bluuebunny/crossref_metadata_2025_split huggingface dataset:
Measurement of PTEN Expression Using Tissue Microarrays to Determine a Race-Specific Prognostic Marker in Breast Cancer
Authors: Winter Jerald Luke , Stackhouse Bodiford L. , Russell Gregory B. , Kute Timothy E. 
Published: February 2021

Abstract
Context.—African American women with breast cancer have worse prognoses than non–African Americans and might benefit with a race-specific prognostic marker such as PTEN (phosphatase and tensin homologue), a tumor suppressor protein. Reduced PTEN expression is associated with worse outcomes and resistance to trastuzumab in human epidermal growth factor receptor 2–positive breast cancers. Standardized PTEN evaluation is therefore needed.
Objective.—To assess PTEN as a race-specific prognostic marker in breast cancer by using a novel semiquantitative score and a percent staining assessment.
Design.—Between 1991 and 1996, 146 patients with invasive ductal adenocarcinoma were grouped by race and recurrence; there was a median follow-up of 7.2 years with 63 recurrences. Immunostaining of PTEN in tissue microarrays was correlated with race, recurrence, node positivity, stage, size, age, estrogen/progesterone receptor status, grade, and DNA ploidy.
Results.—No significant racial difference was detected in mean PTEN values using either the semiquantitative score (P = .46) or the percent staining (P = .54). Unrelated to race, the percentage of tumor cells with positive PTEN expression correlated with longer time to recurrence (P = .047), positive estrogen receptor status (P = .009), and lower tumor grade (P = .005). The semiquantitative score correlated with positive estrogen receptor status (P = .01) and lower tumor grade (P = .001).
Conclusions.—PTEN expression is not a race-specific biologic prognostic marker for invasive ductal adenocarcinoma. Increased PTEN expression correlates with longer time to recurrence, positive estrogen receptor status, and lower tumor grade. The novel semiquantitative score may be used to evaluate PTEN expression, but the approximate percentage of tumor cells with any PTEN staining may be the most useful measure of PTEN expression.
Typing of Amyloidosis in Renal Biopsies: Diagnostic Pitfalls
Authors: Satoskar Anjali A. , Burdge Kelly , Cowden Daniel J. , Nadasdy Gyongyi M. , Hebert Lee A. , Nadasdy Tibor 
Published: February 2021

Abstract
Context.—Amyloidosis represents a group of diseases with extracellular deposition of congophilic fibrils of similar morphology but differing chemical composition. The types commonly involving the kidney are AL (light chain amyloid) and AA (serum amyloid A). Familial amyloidosis can also affect the kidney, but we have not encountered such a case during the study period. Distinguishing between the AL and AA forms of amyloid is clinically important because of the different treatments and outcomes. The classification of amyloidosis is made by immunostaining with antibodies to κ and λ immunoglobulin light chains and for serum amyloid A protein.
Objective.—To draw attention to the nonspecific immunofluorescence staining patterns in renal biopsies with amyloidosis, causing potential diagnostic pitfalls.
Design.—Renal biopsies from 15 patients, including 13 cases of AL and 2 cases of AA amyloidosis, were studied. Immunofluorescence staining with routine antibody panel and immunoperoxidase staining for amyloid A were performed.
Results.—Of the 13 cases of AL amyloidosis, 2 cases showed little difference in staining intensity between κ and λ light chains (2+ and 3+, respectively) and 4 cases showed only moderate intensity (2+) of the predominant light chain. The 2 cases diagnosed as AA amyloidosis also exhibited staining for light chains. One case had strong (3+) signal for κ and moderate (2+) for λ light chain, while the other showed weaker staining.
Conclusions.—Immunofluorescence staining for immunoglobin light chains on renal biopsy, as the first step to differentiate between AL and AA amyloidosis, may sometimes be inconclusive or even misleading. Applying amyloid A immunostain on a routine basis and detailed clinical history are essential to avoid misclassification.
Sarcomatoid Carcinoma of the Lung: Histologic Criteria and Common Lesions in the Differential Diagnosis
Authors: Franks Teri J. , Galvin Jeffrey R. 
Published: February 2021

