bluuebunny/crossref_metadata_2025 huggingface dataset:
Primary and Metastatic Lung Tumors in the Pediatric Population: A Review and 25-Year Experience at a Large Children's Hospital
Authors: Dishop Megan K. , Kuruvilla Supriya
Published: February 2021

Context.—Primary lung neoplasms are rare in children, but they comprise a broad and interesting spectrum of lesions, some of which are familiar from other tissue sites, and some of which are unique to the pediatric lung.

Objective.—To determine the relative incidence of primary and metastatic lung tumors in children and adolescents through a single-institution case series, to compare these data to reports in the medical literature, to discuss the clinical and pathologic features of primary tumors of the tracheobronchial tree and lung parenchyma in children, and to provide recommendations for handling pediatric lung cysts and tumors.

Data Sources.—A 25-year single institutional experience with pediatric lung tumors, based on surgical biopsies and resections at Texas Children's Hospital from June 1982 to May 2007, an additional 40 lung tumors referred in consultation, and a review of the medical literature.

Conclusions.—A total of 204 pediatric lung tumors were diagnosed at our institution, including 20 primary benign lesions (9.8%), 14 primary malignant lesions (6.9%), and 170 secondary lung lesions (83.3%). The ratio of primary benign to primary malignant to secondary malignant neoplasms is 1.4:1:11.6. The common types of lung cancer in adults are exceptional occurrences in the pediatric population. The most common primary lung malignancies in children are pleuropulmonary blastoma and carcinoid tumor. Other primary pediatric lung tumors include congenital peribronchial myofibroblastic tumor and other myofibroblastic lesions, sarcomas, carcinoma, and mesothelioma. Children with primary or acquired immunodeficiency are at risk for Epstein-Barr virus–related smooth muscle tumors, lymphoma, and lymphoproliferative disorders. Metastatic lung tumors are relatively common in children and also comprise a spectrum of neoplasia distinct from the adult population.
Avoiding Underdiagnosis, Overdiagnosis, and Misdiagnosis of Lung Carcinoma
Authors: Butnor Kelly J.
Published: February 2021

Context.—Given the magnitude of the therapeutic and prognostic implications, it is critical that pathologists diagnose lung cancer accurately. This can sometimes be a formidable challenge, as a number of benign entities mimic lung carcinoma and vice versa.

Objective.—To present strategies for recognizing benign entities likely to be confused with lung carcinoma, malignancies of the lung prone to misinterpretation as benign, and commonly misclassified pulmonary neoplasms.

Data Sources.—The medical literature and experience from consultative and surgical practice.

Conclusions.—In addition to understanding the clinical context in which a lung biopsy is procured and the radiographic findings, appreciating the histologic distribution of disease and what, if any, pathologic features are present in the background can go a long way toward averting a misdiagnosis of lung cancer. Recognizing the limitations posed by small samples and communicating clearly to clinicians the level of diagnostic uncertainty are equally as important for establishing an accurate diagnosis of lung cancer.
Diffuse Large B-Cell Lymphoma
Authors: Hunt Kristin E. , Reichard Kaaren K.
Published: February 2021

Diffuse large B-cell lymphoma is the most common lymphoma worldwide. Both morphologically and prognostically it represents a diverse spectrum of disease. Traditional morphologic subclassification often results in poor interobserver reproducibility and has not been particularly helpful in predicting outcome. Recent gene expression profiling studies have classified diffuse large B-cell lymphoma into 2 main subtypes, germinal center B-cell and activated B-cell, with the germinal center type showing an overall better survival. Validation of these subtypes has become possible for the practicing pathologist with the use of surrogate immunohistochemical markers. Importantly however, these prognostic studies were performed on material from the pre-rituximab treatment era. With the now well-accepted addition of rituximab (anti-CD20 antibody) to the typical large B-cell lymphoma chemotherapeutic regimen, a revalidation of any survival differences between the large B-cell lymphoma subgroups is necessary. This short review covers the current clinical, morphologic, immunophenotypic, genetic, gene expression profiling, and prognostic (studies before and after the addition of rituximab) features of de novo diffuse large B-cell lymphoma.
The Thyroid Hürthle (Oncocytic) Cell and Its Associated Pathologic Conditions: A Surgical Pathology and Cytopathology Review
Authors: Montone Kathleen T. , Baloch Zubair W. , LiVolsi Virginia A.
Published: February 2021

Context.—Hürthle cells are eosinophilic, follicular-derived cells that are associated with a variety of nonneoplastic and neoplastic thyroid lesions. The differential diagnosis of Hürthle cell lesions is quite broad.

