bluuebunny/crossref_metadata_2025_split huggingface dataset:
Primary Combined Squamous and Small Cell Carcinoma of the Larynx: A Case Report and Review of the Literature
Authors: Jaiswal Vilkesh R. , Hoang Mai P. 
Published: February 2021

Abstract
Primary laryngeal carcinomas comprise approximately 2% to 5% of all malignancies worldwide. Of these laryngeal carcinomas, approximately 99% are primary squamous cell carcinomas. During the past 30 years, about 160 cases of primary small cell carcinoma of the larynx have been reported. Combined primary squamous and small cell carcinoma of the larynx, the so-called composite tumor of the larynx, is even more rare, with only 13 published cases to date. Although the major risk factors for developing these composite tumors of the larynx are thought to be similar to other more common neoplasms of the larynx, such as squamous cell carcinoma, the treatment and prognosis are different. We report an additional case of combined small cell carcinoma of the larynx and discuss the histogenesis of this unusual neoplasm.
Peliosis Hepatis Associated With Lymphoplasmacytic Lymphoma: An Autopsy Case Report
Authors: Corpa Marcus V. N. , Bacchi Maura M. , Bacchi Carlos E. , Coelho Kunie I. R. 
Published: February 2021

Abstract
A 72-year-old man with no previous history of liver disease was admitted to our university hospital with severe dyspnea, edema of the lower limbs, and weight loss. Within a few days of hospitalization, he died due to severe bleeding in the upper digestive tract. At autopsy, the liver displayed typical gross features of peliosis hepatis. In addition, a diffuse infiltration of liver, spleen, bone marrow, and lymph nodes by lymphoplasmacytic lymphoma was disclosed by light microscopy. In the liver, the neoplastic cells partially filled the peliotic cavities. Peliosis hepatis is a rare liver disease characterized by multiple blood-filled, dilated cavities within the liver parenchyma. Association of lymphoplasmacytic lymphoma and peliosis hepatis has rarely been reported in the literature. The pathologic findings of such an unusual association and a review of the literature are presented.
The -omics Era and Its Impact
Authors: Kiechle Frederick L. , Zhang Xinbo , Holland-Staley Carol A. 
Published: February 2021

AbstractObjective.—To review the advances in clinically useful molecular biologic techniques and to identify their applications, as presented at the 12th Annual William Beaumont Hospital DNA Symposium.Data Sources.—The 7 manuscripts submitted were reviewed and their major findings were compared with literature on the same or related topics.Study Selection.—Manuscripts address the use of molecular techniques in the detection of severe acute respiratory syndrome (SARS) and bacterial ribosome mutations, which may lead to ribosome-targeted drug resistance; pharmacogenomics as a clinical laboratory service and example of warfarin dosing using CYP2C9 mutation analysis; definition of the potential of cytosine arabinoside incorporation into DNA to disrupt transcription using an in vitro model of oligonucleotides; use of laser capture microdissection to isolate solid tumor cells free of nontumor cells; and molecular methods used to classify lymphomas.Data Synthesis.—Two current issues related to the use of molecular tests in the clinical laboratories are (1) decentralization of molecular-based testing to a variety of nonmolecular laboratories and (2) need for wider acceptance of molecular-based testing through its incorporation in clinical practice guidelines. Molecular methods have had a major impact on infectious disease through the rapid identification of new infectious agents, SARS, and the characterization of drug resistance. Pharmacogenomics identifies the genetic basis for heritable and interindividual variation in response to drugs. The incorporation of the nucleoside analog, cytosine arabinoside, into DNA leads to local perturbation of DNA structure and reduces the ability of transcription factors to bind to their specific DNA binding elements as measured by electrophoretic mobility shift assays. Laser capture microdissection of tumor cells can provide an adequate number of cells for whole genome amplification. Gene expression microassay profiles of various lymphomas have modified classification systems and predict prognosis and response to therapy.Conclusions.—The current -omics era will continue to emphasize the use of microarrays and database software for genomic, transcriptomic, and proteomic screening to search for a useful clinical assay. The number of molecular pathologic techniques will expand as additional disease-associated mutations are defined.
Effect of Polymorphisms in the Cytochrome P450 CYP2C9 Gene on Warfarin Anticoagulation
Authors: Adcock Dorothy M. , Koftan Charles , Crisan Domnita , Kiechle Frederick L. 
Published: February 2021

