bluuebunny/crossref_metadata_2025_split huggingface dataset:
Papillary Thyroid Carcinoma With Nodular Fasciitis-like Stroma
Authors: Yang Yi J. , LiVolsi Virginia A. , Khurana Kamal K. 
Published: January 2021

Abstract
Papillary thyroid carcinoma with nodular fasciitis-like stroma is one of the rare variants of papillary thyroid carcinoma. The problems posed by the exuberant nodular fasciitis-like stroma, which obscures the neoplastic nature of the tumor, are recognized in surgical pathology but have received little attention in the cytopathology literature. We report a rare case of papillary thyroid carcinoma in which nodular fasciitis-like stroma posed difficulty on fine-needle aspiration cytology. The differential diagnosis of fibroproliferative processes in thyroid fine-needle aspirations is also discussed.
Impact of Viral Load Testing on Patient Care
Authors: Nolte Frederick S. 
Published: January 2021

Abstract
Quantitative human immunodeficiency virus (HIV) type 1 RNA tests have been essential tools in increasing our understanding of HIV pathogenesis and antiretroviral therapy. The plasma HIV RNA level is among the most powerful predictive tests in modern medicine for disease progression and has rapidly become the standard of practice for guiding clinicians in initiating, monitoring, and changing antiretroviral therapy. In this article the scientific rationale and clinical indications for viral load testing in HIV infection are reviewed.
Laboratory Determination of Hereditary Susceptibility to Breast and Ovarian Cancer
Authors: Frank Tom S. 
Published: January 2021

Abstract
Inherited mutations in the genes BRCA1 and BRCA2 are associated with a significantly increased risk of breast cancer, particularly before the age of 50 years, as well as an increased risk of ovarian cancer. Patients with early-onset breast cancer or ovarian cancer at any age with a family history of either disease are at higher risk of carrying a mutation in BRCA1 or BRCA2. Laboratory analysis of these genes can determine whether a patient has inherited an increased risk of breast and ovarian cancer. In the absence of a mutation that has been previously identified in a family member, most tests for hereditary breast-ovarian cancer risk analyze the entire coding sequences of BRCA1 and BRCA2. The gene sequencing process itself can be automated, but the data must be interpreted by an individual with training in molecular diagnostics. Management options generally available to individuals with hereditary susceptibility to breast and ovarian cancer include heightened surveillance, prophylactic surgery, and chemoprevention. The use of genetic techniques to identify women with increased risk of cancer demonstrates the application of recent advances in the understanding of the genetic basis of malignancy to laboratory medicine and clinical care.
Hereditary Hemochromatosis
Authors: Press Richard D. 
Published: January 2021

Abstract
Objective.—To review the current state-of-the-art regarding the role of iron- and DNA-based testing on the detection, treatment, and prevention of hereditary hemochromatosis (HH), the most common single-gene disorder in white people.
Sources.—Review of the medical literature, with particular emphasis on recent reports of the impact of DNA-based testing on the detection of symptomatic and presymptomatic patients with HH.
Conclusions.—Hereditary hemochromatosis, a common autosomal recessive iron overload disorder (with a population prevalence of 0.3%–0.8%), is a common cause of preventable liver, heart, joint, and endocrine disease. Since the associated clinical signs and symptoms are nonspecific, an accurate HH diagnosis demands both a high index of suspicion and the direct laboratory demonstration of elevated iron parameters. The substantial public health burden of HH as a common, deadly, detectable, and treatable chronic disease has led the College of American Pathologists to recommend that “systematic screening for hemochromatosis is warranted for all persons over the age of 20 years.” The recent discovery that most HH cases are the result of a single well-conserved homozygous missense mutation (C282Y) within a novel transferrin-receptor binding protein (HFE) has given rise to diagnostic clinical tests for the DNA-based detection of this pathologic mutation. This direct HFE mutation test can now be used not only to confirm the diagnosis of HH in those with symptomatic disease, but also, perhaps more importantly, to detect those with presymptomatic iron overload in whom future disease manifestations may be prevented (with phlebotomy therapy).
Dysembryoplastic Neuroepithelial Tumor
Authors: Gyure Kymberly A. , Sandberg Glenn D. , Prayson Richard A. , Morrison Alan L. , Armstrong Regina C. , Wong Kondi 
Published: January 2021