Objective.—To review the pathologic conditions associated with Hürthle cells in the thyroid and to discuss pathology of thyroid lesions associated with oncocytic cytology.

Data Sources.—A variety of thyroid nonneoplastic (autoimmune thyroiditis, multinodular goiter) and neoplastic conditions (Hürthle cell adenoma, Hürthle cell carcinoma) are associated with Hürthle cell cytology. In addition, there are several thyroid neoplasms that should be considered when one observes a Hürthle cell neoplasm in the thyroid (oncocytic variant of medullary carcinoma, several variants of papillary thyroid carcinoma).

Conclusions.—Oncocytic cytology is seen in a variety of thyroid conditions that are associated with a broad differential diagnosis and care must be used for accurate diagnosis. Newer molecular-based techniques may be useful for further classification of thyroid neoplasms with oncocytic pathology.
Nontuberculous Mycobacterial Infections
Authors: Jarzembowski Jason A. , Young Michael B.
Published: February 2021

Context.—Nontuberculous mycobacteria include numerous acid-fast bacilli species, many of which have only recently been recognized as pathogenic. The diagnosis of mycobacterial disease is based on a combination of clinical features, microbiologic data, radiographic findings, and histopathologic studies.

Objective.—To provide an overview of the clinical and pathologic aspects of nontuberculous mycobacteria infection, including diagnostic laboratory methods, classification, epidemiology, clinical presentation, and treatment.

Data Sources.—Review of the pertinent literature and published methodologies.

Conclusions.—Nontuberculous mycobacteria include numerous acid-fast bacilli species, many of which are potentially pathogenic, and are classified according to the Runyon system based on growth rates and pigment production. Their slow growth hinders cultures, which require special medium and prolonged incubation. Although such methods are still used, newer nucleic acid–based technologies (polymerase chain reaction and hybridization assays) can rapidly detect and speciate some mycobacteria—most notably, distinguishing Mycobacterium tuberculosis from other species. Infections caused by these organisms can present as a variety of clinical syndromes, not only in immunocompromised patients but also in immunocompetent hosts. Most common among these are chronic pulmonary infections, superficial lymphadenitis, soft tissue and osteoarticular infections, and disseminated disease. Treatment of nontuberculous mycobacterial infections is difficult, requiring extended courses of multidrug therapy with or without adjunctive surgical intervention.
Pulmonary and Cardiovascular Complications of Obesity: An Autopsy Study of 76 Obese Subjects
Authors: Haque Abida K. , Gadre Swarupa , Taylor Jerrod , Haque Sajid A. , Freeman Daniel , Duarte Alex
Published: February 2021

Context.—Obesity is associated with sleep disordered breathing and cardiovascular morbidity, but the relationship between pulmonary hypertension, heart disease, and obesity is unknown.

Objective.—To determine the prevalence of pulmonary and cardiovascular disease in obese subjects undergoing autopsy at a large medical center.

Design.—A search through autopsy records from an 11-year period identified 76 subjects with a body mass index greater than 30 kg/m2 and 46 age-matched, nonobese controls. Clinical data were collected from medical charts and autopsy records. Formalin-fixed, paraffin-embedded sections of lungs and heart were reviewed for each subject. The presence of pulmonary edema, hemorrhage, diffuse alveolar damage, thrombi, and pulmonary hypertensive changes, including intimal fibrosis, medial hypertrophy, muscularization of arterioles, alveolar capillary hemangiomatosis, hemosiderosis, and iron encrustation were documented. Hearts were examined for the presence of cardiomegaly, ventricular hypertrophy, coronary artery atherosclerosis, acute infarction, fibrosis, and inflammation. Differences between the obese and control groups were compared using a statistical software program.

Results.—The obese group demonstrated a greater occurrence of diabetes mellitus, systemic hypertension, pulmonary edema, hemorrhage, and pulmonary hypertensive changes compared with the control group. Alveolar capillary hemangiomatosis was exclusively observed in the obese subjects. Cardiomegaly and left ventricular hypertrophy were present in all obese subjects; approximately one third of the obese subjects had no coronary atherosclerosis.

