bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mixed Adenocarcinomas of the Lung: Place in New Proposals in Classification, Mandatory for Target Therapy
Authors: Chilosi Marco , Murer Bruno 
Published: February 2021

Abstract
Context.—Lung cancer is one of the most frequent and lethal malignant neoplasms, but knowledge regarding the molecular basis of its pathogenesis is far from complete due to the striking diversity of different forms. The current lung cancer classification (World Health Organization 2004) can efficiently distinguish clinically relevant major subtypes (small cell and non–small cell carcinomas), but its results are partly inadequate when facing prognostic and therapeutic decisions for non–small cell carcinomas, especially for the group of tumors classified as adenocarcinoma. Lung adenocarcinoma comprises a heterogeneous group of tumors characterized by diverse morphologic features and molecular pathogenesis. The category of mixed adenocarcinomas includes most adenocarcinomas (approximately 80%) and, according to World Health Organization criteria, is defined by the occurrence of a mixed array of different patterns (acinar, papillary, bronchioloalveolar, solid with mucin). The histologic recognition of mixed adenocarcinoma is subjective and cannot consistently discriminate between responders and nonresponders to new targeted therapies (eg, tyrosine kinase inhibitors). Diagnostic problems are mainly related to the poor reproducibility of histologic criteria, especially when applied in small biopsies and cytology, and to the difficulty in assigning each form to a precisely defined entity, as needed by updated therapeutic approaches. In this evolving scenario, pathologists face new challenging diagnostic roles that include not only the precise morphologic definition of carcinoma subtypes but also their molecular characterization.
Objective.—To use a comprehensive critical analysis reconciling the overwhelming variety of biologic, morphologic, molecular, and clinical data to define new classification schemes for lung adenocarcinoma.
Data Sources.—Scientific literature and personal data were used.
Conclusions.—A new classification approach should redefine lung adenocarcinoma heterogeneity reconciling classic morphology, immunophenotypic and molecular features of neoplastic cells, and also relevant information provided by stem cell biology. This approach, which has been already successfully applied in World Health Organization classification of other tumors, could improve the recognition of new reproducible profiles for adenocarcinomas, more closely and reproducibly related to clinical features and response to specific therapies, limiting the use of “wastebasket” categories such as mixed adenocarcinoma.
Orthokeratinized Odontogenic Cyst: A Clinicopathologic Study of 61 Cases
Authors: Dong Qing , Pan Shuang , Sun Li-Sha , Li Tie-Jun 
Published: February 2021

Abstract
Context.—Orthokeratinized odontogenic cyst (OOC) is a relatively uncommon developmental cyst comprising about 10% of cases that had been previously coded as odontogenic keratocysts. Odontogenic keratocyst was designated as keratocystic odontogenic tumor (KCOT) in the new World Health Organization classification and OOC should be distinguished from KCOT for differences in histologic features and biologic behavior.
Objective.—To analyze the clinicopathologic features of 61 cases of OOC in a Chinese population.
Design.—Clinicopathologic analysis was performed on 61 cases of OOC. Immunohistochemical expression of Ki-67 and p63 was evaluated in 15 OOCs and 15 typical KCOTs.
Results.—The 61 patients with OOC ranged from 13 to 75 years (average, 38.93 years). The lesions developed mainly in the third and fourth decades (57.38%) with a distinct predilection for males (72.13%). Six (9.84%) lesions were found in the maxilla and 55 (90.16%) in the mandible. The most common sites were in the mandibular molar and ramus region. Of the 54 cases with radiographic record, 47 (87.04%) were unilocular and 7 (12.96%) were multilocular radiolucencies. Twenty-seven of the 54 cysts were associated with an impacted tooth. Follow-up of 42 patients revealed no recurrence during an average period of 76.8 months after surgery. Compared with KCOTs, expression level of Ki-67 and p63 was significantly lower in OOCs, suggesting a lower proliferative activity.
Conclusion.—Orthokeratinized odontogenic cyst is clinicopathologically distinct from KCOT and should constitute its own clinical entity.
Practices of Participants in the College of American Pathologists Interlaboratory Comparison Program in Cervicovaginal Cytology, 2006
Authors: Eversole Galen M. , Moriarty Ann T. , Schwartz Mary R. , Clayton Amy C. , Souers Rhona , Fatheree Lisa A. , Chmara Beth A. , Tench William D. , Henry Michael R. , Wilbur David C. 
Published: February 2021

