bluuebunny/crossref_metadata_2025_split huggingface dataset:
Immunohistochemical Analysis of Lung Carcinomas With Pure or Partial Bronchioloalveolar Differentiation
Authors: Peter Sarantopoulos G. , Gui Dorina , Shintaku Peter , Hong Longshen , Wang Ya-Ying , Yap Cecilia S. , Fishbein Michael C. 
Published: February 2021

Abstract
Context.—In 1999, the World Health Organization redefined bronchioloalveolar carcinomas (BACs) as those neoplasms with only a pure lepidic growth pattern and no invasion.
Objectives.—The present study examined 45 lung cancers with a BAC component (1) to determine whether these tumors would be classified as BACs by current World Health Organization standards, (2) to quantitate the BAC component within these tumors, and (3) to see if phenotypic differences exist between the so-called invasive and noninvasive regions of these tumors.
Design.—Retrospective review of hematoxylin-eosin–stained slides and classification of histologic grade, tumor subtype, and percentage of pure BAC pattern, with further characterization by immunohistochemical staining for thyroid transcription factor 1, cytokeratin 7, cytokeratin 20, and Ki-67 antibodies.
Results.—Only 7 (15.6%) of the 45 tumors examined could be classified as BAC by current strict World Health Organization criteria. Those tumors, classified as nonmucinous and mixed, showed similar immunohistochemical staining for cytokeratin 7, cytokeratin 20, and thyroid transcription factor 1; mucinous tumors showed disparate staining. Significant differences in immunohistochemical staining and tumor cell proliferation were seen for the regions of tumors designated as lepidic, infiltrative, and leading edge and for the regions of tumors with different histologic grades (ie, well, moderately, and poorly differentiated).
Conclusions.—Nonmucinous and mixed BACs are phenotypically similar and show identical immunohistochemical staining patterns; mucinous tumors, on the other hand, show disparate immunohistochemical staining. Pulmonary neoplasms designated as adenocarcinomas with a BAC component represent a heterogenous group with a range of cell types, differentiation, growth, and immunophenotypes. Within an individual neoplasm, there are regional differences in these parameters as well.
Evaluation of a Dimeric Inhibin-A Assay for Assessing Fetal Down Syndrome: Establishment, Comparison, and Monitoring of Median Concentrations for Normal Pregnancies
Authors: Erickson J. Alan , Ashwood Edward R. , Gin Cynthia A. 
Published: February 2021

Abstract
Context.—Several studies report the role of dimeric inhibin-A in assessing risk for fetal Down syndrome. The majority, however, use the Serotec inhibin-A assay and not the newer Diagnostic Systems Laboratories inhibin-A enzyme-linked immunosorbent assay (ELISA).
Objectives.—To establish normal gestational age day-specific medians, to compare our results against previous studies pertaining to the inhibin-A ELISA, and to evaluate long-term assay performance.
Design.—Using the inhibin-A ELISA, 100 specimens were assayed for each completed week of gestation for weeks 15 to 20, 50 specimens for 14 weeks, and 54 specimens for 21 weeks or older. Regressed inhibin-A medians were calculated employing a second-degree polynomial fit of the arithmetic medians. Thereafter, inhibin-A ELISA lot comparisons were performed to evaluate consistency.
Results.—Regressed values of 182, 174, 175, 184, 201, and 226 pg/mL resulted for weeks 15 to 20, respectively [pg/mL inhibin-A = 4.1528(gestational age)2 − 136.49(gestational age) + 1294.9]. A comparison with 2 other studies shows our values to be lower overall by 15 ± 11.4% and 16 ± 2.6%. However, variability between kit lots was as high as 30%.
Conclusions.—The equation derived provides for the calculation of gestational age day-specific inhibin-A medians for integration into maternal serum screening programs with a subsequent decrease in false-positives expected and observed. Our medians differ considerably from those of other studies, with limited data, using the Diagnostic Systems assay. However, lot changes since the initial analysis have exhibited similar inconsistencies. Therefore, we recommend that others incorporating the assay into their screening programs carefully establish, monitor, and adjust their medians accordingly as a result of potential variations.
Role of PTEN in Gastrointestinal Stromal Tumor Progression
Authors: Ricci Riccardo , Maggiano Nicola , Castri Federica , Rinelli Alessandro , Murazio Marino , Pacelli Fabio , Potenza Angelo Eugenio , Vecchio Fabio Maria , Larocca Luigi Maria 
Published: February 2021

