bluuebunny/crossref_metadata_2025_split huggingface dataset:
Adrenocortical Tumors in Brazilian Children: Immunohistochemical Markers and Prognostic Factors
Authors: Sbragia Lourenco , Oliveira-Filho Antonio Goncalves , Vassallo Jose , Pinto Glauce Aparecida , Guerra-Junior Gil , Bustorff-Silva Joaquim 
Published: February 2021

Abstract
Context.—The behavior of adrenocortical tumors (ACTs) is usually difficult to establish in childhood, and the role of immunomarkers in predicting outcome has not yet been elucidated.
Objective.—To investigate the relationship between clinical, pathologic, and immunohistochemical findings and prognosis in a series of children with ACTs.
Patients and Methods.—Clinical data were evaluated retrospectively in 33 children with ACTs, including age at diagnosis, sex, time between first symptoms and diagnosis, clinical signs and symptoms, tumor position, and follow-up. Histologic sections were reviewed, each tumor was classified, and staging was performed according to previously published criteria. Immunohistochemical analysis of p53, Ki-67, c-Erb-B2, and Bcl-2 was performed according to previously published techniques.
Results.—Sixty-four percent (n = 21) of the patients were female, and the age at diagnosis in the cohort ranged from 2 to 96 months. Virilization alone affected 70% (n = 23) of the patients, and 18 patients had stage 1 disease, 9 had stage 2 disease, and 3 each had stage 3 and stage 4 disease. Female sex and stage 1 and stage 2 disease were associated with good outcome. None of the histopathologic criteria evaluated correctly predicted outcome. Only tumors with a volume exceeding 200 mL were associated with malignant behavior. Because only a small number of tumors expressed the antigens, results of these immunohistochemical tests were considered inconclusive.
Conclusion.—In this sample of pediatric ACTs, the clinical and surgical parameters are the most important prognostic factors, while the immunohistochemical markers evaluated were not predictive of outcome.
Frozen Section of Skin Specimens
Authors: Smith-Zagone Megan J. , Schwartz Mary R. 
Published: February 2021

Abstract
Context.—Skin cancers are the most common malignancies in this country. Treatment of these tumors often involves assessment of margins, which may be performed by frozen section.
Objective.—This article discusses indications for frozen section, various approaches to gross examination of specimens, Mohs micrographic surgery, diagnostic pitfalls, methods to improve diagnostic accuracy, and special techniques.
Data Sources.—The authors' extensive experience and review of the published literature.
Conclusions.—Frozen sections play a vital role in the evaluation of margins of basal cell carcinomas and squamous cell carcinomas. The role of frozen sections in evaluation of soft tissue tumors is controversial. With rare exception, they have no role in the evaluation of melanocytic tumors.
Intraoperative Consultation in Gynecologic Pathology
Authors: Coffey Donna , Kaplan Alan L. , Ramzy Ibrahim 
Published: February 2021

Abstract
Context.—Gynecologic specimens are commonly submitted for intraoperative consultation, primarily to confirm the presence and histologic type of malignancy, as well as to determine the adequacy of resection by examining the surgical margins.
Objective.—To review and discuss the application, indications, contraindications, and limitations of intraoperative consultation regarding gynecologic specimens, as well as the causes of false-positive or false-negative frozen section results.
Data Sources.—Review of the pertinent literature and the authors' expertise and experience.
Conclusions.—In most instances, intraoperative consultation regarding gynecologic specimens accurately determines the type of malignancy, the status of the resection margins or the lymph nodes, and the extent and depth of involvement by a tumor. Although the pathologist and the surgeon must be aware of the limitations, the use of intraoperative consultation represents a highly sensitive and specific technique that can play a critical role in the management of gynecologic disease.
Frozen Section of Thyroid and Parathyroid Specimens
Authors: Anton Rose C. , Wheeler Thomas M. 
Published: February 2021

Abstract
Context.—Preoperative fine-needle aspiration of thyroid lesions has greatly diminished the need for surgical evaluation. However, because thyroid nodules are common lesions, many still require surgical intervention and represent a substantial number of cases that the pathologist encounters in the frozen section laboratory.
Objective.—Comprehensive reviews of frozen section indications, as well as gross, cytologic, and histologic features of the most common and diagnostically important thyroid and parathyroid lesions, are presented to provide a guideline for proper triage and management of these cases in the frozen section laboratory. The most common pitfalls are discussed in an attempt to avoid discordant diagnoses.
Data Sources.—Thyroid lobectomy, subtotal or total thyroidectomy, and parathyroid biopsy or parathyroidectomy cases are included in this review.
Conclusions.—The frozen section evaluation of thyroid and parathyroid lesions remains a highly accurate procedure with a low false-positive rate. Gross inspection, complemented by cytologic and histologic review, provides the surgeon with the rapid, reliable, cost-effective information necessary for optimum patient care.
Analytic Bias of Thyroid Function Tests: Analysis of a College of American Pathologists Fresh Frozen Serum Pool by 3900 Clinical Laboratories
Authors: Steele Bernard W. , Wang Edward , Klee George G. , Thienpont Linda M. , Soldin Steven J. , Sokoll Lori J. , Winter William E. , Fuhrman Susan A. , Elin Ronald J. 
Published: February 2021

