bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessment of Sweat-Testing Practices for the Diagnosis of Cystic Fibrosis
Authors: LeGrys Vicky A.
Published: January 2021

Objective.—To describe the results of the College of American Pathologists survey questions assessing the current practice of sweat testing in North America and to identify areas in which improvement is needed.

Data Source.—Results of the supplemental questions to the SW-B 2000 survey.

Study Selection.—Supplemental questions were designed to assess variation in sweat collection, analysis, and interpretation.

Data Extraction.—Extractions of the data were made based on the relevance of the data to the objectives of the review.

Data Synthesis.—The majority of laboratories surveyed performed sweat testing according to the procedures described in the National Committee for Clinical Laboratory Standards' document. The study revealed that a number of laboratories have adopted poor practice standards and are potentially compromising patient care. Areas of concern include the number of laboratories performing few sweat tests per year, the persistence of unreliable methodology, misunderstanding of collection parameters, lack of patient education, and erroneous result reporting.

Conclusions.—The study identified areas of concern toward which educational efforts can be directed. Such efforts include the development of a College of American Pathologists accreditation checklist for sweat testing and targeted responses in the sweat analysis participant summary report.
Pulmonary Thrombotic Arteriopathy in Patients With Sickle Cell Disease
Authors: Adedeji Moses O. , Cespedes Julio , Allen Kay , Subramony Charu , Hughson Michael D.
Published: January 2021

Background.—Shortened life expectancy due to pulmonary hypertension (PH) is seen in 5% to 10% of patients with sickle cell disease. The principal factors suspected of causing PH are pulmonary thromboemboli (PE) and in situ arterial thrombosis.

Objective.—To investigate the possible role that PE or in situ arterial thrombosis play in the development of PH in sickle cell disease.

Methods.—Autopsies of 12 patients with sickle cell disease were correlated with clinical data from medical records.

Results.—Right ventricular hypertrophy was present in 9 of 12 patients. Six patients with right ventricular hypertrophy had thrombi in large elastic pulmonary arteries. All patients with elastic artery thrombi had fresh or organized thrombi in small muscular pulmonary arteries. Hypertensive small arterial changes were present in 5 of these 6 patients. Six patients showed no thrombi in elastic arteries. Among these 6 patients, 3 had right ventricular hypertrophy and recent and organized thrombi, as well as hypertensive changes in small arteries. One of these 3 patients demonstrated plexiform-like lesions and fibrinoid necrosis of small arteries. Three patients without right ventricular hypertrophy had pneumonia or pulmonary edema with no identifiable pulmonary artery pathology.

Conclusions.—Arterial thrombosis with PH and cor pulmonale was regarded as the cause of death among most of these patients. Elastic artery thrombi are pulmonary thromboemboli, but pulmonary thromboemboli are always associated with widespread thrombosis of small arteries. Widespread thrombosis of small arteries alone was associated with PH in some cases. This finding suggests that pulmonary thromboemboli may be a late complication of PH and cor pulmonale and that an in situ thrombotic arteriopathy underlies the development of PH in most patients with sickle cell disease.
Epithelioid Angiosarcoma Arising in the Tuberculous Pyothorax
Authors: Hattori Hideo
Published: January 2021

Chronic pyothorax associated with pulmonary tuberculosis was recently proposed to be one of the predisposing factors of angiosarcoma arising in the chest wall. Separately, several authors have reported pleural angiosarcoma that has a close resemblance to mesothelioma, the latter having no apparent association with a history of pyothorax. I present a detailed pathologic description of an autopsy case of thoracic angiosarcoma arising after long-standing tuberculous pyothorax, for the purpose of better illustrating this condition. In this case, the main tumor mass was situated on the soft tissue of the chest wall outside the rib girdle. On the pleuropulmonary tissue, tumor infiltration was grossly observable as a dark patch, 2 cm in diameter, on the outer surface of the wall of the pyothorax (pleural peel). Infiltration of the tumor was found in the soft tissue just outside of the peel and in the attached rib. However, the tumor was not found in the peel itself, nor was it found in the necrotic content of the pyothorax. This case suggests that angiosarcoma associated with pyothorax is not similar to primary pleural angiosarcoma and shows the rather ordinary feature of the tumor's arising in the soft tissue.
Serous Cystadenoma of the Pancreas With Papillary Features
Authors: Rampy Bill A. , Waxman Irving , Xiao Shu-Yuan , Logroño Roberto
Published: January 2021

Serous cystadenoma of the pancreas is an uncommon neoplasm that occasionally exhibits papillary differentiation. The cytomorphologic structure of pancreatic serous cystadenoma has been rarely described, and, to our knowledge, such papillary morphologic structure has never been reported on fine-needle aspiration cytologic examination. We present a case of serous cystadenoma of the pancreas in a 77-year-old woman. Endoscopic ultrasonography showed a well-demarcated solid/cystic mass in the midbody of the pancreas, suggestive of solid pseudopapillary tumor. Aspiration cytologic examination, performed under endoscopic ultrasound guidance, showed a predominantly papillary epithelial neoplasm consistent with the radiologic impression. Gross and histologic examination of the excised specimen revealed a pancreatic serous cystadenoma with multifocal papillae. This case illustrates the cytomorphologic structure of serous cystadenoma that presents with prominent papillary differentiation on aspiration cytologic examination. The unusual cytologic appearance of this tumor introduces significant diagnostic challenges to the pathologist. Serous cystadenoma must be included in the differential diagnosis of pancreatic neoplasms with papillary morphologic structure as evaluated by fine-needle aspiration cytologic examination.
Estimation of Performance and Sequential Selection of Diagnostic Tests in Patients With Lung Lesions Suspicious for Cancer
Authors: Grzybicki Dana Marie , Gross Thomas , Geisinger Kim R. , Raab Stephen S.
Published: January 2021

Context.—Measuring variation in clinician test ordering behavior for patients with similar indications is an important focus for quality management and cost containment.

