagnostic evaluation of fibroepithelial lesions can be challenging, especially if only limited material is available. Morphologic predictors of local recurrence of phyllodes tumor include cellularity and cytologic atypia, mitotic activity, positive margins, infiltrative borders, fibroproliferative satellite nodules, and past history of fibroadenoma. Predictors of distant metastasis include size, tumor necrosis, and stromal overgrowth. None of these parameters, however, constitutes a definite marker of malignancy. Presently, molecular and immunohistochemical techniques play a limited role in the diagnosis of fibroepithelial lesions.
Best Practices in Contemporary Diagnostic Immunohistochemistry: Panel Approach to Hematolymphoid Proliferations
Authors: Garcia Christine F. , Swerdlow Steven H.
Published: February 2021

Context.—The complexities of diagnostic hematopathology in the modern era are well known, and even in this molecular era, immunophenotypic studies, together with routine histopathology, remain a critical component in the evaluation of many lymphoid proliferations. With numerous antibodies that can be used on routinely fixed, paraffin-embedded tissue sections, immunohistochemistry has become increasingly valuable. It then becomes a challenge knowing the best approach to the selection of antibodies to use and how to interpret them.

Objective.—To present a pragmatic immunohistochemical approach to the evaluation of lymphoid proliferations that stresses the utility of 2 limited panels to deal with the most commonly encountered lymphomas.

Data Sources.—English-language literature published between 1990 and 2008.

Conclusions.—A relatively limited panel of immunohistochemical stains may be used to diagnose and subclassify many of the more common lymphomas, although some cases will require additional stains and others fewer, depending on the case complexity. Immunohistochemical stains must always be interpreted in the context of the histopathologic and other ancillary studies.
Virtopsy: Postmortem Imaging of Laryngeal Foreign Bodies
Authors: Oesterhelweg Lars , Bolliger Stephan A. , Thali Michael J. , Ross Steffen
Published: February 2021

Context.—Death from corpora aliena in the larynx is a well-known entity in forensic pathology. The correct diagnosis of this cause of death is difficult without an autopsy, and misdiagnoses by external examination alone are common.

Objective.—To determine the postmortem usefulness of modern imaging techniques in the diagnosis of foreign bodies in the larynx, multislice computed tomography, magnetic resonance imaging, and postmortem full-body computed tomography–angiography were performed.

Design.—Three decedents with a suspected foreign body in the larynx underwent the 3 different imaging techniques before medicolegal autopsy.

Results.—Multislice computed tomography has a high diagnostic value in the noninvasive localization of a foreign body and abnormalities in the larynx. The differentiation between neoplasm or soft foreign bodies (eg, food) is possible, but difficult, by unenhanced multislice computed tomography. By magnetic resonance imaging, the discrimination of the soft tissue structures and soft foreign bodies is much easier. In addition to the postmortem multislice computed tomography, the combination with postmortem angiography will increase the diagnostic value.

Conclusions.—Postmortem, cross-sectional imaging methods are highly valuable procedures for the noninvasive detection of corpora aliena in the larynx.
Identification and Biologic Significance of Micrometastases in Axillary Lymph Nodes in Patients With Invasive Breast Cancer
Authors: Sahin Aysegul A. , Guray Merih , Hunt Kelly K.
Published: February 2021

Context.—The presence or absence of metastases in axillary lymph nodes is one of the most important prognostic factors for patients with breast cancer. During the past decade sentinel lymph node (SLN) biopsy has been increasingly adopted as a minimally invasive staging alternative to complete axillary node dissection.

Objective.—Sentinel lymph nodes are more likely to contain metastases than non-SLNs. In routine clinical practice SLNs are assessed by diverse methodologies including multiple sectioning, immunohistochemical staining, and molecular diagnostic tests. Despite the lack of standard histopathologic protocols during the years detailed evaluation of SLNs has resulted in an increased detection of small (micro) metastases.