Conclusions.—Pulmonary hypertensive changes, including venous hypertension and capillary hemangiomatosis, were observed in 72% of obese subjects. Cardiomegaly with biventricular hypertrophy was present in all obese subjects and was suggestive of obesity cardiomyopathy.
No Correlation Between Lipoprotein(a) and Biochemical Markers of Renal Function in the General Population
Authors: Lippi Giuseppe , Salvagno Gian Luca , Montagnana Martina , Targher Giovanni , Franchini Massimo , Guidi Gian Cesare
Published: February 2021

Context.—Lipoprotein(a) (Lp(a)) is receiving major emphasis as an independent risk factor for cardiovascular disease. Results of studies on Lp(a) in patients with impaired renal function are contradictory, and no information is available on the association between Lp(a) and estimated glomerular filtration rate and cystatin C.

Objective.—To evaluate the potential relationships among the biochemical markers creatinine, estimated glomerular filtration rate, and cystatin C and their association with Lp(a) in patients with impaired renal function.

Design.—We performed a retrospective analysis using the database of our laboratory to retrieve results of Lp(a), creatinine, and cystatin C tests performed on consecutive outpatients referred by general practitioners for routine blood testing during the last year.

Results.—Cumulative results for all of the above-mentioned variables were retrieved for 150 adults older than 35 years. After stratifying Lp(a) values according to thresholds of creatinine, estimated glomerular filtration rate, and cystatin C, no significant differences in Lp(a) concentration were observed in subjects with abnormal values of these biochemical markers. The prevalence of Lp(a) values greater than or equal to 300 mg/L was not significantly different in subjects with biochemical markers suggestive of impaired renal function, as compared with those without such markers. In multivariable linear regression analysis, none of the parameters tested was significantly associated with Lp(a).

Conclusions.—We suggest that unless renal function is completely compromised, measurement of biochemical markers of renal function might be relatively unimportant to improve clinical usefulness of Lp(a) testing.
Practical Approach to the Pathologic Diagnosis of Gastritis
Authors: Sepulveda Antonia R. , Patil Madhavi
Published: February 2021

Context.—Most types of gastritis can be diagnosed on hematoxylin-eosin stains. The most common type of chronic gastritis is Helicobacter pylori gastritis. Reactive or chemical gastropathy, which is often associated with nonsteroidal anti-inflammatory drug use or bile reflux, is common in most practices. The diagnosis of atrophic gastritis can be challenging if few biopsy samples are available and if the location of the biopsies in the stomach is not known, such as when random biopsies are sampled in one jar. If the biopsy site is not known, immunohistochemical stains, such as a combination of synaptophysin and gastrin, are useful in establishing the biopsy location.

Objective.—To demonstrate a practical approach to achieving a pathologic diagnosis of gastritis by evaluating a limited number of features in mucosal biopsies.

Data Source.—In this article, we present several representative gastric biopsy cases from a gastrointestinal pathology practice to demonstrate the practical application of basic histopathologic methods for the diagnosis of gastritis.

Conclusions.—Limited ancillary tests are usually required for a diagnosis of gastritis. In some cases, special stains, such as acid-fast stains, and immunohistochemical stains, such as for H pylori and viruses, can be useful. Helicobacter pylori immunohistochemical stains can particularly contribute (1) when moderate to severe, chronic gastritis or active gastritis is present but no Helicobacter organisms are identified upon hematoxylin-eosin stain; (2) when extensive intestinal metaplasia is present; and (3) in follow-up biopsies, after antibiotic treatment for H pylori.
“Give Us This Day Our Daily Bread”—Evolving Concepts in Celiac Sprue
Authors: Upton Melissa P.
Published: February 2021

Context.—Celiac sprue affects genetically susceptible individuals, who develop small intestinal injury and malabsorption following dietary exposure to gluten. The histologic features are nonspecific but characteristic.

Objectives.—To outline the histologic features of celiac sprue and the necessary clinical context to permit a diagnosis of celiac sprue, to assist the pathologist to identify artifactual biopsy changes that may mimic sprue, to define the differential diagnosis for conditions with a similar histology, and to review historic investigations of this disease.

Data Sources.—Sources include the historic experiments and clinical work of members of the Gastroenterology Division of the Department of Medicine and experiences with gastrointestinal pathology consultation material at the University of Washington, Seattle, with reference to selected peer-reviewed articles.

