bluuebunny/crossref_metadata_2025 huggingface dataset:
The Role of Biosurgical Agents in Dermatologic Surgery
Authors: Z. Safeer Laraib , Agarwala Saira , C. Krakowski Andrew , P. Johnson Ryan
Published: February 2021

Performed in an outpatient, office-based setting, dermatologic surgery reduces healthcare costs of hospitalization while maintaining low rates of surgical complications such as infection, dehiscence, and hematoma formation. However, the potential for complications requiring hospitalization or IV antibiotic therapy still exists and varies depending on patient risk factors, such as the use of antiplatelet and anticoagulant medications. Furthermore, measured outcomes in dermatologic surgery expand beyond surgical wound complications to include optimization of wound healing and reduction of scar formation, especially in cosmetically sensitive areas of the body. Biosurgical agents are increasingly being used in surgical fields to achieve hemostasis and to optimize wound healing. This chapter reviews the typical methods to achieve hemostasis in dermatologic surgery and examines the current and future role of biosurgical agents in procedural dermatology.
The Association Between Serum Magnesium Level and Microalbuminuria in Type 2 Diabetes Mellitus Patients
Authors: Mohebbi Masoud , Samadi Katayoun , Navari Nazafarin , Ziafati-fahmideh-sani Melika , Nourihosseini Golshid , Ershad Negin , Bahrami Milad , Rezaeizadeh Ali , Taheri Amirhossein , Akbari-javar Mohammad-taha , Zamiri Bidary Mohammad , Kabirian Ali , Hessami Amirhossein , Zeraati Abbas-Ali
Published: February 2021

Background: Diabetic nephropathy occurs in 20 - 30% of diabetic cases globally, and microalbuminuria (MA) is the first symptom of this disorder. Some studies have suggested that there is an association between the serum magnesium (Mg) level and MA. Objectives: Therefore, we investigated the association between the serum Mg level and MA in type 2 diabetes mellitus (T2DM) patients. Methods: We conducted a cross-sectional study on 122 subjects with T2DM. We categorized them into two groups of microalbuminuria (MA) and non-microalbuminuria (NMA) according to their urine albumin-creatinine ratio (UACR). MA was considered as a UACR of 30 to 300 mg/g. Participants were excluded if they had the following conditions: The age of under 16 years, cardiac, renal, or hepatic disorders, using corticosteroids, diuretics, Mg /calcium (Ca) supplements, and antiepileptic drugs, heavy physical activity within 24 hours before the test, pregnant and breastfeeding women, febrile patients, and patients who were unwilling to participate in the study. The analysis was performed using SPSS version 15. A P-value < 0.05 was considered significant. Results: Among the patients, 50.81% were male. Also, the mean body mass index (BMI) of the NMA group was greater than the MA group (29.84 ± 5.64 vs. 27.31 ± 3.14, P-value = 0.003). Mg levels of the MA and NMA groups showed no significant differences (2.13 ± 0.42 and 2.10 ± 0.43, respectively; P-value = 0.67). Overall, data analysis provided no significant difference between Mg level and the urine albumin concentration between the MA and NMA groups (P-value = 0.21 and 0.81, respectively.). Conclusions: Serum Mg level and MA have no significant relationship. Further prospective studies are needed to assay this issue.
The Relationship of Drug Abuse to Unexplained Sudden Death
Authors: Gruszecki Amy C. , McGwin, Jr Gerald , Robinson, Jr C. Andrew , Davis Gregory G.
Published: February 2021

Context.—Forensic pathologists regularly investigate the deaths of individuals with a history of drug abuse. Autopsy, including toxicology testing, reveals no cause for death in a subset of this cohort.

Objective.—To determine whether deaths with an undetermined cause and manner of death are associated with a history of drug abuse.

Design.—Retrospective matched case-control study of 52 decedents whose cause of death remained undetermined following autopsy, matched 1:2 to a control group of living patients admitted for cholecystectomy according to age and date of death or procedure.

Results.—Individuals whose cause of death was undetermined were 5.3 times (95% confidence interval, 1.9– 14.5) more likely to have a history of drug abuse than were patients with cholecystitis.

Conclusions.—Decedents with a history of chronic drug abuse appear to be at an increased risk of dying by their chronic drug abuse, even in the absence of any anatomical or toxicologic finding at autopsy to account for death.
What Is Adequate Sampling of Extraplacental Membranes?: A Randomized, Prospective Analysis
Authors: Winters Ryan , Waters Brenda L.
Published: February 2021

Context.—It is the generally accepted practice to submit 1 or 2 membrane rolls when examining placentas.

Objective.—To determine whether obtaining additional sections would increase diagnostic yield and, if so, to what degree.

Design.—A membrane roll section was prospectively procured from each quadrant of its respective singleton placenta. These placentas were submitted for routine pathologic examination, the process of which was entirely separate from this study. All study sections were randomized and assigned new numbers, thereby blinding the pathologist to the placenta of origin. We evaluated the incidence of acute chorionitis/chorioamnionitis (AC/A) and atherosis when 1, 2, 3, or 4 slides were examined. The diagnostic yield from all possible combinations of single, pairs, and triplets of sections was tabulated. When an additional slide identified more extensive acute inflammation than what was demonstrated initially, the AC/A was upstaged.