Abstract
Context.—In proficiency testing surveys, there are differences in the values reported by users of various analytic methods. Two contributors to this variation are calibrator bias and matrix effects of proficiency testing materials.
Objectives.—(1) To quantify the biases of the analytic methods used to measure thyroid-stimulating hormone, thyroxine, triiodothyronine, free thyroxine, and free triiodothyronine levels; (2) to determine if these biases are within allowable limits; and (3) to ascertain if proficiency testing materials correctly identify these biases.
Design.—A fresh frozen serum specimen was mailed as part of the 2003 College of American Pathologists Ligand and Chemistry surveys. The means and SDs for each analytic method were determined for this sample as well as for a proficiency testing sample from both surveys. In the fresh frozen serum sample, target values for thyroxine and triiodothyronine were determined by isotope dilution/liquid chromatography/tandem mass spectrometry. All other target values in the study were the median of the means obtained for the various analytic methods.
Main Outcome Measures.—Calibration biases were calculated by comparing the mean of each analytic method with the appropriate target values. These biases were evaluated against limits based on intra- and interindividual biological variation. Matrix effects of proficiency testing materials were assessed by comparing the rank of highest to lowest analytic method means (Spearman rank test) for each analyte.
Participants.—Approximately 3900 clinical laboratories were enrolled in the College of American Pathologists Chemistry and Ligand surveys.
Results.—The number of methods in the Ligand Survey that failed to meet the goals for bias was 7 of 17 for thyroid-stimulating hormone and 11 of 13 for free thyroxine. The failure rates were 12 of 16 methods for thyroxine, 8 of 11 for triiodothyronine, and 9 of 11 for free triiodothyronine. The means of the analytic method for the proficiency testing material correlated significantly (P &lt; .05) only with the fresh frozen serum means for thyroxine and thyroid-stimulating hormone in the Chemistry Survey and free triiodothyronine in the Ligand Survey.
Conclusions.—A majority of the methods used in thyroid function testing have biases that limit their clinical utility. Traditional proficiency testing materials do not adequately reflect these biases.
Utility of Immunohistochemistry in Distinguishing Primary Adenocarcinomas From Metastatic Breast Carcinomas in the Gastrointestinal Tract
Authors: O'Connell Fionnuala P. , Wang Helen H. , Odze Robert D. 
Published: February 2021

AbstractContext.—Breast carcinoma often metastasizes to the gastrointestinal tract, especially the stomach, where it is frequently difficult to distinguish from a primary gastric carcinoma.Objective.—To evaluate the utility of immunohistochemical stains in differentiating primary gastric carcinomas from metastatic breast carcinomas.Design.—Mucosal biopsy specimens from 47 adenocarcinomas involving the gastrointestinal tract (28 primary gastric carcinomas and 19 metastatic breast carcinomas) and 16 control cases of primary breast carcinomas without metastasis were immunohistochemically stained for estrogen receptor protein (ER), progesterone receptor protein (PR), gross cystic disease fluid protein (GCDFP), human epidermal growth factor receptor 2 protein, cytokeratin (CK) 5/6, CK/7, CK/20, a panel of mucin glycoprotein antigens (MUC2, MUC3, MUC5AC, and MUC6), monoclonal antibody DAS-1, and caudal-type homeobox transcription factor CDX2 and compared between primary and metastatic adenocarcinomas.Results.—Highly significant proportions of metastatic breast carcinomas were positive for ER (72%), PR (33%), GCDFP (78%), and CK5/6 (61%) compared with primary gastric carcinomas (ER, 0%; PR, 0%; GCDFP, 0%; and CK5/6, 14%) (P &lt; .001, P = .002, P &lt; .001, and P = .004, respectively). Of these immunostains, ER, PR, and GCDFP were 100% specific. Primary breast tumors and their metastases showed a similar phenotypic profile. In contrast, primary gastric carcinomas showed significantly higher proportions of cases that stained with CK20 (50%), MUC2 (54%), MUC5AC (71%), MUC6 (39%), DAS-1 (43%), and CDX2 (67%) compared with metastatic breast carcinomas (CK20, 0%; MUC2, 24%; MUC5AC, 6%; MUC6, 0%; DAS-1, 0%; and CDX2, 0%) (P = .001, P = .01, P &lt; .001, P = .02, P = .009, and P &lt; .001, respectively). No significant differences were observed with regard to any of the other immunostains (human epidermal growth factor receptor 2 protein, CK7, and MUC3) between the patient groups.Conclusions.—Estrogen receptor protein, PR, GCDFP, CK5/6, CK20, MUC5AC, MUC6, DAS-1, and CDX2 are helpful in distinguishing primary gastric carcinomas from metastatic breast carcinomas. Of these, ER, PR, and GCDFP are highly specific for metastatic breast carcinomas, whereas CK20, DAS-1, MUC2, MUC5AC, MUC6, and CDX2 are highly specific for primary gastric carcinomas.
Dendriform Pulmonary Ossification, a Form of Diffuse Pulmonary Ossification: Report of a 26-Year Autopsy Experience
Authors: Lara Jonathan F. , Catroppo James F. , Kim Dae U. , Costa Delineda 
Published: February 2021