Objective.—To obtain information from physicians and nonphysicians regarding their test-ordering behavior and their knowledge of test performance characteristics for diagnostic tests used to work up patients with lung lesions suspicious for cancer.

Design.—A self-administered, voluntary, anonymous questionnaire was distributed to 452 multiple-specialty physicians and 500 nonphysicians in academic and private practice in Pennsylvania, Iowa, and North Carolina. Respondents indicated their estimates of test sensitivities for multiple tests used in the diagnosis of lung lesions and provided their test selection strategy for case simulations of patients with solitary lung lesions. Data were analyzed using descriptive statistics and the χ2 test.

Results.—The response rate was 11.2%. Both physicians and nonphysicians tended to underestimate the sensitivities of all minimally invasive tests, with the greatest underestimations reported for sputum cytology and transthoracic fine-needle aspiration biopsy. There was marked variation in sequential test selection for all the case simulations and no association between respondent perception of test sensitivity and their selection of first diagnostic test. Overall, the most frequently chosen first diagnostic test was bronchoscopy.

Conclusions.—Physicians and nonphysicians tend to underestimate the performance of diagnostic tests used to evaluate solitary lung lesions. However, their misperceptions do not appear to explain the wide variation in test-ordering behavior for patients with lung lesions suspicious for cancer.
Focal Orchitis in Undescended Testes
Authors: Nistal Manuel , Riestra María Luisa , Paniagua Ricardo
Published: January 2021

Objective.—To evaluate seminiferous epithelium lesions in adult cryptorchid testes showing lymphoid infiltrates in seminiferous tubules and interstitium (ie, focal orchitis). Also, to consider the possible role of this lesion in the etiology of tubular atrophy.

Methods.—We performed a histopathologic study of the cryptorchid testes and adjacent epididymides removed from 50 adult men who had not been previously treated for cryptorchidism. The study included morphologic and semiquantitative evaluation of seminiferous tubule pathology (according to germ cell numbers), Sertoli cell morphology, tubular lumen dilation, rete testis pattern (normal, hypoplastic, or cystic), and epididymal pattern (normal or epididymal duct hypoplasia). The study also included immunohistochemical evaluation of immune cell markers. The results were compared with clinical and laboratory findings.

Results.—Focal lymphoid infiltrates (mainly lymphocytes) in seminiferous tubules and interstitium were found in 22 patients (44%), all of whom had unilateral cryptorchidism. The course of orchitis was asymptomatic, and laboratory data were normal. According to the seminiferous tubule pathology, a variety of histopathologic diagnoses, were made: (1) mixed atrophy consisting of Sertoli cell–only tubules intermingled with tubules showing maturation arrest of spermatogonia (11 testes, 4 of which also showed hyalinized tubules); (2) Sertoli cell–only tubules plus hyalinized tubules (4 testes); (3) Sertoli cell–only tubules (3 testes); (4) intratubular germ cell neoplasia (2 testes, 1 of which also showed hyalinized tubules); (5) complete tubular hyalinization (1 testis); and (6) tubular hyalinization plus some groups of tubules with hypospermatogenesis (all germ cell types were present although in lower numbers, 1 testis). Dysgenetic Sertoli cells, that is, Sertoli cells that had undergone anomalous, incomplete maturation, were observed in all nonhyalinized seminiferous tubules with inflammatory infiltrates. Tubular ectasia was observed in 13 cases. The rete testis was hypoplastic and showed cystic transformation in 18 testes, and the epididymis was hypoplastic in 15 testes.

Conclusions.—The causes of these focal inflammatory infiltrates are unknown. It is possible that tubular ectasia and Sertoli cell dysgenesis are involved and that these alterations cause a disruption of the blood-testis barrier and allow antigens to enter the testicular interstitium, giving rise to an autoimmune process.
Measles-Related Appendicitis
Authors: Paik So-Ya , Oh Jung-Tak , Choi Yoon-Jung , Kwon Kye-Won , Yang Woo-Ick
Published: January 2021

Owing to the characteristic Warthin-Finkeldey giant cells found in hyperplastic mucosa-associated lymphoid tissue, it has been emphasized that pathologists can make a diagnosis of measles from appendectomy specimens even in the prodromal stage before diagnostic rashes develop. However, to date, those reported cases of measles-related appendicitis have dealt with the histologic features of the prodromal stage and we found no reports in the English literature describing the histopathologic findings of appendicitis during the full-blown stage of measles. Here, we describe 2 cases of measles-related appendicitis that show contrasting histologic features according to stage, one discovered during the prodromal stage and the other occurring during the full-blown stage. This report describes heretofore unreported histopathologic findings of measles-related appendicitis observed during the full-blown stage of the infection and highlights histopathologic changes caused by replication of the virus in different compartments of the same organ during the course of infection.
Ceruminous Gland Adenoid Cystic Carcinoma With Contralateral Metastasis to the Brain
Authors: Conlin Phillip A. , Mira Jose Luis , Graham Suzanne C. , Kaye Kim Sutker , Cordero Joehassin
Published: January 2021

