bluuebunny/crossref_metadata_2025 huggingface dataset:
Thin Melanoma
Authors: Elder David E
Published: February 2021

Context.—The incidence of malignant melanoma is increasing and a preponderance of the melanomas diagnosed today are “thin” in terms of Breslow criteria. Although thin melanomas, as a group, are associated with a very good prognosis, a subset of these tumors may metastasize and cause death. These cases can be identified by using prognostic models, including the “standard” American Joint Committee on Cancer criteria, and other attributes identified in follow-up studies.

Objective.—To review the history of concepts of prognostic modeling in melanoma, focusing on thin melanomas.

Data Sources.—Selected literature.

Conclusions.—About 40 years ago, it was realized that malignant melanoma, once almost uniformly fatal, could be divided into categories with better or worse prognosis through the use of prognostic models. The first simple models, Clark levels of invasion and Breslow thickness, are still in use. Thickness remains the single most useful variable. Breslow recognized that melanomas less than 0.76 mm in thickness were associated with a very good prognosis, with no metastases in his limited initial study. The American Joint Committee on Cancer selected a cutoff of 1.0 mm, which achieves a similar result, with stage modifiers, although some metastases and deaths do occur with stage I lesions. Clark demonstrated an almost equally good prognosis for his level II invasive melanomas and recognized that most of these lesions, although invasive, lacked the ability to form tumors or to undergo mitosis in the dermis and were therefore “nontumorigenic” and “nonmitogenic” and lacked competence for metastasis. Studies of these low-risk melanomas have led to the development of criteria for earlier diagnosis and a steady, but still inadequate, improvement in prognosis for melanoma overall. Multivariable models currently can identify groups of patients within the “thin melanoma” category whose prognosis varies, from a disease-free survival of close to 100% to about 70%. Prognosis declines more or less linearly with increasing thickness, modified by ulceration, mitotic rate, and other attributes.
The Relevance of Periglomerular Fibrosis in the Evaluation of Routine Needle Core Renal Biopsies
Authors: Jenkins Joseph , Brodsky Sergey V. , Satoskar Anjali A. , Nadasdy Gyongyi , Nadasdy Tibor
Published: February 2021

Context—Renal interstitial fibrosis and, to a lesser extent, sclerotic glomeruli correlate with poor renal function. However, not all nonfunctional glomeruli are sclerotic. Many or most glomeruli with periglomerular fibrosis, while retaining blood flow, probably do not filter; therefore, they may not contribute to renal function.

Objective—To examine the relationship of periglomerular fibrosis and the sum of globally sclerotic glomeruli and glomeruli with periglomerular fibrosis (GSG+PF) with interstitial fibrosis and renal function.

Design—Native kidney biopsies from 177 patients with chronic renal injury were assessed for interstitial fibrosis, glomerular sclerosis, and GSG+PF. Renal biopsies with active or acute lesions were not included. The percentage of globally sclerotic glomeruli and GSG+PF was correlated with the degree of interstitial fibrosis and serum creatinine levels.

Results—The percentage of GSG+PF correlates better with the degree of interstitial fibrosis and renal function than does the percentage of globally sclerotic glomeruli alone. This appears particularly true in chronic renal diseases of patients without diabetes. The number of globally sclerotic glomeruli correlates better with interstitial fibrosis and renal function than does the sum of globally and segmentally sclerotic glomeruli.

Conclusions—The percentage of GSG+PF in a renal biopsy specimen provides a better estimate of chronic renal injury than does the percentage of sclerotic glomeruli alone, probably because many or most glomeruli with periglomerular fibrosis are nonfunctional. Therefore, we recommend that the number of glomeruli with periglomerular fibrosis also be provided in the renal biopsy report.
Sentinel Lymph Nodes in Cutaneous Melanoma: Handling, Examination, and Clinical Repercussion
Authors: Prieto Victor G.
Published: February 2021

Context—Within the last 15 years, evaluation of sentinel lymph nodes (SLNs) has become the most popular method of early staging of several malignancies, including melanoma. Sentinel lymph nodes are usually examined on formalin-fixed, paraffin-embedded sections and by routine histology/immunohistochemistry (research protocols have used other techniques such as polymerase chain reaction). Approximately 20% of patients with cutaneous melanoma have metastasis in the SLN. In most studies, detection of positive SLN conveys a poorer prognosis for patients with cutaneous melanoma.

Objective—To review the morphologic patterns of melanoma metastasis in the SLN, the differential diagnosis, and the quantification of tumor burden as a prognostic factor.

Data Sources—Personal observations and review of the pertinent literature.

Conclusions—Evaluation of sentinel lymph nodes is certainly becoming a widespread technique and most authors agree on its prognostic power for staging patients with cutaneous melanoma. Current studies are evaluating the possible therapeutic value of removal of positive SLNs.
Diagnostic Challenges in the Pathologic Evaluation of Barrett Esophagus
Authors: Yantiss Rhonda K.
Published: February 2021

Context.—Barrett esophagus represents an unstable epithelium resulting from chronic gastroesophageal reflux disease. Patients with Barrett esophagus routinely undergo endoscopic examination to detect dysplasia and early carcinoma. Although appropriate classification of Barrett esophagus and neoplasia is usually straightforward, persistent esophageal inflammation may induce epithelial changes that mimic, or mask, dysplasia. Recent data also indicate that specific molecular changes occur in nondysplastic Barrett mucosa and herald the development of dysplasia and/or carcinoma.

