bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comprehensive Analysis of the Expression of the Metastasis-Associated Gene 1 in Human Neoplastic Tissue
Authors: Hofer Matthias D. , Tapia Coya , Browne Tara Jane , Mirlacher Martina , Sauter Guido , Rubin Mark A. 
Published: February 2021

Abstract
Context.—The metastasis-associated gene 1 (MTA1) is overexpressed in several human cancers. Recent reports suggest that MTA1 may play a role in cancer progression either through transcription repression and/or hormone receptor interactions.
Objective.—To analyze MTA1 expression levels in a wide variety of human tumors.
Design.—We used Oncomine, an Internet-based compendium of expression array data, to query more than 90 expression array studies, and we evaluated tissue microarrays composed of more than 3200 samples representing 138 different localized neoplasms.
Results.—Both analyses show that MTA1 is ubiquitously expressed in benign and malignant tumors. The highest levels of MTA1 expression were observed in diffuse B-cell lymphoma (mean staining intensity, 3.9/4), basal cell carcinomas (3.7/4), and consistently in tumors of neuroendocrine descent such as paraganglioma (3.7/4) and carcinoid tumor (3.1/4).
Conclusions.—This study characterizes MTA1 expression for the first time across a broad spectrum of primary tumors, demonstrating expression in both benign and malignant neoplasms in addition to showing an association with neuroendocrine differentiation. We also found evidence that MTA1 expression is associated with tissue invasion but may not be sufficient for the progression to metastatic stages.
The Criteria for Bone Marrow Recovery Post–Myelosuppressive Therapy for Acute Myelogenous Leukemia: A Quantitative Study
Authors: Khalil Farah , Cualing Hernani , Cogburn Julia , Miles Lili 
Published: February 2021

Abstract
Context.—Although the early post–myelosuppressive chemotherapy pathologic changes of the marrow have been described, the rate and the histologic definition of recovery are not defined.
Objective.—To study the rate of recovery of bone marrow in patients given myelosuppressive therapy for acute myelogenous leukemia, establish the histologic criteria of recovered marrow, and correlate the recovery pattern with those patients who received a bone marrow transplant by using histology, peripheral blood, immunophenotyping, and computerized morphometry and mathematical slope equation.
Design.—We studied the post–myelosuppression recovery of the bone marrow to determine patterns and rate of recovery in 135 serial bone marrow biopsies of 51 patients. These patients were divided into 2 groups: 1 group of 28 cases diagnosed with acute myeloid leukemia, the majority treated with cytarabine (Ara-C) infusion for 7 days and daunorubicin intravenously daily for 3 days (7+3 regimen), and the other control group of 23 cases treated with chemotherapy or allogeneic bone marrow transplantation for a variety of hematologic malignancies. All biopsies during the recovery period were obtained before consolidation regimen. We used morphometry to calculate the cellularity and myeloid to erythroid ratio and quantified megakaryocytes CD10 versus time from day 14 onward. The absolute neutrophil and platelet counts for 28 cases were related to histologic recovery.
Results.—From day 14, we noted a differential slope of recovery of these patients with no difference in male and female patients, P = .45, but a difference between younger and older patients (&gt;58.5 years), P = .03. After regenerative hyperplasia, the cellularity plateaus, the myeloid to erythroid ratio, and the megakaryocytes even out with platelet normalization, and the early CD10+ B cells rise from day 40 onward, P = .01. The patterns of recovery after day 60 of postchemotherapy and posttransplantation patients are similar. Complete histologic and peripheral blood recovery is noted at day 38 and thereafter.
Conclusions.—By linear equation using at least 2 trephine biopsy specimens, the projected rate of cellular recovery may be determined, and 5 histologic features are associated with complete histologic recovery.
Immunophenotypic Characterization of Anal Gland Carcinoma: Loss of p63 and Cytokeratin 5/6
Authors: Lisovsky Mikhail , Patel Keyur , Cymes Karina , Chase Donald , Bhuiya Tawfiqul , Morgenstern Nora 
Published: February 2021

