bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of Numerical Chromosomal Changes Detected by Interphase Fluorescence In Situ Hybridization in High-Grade Prostate Intraepithelial Neoplasia as a Predictor of Carcinoma
Authors: Al-Maghrabi Jaudah , Vorobyova Lada , Toi A. , Chapman William , Zielenska Maria , Squire Jeremy A. 
Published: January 2021

Abstract
Context.—High-grade prostate intraepithelial neoplasia (HPIN) is the most likely precursor of prostate cancer. The condition of many patients with a diagnosis of HPIN in prostate needle core biopsy could, if left untreated, progress to invasive cancer. Currently there is no available clinical, immunohistochemical, or morphologic criteria that are predictive of this progression.
Objective.—To determine whether chromosomal instability in these precursor lesions could increase their predictive value for cancer detection.
Design.—Dual-color interphase fluorescence in situ hybridization analysis was performed on archived prostate needle core biopsies from 54 patients with initial diagnosis of isolated HPIN and follow-up of 3 years or more. We used commercially available centromere probes for chromosomes 4, 7, 8, and 10. We had interpretable results in 44 patients as follows: (1) group A: 24 HPIN patients with persistent HPIN and/or benign lesions in the follow-up biopsies, and (2) group B: 20 HPIN patients with progression to prostate carcinoma.
Results.—Twenty-five percent of the patients in group B displayed numeric chromosomal aberrations. Only 8.3% of the patients from group A had chromosomal abnormalities (P = .1). The observed overall chromosomal changes in HPIN were higher than those in normal or hyperplastic epithelium, with a statistically significant difference (P &lt; .05). All aberrations were detected in the form of chromosomal gain. Overall, the commonest aberration was gain of chromosome 8, followed by gains of chromosomes 7 and 10.
Conclusion.—These results indicated that although no single numeric chromosomal abnormality could be assigned as a predictor of HPIN progression to carcinoma, the overall level of numeric chromosomal abnormalities shows a trend of elevation in HPIN patients whose condition subsequently progressed to carcinoma.
Pseudallescheriasis as an Aggressive Opportunistic Infection in a Bone Marrow Transplant Recipient
Authors: Nonaka Daisuke , Yfantis Harris , Southall Pamela , Sun Chen-Chih 
Published: January 2021

AbstractPseudallescheria boydii is a low-virulence fungus that is the main causative agent of posttraumatic mycetoma in a nonimmunocompromised host. Immunocompromised patients are at high risk for locally invasive or disseminated Pseudallescheria infection. However, aggressive opportunistic infections due to P boydii are reported infrequently because it morphologically resembles other fungi, especially Aspergillus species, on tissue histology; therefore, such infections are not identified and treated properly. We report a case of disseminated P boydii infection in a patient following bone marrow transplantation. The identity of the fungus was not recognized until microbiologic culture results became available. Our case illustrates the importance of recognizing this fungus as an opportunistic infection in immunocompromised patients, as well as the need for culture of biopsy material for proper identification so that appropriate therapy can be instituted.
Cotyledonoid Leiomyoma
Authors: Cheuk W. , Chan John K. C. , Liu John Y. S. 
Published: January 2021

Abstract
Cotyledonoid leiomyoma or “grapelike” leiomyoma is a very rare tumor among the ever-expanding repertoire of growth variants described in benign uterine leiomyoma. We report a case of cotyledonoid leiomyoma in a 55-year-old woman who presented with menorrhagia and uterine prolapse. A large multinodular fungating tumor adhering to the right posterolateral wall of the uterus and extending to the broad ligament was discovered at vaginal hysterectomy. With a provisional diagnosis of sarcoma, total hysterectomy and bilateral salpingo-oophorectomy were performed. Postoperatively, the patient was well with no evidence of recurrence at 14 months. Pathologic examination revealed a 10-cm, red-brown tumor that comprised multiple bulbous processes protruding over the uterine surface, in continuity with a dissecting intramyometrial component. It was composed of fascicles and nodules of bland-looking smooth muscle cells with prominent perinodular hydropic degeneration. Coagulative necrosis, mitoses, and nuclear atypia were absent. Cotyledonoid leiomyoma apparently results from a combination of several uncommon growth patterns operating together, including subserosal growth, dissecting growth, and perinodular hydropic degeneration. Increased awareness of this grossly alarming variant of benign uterine leiomyoma can help avoid overtreatment.
Mental Tools for Thinking About DNA Technologies in New Ways
Authors: Root-Bernstein Robert , Root-Bernstein Michele 
Published: January 2021