Abstract
Context.—The dysembryoplastic neuroepithelial tumor (DNT) is an uncommon lesion characterized by a heterogeneous population of neurons, astrocytes, and oligodendroglia-like cells (OLCs). The basic nature of the DNT and its constituent cells, particularly the OLCs, remains unresolved; some authors favor a neuronal origin, and others propose a glial or mixed origin for these cells.
Design.—We examined 11 DNTs with antibodies to myelin oligodendrocyte glycoprotein, a marker of mature oligodendrocytes.
Results.—All DNTs studied (7 from males, 4 from females; age range of patients, 2–37 years) were composed of varying proportions of neurons, astrocytes, and OLCs. Membrane or cytoplasmic immunoreactivity for myelin oligodendrocyte glycoprotein was found in many OLCs in 9 of 11 cases. The number of myelin oligodendrocyte glycoprotein–positive OLCs was variable: &gt;75% of the OLCs were positive in 5 cases, 25% to 75% of the OLCs were positive in 2 cases, and &lt;25% of the OLCs were positive in 2 cases.
Conclusion.—These findings suggest that many of the OLCs represent mature oligodendrocytes and support the notion that DNTs are heterogenous lesions composed of multiple, mature cell types.
CD44
Authors: Ylagan Lourdes R. , Scholes John , Demopoulos Rita 
Published: January 2021

Abstract
Objective.—To test the hypothesis that CD44 standard (CD44[s]) and its other variants, CD44v6 and CD44v7-8, might be useful markers of squamous differentiation in epithelial tumors.
Design.—We studied expression of CD44(s), CD44v6, and CD44v7-8 using immunohistochemistry in human tumors that had squamous differentiation, glandular differentiation, or both arising in the colon, stomach, esophagus, lung, pancreas, gallbladder, or uterus/cervix, as well as in adjacent nonneoplastic tissues. Formalin-fixed, paraffin-embedded archival tissue specimens of 33 adenosquamous tumors were used. All were stained with monoclonal antibodies against a conserved portion of CD44(s) and its variants, CD44v6 and CD44v7-8, using the avidin-biotin peroxidase method.
Results.—CD44(s) and its variants consistently and strongly stained areas of tumors with well-developed squamous differentiation. These markers also consistently and strongly stained normal squamous mucosa. Reactivity for CD44 and its variants was lacking in normal glandular type epithelium and in adenocarcinomas composed entirely of well-differentiated mucin-producing glands. Areas of well-differentiated carcinoma, both squamous and adenocarcinoma, were consistent with respect to both extent and intensity of staining. Staining in lymph nodes was similar to that in the primary tumors, with well-differentiated squamous foci being consistently positive, well-differentiated mucin-producing adenocarcinoma foci consistently negative, and poorly differentiated foci showing variable staining. Although staining was less intense with the variants, it followed the same staining pattern as found for CD44(s). No differences in the extent or intensity of staining were identified in the metastatic versus primary tumor foci, nor was any difference identified between superficial and deeply invasive areas of primary tumors.
Conclusions.—Our study shows that CD44(s) and its variants are good markers of squamous epithelial differentiation in several types of normal epithelium and tumors, and that these markers can identify areas of well- to moderately differentiated elements in adenosquamous neoplasms. However, poorly differentiated tumors show an inconsistent staining pattern with CD44, such that it cannot be used as a reliable and practical marker of squamous differentiation in poorly differentiated neoplasms.
Overexpression of Cyclin A and Cyclin B1Proteins in Astrocytomas
Authors: Allan Katherine , Jordan Richard C. K. , Ang Lee-Cyn , Taylor Michael , Young Beverley 
Published: January 2021

AbstractBackground.—Cyclins are proteins that are expressed during the progression of a normal cell through the cell cycle. In a number of cancers, overexpression of cyclin A and cyclin B1 proteins has been reported, and in some instances the levels of expression correlated well with the grades of malignancy. The expression of cyclin A and cyclin B1 proteins in astrocytoma may be linked to the histologic grade or proliferative activities.Objective.—To study the expression of cyclin A and cyclin B1 proteins in astrocytomas and correlate the labeling indices (LIs) of cyclin A and cyclin B1 with histologic grade and Ki-67 LI.Design.—The surgical biopsy specimens from 65 adults with astrocytomas were reviewed and divided into grades based on the World Health Organization system. The paraffin sections were immunostained using primary antibodies against Ki-67, cyclin A, and cyclin B1. The LIs of these astrocytomas for the 3 different antibodies were determined by computerized image analysis.Results.—The cyclin A LI showed good correlation with astrocytoma grade and Ki-67 LI. Both the nuclear and cytoplasmic cyclin B LIs correlated well with the tumor grade but showed poor correlation with Ki-67 LI.Conclusions.—This study suggests that although both cyclin A and B protein expression are related to the grade of malignancy in astrocytomas, cyclin A levels more generally reflect the proliferative state of these tumors. We also provide indirect evidence that cyclin B1 is associated with the aberrant progression through the G2-M phase checkpoint in astrocytomas.
Testicular Regression Syndrome
Authors: Spires Susan E. , Woolums C. Stephen , Pulito Andrew R. , Spires Stephen M. 
Published: January 2021