Abstract
Context.—Warfarin is a widely used anticoagulant with efficacy in treatment and prevention of thrombosis. Patient management, however, is difficult because of interindividual variation in response to standard doses due to significant differences in metabolic rates. Warfarin metabolism is under genetic control, involving primarily the CYP2C9 gene encoding the enzyme that catalyzes the conversion of warfarin to inactive metabolites.
Objective.—Several polymorphisms of CYP2C9 have been reported; the variant alleles *2 and *3 have decreased enzymatic activity. The objective of this case study is to investigate the relationship between CYP2C9 genotype and warfarin anticoagulation.
Design.—A case of deep vein thrombosis treated with the standard warfarin dose is investigated for intensity of anticoagulation and CYP2C9 genotype; the case illustrates the relationship between CYP2C9 variant and overanticoagulation with subsequent bleeding complication.
Results.—The patient's genotype, CYP2C9*1*3, correlated with an exaggerated anticoagulant response during the initiation of warfarin therapy at standard dose, and a bleeding episode ensued. Based on heterozygosity for the *3 variant allele, it was recommended that the patient be maintained on a low-dose warfarin regimen.
Conclusions.—The practical implications of identifying genetic risk factors that lead to overanticoagulation are multiple. Genotype knowledge of the CYP2C9 variant alleles may help the clinician to individualize warfarin therapy with the ultimate goals of shortening the initial period of induction therapy, reaching a stable maintenance dose earlier, and minimizing bleeding complications in patients who are high responders and need lower warfarin doses.
Salivary Adenocarcinoma, Not Otherwise Specified: A Collection of Orphans
Authors: Li Jiang , Yiyao Wang Beverly , Nelson Magalie , Li Lei , Hu Yuhua , Urken Mark L. , Brandwein-Gensler Margaret 
Published: February 2021

AbstractContext.—Salivary adenocarcinoma, not otherwise specified, refers to gland-forming malignancies that do not satisfy the diagnostic requirements of other “named” malignancies.Objective.—To review the features of 11 patients with salivary adenocarcinoma, not otherwise specified. To also compare the diagnostic frequencies of 2 databases, one from the Mount Sinai Medical Center (New York, NY), the other from the Shanghai Ninth People's Hospital (Shanghai, People's Republic of China).Design.—Pathology files were searched to establish a database of salivary tumors. All available hematoxylin-eosin– stained slides from the resection specimens diagnosed as either adenocarcinoma, not otherwise specified, or with vague or unusual diagnoses (eg, probable carcinoma-ex-pleomorphic adenoma) were pulled from our files and reexamined. Dates of death were confirmed with the Social Security Death Index.Results.—We identified 11 patients with salivary adenocarcinoma, not otherwise specified, ranging in age from 49 to 80 years (median, 67 years), with a male preponderance. The parotid gland was the most common site of tumor origin. Ten of these tumors were high grade, and 1 was intermediate grade. Two patients were diagnosed at stage II, while the remaining patients were diagnosed at stage III or IV. Histologically, all tumors were invasive, with variable glandular differentiation and diverse architectural patterns. The diverse cytologic tumor cell types included cuboidal, columnar, epithelioid, polygonal, oncocytoid, clear, melanoma-like, mucinous, sebaceous, and plasmacytoid. Four patients died after 4 to 27 months (mean, 15 months), 1 patient is alive with disease at 12 months, 1 patient is disease-free at 14 years, and 3 patients remain disease-free after short follow-ups (10, 12, and 12 months). One patient had surgery just recently, and the remaining patient had no follow-up.Conclusions.—Salivary adenocarcinoma, not otherwise specified, is an aggressive, high-grade malignancy, with a predisposition for the parotid gland. It is characterized by cytologic and architectural diversity and an invasive growth pattern.
Cystic Nephroma: A Histologic and Immunohistochemical Study of 10 Cases
Authors: Mukhopadhyay Sanjay , Valente Alfredo Luis , de la Roza Gustavo 
Published: February 2021