Abstract
Context.—Dendriform pulmonary ossification (DPO) is an uncommon form of diffuse pulmonary ossification that typically affects the pulmonary interstitium in a setting of interstitial fibrosis.
Objective.—To determine the incidence and characteristics of DPO and correlate the clinical, radiographic, and pathologic features in order to better understand its pathogenesis and behavior and facilitate proper therapy.
Design.—Adult autopsies performed at a tertiary care center from 1978 to 2004 were reviewed to identify cases of DPO. Clinical, radiographic, and pathologic findings, including ultrastructural studies in select cases, were analyzed and correlated.
Results.—Eight cases of DPO were identified from 1393 adult autopsies. None of the cases was diagnosed antemortem. The prevalence of DPO was 0.5%, and the incidence was 0.28 cases per year. Most patients had a history of chronic lung disease, and all were 65 years of age or older.
Conclusions.—Dendriform pulmonary ossification is an uncommon and unusual entity seen incidentally at autopsy and associated with chronic lung disease. It is well demonstrated in postmortem examination, confirmed by microscopy and ultrastructural study, but rarely diagnosed and virtually never considered clinically. Clinical diagnoses include bronchiectasis and interstitial pneumonitis based on radiographic evidence. With its associated radiographic/pathologic findings, DPO should be considered in the differential diagnosis of chronic lung disease.
Recurrence of Nodal Diffuse Large B-Cell Lymphoma as Intravascular Large B-Cell Lymphoma: Is an Intravascular Component at Initial Diagnosis Predictive?
Authors: Zhao Xian-Feng , Sands Amy M. , Ostrow Peter T. , Halbiger Regina , Conway James T. , Bagg Adam 
Published: February 2021

Abstract
We report a case of a 59-year-old man who first presented with a nodal diffuse large B-cell lymphoma that later relapsed as an intravascular large B-cell lymphoma. In the initial biopsy specimen, a few intranodal small vessels that contained large lymphoma cells were noted. After 8 months of multiagent chemotherapy, clinical remission was attained. Two years after the initial diagnosis of nodal diffuse large B-cell lymphoma, the patient presented with a rapid onset of multiorgan failure, which at autopsy was shown to be due to intravascular large B-cell lymphoma. Molecular genetic studies showed that these 2 lymphomas had immunoglobulin heavy-chain gene rearrangements that were of identical size, suggesting that they were derived from the same clone. To our knowledge, this is the first report of a nodal large B-cell lymphoma that relapsed as an intravascular large B-cell lymphoma. Although this report is of only a single case, the presence of a relatively inconspicuous intravascular component in an otherwise typical nodal large B-cell lymphoma may be predictive and could affect clinical decisions regarding diagnosis, monitoring, and prognosis of such lymphomas.
Cardiac Aspergillosis in Patients With Acquired Immunodeficiency Syndrome: A Case Report and Review of the Literature
Authors: Xie Linjun , Gebre Wondwossen , Szabo Katarina , Lin Jen H. 
Published: February 2021