We present the case of a 38-year-old man with an adenoid cystic carcinoma originating from the ceruminous glands of the external ear canal. The patient subsequently presented with a contralateral brain mass that was also diagnosed as adenoid cystic carcinoma. To our knowledge, contralateral metastasis to the brain of a patient with an adenoid cystic carcinoma of the ceruminous glands has not been reported previously. This rare neoplasm should be considered in the differential diagnosis of poorly differentiated carcinomas metastatic to the central nervous system in patients with occult malignant neoplasms.
Dermoid Cyst (Mature Cystic Teratoma) of the Cecum
Authors: Schuetz Maurice Joseph , Elsheikh Tarik M.
Published: January 2021

The gastrointestinal tract is an unusual site for teratomas to occur. Only 4 prior cases of teratomas involving the cecum have appeared in the English literature, the latest published in 1977. To the best of our knowledge, this is the first report to describe fine-needle aspiration cytologic findings in addition to histologic features of a mature cystic teratoma involving the gastrointestinal tract. A 30-year-old man presented with right upper quadrant abdominal pain and a palpable abdominal mass. Radiographic studies identified a mass lesion inferior to the liver and in close association with the ascending colon. Fine-needle aspiration biopsy showed scant keratinous material and anucleated squamous cells. Right colectomy revealed a cystic mass in the wall of the cecum that contained keratinous material and was lined by stratified granular squamous epithelium with sebaceous glands. Clinical and pathologic features with review of the literature are presented, and the differential diagnosis for pericolic cystic masses is discussed in detail.
Effective Management of Hepatitis C Molecular Testing Improves Test Use Without Compromising Patient Management
Authors: Kukuczka Sara , Grosso Leonard E.
Published: January 2021

Context.—The availability of effective antiviral therapy for hepatitis C has increased the need for molecular detection and quantification of circulating hepatitis C viral particles. The limits of detection differ for the quantitative and qualitative reverse transcriptase polymerase chain reaction (RT-PCR) assays; furthermore, adequate patient assessment requires both detection of hepatitis C virus when it is present and quantitation of the viral load when possible. The combination of these factors promotes the simultaneous ordering of both tests with the possibility of generating redundant test information.

Objective.—To reduce the number of unnecessary hepatitis C tests performed.

Methods.—We established a reflexive testing protocol for quantitative and qualitative RT-PCR testing for hepatitis C.

Results.—During a 3½-month interval, 170 qualitative RT-PCR hepatitis C tests were eliminated (a 59.4% reduction in the number of these tests). This reduction was achieved without a clinically significant change in turnaround time or a compromise of patient care.

Conclusions.—Establishing the quantitative and qualitative RT-PCR tests in-house and adopting the reflexive testing protocol was cost-effective and did not compromise patient management or care.
Radioimmunohistochemistry of Epidermal Growth Factor Receptor in Breast Cancer
Authors: Robertson Kevin W. , Reeves Jonathon R. , Lannigan Alison K. , Going James J. , Cooke Timothy G. , Stanton Peter D.
Published: January 2021

Context.—Conflicting reports of epidermal growth factor receptor (EGFR) expression in breast cancer and inconstant relationships with established prognostic indicators and outcomes suggest difficulties with EGFR measurement.

Objective.—To compare EGFR measurement in a panel of cell lines and in breast carcinomas by radioimmunohistochemistry (R-IHC), conventional immunohistochemistry (IHC), and a ligand binding (LB) assay.

Design.—Eight EGFR-expressing cell lines and 50 primary breast carcinoma specimens were analyzed for EGFR by IHC, R-IHC, and LB assays. A further 153 primary breast cancer specimens were analyzed by R-IHC alone.

Results.—All 3 assays were in good agreement for the cell lines. In the subset of the 50 carcinoma specimens, EGFR was detected by LB assays in 19 (38%) and by IHC in 24 (48%). However, R-IHC detected EGFR in 46 (92%) of 50 and in 186 (92%) of all 203 carcinoma specimens. The LB assay agreed poorly with R-IHC of carcinomas, possibly because the LB assay is sensitive to EGFR-expressing nontumor breast parenchyma in the tissue analyzed. Both IHC and R-IHC on carcinoma specimens agreed better, but 26 carcinoma specimens (52%) in which EGFR was not detectable by IHC had a 10-fold range in receptor level detectable by R-IHC.

Conclusion.—To elucidate the role of EGFR or other growth factor receptors in breast cancer requires accurate, sensitive receptor assays. With its dynamic range, R-IHC returned meaningful results over the entire range of expression actually present in breast cancer, which LB assays and IHC failed to do.
Autopsy Findings in a Human Immunodeficiency Virus–Infected Population Over 2 Decades
Authors: Morgello Susan , Mahboob Rashid , Yakoushina Tatiana , Khan Shafat , Hague Karin
Published: January 2021

Objectives.—To examine autopsy pathology in an urban population infected with the human immunodeficiency virus (HIV) and to determine if age at death and disease frequencies are associated with gender, HIV risk factors, ethnicity, and therapeutic era.

