bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fascin Expression in Diffuse Large B-Cell Lymphoma, Anaplastic Large Cell Lymphoma, and Classical Hodgkin Lymphoma
Authors: Bakshi Nasir A. , Finn William G. , Schnitzer Bertram , Valdez Riccardo , Ross Charles W. 
Published: February 2021

AbstractContext.—Fascin is an actin-bundling protein involved in the formation of dendritic processes. Fascin is a sensitive marker for classical Reed-Sternberg cells and has a high negative predictive value for diagnosis of classical Hodgkin lymphoma (CHL). Fascin has been used to distinguish CHL from non-Hodgkin lymphoma. Recently, it was shown that fascin might not help differentiate CHL from anaplastic large cell lymphoma (ALCL). Moreover, fascin has not been extensively studied in the context of other large cell lymphomas.Objective.—To analyze fascin expression in diffuse large B-cell lymphoma (DLBCL) and also reexamine its usefulness in discriminating CHL from ALCL.Design.—Formalin-fixed, paraffin-embedded tissue samples from 41 cases of DLBCL, 30 cases of CHL, and 30 cases of ALCL were analyzed. Fascin expression was compared across each type of lymphoma with additional correlation between fascin positivity and ALK-1 expression in ALCL performed.Results.—Only 6 (14.6%) of 41 cases of DLBCL stained positively for fascin, with most neoplastic large cells exhibiting a weak staining pattern. Fifteen (50%) of 30 cases of ALCL showed positivity for fascin, with most large cells staining strongly. All 30 cases of CHL demonstrated intense positive staining. Sixty percent of fascin-positive ALCLs were positive for ALK-1, while 66.7% of fascin-negative ALCLs were positive for ALK-1.Conclusions.—Fascin is highly sensitive for CHL and has a very high negative predictive value (100% in this series) for distinguishing CHL from DLBCL or ALCL. However, the specificity and positive predictive value for fascin are much higher in distinguishing CHL from DLBCL than in distinguishing CHL from ALCL. Expression of fascin appears more useful in the differential diagnosis of CHL versus DLBCL than in the differential diagnosis of CHL versus ALCL.
The Value of CD64 Expression in Distinguishing Acute Myeloid Leukemia With Monocytic Differentiation From Other Subtypes of Acute Myeloid Leukemia: A Flow Cytometric Analysis of 64 Cases
Authors: Dunphy Cherie H. , Tang Wohzan 
Published: February 2021

Abstract
Context.—Flow cytometric immunophenotyping is a useful ancillary tool in the diagnosis and subclassification of acute myeloid leukemias (AMLs). A recent study concluded that CD64 is sensitive and specific for distinguishing AMLs with a monocytic component (ie, AML M4 and AML M5) from other AML subtypes. However, in that study, the intensity of CD64 was not well defined and the number of non-M4/non-M5 AMLs was small.
Objective.—To evaluate the usefulness of CD64 by flow cytometric immunophenotyping in distinguishing AMLs with monocytic differentiation from other AML subtypes.
Design.—Sixty-four AMLs subclassified based on the French-American-British and World Health Organization classifications on pretreatment bone marrows were retrieved from our files (7 M0s, 11 M1s, 17 M2s, 7 M3s, 9 M4s, 7 M5s, 4 M6s, and 2 M7s). A standard panel of markers, including CD2, CD3, CD5, CD7, CD10, CD11b, CD13, CD14, CD15, CD19, CD20, CD33, CD34, CD45, CD56, CD64, CD117, and HLA-DR, were analyzed by flow cytometric immunophenotyping in all AMLs (52 bone marrow samples; 12 peripheral blood samples).
Results.—CD64 was expressed in AML subtypes M0 to M5 in varying intensities: heterogeneously expressed in 1 of 7 M0s; dimly expressed in 3 of 11 M1s; dimly and moderately expressed in 6 and 2 of 17 M2s, respectively; dimly and moderately expressed in 5 and 1 of 7 M3s, respectively; dimly expressed in 4 of 9 M4s; and heterogeneously, moderately, and strongly expressed in 1, 3, and 3 of 7 M5s, respectively.
Conclusions.—Strong CD64 expression distinguishes AML M5; however, heterogeneous, dim, or moderate expression in itself does not distinguish M0 through M4 subtypes from M5 with dim to moderate CD64 expression. However, any CD64 expression associated with strong CD15 expression distinguishes AML M4 or M5, from other AML subtypes.
Comparison of Fungal Culture Versus Surgical Pathology Examination in the Detection of Histoplasma in Surgically Excised Pulmonary Granulomas
Authors: Weydert Jamie A. , Van Natta Timothy L. , DeYoung Barry R. 
Published: February 2021

