bluuebunny/crossref_metadata_2025_split huggingface dataset:
Molecular Classification of Human Cancers Using a 92-Gene Real-Time Quantitative Polymerase Chain Reaction Assay
Authors: Ma Xiao-Jun , Patel Rajesh , Wang Xianqun , Salunga Ranelle , Murage Jaji , Desai Rupal , Tuggle J. Todd , Wang Wei , Chu Shirley , Stecker Kimberly , Raja Rajiv , Robin Howard , Moore Mat , Baunoch David , Sgroi Dennis , Erlander Mark 
Published: February 2021

Abstract
Context.—Correct diagnosis of the tissue origin of a metastatic cancer is the first step in disease management, but it is frequently difficult using standard pathologic methods. Microarray-based gene expression profiling has shown great promise as a new tool to address this challenge.
Objective.—Adoption of microarray technologies in the clinic remains limited. We aimed to bridge this technological gap by developing a real-time quantitative polymerase chain reaction (RT-PCR) assay.
Design.—We constructed a microarray database of 466 frozen and 112 formalin-fixed, paraffin-embedded (FFPE) samples of both primary and metastatic tumors, measuring expression of 22 000 genes. From the microarray database, we used a genetic algorithm to search for gene combinations optimal for multitumor classification. A 92-gene RT-PCR assay was then designed and used to generate a database for 481 frozen and 119 FFPE tumor samples.
Results.—The microarray-based K-nearest neighbor classifier demonstrated 84% accuracy in classifying 39 tumor types via cross-validation and 82% accuracy in predicting 112 independent FFPE samples. We successfully translated the microarray database to the RT-PCR platform, which allowed an overall success rate of 87% in classifying 32 different tumor classes in the validation set of 119 FFPE tumor samples.
Conclusions.—The RT-PCR-based expression assay involving 92 genes represents a powerful tool for accurately and objectively identifying the site of origin for metastatic tumors, especially in the cases of cancer of unknown primary. The assay uses RT-PCR and routine FFPE samples, making it suitable for rapid clinical adoption.
Warthin Tumors Do Not Have Microsatellite Instability and Express Normal DNA Mismatch Repair Proteins
Authors: Hunt Jennifer L. 
Published: February 2021

AbstractContext.—Warthin tumors are controversial entities with a poorly understood etiology. Although some investigators have suggested a neoplastic origin, others have supported a developmental anomaly. A recent study described the absence of staining for hMLH1 and hMSH2 proteins in the epithelial component of Warthin tumors, suggesting that they arise secondary to defects in the DNA mismatch repair system.Objective.—To determine if Warthin tumors exhibit evidence of DNA mismatch repair defects.Design.—Immunostains for hMLH1 and hMSH2 were performed using a standard approach. Microdissection of the epithelial component was followed by DNA extraction from the tissue fragments. Polymerase chain reaction and capillary electrophoresis analyses were performed for the following 5 National Cancer Institute–recommended microsatellites: D2s123, D5s346, D17s250, BAT25, and BAT26.Patients.—Twelve patients with Warthin tumors were included.Results.—The immunostains for hMLH1 and hMSH2 showed preserved expression in the nuclei of the epithelial component of all Warthin tumors. No microsatellite instability was detected, and no loss of heterozygosity was seen.Conclusions.—These results are not concordant with previously reported results showing loss of expression of the hMLH1 and hMSH2 DNA mismatch repair enzymes in the epithelial component of Warthin tumors. Furthermore, no microsatellite instability was detected in the 5 loci tested for each tumor in this series. These data demonstrate that Warthin tumors do not have evidence of DNA mismatch repair defects at the genomic or protein expression level.
Herbal Remedies: Effects on Clinical Laboratory Tests
Authors: Dasgupta Amitava , Bernard David W. 
Published: February 2021