Abstract
Context.—Sarcomatoid carcinoma of the lung is a subset of poorly differentiated non–small cell lung cancers that are diagnostically challenging because they are uncommon, may reveal little of their parent cell of origin, and overlap morphologically with other anaplastic epithelioid and spindle cell tumors that can be primary in, or metastatic to, the lung and pleura.
Objective.—To review the current histologic classification and diagnostic criteria that identify the 5 subtypes of sarcomatoid carcinoma of the lung and to discuss the most common tumors in the differential diagnosis.
Design.—Published classification systems from the World Health Organization and pertinent peer-reviewed articles indexed in PubMed (National Library of Medicine) form the basis of this review.
Conclusions.—Identification of sarcomatoid carcinoma of the lung requires knowledge of specific histologic criteria that define the 5 subgroups, targeted immunohistochemical studies, and correlation with chest imaging to assess distribution of disease and to avoid misdiagnosis.
Is the Epidermal Growth Factor Receptor Status in Lung Cancers Reflected in Clinicopathologic Features?
Authors: Inamura Kentaro , Ninomiya Hironori , Ishikawa Yuichi , Matsubara Osamu 
Published: February 2021

Abstract
Context.—Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors are molecular-targeted drugs that are innovatively effective for non–small cell lung carcinomas with EGFR mutations. Epidermal growth factor receptor is a transmembrane receptor forming dimers on ligand binding. These then stimulate signals by activating receptor autophosphorylation through tyrosine kinase activity. Autophosphorylation triggers intracellular pathways facilitating malignant conversion. The most clinically advanced EGFR inhibition strategies include small-molecule inhibition of the intracellular tyrosine kinase domain (gefitinib and erlotinib) and monoclonal antibody–mediated blockade of the extracellular ligand-binding domain (cetuximab). Lung cancers with EGFR mutations are prevalent among patients who are female, of Asian ethnicity, and nonsmokers; thus, they can obtain benefit from EGFR tyrosine kinase inhibitors.
Objective.—To survey histopathologic findings and examine correlations with EGFR mutations. We mainly focused on component cell types (hobnail, columnar, and polygonal) and presence or absence of bronchioloalveolar carcinoma elements and a micropapillary pattern. Although EGFR mutations can be detected by various methods, including polymerase chain reaction–Invader assay or direct sequencing, these are inconvenient.
Data Sources.—Review of the published literature.
Conclusion.—Detailed pathologic examination showed significant genotype-phenotype correlations between EGFR mutations and presence of a bronchioloalveolar carcinoma component, a micropapillary pattern, and the hobnail cell type. We conclude that these characteristic histologic features are good predictors of EGFR mutations, and patients with these features might be good candidates for and could benefit from therapy with EGFR tyrosine kinase inhibitors.
Basaloid Follicular Hamartoma
Authors: Mills Omie , Thomas L. Brannon 
Published: February 2021

AbstractBasaloid follicular hamartoma is a benign lesion of important consideration because it can be mistaken both clinically and histologically for basal cell carcinoma. The formation of basaloid follicular hamartoma has been linked to a mutation in the patched gene, which is part of the same pathway implicated in nevoid basal cell carcinoma syndrome. While these hamartomas are considered benign lesions, malignant growths have been reported to arise within them, which raises the question, “Is basaloid follicular hamartoma a premalignant lesion?” Correct identification allows for periodic monitoring for malignant transformation, while sparing patients unnecessary surgery. Treatment strategies, including experimental therapies, are reviewed.
The Small Cell Variant of Anaplastic Large Cell Lymphoma
Authors: Summers Thomas A. , Moncur Joel T. 
Published: February 2021

AbstractAnaplastic large cell lymphomas constitute a heterogeneous group of hematopoietic neoplasms that are characterized by immunopositivity for CD30 and the presence, in varying degrees, of large, pleomorphic “hallmark” cells. Primary systemic anaplastic lymphoma kinase-positive anaplastic large cell lymphomas are a subset of this group. Numerous heterogeneous histomorphologic patterns have been described in anaplastic lymphoma kinase-positive anaplastic large cell lymphomas, and all patterns tend to have a better prognosis than that found in anaplastic lymphoma kinase-negative cases. We provide a short review of the small cell variant of anaplastic large cell lymphoma to facilitate the diagnosis of this difficult-to-recognize entity, which may be confused with reactive processes, commonly presents with disseminated disease, and pursues an aggressive clinical course.
Do Liquid-Based Preparations of Urinary Cytology Perform Differently Than Classically Prepared Cases? Observations From the College of American Pathologists Interlaboratory Comparison Program in Nongynecologic Cytology
Authors: Laucirica Rodolfo , Bentz Joel S. , Souers Rhona J. , Wasserman Patricia G. , Crothers Barbara A. , Clayton Amy C. , Henry Michael R. , Chmara Beth Anne , Clary Karen M. , Fraig Mostafa M. , Moriarty Ann T. 
Published: February 2021

