bluuebunny/crossref_metadata_2025 huggingface dataset:
The Assessment of Pathologists/Laboratory Medicine Physicians Through a Multisource Feedback Tool
Authors: Lockyer Jocelyn M. , Violato Claudio , Fidler Herta , Alakija Pauline
Published: February 2021

Context.—There is increasing interest in ensuring that physicians demonstrate the full range of Accreditation Council for Graduate Medical Education competencies.

Objective.—To determine whether it is possible to develop a feasible and reliable multisource feedback instrument for pathologists and laboratory medicine physicians.

Design.—Surveys with 39, 30, and 22 items were developed to assess individual physicians by 8 peers, 8 referring physicians, and 8 coworkers (eg, technologists, secretaries), respectively, using 5-point scales and an unable-to-assess category. Physicians completed a self-assessment survey. Items addressed key competencies related to clinical competence, collaboration, professionalism, and communication.

Results.—Data from 101 pathologists and laboratory medicine physicians were analyzed. The mean number of respondents per physician was 7.6, 7.4, and 7.6 for peers, referring physicians, and coworkers, respectively. The reliability of the internal consistency, measured by Cronbach α, was ≥.95 for the full scale of all instruments. Analysis indicated that the medical peer, referring physician, and coworker instruments achieved a generalizability coefficient of .78, .81, and .81, respectively. Factor analysis showed 4 factors on the peer questionnaire accounted for 68.8% of the total variance: reports and clinical competency, collaboration, educational leadership, and professional behavior. For the referring physician survey, 3 factors accounted for 66.9% of the variance: professionalism, reports, and clinical competency. Two factors on the coworker questionnaire accounted for 59.9% of the total variance: communication and professionalism.

Conclusions.—It is feasible to assess this group of physicians using multisource feedback with instruments that are reliable.
Increased Mean Platelet Volume in Patients With Acute Coronary Syndromes
Authors: Lippi Giuseppe , Filippozzi Luca , Salvagno Gian Luca , Montagnana Martina , Franchini Massimo , Guidi Gian Cesare , Targher Giovanni
Published: February 2021

Context.—Despite remarkable progress, the diagnosis of acute coronary syndromes (ACS) is still challenging.

Objective.—The mean platelet volume (MPV), a simple and reliable indicator of platelet size that correlates with platelet activation, might be an emerging cardiovascular risk marker and potentially helpful in stratifying cardiovascular risk.

Design.—We analyzed MPV values in 2304 adult patients who were consecutively admitted during a 1-year period to the emergency department of the University Hospital of Verona for chest pain suggestive of ACS. In all patients, a baseline blood sample was collected for routine hematologic testing, whereas cardiac troponin T measurements were collected both at baseline and after 4, 6, and 12 hours.

Results.—A total of 456 patients (19.8% of total) had ACS. These patients, all having cardiac troponin T levels of 0.03 ng/mL or greater in addition to ischemic electrocardiographic changes, had higher MPV values than non-ACS patients with normal cardiac troponin T levels (median, 8.0 fL [5th to 95th percentiles, 6.7–10.0 fL] versus median, 7.4 fL [5th to 95th percentiles, 6.5–9.5 fL]; P < .001). The diagnostic accuracy of MPV, calculated as the area under the curve by the receiver operating characteristic analysis, was 0.661 (P < .001). At the 9.0-fL cutoff, the negative and positive predictive values of MPV were 83% and 43%, respectively.

Conclusions.—Because MPV is a simple and inexpensive laboratory measurement, it might be considered a useful rule-out test along with other conventional cardiac biomarkers for the risk stratification of ACS patients admitted to the emergency departments.
Update on Nonneoplastic Pulmonary Lymphoproliferative Disorders and Related Entities
Authors: Guinee Donald G.
Published: February 2021

Context.—Recent discoveries have expanded the spectrum of nonneoplastic pulmonary lymphoproliferative disorders and have provided new insights into their pathogenesis and treatment.

Objective.—To review the thoracic manifestations of immunoglobulin (Ig) G4–related sclerosing disease and summarize current concepts and differential diagnosis of follicular bronchiolitis, lymphocytic interstitial pneumonitis, and nodular lymphoid hyperplasia.

Data sources.—Data sources include recent and old articles, cases from the personal files of the author, and cases borrowed with permission from other authors.

Conclusions.—Additional studies will be needed to further refine and add to observations in this evolving area of pulmonary pathology.
Intraorbital Meningiomas: A Pathologic Review Using Current World Health Organization Criteria
Authors: Jain Deepali , Ebrahimi Katayoon B. , Miller Neil R. , Eberhart Charles G.
Published: February 2021

Context.—Meningiomas represent approximately 4% of all intraorbital tumors and can arise from the optic nerve or extend into the orbit from adjacent structures.

Objective.—To examine a cohort of intraorbital meningiomas and use the current World Health Organization (WHO) scheme to assess the effect of changes to the classification of tumors at this site.

Design.—The histopathology and clinical findings of intraorbital meningiomas resected between 1968 and 2008 at our institution were reviewed according to the WHO 2007 classification scheme.