Conclusions.—Confirmation of a diagnosis of celiac sprue is 2-fold: first, biopsy evidence of a characteristic, but nonspecific, pattern of injury including villous blunting or flattening, surface enterocyte damage, and increased intraepithelial lymphocytes; and second, dramatic clinical response to a gluten-free diet. Complete gluten removal from the diet is effective treatment for patients with symptoms of malabsorption; however, lifelong adherence to the diet is expensive, socially limiting, and nearly impossible on a contemporary diet with manufactured foodstuffs. Therefore, pathologists should avoid overdiagnosis of celiac disease based on minimal, nonspecific histologic changes.
Colorectal Carcinoma: Selected Issues in Pathologic Examination and Staging and Determination of Prognostic Factors
Authors: Kay Washington Mary
Published: February 2021

Context.—Colorectal carcinoma is one of the most common types of cancer in Western countries and is consistently ranked among the top 3 causes of cancer-related deaths, with approximately 150 000 new cases in the United States and 55 000 deaths in 2006. The pathologist's assessment of tumor stage and stage-independent morphologic features, such as vascular/lymphatic invasion, influences treatment strategies for the individual patient, such as the decision to offer adjuvant therapy after surgery. However, although the pathologist influences clinical care in colorectal cancer, certain aspects of staging and evaluation of prognostic factors remain challenging and confusing.

Objectives.—To present the currently used colorectal cancer staging system; to address challenging areas in pathologic staging, including T category considerations and recommendations for the minimum number of lymph nodes sampled; and to discuss assessment of selected stage-independent prognostic factors, such as vascular/ lymphatic invasion.

Data Sources.—This review is based on the current staging manual from the American Joint Committee on Cancer, the College of American Pathologists Protocol for Examination of Specimens From Patients With Primary Carcinomas of the Colon and Rectum, and selected articles pertaining to colorectal carcinoma staging and prognostic factors accessible through Ovid Medline (National Library of Medicine, Bethesda, Md).

Conclusions.—Proper assessment of pathologic staging for colorectal cancer and of morphologic prognostic factors requires a thorough understanding of staging guidelines and careful specimen dissection and sampling.
Comparison of Quantitative Immunofluorescence With Conventional Methods for HER2/neuTesting With Respect to Response to Trastuzumab Therapy in Metastatic Breast Cancer
Authors: Giltnane Jennifer M. , Molinaro Annette , Cheng Huan , Robinson Andrew , Turbin Dmitry , Gelmon Karen , Huntsman David , Rimm David L.
Published: February 2021

Context.—Selection for trastuzumab therapy depends on a companion diagnostic assessment of HER2 by either immunohistochemistry (IHC) for protein overexpression or fluorescence in situ hybridization (FISH) to detect gene amplification. Although many studies have compared IHC to FISH, few have compared the tests to the true gold standard, tumor response.

Objective.—To compare HER2 testing by FISH and IHC along with a third immunofluorescence-based assay (automated quantitative analysis–tissue microarray [AQUA-TMA]) and to assess the value of each test for prediction of response to trastuzumab.

Design.—Immunohistochemistry and FISH assays were done on both whole slides (IHC-WS and FISH-WS) and on TMAs (IHC-TMA and FISH-TMA). AQUA was only done on TMAs (AQUA-TMA). Response was assessed according to modified Response Evaluation Criteria in Solid Tumors.

Results.—AQUA-TMA scores showed a significant linear relationship to both the FISH signal ratio and IHC scores on whole sections and TMAs. Assay assessment by outcome showed no association between response and FISH-WS ratio (P = .96), FISH-TMA (P = .55), IHC-WS (P = .75), or IHC-TMA (P = .06), but a significant relationship between AQUA score and categoric response was observed (P = .01). Assessed as a function of outcome using models of logistic regression, both AQUA-TMA and IHC-TMA were equally significant (P = .01). FISH-WS was the most sensitive assay, with a significantly higher true-positive fraction than all other tests except AQUA-TMA, although it was the least specific. IHC-TMA was the most specific assay. The lowest misclassification rate was achieved using AQUA-TMA (0.30).

Conclusions.—Both AQUA-TMA and IHC-TMA were substantially more predictive than the FISH or IHC-WS tests. Although these results are derived from a small retrospective series, they suggest that accurate measurement of protein expression and unbiased selection of tissue for measurement may be key factors in prediction of response.
CpG Island Methylator Phenotype in Colorectal Cancers: Comparison of the New and Classic CpG Island Methylator Phenotype Marker Panels
Authors: Lee Sun , Cho Nam-Yun , Yoo Eun Joo , Kim Jung Ho , Kang Gyeong Hoon
Published: February 2021

Context.—CpG island methylator phenotype (CIMP) designates a subset of colorectal cancers featuring concordant hypermethylation of multiple promoter CpG islands. Little is known about the clinical outcome or histologic characteristics of CIMP-positive colorectal cancers defined by recently identified CpG island methylator phenotype panels.