AbstractContext.—The vanishing or regressed testis is an entity well known to urologists and pediatric surgeons, affecting approximately 5% of patients with cryptorchidism. However, there is little review and discussion of this entity among pathologists with only 2 of 40 published reviews of testicular regression syndrome (TRS) found in the pathologic literature.Objectives.—To assess recognition of TRS among a subset of pathologists and to determine the applicability of histologic criteria for TRS as published.Design.—An 8-year retrospective review of cases submitted as atrophic or regressed testis was performed. Original diagnosis and diagnosis after review were compared to assess pathologic recognition of TRS. Pathologic assessment included identification of vas deferens, epididymis, dystrophic calcification, hemosiderin, dominant vein, pampiniform plexus–like vessels, and vascularized fibrous nodule formation. At minimum, the presence of a vascularized fibrous nodule (VFN) with calcification or hemosiderin or VFN with cord element(s) was required for diagnosis.Setting and Participants.—Medical records and pathologic specimens of patients undergoing surgery for cryptorchidism or with specimens reviewed at a medium-sized university hospital were analyzed.Results.—The original diagnosis in 3 (23%) of 13 cases was that of TRS. On secondary review, 11 (85%) of 13 cases showed features consistent with TRS. The diagnoses both before and after review showed a concurrence of 23% (3/13 cases). Two (15%) of 13 cases were correctly recognized and diagnosed as TRS at primary review; 1 case originally thought to represent TRS was not confirmed. Pathologic features correlated well with those reported in the literature. Among all 13 cases, the 11 confirmed TRS cases showed VFN in 11 (85%), intranodular calcification in 8 (62%), intranodular hemosiderin in 9 (69%), vas deferens in 9 (69%), epididymal structures in 5 (38%), and a dominant venous structure in 11 (85%). The average size of the VFN was 1.1 cm.Conclusion.—A urologic and pediatric surgical problem, TRS may be unrecognized by many practicing pathologists. In the typical situation in which a blind ending spermatic cord is submitted for tissue analysis, characterization of such cases as consistent with regressed testis is desirable and achievable in a high percentage of cases. Pathologists may play a pivotal role in management of these patients since histologic confirmation of the testis as regressed reassures the surgeon and the family of the correctness of diagnosis and can eliminate the necessity for further intervention.
Hyalinizing Spindle Cell Tumor With Giant Rosettes—A Soft Tissue Tumor With Mesenchymal and Neuroendocrine Features
Authors: Bejarano Pablo A. , Padhya Tapan A. , Smith Roger , Blough Ruthann , Devitt James J. , Gluckman Jack L. 
Published: January 2021

Abstract
Context.—Hyalinizing spindle cell tumor with giant rosettes is a recently described biphasic neoplasm of soft tissues that shares mesenchymal and neuroendocrine features. Its morphologic structure is distinctive, with the presence of hyalinized paucicellular foci that are termed rosettes. The cells around the latter display positive immunoreactivity for neuroendocrine markers. The small number of cases described to date indicates that they tend to be localized in the extremities.
Objective.—To describe the clinicopathologic features of 2 unusual cases of hyalinizing spindle cell tumor with giant rosettes.
Methods and Results.—One tumor was located in the prestyloid parapharyngeal space and the second in the left thigh. Both tumors were well circumscribed and surrounded by a thin capsulelike fibrous band without infiltrating projections. The rosettes were embedded in a spindle cell proliferation. Immunohistochemical stains showed positive results for S100 protein, synaptophysin, CD57, protein gene product 9.5, and neuron-specific enolase exclusively in the cells palisading the rosettes. These markers were negative in the spindle cell portions of the tumor. The latter were immunoreactive for factor XIIIa, vimentin, HAM56, collagen IV, and CD68. Vimentin was the only marker shared by the rosette-forming cells and the spindle cells. Ultrastructurally, the rosette-forming cells contained neurosecretory granules. This study describes the first cytogenetic analysis in this type of tumor revealing 2 cell lines, both containing a balanced translocation between chromosomes 7 and 16. Follow-up of the patients at 16 and 8 months did not disclose evidence of recurrence.
Conclusions.—These 2 new cases increase the awareness of hyalinizing spindle cell tumor with giant rosettes and demonstrate that it is a spindle cell neoplasm of unique cytogenetic rearrangements composed of dendritic, histiocytic, and fibroblastic cells admixed with cells that have neuroendocrine differentiation.
Changes of Biochemical and Biomechanical Properties in Dupuytren Disease
Authors: Melling Mahmoud , Karimian-Teherani Daniela , Mostler Sascha , Behnam Mark , Sobal Grazyna , Menzel Ernst J. 
Published: January 2021