Objective.—To describe problematic aspects of biopsy interpretation in tissue samples of the gastroesophageal junction and distal esophagus, including the diagnostic criteria for Barrett esophagus, the importance of the gastric cardia, and pitfalls to the diagnosis of dysplasia. Ancillary studies that have recently emerged as potential adjuncts to the evaluation of patients with Barrett esophagus will be briefly discussed.

Data Sources.—A comprehensive review of the relevant literature indexed in PubMed (National Library of Medicine) was performed.

Conclusions.—Barrett esophagus is currently defined as the presence of intestinal metaplasia in samples obtained from an endoscopically evident abnormality in the distal esophagus. Diagnosis and grading of dysplasia in mucosal biopsies remain the most reliable method to assess risk for neoplastic progression, but its classification may be hindered by superimposed inflammatory changes and suffers from considerable interobserver variability. Therefore, immunohistochemical studies and molecular assessment for TP53, CDKN2A, and DNA content abnormalities have emerged as potential adjuncts to the detection of dysplasia.
Digital Microscopy: Past, Present, and Future
Authors: Hedvat Cyrus V.
Published: February 2021

Context.—Digital viewing of histologic images is moving from presentations and publications to incorporation into the daily work of practicing pathologists. Many technologic limitations have been overcome recently, which should make widespread adoption more practical. The task now is for pathologists to become actively involved in its development and implementation, to ensure that the technology is developed with the intent to optimize workflow and to maintain diagnostic accuracy. An understanding of the basic precepts of digital imaging is required to make informed decisions related to hardware and software implementation and to collaborate with vendors and professionals outside of pathology (eg, regulatory agencies) as the technology rapidly develops.

Objective.—To describe the state of digital microscopy as it applies to the field of pathology and to define specific issues related to adoption of whole slide imaging systems.

Data Sources.—The information is derived from the experience of the author and review of the literature.

Conclusions.—Digital microscopy is an important tool for surgical pathologists. It is currently an area of intense and rapid technologic development that will likely transform the workflow of many laboratories during the next several years.
Uniform Expression of Notch1, Suppressor of B-Cell–Specific Gene Expression, in Plasmablastic Lymphoma
Authors: Seegmiller Adam C. , Wang Huan-You , Hladik Christa , Chen Weina
Published: February 2021

Context.—Although the loss of B-lineage–specific gene expression is a distinctive feature of plasmablastic lymphoma, the underlying mechanism remains poorly understood. A candidate for this mechanism is Notch1 signaling, which interferes with the activity of B-cell–specific transcription factors E2A and early B-cell factor and positively regulates the mammalian target of rapamycin (mTOR) pathway.

Objective.—To explore the mechanism of loss of B-cell phenotype by correlating expression of B-cell markers with that of Notch1 and downstream targets of the mTOR pathway in plasmablastic lymphoma.

Design.—A combination of flow cytometric and immunohistochemical immunophenotyping techniques was used on 9 cases of plasmablastic lymphoma to correlate loss of B-cell markers with expression of Notch1 and downstream activation of the mTOR pathway. These results are compared with 5 cases of primary effusion lymphoma and 21 cases of plasma cell myeloma.

Results.—Plasmablastic lymphoma cases exhibit nearly complete loss of B-cell–associated markers and uniform expression of Notch1, with a predominantly nuclear staining pattern. There is a concurrent activation of the mTOR pathway, indicated by expression of mTOR targets eukaryotic initiation factor 4E–binding protein 1 and phosphorylated ribosomal protein S6 in most cases. Similar results are seen in cases of primary effusion lymphoma and plasma cell myeloma.

Conclusions.—These findings suggest that activation of Notch1 may be involved in suppression of B-cell–specific gene expression and global loss of the B-cell phenotype in plasmablastic lymphoma, similar to primary effusion lymphoma and plasma cell myeloma. Thus, there might be a role for the Notch1 and mTOR pathways in the pathogenesis and therapy of plasmablastic lymphoma.
Carcinoids and High-Grade Neuroendocrine Carcinomas of the Ampulla of Vater: A Comparative Analysis of 139 Cases From the Surveillance, Epidemiology, and End Results Program—A Population Based Study
Authors: Albores-Saavedra Jorge , Hart Alexandra , Chablé-Montero Fredy , Henson Donald E.
Published: February 2021

Context.—Neuroendocrine tumors of the ampulla of Vater constitute a heterogeneous group of neoplasms clinically and morphologically. Because they are rare, little is known about their demographics and biologic behavior.

Objective.—To analyze the demographics and the 5- and 10-year relative survival rates of 139 patients with carcinoid tumors and high-grade neuroendocrine carcinomas of the ampulla.

Design.—Using data from National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) Program from 1973 to 2006, we analyzed the demographics, morphology, and survival of patients with carcinoids and neuroendocrine carcinomas of the ampulla.

Results.—SEER recorded 6081 cases of malignant neoplasms of the ampulla, of which 82 were carcinoid tumors and 57 were high-grade neuroendocrine carcinomas. Of these 57, 42 were neuroendocrine carcinomas, not otherwise specified; 9 were small cell carcinomas; and 6 were large cell neuroendocrine carcinomas. The incidence was higher in men than in women. Patients with carcinoid tumors were younger (mean age, 61.6 years) than those with high-grade neuroendocrine carcinomas (mean age, 67.5 years). Carcinoid tumors were smaller than high-grade neuroendocrine carcinomas. The frequency of lymph node metastasis was 28.5% for carcinoid tumors and 62% for high-grade neuroendocrine carcinomas. The 5- and 10-year relative survival rates of patients with carcinoid tumors were 82% and 71%, respectively. The 5- and 10-year relative survival rate of patients with high-grade neuroendocrine carcinomas was 15.7%.