Abstract
Context.—Liquid-based preparations (LBPs) and human papillomavirus testing have led to changes in cervical cytology practices. The College of American Pathologists attempts to track practice patterns using a supplemental questionnaire, which allows laboratories to report diagnostic practices.
Objective.—To analyze the 2006 reporting practices and to compare the results with the 2003 survey data.
Design.—Questionnaire was mailed to 1621 laboratories. Participants included laboratories enrolled in the 2006 College of American Pathologists Gynecologic Proficiency Testing Program or the educational Interlaboratory Comparison Program in Gynecologic Cytology.
Results.—Of the 679 responding laboratories (response rate, 42%), most (97.8%; n  =  664) had implemented the Bethesda 2001 terminology. The median rate for all preparations with low-grade squamous intraepithelial lesions was 2.5% (2.9% for LBPs) compared with a 2003 median rate of 2.1%; the increase was confined to LBPs. Rates for high-grade squamous intraepithelial lesions (median, 0.5%) and atypical squamous cells have changed little. High-grade squamous intraepithelial lesions and unsatisfactory rates varied at statistically significant levels between types of LBPs. Most atypical squamous cell cases were subclassified as undetermined significance (median, 4.3%). The median ratio of atypical squamous cells to squamous intraepithelial lesions and carcinomas for all specimen types combined was 1.5, similar to the 2003 median ratio of 1.4. The median rates for findings of squamous cell abnormalities for 2006 were significantly higher for LBPs than for conventional smears.
Conclusions.—Most responding laboratories have implemented the Bethesda 2001 terminology. There is an increase in LBP low-grade squamous intraepithelial lesion rates when compared with 2003 data. Liquid-based preparations have higher median squamous intraepithelial lesion and atypical squamous cell rates.
Pseudoneoplastic Lesions: General Considerations
Authors: Wick Mark R. , Tazelaar Henry D. 
Published: February 2021

Abstract
Pseudoneoplastic lesions (“pseudotumors”) can be seen in virtually all anatomic locations. Some organ sites, such as the lungs and skin, are overrepresented for unknown reasons, and the histologic images seen in pseudoneoplastic lesions are partially overlapping in disparate locations. More than occasionally, the degree of histologic likeness to true neoplasms—often malignant ones—is striking. This overview outlines the spectrum of pseudoneoplastic lesions and divides them into etiologic categories, including reparative, developmental, functional (usually endocrine), iatrogenic, infectious, and idiopathic. Side-by-side pictorial comparisons of selected pseudoneoplastic lesions and their neoplastic mimics are included.
Cardiovascular Pseudoneoplasms
Authors: Miller Dylan V. , Tazelaar Henry D. 
Published: February 2021

Abstract
Context.—Primary cardiac tumors are rare and the great majority are benign neoplasms. Mass-forming reactive and pseudoneoplastic growths are less common, but recognizing and distinguishing these lesions from the neoplasms they resemble is critical to appropriate patient care.
Objective.—The general clinical, imaging, gross pathologic, and histologic features of 5 important pseudoneoplasms (inflammatory myofibroblastic tumor, hamartoma of mature cardiac myocytes, mesothelial/monocytic cardiac excrescences, calcified amorphous tumor, and lipomatous hypertrophy of the atrial septum) are discussed, with an emphasis on features differentiating them from other benign and malignant tumors.
Data Sources.—Pertinent citations of the literature and observations from the authors' experience are drawn upon.
Conclusions.—While lacking malignant potential, these lesions can be associated with considerable morbidity and occasional mortality. Their recognition is important in guiding patient management, providing both guidance for appropriate therapy and avoidance of inappropriately aggressive and toxic treatments.
Amyloidosis—Where Are We Now and Where Are We Heading?
Authors: Picken Maria M. 
Published: February 2021