Abstract
Cardiac aspergillosis is uncommon in patients with acquired immunodeficiency syndrome (AIDS) in the absence of open heart surgery. We report a unique case of a 62-year-old man with AIDS who developed Aspergillus pancarditis with Aspergillus vegetations on mitral valve without evidence of pulmonary aspergillosis. There was extensive embolization to the brain and multiple foci of Aspergillus infection in kidneys and adrenal glands. There are only 10 documented cases of cardiac aspergillosis in the literature (1966–2003) in severely immunocompromised AIDS patients with CD4 T-lymphocyte counts ranging from 10 to 121 cells/μL. The cardiac aspergillosis could result from invasive pulmonary aspergillosis, either by hematogenous dissemination or by direct invasion, and skin Aspergillus infection can be carried through the bloodstream to the right heart in intravenous drug abusers. Most of the reported cases of cardiac aspergillosis were diagnosed at autopsy. Mortality among AIDS patients with cardiac aspergillosis is 100%, despite appropriate therapy.
Detection of Microinvasion in Vulvar and Cervical Intraepithelial Neoplasia Using Double Immunostaining for Cytokeratin and Basement Membrane Components
Authors: Rush Demaretta , Hyjek Elizabeth , Baergen Rebecca N. , Ellenson Lora H. , Pirog Edyta C. 
Published: February 2021

Abstract
Context.—Identification of early invasion in vulvar intraepithelial neoplasia 3 (VIN 3) and cervical intraepithelial neoplasia 3 (CIN 3) may be difficult with the use of routine hematoxylin-eosin staining. Presence of obscuring inflammation and tangential tissue sectioning are the most common diagnostic pitfalls.
Objective.—To examine the utility of double immunostaining for cytokeratin–collagen IV or cytokeratin-laminin in the detection of early invasion in VIN 3 and CIN 3.
Design.—The study group consisted of 10 cases of “VIN 3, suspicious for invasion” and 10 cases of “CIN 3, suspicious for invasion.” The negative control group consisted of VIN 3 (n = 15) and CIN 3 (n = 10). The positive control group consisted of cases of invasive vulvar carcinoma (n = 11) and invasive cervical carcinoma (n = 25). All cases were double immunostained for cytokeratin and collagen IV and, in a separate reaction, for cytokeratin and laminin. The continuity of the basement membrane and the presence of stromal invasion were assessed in the stained sections.
Results.—The staining for collagen IV and laminin yielded identical results. A well-defined, continuous basement membrane was visualized in all cases of VIN 3 and CIN 3. A discontinuous or absent basement membrane was observed around the malignant cells on the invasive tumor front in all cases of vulvar and cervical carcinoma. In 2 of 10 cases of VIN 3, suspicious for invasion and in 4 of 10 cases of CIN 3, suspicious for invasion definitive foci of microinvasion were identified with the use of double immunostaining. A well-defined, continuous basement membrane was present in the remaining cases “suspicious for invasion.”
Conclusion.—Double immunostaining for cytokeratin– collagen IV or cytokeratin-laminin is useful for evaluation of early invasion in equivocal cases of VIN 3 and CIN 3.
Immunohistochemical Expression of β-Catenin in Solitary Fibrous Tumors
Authors: Rakheja Dinesh , Molberg Kyle H. , Roberts Cory A. , Jaiswal Vilkesh R. 
Published: February 2021

AbstractContext.—Immunohistochemical staining for β-catenin may be used as an indicator of the integrity of the Wnt signaling and β-catenin degradation pathways. Among mesenchymal tumors, aberrant nuclear localization of β-catenin is seen in desmoid-type fibromatoses but has not been described for solitary fibrous tumors that may mimic the former lesions, especially in small biopsy samples.Objective.—To study the immunohistochemical expression of β-catenin in solitary fibrous tumors.Design.—We performed immunohistochemical staining for β-catenin in 12 solitary fibrous tumors, one of which showed histologic features of malignancy.Results.—All the tumors showed strong and diffuse reactivity for β-catenin. Four tumors (33%) showed nuclear staining for β-catenin, whereas the remaining tumors showed either a membranous or mixed membranous and cytoplasmic pattern of staining. The only histologically malignant tumor of the group showed a mixed membranous and cytoplasmic pattern of staining for β-catenin.Conclusions.—Immunohistochemical staining for β-catenin in solitary fibrous tumors does not show a consistent pattern, which may be due to differences in tumorigenesis. Larger studies with clinical follow-up are required for estimating the impact of the variable staining pattern on clinical behavior of these tumors.
Sudden Death of a Patient With Pulmonary Langerhans Cell Histiocytosis
Authors: Nakhla Hassan , Jumbelic Mary I. 
Published: February 2021