AbstractContext.—The cytomorphology of liquid-based preparations in urine cytology is different than classic slide preparations.Objectives.—To compare the performance of liquid-based preparation specimens to classically prepared urine specimens with a malignant diagnosis in the College of American Pathologists Interlaboratory Comparison Program in Nongynecologic Cytology.Design.—Participant responses between 2000 and 2007 for urine specimens with a reference diagnosis of high-grade urothelial carcinoma/carcinoma in situ/dysplasia (HGUCA), squamous cell carcinoma, or adenocarcinoma were evaluated. ThinPrep and SurePath challenges were compared with classic preparations (smears, cytospins) for discordant responses.Results.—There were 18 288 pathologist, 11 957 cytotechnologist, and 8086 “laboratory” responses available. Classic preparations comprised 90% (n = 34 551) of urine challenges; 9% (n = 3295) were ThinPrep and 1% (n = 485) were SurePath. Concordance to the general category of “positive-malignant” was seen in 92% of classic preparations, 96.5% of ThinPrep, and 94.6% of SurePath challenges (P &lt; .001). These results were statistically different for the exact reference interpretation of HGUCA (P &lt; .001) but not for adenocarcinoma (P = .22). Cytotechnologists demonstrate statistically better performance for the general category of “positive-malignant” compared with pathologists for all urinary slide types and for the exact reference interpretation of HGUCA (94% versus 91.1%; P &lt; .001) but not adenocarcinoma (96.3% versus 95.8%; P = .77) or squamous cell carcinoma (93.6% versus 87.7%; P = .07).Conclusions.—Liquid-based preparations performed significantly better in urinary cytology challenges when evaluating malignant categories in the College of American Pathologists interlaboratory comparison program. The liquid-based preparation challenges also performed better for the exact reference interpretation of HGUCA, but no difference was observed for adenocarcinoma challenges. Cytotechnologists perform better than pathologists for all slide types, as well as those demonstrating HGUCA. These results suggest that liquid-based preparations facilitate a more accurate diagnosis than conventional preparations.
Clinical Utility of Adjunctive High-Risk Human Papillomavirus DNA Testing in Women With Papanicolaou Test Findings of Atypical Glandular Cells
Authors: Zhao Chengquan , Florea Anca , Austin R. Marshall 
Published: February 2021

Abstract

Context.
Atypical glandular cell (AGC) Papanicolaou (Pap) test interpretations are challenging. Most biopsy findings are benign, but AGC results may also reflect highly significant noninvasive neoplastic and malignant histologic outcomes. High-risk human papillomavirus (hrHPV) test use with AGC Pap test results is evolving.

Objective.
To further evaluate the utility and limitations of hrHPV testing with AGC Pap tests.

Design.
Hospital records were searched for AGC Pap tests results from June 1, 2005, to August 31, 2007. Cases of AGC with hrHPV tests and histopathologic follow-up were included.

Results.
Of the 662 women with AGC Pap test results and follow-up analyzed, hrHPV results were available for 309 (46.7%) and were positive in 75 cases (24.3%). Among the 75 cases with hrHPV+ AGC results, 13 (17.3%) had cervical intraepithelial neoplasia grades 2/3, 10 (13.3%) had adenocarcinoma in situ, and 3 (4.0%) had cervical invasive adenocarcinoma, whereas for 234 women with hrHPV− results, 1 (0.4%) had cervical intraepithelial neoplasia grades 2/3, 1 (0.4%) had adenocarcinoma in situ, 1 each (0.4%) had cervical adenocarcinoma and ovarian carcinoma, and 8 (3.4%) had endometrial carcinoma.

Conclusions.
Positive hrHPV AGC results were most strongly associated with cervical intraepithelial neoplasia grades 2/3 and adenocarcinoma in situ in women younger than 50 years. Positive hrHPV AGC results were also present in all 3 cases of invasive cervical adenocarcinoma in women younger than 50 years. Of note, hrHPV− AGC results were present in 10 of 13 carcinomas (76.9%) detected after AGC Pap tests, all in women 40 years or older with endometrial adenocarcinomas (n  =  8), ovarian carcinoma (n  =  1), and cervical adenosquamous carcinoma in a woman (n  =  1) in her 50s. Testing for hrHPV after AGC Pap testing was most helpful in the detection of cervical intraepithelial neoplasia grades 2/3, adenocarcinoma in situ, and invasive cervical adenocarcinomas in women younger than 50 years.
Well-Differentiated Neuroendocrine (Carcinoid) Tumors of the Extrahepatic Biliary Ducts
Authors: Noronha Yvonne Saldanha , Raza Anwar Sultana 
Published: February 2021