Abstract
Context.—Granulomatous pulmonary nodules are common in areas endemic for Histoplasma infection, and may require surgical excision to exclude neoplasia. Surgeons may elect to routinely send material directly to the clinical microbiology laboratory for fungal and mycobacterial cultures.
Objective.—To determine if tissue from surgically excised pulmonary granulomatous nodules removed from patients in a geographic area endemic for Histoplasma infection should be routinely submitted for fungal culture.
Design.—Retrospective review and comparison of surgical pathology histochemical findings and clinical microbiology results of 30 surgical (wedge) lung excisions that demonstrated granulomatous nodule at the time of frozen section.
Results.—Twenty cases demonstrated fungal organisms consistent with Histoplasma species via histochemical fungal stains. Of these 20 cases, 17 were tested in the microbiology laboratory using direct smear examination and fungal culture; Histoplasma was detected in 1 case (1/17). Eight cases revealed no organisms by surgical pathology. Of these, 6 were tested in the microbiology laboratory, and all 6 were negative by culture and direct smear (0/6). The remaining 2 cases demonstrated organisms other than Histoplasma by surgical pathology examination.
Conclusions.—Surgical pathology examination of granulomatous pulmonary nodules detected Histoplasma organisms with greater sensitivity than culture and direct smear. There were no false-negative surgical pathology diagnoses when compared with microbiological results. These findings suggest that it is not necessary to routinely send material from solitary pulmonary granulomas for fungal culture when the material is removed from immunocompetent patients in a geographic area endemic for histoplasmosis.
Clinical Laboratory Reports in Molecular Pathology
Authors: Gulley Margaret L. , Braziel Rita M. , Halling Kevin C. , Hsi Eric D. , Kant Jeffrey A. , Nikiforova Marina N. , Nowak Jan A. , Ogino Shuji , Oliveira Andre , Polesky Herbert F. , Silverman Lawrence , Tubbs Raymond R. , Van Deerlin Vivianna M. , Vance Gail H. , Versalovic James 
Published: February 2021

Abstract
Context.—Molecular pathology is a rapidly growing area of laboratory medicine in which DNA and RNA are analyzed. The recent introduction of array technology has added another layer of complexity involving massive parallel analysis of multiple genes, transcripts, or proteins.
Objective.—As molecular technologies are increasingly implemented in clinical settings, it is important to bring uniformity to the way that test results are reported.
Data Sources.—The College of American Pathologists Molecular Pathology Resource Committee members summarize elements that are already common to virtually all molecular pathology reports, as set forth in the College of American Pathologists checklists used in the laboratory accreditation process. Consensus recommendations are proposed to improve report format and content, and areas of controversy are discussed. Resources are cited that promote use of proper gene nomenclature and that describe methods for reporting mutations, translocations, microsatellite instability, and other genetic alterations related to inherited disease, cancer, identity testing, microbiology, and pharmacogenetics.
Conclusions.—These resources and recommendations provide a framework for composing patient reports to convey molecular test results and their clinical significance to members of the health care team.
Hyperhomocysteinemia and Thrombosis: An Overview
Authors: Eldibany Mohamed M. , Caprini Joseph A. 
Published: February 2021

Abstract
Context.—Homocysteine, a sulfur-containing amino acid, absent in natural diets, is a metabolic intermediary in transmethylation and transsulfuration reactions. Such reactions are essential to normal cellular growth, differentiation, and function. Excess homocysteine is associated with vascular disease and related disorders.
Objective.—To review homocysteine metabolism, the pathogenesis and classification of hyperhomocysteinemia, and the published literature investigating the association of homocysteine and methylenetetrahydrofolate reductase defects with arterial and venous thromboembolism and related disorders. The role of vitamin supplementation in patients with hyperhomocysteinemia is addressed.
Data Sources.—Published medical and scientific literature. Articles addressing the objectives were selected and reviewed. Pertinent studies and conclusions were summarized, grouped, and contrasted.
Conclusions.—The association of hyperhomocysteinemia and arterial and venous thrombosis is controversial. Severe hyperhomocysteinemia is associated with atherosclerosis. The effect of mild hyperhomocysteinemia is less certain. Coinheritance of methylenetetrahydrofolate reductase defects and factor V Leiden is likely to increase the risk of venous thromboembolism. The association of methylenetetrahydrofolate reductase defects combined with no additional thrombophilic risk factors with venous thrombosis is less clear. High doses of folic acid to lower homocysteine levels might not be necessary.
Sclerosing Angiomatoid Nodular Transformation of the Spleen
Authors: Awamleh Ahlam A. , Perez-Ordoñez Bayardo 
Published: February 2021