Data Sources.—Breast cancer with micrometastases constitutes a heterogenous group of tumors with variable clinical outcome regarding the risk of additional metastases in the remaining axillary lymph nodes and to patients' survival.

Conclusion.—The clinical significance of micrometastases has been subject to great controversy in patients with breast cancer. In this review we highlight controversies regarding micrometastases especially in relation to SLNs.
What Hematopathology Tells Us About the Future of Pathology Informatics
Authors: Hess Jay L.
Published: February 2021

The field of hematopathology has been a leader in the application of new technologies for both diagnostics and therapy. The ready accessibility of blood cells for examination, the ability to quantify important indices, and the relative responsiveness of otherwise fatal hematologic diseases to chemotherapy have all contributed to rapid advances in the field. Hematopathology provides many insights into the challenges that pathology informatics will face in addressing the needs of a growing and aging population in the era of personalized medicine.
Utility of Immunohistochemistry for Endothelial Markers in Distinguishing Epithelioid Hemangioendothelioma From Carcinoma Metastatic to Bone
Authors: Gill Ryan , O'Donnell Richard J. , Horvai Andrew
Published: February 2021

Context.—Epithelioid hemangioendothelioma (EHE) is a rare vascular neoplasm of intermediate malignancy. Epithelioid hemangioendothelioma often presents a difficult diagnostic problem, especially in bone, because the epithelioid morphology and radiographic features raise the possibility of metastatic carcinoma. The current trend of small biopsies obtained with computed tomography–guided techniques exacerbates the problem. The markedly different treatment for EHE and metastatic carcinoma underscores the need for specific markers that can differentiate between these 2 entities.

Objective.—To determine the relative utility of endothelial markers in differentiating EHE from metastatic carcinoma, with emphasis on bone biopsies.

Design.—We used immunohistochemistry in formalin-fixed paraffin-embedded tissue to compare the utility of Fli-1, CD34, CD31, podoplanin, and keratin cocktail in 13 EHEs and 13 morphologically similar carcinomas metastatic to bone. Immunohistochemical data were evaluated using Fisher exact test, and specificity and sensitivity were calculated.

Results.—Significant proportions of EHEs were positive for Fli-1 (100%), CD34 (85%), and CD31 (100%) compared with metastatic carcinoma (Fli-1, 15%; CD34, 15%; CD31, 38%) (P < .001, P = .005, and P = .01, respectively). However, these markers were not 100% specific for EHE. Cytokeratin cocktail stained significantly more metastatic carcinomas (100%) than EHEs (38%) (P = .01) but was not 100% specific. No significant difference was observed regarding immunostaining for podoplanin between the tumor types.

Conclusions.—Fli-1 is most helpful in distinguishing EHE from metastatic carcinoma. However, the absence of complete specificity of any of the endothelial markers for EHE, or of keratin cocktail for carcinoma, suggests that these markers are best used in combination.
Tissue Floaters and Contaminants in the Histology Laboratory
Authors: Platt Eric , Sommer Paul , McDonald Linda , Bennett Ana , Hunt Jennifer
Published: February 2021

Context.—Anatomic pathology diagnosis is often based on morphologic features. In recent years, an appropriate increased attention to patient safety has led to an emphasis on improving maintenance of patient identity. Decreasing or eliminating cross-contamination from one specimen to another is an example of a patient identity issue for which process improvement can be initiated.

Objective.—To quantify the presence of cross-contamination from histology water baths and the slide stainers.

Design.—We assessed for the presence of contaminants in water baths at cutting stations and in linear stainer stain baths. We assessed the potential for tissue discohesion and carryover in tissue samples and we assessed the potential for carryover onto blank slides sent through the stainer.

Results.—In the 13 water baths examined (totalling 195 L of water), only one fragment of tissue was identified. The stain baths, however, contained abundant tissue contaminants, ranging in size from 2 to 3 cells to hundreds of cells. The first sets of xylenes and alcohols were the most heavily contaminated. Cross-contamination to blank slides occurred at a rate of 8%, with the highest frequency in the late afternoon.