AbstractContext.—Complementary and alternative medicine (herbal medicines) can affect laboratory test results by several mechanisms.Objective.—In this review, published reports on effects of herbal remedies on abnormal laboratory test results are summarized and commented on.Data Sources.—All published reports between 1980 and 2005 with the key words herbal remedies or alternative medicine and clinical laboratory test, clinical chemistry test, or drug-herb interaction were searched through Medline. The authors' own publications were also included. Important results were then synthesized.Data Synthesis.—Falsely elevated or falsely lowered digoxin levels may be encountered in a patient taking digoxin and the Chinese medicine Chan Su or Dan Shen, owing to direct interference of a component of Chinese medicine with the antibody used in an immunoassay. St John's wort, a popular herbal antidepressant, increases clearance of many drugs, and abnormally low cyclosporine, digoxin, theophylline, or protease inhibitor concentrations may be observed in a patient taking any of these drugs in combination with St John's wort. Abnormal laboratory results may also be encountered owing to altered pathophysiology. Kava-kava, chaparral, and germander cause liver toxicity, and elevated alanine aminotransferase, aspartate aminotransferase, and bilirubin concentrations may be observed in a healthy individual taking such herbal products. An herbal product may be contaminated with a Western drug, and an unexpected drug level (such as phenytoin in a patient who never took phenytoin but took a Chinese herb) may confuse the laboratory staff and the clinician.Conclusions.—Use of alternative medicines may significantly alter laboratory results, and communication among pathologists, clinical laboratory scientists, and physicians providing care to the patient is important in interpreting these results.
Synchronous Interdigitating Dendritic Cell Sarcoma and B-Cell Small Lymphocytic Lymphoma in a Lymph Node
Authors: Cossu Antonio , Deiana Angelo , Lissia Amelia , Dedola Maria Filomena , Cocco Lucia , Palmieri Giuseppe , Tanda Francesco 
Published: February 2021

Abstract
A gradually enlarging axillary mass in a 79-year-old man was excised. The specimen was processed for light microscopy, immunohistochemical studies, and electron microscopy; gene rearrangement studies were also performed. A diagnosis of an interdigitating dendritic cell tumor of the lymph node and a B-cell small lymphocytic lymphoma occurring in the same anatomic location was made. We found that although rare cases of interdigitating dendritic cell tumor with an associated secondary malignancy have been described in the literature, to our knowledge, this is the first report of interdigitating dendritic cell tumor and synchronous neoplasm diagnosed at the same site. A possible relationship between the 2 disorders is also discussed.
Surgical Pathology—Second Reviews, Institutional Reviews, Audits, and Correlations: What's Out There? Error or Diagnostic Variation?
Authors: Frable William J. 
Published: February 2021

Abstract
Context.—A variety of methodologies have been used to report error rates in surgical pathology within the peer-reviewed medical literature. The media has selectively and superficially reported these error rates creating a climate of disinformation between physicians and the public.
Objectives.—To review the medical literature on diagnostic error in surgical pathology and summarize and compare these data with selected reports in the print and broadcast media.
Design.—A search of the medical literature from the National Library of Medicine database using the heading “Error and Pathology Diagnosis.”
Results.—Three thousand nine hundred ninety-two citations were found, of which 83 directly measured in some manner errors in surgical and cytopathology. Major error rates ranged from 1.5% to 5.7% globally for institutional consults. Error rates were less, 0.26% to 1.2% for global in-house prospective review and 4.0% for in-house and retrospective blinded review. Error rates also varied by anatomic site: skin, institutional consult, 1.4%; prostate, institutional consult, 0.5%; and thyroid, institutional consult, 7.0%. Error rates reported in citations used by the Wall Street Journal were as follows: prostate, Gleason score changed by 1 point, 44% and resultant change in treatment for prostate cancer, 10%; for breast, altered lumpectomy or mastectomy plan, 8%; and diagnosis changed for thyroid lesions, 18%. Errors in second opinion on breast lesions (single pathologist author for the study) fall within the range of global reviews. Errors for second opinions on prostate cancer were principally 81% upgrades in Gleason score for prostate core needle biopsies. However, this resulted in an upgrade of patient risk category in only 10.8% of patients. Data for the article on change in diagnosis of thyroid lesions were incomplete. There appeared to be 3 significant diagnostic errors (4.5%).
Conclusions.—Pathology is not immune to the power of the media to create concern about accuracy of diagnosis in surgical pathology and cytopathology. Detailed analysis of the medical literature cited by the media determines that painting the big picture and hitting the highlights can be profoundly misleading.
Imatinib Resistance: Obstacles and Opportunities
Authors: Litzow Mark R. 
Published: February 2021