AbstractObjective.—To investigate the nature of creative thinking in biomedical science with specific applications to molecular pathologies and DNA technologies.Data Sources.—Accounts of breakthroughs and inventions contained in autobiographies, biographies, interviews, and archival sources.Study Selection.—Discoveries that have altered, or may yet alter, basic textbook accounts of biomedical sciences for which appropriate data sources exist.Data Extraction.—Approximately 1000 data sources were analyzed, both within appropriate sciences and in other creative fields, such as the arts.Data Synthesis.—The current analysis is based on a framework described in our previous book, Sparks of Genius, which outlines a general approach to understanding creative thinking.Conclusions.—Creative thinking in all disciplines depends on a common mental “toolkit” that consists of 13 fundamental tools: observing, imaging, abstracting, pattern recognition, pattern forming, analogizing, body thinking, empathizing, dimensional thinking, modeling, playing, transforming, and synthesizing. Scientists recognize and solve problems by observing data that break the patterns established by theories; exploring a system by creating an abstract model with which they can play; and transforming data into feelings, sounds, and other forms that create surprising analogies to already-understood principles. The result of such personal thinking is knowledge combined with sensation and emotion—feeling and understanding synthesized into complete awareness. We illustrate some of these modes of thinking with reference to recent breakthroughs in DNA-related areas and suggest ways in which the use of “tools for thinking” can increase the probability of making further discoveries in the biomedical sciences.
Multiple Myeloma in Association With Sarcoidosis
Authors: Şen Filiz , Mann Karen P. , Medeiros L. Jeffrey 
Published: January 2021

AbstractThe association of sarcoidosis with Hodgkin disease and non-Hodgkin lymphoma is well known. However, multiple myeloma also can occur rarely in association with sarcoidosis. We describe a patient with sarcoidosis who subsequently developed multiple myeloma. The patient was a 49-year-old woman with a 4-year history of severe, chronic, active sarcoidosis involving her lungs, lymph nodes, eyes, and bone marrow. During the initial clinical workup, a serum monoclonal paraprotein was detected and bone marrow examination revealed a slight increase in plasma cells (4%), in addition to noncaseating granulomas. Thus, the diagnoses of monoclonal gammopathy of undetermined significance and sarcoidosis were established simultaneously. She sought medical attention for her current illness when she developed low back pain and weakness of her lower extremities. Serum protein electrophoresis and immunofixation revealed a monoclonal paraprotein, immunoglobulin (Ig) G κ type, and quantification revealed an IgG level of 46.67 g/L (normal, 5.88–15.73 g/L). Bone marrow aspiration and biopsy revealed multiple myeloma and sarcoidosis. Including this patient, 11 cases of sarcoidosis and multiple myeloma have been reported to date, including 3 patients with monoclonal gammopathy of undetermined significance preceding the onset of multiple myeloma. In this case, as in most of the cases reported previously, sarcoidosis preceded the development of multiple myeloma.
Estimation of Size of Clonal Unit for Keratinocytes in Normal Human Skin
Authors: Chaturvedi Vijaya , Chu Sue , Carrol Mathew , Brenner Jennifer W. , Nickoloff Brian J. 
Published: January 2021