Results.—With 1 section examined, 7 to 10 placentas had AC/A. With 2 sections, 10 to 15 placentas had AC/A; with 3 sections, 16 to 18 cases; and with 4 sections, 19 cases. Additional sections upstaged the AC/A diagnosis infrequently. A total of 4 of 53 placentas had atherosis, based on review of all 4 slides. One slide identified 1 to 3 cases of atherosis. With a second and third section, the yield increased to 2 to 4 and 3 to 4, respectively.

Conclusions.—Review of a single membrane roll identified, at most, 53% of cases of AC/A and 50% of cases of atherosis. Additional sections increased the yield for both diagnoses in a roughly linear manner.
Hepatic Adenomatosis
Authors: Greaves Wesley O. C. , Bhattacharya Baishali
Published: February 2021

Hepatic adenomatosis was first described in 1985 by Flejou et al as multiple adenomas, arbitrarily more than 10, in an otherwise normal liver parenchyma. Several authors have suggested that it is a distinct entity from hepatic adenoma, which is predominantly seen in young women taking oral contraceptives. Although considered a benign disease, it can be associated with potentially fatal complications such as malignant transformation and intraperitoneal hemorrhage due to rupture. Although its etiology and natural history have not been fully elucidated, germline mutation of hepatocyte nuclear factor 1α, which is associated with maturity-onset diabetes of the young type 3, has recently been implicated in a subset of cases. Currently, there is no consensus on patient management. However, surgical removal of large lesions may significantly improve symptoms and reduce the risk of complications. Genetic counseling may now play an important role in case management.
Pediatric Follicular Lymphoma: A Rare Clinicopathologic Entity
Authors: Agrawal Renuka , Wang Jun
Published: February 2021

Follicular lymphoma, although common in adults, is rare in children. Pediatric follicular lymphoma has a more favorable prognosis than adult follicular lymphoma, even though it is often of higher grade. Children with follicular lymphomas are generally at a lower clinical stage, respond well to less aggressive therapy, and have a better survival than adults. Follicular lymphoma must be distinguished from reactive follicular hyperplasia, which it may mimic. Immunohistochemical and molecular markers serve to facilitate this distinction, as well as careful attention to clinical and morphologic details. It is important to recognize pediatric follicular lymphoma as a unique clinicopathologic entity to properly diagnose and manage these patients. It may represent a subset of follicular lymphoma with a particularly good prognosis.
Hamartoma of the Spleen
Authors: Lee Hwajeong , Maeda Koichi
Published: February 2021

Splenic hamartoma is a rare, benign vascular proliferation that is often found incidentally while working up other complaints or at autopsy. Women more commonly present with symptoms related to mass effect than men. Histologic findings consist of unorganized vascular channels of varying width, with intervening red pulp–like disorganized stroma with or without lymphoid follicles. The endothelial cells are similar to those of normal splenic sinuses. Although rendering a diagnosis can be difficult, endothelial cells that are positive for CD8 are a key feature that differentiate hamartoma from other vascular lesions of the spleen. Clinical, radiologic, and histologic correlation is essential to ensure this benign lesion is not mistaken for malignancy.
Human Papillomavirus Typing and Viral Gene Expression Analysis for the Triage of Women With Abnormal Results From Papanicolaou Test Smears to Colposcopy
Authors: Antonishyn Nick A. , Horsman Greg B. , Kelln Rod A. , Severini Alberto
Published: February 2021

Context.—A cascade of molecular tests for human papillomavirus (HPV), as a follow-up to Papanicolaou test screening, could eliminate unnecessary colposcopy. Tests based on detection of HPV E6 messenger RNA (mRNA) are already being used as screening tools, but there is a good biological rationale for expecting that an increase in the relative amounts of HPV E6 mRNA in cervical samples may better predict cancerous transformation.

Objective.—To compare some of the available diagnostic methods and our novel method of relative quantification (RQ) of HPV gene expression for the effective triage of women with abnormal results from Papanicolaou tests to colposcopy.

Design.—Sensitivities, specificities, and likelihood ratios were calculated for repeat Papanicolaou test smears, HPV DNA polymerase chain reactions, HPV genotyping, HPV-16 E6 mRNA detection, and the RQ of HPV-16 E6 mRNA calibrated to cellular RNA and DNA levels and standardized to viral load.

Results.—Human papillomavirus genotype in combination with a repeat Papanicolaou test can be used to categorize most women (96%) with cervical intraepithelial neoplasia of grade 2 or higher for colposcopy while eliminating 44% of women with cervical intraepithelial neoplasia 1 or less. The presence of HPV-16 E6 mRNA (P < .001) and RQ of HPV-16 E6 mRNA (P < .001) displayed significant median differences among the various grades of cervical intraepithelial neoplasia. Further testing of women who are positive for HPV-16 demonstrated that the RQ of E6 mRNA has diagnostic potential when combined with Papanicolaou testing in populations with higher disease prevalence.