Abstract
Context.—Cystic nephroma is a rare and controversial benign multicystic renal tumor. While the clinical, radiologic, and histologic features of cystic nephroma are well described, the immunohistochemical features are not. The role of immunohistochemistry in the differential diagnosis, which includes multicystic renal cell carcinoma, is also unknown.
Objective.—To define the histologic and immunohistochemical features of cystic nephroma.
Design.—Ten cases of cystic nephroma diagnosed at 2 institutions during a period of 10 years were stained with an immunohistochemical panel consisting of 20 immunostains.
Results.—Median age at diagnosis was 61 years, with a range from 31 to 79 years. The female-to-male ratio was 9:1. Grossly, the tumors were multicystic masses without solid nodules. Histologic features included cysts lined by flat, cuboidal, or hobnail epithelium and septa variably lined by fibrous (10/10 cases) and/or ovarian-like (7/10 cases) stroma. Corpus albicans–like acellular hyalinized structures were noted in the septa in 9 of 10 cases. The cyst epithelium showed consistent positivity for distal tubule/collecting duct markers (cytokeratin 19, cytokeratin AE1/AE3, epithelial membrane antigen) and variable positivity for proximal tubule markers (α1-antitrypsin, lysozyme, CD15, CD10). The ovarian-like stroma (present in 7/10 cases) stained positively for progesterone receptors (6/7 cases) and estrogen receptors (4/7 cases).
Conclusions.—Our immunohistochemical findings confirm a previous report of both distal tubule/collecting duct and proximal tubule differentiation in cystic nephroma. Stromal estrogen and/or progesterone receptor positivity in the majority of cases of cystic nephroma is a novel finding.
Idiopathic Bilateral Auricular Ossificans: A Case Report and Review of the Literature
Authors: High Whitney A. , Larson Matthew J. , Hoang Mai P. 
Published: February 2021

AbstractPetrification of the auricle results in a rigid and immalleable ear. The etiology of such a finding is usually ectopic calcification. The condition has been associated with injurious processes, such as cold injury, and with various endocrinopathies, including Addison disease. In a significant number of cases, ossification occurs without knowledge of the precipitating cause or event. True auricular ossification is a rare occurrence, with only 12 histologically confirmed cases in the literature. We herein present the clinical and pathologic findings of another case. A 60-year-old man with diet-controlled diabetes presented with a 10-year history of slowly and insidiously stiffened auricles. He denied any precipitating historical events. Routine testing did not demonstrate systemic abnormalities. Radiographic examination revealed opacities consistent with bony structure in the auricles of the ears, with the right more prominent than the left. Histologic sampling demonstrated ossification with deposition of trabecular bone in proximity to normal elastic cartilage.
Gastrointestinal Stromal Tumor Presenting as a Recurrent Vaginal Mass
Authors: Ceballos Katherine M. , Francis Julie-Ann , Mazurka John L. 
Published: February 2021

Abstract
Gastrointestinal stromal tumors are CD117 (c-Kit)–positive mesenchymal neoplasms with histologic and ultrastructural features of the interstitial cell of Cajal. While tumors outside of the gastrointestinal tract have been described, to our knowledge the case we present is the first such case in the vagina. We describe a 75-year-old woman with a recurrent vaginal gastrointestinal stromal tumor without apparent rectal involvement. This tumor was characterized by short intersecting fascicles of spindled cells, focal necrosis, and 12 to 15 mitoses per 50 high-power fields. Immunohistochemistry revealed diffuse cytoplasmic positivity for CD117 (c-Kit), CD34, vimentin, and h-caldesmon. Tumor cells were negative for S100, desmin, actin, and CAM 5.2. The differential diagnosis in this case included a vaginal smooth muscle tumor. While histologically similar to a smooth muscle neoplasm, the immunohistochemical profile ruled out smooth muscle differentiation. Gastrointestinal stromal tumor should be considered in the differential diagnosis of vaginal mesenchymal neoplasms.
Leukemoid Reaction: A Diagnostic Clue in Metastatic Carcinoma Mimicking Classic Hodgkin Lymphoma
Authors: Mukhopadhyay Sanjay , Mukhopadhyay Surabhi , Banki Katalin , Mahajan Shirish 
Published: February 2021

Abstract
We report on 2 patients who were initially suspected to have classic Hodgkin lymphoma because of lymphadenopathy and the presence of Reed-Sternberg–like cells. Both patients had an associated leukemoid reaction (using a threshold leukocyte count of 50 000/μL) and were eventually diagnosed with metastatic carcinoma. Disseminated carcinoma can mimic Hodgkin lymphoma clinically, radiologically, and histologically. Reed-Sternberg–like cells may be found in carcinomas, and they represent a particularly challenging diagnostic pitfall for the unwary. When these cells lead to a suspicion of Hodgkin lymphoma, the presence of a leukemoid reaction should prompt the pathologist to question the diagnosis. Misdiagnosis can be avoided by the use of cytokeratin whenever a leukemoid reaction is present in a suspected case of Hodgkin lymphoma.
Fibrolamellar Hepatocellular Carcinoma Occurring 5 Years After Hepatocellular Adenoma in a 14-Year-Old Girl: A Case Report With Comparative Genomic Hybridization Analysis
Authors: Terracciano Luigi Maria , Tornillo Luigi , Avoledo Pierino , von Schweinitz Dietrich , Kühne Thomas , Bruder Elisabeth 
Published: February 2021