Abstract
Context.—Amyloidoses are disorders of diverse etiology in which deposits of abnormally folded proteins share distinctive staining properties and fibrillar ultrastructural appearance. Amyloidosis ultimately leads to destruction of tissues and progressive disease. With recent advances in the treatment of systemic amyloidoses the importance of an early diagnosis of amyloid, and a correct diagnosis of its type, has been realized.
Objective.—To summarize current recommendations for the diagnosis of amyloidosis.
Data Sources.—Presentation given at the 4th Annual Renal Pathology Society Satellite meeting in Istanbul based on discussions and recommendations formulated during an interactive diagnostic session held at the XIth International Symposium on Amyloidosis in Woods Hole, Massachusetts.
Conclusions.—Congo red stain is currently the gold standard for amyloid detection and the goal is to detect amyloid early. Diagnosis of the amyloid type must be based on the identification of amyloid protein within the deposits and not solely by reliance on clinical or DNA studies. However, the latter are recommended for confirmation of the amyloid type based on evaluation of the protein in deposits. Immunohistochemistry must be performed and interpreted with caution and inconclusive results must be evaluated further using the more sophisticated methods available in referral centers. An adequate amount and quality of tissue must be available for amyloid diagnosis and typing with emphasis on the use of fresh tissue and greater use of abdominal fat biopsy. The development of new technologies underscores the need for regular review of recommendations and standards for the clinical diagnosis of amyloidosis.
The Classification of Renal Cystic Diseases and Other Congenital Malformations of the Kidney and Urinary Tract
Authors: Bonsib Stephen M. 
Published: February 2021

AbstractContext.—Renal cystic diseases and congenital abnormalities of the kidney and urinary tract comprise a heterogeneous group of lesions whose pathogenesis has eluded physicians for centuries. Recent advances in molecular and genetic understanding of these diseases may provide the solution to this riddle.Objective.—The formulation of an effective classification system for these disorders has been elusive but is needed to introduce order while providing a conceptual framework for diagnosis.Data sources.—This review discusses the evolution, beginning in the 19th century, of postulates regarding the pathogenesis of cystic and developmental renal diseases. Selected classification systems proffered during this period are discussed in pursuit of an ideal classification schema that would account for morphologic features and their clinical importance, with logical links to pathogenesis and treatment. Although this remains an elusive target, its general outline is becoming clearer. A classification approach favored by the author is presented, which incorporates many of the strengths contained in several previous classifications.Conclusions.—Genetic-and molecular-based postulates regarding the pathogenesis of the renal cystic and developmental diseases have implicated mutated master genes and the modification of genes that are crucial in renal development and genes that are central to the sensory effects of the renal tubular primary cilium on cell physiology. These scientific advances provide pathogenetic links between morphologically and genetically distinct entities and certain cystic and neoplastic entities, associations that seemed implausible not long ago. These advances may eventually provide the basis for future classification systems while suggesting targets for therapeutic approaches in the prevention and treatment of these diseases.
Granulomatous Lung Disease: An Approach to the Differential Diagnosis
Authors: Mukhopadhyay Sanjay , Gal Anthony A. 
Published: February 2021

Abstract
Context.—Granulomas are among the most commonly encountered abnormalities in pulmonary pathology and often pose a diagnostic challenge. Although most pathologists are aware of the need to exclude an infection in this setting, there is less familiarity with the specific histologic features that aid in the differential diagnosis.
Objective.—To review the differential diagnosis, suggest a practical diagnostic approach, and emphasize major diagnostically useful histologic features. This review is aimed at surgical pathologists who encounter granulomas in lung specimens.
Data sources.—Pertinent recent and classic peer-reviewed literature retrieved from PubMed (US National Library of Medicine) and primary material from the institutions of both authors.
Conclusions.—Most granulomas in the lung are caused by mycobacterial or fungal infection. The diagnosis requires familiarity with the tissue reaction as well as with the morphologic features of the organisms, including appropriate interpretation of special stains. The major noninfectious causes of granulomatous lung disease are sarcoidosis, Wegener granulomatosis, hypersensitivity pneumonitis, hot tub lung, aspiration pneumonia, and talc granulomatosis.
Interpretation and Utility of Drug of Abuse Immunoassays: Lessons From Laboratory Drug Testing Surveys
Authors: Melanson Stacy E. F. , Baskin Leland , Magnani Barbarajean , Kwong Tai C. , Dizon Annabel , Wu Alan H. B. 
Published: February 2021