Results.—A total of 51 intraorbital meningiomas were reviewed. The mean age at presentation was 45 years, but 5 tumors arose in children. Two patients were known to have neurofibromatosis type 2, and 1 had inherited retinoblastoma. Orbital meningiomas were more frequently encountered in women (30 cases) than in men (21 cases). In 21 patients, the tumor was associated with the optic nerve. The most common (25 of 51 tumors; 49%) histopathologic subtype was meningothelial. Most (47 of 51; 92%) of the tumors were WHO grade I. Four tumors (8%) were WHO grade II, with 4 or more mitotic figures per 10 high-power fields, brain invasion, chordoid histology, or a combination of these features.

Conclusions.—Intraorbital meningiomas were most frequently of the meningothelial or transitional subtypes and were WHO grade I. One relatively common intracranial subtype, fibrous meningioma, was not encountered. The percentage of WHO grade II tumors in the orbit (8%) is similar to that reported for intracranial tumors using the current grading scheme.
Colorectal Dysplasia in Chronic Inflammatory Bowel Disease: Pathology, Clinical Implications, and Pathogenesis
Authors: Harpaz Noam , Polydorides Alexandros D.
Published: February 2021

Context.—Colorectal cancer, the most lethal long-term complication of chronic inflammatory bowel disease (IBD), is the culmination of a complex sequence of molecular and histologic derangements of the intestinal epithelium that are initiated and at least partially sustained by chronic inflammation. Dysplasia, the earliest histologic manifestation of this process, plays an important role in cancer prevention by providing the first clinical alert that this sequence is underway and serving as an endpoint in colonoscopic surveillance of patients at high risk for colorectal cancer.

Objective.—To review the histology, nomenclature, clinical implications, and molecular pathogenesis of dysplasia in IBD.

Data Source.—Literature review and illustrations from case material.

Conclusions.—The diagnosis and grading of dysplasia in endoscopic surveillance biopsies play a decisive role in the management of patients with IBD. Although interpathologist variation, endoscopic sampling problems, and incomplete information regarding the natural history of dysplastic lesions are important limiting factors, indirect evidence that surveillance may be an effective means of reducing cancer-related mortality in the population with IBD has helped validate the histologic criteria, nomenclature, and clinical recommendations that are the basis of current practice among pathologists and clinicians. Emerging technologic advances in endoscopy may permit more effective surveillance, but ultimately the greatest promise for cancer prevention in IBD lies in expanding our thus far limited understanding of the molecular pathogenetic relationships between neoplasia and chronic inflammation.
Advances in Microscopy Techniques
Authors: Schmolze Daniel B , Standley Clive , Fogarty Kevin E , Fischer Andrew H
Published: February 2021

Context.—Advances in microscopy enable visualization of a broad range of new morphologic features.

Objective.—To review and illustrate advances in microscopy with relevance to pathologists.

Data Sources.—Literature review and new observations.

Results.—Fluorescence microscopy enables multiantigen detection; allows novel optical-sectioning techniques, with some advantages compared to paraffin sectioning; and permits live-cell imaging. Live-cell imaging allows pathologists to move from a period when all diagnostic expertise was reliant on interpreting static images to a period when cellular dynamics can play a role in diagnosis. New techniques have bypassed by about 100-fold what had long been believed to be a limit to the resolution of light microscopy. Fluorescence resonance energy transfer (FRET) appears capable of visualizing diagnostically relevant molecular events in living or fixed cells that are immeasurable by other molecular techniques. We describe applications of 2-photon microscopy, FRET, structured illumination, and the subdiffraction techniques of near-field microscopy, photoactivated localization microscopy, stochastic optical reconstruction microscopy, and stimulated emission depletion microscopy.

Conclusion.—New microscopy techniques present opportunities for pathologists to develop improved diagnostic tests.
Pathology Economic Model Tool: A Novel Approach to Workflow and Budget Cost Analysis in an Anatomic Pathology Laboratory
Authors: Muirhead David , Aoun Patricia , Powell Michael , Juncker Flemming , Mollerup Jens
Published: February 2021

Context.—The need for higher efficiency, maximum quality, and faster turnaround time is a continuous focus for anatomic pathology laboratories and drives changes in work scheduling, instrumentation, and management control systems.

Objective.—To determine the costs of generating routine, special, and immunohistochemical microscopic slides in a large, academic anatomic pathology laboratory using a top-down approach.

Design.—The Pathology Economic Model Tool was used to analyze workflow processes at The Nebraska Medical Center's anatomic pathology laboratory. Data from the analysis were used to generate complete cost estimates, which included not only materials, consumables, and instrumentation but also specific labor and overhead components for each of the laboratory's subareas. The cost data generated by the Pathology Economic Model Tool were compared with the cost estimates generated using relative value units.

Results.—Despite the use of automated systems for different processes, the workflow in the laboratory was found to be relatively labor intensive. The effect of labor and overhead on per-slide costs was significantly underestimated by traditional relative-value unit calculations when compared with the Pathology Economic Model Tool. Specific workflow defects with significant contributions to the cost per slide were identified.