Abstract
An unusual case of fibrolamellar carcinoma of the liver developed 5 years after removal of a hepatocellular adenoma in a 14-year-old girl belonging to a family with Carney syndrome. Both tumors were studied by light and electron microscopy, flow cytometry, and comparative genomic hybridization. The first tumor, removed at the age of 9, was a bulky well-circumscribed liver mass composed of large eosinophilic cells with a focal pseudoglandular pattern but without cytologic atypia or sclerosis. A diagnosis of hepatocellular adenoma was rendered. Five years later, another hepatic tumor was removed from the right lobe. Microscopic examination revealed polygonal cells, each with a large amount of eosinophilic cytoplasm and a round nucleus with a conspicuous nucleolus. These cells were arranged in nests and strands and separated by bands of dense fibrous tissue, leading to a diagnosis of fibrolamellar carcinoma. Comparative genomic hybridization analysis revealed no genetic alteration in the adenoma; however, several chromosomal aberrations (loss of chromosome regions 1p and 4p and gains of chromosome regions 6q, 13q, and Xq) were detected in the fibrolamellar carcinoma. To our knowledge, this is the first report of an association between hepatocellular adenoma and fibrolamellar carcinoma.
Collagenous Gastritis: An Unusual Association With Profound Weight Loss
Authors: Wang Hanlin L. , Shah Amit G. , Yerian Lisa M. , Cohen Russell D. , Hart John 
Published: February 2021

Abstract
Collagenous gastritis is a distinctive disorder characterized by thickening of the subepithelial collagen layer in the gastric mucosa. Although this entity was recognized in 1989, its etiology, pathogenesis, and clinicopathologic features remain poorly understood because of its rarity. An unusual case of collagenous gastritis was observed in a 37-year-old man who presented with profound weight loss, a feature that has not previously been emphasized.
Molecular Analysis to Demonstrate That Odontogenic Keratocysts Are Neoplastic
Authors: Agaram Narasimhan P. , Collins Bobby M. , Barnes Leon , Lomago Deren , Aldeeb Dalal , Swalsky Patricia , Finkelstein Sydney , Hunt Jennifer L. 
Published: February 2021

Abstract
Context.—Odontogenic keratocysts (OKCs) are unique odontogenic lesions that have the potential to behave aggressively, that can recur, and that can be associated with the nevoid basal cell carcinoma syndrome. Whether they are developmental or neoplastic continues to be debated.
Objectives.—To identify loss of heterozygosity of tumor suppressor genes in OKCs and to suggest a pathogenetic origin for these lesions.
Design.—We examined 10 OKCs for loss of heterozygosity of tumor suppressor genes, using a microdissection and semiquantitative genotyping analysis. The genes analyzed included 10 common tumor suppressor genes, as well as the PTCH gene, which is mutated in nevoid basal cell carcinoma syndrome.
Results.—Loss of heterozygosity was seen in 7 of 10 cases, with a frequency between 11% and 80% of the genes studied. The genes that exhibited the most frequent allelic losses were p16, p53, PTCH, and MCC (75%, 66%, 60%, and 60%, respectively). Daughter cysts were associated with a higher frequency of allelic loss (P = .02), but epithelial budding was not.
Conclusions.—Our study indicates that a significant number of OKCs show clonal loss of heterozygosity of common tumor suppressor genes. The finding of clonal deletion mutations of genomic DNA in these cysts supports the hypothesis that they are neoplastic rather than developmental in origin.
Comorbidity in Dementia
Authors: Fu Catherina , Chute Dennis J. , Farag Emad S. , Garakian Justine , Cummings Jeffrey L. , Vinters Harry V. 
Published: February 2021