Conclusions.—Carcinoids of the ampulla of Vater are relatively rare. Carcinoids and high-grade neuroendocrine carcinomas of the ampulla are biologically and clinically similar to these tumors arising in other sites. Carcinoids were smaller and metastasized less frequently than high-grade neuroendocrine carcinomas.
Blue Nevus of the Prostate
Authors: Dailey Virginia L. , Hameed Omar
Published: February 2021

Blue nevus is one of the melanotic lesions that can incidentally arise in the prostate gland. A literature review identified 28 previously reported cases, and although rare, the blue nevus appeared to be the commonest melanocytic lesion arising in the prostate. The differential diagnosis includes melanosis and malignant melanoma, as well as nonmelanotic lesions due to deposition of lipofuscin, hemosiderin and, rarely, homogentisic acid. The distinction among these lesions can typically be made based on morphologic grounds but may also be aided by histochemical and immunohistochemical stains such as stains for iron, S100 protein, HMB-45, and CD68 as needed. Blue nevus of the prostate is a benign lesion with no malignant potential to date, so no further treatment is warranted.
Follow-up Findings in Young Females With High-Grade Squamous Intraepithelial Lesion Papanicolaou Test Results
Authors: Zhao Chengquan , Kalposi-Novak Pal , Austin R. Marshall
Published: February 2021

Context.—New guidelines discourage cervical screening and procedures in young females, given available human papillomavirus vaccines, concerns regarding procedure-associated harms, and the rarity of cervical cancers.

Objective.—To analyze histopathologic follow-up data on a large number of young females with high-grade squamous intraepithelial lesion (HSIL) Papanicolaou (Pap) test results.

Design.—Hospital records were searched for HSIL Pap test results in females 20 years or younger between January 2002 and December 2007. Histopathologic and Pap test follow-up, age group variations, and impact of Pap test transformation zone/endocervical sampling were analyzed.

Results.—Four hundred seventy-four females aged 20 years or younger had HSIL Pap test results during the study period. Three hundred thirty-five young females with at least one cervical biopsy were included. The average age was 18.6 years (range, 13–20 years). The average follow-up period was 24 months (range, 0.1–75 months), with a median of 22 months. Histopathologic detection rates were 44.2% for cervical intraepithelial neoplasia (CIN) 2/3 and 47.8% for CIN 1. The average period between the HSIL Pap test result and an initial diagnosis of CIN 2/3 was 5 months (range, 0.1–62 months), with a median of 2 months. Neither invasive carcinoma nor adenocarcinoma in situ was identified. Presence or absence of a transformation zone/endocervical sample did not significantly impact CIN 2/3 risk (44.5% versus 38.9%, P  =  .64).

Conclusions.—Histopathologic CIN 2/3 was documented in 148 of 335 (44%) of biopsied young females with HSIL Pap results, likely reflecting both the reported high likelihood of HSIL regression in younger females and the challenge of colposcopic sampling of relatively short-lived smaller CIN 2/3 lesions. Although no cases of invasive carcinoma were identified in this study, updated guidelines pose new risks for maturing females with undetected cervical precancer.
A Survey-Based Assessment of United States Clinical Laboratory Response to the 2009 H1N1 Influenza Outbreak
Authors: Hayden Randall T. , Wick Megan T. , Rodriguez Alicia B. , Caliendo Angela M. , Mitchell Michael J. , Ginocchio Christine C. ,   for the Microbiology Resource Committee of the College of American Pathologists
Published: February 2021

Context.—The recent outbreak of pandemic influenza created enormous economic, logistical, and analytical challenges for clinical laboratories. Laboratory response represented a critical element in the care of affected patients, but little has been published regarding this aspect of the pandemic.

Objective.—To assess the overall response of clinical diagnostic laboratories across the United States to the initial phase of the 2009 H1N1 influenza A pandemic.

Design.—A 24-question survey was developed and distributed by e-mail to determine current influenza testing practices and how those practices were changed in response to the outbreak of 2009 H1N1 influenza. The survey was distributed to participants in the College of American Pathologists proficiency testing programs related to viral diagnostics. Survey questions focused on laboratory safety, communication of results, testing volume and resources, and whether changes in resource allocation or laboratory practice were anticipated in preparation for the 2009–2010 influenza season.

Results.—A total of 24.3% (931) of laboratories responded to the survey. Overall, few laboratories reported changes in methodology in response to the 2009 H1N1 influenza outbreak, although, notably, the number of centers using molecular amplification methods more than doubled, from 41 to 91. Turn-around time for result reporting and safety methods used were largely as expected for individual testing modalities. Shortages in staffing, testing supplies, and personal protective equipment were reported, but most sites were able to maintain operations and did not feel that patient care was negatively affected.