Conclusions.—The RQ of HPV E6 mRNA and HPV genotype could be useful in a cascade of diagnostic testing designed to refer women with findings of cervical abnormalities for colposcopy or treatment while reducing triage numbers.
Drug-Induced Thrombocytopenia
Authors: Kenney Barton , Stack Gary
Published: February 2021

Drug-induced thrombocytopenia was first described in the 19th century, yet our understanding of its pathogenesis continues to evolve. The list of drugs implicated in drug-induced thrombocytopenia is extensive and growing. Many, if not most, of these medications induce thrombocytopenia by immune mechanisms. Because the degree of thrombocytopenia can put patients at risk for serious bleeding, a prompt diagnosis is key to clinical management. The laboratory approach to diagnosing drug-induced thrombocytopenia is 2-pronged. First, nondrug causes of thrombocytopenia must be ruled out. Second, testing for drug-dependent platelet antibodies, available at specialized reference laboratories, often can identify the offending medication, although usually not in time for initial clinical management. Once a medication is suspected of causing thrombocytopenia, it must be discontinued promptly, and the patient should be monitored closely. Thrombocytopenia generally resolves quickly after offending medication withdrawal, and the prognosis of drug-induced thrombocytopenia is then excellent.
Relation Between Red Blood Cell Distribution Width and Inflammatory Biomarkers in a Large Cohort of Unselected Outpatients
Authors: Lippi Giuseppe , Targher Giovanni , Montagnana Martina , Salvagno Gian Luca , Zoppini Giacomo , Guidi Gian Cesare
Published: February 2021

Context.—A strong independent association has been recently observed between elevated red blood cell distribution width (RDW) and increased incidence of cardiovascular events.

Objective.—To assess whether RDW is associated with plasma markers of inflammation since the mechanism(s) underlying this association remain unknown.

Design.—We retrospectively analyzed results of RDW, hemoglobin, mean corpuscular volume, ferritin, high-sensitivity C-reactive protein (hsCRP), and erythrocyte sedimentation rate (ESR) in a large cohort of unselected adult outpatients who were consecutively referred by general practitioners for routine medical check-up.

Results.—Cumulative results of RDW and other factors were retrieved from the database of our laboratory information system for 3845 adult outpatients during a 3-year period. When participants were grouped according to RDW quartiles, there were strong, graded increases of ESR and hsCRP (P < .001), both parameters being up to 3-fold higher in the fourth versus the first quartile. Accordingly, the percentages of those with hsCRP greater than 3 mg/L (from 28% to 63%; P < .001) and ESR greater than 40 mm/h (from 8% to 40%; P < .001) increased steadily across RDW quartiles. In multivariable regression analysis, ESR and hsCRP predicted RDW independently of age, sex, mean corpuscular volume, hemoglobin, and ferritin.

Conclusions.—To our knowledge, our study demonstrates for the first time a strong, graded association of RDW with hsCRP and ESR independent of numerous confounding factors. If confirmed in future follow-up studies, this association might provide a rationale to introduce the easy, inexpensive RDW in algorithms for cardiovascular risk prediction.
Pathology of Breast Carcinomas After Neoadjuvant Chemotherapy: An Overview With Recommendations on Specimen Processing and Reporting
Authors: Sahoo Sunati , Lester Susan C.
Published: February 2021

Context.—Currently, more women are being treated with chemotherapy or hormonal agents before surgery (neoadjuvant chemoendocrine therapy) for earlier-stage operable breast carcinoma. The pathologic examination of these specimens can be quite challenging.

Objective.—To give an overview of (1) pathologic changes that occur during treatment, (2) systems for evaluating response to treatment, and (3) recommendations for pathologic examination and reporting of such cases.

Data Sources.—The recommendations are based on the review of selected literature on breast carcinoma after neoadjuvant therapy and the authors' personal experience with the clinical and pathologic characteristics of cases from each of the authors' own institutions.

Conclusions.—Pathologists play a key role in the evaluation of pathologic response, which is extremely important as a prognostic factor for individual patients, as a short-term endpoint for clinical trials, and as an adjunct for research studies. Therefore, surgical pathologists must be familiar with the gross examination, sampling, and reporting of breast carcinomas after neoadjuvant therapy.
Sclerosing Hemangioma of the Lung
Authors: Keylock C. P. T. Joren B. , Galvin Jeffrey R. , Franks Teri J.
Published: February 2021

We present a brief review of sclerosing hemangioma, an uncommon but histologically distinctive neoplasm of the lung. Based on immunohistochemical and molecular findings, sclerosing hemangioma is thought to be derived from incompletely differentiated respiratory epithelium. Sclerosing hemangiomas typically present as asymptomatic, peripheral, solitary, well-circumscribed lesions in women with a mean age at diagnosis in the fifth decade. Rare cases are reported to have regional lymph node metastases; however, metastases do not appear to affect long-term survival. Histologically, sclerosing hemangioma is characterized by a distinct constellation of findings including 2 epithelial cell types, surface cells and round cells, which form 4 architectural patterns, papillary, sclerotic, solid, and hemorrhagic. Sclerosing hemangioma of the lung is generally considered to be a benign lesion, and surgical excision is curative without the need for additional treatment.
The Role of Computer-Aided 3-Dimensional Analytic Tools and Virtual Microscopy in the Investigation of Radiologic-Pathologic Correlation
Authors: Furuya Keizo , Maeda Toshiharu , Nakanura Seiji , Kikuchi Takanori
Published: February 2021