Abstract
Context.—There is a paucity of accurate postmortem data pertinent to comorbid medical conditions in patients with dementia, including Alzheimer disease.
Objectives.—The purposes of this study were (a) to examine general autopsy findings in patients with a dementia syndrome and (b) to establish patterns of central nervous system comorbidity in these patients.
Design.—Review of autopsy reports and selected case material from 202 demented patients who had “brain-only” autopsies during a 17-year period (1984–2000) and from 52 demented patients who had general autopsies during a 6-year period (1995–2000).
Setting.—Large academic medical center performing approximately 200 autopsies per year.
Results.—Among the 52 patients who underwent complete autopsy, the most common cause of death was bronchopneumonia, which was found in 24 cases (46.1%). Other respiratory problems included emphysema, found in 19 (36.5%) of 52 patients, and pulmonary thromboembolism, found in 9 (17.3%) of 52 patients. In 6 cases, pulmonary thromboembolism was the proximate cause of death. Twenty-one (40.3%) of the 52 patients had evidence of a myocardial infarct (varying ages) and 38 (73.1%) had atherosclerotic cardiovascular disease, 27 of a moderate to severe degree. Four clinically unsuspected malignancies were found: 1 each of glioblastoma multiforme, diffusely infiltrative central nervous system lymphoma, pancreatic adenocarcinoma, and adenocarcinoma of the lung. One patient with frontotemporal dementia and amyotrophic lateral sclerosis died of severe meningoencephalitis/ventriculitis, probably secondary to seeding of the central nervous system by an infected cardiac valve. Of the 202 demented patients who underwent brain-only autopsies, the following types of dementia were found: 129 (63.8%) cases showed changes of severe Alzheimer disease, 21 (10.4%) showed combined neuropathologic abnormalities (Alzheimer disease plus another type of lesion, such as significant ischemic infarcts or diffuse Lewy body disease), 12 (5.9%) cases of relatively pure ischemic vascular dementia, 13 (6.4%) cases of diffuse Lewy body disease, and 8 (4.0%) cases of frontotemporal dementia. The remaining 19 (9.4%) patients showed miscellaneous neuropathologic diagnoses, including normal pressure hydrocephalus and progressive supranuclear palsy. Among the demented patients, 92 (45.5%) had cerebral atherosclerosis, which was moderate to severe in 65 patients (32.2%).
Conclusions.—Some of the conditions found at autopsy, had they been known antemortem, would likely have affected clinical management of the patients. Autopsy findings may be used as a quality-of-care measure in patients who have been hospitalized in chronic care facilities for a neurodegenerative disorder.
Cellular Proliferative Fraction Measured With Topoisomerase IIα Predicts Malignancy in Endocrine Pancreatic Tumors
Authors: Diaz-Rubio Jose Luis , Duarte-Rojo Andres , Saqui-Salces Milena , Gamboa-Dominguez Armando , Robles-Diaz Guillermo 
Published: February 2021

Abstract
Context.—Endocrine pancreatic tumors (EPTs) are rare lesions with varying biological behavior. Establishing malignancy is a challenge for clinicians and pathologists.
Objective.—To establish the role of proliferative, apoptotic, angiogenic, and hormonal markers as predictors of malignancy in EPTs.
Design.—Paraffin-embedded EPT samples were studied for prognostic markers.
Patients.—Twenty-one consecutive patients with a diagnosis of EPT.
Main Outcome Measures.—The proliferative fraction (topoisomerase IIα), microvascular density (CD34), vascular endothelial growth factor expression, and estrogen receptor-beta (ERβ) expression were studied by immunohistochemistry on all EPTs. Apoptosis was also assessed with terminal deoxynucleotidyl transferase nick-end labeling.
Results.—We identified 13 benign and 8 malignant tumors. Topoisomerase IIα was significantly increased in malignant tumors (P = .001), while there were no differences in apoptosis, microvascular density, or vascular endothelial growth factor expression in association with malignancy. No correlation could be identified between microvascular density and vascular endothelial growth factor expression, and ERβ was not detected. A receiver operating characteristic curve for topoisomerase IIα disclosed that above a labeling index of 13, the test had 88% sensitivity and 100% specificity for predicting malignancy.
Conclusion.—Cellular proliferation measured with topoisomerase IIα is a simple prognostic marker for malignancy in EPTs, unlike apoptosis, angiogenesis, or the presence of ERβ, which were not associated with malignant behavior. These findings designate a defined field for future research on endocrine pancreatic carcinogenesis and a possible target for chemotherapeutic agents.