Conclusion.—This report provides a comprehensive picture of clinical laboratory responses in the early stages of the 2009 H1N1 influenza pandemic. These data should assist in the continued laboratory management of this outbreak and in planning for future emerging infections.
Sinonasal Glomangiopericytoma: Case Report With Emphasis on the Differential Diagnosis
Authors: Dandekar Monisha , McHugh Jonathan B.
Published: February 2021

Glomangiopericytoma (sinonasal-type hemangiopericytoma) is an uncommon sinonasal neoplasm with a perivascular myoid phenotype. This tumor differs from conventional soft tissue hemangiopericytoma in location, biologic behavior, and histologic features. The proposed cell of origin is a modified perivascular glomuslike myoid cell. Glomangiopericytoma is an indolent tumor that tends to arise in the sinonasal tract of older adults and has a low malignant potential with excellent prognosis after surgical resection. Histologically, this lesion is composed of a diffuse, subepithelial proliferation of bland, uniform, closely packed spindled cells growing in a variety of patterns. A distinctive vascular network composed of variably sized vascular channels, the smaller of which demonstrate perivascular hyalinization, is often present. We report the case of a 48-year-old woman with epistaxis and nasal obstruction who was diagnosed with glomangiopericytoma and discuss the histologic differential diagnosis.
Fine-Needle Aspiration of Intrapancreatic Accessory Spleen, Mimic of Pancreatic Neoplasms
Authors: Lin Jingmei , Jing Xin
Published: February 2021

Intrapancreatic accessory spleen (IPAS) is a congenital abnormality, which mimics neoplasm. Distinguishing IPAS from pancreatic neoplasm/malignancy is extremely important from a treatment perspective. We report the case of a 67-year-old asymptomatic man who had a 1.3-cm, incidentally detected, pancreatic tail mass. The mass was round, well-circumscribed, and hypervascular with uniform enhancement. The image findings were highly suggestive of a pancreatic endocrine neoplasm. An endoscopic ultrasound-guided fine-needle aspiration was performed. Conventional smears revealed a polymorphous population of lymphocytes admixed with a subset of other inflammatory cells. Hematoxylin-eosin–stained cell block sections showed conspicuous thin-walled blood vessels in addition to inflammatory cells. Immunostaining for CD8 demonstrated strong positivity in endothelial cells of the thin-walled vessels. By correlating the cytologic findings with the result of immunostaining, we rendered the diagnosis of IPAS. Our experience supports the view that endoscopic ultrasound-guided fine-needle aspiration may enable a reliable, preoperative diagnosis of IPAS and thus prevent unnecessary surgery.
Acute Myeloid Leukemia Diagnosis in the 21st Century
Authors: Betz Bryan L. , Hess Jay L.
Published: February 2021

Context.—Rapid advances in understanding the molecular biology of acute myeloid leukemia are transforming the approach to diagnosis, prognostication, and treatment of these cases.

Objective.—To briefly review the current state of AML classification with a particular emphasis on the role of molecular studies and their impact on the management of acute myeloid leukemia and other malignancies.

Data Sources.—Current literature and experience of the authors.

Conclusions.—While morphology, immunophenotyping, cytogenetics, and clinical history continue to play an important role, an increasing number of molecular tests are now required to properly classify these cases.
The Collagenous Gastroenteritides: Similarities and Differences
Authors: Gopal Purva , McKenna Barbara J.
Published: February 2021

Collagenous gastritis, collagenous sprue, and collagenous colitis share striking histologic similarities and occur together in some patients. They also share some drug and disease associations. Pediatric cases of collagenous gastritis, however, lack most of these associations. The etiologies of the collagenous gastroenteritides are not known, so it is not clear whether they are similar because they share pathogeneses, or because they indicate a common histologic response to varying injuries. The features, disease and drug associations, and the inquiries into the pathogenesis of these disorders are reviewed.
Adrenocortical Tumors: An Integrated Clinical, Pathologic, and Molecular Approach at the University of Michigan
Authors: Giordano Thomas J.
Published: February 2021

Context.—The University of Michigan Health System has a rich tradition in the study and treatment of endocrine neoplasia. Recently, an integrated clinical and research program focused on primary cancer of the adrenal gland has been developed.

Objective.—To discuss the foundation of the University of Michigan Adrenal Cancer Program that consists of 3 components: (1) advancement of excellent clinical care, (2) dissemination of resources and knowledge, and (3) scientific discovery.

Data Sources.—Recent programmatic activity includes genome-wide transcriptomic evaluation of human adrenocortical tumors for diagnostic and prognostic evaluation; interrogation of the Wnt signaling pathway in adrenocortical carcinoma, using mouse models and transcriptome profiling; and clinical trials with targeted therapy focused on inhibition of insulin-like growth factor signaling pathway.

Conclusions.—This review article presents an overview of this program and its recent activity.
Acidophilic Nuclear Inclusions Are Specific for Florid Ductal Hyperplasia Among Proliferative Breast Lesions
Authors: Lauer Scott , Oprea-Ilies Gabriela , Cohen Cynthia , Adsay Volkan , Adams Amy L.
Published: February 2021

Context.—Recently we have observed distinctive acidophilic intranuclear inclusions in cases of usual intraductal hyperplasia of the breast. Similar inclusions were described almost 20 years ago in cases of mammary hyperplasia. These correlated ultrastructurally with so-called helioid inclusions. However, there since has been little discussion of these inclusions in the literature.

Objective.—To examine the incidence and specificity of these inclusions in proliferative lesions of the breast.

Design.—Forty cases of usual intraductal hyperplasia, 15 cases of atypical ductal hyperplasia, and 34 cases of low-grade ductal carcinoma in situ were examined for the presence of acidophilic intranuclear inclusions.