Abstract
Sclerosing angiomatoid nodular transformation (SANT) is a recently recognized nonneoplastic vascular lesion of the spleen with fewer than 30 cases described. Microscopically, SANT consists of multiple well-circumscribed vascular/ angiomatoid nodules showing plump endothelial cell and extravasated erythrocytes. The nodules are surrounded by a variable lymphoplasmacytic infiltrate, spindle cells, and collagenous stroma. The vascular nodules display a complex mixture of endothelial phenotypes resembling splenic sinusoids (CD34−/CD31+/CD8+), capillaries (CD34+/ CD31+/CD8−), and small veins (CD34−/CD31+/CD8−). Focal expression of CD68 can also be seen. The differential diagnosis of SANT includes splenic hamartoma, inflammatory myofibroblastic tumor, littoral cell angioma, and hemangioendothelioma. It has been postulated that SANT represents a peculiar hamartomatous transformation of splenic red pulp in response to an exaggerated nonneoplastic stromal proliferation. SANT has a benign clinical course with splenectomy being curative.
Gastrointestinal Stromal Tumors: A Review of the Literature
Authors: Laurini Javier A. , Carter J. Elliot 
Published: February 2021

Abstract
Gastrointestinal stromal tumors are mesenchymal neoplasms with a spectrum of histologic appearances and biologic activity. The morphologic classification of these lesions has evolved over time, and molecular analysis has led to a better understanding of their nature. The histologic differential diagnosis for these lesions is broad and includes many spindle cell lesions of the gastrointestinal tract, including neoplasms of true smooth muscle and neural origin, proliferating fibrous lesions, metastatic neoplasms, and primary sarcomas of vascular and adipose origin. Immunohistochemical studies that include CD117 have become invaluable in the classification of mesenchymal lesions arising in the gastrointestinal tract. Treatment of gastrointestinal stromal tumors has historically been involved surgery, but the use of the chemotherapeutic agent imatinib mesylate for advanced disease has made accurate classification even more important. The molecular features have not only allowed us to understand the pathogenesis of these tumors but also have proven to be associated with response to kinase inhibitors.
Initial Margin Status for Invasive Ductal Carcinoma of the Breast and Subsequent Identification of Carcinoma in Reexcision Specimens
Authors: Skripenova Silvia , Layfield Lester J. 
Published: February 2021

Abstract

Context.
Margin status of lumpectomy specimens is related to frequency of local recurrence. Optimal surgical technique requires microscopic margins free of carcinoma by at least 2 mm. Recurrence following lumpectomy is associated with residual carcinoma secondary to inadequate resection.

Objective.
To review our series of breast excisions to determine the frequency of residual carcinoma for positive, close, and negative margins.

Design.
We reviewed lumpectomies and excisional biopsies for invasive ductal carcinoma that had subsequent reexcisions. Margin status of specimens was recorded as positive, less than 1 mm, 1 to 2 mm, or greater than 2 mm.

Results.
A total of 123 lumpectomies and excisional biopsies of invasive ductal carcinoma with reexcision were reviewed. Residual invasive carcinoma was found in 44% (17), 25% (6), 28% (8), and 16% (5) of cases with positive, less than 1 mm, 1 to 2 mm, and greater than 2 mm margins, respectively. Residual invasive carcinomas were found in 57% (8), 100% (5), 67% (2), and 100% (2) of mastectomies with positive, less than 1 mm, 1 to 2 mm, and greater than 2 mm margins, respectively, in the initial lumpectomy or excisional biopsy.