AbstractAnal gland carcinoma (AGC) is a rare perianal invasive cancer composed of tubular glands lined by cuboidal epithelium. The clinical features and histogenesis of AGC are not well understood and its origin from anal glands is often difficult to prove. Little is known about immunophenotypic features of AGC that could be useful in establishing the diagnosis. This study evaluated the immunohistochemical profile of 2 cases of AGC in comparison to anal glands from 11 hemorrhoidectomy specimens. Sections from the specimens were routinely processed and immunostained using commercial antibodies to cytokeratin (CK) 7, CK20, CK5/ 6, p63, CDX2, smooth muscle actin, calponin, heavy chain smooth muscle myosin, p53, and p16. In case 1 of AGC, radiation and chemotherapy preceded an abdominoperineal resection. In biopsies from this case, the neoplastic anal glands had a tubular pattern, whereas most glands in the resection specimen exhibited mucinous features. The histologic pattern in case 2 was tubular. Normal anal glands showed immunoreactivity for myoepithelial and basal cell markers CK5/6 and p63 in basal and parabasal cell layers and for CK7 in superficial cell layers. In contrast, both cases of AGC were negative for CK5/6 and p63 and were diffusely positive for CK7. Normal glands and both cases of AGC were negative for the intestinal differentiation marker CDX2, CK20, smooth muscle actin, calponin, smooth muscle myosin heavy chain, p16, and p53. Our data suggest that loss of p63 and CK5/6 expression is a feature of AGC. Anal gland carcinoma shares negativity for CDX2 and CK7+/CK20− profile with normal anal glands. No evidence of myoepithelial cells was found in normal or malignant anal glands. These data may be useful in establishing the diagnosis of AGC.
Imatinib in the Management of Multiple Gastrointestinal Stromal Tumors Associated With a Germline KIT K642E Mutation
Authors: Graham Janet , Debiec-Rychter Maria , Corless Christopher L. , Reid Robin , Davidson Rosemarie , White Jeff D. 
Published: February 2021

Abstract
Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gut and are distinguished by expression of CD117 (c-Kit). Oncogenic mutations in the KIT or PDGFRA gene are detected in approximately 85% of sporadic GISTs. In recent years, examples of familial GIST have been reported in which germline mutations of KIT or PDGFRA result in multiple GISTs, skin disorders, and other abnormalities. The most common germline mutations are in KIT exon 11, mutations in exons 8 and 17 have also been described, and there are 2 families with germline PDGFRA mutations. We present a case in which a germline KIT exon 13 mutation (K642E) was discovered in a patient with multiple GISTs of rectum, small intestine, and esophagus, as well as diffuse hyperplasia of the interstitial cells of Cajal. To our knowledge, this is only the second germline example of this particular mutation. The patient's esophageal tumors were stabilized with imatinib.
An Extranodal Nasal Natural Killer/T-Cell Lymphoma With Isochromosome 7q10 as the Sole Cytogenetic Aberration Was Initially Diagnosed Via Bone Marrow Biopsy
Authors: Wang Huan-You , Wilson Kathleen S. , McKenna Robert W. , Xu Yin , Karandikar Nitin 
Published: February 2021

Abstract
We report a 58-year-old man who presented with fever, pancytopenia, hepatosplenomegaly, and “sinusitis” of his right nostril. Flow cytometric analysis of his bone marrow aspirate revealed a population of cells that were CD56+ (bright), CD2+ (dim), and CD7+ (slight brightly) but negative for CD3, CD4, CD5, CD8, CD11b, CD16, CD57, and T-cell receptors, consistent with aberrant natural killer cells. Bone marrow biopsy showed an atypical lymphoid infiltrate expressing CD56 as well as Epstein-Barr virus– encoded RNA and histiocytic hyperplasia with hemophagocytosis. Subsequent biopsy of his right nasal vestibule demonstrated an atypical lymphoid infiltrate, which was cytoplasmic CD3+, CD56+, and Epstein-Barr virus–encoded RNA positive, consistent with an extranodal nasal natural killer cell lymphoma. Conventional cytogenetic studies of the bone marrow revealed isochromosome 7q10 [i(7)(q10)] as the sole chromosomal aberration. To our knowledge, this is the first report demonstrating i(7)(q10) as a primary cytogenetic abnormality in an extranodal nasal natural killer cell lymphoma.
Lymphoepithelioma-like Carcinoma of the Ovary: A Case Report and Review of the Literature
Authors: Lee Sun , Park Sang Yoon , Hong Eun Kyung , Ro Jae Yoon 
Published: February 2021