Abstract
Background.—The major biochemical characteristic of Dupuytren disease is the progressive and irreversible deposition of excess fibrous collagen characterized by an enhanced type III collagen proportion.
Objective.—To investigate the influence of changes of the collagen spectrum on the biophysical properties of the palmar aponeurosis.
Design.—Variably affected palmar regions from 30 individuals with Dupuytren disease were classified according to histologic test results and clinical stage. Biochemical, biomechanical, and thermal contracture studies were performed.
Results.—The relative type III collagen content increased with increasing tissue involvement and was found to correlate with calorimetric and biomechanical properties with the exception of the Young modulus. In experiments on the thermal isometric contracture, the collagen denaturation temperature decreased with increasing type III collagen content, ie, increasing involvement. To study the dependence of biophysical properties from the collagen type distribution independent of structural changes, as seen in Dupuytren disease, we investigated rat skins from animals of an age range characterized by dramatic changes in type III collagen content (0–18 months). Biomechanical data also correlated significantly with type III collagen content in rat skin with the exception of the time constant of stress relaxation.
Conclusion.—In light of these results, we suggest that structural changes, such as reduced collagen fibril diameters, associated with alterations in the type III collagen proportion may influence biophysical properties of connective tissues in the involved palmar aponeurosis in addition to alterations of the cross-linking pattern.
Evaluation of Apoptotic Leukocytes in Peripheral Blood Smears
Authors: Shidham Vinod B. , Swami Vanlila K. 
Published: January 2021

Abstract
Objectives.—Apoptosis is a phenomenon of physiological cell death in which each step is regulated, similar to the process of mitosis. We observed apoptosis in leukocytes during the review of peripheral blood smears. This study was undertaken to evaluate the morphologic features of apoptotic leukocytes in peripheral blood smears and to ascertain their clinical significance.
Design.—Sixty cases (23 males and 37 females, aged newborn to 92 years) exhibiting apoptotic leukocytes in peripheral blood smears were studied. Medical records for each case were reviewed, and patients were categorized according to their clinical diagnoses.
Results.—Neutrophils were the most common apoptotic leukocytes identified (85%), followed by lymphocytes (18%) and eosinophils (2%). The diagnosis most frequently associated with the presence of apoptotic leukocytes was infection (55%). Apoptosis in lymphocytes was comparatively less common, but when present, the most common associations were diabetes mellitus, glucocorticoid administration, and neoplastic diseases.
Conclusions.—Our findings suggest that the presence of apoptotic leukocytes in peripheral blood smears may help in the differential diagnosis and may be related to the severity of disease. We recommend further evaluation using additional special techniques for detecting apoptotic leukocytes.
Morphometric and Electron Microscopic Analyses of the Effect of Gonadotropin-Releasing Hormone Agonist Treatment on Arteriole Size in Uterine Leiomyomas
Authors: Kalir Tamara , Wu Haishan , Gordon Ronald E. , Gil Joan 
Published: January 2021

