bluuebunny/crossref_metadata_2025_split huggingface dataset:
Novel Method for Simultaneous Analysis of p53 and K-ras Mutations and p53 Protein Expression in Single Histologic Sections
Authors: Yamashita Kazuya , Yoshida Tsutomu , Shinoda Hiroshi , Okayasu Isao 
Published: January 2021

Abstract
Background and Objective.—Abnormal protein expression and gene mutation should be examined on exactly identified lesions. To perform simultaneous analyses of oncogene or tumor suppressor gene mutations and related protein expression in single histologic sections, we have developed a novel method using an antigen-retrieval solution for a polymerase chain reaction template before immunohistochemical staining.
Methods.—Using 20 cases of sporadic colorectal carcinoma, several kinds of antigen-retrieval solutions were tested after heating rehydrated, 4-μm-thick, formalin-fixed, paraffin-embedded histologic sections at 96°C for 20 minutes. Polymerase chain reaction–single-strand conformation polymorphism analysis was conducted for p53 (exons 5 through 9) and K-ras (exons 1 and 2), and the histologic sections were then immunostained with monoclonal antibody against p53.
Results.—DNA analysis of antigen-retrieval solutions was possible in all 20 cases and revealed completely consistent results (100%) with fresh cancer tissue and microdissected cancer tissue of paraffin-embedded histologic sections. With this method, K-ras mutations were positive in 10 of 20 cases (exon 1 in 9 cases and exon 2 in 1 case) and p53 mutations were positive in 9 of 20 cases (exon 5 in 4 cases, exon 6 in 1, exon 7 in 3, and exon 8 in 1 case), with 8 of the 9 p53 mutation cases showing diffuse p53 protein expression on immunostaining. Base alterations of all abnormal conformers were confirmed with direct sequencing. For polymerase chain reaction–single-strand conformation polymorphism analysis, sodium citrate buffer (pH 6.0) was found to be the optimal antigen-retrieval solution.
Conclusions.—This newly developed method can be used for routine immunostaining and genetic analysis with single histologic sections.
Goblet Cell Carcinoids of the Appendix
Authors: Kanthan R. , Saxena A. , Kanthan S. C. 
Published: January 2021

Abstract
Background.—Goblet cell carcinoids of the appendix are rare neoplasms with uncertain biological behavior.
Objective.—The aims of our study were to evaluate the immunophenotype of this neoplasm with cell cycle/cell proliferation markers and to understand their histogenesis with ultrastructural analysis using conventional carcinoids as a frame of reference.
Methods.—Clinical data and archival pathologic material of all goblet cell carcinoids of the appendix recorded by the Saskatchewan Cancer Registry between 1970 and 1998 were reviewed and evaluated by light microscopy, histochemistry, immunohistochemistry, and electron microscopy.
Results.—Seven cases of goblet cell carcinoids were identified among 110 cases of conventional carcinoids of the appendix. Histopathology revealed widespread infiltration of the periappendiceal fat in all cases, with extensive perineural invasion. The cells stained strongly positive for mucicarmine, periodic acid–Schiff, periodic acid–Schiff diastase, Alcian blue, cytokeratin, and carcinoembryonic antigen. Most cases were positive for synaptophysin. Increased expression of cell proliferation markers and cell cycle markers was observed. Expression of p53 was strong in one case. Electron microscopy demonstrated the presence of mucinous vacuoles of varying sizes and occasional membrane-bound neuroendocrine granules.
Conclusions.—Goblet cell carcinoids of the appendix arise from a pluripotent cell with divergent neuroendocrine and mucinous differentiation. These neoplasms are widely invasive; they demonstrate a high cellular proliferation rate and dysregulation of the cell cycle with up-regulation of cyclin D1 and p21, and down-regulation of p16. Complete removal of the tumor is recommended because of the unpredictable biological behavior of this tumor, which includes delayed local recurrences and lung metastases.
Morphometry and Histology of Gonads From 13 Children With Dysgenetic Male Pseudohermaphroditism
Authors: Scolfaro Márcia Ribeiro , Cardinalli Izilda Aparecida , Stuchi-Perez Eliana Gabas , de Mello Maricilda Palandi , de Godoy Assumpção Juliana , Baptista Maria Tereza Matias , Silva Joaquim Murray Bustorff , Maciel-Guerra Andréa Trevas , Júnior Gil Guerra 
Published: January 2021