Abstract
Context.—Gastrointestinal stromal tumors (GISTs) are Kit/CD117-expressing mesenchymal neoplasms of uncertain malignant potential. The lack of a reliable method of prognostication hampers the selection of patients eligible for STI571 therapy. 10q22-q23 is a region involved in chromosomal losses found in a fraction of malignant primary and metastatic GISTs harboring PTEN (phosphatase and tensin homologue deleted on chromosome 10), a tumor suppressor gene often altered in human neoplasms.
Objective.—To investigate the role of PTEN in GISTs, an issue that to our knowledge has not been addressed previously.
Design.—PTEN status was determined in a series of 21 GISTs, with follow-up ranging between 6 and 198 months, using immunohistochemistry correlated with clinical data.
Results.—A greater than 25% fraction of cells with low or absent PTEN immunostaining was detected in 9 GISTs, including all those showing malignancy. By the log-rank test, a fraction of PTEN-deficient cells greater than 25% was associated with malignancy (P &lt; .001). Percentage of cells underexpressing PTEN, size, cellularity, MIB-1 immunoreactivity, and coagulative necrosis proved to be associated with malignancy by Cox proportional hazards univariate analysis; low or absent expression of PTEN was the only factor selected by multivariate analysis (P = .03).
Conclusions.—PTEN downregulation is implied in GIST progression. The immunohistochemical assessment of PTEN status appears to be a promising method of GIST prognostication.
Hemoglobin C and Hemoglobin O-Arab Variants Can Be Diagnosed Using the Bio-Rad Variant IIHigh-Performance Liquid Chromatography SystemWithout Further Confirmatory Tests
Authors: Joutovsky Alla , Nardi Michael 
Published: February 2021

Abstract
Context.—Current standards for laboratory accreditation from the College of American Pathologists state that when high-performance liquid chromatography (HPLC) is used as a screening test, all non-A, non-S abnormal hemoglobin (Hb) variants must be confirmed by an alternative method, including alkaline and acid electrophoresis.
Objective.—To determine whether confirmation of Hb C and Hb O-Arab variants by an alternative method is required when using the Bio-Rad Variant II HPLC system.
Design.—We reviewed 48 478 consecutive hemoglobin identification test results performed on the Bio-Rad Variant II HPLC system during the period November 15, 2000 to January 15, 2003.
Setting.—Special Hematology Laboratory, Department of Pathology, Bellevue Hospital Center, New York, NY.
Main Outcome Measures.—The chromatogram patterns and retention times (RTs) for specimens containing Hb C and Hb O-Arab were analyzed. We compared the results by the HPLC method with those by the confirmatory tests (alkaline and acid electrophoresis) for both variants.
Results.—We identified 3668 cases of abnormal hemoglobin variants, including 660 cases of Hb C trait (17%), 5 cases of Hb O-Arab trait (0.1%), and 1 case of Hb SO-Arab (0.03%). A unique pattern of separation on the chromatogram for Hb O-Arab was revealed, presenting as 2 distinct peaks in 2 different manufacturer-defined RT windows, namely, D and C. The chromatogram for Hb C did not show the D window in any of the reviewed cases. The RT in the C window (C-RT) revealed a statistically significant difference for Hb C and Hb O-Arab (5.18 ± 0.01 minutes and 4.91 ± 0.01 minutes, respectively; P &lt; .001).
Conclusion.—According to our review, the identification of Hb C and Hb O-Arab is accurate using HPLC methodology, as performed by the Bio-Rad Variant II HPLC system. This method can be both confirmatory and diagnostic at the same time.
Malignant Gastrointestinal Leiomyosarcoma and Gastrointestinal Stromal Tumor With Prominent Osteoclast-like Giant Cells
Authors: Insabato Luigi , Di Vizio Dolores , Ciancia Giuseppe , Pettinato Guido , Tornillo Luigi , Terracciano Luigi 
Published: February 2021