To cope with recent advances in radiologic imaging technology, a corresponding method for pathomorphologic demonstration should be developed to promote better understanding of radiologic-pathologic correlation. We attempted to obtain gross and microscopic images by using a 3-dimensional analytic tool and virtual microscopy and to link these images with multidetector computed tomography images. Surgically resected specimens were sliced to a thickness of 3 mm, and the digital images of each slice were 3-dimensionally reconstructed with RATOC TRI/3D SRF II software. Histology slides were digitized by using virtual microscopy with an Olympus VS-100. We obtained clear gross pathologic images in arbitrary cut sections of organs, and it was possible to rotate these 3-dimensional images at any angle. Furthermore, we created synchronous cut-section movies of computed tomography and gross pathologic images. Subsequently, we switched from these cut-section movies to virtual microscopy images by clicking on the hyperlink button to observe radiologic-pathologic correlation.
Significant and Unexpected, and Critical Diagnoses in Surgical Pathology: A College of American Pathologists' Survey of 1130 Laboratories
Authors: Nakhleh Raouf E. , Souers Rhona , Brown Richard W.
Published: February 2021

Context.—The Joint Commission and the College of American Pathologists have emphasized improved communication as a strategy to improve patient safety and reduce errors.

Objective.—To determine current policies and practices concerning critical and/or significant and unexpected results in anatomic pathology.

Design.—A survey was distributed with the 2007 D mailing of the Performance Improvement Program slides. The survey included questions that determined laboratory size, practice setting, and anatomic pathology critical and/or significant and unexpected result policies and practices.

Results.—Surveys from 1130 laboratories were received. A total of 75% had a written policy regarding anatomic pathology critical and/or significant and unexpected results; 25% did not. A total of 30% of laboratories with written policies stated that their policies included guidelines but did not include specific examples. A total of 33% listed 5 or fewer specific examples, 18% listed more than 5 examples, and 19% stated that they had a specifically defined list of significant and unexpected and/or critical diagnoses. The conditions that were listed included malignancies (48% of all laboratories), findings not expected by the clinical history (45%), life-threatening infections (45%), no chorionic villi in products of conception (37%), inflammatory or immunologic processes (19%), and organ rejection (14%). Laboratories with a higher median number of accessioned surgical and cytology cases and independent laboratories tended to have policies with more than 5 specific examples or precise lists of must-call diagnoses (P < .001).

Conclusions.—This survey illustrates current anatomic pathology policies and practices with respect to critical and significant and unexpected results.
The RAV12 Monoclonal Antibody Recognizes the N-Linked Glycotope RAAG12: Expression in Human Normal and Tumor Tissues
Authors: Coberly Suzanne K. , Chen Francine Z. , Armanini Mark P. , Chen Yan , Young Peter F. , Mather Jennie P. , Loo Deryk T.
Published: February 2021

Context.—RAAG12 is a primate-restricted N-linked carbohydrate antigen present on multiple membrane-associated proteins. RAAG12 is recognized by the RAV12 monoclonal antibody. RAV12 binds to RAAG12-expressing gastrointestinal adenocarcinomas, modifies growth factor-mediated signaling, induces oncotic cell death in vitro, and has antitumor activity toward gastrointestinal tumor xenografts.

Objective.—To determine the expression pattern of RAAG12 in normal and tumor tissue to identify indications for clinical study and potential safety issues.

Design.—Immunohistochemistry of 36 normal human tissues and a broad range of tumor tissues to profile RAAG12 expression.

Results.—More than 90% of colon, gastric, and pancreatic adenocarcinomas expressed RAAG12, and expression was uniform in most samples. Expression of RAAG12 at lower frequency and/or uniformity was observed in other cancers, including esophageal, ovarian, liver, breast, and prostate carcinomas and adenocarcinomas. Similar RAAG12 expression was observed between primary and metastatic colon adenocarcinomas. No staining was seen on cardiovascular, endocrine, neuromuscular, hematopoietic, or nervous system tissue from non–tumor-bearing individuals. RAAG12 was expressed on mucosal and glandular/ductal epithelium. The gastrointestinal tract mucosa and pancreatic/biliary ducts displayed the most uniform reactivity. RAAG12 exhibited differential subcellular localization in these normal, compared with tumor, tissues. Normal polarized epithelia primarily displayed apical membrane and cytoplasmic staining, whereas tumors exhibited whole membrane staining that increased with decreasing differentiation.

Conclusions.—High expression of RAAG12 on tumors of gastrointestinal origin suggests these cancers are appropriate targets for RAV12 therapy. Differential subcellular location of RAAG12 on normal epithelia may limit accessibility of RAV12 to the subset of normal tissues that exhibit antigen expression.
Henrietta Lacks, HeLa Cells, and Cell Culture Contamination
Authors: Lucey Brendan P. , Nelson-Rees Walter A. , Hutchins Grover M.
Published: February 2021