Abstract
Lymphoepithelioma-like carcinoma is an undifferentiated carcinoma morphologically characterized by sheets of pleomorphic epithelioid cells with an intense lymphoid infiltrate. A 51-year-old woman presenting with low abdominal pain was found to have a right ovarian mass and enlarged pelvic, left para-aortic, and left supraclavicular lymph nodes. Based on a clinical diagnosis of right ovarian carcinoma with lymph node metastases, she received 9 cycles of chemotherapy, resulting in a reduction of her ovarian tumor, disappearance of the enlarged pelvic and para-aortic lymph nodes, and normalization of serum CA 125 level. The residual mass was removed surgically. The histology of the multinodular tumor resembled that of lymphoepithelioma of the nasopharynx and was observed in the right ovary. However, there was no viable tumor in either supraclavicular or para-aortic lymph nodes. Seven months after surgery, the patient has no evidence of disease. Lymphoepithelioma-like carcinoma appears to be rare in the female genital tract.
Follicular Lymphoma in Staging Bone Marrow Specimens: Correlation of Histologic Findings With the Results of Flow Cytometry Immunophenotypic Analysis
Authors: Iancu Dan , Hao Suyang , Lin Pei , Anderson S. Keith , Jorgensen Jeffrey L. , McLaughlin Peter , Medeiros L. Jeffrey 
Published: February 2021

Abstract
Context.—Bone marrow (BM) examination is part of the staging workup of lymphoma patients. Few studies have compared BM histologic findings with results of flow cytometric immunophenotyping analysis in follicular lymphoma (FL) patients.
Objective.—To correlate histologic findings with immunophenotypic data in staging BM biopsy and aspiration specimens of FL patients.
Design.—Bone marrow biopsy specimens of untreated FL patients were reviewed. Histologic findings were correlated with 3-color flow cytometric immunophenotyping results on corresponding BM aspirates.
Results.—Bone marrow biopsy specimens (with or without aspirates) of 114 patients with histologic evidence of FL in BM were reviewed. There were 76 bilateral and 38 unilateral biopsies performed, resulting in 190 specimens: 187 involved by FL and 3 negative (in patients with a positive contralateral specimen). The extent of BM involvement was &lt;5% in 32 (17.1%), ≥5% and ≤25% in 102 (54.6%), &gt;25% and ≤50% in 27 (14.4%), and &gt;50% in 26 (13.9%) specimens. The pattern of involvement was purely paratrabecular in 81 (43.3%), mixed in 80 (42.8%), and purely nonparatrabecular in 26 (13.9%). Immunophenotyping was only performed unilaterally, on BM aspirates of 92 patients, and was positive for a monoclonal B-cell population in 53 (57.6%) patients. Immunophenotyping was more often negative when biopsy specimens showed FL with a purely paratrabecular pattern. For comparison, we assessed 163 FL patients without histologic evidence of FL in BM also analyzed by flow cytometric immunophenotyping. A monoclonal B-cell population was identified in 5 patients (3%).
Conclusions.—Our data suggest that 3-color flow cytometric immunophenotyping adds little information to the evaluation of staging BM specimens of FL patients.
Diagnosis of Prostatic Carcinoma After Therapy
Authors: Bostwick David G. , Meiers Isabelle 
Published: February 2021

Abstract
Context.—Prostate cancer is the most common cancer of men in the United States and is third only to lung and colon cancer as a cause of cancer death. In 2006, 27 350 Americans will die of prostate cancer, and 234 460 new cases will be diagnosed. Treatment changes in the benign and cancerous prostate create diagnostic challenges in pathologic interpretation, particularly in needle biopsy specimens and in evaluation of extraprostatic metastases.
Objective.—To summarize therapy-related pathologic findings in the prostate with emphasis on recognition of treated adenocarcinoma.
Data Sources.—Extensive review of published literature and the authors' experience.
Conclusions.—Following therapy for prostate cancer, it is critical that the clinician provide the pertinent history of androgen deprivation or radiation therapy to assist the pathologist in rendering the correct diagnosis.
Parvovirus B19 Infection in the Immunocompromised Host
Authors: Florea Anca V. , Ionescu Diana N. , Melhem Mona F. 
Published: February 2021