Objective.—To investigate and compare the molecular and clinicopathologic features of CIMP-positive colorectal cancers defined by classic (p16, hMLH1, MINT1, MINT2, MINT31) and new (CACNA1G, IGF2, NEUROG1, RUNX3, SOCS1) CIMP panels.

Design.—We analyzed 130 colorectal cancers for hypermethylation of both panels using methylation-specific polymerase chain reaction.

Results.—With at least 2 markers methylated, both classic (39/130; 23.1%) and new (23.1%) CIMP-positive colorectal cancers were significantly associated with proximal tumor location, microsatellite instability, and BRAF mutation (all P values were less than .05). The new panel outperformed the classic panel in detecting these features. With at least 3 markers methylated, new CIMP-positive colorectal cancers (16.9%) were closely associated with proximal tumor location, low frequency of KRAS mutation, and high frequency of BRAF mutation (all P values were less than .05), whereas classic CIMP-positive colorectal cancers (18.5%) were closely associated with proximal tumor location, frequent microsatellite instability, and frequent BRAF mutation (all P values were less than .05). Analyzing a combination of CIMP and microsatellite instability status, CIMP-positive/microsatellite instability–negative colorectal cancers had the worst clinical outcomes.

Conclusions.—Whereas the classic panel outperformed in predicting clinical outcome, the new panel was superior in detecting known clinicopathologic features of CIMP but inferior in prognostication power.
Diagnostic Problems With Trophoblastic Lesions
Authors: Deavers Michael T. , Kalhor Neda , Silva Elvio G.
Published: February 2021

The purpose of this review is to address some common problems involving the diagnosis of trophoblastic lesions.
Accuracy of Send-Out Test Ordering: A College of American Pathologists Q-Probes Study of Ordering Accuracy in 97 Clinical Laboratories
Authors: Valenstein Paul N. , Walsh Molly K. , Stankovic Ana K.
Published: February 2021

Context.—Errors entering orders for send-out laboratory tests into computer systems waste health care resources and can delay patient evaluation and management.

Objectives.—To determine (1) the accuracy of send-out test order entry under “real world” conditions and (2) whether any of several practices are associated with improved order accuracy.

Design.—Representatives from 97 clinical laboratories provided information about the processes they use to send tests to reference facilities and their order entry and specimen routing error rates.

Results.—In aggregate, 98% of send-out tests were correctly ordered and 99.4% of send-out tests were routed to the proper reference laboratory. There was wide variation among laboratories in the rate of send-out test order entry errors. In the bottom fourth of laboratories, more than 5% of send-out tests were ordered incorrectly, while in the top fourth of laboratories fewer than 0.3% of tests were ordered incorrectly. Order entry errors were less frequent when a miscellaneous test code was used than when a specific test code was used (3.9% vs 5.6%; P = .003).

Conclusions.—Computer order entry errors for send-out tests occur approximately twice as frequently as order entry errors for other types of tests. Filing more specific test codes in a referring institution's information system is unlikely to reduce order entry errors and may make error rates worse.
Did Sir William Osler Perform an Autopsy at The Johns Hopkins Hospital?
Authors: Lucey Brendan P. , Hutchins Grover M.
Published: February 2021

Sir William Osler was the preeminent internist of his time, who also worked as a pathologist for a considerable period during his career. Between 1876 and 1889, he performed nearly 1000 autopsies in Montreal, Quebec, and Philadelphia, Pa. Many authors concluded that Osler stopped performing autopsies once he moved to Baltimore, Md, because the autopsy service was organized under William Welch, the professor of pathology. However, this assertion has been contradicted by a recent biography of Dr Osler. To reexamine this issue, the autopsy records of The Johns Hopkins Hospital and relevant publications were examined. The evidence suggests that Dr Osler was an enthusiastic, and sometimes engaged, observer of Hopkins autopsies but that he did not function as an autopsy prosector.
Undifferentiated Tumor: True Identity by Immunohistochemistry
Authors: Bahrami Armita , Truong Luan D. , Ro Jae Y.
Published: February 2021

Context.—“Undifferentiated tumor” refers to a heterogeneous group of neoplasms with little or no evidence of differentiation on routine light microscopic morphology.