Henrietta Lacks died in 1951 of an aggressive adenocarcinoma of the cervix. A tissue biopsy obtained for diagnostic evaluation yielded additional tissue for Dr George O. Gey's tissue culture laboratory at Johns Hopkins (Baltimore, Maryland). The cancer cells, now called HeLa cells, grew rapidly in cell culture and became the first human cell line. HeLa cells were used by researchers around the world. However, 20 years after Henrietta Lacks' death, mounting evidence suggested that HeLa cells contaminated and overgrew other cell lines. Cultures, supposedly of tissues such as breast cancer or mouse, proved to be HeLa cells. We describe the history behind the development of HeLa cells, including the first published description of Ms Lacks' autopsy, and the cell culture contamination that resulted. The debate over cell culture contamination began in the 1970s and was not harmonious. Ultimately, the problem was not resolved and it continues today. Finally, we discuss the philosophical implications of the immortal HeLa cell line.
Pulmonary Pathologic Findings of Fatal 2009 Pandemic Influenza A/H1N1 Viral Infections
Authors: Gill James R. , Sheng Zong-Mei , Ely Susan F. , Guinee Donald G. , Beasley Mary B. , Suh James , Deshpande Charuhas , Mollura Daniel J. , Morens David M. , Bray Mike , Travis William D. , Taubenberger Jeffery K.
Published: February 2021

Context

In March 2009, a novel swine-origin influenza A/H1N1 virus was identified. After global spread, the World Health Organization in June declared the first influenza pandemic in 41 years.

Objective

To describe the clinicopathologic characteristics of 34 people who died following confirmed A/H1N1 infection with emphasis on the pulmonary pathology findings.

Design

We reviewed medical records, autopsy reports, microbiologic studies, and microscopic slides of 34 people who died between May 15 and July 9, 2009, and were investigated either by the New York City Office of Chief Medical Examiner (32 deaths) or through the consultation service of a coauthor (2 deaths).

Results

Most of the 34 decedents (62%) were between 25 and 49 years old (median, 41.5 years). Tracheitis, bronchiolitis, and diffuse alveolar damage were noted in most cases. Influenza viral antigen was observed most commonly in the epithelium of the tracheobronchial tree but also in alveolar epithelial cells and macrophages. Most cases were reverse transcription–polymerase chain reaction positive for influenza. Histologic and microbiologic autopsy evidence of bacterial pneumonia was detected in 55% of cases. Underlying medical conditions including cardiorespiratory diseases and immunosuppression were present in 91% of cases. Obesity (body mass index, >30) was noted in 72% of adult and adolescent cases.

Conclusions

The pulmonary pathologic findings in fatal disease caused by the novel pandemic influenza virus are similar to findings identified in past pandemics. Superimposed bacterial infections of the respiratory tract were common. Preexisting obesity, cardiorespiratory diseases, and other comorbidities also were prominent findings among the decedents.
Intraosseous Benign Notochordal Cell Tumor
Authors: Amer Hoda Zeinab M. , Hameed Meera
Published: February 2021

Intraosseous benign notochordal cell tumor is a presumably benign, intravertebral lesion of notochord origin, which can be found incidentally on removal of the vertebra for unrelated lesions or during an autopsy. The notion of a larger benign notochordal cell tumor that is macroscopic, occasionally symptomatic, and seen radiologically was recently introduced, and described as giant vertebral notochordal rest, giant notochordal hamartoma of intraosseous origin, and benign chordoma. Because of the location, size, and similar histologic and immunohistochemical characteristics, larger benign notochordal cell tumors are easily misdiagnosed as the malignant notochord-type of tumor/chordoma, with critical implications. In this review, we attempt to shed light on the major differences between benign notochordal cell tumors and chordoma and other related notochord lesions, such as notochordal vestiges of the intervertebral disk and ecchordosis physaliphora.
The Pathologist's Approach to Acute Lung Injury
Authors: Beasley Mary Beth
Published: February 2021

Context.—Acute lung injury and acute respiratory distress syndrome are significant causes of pulmonary morbidity and are frequently fatal. These 2 entities have precise definitions from a clinical standpoint. Histologically, cases from patients with clinical acute lung injury typically exhibit diffuse alveolar damage, but other histologic patterns may occasionally be encountered such as acute fibrinous and organizing pneumonia, acute eosinophilic pneumonia, and diffuse hemorrhage with capillaritis.

Objective.—To review the diagnostic criteria for various histologic patterns associated with a clinical presentation of acute lung injury and to provide diagnostic aids and discuss the differential diagnosis.

Data sources.—The review is drawn from pertinent peer-reviewed literature and the author's personal experience.

Conclusions.—Acute lung injury remains a significant cause of morbidity and mortality. The pathologist should be aware of histologic patterns of lung disease other than diffuse alveolar damage, which are associated with a clinical presentation of acute lung injury. Identification of these alternative histologic findings, as well as identification of potential etiologic agents, especially infection, may impact patient treatment and disease outcome.
American Society of Clinical Oncology/College of American Pathologists Guideline Recommendations for Immunohistochemical Testing of Estrogen and Progesterone Receptors in Breast Cancer
Authors: Hammond M. Elizabeth H. , Hayes Daniel F. , Dowsett Mitch , Allred D. Craig , Hagerty Karen L. , Badve Sunil , Fitzgibbons Patrick L. , Francis Glenn , Goldstein Neil S. , Hayes Malcolm , Hicks David G. , Lester Susan , Love Richard , Mangu Pamela B. , McShane Lisa , Miller Keith , Osborne C. Kent , Paik Soonmyung , Perlmutter Jane , Rhodes Anthony , Sasano Hironobu , Schwartz Jared N. , Sweep Fred C. G. , Taube Sheila , Torlakovic Emina Emilia , Valenstein Paul , Viale Giuseppe , Visscher Daniel , Wheeler Thomas , Williams R. Bruce , Wittliff James L. , Wolff Antonio C.
Published: February 2021

Purpose.—To develop a guideline to improve the accuracy of immunohistochemical (IHC) estrogen receptor (ER) and progesterone receptor (PgR) testing in breast cancer and the utility of these receptors as predictive markers.