Conclusions.
Frequency of residual invasive carcinoma was related to margin status of the original lumpectomy/biopsy. Even when margins were positive, most reexcisions were free of carcinoma. Residual invasive carcinoma was found in greater than 25% of patients with margins less than 2 mm, supporting reexcision for patients with margins of less than 2 mm. Sixteen percent of cases with margins greater than 2 mm harbored residual invasive carcinoma. Evaluation of margin status was complicated by tissue distortion and fragmentation.
Tumor-to-Tumor Metastasis: Report of 2 Cases of Metastatic Carcinoma to Angiomyolipoma of the Kidney
Authors: Ricketts Reva , Tamboli Pheroze , Czerniak Bogdan , Guo Charles C. 
Published: February 2021

Abstract
Tumor-to-tumor metastasis is a rare phenomenon. Renal cell carcinoma is the most common recipient of tumor-to-tumor metastasis in malignant tumors. However, renal angiomyolipoma has not been reported to be a recipient. Here we report 2 cases of tumor-to-tumor metastasis to renal angiomyolipoma. In one case, the donor tumor originated from neuroendocrine carcinoma of the pancreas, and in the other case the donor tumor was from adenocarcinoma of the lung. The donor tumors showed morphologic features that did not easily fit into renal angiomyolipoma, and they also demonstrated patterns of immunoreactivity consistent with the primary tumors rather than with renal angiomyolipoma. To our knowledge, these are the first reported cases of tumor-to-tumor metastasis to renal angiomyolipoma. An awareness of this phenomenon is important to avoid an incorrect diagnosis when encountering unusual morphologic features in renal angiomyolipoma.
Concurrent Megakaryocytic and Erythroid Chronic Myelogenous Leukemia Blast Crisis
Authors: Westfall Danielle E. , Zhang Ling , Song Sophie , Lee Stephen 
Published: February 2021

Abstract
Chronic myelogenous leukemia with blast crisis is seen in 15% to 20% of patients with chronic myelogenous leukemia. Chronic myelogenous leukemia with either erythroid or megakaryocytic blast crisis is not uncommon in the clinical setting. The incidence ranges from 0% to 33% in accordance with literature reports. The diagnosis of erythroid or megakaryocytic blast phase is often challenging because the percentage of blasts in the blood or bone marrow required for diagnosis has not been firmly established. Also, some myeloblasts can have aberrant expression of either erythroid or megakaryocytic markers by flow cytometry during clonal evolution. Early recognition of this entity is crucial because either megakaryocytic or erythroid blast crisis predicts an aggressive clinical course. To our knowledge, the coexistence of megakaryocytic and erythroid blasts has not been reported. We report a unique case of chronic myelogenous leukemia with this rare bilineage blast crisis in the background of dysplasia and marked myelofibrosis. Related literature is also reviewed.
Benign Tumors and Tumorlike Conditions of the Lung
Authors: Borczuk Alain C. 
Published: February 2021

Abstract
Context.—Benign tumors and tumorlike conditions of the lung are encountered in the pathologic evaluation of asymptomatic and symptomatic lung nodules. Since many of these lesions are uncommon, they can be diagnostically challenging.
Objective.—To review the current classification of benign lung tumors, with emphasis on histopathology and useful ancillary studies.
Data Sources.—The current World Health Organization classification system for lung neoplasms and review of relevant publications.
Conclusions.—Despite improved imaging techniques, benign lung nodules are encountered in wedge biopsy and resection specimens. Histopathology, immunohistochemistry, and molecular techniques ensure accurate pathologic diagnosis and have shed light on the histogenesis of these unusual lesions.
Primary Pleural Neoplasia: Entities Other Than Diffuse Malignant Mesothelioma
Authors: Guinee Donald G. , Allen Timothy Craig 
Published: February 2021

AbstractContext.—Overwhelmingly, the most common neoplasm involving the pleura is metastatic carcinoma. In contrast, diffuse malignant mesothelioma occurs relatively rarely; however, it is nonetheless the most common neoplasm primary to the pleura. Metastatic carcinoma and diffuse malignant mesothelioma each have their own prognostic and therapeutic characteristics. Other primary pleural neoplasms occur uncommonly or rarely, with their own prognostic and therapeutic characteristics.Objective.—To review primary pleural neoplasms other than diffuse malignant mesothelioma, to better ensure correct diagnosis and optimal assessment of prognosis and treatment.Data Sources.—Literature review and primary material from the authors' institutions.Conclusions.—A nonexhaustive group of uncommon to rare benign and malignant primary pleural neoplasms— other than diffuse malignant mesothelioma—are presented, of which one must be aware in order to maintain an appropriate index of suspicion to include them in the differential diagnosis of a pleural tumor.
Lesions of the Adrenal Cortex
Authors: McNicol Anne Marie 
Published: February 2021