Design and Methods.—Retrospective analysis of autopsy data from 394 HIV-infected adults. The population was divided into 3 therapeutic eras for analysis: group A, 1979–1986; group B, 1987–1995; and group C, 1996–2000.

Results.—Women died at significantly younger ages than men (mean ± SEM age, 38.9 ± 1.0 years vs 42.5 ± 0.64 years), even after adjustment for risk factors, ethnicity, and therapeutic era. This age discrepancy occurred despite a lower prevalence of arteriosclerosis, cachexia, and hepatitis B in women and no significant differences in the frequencies of other infectious diseases. Whites had a longer survival than patients of other ethnicities (mean age at death, 44.7 ± 1.2 years for whites, 39.9 ± 0.80 years for blacks, and 41.3 ± 0.87 years for Hispanic individuals). Renal, cardiac, and splenic pathologies, Mycobacterium avium-intracellulare (MAI) infection, and cachexia were more common in blacks than in whites and/or Hispanic individuals, and cytomegalovirus and systemic lymphoma were more common in whites and Hispanic individuals than in blacks. Diseases associated with intravenous drug use were hepatitis C, cirrhosis, and tuberculosis; those with all sexual risk factors, cytomegalovirus infection, herpes simplex virus infection, and Pneumocystis carinii pneumonia; and those with homosexual risk, Kaposi sarcoma and MAI infection. The prevalence of many disease entities changed over time: compared with the other groups, group C had lower prevalences of many viral and fungal illnesses, MAI infection, systemic lymphoma, cachexia, and Kaposi sarcoma and higher prevalences of hepatitis, cirrhosis, arteriosclerosis, staphylococcal and streptococcal infections, and traumatic lesions. When the data were adjusted for changing demographic and risk composition, the only significant changes in disease frequency for period C were decreased prevalences of PCP and Kaposi sarcoma and increased prevalences of cirrhosis and arteriosclerosis.

Conclusions.—Significant gender- and ethnicity-related differences in age of death occurred in this HIV-infected population, and these differences were not explained by the frequencies of diseases. The lower prevalences of PCP and Kaposi sarcoma in group C are likely a reflection of the impact of potent therapies on causes of mortality. The higher prevalences of cirrhosis and arteriosclerosis suggest that entities not targeted by antiretroviral reconstitution of immunity will play an increasingly important role in HIV-related mortality in the future.
The Postgenomic Era
Authors: Kiechle Frederick L. , Zhang Xinbo
Published: January 2021

Objectives.—To review the advances in clinically useful molecular biological techniques and to identify their applications in clinical practice, as presented at the Tenth Annual William Beaumont Hospital DNA Symposium.

Data Sources.—The 11 manuscripts submitted were reviewed and their major findings were compared with literature on the same topic.

Study Selection.—Manuscripts address creative thinking techniques applied to DNA discovery, extraction of DNA from clotted blood, the relationship of mitochondrial dysfunction in neurodegenerative disorders, and molecular methods to identify human lymphocyte antigen class I and class II loci. Two other manuscripts review current issues in molecular microbiology, including detection of hepatitis C virus and biological warfare. The last 5 manuscripts describe current issues in molecular cardiovascular disease, including assessing thrombotic risk, genomic analysis, gene therapy, and a device for aiding in cardiac angiogenesis.

Data Synthesis.—Novel problem-solving techniques have been used in the past and will be required in the future in DNA discovery. The extraction of DNA from clotted blood demonstrates a potential cost-effective strategy. Cybrids created from mitochondrial DNA-depleted cells and mitochondrial DNA from a platelet donor have been useful in defining the role mitochondria play in neurodegeneration. Mitochondrial depletion has been reported as a genetically inherited disorder or after human immunodeficiency virus therapy. Hepatitis C viral detection by qualitative, quantitative, or genotyping techniques is useful clinically. Preparedness for potential biological warfare is a responsibility of all clinical laboratorians. Thrombotic risk in cardiovascular disorders may be assessed by coagulation screening assays and further defined by mutation analysis for specific genes for prothrombin and factor V Leiden. Gene therapy for reducing arteriosclerotic risk has been hindered primarily by complications introduced by the vectors used to introduce the therapeutic genes. Neovascularization in cardiac muscle with occluded vessels represents a promising method for recovery of viable tissue following ischemia.

Conclusions.—The sequence of the human genome was reported by 2 groups in February 2001. The postgenomic era will emphasize the use of microarrays and database software for genomic and proteomic screening in the search for useful clinical assays. The number of molecular pathologic techniques and assays will expand as additional disease-associated mutations are defined. Gene therapy and tissue engineering will represent successful therapeutic adjuncts.
Influence of Platelet Collagen Receptor Polymorphisms on Risk for Arterial Thrombosis
Authors: Furihata Kenichi , Nugent Diane J. , Kunicki Thomas J.
Published: January 2021

Context.—Collagens are major components of the vascular subendothelium, and the interaction of platelets with collagens initiates normal hemostasis or pathologic arteriothrombosis. Genetic factors that affect the interaction of platelets with collagens could represent risk factors for either arteriothrombosis or excessive hemorrhage. In this regard, we first found that platelet levels of one of the major platelet collagen receptors, integrin α2β1, vary up to 10-fold in normal healthy individuals and that the higher-level phenotype is associated with allele 1 (807T) of the integrin α2 gene. More recently, we found that there is roughly a fivefold range in platelet glycoprotein VI content among normal individuals, which may also influence risk for thromboembolism.