Conclusions.—Cross-contamination can present a significant challenge in the histology laboratory. Although the histotechnologists' water baths are not heavily contaminated, the stainer baths do contain contaminating tissue fragments. Cross-contamination does occur onto blank slides in the experimental setting.
Recent Developments in the Pathology of Renal Tumors: Morphology and Molecular Characteristics of Select Entities
Authors: Yan Benjamin C. , Mackinnon A. Craig , Al-Ahmadie Hikmat A.
Published: February 2021

Context.—Renal cell carcinoma is a heterogeneous group of tumors with distinct histopathologic features, molecular characteristics, and clinical outcome. These tumors can be sporadic as well as familial or associated with syndromes. The genetic abnormalities underlying these syndromes have been identified and were subsequently found in corresponding sporadic renal tumors.

Objective.—To review the recent molecular and genetic advancements relating to sporadic and familial renal carcinomas as well as those related to Xp11.2 translocation– associated renal cell carcinoma and renal medullary carcinoma.

Data Sources.—Literature review, personal experience, and material from the University of Chicago.

Conclusions.—Molecular genetic diagnostic techniques will continue to introduce new biomarkers that will aid in the differential diagnosis of difficult cases. The identification of specific signaling pathways that are defective in certain renal tumors also makes possible the development of new therapies that selectively target the aberrant activity of the defective proteins.
Diffuse Large B-Cell Lymphoma—More Than a Diffuse Collection of Large B Cells: An Entity in Search of a Meaningful Classification
Authors: Gurbaxani Sandeep , Anastasi John , Hyjek Elizabeth
Published: February 2021

Context.—Diffuse large B-cell lymphoma is a heterogenous group of lymphomas. In this review, we present a brief description of the large number of entities recognized in the recently published (2008) World Health Organization classification of tumors of hematopoietic and lymphoid tissues.

Objective.—We highlight the unique clinicopathologic and molecular genetic features of these new and previously recognized entities, to illustrate the rational for the development of this classification. To help simplify the understanding of this now large and complex group of diseases, we have attempted to create broader subgroups of related entities. We discuss large B-cell lymphoma that are not otherwise specified, those that are based on anatomic site, those that have unique histology or phenotype or genotype, those that are associated with Epstein-Barr virus or Kaposi sarcoma–associated herpesvirus and herpesvirus 8, and those that are unclassifiable.

Data Sources.—World Health Organization classification of tumors of hematopoietic and lymphoid tissues (2008), published literature from PubMed (National Library of Medicine), and primary material from the authors' institution were reviewed.

Conclusions.—Recognition of the different subtypes of diffuse large B-cell lymphoma as described in the World Health Organization classification scheme will lead to improved understanding of the unique clinicopathologic and genetic features associated with these subtypes of lymphoma.
Lack of Association of High-Risk Human Papillomavirus in Ocular Surface Squamous Neoplasia in India
Authors: Manderwad Guru Prasad , Kannabiran Chitra , Honavar Santosh G. , Vemuganti Geeta K.
Published: February 2021

Context.—Ocular surface squamous neoplasia (OSSN) represents a spectrum of ocular surface tumors ranging from intraepithelial to invasive. The genesis of OSSN is multifactorial, possibly including human papillomavirus (HPV) infection, the role of which is controversial.

Objective.—To evaluate the role of high-risk HPV16 and HPV18 in OSSN.

Design.—Retrospective and prospective noncomparative case series. In this study, histologically proven cases of OSSN were evaluated in formalin-fixed, paraffin-embedded sections (n = 50) and fresh tissues (n = 7) for the presence of HPV by polymerase chain reaction using MY09/MY11 consensus primers, HPV16 and HPV18 type-specific primers, and in situ hybridization–catalyzed reporter deposition (ISH-CARD). Cervical tumors (n = 19) along with SiHa and HeLa cell lines served as positive controls for HPV analysis.