Results.—Acidophilic intranuclear inclusions were present in 50% of cases of usual intraductal hyperplasia (20 of 40) but were not identified in any cases of atypical ductal hyperplasia (0 of 15) or low-grade ductal carcinoma in situ (0 of 34).

Conclusions.—Acidophilic intranuclear inclusions appear to be a common, specific feature found in usual intraductal hyperplasia and may be helpful in distinguishing it from atypical ductal hyperplasia and low-grade ductal carcinoma in situ in some cases. Elucidating the nature of these inclusions may provide insight into the pathogenesis of usual intraductal hyperplasia.
Emergence of a High-Grade Sarcoma in a Recurrent Meningioma: Malignant Progression or Collision Tumor?
Authors: Oz Buge , Pekmezci Melike , Dashti Reza , Karaman Kutlay , Kuday Cengiz , Tihan Tarik
Published: February 2021

Anaplastic meningiomas that resemble sarcomas often reveal clues to their meningothelial differentiation or develop in a plausible setting that confirms their meningothelial origin. Malignant mesenchymal neoplasms without obvious evidence of meningothelial differentiation or origin are more likely to be true primary or metastatic sarcomas. Because of their clinical and biological differences, it is important to distinguish anaplastic meningioma from a sarcoma. We present a 67-year-old woman with multiple meningiomas, who developed a high-grade spindle cell tumor 6 months after the resection of a World Health Organization grade I meningioma. It was not clear whether this tumor represented a malignant transformation of meningioma or a primary sarcoma. Malignant transformation of a meningioma is exceptional within this short period and a coexisting sarcoma and meningioma are equally uncommon. Even though these malignant neoplasms are rare in general, they appear to be more prevalent in patients with multiple meningiomas including those with neurofibromatosis type 2.
Trainable Immunohistochemical HER2/neu Image Analysis: A Multisite Performance Study Using 260 Breast Tissue Specimens
Authors: Nassar Aziza , Cohen Cynthia , Agersborg Sally S. , Zhou Weidong , Lynch Kathleen A. , Albitar Maher , Barker Edward A. , Vanderbilt Burton L. , Thompson Jim , Heyman Eugene R. , Lange Holger , Olson Allen , Siddiqui Momin T.
Published: February 2021

Context.—Aperio Technologies, Inc (Vista, California) provides a new immunohistochemistry (IHC) HER2 Image Analysis (IA) system that allows tuning of the intensity thresholds of the HER2/neu scoring scheme to adapt to the staining characteristics of different reagents.

Objective.—To compare the trainable IHC HER2 IA system for different reagents to conventional manual microscopy (MM) in a multisite study.

Design.—Two hundred sixty formalin-fixed, paraffin-embedded breast cancer specimens from 3 clinical sites were assayed: 180 specimens stained with Dako's HercepTest (Carpinteria, California), and 80 specimens stained with Ventana's PATHWAY HER-2/neu (Tucson, California). At each site, 3 pathologists performed a blinded reading of the glass slides with the use of a light microscope. The glass slides were then scanned and after a wash-out period and randomization, the same pathologists outlined a representative set of tumor regions to be analyzed by IHC HER2 IA. Each of the methods, MM and IA, was evaluated separately and comparatively by using κ statistics of negative HER2/neu scores (0, 1+) versus equivocal HER2/neu scores (2+) versus positive HER2/neu scores (3+) among the different pathologists.

Results.—κ Values for IA and MM were obtained across all sites. MM: 0.565–0.864; IA: 0.895–0.947; MM versus IA: 0.683–0.892 for site 1; MM: 0.771–0.837; IA: 0.726–0.917; MM versus IA: 0.687–0.877 for site 2; MM: 0.463–0.674; IA: 0.864–0.918; MM versus IA: 0.497–0.626 for site 3.

Conclusion.—Aperio's trainable IHC HER2 IA system shows substantial equivalence to MM for Dako's HercepTest and Ventana's PATHWAY HER-2/neu at 3 clinical sites. Image analysis improved interpathologist agreement in the different clinical sites.
CallWall: Tracking Resident Calls to Improve Clinical Utilization of Pathology Laboratories
Authors: Buck Thomas P. , Connor Ian M. , Horowitz Gary L. , Arnaout Ramy A.
Published: February 2021

Context.—Clinical pathology (CP) laboratories are used for millions of tests each year. These lead to thousands of calls to CP residents. However, although laboratory utilization is a frequent topic of study, clinical utilization—the content of the interactions between clinicians and CP residents—is not. Because it reflects questions about laboratory utilization, clinical utilization could suggest ways to improve both training and care by reducing diagnostic error.

Objectives.—To build and implement a secure, scalable Web-based system to allow CP residents at any hospital to track the calls they receive, the interaction's context, and the action taken as a result, with evidence where applicable, and to use this system to report on clinical utilization at a major academic hospital.

Design.—Entries were analyzed from a nearly year-long period to describe the clinical utilization of CP at a large academic teaching hospital.

Results.—Sixteen residents logged 847 calls during 10 months, roughly evenly distributed among transfusion medicine, chemistry, microbiology, and hematopathology. Calls covered 94 different analytes in chemistry and 71 different organisms or tests in microbiology. Analysis revealed areas where CP can improve clinical care through educating the clinical services, for example, about ordering Rh immune globulin, testosterone testing, and diagnosis of tick-borne diseases. Documenting calls also highlighted patterns among residents.