Abstract
Background.—Dysgenetic male pseudohermaphroditism (DMP) is a sexual differentiation disorder characterized by bilateral dysgenetic testes, persistent müllerian structures, and cryptorchidism in individuals with a 46,XY karyotype. However, the histologic criteria for the diagnosis of DMP are poorly established.
Objective.—To determine gonadal histology in children with DMP.
Patients and Methods.—Between 1996 and 1998, 13 patients with DMP were evaluated on our service. The clinical diagnosis of DMP was based on a 46,XY karyotype, sex ambiguity, high levels of follicle-stimulating hormone and low levels of antimüllerian hormone, a decreased testosterone response to human chorionic gonadotropin stimulation without accumulation of testosterone precursors, and the presence of müllerian structures. Molecular sequencing the HMGbox region of the SRY gene did not reveal any mutations. Biopsies were performed for 22 of 26 gonads (patient age at the time of biopsy, 16 months to 10 years). Conventional microscopy was used to evaluate mean tubular diameter, tubular fertility index, and number of Sertoli cells per tubular profile.
Results.—All 26 gonads were located outside of the labioscrotal folds. Their histologic features varied from only a reduction in tubular size to features of a streak gonad. Five of the 22 gonads grossly resembled a streak gonad. The mean tubular diameter was severely reduced (&gt;30% reduction relative to the normal tubular diameter for the patient's age) in 4 gonads, markedly reduced (10%–30%) in 11 gonads, slightly reduced (&lt;10%) in one gonad, and normal in one gonad. The tubular fertililty index, expressed as the percentage of tubular profiles containing germ cells, was severely reduced (&lt;30% of normal values) in 9 gonads, markedly reduced (50%–30%) in 2 gonads, and normal in 6 gonads. The number of Sertoli cells per tubular profile was elevated in 16 gonads and normal in one gonad. Thin tubules surrounded by fibrous tissue were occasionally observed.
Conclusion.—The histologic findings confirmed the clinical diagnosis of DMP in every patient in the present series. However, gonadal histology was variable, and careful morphometric evaluation may be necessary to establish the diagnosis.
Nasal Natural Killer Lymphoma Associated With Epstein-Barr Virus in a Patient Infected With Human Immunodeficiency Virus
Authors: Canioni Danielle , Arnulf Bertrand , Asso-Bonnet Marianne , Raphael Martine , Brousse Nicole 
Published: January 2021

Abstract
Nasal natural killer (NK) lymphoma associated with Epstein-Barr virus (EBV) is a rare lymphoma that has not yet been reported in patients with human immunodeficiency virus (HIV). This report describes the first case, to our knowledge, of nasal NK cell lymphoma in an HIV-positive patient. A 50-year-old African man presented with an obstructive nasopharyngeal tumor, leading to the diagnosis of HIV infection. Nasal biopsy specimens showed NK cell lymphoma, confirmed on nasal tissues by morphologic, immunohistochemical, and polymerase chain reaction studies using a denaturing gradient gel electrophoresis technique that showed no T-cell receptor γ rearrangement. The EBV was detected by in situ hybridization. The patient received chemotherapy but died from infection. To our knowledge, this is the first reported case of nasal NK cell lymphoma associated with EBV in an HIV patient. Involvement of EBV in HIV non–B-cell lymphomas may represent a further manifestation of opportunistic EBV infection arising in these patients.
Blastomyces dermatitidis With Large Yeast Forms
Authors: Hussain Zakir , Martin Anita , Youngberg George A. 
Published: January 2021

Abstract
Yeast forms of Blastomyces dermatitidis typically range from 8 to 20 μm in largest diameter. We report a rare case of primary pulmonary blastomycosis with an unusual morphology, in which we found significant numbers of large yeast forms ranging from 30 to 35 μm in diameter. To our knowledge, this is only the second reported case of giant forms of B dermatitidis. We also review the literature and discuss the possible association of this unusual morphology with immunosuppression in general and glucocorticoid use in particular.
Pigmented Cardiac Paraganglioma
Authors: Mikolaenko Irina , Galliani Carlos A. , Davis Gregory G. 
Published: January 2021

AbstractA pigmented left atrial paraganglioma was found at autopsy in a 40-year-old black man who died unexpectedly. The cause of death was ascribed to coronary artery disease. The atrial mass was sharply demarcated and polypoid, measured 4 cm in greatest dimension, and had a cut surface that revealed dark red-brown soft tumor tissue. Histopathologically, the neoplasm exhibited a classic organoid clustering of cells (zellballen) with a prominent capillary network. The chief cells contained a brown-black pigment with histochemical characteristics of melanin. We report a case of pigmented cardiac paraganglioma because of its rarity. To our knowledge, no mention has been made of the presence of pigment in previously reported cases of cardiac paragangliomas.
Squamous Carcinoma in a Major Salivary Gland
Authors: Taxy Jerome B. 
Published: January 2021