AbstractHuman parvovirus B19 is a single-stranded DNA virus with a predilection for infecting rapidly dividing cell lines, such as bone marrow erythroid progenitor cells. People with defective cell-mediated immunity (eg, severe combined immunodeficiency syndrome; acquired immunodeficiency syndrome; and patients receiving immunosuppressive therapy, ie, post organ transplant) can develop pure red cell aplasia, in which suppression of erythroid precursors is permanent. Identification of parvovirus inclusions in marrow biopsies and subsequent confirmation of infection by in situ hybridization is important in the assessment of anemia in immunodeficient patients. Our objective is to provide a general overview of the parvovirus B19 infection and its characteristics in immunocompromised patients and to summarize updated information regarding the clinicopathologic features, pathobiology, and laboratory diagnosis of this subject. The pathologist should be aware of the wide spectrum of manifestations of parvovirus B19 infection depending on the patient's hematologic and immunologic status.
Methylation Profiles of Multiple CpG Island Loci in Extrahepatic Cholangiocarcinoma Versus Those of Intrahepatic Cholangiocarcinomas
Authors: Kim Baek-Hee , Cho Nam-Yun , Choi Minhee , Lee Sun , Jang Ja June , Kang Gyeong Hoon 
Published: February 2021

AbstractContext.—CpG island hypermethylation is attracting attention because of its importance as a tumor marker and its potential mechanism for the development of human cancers. Extrahepatic cholangiocarcinoma has been poorly investigated with respect to CpG island hypermethylation, and the number of genes known to be methylated in extrahepatic cholangiocarcinomas is fewer than 20.Objective.—To generate methylation profiles of 24 CpG island loci in extrahepatic cholangiocarcinomas, to correlate methylation findings with clinicopathologic findings, and to compare these findings with those of intrahepatic cholangiocarcinomas.Design.—Sixty-three extrahepatic cholangiocarcinomas and 48 intrahepatic cholangiocarcinomas were investigated for hypermethylation in 24 CpG island loci by using methylation-specific polymerase chain reaction.Results.—A total of 61 (96.8%) of 63 extrahepatic cholangiocarcinomas showed hypermethylation in at least one of the examined loci, and a high methylation frequency was seen in HOXA1 (95.2%), HPP1 (69.8%), and NEUROG1 (61.9%). The number of methylated CpG island loci was greater in extrahepatic cholangiocarcinomas with nodal metastasis than in those without nodal metastasis (P = .047), and hypermethylation of TIG1 was closely associated with nodal metastasis of extrahepatic cholangiocarcinomas (P = .007). CDH1 and NEUROG1 were more frequently methylated in extrahepatic cholangiocarcinoma than in intrahepatic cholangiocarcinoma, whereas CHFR, GSTP1, IGF2, MGMT, MINT31, p14, and RBP1 were more frequently methylated in intrahepatic cholangiocarcinoma: the differences was statistically significant (P &lt; .05).Conclusions.—A close relationship exists between CpG island hypermethylation and nodal metastasis of extrahepatic cholangiocarcinomas. Methylation profiles of extrahepatic cholangiocarcinomas are somewhat similar to but distinct from those of intrahepatic cholangiocarcinomas.
Promoter Hypermethylation for Molecular Nodal Staging in Non–Small Cell Lung Cancer
Authors: Safar A. Mazin , Spencer Horace , Su Xiaobo , Cooney Craig A. , Shwaiki Ali , Fan Chun-Yang 
Published: February 2021