Conclusions.—Clinical utilization is a potentially rich knowledge base for improving patient care and resident training. Our resident call-tracking system is a useful way for measuring clinical utilization and mining it for actionable information.
Anaplastic Large Cell Lymphoma: Twenty-Five Years of Discovery
Authors: Kinney Marsha C. , Higgins Russell A. , Medina Edward A.
Published: February 2021

Context—The year 2010 commemorates the 25th year since the seminal publication by Karl Lennert and Harald Stein and others in Kiel, West Germany, describing an unusual large cell lymphoma now known as anaplastic large cell lymphoma (ALCL). Investigators at many universities and hospitals worldwide have contributed to our current in-depth understanding of this unique peripheral T-cell lymphoma, which in its systemic form, principally occurs in children and young adults.

Objective—To summarize our current knowledge of the clinical and pathologic features of systemic and primary cutaneous ALCL. Particular emphasis is given to the biology and pathogenesis of ALCL.

Data Sources—Search of the medical literature (Ovid MEDLINE In-Process & Other Non-Indexed Citations and Ovid MEDLINE: 1950 to Present [National Library of Medicine]) and more than 20 years of diagnostic experience were used as the source of data for review.

Conclusions—Based on immunostaining for activation antigen CD30 and the presence of dysregulation of the anaplastic lymphoma kinase gene (2p23), the diagnosis of ALCL has become relatively straightforward for most patients. Major strides have been made during the last decade in our understanding of the complex pathogenesis of ALCL. Constitutive NPM-ALK signaling has been shown to drive oncogenesis via an intricate network of redundant and interacting pathways that regulate cell proliferation, cell fate, and cytoskeletal modeling. Nevertheless, pathomechanistic, therapeutic, and diagnostic challenges remain that should be resolved as we embark on the next generation of discovery.
Molecular Diagnostics of Soft Tissue Tumors
Authors: Bridge Julia A. , Cushman-Vokoun Allison M.
Published: February 2021

Context.—Soft tissue pathology encompasses a remarkably diverse assortment of benign and malignant soft tissue tumors. Rendering a definitive diagnosis is complicated not only by the large volume of existing histologic subtypes (>100) but also frequently by the presence of overlapping clinical, histologic, immunohistochemical, and/or radiographic features. During the past 3 decades, mesenchymal tumor–specific, cytogenetic and molecular genetic abnormalities have demonstrated an increasingly important, ancillary role in mesenchymal tumor diagnostics.

Objectives.—To review molecular diagnostic tools available to the pathologist to further classify specific soft tissue tumor types and recurrent aberrations frequently examined. Advantages and limitations of individual approaches will also be highlighted.

Data Sources.—Previously published review articles, peer-reviewed research publications, and the extensive cytogenetic and molecular diagnostic experience of the authors to include case files of The University of Nebraska Medical Center.

Conclusions.—Cytogenetic and molecular genetic assays are used routinely for diagnostic purposes in soft tissue pathology and represent a powerful adjunct to complement conventional microscopy and clinicoradiographic evaluation in the formulation of an accurate diagnosis. Care should be taken, however, to recognize the limitations of these approaches. Ideally, more than one technical approach should be available to a diagnostic laboratory to compensate for the shortcomings of each approach in the assessment of individual specimens.
Molecular Diagnostics of Lung Carcinomas
Authors: Dacic Sanja
Published: February 2021

Context.—The development of targeted therapies in the treatment of lung carcinoma is a rapidly growing area that requires a precise histologic classification of lung carcinomas and the implementation into clinical practice of testing for predictive biomarkers of therapy response. Molecular testing has added another layer of complexity in the routine workup of rather limited diagnostic tumor tissue.

Objective.—To review the most important lung carcinoma biomarkers predictive of response and to discuss proposed routine molecular testing in clinical practice.

Data Sources.—PubMed (US National Library of Medicine)–available review articles, peer-reviewed original articles, and experience of the author.

Conclusions.—Histologic profile, clinical characteristics, and mutational profile of lung carcinoma have all been reported as predictive factors of response to epidermal growth factor receptor–tyrosine kinase inhibitors (EGFR-TKIs) and other targeted therapies. Recently published results of large clinical trials indicate that mutational profiling, particularly identification of activating epidermal growth factor receptor (EGFR) mutations, is the best predictor for EGFR-TKI response. Despite all these observations, molecular profiling of lung carcinomas has not been standardized or validated in clinical practice. Rapid development of targeted therapies will probably require molecular testing for a panel of mutations to identify molecular subtypes of non–small cell lung carcinomas that will benefit from new therapeutic approaches in personalized patient care.
Reflex Testing for Epidermal Growth Factor Receptor Mutation and Anaplastic Lymphoma Kinase Fluorescence In Situ Hybridization in Non–Small Cell Lung Cancer
Authors: Mino-Kenudson Mari , Mark Eugene J.
Published: February 2021

Context.—Non–small cell lung cancer (NSCLC) is a poor-prognosis malignancy for which more effective treatments are needed, with accumulating clinical experiences supporting benefits of receptor tyrosine kinase inhibitors for patients with tumors harboring an epidermal growth factor receptor (EGFR) mutation or anaplastic lymphoma kinase (ALK) rearrangement.

Objective.—To review completed and ongoing clinical trials of EGFR tyrosine kinase inhibitors for EGFR mutation–positive NSCLC and an ALK inhibitor for those with ALK rearrangement, while also exploring practical issues surrounding the implementation of molecular testing as a routine component of the diagnostic workup of NSCLC in the United States.