Abstract
Context.—Squamous carcinoma in a major salivary gland has several possible sources: (1) high-grade mucoepidermoid carcinoma, (2) metastasis or direct invasion from a primary skin carcinoma, (3) metastasis from a distant primary carcinoma, or (4) a primary malignant neoplasm. The latter is conventionally regarded as a diagnosis of exclusion after a history of squamous carcinoma elsewhere has been obtained or there is a positive mucin stain.
Design.—Eleven cases of squamous carcinoma in a major salivary gland are presented and the literature reviewed.
Results.—Two cases, 1 metastatic from a histologically identical squamous carcinoma from the ipsilateral tonsil and 1 with in situ squamous carcinoma in a duct, demonstrated positive mucicarmine stains. Two cases were high-grade mucoepidermoid carcinomas, also with positive mucin stains. Five cases represented metastases from cutaneous squamous carcinomas. Only 2 cases were regarded as primary carcinomas. There were no histologic clues as to correct subclassification. Six patients died, 4 from their disease. Three of the 5 still alive had recurrence or metastasis.
Conclusion.—The occurrence of squamous carcinoma in a major salivary gland exhibits a histologic sameness that precludes accurate subclassification and assignation of origin. Also irrespective of tumor origin, the clinical approach to diagnosis and treatment is similar. Adjuvant therapy (eg, radical neck dissection, radiation, chemotherapy) is not uniformly applied. Most patients present with a sizable (&gt;3-cm) mass for which total excision is attempted. The natural evolution of the tumor is aggressive, irrespective of clinical context. The traditional subclassification of squamous carcinoma in a major salivary gland may not be clinically relevant.
Varicella-Zoster Virus Infections of the Nervous System
Authors: Kleinschmidt-DeMasters B. K. , Gilden Donald H. 
Published: January 2021

AbstractBackground.—Diseases that present with protean manifestations are the diseases most likely to pose diagnostic challenges for both clinicians and pathologists. Among the most diverse disorders caused by a single known toxic, metabolic, neoplastic, or infectious agent are the central and peripheral nervous system complications of varicella-zoster virus (VZV).Methods.—The pathologic correlates of the neurologic complications of VZV infection, as well as current methods for detecting viral infections, are discussed and presented in pictorial format for the practicing pathologist.Results.—Varicella-zoster virus causes chickenpox (varicella), usually in childhood; most children manifest only mild neurologic sequelae. After chickenpox resolves, the virus becomes latent in neurons of cranial and spinal ganglia of nearly all individuals. In elderly and immunocompromised individuals, the virus may reactivate to produce shingles (zoster). After zoster resolves, many elderly patients experience postherpetic neuralgia. Uncommonly, VZV can spread to large cerebral arteries to cause a spectrum of large-vessel vascular damage, ranging from vasculopathy to vasculitis, with stroke. In immunocompromised individuals, especially those with cancer or acquired immunodeficiency syndrome, deeper tissue penetration of the virus may occur (as compared with immunocompetent individuals), with resultant myelitis, small-vessel vasculopathy, ventriculitis, and meningoencephalitis. Detection of the virus in neurons, oligodendrocytes, meningeal cells, ependymal cells, or the blood vessel wall often requires a combination of morphologic, immunohistochemical, in situ hybridization, and polymerase chain reaction (PCR) methods. The PCR analysis of cerebrospinal fluid remains the mainstay for diagnosing the neurologic complications of VZV during life.Conclusions.—Varicella-zoster virus infects a wide variety of cell types in the central and peripheral nervous system, explaining the diversity of clinical disorders associated with the virus.
Induction of Human Immunodeficiency Virus 1 Replication by Human Herpesvirus 8
Authors: Mercader Maria , Nickoloff Brian J. , Foreman Kimberly E. 
Published: January 2021