Conclusions.—The cost of providing routine, special, and immunohistochemical slides may be significantly underestimated by traditional methods that rely on relative value units. Furthermore, a comprehensive analysis may identify specific workflow processes requiring improvement.
Pick Disease: A Brief Overview
Authors: Frederick Justin
Published: February 2021

This article is a brief review of the clinical, radiographic, and pathologic features of Pick disease. It is directed toward residents and fellows in training as well as practicing physicians who might wish to find a concise treatise on this clinicopathologic entity. The pathogenesis and genetics of this disorder are discussed. Included are medical journal articles accessed from computerized medical literature searches of articles published in the last 10 years. Pertinent images have been included where necessary. Although ubiquitously discussed in medical school and residency, Pick disease is nevertheless a relatively uncommon clinicopathologic entity. Recognition of its clinical and pathologic manifestations is critical in correctly diagnosing this illness and subsequently educating family members of the deceased.
Malpractice in Pathology: What to Do When You Are Sued
Authors: Davis Gregory G.
Published: February 2021

A malpractice suit arises when a patient brings legal charges against a physician for suffering that the patient claims to have endured because the physician failed to provide appropriate care. Suffering usually encompasses a measure of misdiagnosis and of rude treatment of the patient by medical staff. Polite treatment of all patients by all laboratory staff will prevent some disputes from ever forming, thus preventing some charges of malpractice. Even if a patient is treated rudely, that rudeness alone is insufficient to justify a charge of malpractice. Attorneys must follow legal guidelines to determine whether the physician's actions caused actual damage. As soon as a physician is served notice of a lawsuit, the physician must notify the office that insures him or her against claims of malpractice (eg, the office of risk management or the physician's malpractice insurance carrier). Being sued creates an overwhelming urge to talk about the case, but a physician who has been sued must not talk to anyone about the lawsuit or the case involved. Conversations about the lawsuit may only safely be had with the attorney who will defend the physician against the charge of malpractice. Despite any frustrations with the legal system, the physician must work with and even trust the attorney handling the defense. It is possible to overcome a charge of malpractice, but not if the physician creates an indefensible situation by committing fraud. Examples of fraud are changing the medical record or destroying the pertinent microscope slide.
Thyroid Tumors With a Follicular Growth Pattern: Problems in Differential Diagnosis
Authors: Suster Saul
Published: February 2021

Tumors of the thyroid characterized by a follicular growth pattern constitute the most common type of lesion of this organ encountered by pathologists. The vast majority of such lesions do not pose difficulties for histopathologic interpretation. A subset of these tumors, however, can represent a serious challenge for diagnosis. Thyroid tumors with a follicular growth pattern include a broad range of lesions that range from benign, hyperplastic nodules to follicular adenomas to follicular carcinomas. In addition, other types of tumors belonging in separate diagnostic categories can also present histologically with a follicular growth pattern, including the follicular variant of papillary thyroid carcinoma and medullary carcinoma. The histologic features and diagnostic criteria used for distinguishing among these conditions can often be subtle and subjective.
Detection of the JAK2V617F Mutation in Myeloproliferative Disorders by Melting Curve Analysis Using the LightCycler System
Authors: Olsen Randall J. , Tang Zhouwen , Farkas Daniel H. , Bernard David W. , Zu Youli , Chang Chung-Che
Published: February 2021

Context.—A specific mutation, JAK2V617F, was recently recognized as having diagnostic value for myeloproliferative disorders. No practical assay is currently available for routine use in a clinical laboratory.

Objective.—We report the development of a real-time polymerase chain reaction melting curve analysis assay that is appropriate for molecular diagnostics testing.

Design.—Specific primers and fluorescence resonance energy transfer probes were designed, and patients with a previously diagnosed myeloproliferative disorder, de novo acute myeloid leukemia, or reactive condition were selected. The DNA was extracted from fresh and archived peripheral blood and bone marrow specimens, and real-time polymerase chain reaction melting curve analysis was performed on the LightCycler platform (Roche Applied Science, Indianapolis, Ind).

Results.—The JAK2 region was successfully amplified, and wild-type amplicons were reproducibly discriminated from JAK2V617F amplicons. Titration studies using homozygous wild-type and mutant cell lines showed the relative areas under a melting curve were proportional to allele proportion, and the assay reliably detected one mutant in 20 total cells. JAK2V617F was identified in patients previously diagnosed with a myeloproliferative disorder or acute myeloid leukemia transformed from myeloproliferative disorder, whereas a wild-type genotype was identified in patients with reactive conditions or de novo acute myeloid leukemia.

Conclusions.—These findings demonstrate the suitability of this assay for identifying JAK2V617F in a clinical laboratory setting. Furthermore, the semiquantitative detection of JAK2V617F in archived specimens provides a new tool for studying the prognostic significance of this mutation.
BRAF Mutations in Melanocytic Lesions and Papillary Thyroid Carcinoma Samples Identified Using Melting Curve Analysis of Polymerase Chain Reaction Products
Authors: Hay Robert , MacRae Erin , Barber Duane , Khalil Moosa , Demetrick Douglas J.
Published: February 2021

Context.—Mutations of the proto-oncogene B-raf (BRAF) have been detected in melanocytic lesions and papillary carcinomas of the thyroid, and identification of these mutations could be useful in resolving some diagnostic problems.

Objective.—To develop a method to evaluate mutations of BRAF that could provide results much more rapidly than conventional polymerase chain reaction and DNA sequencing assays.

Design.—An assay using a LightCycler was developed to evaluate DNA sequences encoding amino acids within the activation loop of BRAF.