Abstract
Context.—To assist with patient diagnosis and management, physicians from pain services, drug treatment programs, and the emergency department frequently request that urine be tested for drugs of abuse. However, urine immunoassays for drugs of abuse have limitations.
Objective.—To use data from the College of American Pathologists Proficiency Testing Surveys to determine and summarize the characteristics, performance, and limitations of urine immunoassays for drugs of abuse.
Design.—Six years of urine drug testing proficiency surveys were reviewed.
Results.—Lysergic acid diethylamide and methaqualone are infrequently prescribed or abused and, therefore, testing may be unnecessary. However, implementation of more specific testing for methylenedioxymethamphetamine and oxycodone may be warranted. Each drug of abuse immunoassay exhibits a different cross-reactivity profile. Depending on the cross-reactivity profile, patients with clinically insignificant concentrations of drugs may have false-positive results, and patients with clinically significant concentrations of drugs may have false-negative results.
Conclusions.—Laboratory directors should be aware of the characteristics of their laboratories' assays and should communicate these characteristics to physicians so that qualitative results can be interpreted more accurately. Furthermore, manufacturer's claims should be interpreted with caution and should be verified in each organization's patient population, if possible.
Practical and Molecular Evaluation of Colorectal Cancer: New Roles for the Pathologist in the Era of Targeted Therapy
Authors: De Hertogh Gert , Geboes Karen Paula 
Published: February 2021

AbstractContext.—Colorectal cancer is the third most common cancer and the fourth most common cause of cancer death worldwide. Patient cases are discussed in multidisciplinary meetings to decide on the best management on an individual basis. Until recently, the main task of the pathologist in such teams was to provide clinically useful reports comprising staging of colorectal cancer in surgical specimens. The advent of total mesorectal excision and the application of anti-epidermal growth factor receptor (EGFR)–targeted therapies for selected patients with metastasized colorectal cancer have changed the role of the pathologist.Objectives.—To present the traditional role of the pathologist in the multidisciplinary team treating patients with colorectal cancer, to address the technique of total mesorectal excision and its implications for the evaluation of surgical specimens, to offer background information on the various EGFR-targeted therapies, and to review the currently investigated tissue biomarkers assumed to be predictive for efficacy of such therapies, with a focus on the role of the pathologist in determining the status of such biomarkers in individual tumors.Data Sources.—This article is based on selected articles pertaining to biopsy evaluation of colorectal carcinoma and reviews of EGFR-targeted therapies for this cancer. All references are accessible via the PubMed database (US National Library of Medicine and the National Institutes of Health).Conclusions.—Pathologists play an increasingly important role in the diagnosis and management of colorectal cancer because of the advent of new surgical techniques and of targeted therapies. It is expected that this role will increase further in the near future.
Virtual Surgical Pathology in Underdeveloped Countries: The Zambia Project
Authors: Pagni Fabio , Bono Francesca , Di Bella Camillo , Faravelli Agostino , Cappellini Anna 
Published: February 2021

Abstract
Only 1 surgical pathology laboratory is available in Zambia, a country with a population of 12 million people. Since 2004 the Italian association of pathologists Patologi Oltre Frontiera has been working to create a virtual laboratory through the use of telemedicine. The project has involved staining histologic preparations on site, with the interpretation of imaged slides performed abroad through telepathology. Starting in April 2007, all surgical specimens obtained in Mtendere Mission Hospital, Chirundu, Zambia, were submitted for microscopic examination through whole-slide scans. Two independent Italian pathologists evaluated the cases by means of satellite connection and the final diagnoses were sent to Zambian clinicians via the internet. This article describes the spectrum of diagnoses made via telepathology for the Zambian population. Also, we analyze the concordant and discordant data between this telepathology method and traditional microscopy in a developing country. Moreover, we provide possible solutions for providing pathology services in other underdeveloped countries.
Inflammatory Myofibroblastic Tumor With Thrombocytosis and a Unique Chromosomal Translocation With ALK Rearrangement
Authors: Cole Bonnie , Zhou Holly , McAllister Nancy , Afify Zeinab , Coffin Cheryl M. 
Published: February 2021