Abstract
Primary, well-differentiated neuroendocrine (carcinoid) tumors of the extrahepatic biliary ducts are an uncommon cause of biliary obstruction. As compared to cholangiocarcinomas, which are more commonly seen at this location, these tumors tend to behave less aggressively, and only one-third metastasize. Tumor size (&gt;2 cm) appears to be the best predictor of aggressive behavior. Surgery is the mainstay of treatment and complete resection offers prolonged disease-free survival. Accurate preoperative diagnosis is therefore important and can be made by examining brush cytology specimens obtained during endoscopic retrograde cholangiopancreatography and/or endoscopic ultrasound-guided fine-needle aspiration. It is important to keep this entity in mind, especially when examining cytologic or small biopsy specimens, so that appropriate immunohistochemical stains can be used to arrive at the correct diagnosis.
Variation in Human Erythrocyte Membrane Unsaturated Fatty Acids: Correlation With Cardiovascular Disease
Authors: Sepulveda Jorge L. , Tanhehco Yvette C. , Frey Monica , Guo Lida , Cropcho Lorna J. , Gibson K. Michael , Blair Harry C. 
Published: February 2021

Abstract
Context.—Whether cell membrane fatty acid (FA) composition is a useful indicator of vascular disease is unclear.
Objective.—To study variation of erythrocyte (RBC) membrane FA in samples from healthy volunteers, hospitalized patients, and cardiac troponin I–elevated patients with myocardial damage without a priori assumptions as to FA composition.
Design.—We separated FAs extracted from RBCs by gas chromatography and identified them by mass spectrometry. Fatty acids with abundance greater than 1% of total were quantified and compared: hexadecanoic (C16:0), octadecadienoic (C18:2), cis- and trans-octadecenoic (C18:1), and eicosatetraenoic (C20:4) acids. Deuterated standards established proportionality of FA recovery. The cis- and trans-C18:1 identification was verified by comparison with standards.
Results.—In troponin-positive samples, C18:2 to C18:1 ratios were increased 30% compared with healthy controls or with random patient samples. Erythrocyte trans-C18:1 had a wide variation, ∼10-fold, in all groups but without differences between groups. Replicates showed that the wide range of RBC trans-FA load is not due to analytic variation. In healthy subjects, the RBC content of lower– molecular weight FAs (C16-C18) correlated with serum low-density lipoprotein cholesterol, but despite the established relationship between dietary trans-FA and increased low-density lipoprotein cholesterol, lipid profiles had no correlation with RBC trans-FA content.
Conclusions.—Erythrocyte accumulation of unsaturated FA may be a useful indicator of vascular disease, whereas the wide range in trans-FAs suggests that both diet and genetic variation affect RBC trans-FA accumulation. Unsaturated FAs increase membrane fluidity and may reflect a natural response to subclinical vascular changes, which may in turn reflect increased risk of clinical disease.
Trastuzumab as Adjuvant Therapy for Early Breast Cancer: The Importance of Accurate Human Epidermal Growth Factor Receptor 2 Testing
Authors: Hicks David G. , Kulkarni Swati 
Published: February 2021

Abstract
Context.—Overexpression of human epidermal growth factor receptor 2 (HER2) is an adverse prognostic parameter for patients with breast cancer. Patients with HER2-positive tumors are, however, likely to gain significant benefit from targeted therapy with trastuzumab. Four large-scale trials have assessed the efficacy and safety of adjuvant trastuzumab. In all 4 trials, disease-free survival and overall survival were significantly improved with adjuvant trastuzumab (36%–52% and 33%–41%, respectively), and improvements were observed in all patient subgroups.
Objective.—To describe, in detail, the clinical benefits of using trastuzumab in the adjuvant setting, and to emphasize the importance this places on the pathologist to correctly identify all patients with HER2-positive tumors with a high degree of accuracy.
Data Sources.—Published literature on both HER2 testing and the adjuvant use of trastuzumab.
Conclusions.—Immunohistochemistry and/or fluorescence in situ hybridization are routinely used to determine HER2 status. Maintaining quality assurance throughout a standardized testing process is essential to achieve accurate and reproducible assay results. Adherence to the new American Society of Clinical Oncology/College of American Pathologists HER2 testing guidelines will help to ensure correct identification of all patients who may benefit from adjuvant trastuzumab and has significant implications for patient outcomes.
Practical Pituitary Pathology: What Does the Pathologist Need to Know?
Authors: Asa Sylvia L. 
Published: February 2021