Objective.—To determine if genetic polymorphisms of platelet glycoproteins involved in collagen-related function are associated with higher risk for thrombotic disorders, such as coronary heart disease, myocardial infarction, or stroke.

Methods.—We examined the genetic mechanisms responsible for variation in expression levels of the collagen receptor integrin α2β1 and the potential influence of this variation on risk for thrombotic diseases.

Results.—We found that patients with arteriothrombotic diseases have a higher frequency of α2 allele 1 (associated with higher levels of platelet integrin α2β1). We further found that platelet glycoprotein VI content directly correlates with platelet prothrombinase activity, suggesting that a higher phenotype of platelet glycoprotein VI also may contribute to increased risk of arteriothrombotic diseases.

Conclusion.—Genetic polymorphisms that influence the level or function of platelet collagen receptors need to be seriously considered as genetic risk factors for arteriothrombotic diseases.
Prospects for Microtechnology and Nanotechnology in Bioengineering of Replacement Microvessels
Authors: Moldovan Nicanor I. , Ferrari Mauro
Published: January 2021

Context.—Due to its anticipated curative potential, therapeutic angiogenesis recently became a major preoccupation for the biomedical research community. Most of the related work reported to date employs either biochemical or genetic tools.

Objective.—To identify opportunities for application of the current developments in microtechnology and nanotechnology to the field of therapeutic angiogenesis.

Data Sources.—Survey of recent English-language literature on microvascular tissue engineering in the context of therapeutic angiogenesis. We include our results regarding the role played by microtopographical cues in the progression of angiogenesis, such as those produced during processing of the extracellular matrix by chronic inflammatory cells.

Conclusion.—While notable accomplishments have been identified in the field of tissue engineering of larger vessels, reports on purposeful assembly of microvascular structures with the ability to be transferred in vivo by implantation are still scarce. Under these circumstances, we suggest the development of a new class of implantable biomedical microdevices, that is, “angiogenesis assist devices” (or “angiochips”), and we indicate some of their conceivable applications.
Changes in Automated Complete Blood Cell Count and Differential Leukocyte Count Results Induced by Storage of Blood at Room Temperature
Authors: Gulati Gene L. , Hyland Lawrence J. , Kocher William , Schwarting Rolland
Published: January 2021

Objective.—To delineate changes that occur in various parameters of automated complete blood cell count (CBC) and differential leukocyte count (differential) on prolonged storage of blood at room temperature.

Design.—A CBC and an automated differential were performed on the Coulter Gen.S on 40 K3 (tripotassium ethylenediamine-tetraacetate) EDTA-anticoagulated blood specimens once daily, specimen volume permitting, for 3 to 7 days. Specimens were kept at room temperature throughout the study. The results were tabulated using a personal computer with Excel software. Percent change or absolute difference from the initial value for each parameter for each subsequent day of the study period was calculated.

Results.—Among the CBC parameters, hemoglobin, red blood cell count, and mean corpuscular hemoglobin were stable for the duration of the study (7 days), white blood cell count was stable for at least 3 days (up to 7 days, if the count was within or above the normal range), and platelet count was stable for at least 4 days (up to 7 days, if the count was within or above the normal range). The mean corpuscular volume, mean platelet volume, hematocrit, and red blood cell distribution width each increased, and the mean corpuscular hemoglobin concentration decreased from day 2 onward. Among the differential parameters, the relative percentages and absolute numbers of neutrophils, lymphocytes, and eosinophils tended to increase, whereas those of monocytes trended downward over time. Limited data on basophils did not reveal an appreciable change.

Conclusion.—Blood specimens stored at room temperature for more than 1 day (up to 3 days or possibly longer) were found to be acceptable with some limitations for CBC but not for the differential.
Cavernous Hemangioma of Spermatic Cord
Authors: Liokumovich Pavel , Herbert Mehrdad , Sandbank Judith , Schvimer Michael , Dolberg Leah
Published: January 2021

We present a case of spermatic cord cavernous hemangioma. A 32-year-old man presented with a circumscribed, painless mass in the left side of the spermatic cord. An orchiectomy of the left testicle was performed. A 3 × 3 × 2.5-cm mass was present in the spermatic cord area. Histologic examination and immunohistochemical study showed a benign vascular tumor composed of vascular spaces of varying size. Although cavernous hemangioma can occur in any location, the spermatic cord is an extremely rare site, and, to our knowledge, only a few cases have been previously reported.
Mesenteric Paraganglioma
Authors: Jaffer Shabnam , Harpaz Noam
Published: January 2021

Approximately 5% to 10% of paragangliomas occur in extra-adrenal sites, which can extend from the upper cervical region to the pelvis, parallel to the autonomic nervous system. This distribution corresponds to the embryologic development of the paraganglia from neural crest cells. Rarely, extra-adrenal paragangliomas can also occur aberrantly outside this distribution. We report such a case of extra-adrenal paraganglioma occurring in the anterior mesentery in a 76-year-old man. Two case reports exist in the literature describing extra-adrenal paragangliomas in the posterior mesentery. Normal paraganglionic tissue has been described at the roots of the superior and inferior mesenteric arteries, theoretically explaining the origin of the posterior mesenteric paragangliomas. Our case can best be attributed to the ventral migration of paraganglionic tissue through these vessels to reach the anterior mesentery, where they could potentially give rise to paragangliomas in this site.
Epithelial-Type and Neural-Type Cadherin Expression in Malignant Noncarcinomatous Neoplasms With Epithelioid Features That Involve the Soft Tissues
Authors: Laskin William B. , Miettinen Markku
Published: January 2021

Context.—Transmembrane adhesion molecules, epithelial-type cadherin (ECAD) and neural-type cadherin (NCAD), help in regulating transformations between epithelial and mesenchymal cells in the developing embryo and in maintaining the epithelioid phenotype. Consequently, the presence of epithelioid cells in certain malignant noncarcinomatous neoplasms raises speculation that the expression of ECAD and NCAD in these neoplasms may have diagnostic significance.