Abstract
Context.—One case of leiomyosarcoma and one case of gastrointestinal stromal tumor with prominent osteoclast-like giant cells have so far been reported in the digestive tract.
Objective.—To ascertain the clinicopathologic features and biologic behavior of these tumors, we report 3 additional cases of leiomyosarcoma of the gastrointestinal tract and one malignant gastrointestinal stromal tumor.
Design.—Histologic and immunohistochemical examinations were performed. Clinical and follow-up data were recorded, and the literature was reviewed.
Results.—The age of the patients ranged from 50 to 68 years (mean, 62 years). One of the lesions arose in the stomach, one in the ileum, and 2 in the colon. Three tumors showed a strong positivity for muscle actin and desmin and were diagnosed as leiomyosarcomas, 2 of them showing spindle cells and 1 of them showing epithelioid cells. The fourth tumor reacted strongly positive for c-Kit (CD117) and vimentin, and it was diagnosed as an epithelioid malignant gastrointestinal stromal tumor. All tumors were characterized by numerous osteoclast-like giant cells that were unevenly distributed and that, using immunohistochemistry, reacted strongly with CD68.
Conclusions.—Malignant stromal tumors with osteoclast-like giant cells of the gastrointestinal tract are rare entities, are more commonly of a myogenic origin such as leiomyosarcoma, and seem to have an aggressive behavior.
Biphasic Acute Myeloid Leukemia With Near-Tetraploidy and Immunophenotypic Transformation
Authors: Imkie Marwa , Davis Marilyn K. , Persons Diane L. , Cunningham Mark T. 
Published: February 2021

AbstractThis report describes a case of acute myeloid leukemia (subtype M1) with biphasic morphology. The bone marrow biopsy showed 2 distinct regions of blasts, one containing large cells and the other small cells. Morphometric and DNA ploidy analysis showed that the mean nuclear area and mean DNA index for the large cell region were 2-fold higher than those for the small cell region. Cytogenetic analysis showed an abnormal near-tetraploid clone. The tumor relapsed following aggressive therapy. The cells from the relapse specimen were similar to the original small cell region with respect to nuclear area and DNA index; however, there was immunophenotypic transformation with gain of CD7 and gain of CD56. Cytogenetically, the relapse specimen showed no evidence of the near-tetraploid clone, but instead had a previously unidentified abnormal clone containing 46 chromosomes and structural abnormalities of 2q and 7q. Biphasic morphology in acute myeloid leukemia may be predictive of a near-tetraploid subclone and immunophenotypic transformation.
Analysis of On-Line Clinical Laboratory Manuals and Practical Recommendations
Authors: Beckwith Bruce , Schwartz Robert , Pantanowitz Liron 
Published: February 2021

Abstract
Context.—On-line clinical laboratory manuals are a valuable resource for medical professionals. To our knowledge, no recommendations currently exist for their content or design.
Objective.—To analyze publicly accessible on-line clinical laboratory manuals and to propose guidelines for their content.
Design.—We conducted an Internet search for clinical laboratory manuals written in English with individual test listings. Four individual test listings in each manual were evaluated for 16 data elements, including sample requirements, test methodology, units of measure, reference range, and critical values. Web sites were also evaluated for supplementary information and search functions.
Results.—We identified 48 on-line laboratory manuals, including 24 academic or community hospital laboratories and 24 commercial or reference laboratories. All manuals had search engines and/or test indices. No single manual contained all 16 data elements evaluated. An average of 8.9 (56%) elements were present (range, 4–14). Basic sample requirements (specimen and volume needed) were the elements most commonly present (98% of manuals). The frequency of the remaining data elements varied from 10% to 90%.
Conclusions.—On-line clinical laboratory manuals originate from both hospital and commercial laboratories. While most manuals were user-friendly and contained adequate specimen-collection information, other important elements, such as reference ranges, were frequently absent. To ensure that clinical laboratory manuals are of maximal utility, we propose the following 13 data elements be included in individual test listings: test name, synonyms, test description, test methodology, sample requirements, volume requirements, collection guidelines, transport guidelines, units of measure, reference range, critical values, test availability, and date of latest revision.
Practice Patterns of Clinicians Following Isolated Diagnoses of Atypical Small Acinar Proliferation on Prostate Biopsy Specimens
Authors: Fadare Oluwole , Wang Sa , Rajan Mariappan M. 
Published: February 2021