Methods.—The American Society of Clinical Oncology and the College of American Pathologists convened an international Expert Panel that conducted a systematic review and evaluation of the literature in partnership with Cancer Care Ontario and developed recommendations for optimal IHC ER/PgR testing performance.

Results.—Up to 20% of current IHC determinations of ER and PgR testing worldwide may be inaccurate (false negative or false positive). Most of the issues with testing have occurred because of variation in preanalytic variables, thresholds for positivity, and interpretation criteria.

Recommendations.—The Panel recommends that ER and PgR status be determined on all invasive breast cancers and breast cancer recurrences. A testing algorithm that relies on accurate, reproducible assay performance is proposed. Elements to reliably reduce assay variation are specified. It is recommended that ER and PgR assays be considered positive if there are at least 1% positive tumor nuclei in the sample on testing in the presence of expected reactivity of internal (normal epithelial elements) and external controls. The absence of benefit from endocrine therapy for women with ER-negative invasive breast cancers has been confirmed in large overviews of randomized clinical trials.
The Future of Telepathology for the Developing World
Authors: Hitchcock Charles L
Published: February 2021

Physician shortages are acute in developing countries, where disease burden is the greatest and resources for health care are very limited. A lack of pathologists in these countries has lead to delays in diagnosis and misdiagnoses that adversely affect patient care and survival. The introduction of telepathology into countries with limited resources for health care is but one of multiple approaches that can be used to alleviate the problem.

Telepathology is the electronic transmission of digital images that can be used for education and diagnostic consultation. A basic system consists of a microscope with a mounted digital camera linked to a computer. The ability to produce histologic slides, to repair and maintain equipment, and to provide training are also needed for the successful use of this technology.

iPath is a Web-based, open platform, software application which was developed at the University of Basel, Switzerland, for telepathology and which brings together pathologists from around the world to provide telepathology support for diagnostic consultation and provides education to centers with limited resources. The use of virtual-slide technology to provide a digital image of an entire glass slide is another technology for diagnostic consultation and pathology education. This technology requires more costly resources to support it, which may limit its utility in many areas. Telepathology can generate collections of digital images and virtual slides needed for training indigenous pathologists in their countries to become self-sufficient. Thus, the long-term goal of this technology is to improve patient care and survival.
The Tissue Microarray Object Model: A Data Model for Storage, Analysis, and Exchange of Tissue Microarray Experimental Data
Authors: Lee Hye Won , Park Yu Rang , Sim Jaehyun , Park Rae Woong , Kim Woo Ho , Kim Ju Han
Published: February 2021

Context.—Tissue microarray (TMA) is an array-based technology allowing the examination of hundreds of tissue samples on a single slide. To handle, exchange, and disseminate TMA data, we need standard representations of the methods used, of the data generated, and of the clinical and histopathologic information related to TMA data analysis.

Objective.—To create a comprehensive data model with flexibility that supports diverse experimental designs and with expressivity and extensibility that enables an adequate and comprehensive description of new clinical and histopathologic data elements.

Design.—We designed a tissue microarray object model (TMA-OM). Both the array information and the experimental procedure models are created by referring to the microarray gene expression object model, minimum information specification for in situ hybridization and immunohistochemistry experiments, and the TMA data exchange specifications. The clinical and histopathologic information model is created by using College of American Pathologists cancer protocols and National Cancer Institute common data elements. Microarray Gene Expression Data Ontology, the Unified Medical Language System, and the terms extracted from College of American Pathologists cancer protocols and NCI common data elements are used to create a controlled vocabulary for unambiguous annotation.

Result.—The TMA-OM consists of 111 classes in 17 packages to represent clinical and histopathologic information as well as experimental data for any type of cancer. We implemented a Web-based application for TMA-OM, supporting data export in XML format conforming to the TMA data exchange specifications or the document type definition derived from TMA-OM.