Objective.—To identify the true identity of undifferentiated tumors by immunohistochemical analysis.

Data Sources.—Review of the pertinent literature and the authors' experience.

Conclusions.—For treatment and prognostic evaluation, it is crucial to delineate whether an undifferentiated neoplasm is epithelial, mesenchymal, melanocytic, or hematopoietic in nature. Application of a screening panel to demonstrate the expression of markers of major lineages is fundamental for determination of the broad category of neoplasia. Because poorly differentiated carcinomas and in particular sarcomatoid carcinomas are known to be heterogeneous in their antigen expression, several epithelial markers in combination may be required to establish the carcinomatous nature of tumor. A diagnostic misinterpretation as a consequence of occasional aberrant or unexpected antigen expression is best avoided by using a broad panel that includes both antibodies that are anticipated to be positive and those that are expected to be negative. In this treatise, the immunohistochemical dissection of undifferentiated tumors on the basis of their morphologic features is outlined, supplemented with algorithmic immunohistochemical analysis for each morphologic category of small round cell tumors, carcinomatous tumors, sarcomatous (or sarcoma-like) tumors, and tumors with histologically overlapping features, including hematolymphoid malignancies, melanoma, and sarcomas with epithelioid appearance. The utility of several organ- or tissue-specific markers in the context of undifferentiated tumors is reviewed.
Application of Immunohistochemistry to the Diagnosis of Primary and Metastatic Carcinoma to the Lung
Authors: Jagirdar Jaishree
Published: February 2021

Context.—Immunohistochemistry is a very valuable and often used tool in the differential diagnosis of lung carcinomas whether primary or secondary to the lung. The most useful application is in distinguishing primary lung tumors from metastatic tumors to the lung from common sites (colon, breast, prostate, pancreas, stomach, kidney, bladder, ovaries, and uterus). Immunohistochemistry also aids in the separation of small cell carcinoma from non–small cell carcinoma and carcinoids particularly in small biopsy specimens limited by artifact. Although there is no “lung-specific tumor marker,” with the help of a relatively restricted marker, thyroid transcription factor 1, it is possible to separate a lung primary from a metastasis with a reasonable degree of certainty. Another lung-specific marker on the horizon is napsin A, which appears to complement thyroid transcription factor 1 in defining a lung primary.

Objective.—To present a practical review and to critique commonly used markers in the differential diagnosis of lung neoplasms and to list valuable immunohistochemical prognostic markers that the pathologist is called on to perform and interpret.

Data Sources.—A comprehensive PubMed data search and personal practical experience.

Conclusions.—With a panel of immunohistochemical markers, it is possible to distinguish or narrow down most lung neoplasms and separate them into meaningful therapeutic categories. In the future as more proteomic and genomic data surface, immunohistochemical markers to newly discovered antigens may become a routine part of prognostication.
Extranodal Lymphoma
Authors: Ferry Judith A.
Published: February 2021

Lymphomas arising in extranodal sites are intriguing. The types of lymphomas encountered vary widely from one extranodal site to another. For many types of extranodal lymphomas, there are distinctive clinicopathologic features, sometimes including association with an underlying immunodeficiency syndrome, autoimmune disease, infection, or other immunologic disorder, or a predilection to affect patients of certain ethnic origins. Presented below is a review of lymphomas that are encountered most often in extranodal sites.
How Well Do We Communicate Autopsy Findings to Next of Kin?
Authors: Keys Elizabeth , Brownlee Carolyn , Ruff Monica , Baxter Cynthia , Steele Lisa , Green Francis H. Y.
Published: February 2021

Context.—A failure of communication among families, physicians, and pathologists is recognized as a major cause of declining autopsy rates and may be involved in increased litigation.

Objective.—To determine how effectively autopsy results are communicated to the next of kin and how satisfied families are with the process from consent to relaying of the results.

Design.—A retrospective telephone survey of next of kin of 106 consecutive patients autopsied at a major teaching hospital. The family was asked questions on the process of obtaining consent and the information they received back from health care providers.