AbstractObjective.—It has been suggested that keratinocyte (KC) stem cells reside at the epicenter of a clonal population of cells. To estimate the territory or surface area covered by a single stem-cell–derived KC population in human skin, clonal skin maps were created from 3 healthy adult women and from normal skin of a psoriatic patient.Design.—Two hundred fifty-eight punch biopsy samples of various sizes (ranging from 2 to 8 mm in diameter) were analyzed for clonality employing X chromosome inactivation patterns at the human androgen receptor gene (HUMARA) locus. DNA was isolated and clonality established by significant decrease of either maternal or paternal X chromosome band patterns following restriction enzyme digestion, polymerase chain reaction amplification, and gel electrophoresis.Results.—Fifty-three (41%) of 128 two-mm biopsies were clonal, whereas only 6 (14%) of 43 three-mm, 5 (14%) of 36 four-mm, and 3 (8%) of 35 five-mm biopsies revealed a clonal population of KCs. By contrast, in 5 different biopsies from a psoriatic patient, including 4- or 5-mm sizes, all but 1 were clonal; even an 8-mm biopsy contained a clonal population of KCs. Mantel-Haenszel χ2 analysis revealed a P value of .001, reflecting a strong trend in probability for presence of a single clone of KCs as related to size of the biopsy sample. By sequentially analyzing 30 contiguous 2-mm biopsy samples within a given strip of skin, 10 clonal domain changes, as reflected in maternal versus paternal switches, were observed.Conclusions.—These results provide direct evidence of a clonal population of KCs in normal and psoriatic lesion-free skin, and indicate that a clonal epidermal unit of KCs frequently can be detected in small biopsies (2 mm), but that in normal skin sampling, overlapping clones are apparently present in larger (ie, 4–5-mm) biopsies, producing nonclonal patterns. The clonal domain of progeny in normal skin has a rather limited territorial boundary (2 mm in diameter). However, in lesion-free skin from a psoriatic patient, there may be clonal expansion of KCs due to perturbation in epidermopoiesis and/or stem cell distribution.
p53 Protein Overexpression in Bone Marrow Biopsies of Patients With Shwachman-Diamond Syndrome Has a Prevalence Similar to That of Patients With Refractory Anemia
Authors: Elghetany M. Tarek , Alter Blanche P. 
Published: January 2021

Abstract
Context.—Shwachman-Diamond syndrome (SDS) is a rare inherited disorder characterized by pancreatic insufficiency, neutropenia, and in some patients, metaphyseal dysostosis. Patients with SDS are at a high risk for development of bone marrow failure, myelodysplastic syndrome, and acute leukemia. The p53 gene plays a major role in cell-cycle regulation, particularly in the presence of a genetic alteration in DNA, a critical step for the initiation of leukemogenesis. p53 gene up-regulation and p53 protein overexpression may occur as a cellular reaction to significant DNA damage. Shwachman-Diamond syndrome and refractory anemia patients have close similarities in the prevalence of acute leukemia and in cell-cycle changes in bone marrow cells. This similarity was further investigated for p53 protein overexpression using archived tissue from patients with hematologic diseases having various leukemic propensities, including SDS and refractory anemia.
Methods.—Immunohistochemical staining for p53 protein overexpression was performed on bone marrow biopsies from 9 patients with SDS. These specimens were compared with biopsies from 71 patients with acquired hematologic disorders with variable risk levels for leukemia, including acquired aplastic anemia (n = 14), refractory anemia (n = 46), and various acquired cytopenias (n = 11), as well as 37 control subjects.
Results.—p53 protein overexpression was identified only in patients with SDS and in patients with refractory anemia; these groups exhibited comparable prevalences of 78% and 72%, respectively. None of the patients with acquired aplastic anemia, acquired cytopenias, or in the control group showed overexpression of p53 protein.
Conclusion.—The prevalence of p53 protein overexpression in SDS is significantly different from that in acquired aplastic anemia and acquired cytopenias, but it is similar to the prevalence in refractory anemia. We speculate that p53 protein overexpression in this bone marrow failure syndrome may represent an early indicator of significant DNA genetic alteration, which is a crucial step in the process of leukemogenesis.
Validation of p53 Immunohistochemistry as a Prognostic Factor in Breast Cancer in Clinical Practice
Authors: Bartley Angela N. , Ross Dennis W. 
Published: January 2021