Abstract
Context.—The controversial diagnostic term atypical small acinar proliferation (ASAP) has gained some acceptance as a legitimate way for pathologists to describe minute foci of small prostatic acini that raise the suspicion of carcinoma but that fail to attain the requisite diagnostic threshold for carcinoma.
Objective.—To investigate the practice patterns of clinicians following this diagnosis and to identify clinicopathologic parameters that may be of influence.
Design.—All cases with a diagnosis of ASAP on a prostate biopsy specimen during a 7-year period were retrieved from our computerized database. Cases with concurrent diagnoses of adenocarcinoma and/or prostatic intraepithelial neoplasia were excluded. Medical and pathologic records for the remaining patients were reviewed and correlated with pathologic data.
Results.—Fifty-five (2.8%) of 1964 prostate biopsies performed during this period provided the diagnosis of ASAP, of which 36 met our study criteria. The average age of the patients was 65 years, and the mean total prostate-specific antigen (PSA) level was 6.41 ng/mL. The rate of biopsy subsequent to an ASAP diagnosis was 67% (24/36), and the mean duration to subsequent biopsy was 246 days (median, 182 days; range, 71–728 days). Adenocarcinoma was diagnosed in 9 (38%) of 24 specimens taken during the subsequent biopsy. Neither age nor PSA level significantly predicted a greater likelihood for subsequent biopsy. Additionally, among patients who received a subsequent biopsy, the aforementioned parameters were not predictive of carcinoma in the second biopsy. The average number of cores following an ASAP diagnosis (6 cores) did not differ significantly from the average at initial biopsy (7.18 cores, P = .64). Pathology report characteristics, such as inclusion of a descriptive note or explicit recommendation of a second biopsy, did not significantly increase the likelihood of a subsequent biopsy. Reasons for a delay in or lack of a subsequent biopsy following an ASAP diagnosis were miscellaneous and attributable to the patients in most cases.
Conclusion.—The diagnosis of ASAP generates a subsequent biopsy in two thirds of cases after an average duration of 246 days. Although closer follow-up may be recommended based on the high rate of association with carcinoma on subsequent biopsy, we found no evidence that any delays in or lack of a subsequent biopsy is attributable to a lack of understanding on the part of urologists of the significance of the diagnosis.
Melanosis Coli Involving Pericolonic Lymph Nodes Associated With the Herbal Laxative Swiss Kriss: A Rare and Incidental Finding in a Patient With Colonic Adenocarcinoma
Authors: Ewing C. Alexander , Kalan Mohammed , Chucker Francis , Ozdemirli Metin 
Published: February 2021

Abstract
Melanosis coli is a well-known condition in which macrophages filled with a lipofuscin-like pigment are found in the colonic lamina propria. The condition has been associated with the ingestion of anthracene laxatives and is believed to be caused by increased epithelial apoptosis. Although melanosis coli is a frequent finding in colonic biopsies and resection specimens, to our knowledge the presence of identical pigment in macrophages of pericolonic lymph nodes has been reported in only 4 other patients in the English literature. We report the case of a patient who underwent a left hemicolectomy for colonic adenocarcinoma and was found incidentally to have melanosis coli associated with long-term use of the herbal laxative Swiss Kriss, not only in his colonic mucosa, but also in the colonic submucosa and in his pericolonic lymph nodes.
Epiglottic Histoplasmosis Presenting in a Nonendemic Region: A Clinical Mimic of Laryngeal Carcinoma
Authors: O'Hara Carolyn D. , Allegretto Michael W. , Taylor Geoffrey D. , Isotalo Phillip A. 
Published: February 2021

Abstract
Histoplasma capsulatum is a dimorphic fungus endemic to North America. Histoplasmosis is primarily an inhalation-acquired mycosis that is encountered rarely outside of endemic regions. In nonendemic regions, histoplasmosis may present a diagnostic challenge and both clinical and laboratory vigilance are required to accurately identify infection. Unusual clinical presentations with limited physical findings may compound the difficulty in diagnosis. We describe a 78-year-old retired soil science professor who presented with an eroded epiglottic mass secondary to disseminated histoplasmosis in a nonendemic region (Alberta). Clinically, this mass was thought to represent a primary laryngeal carcinoma, as no other buccal or oropharyngeal ulcers were identified. Histoplasmosis was confirmed by tissue biopsy and a positive immunodiffusion test for immunoglobulin G. Disseminated histoplasmosis is often associated with laryngeal and oropharyngeal disease; however, isolated epiglottic histoplasmosis is rare. Histoplasmosis should be included in the differential diagnosis of neoplasms and chronic ulcers of the upper aerodigestive tract.
Comparative Assays for the HER-2/neu Oncogene Status in Breast Cancer
Authors: Vera-Román JoséMaría , Rubio-Martínez Luis Alberto 
Published: February 2021