Objective.—To investigate the utility of ECAD and NCAD immunoexpression in distinguishing malignant (noncarcinomatous) neoplasms with epithelioid features that involve the soft tissues.

Design.—Membranous immunoreactivity of anti-ECAD and anti-NCAD was evaluated on archived cases selected from the files of the Armed Forces Institute of Pathology.

Results.—Epithelial-type cadherin was found in biphasic synovial sarcoma (35 of 35 cases), malignant melanoma (13/21), monophasic fibrous synovial sarcoma (13/26), clear cell sarcoma (4/9), poorly differentiated synovial sarcoma (3/13), diffuse mesothelioma (4/20), malignant epithelioid peripheral nerve sheath tumor (1/6), and epithelioid sarcoma (5/62). Neural-type cadherin was observed in chordoma (11/11), biphasic synovial sarcoma (30/35), diffuse mesothelioma (14/20), malignant melanoma (14/25), epithelioid sarcoma (24/63), epithelioid angiosarcoma (1/4), poorly differentiated synovial sarcoma (2/13), clear cell sarcoma (1/10), and monophasic fibrous synovial sarcoma (1/26). Eighteen cases of primary cutaneous squamous cell carcinomas all tested positive for ECAD, whereas NCAD was focally observed in 5 cases. No expression of either molecule was observed in cases of epithelioid hemangioendothelioma (n = 9), alveolar soft part sarcoma (n = 8), and extraskeletal myxoid chondrosarcoma (n = 7).

Conclusions.—Epithelial-type and neural-type cadherins are found in a variety of noncarcinomatous neoplasms with epithelioid features that involve the soft tissues and can be utilized, in association with other immunomarkers, in distinguishing chordoma (100% NCAD) from extraskeletal myxoid chondrosarcoma and conventional chondrosarcoma of bone (0% NCAD), squamous cell carcinoma (100% ECAD) from epithelioid sarcoma (8% ECAD), and biphasic synovial sarcoma (100% ECAD) from diffuse mesothelioma (20% ECAD).
Pathologists in a Teaching Institution Assess the Value of the Autopsy
Authors: Bayer-Garner Ilene B. , Fink Louis M. , Lamps Laura W.
Published: January 2021

Context.—With the advent of modern diagnostic technology, use of the autopsy as a means of assessing diagnostic accuracy has declined precipitously. Interestingly, during the same period, the rate of misdiagnosis found at autopsy has not changed.

Objectives.—To ascertain why an autopsy was requested, whether or not questions asked by clinicians were specifically addressed, and what types of misdiagnoses were found.

Design.—One hundred forty-two consecutive autopsy records from the University of Arkansas for Medical Sciences Hospital were reviewed. In the same period, 715 deaths occurred, giving an overall autopsy rate of 20.14%.

Results.—Of the 125 autopsies in which the problem-oriented autopsy request was available for review, a reason for the autopsy was given in only 69 cases (55%). One hundred three clinical questions were asked, and of these, 81 were specifically addressed in the final anatomic diagnosis, 10 were addressed in some part of the autopsy report but not in the final anatomic diagnosis, 10 were not addressed at all, and 2 could not be answered by the autopsy. Sixty-one autopsies revealed 81 misdiagnoses: 47 class I (missed major diagnosis that, if detected before death, could have led to a change in management that might have resulted in cure or prolonged survival) and 34 class II misdiagnoses (missed major diagnosis in which antemortem detection would have not led to a change in management).

Conclusions.—The autopsy continues to be a vital part of medical education and quality assurance. It is important for the clinician to provide a clinical summary and specific clinical questions to be addressed or to speak directly with the pathologist and for the pathologist to provide answers that are easily accessible within the autopsy report. In this way, a problem-oriented autopsy can be performed based on questions raised by the clinician and the pathologist as a result of the gross dissection and microscopic evaluation.
MYCC and MYCN Oncogene Amplification in Medulloblastoma
Authors: Aldosari Naji , Bigner Sandra H. , Burger Peter C. , Becker Laurence , Kepner James L. , Friedman Henry S. , McLendon Roger E.
Published: January 2021

Context.—Brain tumors are the most common solid tumor in childhood, and medulloblastoma is the most common malignant brain tumor in this age group. Cytogenetic abnormalities that have been described in childhood medulloblastoma include loss of 17p, amplification of MYCC (c-myc), amplification of MYCN (N-myc), and isochromosome 17q. Data on these tumors indicate that the frequency of MYCC amplification is 5% to 10%. Fluorescence in situ hybridization is a powerful tool for investigating these features on archival material.

Objectives.—To determine if intratumoral heterogeneity exists for MYCC and MYCN in medulloblastomas and if tumors with amplified MYCC or MYCN exhibit consistent histologic patterns.