Abstract
Context.— Even among cases of non–small cell lung cancer (NSCLC) in the most favorable stage (IA), the disease-specific mortality is 25% or greater. One plausible explanation implicates the simplistic standard pathologic procedures used to designate lymph node involvement. A more sensitive assessment of the nodal status may improve staging.
Objective.—To determine the prognostic impact of detecting an abnormal molecular event (promoter hypermethylation in a set of relevant genes) in histologically uninvolved lymph nodes in resected NSCLC.
Design.—In this retrospective analysis of archived material, we examined DNA extracted from lymph nodes of stage I NSCLC (n = 180). Patients underwent surgery between 1991 and 1995 in a single institution. Methylation-specific polymerase chain reaction was used to detect promoter hypermethylation in a panel of 8 genes. Survival data were extracted from the computerized database at the Tumor Registry.
Results.—Evidence of promoter hypermethylation in at least 1 gene was detected in 67% of these N0 nodes. The most commonly hypermethylated gene was E-cadherin (53%). The hypermethylation frequency for the remaining genes were as follows: APC, 5%; p16, 9%; MGMT, 11%; hMLH1, 15%; RASSF1A, 4%; DAP kinase, 9%; and ATM, 19%. The presence of promoter hypermethylation in 2 or more genes did not influence the overall, median, or 5-year survival rates.
Conclusions.—Identifying promoter hypermethylation (in our panel) in N0 lymph nodes in stage I NSCLC cannot be recommended for clinical decision making. Molecular abnormalities, including those found in cancer by qualitative methylation-specific polymerase chain reaction, are not synonymous with established, histologically detectable metastasis.
Mass Spectrometry–Based Proteomics: Principles, Perspectives, and Challenges
Authors: Wiśniewski Jacek R. 
Published: February 2021

Abstract
Mass spectrometry–based proteomics is a modern and rapidly developing methodology for qualitative and quantitative characterization of proteins and their posttranslational modification, subcellular localization, and interaction partners. It enables characterization of entire proteomes with unprecedented sensitivity and precision, providing platforms for identification of biomarkers and drug targets.
Suggested Guidelines for the Management of High-Profile Fatality Cases
Authors: Perper Joshua A. , Juste Gertrude M. , Schueler Harold E. , Motte Reinhard W. , Cina Stephen J. 
Published: February 2021

Abstract
Context.—The investigation of high-profile fatalities poses special challenges to medical examiners and coroners. Most high-profile cases can be readily recognized early in the course of the investigation. Commonly encountered examples include police-related fatalities or deaths in custody, deaths of celebrities, and mass fatalities or clustered deaths (eg, serial killers). Medical examiner and coroner offices should have policies and procedures in place for adequately handling such cases. A rational approach to these high-profile cases includes activating medical examiner or coroner investigative teams, preplanning before the autopsy, using special autopsy techniques and toxicology procedures, skillful questioning of key witnesses, preparing detailed and comprehensive reports, and planning effective communication with the media.
Objective.—The investigation of the sudden and unexpected death of Anna Nicole Smith, an entertainment personality, is presented as an example of how to address the challenging issues inherent in high-profile fatalities and how to adequately prepare for the forensic investigation of high-profile cases.
Design.—This article presents a methodical approach to the investigation of high-profile deaths.
Results.—A comprehensive, preplanned forensic investigation and autopsy (including use of adjunctive studies) following the death of Anna Nicole Smith resulted in the accurate determination of the cause and manner of her death while adequately convincing the public of the objectivity and reliability of the Medical Examiners Office with respect to its conclusions.
Conclusion.—The forensic investigation of death in high-profile cases can be much more tedious and demanding than the investigation of routine cases. It requires more stringent safekeeping of the body and its evidence, more extensive and sophisticated dissection techniques on occasion, and exhaustive toxicologic analysis to exclude low-probability allegations. Procedures for honest, unbiased, and judicious communication with outside agencies and the media must be followed. Failure to follow such procedures might have serious consequences for the medical examiner, the family of the deceased, and the community at large. Adherence to these suggested guidelines may resolve most of the intricate problems involved in the investigation of these types of cases.
Extranodal Follicular Dendritic Cell Sarcoma
Authors: Youens Kenneth E. , Waugh Michael S. 
Published: February 2021

Abstract
Extranodal follicular dendritic cell sarcoma is a rare tumor of follicular dendritic cells that can occur in a wide variety of sites. Although fairly well characterized histologically, with a distinct immunophenotype, it remains underrecognized, with as many as one third of cases initially misdiagnosed. This is often due to a failure to consider the entity. Patients with this tumor may have a worse prognosis than originally described. Prompted by a recent case at our institution, we briefly review the clinical features, etiology, histologic, and cytologic appearance of the tumor, as well as the ancillary studies useful in resolving diagnostic issues, primarily in an attempt to increase recognition of this rare neoplasm.