Results.—Using this real-time polymerase chain reaction method, we analyzed 55 paraffin-embedded melanoma or nevus samples. The V600E mutation was found in 0 (0%) of 13 samples diagnosed histologically as Spitz nevi, 9 (24.3%) of 37 invasive melanomas, and 5 (100%) of 5 other melanocytic nevi. Two additional mutations, V600K and VK600-1E, also were identified in cases of invasive melanoma. We analyzed 14 paraffin-embedded papillary thyroid cancer (PTC) samples, 6 of which showed the V600E mutation. We found that our test worked efficiently with fine-needle aspirate specimens, and it identified 6 V600E mutations in 10 fine-needle aspirate specimens diagnosed as PTC. We also identified 4 V600E mutations in 6 specimens of PTC metastatic to lymph node. Unlike the melanocytic lesions, the PTC specimens yielded only V600E mutations. Comparison of our real-time polymerase chain reaction results with conventional polymerase chain reaction and DNA sequencing demonstrated 100% concordance. Surprisingly, we did not identify the previously reported VK600-1E or K601E mutations in our PTC specimens.

Conclusions.—Our results show that the real-time polymerase chain reaction method is a rapid and accurate method for identifying BRAF mutations, such as V600E, in both paraffin-embedded tissue and fine-needle aspirate specimens.
Epithelioid and Epithelial Neoplasms of Bone
Authors: Deyrup Andrea T. , Montag Anthony G.
Published: February 2021

Context.—Epithelioid and epithelial neoplasms seen in bone are rare and include epithelioid variants of vascular lesions, osteoblastoma, osteosarcoma, chordoma, and chondroblastoma as well as adamantinoma and metastatic carcinoma.

Objective.—To provide an overview of tumors with epithelioid histology and address the clinical context and diagnostic issues.

Data Sources.—Pertinent literature is reviewed with emphasis on recent and controversial issues.

Conclusions.—The differential diagnosis in epithelioid/ epithelial lesions of bone is limited. The primary consideration in many cases is distinguishing primary from metastatic lesions.
Overexpression of CD24: Association With Invasiveness in Urothelial Carcinoma of the Bladder
Authors: Choi Yoon-La , Lee Seung-Hyun , Kwon Ghee-Young , Park Cheol-Keun , Han Jae-Joon , Choi Jong Sun , Choi Han Yong , Kim Seok-Hyung , Shin Young Kee
Published: February 2021

Context.—CD24, originally described as a B-cell marker, has gained considerable attention in tumor research. High rates of CD24 expression have been found in several types of carcinomas that are significantly associated with a more aggressive course of the disease. To our knowledge, the expression of CD24 in urothelial carcinoma (UC) of the bladder has not been previously reported.

Objective.—To determine the expression of CD24 in UCs and the association between CD24 levels and tumor grade and stage.

Design.—Urothelial carcinomas (48 cystectomy, 87 transurethral biopsy), including 56 pTa, 29 pT1, 19 pT2, and 31 pT3, were analyzed immunohistochemically using an anti-CD24 monoclonal antibody. The intensity of CD24 staining was semiquantitatively scored as high-level or low-level expression.

Results.—In normal urothelium, CD24 was localized to the cytoplasm of the luminal cell layer with very low intensity. CD24 expression was upregulated in noninvasive UCs, and a high level of expression was correlated with the tumor grade (P = .003). Invasive UCs demonstrated strong diffuse cytoplasmic overexpression of CD24 and the difference in CD24 expression between invasive and noninvasive UC was statistically significant (P < .001).

Conclusions.—CD24 protein is overexpressed in a significant number of bladder UCs. The high level of CD24 expression with loss of apical localization is a marker for stromal invasion and high tumor grade in UC. This study provides the basis for future investigations of CD24 as a potential serum marker or target of antibody-based therapeutics in bladder UC.
Selected Diagnostic Problems in Neoplastic Dermatopathology
Authors: DiCaudo David J. , McCalmont Timothy H. , Wick Mark R.
Published: February 2021

Context.—Selected cutaneous neoplasms share features with benign counterparts or have subtle morphologic features that could be overlooked by the pathologist.

Objective.—To present clues to the diagnosis of potentially deceptive malignancies, including desmoplastic malignant melanoma, nevoid malignant melanoma, subcutaneous lymphoma, metastatic breast carcinoma, and epithelioid sarcoma.

Data Sources.—Published literature and personal experience.

Conclusions.—Knowledge of commonly misdiagnosed cutaneous neoplasms will help the general surgical pathologist avoid these potential pitfalls in neoplastic dermatopathology.
Histopathology of Serrated Adenoma, Its Variants, and Differentiation From Conventional Adenomatous and Hyperplastic Polyps
Authors: Li Shuan C. , Burgart Lawrence
Published: February 2021

Context.—Serrated adenomas can be morphologically subdivided into traditional and sessile types. They are thought to have a comparable rate of cancer progression like conventional adenomas, but they potentially have a faster rate of growth through methylation pathway(s). They share similar morphologic features with both the conventional adenoma and the hyperplastic polyp in a fashion that is different from a mixed adenoma and a hyperplastic polyp.

Objective.—To describe the histopathologic features of traditional serrated adenoma and sessile serrated adenoma and their comparison with traditional adenomas and hyperplastic polyp.

Data Sources.—Relevant articles in peer-review journals and the authors' working experience as practicing surgical pathologists with a specific interest in gastrointestinal pathology.