Design.—In this fluorescence in situ hybridization study, we investigated the frequency and prognostic significance of MYCC and MYCN amplification in 77 medulloblastomas derived from the Children's Oncology Group.

Results.—MYCC amplification occurred in only 4 (5.2%) of 77 tumors. The 4 patients died of clinically aggressive neoplasms within 7 months of diagnosis. Similarly, 4 of 77 patients' tumors were found to exhibit MYCN amplification, but survival data are incomplete at present, therefore prognostic significance cannot be characterized.

Conclusions.—These data establish the frequency of MYCC amplification in a large cohort of children with medulloblastoma and further suggest that MYCC amplification may be a marker of poor prognosis. Intratumoral heterogeneity was identified for these oncogenes in that 1 patient's tumor exhibited evidence of both MYCN and MYCC amplification, and this patient experienced a shortened survival time.
Placental Transmogrification of the Lung Is a Histologic Pattern Frequently Associated With Pulmonary Fibrochondromatous Hamartoma
Authors: Xu Ruliang , Murray Melissa , Jagirdar Jaishree , Delgado Yara , Melamed Jonathan
Published: January 2021

Context.—Placental transmogrification of the lung is a term introduced to describe a peculiar histologic pattern characterized by formation of placental villuslike structures in the lung parenchyma. It has been reported to occur in association with bullous emphysema and lipomatosis.

Objectives.—To study the relationship between placental transmogrification and pulmonary hamartomas.

Design and Methods.—Reports of 38 cases of pulmonary hamartomas during 18 years (1982–1999) were reviewed. All histologic slides of these cases were examined for the presence of villuslike papillary projections and placenta-like structures. Hamartomas with prominent papillary projections or placenta-like structures were further investigated to assess the histogenesis and proliferation of epithelial and stromal cells. Immunohistochemical analysis was performed on paraffin-embedded tissue using monoclonal antibodies against Ki-67 and thyroid transcription factor 1 (TTF-1) and polyclonal antibodies against c-Kit antigen (a stem cell factor receptor/mast cell growth factor receptor) in conjunction with Leder stain for naphthol-ASD-chloroacetate esterase.

Results.—Placental transmogrification was identified in 6 of 38 cases of pulmonary fibrochondromatous hamartomas. The histologic change consisted of an abundant myxoid or edematous fibroadipose stroma with a respiratory epithelial lining, resulting in papillary projections that resembled immature placental villi. Epithelium lining the papillary projections was positive for TTF-1 (70%–90%) and Ki-67 (3%–5%). In contrast, stromal cells were negative for TTF-1 with only rare cells immunoreactive for Ki-67. A number of stromal spindle cells and occasional cells in epithelium were c-Kit immunoreactive; however, concurrent Leder stain demonstrated that these c-Kit–positive cells were mast cells and not stem cells.

Conclusions.—Placental transmogrification is frequently associated with pulmonary fibrochondromatous hamartomas and may be induced by or associated with a proliferation of lining epithelial components in the hamartomas. The significance of numerous mast cells within stroma of placental transmogrification is unclear and their possible role in inducing stromal proliferation needs to be further evaluated.
False-Positive AxSYM Cardiac Troponin I Results in a 53-Year-Old Woman
Authors: Knoblock Ronald J. , Lehman Christopher M. , Smith Ruth A. , Apple Fred S. , Roberts William L.
Published: January 2021

A number of classes of endogenous antibodies, including heterophile, rheumatoid factor, and autoantibodies, can interfere with immunoassay measurements of many different analytes. Heterophile and rheumatoid factor antibody interferences have been described previously for the AxSYM cardiac troponin I assay. Several commercial products have been developed to neutralize heterophile antibody interferences. We describe a patient with multiple apparently falsely elevated cardiac troponin I results that were unique to the AxSYM analyzer. These cardiac troponin I results diluted linearly. When treated with 2 different heterophile-blocking reagents, the magnitudes of the falsely elevated results increased 17- and 26-fold, and these results also demonstrated dilution linearity. This interfering substance could be removed by passage through an immobilized protein A column and by polyethylene glycol precipitation. It does not appear to be a classic heterophile antibody, nor is it a paraprotein. Laboratorians must remain constantly vigilant for immunoassay interferences that lead to clinically significant inaccurate results and must recognize that accepted methods for detecting and neutralizing the interference may be ineffective.
Megakaryocytes Mimicking Metastatic Breast Carcinoma
Authors: Hoda Syed A. , Resetkova Erika , Yusuf Yasmin , Cahan Anthony , Rosen Paul P.
Published: January 2021

False-positive diagnosis of lymph nodes occurs when a benign element in a lymph node, or in its capsule, is interpreted as metastatic carcinoma. This report describes a patient with breast carcinoma who had megakaryocytes in axillary sentinel lymph nodes mimicking metastatic carcinoma. The patient had no history of a hematologic disease, and we found no evidence of a concurrent hematopoietic disorder. The megakaryocytes were reactive for CD31, CD61, and von Willebrand factor, but not for cytokeratin (AE1/AE3). Megakaryocytes should be added to the list of benign histologic abnormalities that may simulate metastatic carcinoma in a sentinel lymph node.
Increased Apoptosis in Infiltrating Mononuclear Cells of Colorectal Cancer
Authors: Chen George G. , Lee Janet F. Y. , Chan Ursula P. F. , Xu Hu , Ip Ping C. , Lau Wan Y.
Published: January 2021

Context.—Disturbance in apoptosis has been proposed as one of the mechanisms involved in the immune response targeting tumor outgrowth. How colorectal cancer cells escape from attack by the immune system is not yet fully understood.