Abstract
Context.—In surgical pathology practice adrenal cortical tumors are rare. However, in autopsy series adrenal cortical nodules are found frequently. These are now being identified more commonly in life when the abdomen is scanned for other disease. It is important to differentiate between benign and malignant lesions as adrenal cortical carcinoma is an aggressive tumor. Molecular genetic investigations are providing new information on both pathogenesis of adrenal tumors and basic adrenal development and physiology.
Objective.—To provide an overview of current knowledge on adrenal cortical development and structure that informs our understanding of genetic diseases of the adrenal cortex and adrenal cortical tumors.
Data Sources.—Literature review using PubMed via the Endnote bibliography tool.
Conclusions.—The understanding of basic developmental and physiologic processes permits a better understanding of diseases of the adrenal cortex. The information coming from investigation of the molecular pathology of adrenal cortical tumors is beginning to provide additional tests for the assessment of malignant potential in diagnosis but the mainstay remains traditional histologic analysis.
Pheochromocytoma and Extra-adrenal Paraganglioma: Updates
Authors: Tischler Arthur S. 
Published: February 2021

Abstract
Context.—Advances in genetics and gene expression profiling have led to new ways of thinking about the pathobiology of pheochromocytoma and extra-adrenal paraganglioma. These developments are concurrent with the publication and dissemination of the 2004 World Health Organization bluebook on pathology and genetics of endocrine tumors.
Objective.—To summarize new information required by pathologists for effective participation in patient management and research.
Data Sources.—Literature review and primary material from Tufts Medical Center.
Conclusions.—The World Health Organization reserves the term pheochromocytoma for tumors arising from chromaffin cells in the adrenal medulla. Closely related tumors in extra-adrenal sympathetic and parasympathetic paraganglia are classified as extra-adrenal paragangliomas. A pheochromocytoma is an intra-adrenal sympathetic paraganglioma. Although arbitrary, this nomenclature emphasizes important distinctive properties of intra-adrenal tumors, including an often adrenergic phenotype, relatively low rate of malignancy, and predilection to occur in particular hereditary syndromes. Malignancy is defined by presence of metastases not local invasion. Occult germline mutations characteristic of familial syndromes are now found in more than 20% of patients with apparently sporadic tumors, bringing the percentage of tumors with a known genetic basis close to 30%. In addition, tumor location and risk of malignancy vary with the underlying genetic defect. The “10 percent rule” for pheochromocytoma/paraganglioma—10% familial, 10% malignant, 10% extra-adrenal—is therefore no longer tenable. Current roles of pathology are limited to diagnosing primary or metastatic tumors and identifying features suggestive of malignant potential or hereditary disease. Future roles may involve more definitive assessment of malignancy, genotype-phenotype correlation, and identification of targets for therapy.
An Overview of Practical Issues in the Diagnosis of Gastroenteropancreatic Neuroendocrine Pathology
Authors: Chetty Runjan 
Published: February 2021

Abstract
Context.—Although somewhat uncommon, neuroendocrine tumors of the gastrointestinal tract and pancreas have come under scrutiny in recent times. With advances in imaging techniques, more of these tumors are being removed and sent for pathologic evaluation. It is important for the diagnostic pathologist to be aware of recent developments in this field.
Objective.—This overview focuses on nomenclature/terminology, classification, practical issues related to recent developments in immunohistochemical markers that aid diagnosis and may relate to prognosis, and molecular advances.
Data Sources.—Currently available literature and personal experience in the field of neuroendocrine pathology.
Conclusions.—The preferred terminology is neuroendocrine/tumor/carcinoma and it is recommended that the World Health Organization classification be used, taking note of the site variations that may occur. A large number of immunohistochemical markers are available but a core panel that is relevant to the site should be used. Cytokeratin 19 positivity is an independent marker of aggressive behavior in pancreatic neuroendocrine tumors. Gastrointestinal neuroendocrine tumors arise via the CpG island methylator phenotype pathway, whereas their pancreatic counterparts arise as a result of chromosomal instability. The MEN1 gene is implicated in both syndromic and sporadic forms of these tumors.