Data Sources.—Published biomedical literature, abstracts presented at recent major oncology meetings, and ClinicalTrials.gov.

Conclusions.—Continually evolving evidence indicates the possible efficacy of molecularly targeted agents for the treatment of advanced NSCLC, especially adenocarcinoma. To identify patients who will most likely benefit from the targeted therapy, routine determination of the corresponding genetic alterations after histologic diagnosis of NSCLC (reflex molecular testing for EGFR mutations and ALK rearrangement) should be considered.
#TwitterHomework During Pathology Electives: Transforming Pathology Pedagogy
Authors: Hamnvåg Hans Magne , McHenry Austin , Ahmed Aadil , Trabzonlu Levent , Arnold Christina A. , Mirza Kamran M.
Published: February 2021

Context.—

Twitter has become a popular platform for pathologists, where they share cases and educational content, arrange journal club meetings, network, and collaborate.

Objective.—

To determine if composing original tweets or retweeting existing content can be used as an educational and networking tool for medical students during pathology electives.

Design.—

In this retrospective study, a survey was sent to assess if medical students who used Twitter during their pathology electives found the platform useful for the attainment of medical knowledge, and for networking and professional development. A similar survey was sent to rotating students who did not use Twitter, asking if they thought using the platform could be beneficial. Additionally, we used Twitter analytical software (Symplur Signals) to determine the potential for networking by analyzing the number of retweets and impressions.

Results.—

Most respondents who used Twitter described using the platform as helpful in increasing their medical knowledge and useful for networking and professional development. From August 1, 2017, to January 2, 2019, thirty-seven elective medical students composed a total of 527 original tweets. The tweets were retweeted a total of 3399 times by 810 nonstudent users, and this engagement resulted in 6 360 731 impressions. Most of the retweeting was done by pathologists and pathology residents.

Conclusions.—

The responses from the survey suggest that Twitter can be an educational tool during pathology electives and be useful for networking purposes. The number of retweets and impressions, and the demographics of the users who retweeted the students confirm the networking potential of Twitter.
Group physiotherapy with survivors of torture in urban and camp settings in Jordan and Kenya
Authors: Gueron Laura Janet Pizer , Amoyi Arobogust , Chao Winnie , Chepngetich Justine , Kibet Jepkemoi Joanne , Nyambok Stephen , Wesonga Joseph
Published: February 2021

Introduction:  In this paper we report provisional field results on the impact of CVT’s (the Center for Victims of Torture) interdisciplinary group treatment on physiotherapy indicators in refugees living in urban and camp settings in Kenya and Jordan. The physiotherapy component of this model includes pain neuroscience education, sleep hygiene, posture and body mechanics instruction and healing of pain and trauma from a biopsychosocial perspective, in a program of ten weekly sessions. This program is supported by a clinical assessment that records a broad set of indicators of participant experience and functioning. In addition, some survivors report having pelvic floor dysfunction and data will be offered about a subset of survivors looking at prevalence of these issues.

Methods: Survivors are identified through referral systems, community education and sensitization campaigns, contacts and trainings with other NGOs and health care providers. Prospective survivors are screened into CVT services or referred to other agencies that can better meet their needs. CVT focuses its services on refugees with physical and emotional difficulties that may be effectively treated through its interdisciplinary treatment model and who have survived torture or related human rights violations. Following an informed consent process, survivors participate in a comprehensive individual assessment and then progress to the 10-week program. Wherever possible, follow-up assessments are conducted 2 weeks after the sessions end, and at 3, and 9 months following completion of the 10-week long intervention.

Results: On average, participants who completed 3-month follow-up assessments showed statistically and clinically significant improvements on physiotherapy indicators.

Discussion: Provisional results are encouraging and suggest that the model is adaptable to the needs of different populations and settings. As nearly all participants receive both counseling and physiotherapy, it is difficult to know which benefits can be attributed to physiotherapy alone.
Hunger
Authors: Pérez-Sales Pau
Published: February 2021

Editorial
Call for Papers og sammendrag av samtlige foredrag
Authors: Aspaas Per Pippin , Davenport Randi Lise , Klein Andreas , Nilsen Fredrik , Himmelmann Beatrix , Rasmussen Siv , Evju Håkon Andreas
Published: February 2021

Denne utgaven av Septentrio Conference Series inneholder dokumentasjon fra Norsk selskap for 1700-tallsstudiers konferanse "Naturen og det naturlige på 1700-tallet", avholdt 3.–5. februar 2021.  Inkludert i PDF-format er Call for Papers (slik det ble publisert på www.1700-tallet.no 9. september 2020) med det endelige konferanseprogrammet med sammendrag av samtlige foredrag. Opptak av hovedforedragsholdernes bidrag ble foretatt med verktøyet Zoom. De øvrige foredragene ble ikke tatt opp.
Change in Trauma Patterns in Hilly Areas of Northern India during Nationwide Lockdown: A Cross-sectional Study
Authors: Rathore Lakshya Prateek , Kalia Sandeep , Gupta Lokesh , Negi Virender , Vatsyan Kuldeep , Katoch Punit , Rana Anurag
Published: February 2021