Abstract
Context.—Abnormal p53 tumor suppressor gene expression as detected by immunohistochemistry is a possible prognostic factor in breast cancer. The difference in techniques used to evaluate the expression of mutated p53 protein is under intense scrutiny, as well as its uses either independently or in conjunction with other prognostic factors in breast cancer.
Objective.—To determine whether p53 immunohistochemistry can be used as a reliable indicator of the presence of mutated nuclear p53 protein, and whether this method can be performed reliably in a community hospital's clinical practice.
Design.—One hundred twenty-two cases of breast carcinoma were stained and analyzed for the presence of p53 protein using DO-7 (Dako Corporation, Carpinteria, Calif) p53 antibody.
Results.—Of the 122 cases of invasive carcinoma studied, 23 (18.7%) were positive for p53, and 16 (16.3%) of 98 cases with coexisting ductal carcinoma in situ were positive for p53. This finding is in agreement with comparable published studies.
Conclusions.—Based on the results of this study, we conclude that p53 immunohistochemistry qualifies as a diagnostic technique suitable for clinical practice in a community hospital. Its detection may be particularly promising in clinical trials of new molecular therapies directed at the p53 tumor suppressor gene.
Gastric Endocrine Pancreatic Heterotopia
Authors: Hammock Lauren , Jorda Merce 
Published: January 2021

Abstract
Heterotopic pancreas is a relatively infrequent lesion most often found in the stomach. Four histologic types are recognized: total, canalicular, exocrine, and endocrine heterotopia. To our knowledge, only 2 cases of purely endocrine heterotopic pancreas have been reported in detail. We describe the case of a patient with gastric and duodenal ulcers and gastric endocrine heterotopia. The lack of mass formation, histomorphology, and immunohistochemical features simulating islets of Langerhans supported the diagnosis. We conclude that purely endocrine heterotopic pancreas is a very rare entity that, when present, can simulate a primary or metastatic neuroendocrine tumor. Adequate sampling of the specimen, histomorphologic pattern, and immunohistochemistry are important for the purpose of distinguishing between a neuroendocrine tumor and purely endocrine pancreatic heterotopia.
Transient Myeloproliferative Disorder With Erythroid Differentiation in Down Syndrome
Authors: Bozner Peter 
Published: January 2021

AbstractA newborn with a karyotype of 47, XY, +21 presented at birth with a white blood cell count of 27 700/μL of which 61% were blast cells. The blast cell morphologic structure was initially not characteristic of any particular lineage, although the cytoplasm contained fine granules and occasional small vacuoles. Routine cytochemical stains were negative, except one for nonspecific esterase that was faintly positive in most of the blast cells. Flow cytometric analyses showed that the blast cells expressed glycophorin A with a subset dimly coexpressing CD45 and were negative for CD34, CD71, myeloid, lymphoid, and platelet-associated antigens. These immunophenotypic findings were consistent with an abnormal erythroid phenotype. A few days postpartum, markedly dysplastic erythroid precursor cells appeared in the peripheral blood and increased in number as the early blast cells decreased. After a period of subdued blast cell production, a second wave of increase in the number of blast cells and dysplastic erythroblasts followed and ended with the disappearance of circulating abnormal cells. The child is now 5 years old and no major illness has been reported since the remission of this disorder. This case most likely belongs to the category of transient myeloproliferative disorders, although the erythroid-like phenotype of blast cells and the evidence of single-lineage maturation to circulating dysplastic erythroid precursors allow the suggestion that this process could represent a special form of a self-limited hematologic disorder in Down syndrome.
Fine-Needle Aspiration of Renal Angiosarcoma
Authors: Johnson Viviana V. , Gaertner Erich M. , Crothers Barbara A. 
Published: January 2021

Abstract
Angiosarcoma of the kidney is an unusual neoplasm, and primary renal angiosarcoma is exceedingly rare, with fewer than 11 well-documented cases reported to date. To our knowledge, no publication to date has correlated the fine-needle aspiration cytologic findings in renal angiosarcoma with the gross, histologic, and immunohistochemical findings. A 50-year-old man presented with a left kidney mass and multiple liver and pulmonary nodules. Computed tomography–guided fine-needle aspiration biopsies of the renal mass and a hepatic nodule were performed and demonstrated malignant spindle cells consistent with angiosarcoma. The diagnosis was confirmed at autopsy through histologic examination and associated ancillary studies. This case presents the fine-needle aspiration cytologic findings in renal angiosarcoma and correlates these findings with the gross pathologic, histologic, and immunohistochemical findings.
Malignant Stromal Tumor of the Gallbladder With Interstitial Cells of Cajal Phenotype
Authors: Mendoza-Marin Marisela , Hoang Mai P. , Albores-Saavedra Jorge 
Published: January 2021