Abstract
Objective.—To review the current status of resistance to imatinib mesylate (IM) in patients with chronic myelogenous leukemia, and the obstacles and opportunities presented by the development of this resistance.
Data Sources and Study Selection.—Review of selected studies obtained from a MEDLINE search encompassing the years 1950 to 2004.
Data Extraction and Data Synthesis.—Relevant information from the selected studies was abstracted and summarized.
Conclusions.—The identification of the Philadelphia chromosome and the subsequent discovery that it represents a translocation between the long arms of chromosomes 9 and 22 producing an aberrant tyrosine kinase, known as BCR-ABL1, has catalyzed our understanding and treatment of this hematologic malignancy. An extensive search for molecules to block the aberrant BCR-ABL1 protein resulted in the development of IM as an orally bioavailable agent with remarkable efficacy in producing hematologic, cytogenetic, and molecular remissions. However, follow-up of patients treated with IM has demonstrated that some patients can develop resistance to IM with progression of their leukemia. Multiple mechanisms of resistance have been identified. The dominant mechanism appears to be mutations in the kinase domain of BCR-ABL1, which result in altered affinity of IM for the BCR-ABL1 protein. Recently, small-molecule, combined SRC and ABL1 inhibitors have been developed and entered into clinical trials. These inhibitors appear effective in inhibiting most of the mutant BCR-ABL1 molecules that are resistant to IM. The rapid development of new therapies for treatment of chronic myelogenous leukemia brings the promise that this disorder can be cured or controlled in many patients with oral drugs that have a low toxicity profile.
Evaluation of HER-2/neu Gene Status in Osteosarcoma by Fluorescence In Situ Hybridization and Multiplex and Monoplex Polymerase Chain Reactions
Authors: Willmore-Payne Carlynn , Holden Joseph A. , Zhou Holly , Gupta Dilip , Hirschowitz Sharon , Wittwer Carl T. , Layfield Lester J. 
Published: February 2021

Abstract
Context.—Previous reports suggest that the human epidermal growth factor 2 (HER-2/neu) receptor may be overexpressed in osteosarcoma.
Objective.—To determine whether osteosarcomas have amplifications of the HER-2/neu gene.
Design.—We studied a series of osteosarcomas by fluorescence in situ hybridization (FISH) and by 2 real-time polymerase chain reaction assays that measure the amount of HER-2/neu DNA relative to a control gene. The HER-2/ neu monoplex and multiplex assays were capable of identifying those cases of breast cancer that were known to overexpress HER-2/neu as assessed by FISH. We initially studied 21 cases of osteosarcoma by FISH analysis (using a technique that included a probe for chromosome 17), 11 of which had their HER-2/neu gene amplification status previously reported.
Results.—None of these osteosarcoma cases showed HER-2/neu amplification by our FISH analysis and subsequent quantitative (multiplex) polymerase chain reaction. Apparent expression of HER-2/neu protein was observed in several of the cases but the immunoreactivity was localized to the cytoplasm and was not membranous in character. An additional 35 osteosarcoma specimens were subjected to monoplex polymerase chain reaction analysis, and amplifiable DNA was recovered from 19 specimens (54%). None of these samples had HER-2/neu amplification by monoplex PCR analysis and only one case had membranous immunoreactivity graded as 1+.
Conclusion.—Although a small subset of osteosarcomas had weak noncircumferential membranous immunoreactivity for HER-2/neu protein, no osteosarcomas demonstrated positive (2+ or 3+) immunoreactivity for HER-2/ neu protein and none showed HER-2/neu gene amplification by either FISH or polymerase chain reaction.
β-Catenin Nuclear Expression Correlates With Cyclin D1 Expression in Primary and Metastatic Synovial Sarcoma: A Tissue Microarray Study
Authors: Horvai Andrew E. , Kramer Miranda J. , O'Donnell Richard 
Published: February 2021

Abstract
Context.—The association between aberrant (nuclear) β-catenin expression and cyclin D1 accumulation has been demonstrated in diverse neoplasms. In synovial sarcoma (SS), aberrant β-catenin expression has prognostic relevance, but the association with cyclin D1 has not been established. The SYT-SSX fusion protein, unique to SS, may independently increase cyclin D1.
Objective.—To determine whether nuclear β-catenin is associated with cyclin D1 overexpression in SS and whether primary and metastatic SS differ in the expression of these markers.
Design.—We incorporated 82 tumors initially diagnosed as SS into a tissue array. Fluorescence in situ hybridization with custom probes was used to select t(X;18) positive tumors. Clinical data, tumor type and outcome were tabulated. The tumors were tested for the association between nuclear β-catenin and cyclin D1 immunostaining. Primary and metastatic tumors were compared.
Results.—Fifty-one tumors (41 primary and 10 metastatic) from 43 patients demonstrated t(X;18). Cyclin D1 staining was identified in 21 (59%) primary and 8 (80%) metastatic tumors, respectively, and nuclear β-catenin in 24 (41%) primary and 7 (70%) metastatic tumors, respectively. No significant difference was noted between primary and metastatic tumors with respect to the above markers. The presence of nuclear β-catenin showed a significant association with cyclin D1 expression (P &lt; .001). A small number of cyclin D1 cases were negative for nuclear β-catenin but positive for phosphorylated Akt.
Conclusions.—Increased cyclin D1 in SS may be driven by abnormally expressed β-catenin, similar to other neoplasms. The pattern of expression of these markers is established early during tumorigenesis.
Mucin Profiles in Signet-ring Cell Carcinoma
Authors: Nguyen; Minh D. , Plasil Brian , Wen Ping , Frankel Wendy L. 
Published: February 2021