Conclusions.—Both types of serrated adenomas, traditional serrated adenoma and sessile serrated adenoma, are morphologically distinct, clinically important entities, and they can be diagnosed accurately in routine practice.
Basal/Myoepithelial Cells in Chronic Sinusitis, Respiratory Epithelial Adenomatoid Hamartoma, Inverted Papilloma, and Intestinal-Type and Nonintestinal-Type Sinonasal Adenocarcinoma: An Immunohistochemical Study
Authors: Ozolek John A. , Barnes E. Leon , Hunt Jennifer L.
Published: February 2021

Context.—The pathogenesis of respiratory epithelial adenomatoid hamartoma (REAH) and inverted papilloma (IP) is poorly understood, especially compared with sinonasal adenocarcinoma (SNAC). One feature of malignant glandular lesions is loss of the basal/myoepithelial layer. The immunophenotype of the basal/myoepithelial layer has not been fully examined in benign glandular lesions of the sinonasal tract.

Objective.—To examine benign and malignant glandular lesions in the sinonasal tract for the immunophenotype of basal/myoepithelial cells, proliferation index, and cytokeratin and intestinal differentiation profiles.

Design.—Sinonasal adenocarcinoma (intestinal-type adenocarcinoma [ITAC] and nonintestinal type adenocarcinoma [non-ITAC]), REAH, IP, and chronic sinusitis (CS) were stained for cytokeratin (CK) 7, CK20, 34βE12, CDX-2, p63, Ki-67, smooth muscle actin (SMA), S100 protein, and calponin.

Results.—Basal/myoepithelial cells in CS and REAH were positive for p63 and 34βE12 but negative for SMA, S100 protein, and calponin. Proliferative activity was localized to the compartment containing p63-positive cells. Inverted papilloma demonstrated broad areas staining for p63 and 34βE12, with intermediate proliferative activity in these areas. Sinonasal adenocarcinoma had the highest Ki-67 labeling index, and p63-positive SNACs had higher proliferation indices than p63-negative SNACs. REAH, IP, CS, and most SNACs expressed CK7. Only SNAC expressed CK20. Sixty percent of morphologic ITACs expressed CDX-2.

Conclusions.—Basal/myoepithelial cells in CS and REAH should be considered basal and not myoepithelial cells. In benign lesions, proliferative activity is limited to the compartments with p63 staining. In SNAC and IP, p63 expression correlates with proliferation index. REAH, IP, and CS share similar immunoprofiles (CK7+, CK20−, and CDX-2−), contrasting with SNAC (CK7+, CK20+/−, CDX-2−/+).
MUC4 Expression in Non–Small Cell Lung Carcinomas: Relationship to Tumor Histology and Patient Survival
Authors: Kwon Kun Y. , Ro Jae Y. , Singhal Nicholas , Killen Deanna E. , Sienko Anna , Allen Timothy C. , Zander Dani S. , Barrios Roberto , Haque Abida , Cagle Philip T.
Published: February 2021

Context.—Mucin 4 (MUC4) is a high-molecular-weight membrane–bound glycoprotein that is expressed in the foregut before epithelial differentiation. It is found in normal adult airway epithelium, non–small cell lung carcinoma (NSCLC) and in other human malignancies independent of mucus secretion. Although its tissue distribution has been studied, its utility in predicting prognosis in NSCLC is unknown.

Objective.—To evaluate the relationship between MUC4 overexpression and long-term survival in patients with NSCLC.

Design.—Immunohistochemical staining for MUC4 was performed on formalin-fixed, paraffin-embedded tissue samples from 343 cases of NSCLC arranged in a high-density tissue microarray. Information about long-term survival and tumor stage was collected for all patients. Semiquantitative assessment of MUC4 staining was correlated with survival (Kaplan-Meier analysis).

Results.—MUC4 was frequently expressed in adenocarcinomas (151/187 [81%]), squamous cell carcinomas (69/ 88 [78%]), adenosquamous carcinomas (6/8 [75%]), and large cell carcinomas (33/60 [55%]). High levels of expression (combined score, 2+/3+) for MUC4 were more characteristic of adenocarcinomas (126/187 [68%]) and adenosquamous carcinomas (6/8 [75%]) than of squamous cell carcinomas (46/88 [52%]) and large cell carcinomas (17/60 [28%]) (P < .001). In patients with stage I and II adenocarcinoma, there was a trend toward longer patient survival with higher levels of MUC4 immunoreactivity compared with lower levels (P = .11).

Conclusion.—MUC4 expression is common in pulmonary adenocarcinomas and may indicate a more favorable prognosis in early-stage adenocarcinomas.
Current Risks of Transfusion-Transmitted Agents: A Review
Authors: Stramer Susan L.
Published: February 2021

Context.—Infectious disease testing has dramatically improved the safety of blood for transfusion in the United States, especially since the introduction in 1999 of nucleic acid amplification testing. In 2004, methods (primarily culturing) for detecting bacteria in platelets were also added.

Objective.—To provide current risk estimates for the likelihood of viral transmission by test-negative blood components and to illustrate the safety improvements since the introduction of bacterial testing of platelets.

Data Sources.—Published literature from 1999 through 2006 and unpublished American Red Cross data sources.