Abstract
Background.—Few studies have been performed on the vascular changes in leiomyomas from patients treated with gonadotropin-releasing hormone agonists (GnRHAs).
Objective.—To measure luminal diameter and wall thickness of arterioles in uterine leiomyomas using a quantitative stereologic method of analysis.
Design.—Thirty leiomyomas from 3 study groups were used: (1) patients treated with GnRHAs (10 patient samples), (2) age-matched controls (10 patient samples), and (3) postmenopausal women (10 patient samples). Measurements of arteriolar luminal diameter and wall thickness were made using a video-based, computerized system attached to the microscope, for which a morphometric ad hoc program was written. Electron micrographs were made of random arterioles from the first 2 groups (GnRHA-treated patients and age-matched controls).
Setting.—Department of Pathology, Mount Sinai School of Medicine, New York, NY.
Patients.—A total of 30 patient samples were studied, with 3 groups comprising 10 samples each, including patients treated with GnRHAs, age-matched control patients, and postmenopausal women.
Results.—Arterioles in myomas from patients treated with GnRHAs had slightly larger luminal diameters and significantly thicker walls than age-matched controls and resembled arterioles from postmenopausal women. The thickening was due to smooth muscle cell hyperplasia in the muscularis media.
Conclusions.—Treatment with GnRHAs causes a thickening of the walls of intramyomatous arterioles, which resemble those of postmenopausal women. This thickening may play a role in the decreased flow of blood reported in GnRHA treatment.
Prostate Elastosis
Authors: Billis Athanase , Magna Luis A. 
Published: January 2021

Abstract
Background.—Elastosis of the prostate may be seen on needle biopsy and radical prostatectomy specimens, but its significance is unknown. Prostatic atrophy (or postatrophic hyperplasia) is one of the most frequent mimics of prostatic adenocarcinoma.
Objective.—To observe the frequent occurrence of elastosis of the prostate stroma in areas of postatrophic hyperplasia.
Design.—A step-section method was used to cut the posterior lobe (or peripheral zone) in coronal planes at intervals of 0.3 to 0.5 cm in 100 consecutive autopsy specimens of men older than 40 years. Elastosis was detected because of a basophilic tinge of the stroma on hematoxylin-eosin stain and confirmed using elastic fiber stains. Presence of elastosis correlated with the following variables: age, prostatic atrophy (simple, hyperplastic, or sclerotic), local arteriosclerosis, histologic carcinoma, high-grade prostatic intraepithelial neoplasia, benign or malignant nephrosclerosis, generalized atherosclerosis, nodular prostatic hyperplasia, and acute inflammation. For statistics, a stepwise linear regression method adjusted for age was used.
Results and Conclusions.—Elastosis was found in 65 of the prostates examined and was significantly more frequent with increasing age (P &lt; .001), prostatic atrophy (P &lt; .001), and local arteriosclerosis (P &lt; .02). There was no significant relation to histologic carcinoma, high-grade prostatic intraepithelial neoplasia, benign or malignant nephrosclerosis, generalized atherosclerosis, nodular prostatic hyperplasia, and acute inflammation. The correlation with local arteriosclerosis favors a possible role of ischemia to its etiopathogenesis. The absence of correlation to neoplastic and preneoplastic lesions and the striking spatial relationship of elastosis to prostatic atrophy (or postatrophic hyperplasia) add a new microscopic feature for the diagnosis of this latter lesion, helping in the differential diagnosis with prostate adenocarcinoma.
An Algorithm to Aid in the Investigation of Thalassemia Trait in Multicultural Populations
Authors: Kiss Thomas L. , Ali Mahmoud A. M. , Levine Mitchell , Lafferty John D. 
Published: January 2021

Abstract
Context.—The differentiation between iron deficiency and a thalassemia syndrome is an important consideration in the investigation of microcytic anemia.
Objective.—An established statistical method was used to demonstrate the importance of considering ethnic background in combination with mean cell volume (MCV) in the investigation of β-thalassemia trait in a multicultural urban population.
Design.—Posttest probabilities for β-thalassemia trait were calculated using likelihood ratios for various microcytic MCV ranges in conjunction with published pretest probabilities for β-thalassemia trait based on ethnic background.
Setting.—Regional hemoglobinopathy laboratory, St Joseph's Hospital, Hamilton, Ontario, Canada.
Patients.—Patient data were derived from a previously published study. The original study cohort consisted of 789 patients aged 18 years or older who had an MCV less than 80 fL and were referred for routine complete blood count during a 6-month period.
Main Outcome Measures.—Posttest probabilities.
Results.—Simplified tables for the determination of posttest probabilities for β-thalassemia trait in individual patients based on ethnic background and MCV are provided. An algorithm to assist in determining when thalassemia investigations are indicated is presented.
Conclusions.—A high index of suspicion based on ethnic background and low MCV can provide increased sensitivity and specificity for the detection of thalassemia trait in centers with multicultural populations similar to the study population.