Introduction: The countries all over the world are experiencing COVID-19 pandemic. This has led to a change in the operational guidelines in all trauma centres. Lockdown, limiting vehicle traffic, has affected trauma patterns everywhere. Aim: To study the effect of lockdown on orthopaedic trauma in hilly areas of Northern India. Materials and Methods: A cross-sectional retrospectively study collected the data of patients admitted in the emergency trauma ward like age, gender, mechanism of injury, fracture type, number of emergency admissions, and number of surgeries pertaining to the complete lockdown period (25th March to 3rd May 2020 i.e., 40 days) at our hospital situated in the hilly areas of North India. This was compared with the trauma cases dealt during the same time period last year (2019). Results: More than 50% decrease in the outpatient load did not parallel to decrease in admissions in emergency department (164 in 2019 vs 169 in 2020). However, operated trauma cases did decline from 62 in 2019 to 51 in 2020. Some injuries like fracture proximal tibia, cut injuries of hand with sharp object increased while incidence of fragility fractures has remained the same. Conclusion: The trauma pattern in and around the hilly places in our area of Northern India portrays a unique picture where one does not see a foreseeable decline in trauma despite the lockdown. With the lockdown in effect, some patterns have emerged which may prove to be useful adjuncts in our efforts to improve public health and the trauma burden.
Growth and Instability Analysis of Groundnut Price of Major Markets in Saurashtra Region of Gujarat State
Authors: Vekariya P. R. , Dudhat A. S. , Shitap M. S. , Patel D. V.
Published: February 2021

The present study was carried out by using time series data of price from 1998 to 2018, to compare the price variation, to measure the price instability of major domestic groundnut markets of Saurashtra region of Gujarat state i.e. Rajkot, Junagadh, Amreli and Gondal. Data were collected from the registers maintained in the respective Agricultural Produce Market Committees (APMCs). The price variation had been compared by using descriptive statistics in which Range and standard deviation indicated wide variation in the price level of all the markets as well as markets have positively skewed (γ1 > 0) and mesokurtic (β2 ~ 0) distribution. The price instability based on trend model was measured. Fitting of trend model is done by regressing the variable under consideration on chronological time period. Estimates of fitted cubic trend model for all the markets were significant. Higher instability was observed for Gondal market.
Experimental Study of Charcoal Savings Achieved by an Insulated Oven with Terracotta Bricks: Implications for the Protection of Forest Resources
Authors: Igo Serge Wendsida , Sawadogo Gaël Lassina , Ouedraogo Drissa , Compaoré Abdoulaye , Namoano David , Bathiébo Joseph Dieudonné
Published: February 2021

This work is devoted to an experimental study of charcoal savings achieved by an isolated barbecue oven with terracotta bricks compared to the same non-insulated oven. The methodology is based on the simultaneous monitoring of ovens temperatures at the grills level using thermocouples and an infrared imaging camera. The results show that for the same quantity of charcoal used, the temperatures reached in the grill of the insulated oven are above those of the non-insulated oven and the energy losses to the outside environment are very significant in the non-insulated oven. As a result, with a reduction in the amount of charcoal by 35%, the insulated oven achieves the same performance as the non-insulated one. These results highlight the importance of insulating barbecue ovens, particularly with terracotta bricks in reducing of charcoal consumption in Burkina Faso, and consequently in the safeguard of forest resources.
Healthcare Expenditure and Life Expectancy in Africa: A Panel Study
Authors: Abdulganiyu Salami , Tijjani Mamman
Published: February 2021

Objective of the Study: The study examined the nature of relationship between healthcare expenditure and life expectancy in a panel of 45 African Countries, disaggregated into different sub-regions in the continent.

Methodology: The study used fixed effect method and two-stage least square technique to investigate the relationship between life expectancy and life expectancy in the selected African countries, from 2000 to 2015. Aside from the major variables of interest, GDP per capita, basic sanitation and urban population were used as control variables. The choice of countries and time frame were based on availability of data. The data used was sourced from World Bank website, and analyzed using STATA software.

Main Findings: The fixed effect method found that healthcare spending is an important predictor of life expectancy in Africa. It was found to positively and significantly influence life expectancy in West Africa, but significantly and negatively influences life expectancy in Central and Southern regions of Africa. Contrariwise, the two-stage least square shows that healthcare spending is a negative predictor of life expectancy in Central Africa, but not a significant predictor in Eastern, Northern, Southern and Western Africa.

Conclusion: Conclusions from the study are two-fold. It can be concluded that fixed effect method is not a suitable estimation technique for models with endogeneity and reversed causation issues, and that healthcare expenditure is significant negative predictor of life expectancy in Central Africa; but not a significant predictor of life expectancy in Eastern, Northern, Southern and Western regions of Africa.
Thermodynamic Resolution of Pharmaceutical Precursor Modafinil Acid on the Basis of Chiral‐at‐Metal Strategy
Authors: Cao Man‐Li , Zhu Jun‐Ling , Zhi Zhong‐Lan , Ye Bao‐Hui , Yao Su‐Yang , Zhang Xiu‐Lian
Published: February 2021

Main observation and conclusion

Chiral‐at‐metal strategy was developed to resolve the essential sulfoxide pharmaceutical intermediates R‐modafinil acid and its analogues with high yields and ee values. The efficient resolution process was achieved based on the diastereoselective discrimination caused by hydrogen bond and intramolecular π‐π interaction between chiral‐at‐metal center and the coordinated chiral sulfoxide ligands. Moreover, the chiral Ir(III) receptor can be reused with complete retention of their configurations and without the loss of reaction activity and enantioselectivity. This work provides a new access to synthesize R‐modafinil acid as well as its analogues and develops the application of chiral‐at‐metal strategy in chiral resolution.