Conclusions.—The TMA-OM provides a comprehensive data model for storage, analysis, and exchange of TMA data and facilitates model-level integration of other biological models.
Eosinophilic Neuritis and Eosinophilic Panniculitis in a Patient With Advanced Acquired Immunodeficiency Syndrome
Authors: Soldano Anthony C. , Walters Ruth , Groben Pamela A.
Published: February 2021

The pruritic, papular eruption of human immunodeficiency virus with associated peripheral eosinophilia is well documented. We describe a 32-year-old African American man with advanced acquired immunodeficiency syndrome; a generalized painful, pruritic, papular rash; peripheral blood eosinophilia; and perineural eosinophilic infiltrates with eosinophilic panniculitis. To our knowledge, the latter 2 features have not been previously described in the literature on human immunodeficiency virus dermatoses. We propose that eosinophilic neuritis and eosinophilic panniculitis may represent additional findings in the spectrum of cutaneous disease seen in patients with advanced acquired immunodeficiency syndrome.
Pulmonary Adenocarcinoma: The Expanding Spectrum of Histologic Variants
Authors: Moran Cesar A.
Published: February 2021

Pulmonary adenocarcinoma is one of the most common types of lung cancer. Traditionally, adenocarcinomas have been divided based on their degree of resemblance to their parent tissues into 3 histopathologic types: well, moderately, and poorly differentiated. In the majority of cases, this schema is sufficient to categorize these lung tumors. However, there is a considerable group of tumors in which the histology is not that of the classic gland-forming neoplasm. Thus, although the terminology of adenocarcinoma is applied in such cases, the histopathologic features are different from those of the more conventional variants. The current review addresses these unusual variants and the importance of recognizing and properly categorizing them to avoid unnecessary additional workup or possible misdiagnosis.
Primary Testicular and Paratesticular Lymphoma: A Retrospective Clinicopathologic Study of 34 Cases With Emphasis on Differential Diagnosis
Authors: Al-Abbadi Mousa A. , Hattab Eyas M. , Tarawneh Musleh , Orazi Attilio , Ulbright Thomas M.
Published: February 2021

Context.—Recent reports indicate the rate of primary testicular lymphomas is on the rise and misdiagnosis can still occur.

Objective.—To review and investigate the clinicopathologic features of primary testicular lymphoma with emphasis on the differential diagnosis. Discussion about the issue of misdiagnosis is also presented.

Design.—Retrospective review of pathology archives in 3 medical centers for cases fulfilling criteria of primary testicular lymphoma or paratesticular lymphoma was carried out. Clinicopathologic and immunohistochemical features were studied and analyzed.

Results.—The search identified 34 cases. Patients ranged from 4 to 87 years of age (mean, 55 years). All presented with a testicular/paratesticular mass and were stage I. The masses ranged from 2.5 to 13 cm (mean, 5.6 cm). Microscopically, the tumors often had an intertubular growth pattern or diffuse arrangement of predominantly large cells with pleomorphic, twisted nuclei and small nucleoli. Mitotic activity was brisk and apoptotic bodies were abundant. Thirty-two tumors were classified as diffuse large cell lymphomas; immunophenotype was determined in 21 of these and all were of B-cell type. The median survival was 96 months. The rate of initial misdiagnosis was unexpectedly high (5 cases, 15%).

Conclusions.—Most cases of primary testicular lymphoma fall into the broad category of diffuse large cell lymphoma and the majority are B-cell type with particularly high proliferative activity when characterized by appropriate immunophenotyping. Misdiagnosis can occur, especially in those cases in which presentation occurs at an age similar to that for germ cell tumors, showing the need for caution and appropriate immunostaining when a testicular neoplasm has an atypical appearance for a germ cell tumor.
Selecting Automation for the Clinical Chemistry Laboratory
Authors: Melanson Stacy E. F. , Lindeman Neal I. , Jarolim Petr
Published: February 2021

Context.—Laboratory automation proposes to improve the quality and efficiency of laboratory operations, and may provide a solution to the quality demands and staff shortages faced by today's clinical laboratories. Several vendors offer automation systems in the United States, with both subtle and obvious differences. Arriving at a decision to automate, and the ensuing evaluation of available products, can be time-consuming and challenging. Although considerable discussion concerning the decision to automate has been published, relatively little attention has been paid to the process of evaluating and selecting automation systems.

Objective.—To outline a process for evaluating and selecting automation systems as a reference for laboratories contemplating laboratory automation.

Design.—Our Clinical Chemistry Laboratory staff recently evaluated all major laboratory automation systems in the United States, with their respective chemistry and immunochemistry analyzers. Our experience is described and organized according to the selection process, the important considerations in clinical chemistry automation, decisions and implementation, and we give conclusions pertaining to this experience.

Results.—Including the formation of a committee, workflow analysis, submitting a request for proposal, site visits, and making a final decision, the process of selecting chemistry automation took approximately 14 months. We outline important considerations in automation design, preanalytical processing, analyzer selection, postanalytical storage, and data management.

Conclusions.—Selecting clinical chemistry laboratory automation is a complex, time-consuming process. Laboratories considering laboratory automation may benefit from the concise overview and narrative and tabular suggestions provided.
Multifocal, Extranodal Sinus Histiocytosis With Massive Lymphadenopathy: An Overview
Authors: Gaitonde Sujata
Published: February 2021

Context.—This article provides an overview of the major pathologic manifestations of sinus histiocytosis with massive lymphadenopathy, including patient characteristics and current knowledge about its pathogenesis, with an emphasis on multifocal and extranodal presentation. Sinus histiocytosis with massive lymphadenopathy is a rare, nonneoplastic, idiopathic, proliferative histiocytic disorder; recognition of this disorder is important to avoid misinterpretation and subsequent unnecessary treatment. This is especially true for primary extranodal manifestation of this rare disorder. Although accurate diagnosis of this entity requires a correlation of clinical, radiologic, laboratory, and pathologic studies in most cases, it remains a disorder primarily defined by its histopathologic features and pathologic manifestations, which are key to the diagnosis.