Conclusions.—The risk of human immunodeficiency virus and hepatitis C virus transmission through blood transfusion since the introduction of nucleic acid amplification testing is approximately 1 in 2 million. Hepatitis B virus risk, for which nucleic acid amplification testing is not performed routinely, remains at 1 in 200 000 to 500 000 using a combination of anti–hepatitis B core and hepatitis B surface antigen testing. Seven cases of transfusion-transmitted West Nile virus have been reported since the introduction of nucleic acid amplification testing in 2003, but none has been reported since system-wide implementation of processes to increase the test sensitivity for use in epidemic areas. The residual risk of receiving a bacterially contaminated platelet component with clinical consequences is estimated at approximately 1 in 75 000, if culture negative and 1 in 33 000 if not tested by culture methods.
Adenoid Cystic Carcinoma of the Bartholin Gland: An Overview
Authors: Woida Francesca Maia , Ribeiro-Silva Alfredo
Published: February 2021

Vulvar carcinoma is the fourth most frequently encountered malignancy of the female reproductive tract. Among vulvar neoplasms, 0.1% to 5% are of Bartholin gland origin. Primary adenoid cystic carcinoma of the Bartholin gland is very rare. To date, only about 60 cases have been reported in the world literature. Microscopic examination reveals a neoplasm of cribriform pattern composed of nests and columns of cells of bland appearance arranged concentrically around glandlike spaces filled with eosinophilic periodic acid-Schiff–positive diastase-resistant material. Immunohistochemically, the tumor cells express low-molecular-weight keratins, carcinoembryonic antigen, lysozyme, α1-antichymotrypsin, S100, and type IV collagen. Adenoid cystic carcinoma of the Bartholin gland is a slow-growing but locally very aggressive neoplasm with high capacity for recurrence. Perineural and lymphatic invasion is characteristic of this tumor and may explain its propensity for causing pain and recurrence. The treatment may range from simple local excision to radical vulvectomy, with or without partial to complete regional lymphadenectomy.
Lupus Anticoagulant Assays: Questions Answered and to Be Answered
Authors: Teruya Jun , West Aaron G. , Suell Mary Nell
Published: February 2021

Context.—Lupus anticoagulants are antibodies with heterogenous specificities to phospholipids. They have been associated with clinical syndromes consisting of thrombosis and recurrent fetal loss.

Objective.—To address questions about the laboratory assay aspects of lupus anticoagulants. This review is intended for clinicians managing lupus anticoagulant testing in clinical laboratories.

Data Sources.—Published literature on lupus anticoagulants, with emphasis on laboratory assay methods.

Conclusions.—Although there are published criteria for confirming the presence of a lupus anticoagulant, there is no consensus on assay methods for lupus anticoagulant testing. The mixing study is a useful screening test for lupus anticoagulants, but it may have limited utility. Clinical context may necessitate the performance of factor assays in addition to lupus anticoagulant testing to rule out factor deficiency or factor-specific inhibitor. Additionally, the presence of different anticoagulants may affect the reliability of lupus anticoagulant assays. Lupus anticoagulants are an independent risk factor for thrombosis. It may be useful to use different assays when there is clinical suspicion for a lupus anticoagulant. When testing for lupus anticoagulants, clinicians must carefully consider the clinical context because factor assays may also be indicated.
Signet-Ring Cell Adenocarcinoma of Sinonasal Tract: An Immunohistochemical Study of the Mucins Profile
Authors: Castillo Christine , Buob David , Mortuaire Geoffrey , Chevalier Dominique , Aubert Sebastien , Copin Marie-Christine , Leroy Xavier
Published: February 2021

Context.—Adenocarcinomas of the sinonasal tract are classified into 4 categories: salivary-type, intestinal-type, nonintestinal-type, and metastatic. Signet-ring cell carcinoma is the rarest form of intestinal-type adenocarcinoma. Only isolated cases have been reported in the literature.

Objective.—To evaluate clinical attributes, morphology, and immunohistochemistry in signet-ring cell carcinoma of the sinonasal tract.

Design.—Seventy-three cases of primary sinonasal adenocarcinomas were retrieved from the files. Only 5 signet-ring cell adenocarcinomas (tumors composed of more than 90% signet-ring cells) were identified. In all cases, clinical data and histologic slides were available and were reviewed. Consecutive tissue sections were immunostained with monoclonal antibodies against MUC2, MUC5AC, MUC5B, MUC6, p53 protein, and MIB-1.

Results.—Four of our 5 patients were woodworkers. They were treated by surgical excision and radiotherapy. Patient follow-up ranged from 11 to 84 months. Three patients presented an unfavorable evolution and died of metastatic spread. Microscopically, the tumors produced abundant mucin deposits, which accumulated in large extracellular pools. Tumor cells were predominantly signet-ring cells floating in the pools of mucin. The mucins profile was MUC2+, MUC5AC+, MUC5B+, and MUC6−. Eighty percent of cells were immunostained by p53 protein antibody and 60% cells with MIB-1 antibody.

Conclusions.—The mucin profile is similar to the profile described in digestive tract adenocarcinoma. It is not useful to differentiate between metastatic adenocarcinoma and primary intestinal-type sinonasal adenocarcinoma. Clinical data and immunochemistry with p53 protein and MIB-1 confirm that sinonasal signet-ring cell carcinoma is a high-grade and aggressive tumor.
Pulmonary Sarcomatous Tumors
Authors: Litzky Leslie A.
Published: February 2021

Context.—Sarcomatous pulmonary neoplasms are a rare and diagnostically challenging group of tumors. Primary pulmonary sarcomas must be distinguished from the more frequent occurrence of sarcoma metastatic to the lung, primary pulmonary sarcomatoid carcinoma, and diffuse malignant mesothelioma involving the lung. In current practice, the general availability of ancillary diagnostic techniques, such as immunohistochemistry and molecular analysis, can reliably classify many sarcomatoid lesions.