Results.—The study included 48 patients with OSSN who accounted for 57 specimens, with a median patient age of 28.5 years (range, 1.5–70 years). These specimens included 36 squamous cell carcinomas and 21 conjunctival intraepithelial neoplasias. All of the cases were found to be negative for high-risk HPV using polymerase chain reaction and ISH-CARD assay, whereas the SiHa and HeLa cell lines were appropriately positive. Of the cervical tumors that served as positive controls, 18 were positive for HPV16, and 1 was positive for HPV18.

Conclusions.—Sensitive, type-specific polymerase chain reaction for detection of HPV16 and HPV18, polymerase chain reaction assay for consensus HPV sequences, and ISH-CARD did not show the presence of high-risk HPV in OSSN. Thus, HPV appears to play no significant role in the etiology of OSSN in India.
Introduction of the 7th Edition Eyelid Carcinoma Classification System From the American Joint Committee on Cancer–International Union Against Cancer Staging Manual
Authors: Ainbinder Darryl J. , Esmaeli Bita , Groo Stephen C. , Finger Paul T. , Brooks Joseph P.
Published: February 2021

Context.—The American Joint Committee on Cancer (AJCC) and the International Union Against Cancer commissioned the Ophthalmic Oncology Task Force to modify and update the ophthalmic chapters of the 7th edition of the AJCC Cancer Staging Manual.

Objective.—To review the existing eyelid carcinoma chapter in the 6th edition of the AJCC Cancer Staging Manual for its clinical and research utility and to seek evidence-based revisions with the strongest medical foundation to use in updating the anatomically based TNM cancer staging system manual.

Data Sources.—The 4-year Ophthalmic Oncology Task Force consisted of 45 tumor specialists from 10 countries and an extensive internal and external peer review process. The 10-member Carcinoma of the Eyelid team included a diverse group of international authors. The group included extensive representation by clinicians, pathologists, surgeons, radiation therapists, and cancer registrars, all with advanced, ophthalmic cancer–related areas of subspecialty. Data sources included the above expertise applying a worldwide medical literature search, with no discrimination based on language, country of origin, discipline source, specialty source, or surgical practice.

Conclusions.—Revisions were made to the TNM classification in areas with the strongest basis in evidence and practical effect. Lymph node staging data were expanded markedly to reflect its significant prognostic value. T3 and T4 were redefined and stage groupings were added that applied current understanding in tumor biology, respected site-specific risk factors, and provided greater correlation with the common language of the overall AJCC Cancer Staging Manual. Evidence-based biomarkers and data-field modifiers were included to capture additional pathologically and clinically substantiated prognostic factors.
A TNM-Based Clinical Staging System of Ocular Adnexal Lymphomas
Authors: Coupland Sarah E. , White Valerie A. , Rootman Jack , Damato Bertil , Finger Paul T.
Published: February 2021

Context.—The ocular adnexal lymphomas (OAL) arise in the conjunctiva, orbit, lacrimal gland, and eyelids. To date, they have been clinically staged using the Ann Arbor staging system, first designed for Hodgkin and later for nodal, non–Hodgkin lymphoma. The Ann Arbor system has several shortcomings, particularly when staging extranodal non– Hodgkin lymphomas, such as OAL, which show different dissemination patterns from nodal lymphomas.

Objective.—To describe the first TNM-based clinical staging system for OAL.

Design.—Retrospective literature review.

Results.—We have developed, to our knowledge, the first American Joint Committee on Cancer–International Union Against Cancer TNM-based staging system for OAL to overcome the limitations of the Ann Arbor system. Our staging system defines disease extent more precisely within the various anatomic compartments of the ocular adnexa and allows for analysis of site-specific factors not addressed previously. It aims to facilitate future studies by identifying clinical and histomorphologic features of prognostic significance. This system is for primary OAL only and is not intended for intraocular lymphomas.