Objective.—To summarize the scientific literature, provide a concise review, and emphasize the diagnostic histopathologic features of extranodal sinus histiocytosis with massive lymphadenopathy.

Data Sources.—A comprehensive literature review was undertaken to summarize the clinical and pathologic features of this disorder.

Conclusions.—Sinus histiocytosis with massive lymphadenopathy is characterized by a rare, acquired, nonmalignant proliferation of distinctive histiocytes that present with lymphadenopathy or extranodal disease, primarily in children and young adults. It exhibits a broad range of clinical presentations, thus eliciting a wide differential diagnosis. The diverse clinical manifestations and frequent association with subtle or severe immunologic abnormalities suggest an immune-mediated cause. Additional studies are needed to characterize the interplay between death receptors and cytotoxic mediators and to further elucidate the loss of immune hemostasis that may underlie idiopathic histiocytic proliferations such as this.
An Overview of Testicular Germ Cell Tumors
Authors: Bahrami Armita , Ro Jae Y. , Ayala Alberto G.
Published: February 2021

Context.—More than 90% of testicular neoplasms originate from germ cells. Testicular germ cell tumors (GCTs) are a heterogeneous group of neoplasms with diverse histopathology and clinical behavior.

Objective.—To help the readers distinguish various subtypes of GCTs, to highlight the clinical manifestations and pathologic features of these tumors, and to review several newly developed immunohistochemical markers for GCTs.

Data Sources.—Review of the pertinent literature and our experience.

Conclusions.—The etiology of GCTs is largely unknown. Cytogenetic studies suggest a different pathogenesis for each group of infantile/prepubertal GCTs, postpubertal GCTs, and spermatocytic seminoma. Unclassified intratubular germ cell neoplasia is the precursor of all GCTs, excluding spermatocytic seminoma and infantile/prepubertal GCTs. Seminoma, the most common GCT in adults, does not occur before 5 years of age. Spermatocytic seminoma, a tumor of elderly men, typically has an indolent clinical behavior, but rarely it undergoes sarcomatous transformation associated with an aggressive behavior. Embryonal carcinoma is the most common component in mixed GCTs. Eighty percent or more of embryonal carcinoma component and vascular invasion are recognized predictors of occult metastasis for clinical stage I mixed GCTs. Most patients with prepubertal yolk sac tumor, the most common pediatric GCT, have stage I disease at presentation. Most choriocarcinomas present with metastatic symptoms because of the propensity for rapid hematogenous dissemination. Teratomas in children regardless of maturity and dermoid cysts in adults are benign; in contrast, teratomas in adults have a malignant behavior. With appropriate therapy, the majority of testicular GCTs are curable.
Small Round Cell Tumors of Bone
Authors: Hameed Meera
Published: February 2021

Context.—Primary small round cell tumors of the bone are a heterogeneous group of malignant neoplasms presenting predominantly in children and adolescents. They include Ewing sarcoma/peripheral neuroectodermal tumor or Ewing family tumors, lymphoma, mesenchymal chondrosarcoma, and small cell osteosarcoma. Even though they share many morphological similarities, their unique biological and genetic characteristics have provided substantial insights into the pathology of these diverse neoplasms.

Objective.—To provide an overview of the clinical, radiologic, pathologic, and genetic characteristics of these tumors along with a pertinent review of the literature.

Data Sources.—A literature search using PubMed and Ovid MEDLINE was performed, and data were obtained from various articles pertaining to clinicopathologic, biological, and genetic findings in these tumors. Additionally, findings from rare cases have been included from author's subspecialty experience.

Conclusion.—The diagnosis of small round cell tumors can be made accurately by applying clinicopathologic criteria, as well as a panel of immunohistochemical and genetic studies in appropriate cases. Molecular genetic studies may provide further insight into the biology, histogenesis, and prognosis of these tumors.
Clinicopathologic Aspects of 1p/19q Loss and the Diagnosis of Oligodendroglioma
Authors: Aldape Kenneth , Burger Peter C. , Perry Arie
Published: February 2021

Context.—Significant interobserver variability exists with respect to the diagnosis of oligodendroglial neoplasms, especially their distinction from astrocytoma and mixed oligoastrocytoma. Combined loss of the short arm of chromosome 1 and the long arm of chromosome 19 has been shown to be both relatively specific to oligodendroglioma and, when present, a marker of improved prognosis in patients with these tumors. In addition, 1p/19q loss has been shown to be a marker of “classic” oligodendroglial histology. These findings raise questions as to the role of 1p/19q testing in clinical practice, both as a prognostic marker and as a potential diagnostic marker among infiltrating glial neoplasms.

Objective.—This review discusses the issues raised above and tries to clarify the current status of 1p/19q evaluation in the diagnosis of oligodendroglioma.

Data Sources.—Sources for this review include recent literature as well as the experience of 3 practicing neuropathologists.

Conclusions.—1p/19q status is an important marker in oligodendroglioma. Loss of 1p/19q is associated with classic oligodendroglioma histology as well as improved prognosis. The combined 1p/19q marker will continue to be a clinically useful marker of prognosis and could potentially be incorporated into diagnostic criteria in the future.