Abstract
Background.—Human immunodeficiency virus 1 (HIV-1)–infected individuals are commonly infected with herpesviruses, including cytomegalovirus, herpes simplex virus, varicella-zoster virus, and human herpesvirus 8 (HHV-8, also known as Kaposi sarcoma–associated herpesvirus [KSHV]). Previous studies have demonstrated that coinfection with herpesviruses can modulate HIV-1 replication. This can occur either through direct interaction between the 2 viruses or through secondary effects resulting from the release of cellular factors in response to infection.
Objective.—To investigate HIV-1 replication in the presence and absence of HHV-8.
Design and Methods.—HIV-1 replication was analyzed following culture of HIV-1–infected CD4+ T cells in the presence of HHV-8 infected B-cell lines or control, uninfected B-cell lines. To confirm and extend the results of these in vitro studies, HIV-1–infected T cells were injected into human skin transplanted onto severe combined immunodeficient mice. The human skin was also injected with purified HHV-8 or phosphate-buffered saline as a control and HIV replication measured in biopsy specimens taken 5 to 8 days later.
Results and Conclusions.—The results demonstrated a significant increase in HIV-1 replication in the presence of HHV-8 in both the in vitro and in vivo model systems. Although the mechanism responsible for HHV-8 induction of HIV-1 replication remains to be identified, the results indicate that these 2 viruses may interact at the molecular level in coinfected patients, resulting in increased HIV-1 viral load.
Osteosarcoma of the Urinary Bladder Occurring Simultaneously With Prostate and Bowel Carcinomas
Authors: Ghalayini Ibrahim F. , Bani-Hani Ibrahim H. , Almasri Nidal M. 
Published: January 2021

Abstract
Osteosarcoma is a very rare tumor of the urinary bladder, with only 28 well-documented cases reported in the literature to date. The tumors have characteristically been large and polypoid and most commonly have been located in the trigone. An abdominal mass has occasionally been palpated, and rectal examination has frequently revealed a mass in the region of the bladder. The prognosis for this tumor is very poor. In this report, a 75-year-old man with hematuria was found to have a primary osteosarcoma of the urinary bladder with superficial invasion. Radical cystoprostatectomy and ileal conduit urinary diversion were performed. During surgery, a synchronous mucinous adenocarcinoma of the ascending colon was found, and a right hemicolectomy was performed. Prostatic adenocarcinoma was discovered from the histology. The patient died 7 months after surgery with systemic spread of the osteosarcoma. Osteosarcoma of the bladder should be distinguished from other bladder tumors that may be associated with bone formation, such as carcinosarcomas and transitional cell carcinomas with osseous metaplasia of their stroma, both of which have a better prognosis than osteosarcoma.
Small Cell Carcinoma of the Kidney
Authors: González-Lois Carmen , Madero Santiago , Redondo Pilar , Alonso Isabel , Salas Ana , Montalbán M. Angeles 
Published: January 2021

Abstract
Small cell carcinoma is a malignant tumor composed of small cells with a diffuse growth pattern. It has immunohistochemical and ultrastructural features of both neuroendocrine and epithelial neoplasms. These tumors constitute 10% to 20% of malignant tumors in the lung, which is their most frequent site. They have been described in other extrapulmonary sites, where they are defined using the same criteria as used in the lung. These tumors are rarely found in the genitourinary tract. Fewer than 30 cases have been reported in the kidney. The differential diagnosis mainly includes other small round cell tumors and metastatic small cell lung carcinoma. We present and discuss a primary small cell carcinoma of the kidney (to our knowledge the 9th to be reported in the literature), which we studied with light microscopy, immunohistochemistry, electron microscopy, and, for the first time, flow cytometry.
Glassy Cell Carcinoma of the Endometrium
Authors: Mhawech Paulette , Dellas Athanassios , Terracciano Luigi M. 
Published: January 2021

Abstract
Endometrial glassy cell carcinoma (GCC) is a rare neoplasm, with 11 cases reported in the literature. Although GCC is considered to be a poorly differentiated variant of adenosquamous carcinoma, its real nature is still debatable. We report a case of GCC of the endometrium in a 60-year-old woman and review the literature. The patient presented with vaginal bleeding, and pelvic computed tomographic scan showed a polypoid lesion in the uterine fundus. Histologically, the tumor showed 2 components: a moderately differentiated adenocarcinoma with extensive areas of squamous metaplasia (adenoacanthoma) and a GCC. The clinical stage of the patient's disease was IB as classified by the International Federation of Gynecology and Obstetrics. She was treated by a total abdominal hysterectomy, bilateral salpingo-oophorectomy, and pelvic radiation therapy. The patient was still alive and free of disease at 5 years of follow-up.
Physician Satisfaction and Emergency Department Laboratory Test Turnaround Time
Authors: Steindel Steven J. , Howanitz Peter J. 
Published: January 2021