Abstract
Context.—Signet-ring cell carcinoma (SRCC) is a poorly differentiated mucin-producing adenocarcinoma that may arise from many different organs, but all SRCCs share identical morphology. It is not possible to differentiate sites of origin for metastatic SRCC based on morphology alone. Mucins are high-molecular-weight glycoproteins differentially expressed in glandular epithelia and in adenocarcinomas.
Objective.—To identify mucin profiles of primary and metastatic SRCCs using immunohistochemistry to determine whether mucin staining could help distinguish sites of origin.
Design.—Forty-seven SRCCs, including 38 primary (21 stomach, 11 colorectum, and 6 breast) and 9 metastases from these primary sites were retrieved from archival files. Consecutive tissue sections were immunostained with monoclonal antibodies against MUC1, MUC2, MUC4, MUC5AC (MUC5), and MUC6 on separate slides. Cytoplasmic staining was scored based on proportion of positive tumor cells as follows: 0+ (&lt;5%), 1+ (5%–25%), 2+ (26%–50%), and 3+ (&gt;50%). Mucin profiles were recorded as MUC+, MUCv, and MUC− for consistent, variable, and negative expression, respectively.
Results.—The mucin profiles for gastric, colorectum, and breast SRCCs are MUC1·2·4·5·6v, MUC2·4+/MUC5v/ MUC1·6−, and MUC1+/MUC2·5·6v/MUC4−, respectively. Mucin profiles of metastatic cases shared profiles with their respective primaries.
Conclusions.—Signet-ring cell carcinomas of the stomach, colorectum, and breast have distinct mucin expression patterns that are maintained in metastases. Mucin profiling may be useful to identify the origin of a metastatic SRCC of unknown primary.
Current Prostate Biopsy Interpretation: Criteria for Cancer, Atypical Small Acinar Proliferation, High-Grade Prostatic Intraepithelial Neoplasia, and Use of Immunostains
Authors: Iczkowski Kenneth A. 
Published: February 2021

Abstract
Context.—The past decade has brought major changes in prostate biopsy sampling, interpretation, and reporting.
Objective.—To summarize current information on diagnostic decision making, Gleason grading, “atypical” diagnoses, and use of immunostaining.
Data Sources.—Pertinent literature from 1985 to 2005 is reviewed, emphasizing recent findings.
Conclusions.—Diagnosis begins by evaluating a focus of atypical single-cell layer lined acini according to the 3 minimal diagnostic criteria for cancer: an infiltrative pattern, nuclear enlargement and hyperchromasia, and prominent nucleoli. The Gleason score and linear extent or percent of each core containing cancer should be reported. Atypical small acinar proliferation suspicious for malignancy designates foci that have either qualitative or quantitative limitations in atypia precluding a definite cancer diagnosis. It has about a 3% incidence as an isolated finding. Contemporary studies indicate a 39% predictive value for cancer on repeat biopsy. Isolated high-grade prostatic intraepithelial neoplasia has a 3% to 14% incidence and predicts cancer on repeat biopsy in 23% of cases. Immunostaining for a marker of benign prostate (cytoplasmic keratin 34βE12 or nuclear p63) and a marker of cancer (α-methylacyl coA racemase, clone P504S) may or may not resolve atypical small acinar proliferation diagnoses. Performance of 34βE12 and P504S immunostains resolved 76% of atypical small acinar proliferation diagnoses per consensus of 3 urologic pathologists studied; a technical limitation is preservation of the focus in question on the levels used for immunostaining.
Malignant Solitary Fibrous Tumor of the Kidney: Report of a Case and Comprehensive Review of the Literature
Authors: Fine Samson W. , McCarthy Denis M. , Chan Theresa Y. , Epstein Jonathan I. , Argani Pedram 
Published: February 2021