Abstract
We describe a case of inflammatory myofibroblastic tumor with an unusual constellation of clinical, pathologic, and genetic findings. A 7-year-old girl had an 11-cm abdominopelvic mass accompanied by thrombocytosis, anemia, elevated erythrocyte sedimentation rate, and elevated C-reactive protein. The inflammatory myofibroblastic tumor displayed unusual histologic features of zonal coagulative necrosis, high cellularity with a herringbone pattern, and tumor-associated osteoclast-like giant cells. The complex tumor karyotype included a translocation t(1;2)(q21; p23). Following resection, the laboratory abnormalities resolved. The patient is well and free of recurrence at 3 years following resection. This case raises interesting questions about clinical, pathologic, prognostic, and molecular genetic interrelationships in inflammatory myofibroblastic tumor.
Commonly Encountered Difficulties in Pathologic Staging of Lung Cancer
Authors: Flieder Douglas B. 
Published: February 2021

Abstract
Context.—Lung cancer is the leading cause of cancer mortality worldwide. Despite technological, therapeutic, and scientific advances, most patients present with incurable disease and a poor chance of long-term survival. For those with potentially curable disease, lung cancer staging greatly influences therapeutic decisions. Therefore, surgical pathologists determine many facets of lung cancer patient care.
Objective.—To present the current lung cancer staging system and examine the importance of mediastinal lymph node sampling, and also to discuss particularly confusing and/or challenging areas in lung cancer staging, including assessment of visceral pleura invasion, bronchial and carinal involvement, and the staging of synchronous carcinomas.
Data Sources.—Published current and prior staging manuals from the American Joint Committee on Cancer and the International Union Against Cancer as well as selected articles pertaining to lung cancer staging and diagnosis accessible through PubMed (National Library of Medicine) form the basis of this review.
Conclusions.—Proper lung cancer staging requires more than a superficial appreciation of the staging system. Clinically relevant specimen gross examination and histologic review depend on a thorough understanding of the staging guidelines. Common sense is also required when one is confronted with a tumor specimen that defies easy assignment to the TNM staging system.
Cytodiagnosis in the Autopsy Suite: A Tool for Improving Autopsy Quality and Resident Education
Authors: Schnadig Vicki J. , Molina Claudia P. , Aronson Judith F. 
Published: February 2021

Abstract
Context.—Despite several publications attesting to its accuracy and value, cytology is rarely used for preliminary autopsy diagnosis in the United States. Postmortem cytodiagnosis has the potential to increase the accuracy and specificity of the provisional and final autopsy diagnoses, increase resident interest in cytodiagnostic techniques, and direct pathologists to request pertinent special studies, such as microbial cultures and special stains.
Objective.—To assess and illustrate the value of cytodiagnostic techniques for improving autopsy quality assurance and resident education.
Design.—Eighty-five samples were evaluated from 49 nonconsecutive autopsies. Sixty-five focal lesions were sampled by direct scraping. Diffuse lung consolidation was sampled by fine-needle aspiration (20 samples). Smears and cytocentrifuge preparations of fine-needle aspirations were routinely stained by both Papanicolaou and Romanowski methods. Cytologic diagnoses were compared with final autopsy diagnoses, and both cytology and pertinent histology were reviewed.
Results.—Clinical or radiographic antemortem site-specific diagnoses had been made in 28 (33%) of the 85 samples. A definite diagnosis was made by postmortem cytology in 68 (80%) of 85 samples, and these diagnoses could contribute to provisional autopsy diagnosis in 46 instances (68%). Resident and faculty enthusiasm for the use of cytology in the autopsy suite has increased during the 7 years following the study. Case examples illustrating the benefits of postmortem cytology are provided.
Conclusions.—Postmortem cytology benefits both autopsy quality and resident education.