Abstract
Context.—The sellar region is the site of frequent pathology. The pituitary is affected by a large number of pathologic entities arising from the gland itself and from adjacent anatomical structures including brain, blood vessels, nerves, and meninges. The surgical pathology of this area requires the accurate characterization of primary adenohypophysial tumors, craniopharyngiomas, neurologic neoplasms, germ cell tumors, hematologic malignancies, and metastases as well as nonneoplastic lesions such as cysts, hyperplasias, and inflammatory disorders.
Objective.—To provide a practical approach to the diagnosis of pituitary specimens.
Data Sources.—Literature review and primary material from the University of Toronto.
Conclusions.—The initial examination requires routine hematoxylin-eosin to establish whether the lesion is a primary adenohypophysial proliferation or one of the many other types of pathology that occur in this area. The most common lesions resected surgically are pituitary adenomas. These are evaluated with a number of special stains and immunohistochemical markers that are now available to accurately classify these tumors. The complex subclassification of pituitary adenomas is now recognized to reflect specific clinical features and genetic alterations that predict targeted therapies for patients with pituitary disorders.
Expression of Melanoma Antigens in Epithelioid Gastrointestinal Stromal Tumors: A Potential Diagnostic Pitfall
Authors: Guler Mehmet L. , Daniels Jason A. , Abraham Susan C. , Montgomery Elizabeth A. 
Published: February 2021

Abstract
Context.—Most gastric gastrointestinal stromal tumors (GISTs) express CD117/c-kit, as do a subset of metastatic melanomas, leading to a diagnostic dilemma in some cases.
Objective.—To further differentiate GISTs from melanoma, we investigated expression of melanoma markers in GISTs using a well-characterized set of gastric lesions on tissue microarrays.
Design.—Tissue microarrays from paraffin-embedded tissue cores from 38 patients were stained with S100 protein, HMB-45, and Melan-A antibodies. All cases had been previously stained with CD117/c-kit and CD34 antibodies. All were reactive with CD117/c-kit, and 88.2% expressed CD34.
Results.—S100 protein was focally expressed in 2 (5.3%) of 38 GISTs; these lesions lacked HMB-45 and Melan-A labeling. No tumor labeled with HMB-45, but 4 (10.6%) of 38 cases labeled with Melan-A antibodies. The Melan-A–reactive cases were all S100 negative and CD34 positive. The S100-reactive cases were spindle cell neoplasms, whereas the Melan-A–reactive cases were epithelioid neoplasms (4/9; 44%). An additional 15 standard sections of separate cases of epithelioid GISTs were then labeled with Melan-A, and 5 (33%) of 15 showed at least focal labeling.
Conclusions.—Melan-A staining can be encountered in a subset of epithelioid GISTs, a finding that can suggest a differential diagnosis of melanoma. In this series, the Melan-A–reactive cases lacked S100 protein and expressed CD34, both of which would be unlikely in melanoma. As such, a panel approach is best in differentiating epithelioid GISTs from melanoma.
How Much Tissue Sampling Is Required When Unsuspected Minimal Prostate Carcinoma Is Identified on Transurethral Resection?
Authors: Trpkov Kiril , Thompson Jenny , Kulaga Andrew , Yilmaz Asli 
Published: February 2021

Abstract
Context.—When minimal prostate cancer is detected in the initial transurethral resection of the prostate (TURP) sample, it is uncertain how extensively the remaining tissue should be sampled for accurate grading and staging.
Objective.—To identify whether additional partial or complete sampling is required to accurately evaluate TURP samples with minimal cancer (stage T1a).
Design.—We prospectively examined all TURP samples in our institution during 1 year. All specimens were sampled randomly in 6 cassettes. When minimal cancer was found, we performed additional partial sampling (1 block per 5 g of remaining tissue), followed by complete submission of all remaining tissue. All samples were evaluated separately to identify possible changes in Gleason score and tumor volume. We performed a cost analysis for the additional tissue sampling.
Results.—Of 747 TURP samples evaluated on the initial 6 cassettes, 125 (16.7%) contained prostate cancer. Minimal cancer involving less than 5% of sampled tissue was found in the initial submission in 26 (3.5%) patients. Additional partial examination required 3.5 blocks per case (median; range, 1–23), while complete processing required an additional 5.5 blocks per case (median; range, 2–25). Initial Gleason scores and tumor volumes were not changed in any of the studied cases after evaluating the additional partial and complete samples. In our laboratory, we calculated a cost of $4336 per year for the additional sampling of TURPs with minimal cancer ($1681 for partial and $2655 for complete sampling).
Conclusions.—When minimal cancer was found in the first 6 cassettes of transurethral resections, additional partial and complete sampling did not change the initial Gleason scores and tumor volumes.