Conclusions.—Our TNM-based staging system for OAL is a user-friendly, anatomic documentation of disease extent, which creates a common language for multicenter and international collaboration. Data points will be collected with the aim of identifying biomarkers to be incorporated into the staging system.
Changes in the 7th Edition of the AJCC TNM Classification and Recommendations for Pathologic Analysis of Lacrimal Gland Tumors
Authors: Rootman Jack , White Valerie A.
Published: February 2021

In our recent work to update the American Joint Committee on Cancer's AJCC Cancer Staging Manual, we brought the staging system in line with that of salivary gland malignancies to better describe the range of these tumors. In addition, we have suggested that information be collected on biomarkers and clinical and histologic data points. This revised staging, along with careful histologic analysis and patient follow-up, may provide information that helps develop more targeted management for these lesions.
Patient Misidentification in Papanicolaou Tests: A Systems-Based Approach to Reducing Errors
Authors: Meyer Erin , Underwood R. Shawn , Padmanabhan Vijayalakshmi
Published: February 2021

Context.—Patient safety is of prime concern in every laboratory. Double labeling of glass slides is performed in many cytology laboratories where handwritten patient information on the frosted portion of the glass is overlaid with paper labels (sometimes containing bar codes). The cytotechnologists match this information by turning slides over. We use SurePath liquid-based cytology for Papanicolaou tests in our laboratory and noticed patient misidentification because of slide labeling errors, a problem that has not been addressed in the literature.

Objective.—To reduce slide labeling errors without increasing costs, using a systems-based approach.

Design.—All errors from mislabeled slides during November 2006 were documented, and an informal root-cause analysis was performed. Slides were labeled on opposite ends and monitored for errors.

Results.—Labeling on different ends of the glass slide reduced our error rate from 0.59% to 0%, made visual matching easy, and did not alter costs.

Conclusions.—The practice of overlaying handwritten information with printed labels for liquid-based Papanicolaou tests should be strongly discouraged and replaced with placing patient information in separate portions of the glass slide so that crucial patient identification is not hidden and visual matching is easy.
Anaplastic Large Cell Lymphoma Involving the Breast: A Clinicopathologic Study of 6 Cases and Review of the Literature
Authors: Miranda Roberto N. , Lin Lin , Talwalkar Sameer S. , Manning John T. , Medeiros L. Jeffrey
Published: February 2021

Context.—Lymphomas involving the breast are rare, and most cases are of B-cell lineage; T-cell neoplasms represent less than 10% of all breast lymphomas.

Objective.—To define the clinicopathologic spectrum of anaplastic large cell lymphomas (ALCLs) involving the breast.

Design.—Six cases of ALCL involving the breast were identified at a single institution during 21 years. The clinicopathologic and immunophenotypic features are presented, and the literature is reviewed.

Results.—All patients were women, with a median age of 52 years. There were 4 anaplastic lymphoma kinase– negative (ALK−) ALCL cases; 3 of these neoplasms developed around breast implants. Two patients with ALK− ALCL had a history of cutaneous ALCL. There were 2 ALK+ ALCLs; both patients had stage IV disease. Histologically, all neoplasms were composed of large anaplastic cells that were uniformly CD30+ and expressed markers of T-cell lineage. Four patients with adequate follow-up are alive, with a mean of 4.1 years (range, 1.5–9 years) after diagnosis of the breast tumor. Included in this group are 2 patients with ALK− ALCL associated with breast implants who were alive 4 years and 9 years after diagnosis.