Objective.—To review the literature and report on additional primary material about the application of immunohistochemistry and molecular analysis in the differential diagnosis pulmonary sarcomatous neoplasms.

Data Sources.—Literature review of relevant articles indexed in PubMed (National Library of Medicine) between 1961 and 2007 and primary material from the author's institution.

Conclusions.—This review discusses specific criteria for the diagnosis of primary lung sarcomas and offers a practical approach to excluding other sarcoma-like lesions involving the lung. The pathologist has an essential role in evaluating these tumors and will often be the first to suggest an unusual, alternative diagnosis, which may have significant implications for patient care, therapy, and prognosis.
Primary Hyperparathyroidism: A Current Perspective
Authors: DeLellis Ronald A. , Mazzaglia Peter , Mangray Shamlal
Published: February 2021

Context.—Primary hyperparathyroidism (P-HPT) is one of the most common of all endocrine disorders. Eighty percent to 85% of cases are due to parathyroid adenomas while hyperplasia and carcinoma account for 10% to 15% and less than 1%, of cases, respectively. The past decade has witnessed remarkable advances in the understanding of the molecular basis of parathyroid hyperplasia and neoplasia. Additionally, imaging studies and the development of the intraoperative assay for parathyroid hormone have transformed the diagnosis and management of patients with these disorders.

Objective.—To review the pathology of parathyroid lesions associated with P-HPT, their molecular and genetic bases, including heritable hyperparathyroidism syndromes, and their clinical diagnosis and management.

Data Sources.—Review of pertinent epidemiology, pathology, radiology, and surgery literature on the diagnosis, classification, and treatment of P-HPT.

Conclusions.—Although heritable causes of P-HPT including multiple endocrine neoplasia 1 and 2A and hyperparathyroidism–jaw tumor syndrome account for a minority of cases of P-HPT, advances in the characterization of the affected genes have provided insights into the genetic basis of sporadic parathyroid neoplasms. Alterations in cyclin D1 and loss of heterozygosity of chromosome 11q in adenomas and hyperplasias have provided support for clonality of these lesions. Parafibromin, the protein product of the HRPT2 gene responsible for hyperparathyroidism–jaw tumor syndrome, has been implicated in the development of sporadic parathyroid carcinomas and loss of immunohistochemical expression of this protein has been suggested to be of value in making the diagnosis of parathyroid carcinoma. Sestamibi scanning and ultrasound have revolutionized the planning of surgical approaches and the intraoperative parathyroid hormone assay has become the standard in guiding completion or extension of surgery.
Human Papillomavirus Testing and Reporting Rates: Practices of Participants in the College of American Pathologists Interlaboratory Comparison Program in Gynecologic Cytology in 2006
Authors: Moriarty Ann T. , Schwartz Mary R. , Eversole Galen , Means Marilee , Clayton Amy , Souers Rhona , Fatheree Lisa , Tench William D. , Henry Michael , Wilbur David C.
Published: February 2021

Context.—Oncogenic, high-risk human papillomavirus (HR-HPV) testing is used to evaluate women who are older than 20 years with atypical squamous cells of undetermined significance (ASC-US) and in conjunction with a screening Papanicolaou test in women older than 30 years.

Objectives.—To evaluate the 2006 laboratory practice data from laboratories incorporating human papillomavirus (HPV) testing with the Papanicolaou test.

Design.—To use the College of American Pathologists (CAP) Supplemental Questionnaire Survey for 2006 to determine laboratory practices of participants in the CAP Interlaboratory Comparison Program in Cervicovaginal Cytology.

Results.—A total of 679 laboratories responded to the questionnaire. Most (73%) refer HPV testing to reference laboratories. Nine percent perform HPV testing in cytology. Forty-five percent offer low-risk HPV (LR-HPV) testing. The most common reflex is ASC-US, although HR-HPV is also offered with low-grade squamous intraepithelial lesion (LSIL), high-grade squamous intraepithelial lesion (HSIL), or any other Papanicolaou test result. Digene Hybrid Capture II is the most common method. Human papilloma virus median test volumes are 55 monthly. Frequency distributions of HPV test volumes are significantly different from those found in 2003. Laboratories performing in-house testing reported significantly higher monthly HPV volumes (P < .001). Median rates for HR-HPV positivity are 36.6% for ASC-US, 50.0% for atypical squamous cells, cannot exclude HSIL (ASC-H), and 4% for women 30 years of age and older in conjunction with a screening Papanicolaou test.