AbstractWe report a case of sudden death due to bilateral pneumothorax in a previously healthy 16-year-old adolescent white girl. She presented with sudden onset of shortness of breath followed by loss of consciousness. Postmortem chest radiograph showed bilateral pneumothoraces. Autopsy confirmed the bilateral pneumothorax and additionally showed emphysematous changes and bullae throughout the lung tissue. Microscopic sections of the lungs showed Langerhans cell histiocytosis. To the best of our knowledge, this is the first reported case of fatal presentation of pulmonary Langerhans cell histiocytosis.
Malignant Glomus Tumor of the Urinary Bladder
Authors: Shim Hyo Sub , Choi Young Deuk , Cho Nam Hoon 
Published: February 2021

Abstract
We present a case of a malignant glomus tumor arising in the urinary bladder of a 57-year-old woman with metastatic pulmonary nodules who died 2 months later. Pathologically and clinically confirmed malignant glomus tumors are exceedingly rare, especially those that arise in the visceral organs. The present case retained its architectural similarity to a benign glomus tumor and consisted of sheets of highly malignant round cells showing cytoplasmic positivity for smooth muscle actin. On reticulin histochemical staining, we found that reticulum fibrils surrounded individual tumor cells, suggesting cellular investment by basement membrane. We discuss the concept of malignant glomus tumors and emphasize the criteria that distinguish them from other malignant tumors.
Cytomegalovirus Infection Masquerading as Carcinoma in a Lung Transplant Patient
Authors: Allen Timothy Craig , Bag Remzi , Zander Dani S. , Cagle Philip T. 
Published: February 2021

Abstract
In lung transplant patients, most infections produce radiographically diffuse or lobar infiltrates. Solitary nodules suggesting neoplasm may arise in lung transplant patients with lung infections. We describe a 45-year-old woman who underwent bilateral lung transplantation to treat bilateral bronchiectasis and lung fibrosis resulting from Hodgkin disease. Five months later, a solitary mass was identified on chest radiograph in the left upper lobe and left superior mediastinum. Low-power examination of wedge biopsies of the mass showed a florid proliferation of cells with clear to bubbly to eosinophilic cytoplasm and moderate nuclear atypia, proliferating fibroblasts, and necrosis, suggesting a clear cell carcinoma (possibly metastatic renal cell carcinoma). Intranuclear inclusions compatible with cytomegalovirus were identified on high-power examination and confirmed by immunohistochemistry. In lung transplant patients, a cytomegalovirus infection may mimic malignancy both radiographically and on initial histopathologic examination.
Clear Cell Hidradenoma: A Mimic of Metastatic Clear Cell Tumors
Authors: Volmar Keith E. , Cummings Thomas J. , Wang Wei Hua , Creager Andrew J. , Tyler Douglas S. , Xie H. Bill 
Published: February 2021

Abstract
Clear cell hidradenoma is a benign skin appendage tumor that may mimic conventional-type renal cell carcinoma. Histologically, clear cell hidradenoma contains small ductular lumens, focal apocrine and squamoid change, and a less prominent vascular pattern than renal cell carcinoma. Furthermore, immunohistochemical studies can aid in distinguishing the 2 tumors. Knowing the cytologic features of primary skin adnexal neoplasms helps distinguish them from cutaneous metastases, which are more commonly referred for fine-needle aspiration biopsy evaluation. Detailed clinical history, physical findings, and ancillary studies are essential for correct diagnosis and categorization of these tumors. We report the rare case of a patient with renal cell carcinoma who underwent excision of an axillary clear cell hidradenoma, which was clinically suggestive of cutaneous metastatic disease.
Adrenocortical Carcinoma With Concomitant Myelolipoma in a Patient With Hyperaldosteronism
Authors: Sun Xichun , Ayala Alberto , Castro Claudia Y. 
Published: February 2021

Abstract
We present a case of aldosterone-secreting adrenocortical carcinoma with concomitant myelolipoma. To the best of our knowledge, this is the first such reported case. The patient was a 43-year-old man with severe hypertension. Clinical workup revealed an increased serum aldosterone level, hypokalemia, and metabolic alkalosis, and a left adrenal mass was found on computed tomography. The patient underwent a unilateral adrenalectomy, which led to improvement in blood pressure, the serum potassium level, and aldosterone concentration. The tumor weighed 70 g and measured 5.0 cm. On microscopic examination, we found necrosis, focal cytologic atypia, diffuse eosinophilic cells comprising more than 75% of the tumor, 5 to 7 mitotic figures per 50 high-power fields, rare atypical mitosis, and venous invasion. At the periphery of the tumor but within the capsule, microscopic areas of myelolipoma were seen. Ki-67 staining was positive in 20% of the tumor cells. Although rare, aldosterone-secreting carcinoma associated with myelolipoma should be included in the differential diagnosis of adrenal gland masses.