Conclusions.—Including the 6 cases we describe, a total of 21 cases of ALCL involving the breast are reported. Fifteen cases, all ALK−, were associated with breast implants, suggesting a possible pathogenetic relationship, and associated with an excellent prognosis. Patients with cutaneous ALCL can subsequently develop ALK− ALCL involving the breast, and these tumors can be associated with breast implants.
Standardization of HER2 Immunohistochemistry in Breast Cancer by Automated Quantitative Analysis
Authors: Gustavson Mark D. , Bourke-Martin Brian , Reilly Dylan , Cregger Melissa , Williams Christine , Mayotte Jane , Zerkowski Maciej , Tedeschi Greg , Pinard Robert , Christiansen Jason
Published: February 2021

Context.—There is critical need for standardization of HER2 immunohistochemistry testing in the clinical laboratory setting. Recently, the American Society of Clinical Oncology and the College of American Pathologists have submitted guidelines recommending that laboratories achieve 95% concordance between assays and observers for HER2 testing.

Objective.—As a potential aid to pathologists for achieving these new guidelines, we have conducted an examination using automated quantitative analysis (AQUA analysis) to provide a standardized HER2 immunohistochemistry expression score across instruments (sites), operators, and staining runs.

Design.—We analyzed HER2 expression by immunohistochemistry in a cohort (n = 669) of invasive breast cancers in tissue microarray format across different instruments (n = 3), operators (n = 3), and staining runs (n = 3). Using light source, instrument calibration techniques, and a new generation of image analysis software, we produced normalized AQUA scores for each parameter and examined their reproducibility.

Results.—The average percent coefficients of variation across instruments, operators, and staining runs were 1.8%, 2.0%, and 5.1%, respectively. For positive/negative classification between parameters, concordance rates ranged from 94.5% to 99.3% for all cases. Differentially classified cases only occurred around the determined cut point, not over the entire distribution.

Conclusions.—These data demonstrate that AQUA analysis can provide a standardized HER2 immunohistochemistry test that can meet current guidelines by the American Society of Clinical Oncology/College of American Pathologists. The use of AQUA analysis could allow for standardized and objective HER2 testing in clinical laboratories.
Presence of c-KIT–Positive Mast Cells in Obliterative Bronchiolitis From Diverse Causes
Authors: Fuehrer Neil E. , Marchevsky Alberto M. , Jagirdar Jaishree
Published: February 2021

Context.—The mechanism of fibrosis is not clear in patients with obliterative bronchiolitis after a remote injury. Immune-mediated progression may be a reason. c-KIT (CD117)–positive mast cells have been associated with chronic fibrosing diseases and may potentially be treated with imatinib (Gleevec), a c-KIT blocker.

Objective.—To evaluate the role of mast cells in fibrosis associated with obliterative bronchiolitis.

Design.—Four cases of obliterative bronchiolitis (household cleaner exposure, ammonia exposure, idiopathic, and posttransplantation) were compared with asthma/emphysema. Small and large airways were stained for CD20, CD3, CD4, CD8, CD117, CD34, CD25, stem cell factor (c-KIT ligand) and with toluidine blue, hematoxylin-eosin, and trichrome. c-KIT (CD117)–stained slides were digitally scanned with Aperio ScanScope and stained cells within the epithelium and subepithelium of small and large airways were counted (per millimeter of basement membrane).

Results.—Mast cells were concentrated within the involved subepithelium of small airways in obliterative bronchiolitis (122 cells/mm), unlike asthma/emphysema (25 cells/mm). Conversely, there were more mast cells in the epithelium in cases of asthma/emphysema than in obliterative bronchiolitis (7 cells/mm and 2 cells/mm, respectively). Mast cells were significantly increased around involved airways versus uninvolved airways (52 cells/mm vs 14 cells/mm). Large airways in either group had similar c-KIT (CD117) expression. Stem cell factor was not increased.

Conclusions.—Mast cells appear to be concentrated in the lesional small-airway subepithelium in obliterative bronchiolitis. The possible role of c-KIT inhibitors such as imatinib (Gleevec) in the progression of fibrosis preceding the development of obliterative bronchiolitis is discussed.