Abstract
Malignant mesenchymal tumors of the gallbladder are exceedingly rare. We report a malignant stromal tumor of the gallbladder with a phenotype of interstitial cells of Cajal. To our knowledge, only the benign counterpart of this tumor has been described previously. A 34-year-old woman presented with right upper quadrant abdominal pain. At the time of cholecystectomy, the gallbladder was noted to have a thickened wall and a polypoid mass arising in the neck of the gallbladder. Histologic sections showed a cellular proliferation of spindle neoplastic cells that were arranged in short fascicles. Numerous mitotic figures and foci of necrosis were noted. The neoplastic cells expressed CD117 (c-Kit protein) and vimentin. They were negative for smooth muscle actin, desmin, myoglobin, cytokeratin, S100 protein, and CD34. Our case demonstrates that a malignant stromal tumor that is histologically and immunohistochemically identical to gastrointestinal stromal tumor can occur in the gallbladder, and that the expression of CD117 may be of therapeutic importance.
Laboratory Diagnosis of Dysfibrinogenemia
Authors: Cunningham Mark T. , Brandt John T. , Laposata Michael , Olson John D. 
Published: January 2021

AbstractDysfibrinogenemia is a coagulation disorder caused by a variety of structural abnormalities in the fibrinogen molecule that result in abnormal fibrinogen function. It can be inherited or acquired. The inherited form is associated with increased risk of bleeding, thrombosis, or both in the same patient or family. Traditionally, dysfibrinogenemia is diagnosed by abnormal tests of fibrin clot formation; the thrombin time and reptilase time are the screening tests, and the fibrinogen clotting activity–antigen ratio is the confirmatory test. The inherited form is diagnosed by demonstrating similar laboratory test abnormalities in family members, and if necessary by analysis of the fibrinogen protein or fibrinogen genes in the patient. The acquired form is diagnosed by demonstrating abnormal liver function tests and by ruling out dysfibrinogenemia in family members. This article reviews the laboratory testing of dysfibrinogenemia and presents an algorithm for sequential test selection that can be used for diagnosis.
Malignant Eccrine Spiradenoma
Authors: Mirza Imran , Kloss Robert , Sieber Steven C. 
Published: January 2021

AbstractMalignant transformation of eccrine spiradenoma is extremely rare. We describe the case of a 70-year-old man with malignant eccrine spiradenoma of the forearm and metastases to the axillary lymph nodes. Surgical excision with adequate margins and lymph node dissection was performed. Tamoxifen therapy was instituted after obtaining positive immunostaining results for estrogen receptor. After 41 months of follow-up, there has been no recurrence or distant metastases. Wide local excision and close follow-up are crucial in the management of malignant eccrine spiradenoma. The role of other therapeutic modalities, including hormonal therapy, remains to be determined.
Oncocytoma-like Angiomyolipoma
Authors: Martignoni Guido , Pea Maurizio , Bonetti Franco , Brunelli Matteo , Eble John N. 
Published: January 2021

AbstractWe report the clinical, pathologic, and immunohistochemical features of an unusual tumor of the kidney composed of densely eosinophilic, polygonal epithelioid cells. The patients were a 56-year-old woman and a 35-year-old man. The renal tumors were discovered during follow-up for breast carcinoma and evaluation for abdominal pain, respectively. The tumors closely resembled oncocytoma in routine sections, but were negative for epithelial markers and positive for HMB-45, a pattern of reactions characteristic of angiomyolipoma. In the woman, a single additional microscopic angiomyolipoma was present in the renal parenchyma at a distance from the main tumor. Both patients are alive without recurrence 7 and 10 years after surgery, respectively. Based on clinical, morphologic, and immunophenotypic features, we conclude that these tumors are oncocytoma-like angiomyolipomas.