Abstract
Objectives.—To determine the length of time for the components of the emergency department (ED) turnaround time (TAT) study in 1998 and to ascertain physician satisfaction concerning laboratory services to the ED.
Methods.—Using forms supplied by the College of American Pathologists Q-Probes program, participants conducted a self-directed study of ED TAT over a 4-week period. Data requested included various times of day associated with the ordering, specimen collection, laboratory receipt, and result-reporting stages of stat ED TATs for potassium and hemoglobin. Additionally, practice-related questions associated with the laboratory were asked. Participating laboratories also provided a physician satisfaction survey for up to 4 physicians who were users of ED services. Results of both the TAT study and the physician satisfaction survey were returned by mail. Participants were drawn from the 952 hospital laboratories enrolled in the 1998 College of American Pathologists Q-Probes study on ED TAT. The main outcome measures included the components of the ED TAT process, factors associated with decreases in ED TAT, and the results of the physician satisfaction survey.
Results.—Six hundred ninety hospital laboratories (72.4% response rate) returned data on up to 18 230 hemoglobin and 18 259 potassium specimens. Half of these laboratories responded that 90% of potassium tests were ordered and reported in 69 minutes or less, whereas the TAT for 90% of hemoglobin results was 55 minutes or less. Comparison of the components of TAT for both potassium and hemoglobin with similar studies done in 1990 and 1993 showed no change. Factors found to statistically contribute to faster TATs for both tests were laboratory control of specimen handling and rapid transport time. When whole blood specimens were used for potassium determination, TAT improved. Emergency department physicians chose the study-defined lower satisfaction categories of Often, Sometimes, Rarely, and Never for the questions concerning the laboratory being sensitive to stat testing needs (39.1%) and meeting physician needs (47.6%). Many of the physicians surveyed believed that laboratory TAT caused delayed ED treatment more than 50% of the time (42.9%) and increased ED length of stay more than 50% of the time (61.4%) when compared with other specialty users of the ED.
Conclusions.—Laboratory ED TATs have remained unchanged for almost a decade. Emergency department physicians are not satisfied with laboratory services. Although it appears that one issue may relate to the other, the interaction between the laboratory and the ED is quite complex and has been evolving for at least 30 years. Improvement in interoperability between the departments is essential for operational efficiency and patient care. Effective communication channels need to be established to achieve these goals.
Three-Dimensional Morphology of c-Kit–Positive Cellular Network and Nitrergic Innervation in the Human Gut
Authors: Nemeth Laszlo , Puri Prem 
Published: January 2021

AbstractContext.—c-Kit–positive interstitial cells of Cajal (ICC) appear to play a key role in the normal motility function and development of intestine. Nitric oxide is considered to be the most important messenger of inhibitory nonadrenergic, noncholinergic nerves in the enteric nervous system.Objectives.—The aims of this study were to examine the distribution of nitrergic innervation and ICCs in normal human bowel and to demonstrate interconnections between ICCs and nitrergic nerves and smooth muscle fibers using histochemical and immunohistochemical double-staining methods with a whole-mount preparation technique and confocal laser scanning microscopy.Methods.—Full-thickness small and large bowel specimens were obtained at autopsy from 18 children who died of nongastrointestinal diseases. A whole-mount preparation was performed for all specimens, and double staining was carried out with nicotinamide adenine dinucleotide phosphate (reduced form, NADPH)-diaphorase and c-Kit immunohistochemistry. Double immunofluorohistochemistry with neuronal nitric oxide synthase and c-Kit using confocal laser scanning microscopy was also performed in all specimens.Results.—The whole-mount preparation facilitated 3-dimensional visualization of the meshlike network of NADPH-diaphorase–positive nerve fibers in the myenteric plexus surrounded by a reticular network of c-Kit–positive ICCs. The dense c-Kit–positive cellular network located between longitudinal and circular muscle layers and at the innermost part of circular muscle layer intermingled with the myenteric plexus. Short, fine processes of ICCs made connections with the muscle fibers and c-Kit–positive cells.Conclusions.—The development of double–NADPH-diaphorase histochemistry and c-Kit immunohistochemistry staining technique in a whole-mount preparation provides an easy and useful method for investigating the association between c-Kit–positive cellular network and nitrergic neuronal network in the human bowel wall. The characteristic profiles of the c-Kit–positive cellular network and nitrergic neuronal network and their relationship with the smooth muscle fibers provide a morphologic basis for investigating intestinal motility disorders.