Objective.—To investigate apoptotic molecules associated with colorectal cancer counterattack.

Design and Setting.—Tissue samples of colon from 12 patients with colorectal cancer were collected and analyzed by immunostaining. In addition to tumorous tissues, corresponding nontumorous specimens of colon were obtained as controls.

Main Outcome Measures.—We examined the expression of Bcl-2, Bcl-xl, Bax, caspase-3, and inducible nitric oxide synthase in infiltrating mononuclear cells of colorectal cancer tissues and also in colorectal cancer tissues. The TUNEL assay was used to detect in situ apoptosis.

Results.—Apoptosis was barely detectable in specimens of colorectal cancer, which was consistent with an increase in Bcl-2 level and a decrease in caspase-3 level. In contrast, infiltrating mononuclear cells of tumorous tissues showed a marked increase in apoptosis compared with those of nontumorous tissues. The increased apoptosis might have resulted from an imbalance of antiapoptotic and proapoptotic molecules, as reflected by reduction of Bcl-2 level and elevation of Bax level. The elevated caspase-3 levels found in this study could be a downstream effector of the Bcl-2 and Bax apoptotic pathways. A significant increase in inducible nitric oxide synthase observed in the infiltrating mononuclear cells might contribute to immunosuppression seen in colorectal cancer.

Conclusion.—It is tempting to speculate that aberrant expression of apoptotic molecules and inducible nitric oxide synthase in infiltrating mononuclear cells provides the underlying mechanism through which colorectal cancer cells escape attack by the immune system and subsequently grow without control.
Carcinomatous Arteriopathy as an Unusual Feature of Pulmonary Spread of Cholangiocarcinoma Arising in Caroli Disease
Authors: Wang Hanlin L.
Published: January 2021

Carcinomatous arteriopathy is a rare and distinct form of pulmonary spread of solid malignant tumors characterized by fibrointimal proliferation of small pulmonary arteries and arterioles initiated by tumor emboli. Although it has been reported in many types of adenocarcinomas, no case of carcinomatous arteriopathy induced by cholangiocarcinoma has been described in the literature. We report a unique case of cholangiocarcinoma that arose in Caroli disease. Postmortem examination revealed extensive pulmonary vascular spread in the form of carcinomatous arteriopathy.
Brunner Gland Hamartoma With Predominant Adipose Tissue and Ciliated Cysts
Authors: Chatelain Denis , Maillet Evelyne , Boyer Luc , Checkouri Gérard , Mourra Najat , Flejou Jean-François
Published: January 2021

We report an unusual case of Brunner gland hamartoma of the duodenal bulb with multiple ciliated cysts in a 43-year-old man. The patient presented with regurgitation. An endoscopy of the upper digestive tract revealed the presence of a pedunculated tumor of the first duodenum. Surgical resection of the antrum and first duodenum was performed. The polypoid lesion measured 3.5 cm and was located in the submucosa. It was composed of predominant adipose tissue containing hyperplastic lobules of Brunner gland and cystic ducts lined by ciliated cells. Brunner gland hamartoma is a rare benign duodenal lesion; it is usually composed of mature but disorganized tissues and is found most commonly in the duodenum. The presence of ciliated cells in the gut mucosa is a rare phenomenon, which has already been described in the esophagus and stomach. We report an unusual case of ciliated metaplasia in a duodenal Brunner gland hamartoma.
Cystic Adenomatoid Change Is Common to Various Forms of Cystic Lung Diseases of Children
Authors: Imai Yukihiro , Mark Eugene J.
Published: January 2021

Context.—Congenital cystic adenomatoid malformation, intralobar sequestration, extralobar sequestration, bronchopulmonary foregut malformation, bronchial atresia, and lobar emphysema generally are treated as separate entities, but there are commonalities among them.

Objective.—To clarify the identity of congenital cystic adenomatoid malformation in relation to other cystic diseases.

Design.—We studied 10 consecutive cases of surgically resected cystic lung disease in children. We studied the bronchial and vascular trees by mapping bronchi, pulmonary blood vessels, systemic blood vessels, the size and configuration of cysts, and associated scarring.

Results.—The cystic lesions proved to be the following: 1 case of congenital cystic adenomatoid malformation, 2 cases of bronchial atresia with congenital cystic adenomatoid malformation, 1 hybrid case of congenital cystic adenomatoid malformation and intralobar sequestration, 1 case of intralobar sequestration with an aberrant hilum, 3 cases of intralobar sequestration with bronchial obliteration, 1 case of lung abscess, and 1 case of lobar emphysema. Congenital cystic adenomatoid malformation was the sole pathologic diagnosis in 1 case, but 7 other specimens had cystic adenomatoid change to various degrees. There was no bronchial connection between the cystic lesions and the patient's airway in 8 cases. The bronchial tree was absent in the cystic lung in 2 cases. Bronchus tapered into scar near the cystic lesion in 4 cases. Only 1 case had no significant bronchial abnormality.

Conclusion.—The high incidence of cystic adenomatoid change in cystic lung disease associated with an abnormality of the bronchial tree suggests that cystic adenomatoid change may develop together with and be related to other congenital or acquired conditions in the lung.