Abstract
Context.—Tumor marker assays, especially those used to indicate the right therapy, should be standardized.
Objective.—To analyze the current methods for the HER-2/neu (h2n) oncogene status by immunohistochemical (IHC) analysis, fluorescence in situ hybridization (FISH), and chromogenic in situ hybridization (CISH) and compare those results with the chromosome 17 copy number and the status of the topoisomerase II alpha (TPIIα) gene.
Design.—We tested 50 infiltrating ductal breast carcinomas (pTNM status varied from pT1 N0 to pT4 N1) using the Food and Drug Administration (FDA)–approved methods HercepTest and Pathway for overexpression of h2n. We also used FISH and CISH to test for h2n amplification and CISH to test for chromosome 17 (c17) and TPIIα. The p53 and Ki-67 factors were also evaluated by IHC analysis.
Results.—h2n overexpression (3+) and amplification were observed in only 6 (12%) of 50 cases by IHC analysis, FISH, and CISH. Three cases that initially scored 3+ and 2+ had 4 to 5.95 signals (equivocal) by FISH but when corrected by the h2n/c17 ratio were nonamplified. TPIIα isomerase was amplified in only 2 (4%) of the 50 cases. Nineteen (38%) of the 50 cases were aneuploidic. All h2n amplified cases had high proliferative activity, but only 2 of 6 had p53 protein alterations.
Conclusions.—The HercepTest and Pathway IHC assay h2n were fully concordant for the 3+ cases. The 3+ cases had to be confirmed in 75% of the tumor area examined. These 2 IHC assays were fully concordant with FISH and CISH. The 2 in situ hybridization (ISH) assays were 94% concordant for the 50 cases. The cutoff signal points for both ISH assays should be 6 or more. Thus, there is no need for the c17 ratio correction. Tumor heterogeneity appears not be a major problem, but our percentage of amplified cases is lower than previously reported. The FDA-approved IHC and ISH assays should give relatively uniform results when used following our recommendations.
Total Fibrous Obliteration of Main Portal Vein and Portal Foam Cell Venopathy in Chronic Hepatic Allograft Rejection
Authors: Jain Dhanpat , Robert Marie E. , Navarro Victor , Friedman Amy L. , Crawford James M. 
Published: February 2021

Abstract
Context.—Chronic hepatic allograft rejection is characterized by arteriopathy and bile duct loss. Pathology of the portal vein or its branches is not considered to play a major role in chronic rejection.
Objective.—A recent case of chronic rejection with total fibrous obliteration of the portal vein at the hilum and graft loss prompted us to retrospectively analyze cases of failed allografts for portal vein changes.
Design.—Six cases of failed hepatic allograft recorded in our files from 1994 to 1998 were selected for the study. For comparison, 4 cases of hepatitis C cirrhosis were included. Clinical features, including arteriograms or Doppler studies, were reviewed whenever available. Sections taken from the hilum and random parenchyma stained with routine hematoxylin-eosin, elastic van Gieson, and Masson trichrome were examined by 3 experienced liver pathologists in a randomized, blinded fashion.
Results.—Significant hepatic artery occlusion with foam cell change and bile duct loss was seen in all cases of chronic rejection (3/3), but not in the other cases. Foam cell change in the portal vein at the hilum (3/3) and occasionally into the distal branches (2/3) with variable occlusion of the lumen was seen only in cases of chronic hepatic allograft rejection. Mild luminal narrowing was observed in all the cases of cirrhosis (4/4) as a result of phlebosclerosis, most likely representing a change secondary to portal hypertension. Total obliteration of the portal vein at the hilum was seen in the index case (case 1) only.
Conclusion.—Portal venopathy can be a significant finding in chronic hepatic allograft rejection and may contribute to graft dysfunction or failure. Two-vessel disease must be considered in cases of chronic hepatic allograft rejection, and pathologists should thoroughly examine the hilum in explanted hepatic allografts.
Detection of Clonality With κ and λ Immunohistochemical Analysis in Cutaneous Plasmacytomas
Authors: Bayer-Garner Ilene B. , Prieto Victor G. , Smoller Bruce R. 
Published: February 2021

Abstract
Context.—Cutaneous plasmacytomas rarely occur in the setting of multiple myeloma. However, since poorly differentiated lesions may resemble other neoplasms, such as carcinoma, melanoma, and lymphoma, the diagnosis of cutaneous plasmacytoma may be difficult.
Objective.—To demonstrate clonality using κ and λ immunohistochemical analysis in cutaneous plasmacytomas and to ascertain whether or not interpretation is hindered by background staining.
Design.—Pathology reports of all patients with the diagnosis of multiple myeloma were reviewed. Twelve patients had cutaneous lesions diagnosed as plasmacytoma, and these lesions were analyzed for light chain restriction with κ and λ immunohistochemical analysis.
Results.—In most cases (11 of 12), monoclonality was demonstrated. In the remaining case, monoclonality could not be established because most cells did not stain for either κ or λ.
Conclusions.—Light chain restriction can be demonstrated in most multiple myeloma–related cutaneous plasmacytomas, establishing the neoplastic nature of the infiltrate.