Conclusions.—Reference HPV testing remains the most common pattern. The most common reflex indication is for ASC-US, but HPV testing is modified locally to include a variety of scenarios. LR-HPV testing is commonly offered despite its lack of clinical significance. These data form a baseline for ongoing monitoring of HPV testing practice trends.
Choroid Plexus Carcinoma
Authors: Gopal Purva , Parker John R. , Debski Robert , Parker, Jr Joseph C.
Published: February 2021

Choroid plexus carcinoma is an uncommon neoplasm of the central nervous system most commonly found in the pediatric population. It is associated with a dismal prognosis, especially if incompletely resected. Accurate histopathologic diagnosis is imperative, and this neoplasm should always be included in the differential diagnosis of a papillary intraventricular tumor. Histopathologic features include blurring of papillary architecture, layers of neoplastic choroid plexus epithelial cells with pleomorphic nuclei, increased nuclear-to-cytoplasmic ratio, increased mitotic activity, areas of necrosis, and brain invasion. Current accepted treatment is gross total surgical resection of the tumor as the goal. Use of adjuvant chemotherapy is controversial at this time; however, it is considered in some cases.
Lipoblastoma: Appreciation of an Expanded Spectrum of Disease Through Cytogenetic Analysis
Authors: Ende Lauren , Upton Joseph , Richkind Kathleen E. , Vargas Sara O.
Published: February 2021

Lipoblastomas are rare soft tissue tumors that predominantly affect the pediatric population. We describe a lipoblastoma of the right hand in a 16-month-old boy. Radiographically the tumor appeared large but fairly well circumscribed and composed primarily of fat. Pathologic evaluation revealed variably sized lobules of adipose tissue and myxoid immature mesenchymal tissue separated by prominent fibrous trabeculae. Cytogenetic analysis showed a clonal chromosomal rearrangement with a breakpoint involving chromosome 8q11.2, confirming the diagnosis of lipoblastoma and thus helping to expand the clinicopathologic spectrum of tumors in this diagnostic category.
An Integrative Approach for Analyzing the Interplay of Genetic and Epigenetic Changes in Tumors
Authors: Muradyan Artur , Boldt Vivien , Steininger Anne , Stabentheiner Stephanie , Tebel Katrin , Kreutzberger Jürgen , Müller; Ines , Madle; Hannelore , Popper Helmut H. , Ullmann Reinhard
Published: February 2021

The accumulation of chromosomal aberrations is a characteristic feature of tumor development. However, an understanding of tumorigenesis that assumes that changes in DNA copy number always cause equivalent changes in the corresponding RNA and protein levels is an oversimplification and completely ignores the individual genetic and epigenetic context in which an aberration has to be evaluated. We present a brief introduction to various techniques dedicated to the genome-wide analysis of genetic and epigenetic changes, and illustrate how complementary information derived from these various DNA array-based technologies can lead to a better understanding of the consequences of chromosomal aberrations.
Survey of Critical Value Reporting and Reduction of False-Positive Critical Value Results
Authors: Dighe Anand S. , Jones Jay B. , Parham Sue , Lewandrowski Kent B.
Published: February 2021

Context.—Reporting of laboratory critical values has become an issue of national attention because of important regulatory, medicolegal, and clinical concerns.

Objective.—To survey aspects of the laboratory critical-value reporting process at a broad range of institutions.

Design.—A survey was developed regarding the operational and information-technology aspects of critical value reporting.

Results.—More than 730 responses were obtained from a broad distribution of hospitals. In addition, we analyzed more than 700 written responses from survey participants.

Conclusions.—The survey results provide insight into the standard of practice and level of compliance with current Joint Commission and College of American Pathologists requirements for critical values, demonstrate considerable heterogeneity, and suggest areas for improvement. A common issue raised during the survey and follow-up teleconference was the incidence of outpatient false-positive critical values. In this report, we also demonstrate that attention to preanalytic transport and processing issues can assist in minimizing this issue.
Immunohistochemistry in Gynecologic Pathology
Authors: Deavers Michael T.
Published: February 2021

Although most diagnoses in gynecologic pathology are established through the examination of routine hematoxylin-eosin–stained slides, immunohistochemical studies can be of assistance in some cases. The following case studies are used to illustrate the value of some relatively new markers in the diagnosis of gynecologic neoplasms and to highlight potential diagnostic pitfalls.
Application of Immunohistochemistry to the Genitourinary System (Prostate, Urinary Bladder, Testis, and Kidney)
Authors: Hammerich Kai Hans , Ayala Gustavo E. , Wheeler Thomas M.
Published: February 2021

Context.—The variety of morphologic patterns of different entities of the genitourinary tract can present a diagnostic dilemma for the pathologist. This is especially true in cases of mimics of cancer, a cancer of unknown primary, or poorly differentiated tumors, in which it is hard to assign histogenesis needed to plan the correct therapy for the patient. Immunohistochemistry offers a better capacity than hematoxylin-eosin staining alone to differentiate human tissue types. Also, in the past decades, several techniques had been developed to differentiate between benign and malignant processes with morphologic overlap. By using immunohistochemistry in selected cases, the rate of false-negative and false-positive diagnoses can be reduced, and some patients are afforded the opportunity to get more specific or effective therapy as a result.

Objective.—For each subgroup of genitourinary system tumors, common diagnostic problems are reviewed, and immunohistochemical markers useful in addressing these problems are discussed, along with expected patterns of immunoreactivity.

Data Sources.—The pertinent literature, with focus on immunohistochemical staining of tumors of the genitourinary tract.

Conclusions.—The addition of immunohistochemistry to the diagnostic armamentarium for genitourinary pathologic diagnosis has increased the sensitivity and specificity of diagnoses and aided in the selection of optional therapeutic regimens in selected cases.