Abstract
Renal solitary fibrous tumors (SFTs) have been reported infrequently. We report a 76-year-old man with a left renal mass that had previously been shown radiographically to be stable, but was now growing. Grossly, the mass measured 12 cm, was poorly circumscribed, and invaded beyond the renal capsule. Approximately 10% of the neoplasm consisted of haphazardly arranged spindle cells admixed with dense collagenous bands, which is typical of benign SFT. However, the remainder of the mass was composed of pleomorphic, spindled sarcoma cells with frequent mitoses and foci of necrosis. Immunohistochemically, we observed CD34 labeling in the benign SFT component with loss of expression in the sarcomatous component, focal labeling for Bcl-2 protein in both areas, and absence of labeling for cytokeratin, renal cell carcinoma marker, S100 protein, CD117, and muscle markers in both areas. To our knowledge, this is the first reported case of malignant renal SFT, likely representing transformation from a histologically documented benign SFT component.
Paratesticular Papillary Mesothelioma: A Case With Borderline Features
Authors: Cabay Robert J. , Siddiqui Noman H. , Alam Shumyle 
Published: February 2021

Abstract
Most often, mesotheliomas involve the serosal (serous) membranes of the pleura and peritoneum. Sometimes, mesothelial proliferations are identified in other locations. On very rare occasions, a mesothelioma is found within the tunica vaginalis of the paratesticular region. We report a case of papillary mesothelioma of the tunica vaginalis in a 52-year-old man. Although this lesion had papillary structures lined by a single layer of mesothelial cells with predominantly bland nuclear and cytologic features, there was evidence of a minimal presence of mesothelial cells in the underlying stroma. This combination of benign and semimalignant characteristics can make the diagnosis of such a lesion problematic. We think that a diagnosis of “borderline papillary mesothelioma” can be considered for similar mesothelial proliferations to allow for a possible increase in diagnostic accuracy and provide an enhanced informational platform from which patients and clinicians can benefit.
Acquired Pelger-Huët Anomaly in Association With Concomitant Tacrolimus and Mycophenolate Mofetil in a Liver Transplant Patient: A Case Report and Review of the Literature
Authors: Etzell Joan E. , Wang Endi 
Published: February 2021

Abstract
Pelger-Huët anomaly is a congenital or acquired abnormality of neutrophil nuclear segmentation. The acquired form may be a result of a clonal myeloid malignancy, such as myelodysplastic syndrome, or may be a secondary nonclonal change related to a variety of underlying causes, including infections and medications. We report a case of a 56-year-old man who developed acquired Pelger-Huët anomaly following liver transplantation while on the immunosuppressive agents tacrolimus and mycophenolate mofetil. These medications have been reported in association with this abnormality, but usually as a single agent or in combination with other drugs. In our case, the Pelger-Huët anomaly may be the result of the combination of these 2 drugs or mycophenolate alone with subsequent desensitization because resolution of the abnormality occurred after a reduction in mycophenolate mofetil dose, and the abnormality did not recur when mycophenolate mofetil was increased to a dose previously associated with Pelger-Huët anomaly during the time that tacrolimus was discontinued.
Unusual Forms of Immature Sporulating Coccidioides immitis Diagnosed by Fine-Needle Aspiration Biopsy
Authors: Ke Yong , Smith Corey W. , Salaru Gratian , Joho Kim L. , Deen Malik F. 
Published: February 2021

Abstract
Coccidioidomycosis is an endemic infection acquired by inhalation of the spores (arthroconidia) of the thermally dimorphic fungus, Coccidioides immitis. The arthroconidia transform into spherical cells called mature spherules in the lung. Immature spherules and other atypical forms of immature C immitis have rarely been found in vivo. We report on a case that presented unusual forms of immature sporulating C immitis in a fine-needle aspiration specimen. A 36-year-old Chinese woman, living in New Jersey for the past 10 years, presented with fever, night sweats, hemoptysis, and an abnormal chest radiograph approximately 9 months after a brief vacation trip to the Grand Canyon in Arizona. She was treated with antibiotics for 4 weeks without improvement. Subsequent chest computed tomography showed a 3-cm cavitary lesion in the right lower lobe of the lung. Fine-needle aspiration biopsy revealed diverse morphologic forms of a fungus that was confirmed by culture as immature sporulating C immitis.