Results.—Thirty-two percent of relatives indicated that they were not adequately informed as to the purpose of the autopsy. Eighty percent of respondents were notified of or obtained the results. The ways in which the autopsy findings were communicated varied, but 54% were involved in a discussion of the results with a medical professional. More than half of the families wished to have a copy of the results. Two-thirds felt they were satisfied with the explanation of the results, but an important cause of dissatisfaction was the use of unfamiliar medical terminology. When the family's understanding of the cause of death was compared with the diagnoses on the autopsy reports, 65% of families demonstrated an accurate knowledge of the autopsy findings, 28% had a general understanding, and for only 8% was their knowledge judged inaccurate. Overall, 92% of notified respondents felt the autopsy had served a useful purpose, mostly for personal reasons.

Conclusions.—We conclude that the autopsy fulfills an important need for many families; however, the purpose of the autopsy and the findings need to be more effectively communicated.
Evaluation of the BiliChek Being Used on Hyperbilirubinemic Newborns Undergoing Home Phototherapy
Authors: Reyes Christine A. , Stednitz Donald R. , Hahn Carol , Mutchie Kelly D. , McCullough Steven R. , Kronberg Kent
Published: February 2021

Context.—Newborns are often screened prior to discharge for hyperbilirubinemia. Transcutaneous bilirubin analyzers, such as the BiliChek, are promoted as screening tools, but it is unclear whether they also function well as monitoring devices. Newborns on home phototherapy require frequent determinations of serum bilirubin levels to monitor therapy effects. A transcutaneous bilirubin analyzer would be helpful to limit blood draws and enhance staff efficiency. We evaluated the accuracy of the BiliChek analyzer in this setting.

Objective.—Is the BiliChek sufficiently accurate to monitor the effectiveness of home phototherapy and establish when to terminate therapy?

Design.—Paired serum bilirubin results and results from the BiliChek were obtained from newborns on home phototherapy during daily home health care visits.

Results.—The BiliChek demonstrates a negative bias (mean bias, −1.71 mg/dL; 95% confidence interval, −1.89 to −1.52 mg/dL) compared with serum bilirubin values. This bias worsens as the serum bilirubin level rises. If a value of 14 mg/dL or less obtained using the BiliChek had been used as the cutoff for termination of phototherapy, 45% of newborns would have had therapy terminated prematurely. If, knowing the negative bias of the BiliChek, the cutoff for termination of therapy was set at less than or equal to 11 mg/dL, then 29% of newborns would have had therapy terminated prematurely.

Conclusions.—The values obtained using the BiliChek, compared to serum bilirubin values, have a negative bias that worsens at the higher bilirubin levels expected in newborns at home on phototherapy. The BiliChek does not provide sufficient accuracy to be utilized to monitor newborns on home phototherapy or to ascertain when to discontinue such therapy.
Monophasic Synovial Sarcoma Arising in the Vulva: A Case Report and Review of the Literature
Authors: White Beverly E. , Kaplan Alan , Lopez-Terrada Dolores H. , Ro Jae Y. , Benjamin Robert S. , Ayala Alberto G.
Published: February 2021

Synovial sarcomas most commonly arise in the soft tissue of the extremities. Less commonly, these tumors present in the head and neck, abdominal wall, and other sites. However, synovial sarcoma occurring in the vulvar area is extremely rare. Only 2 previous cases of biphasic synovial sarcoma of the vulva have been reported, but no case of vulvar monophasic synovial sarcoma has been described in the English literature. We report the third case of synovial sarcoma and apparently the first case of monophasic synovial sarcoma arising in soft tissues of the vulva. The patient was a 33-year-old woman who presented for evaluation of a painless vulvar mass. The tumor was located in the deep fibroadipose tissue of the right vulva (6.5 × 4.2 × 3.5 cm). The histology of the lesion was that of a monophasic synovial sarcoma with a hemangiopericytic vascular pattern. A subsequent molecular analysis revealed SYT-SSX2 gene fusion, which confirmed the diagnosis of synovial sarcoma. After an initial wide local excision, the patient developed a recurrence in the right groin and received chemotherapy and additional surgery. The patient is currently disease free, on adjuvant chemotherapy, and being followed up closely.
Immunophenotypic Study of Basophils by Multiparameter Flow Cytometry
Authors: Han Xiaohong , Jorgensen Jeffrey L. , Brahmandam Archana , Schlette Ellen , Huh Yang O. , Shi Yuankai , Awagu Sylvester , Chen Weina
Published: February 2021

Context.—The immunophenotypic profile of basophils is not yet fully established, and the immunophenotypic changes in chronic myelogenous leukemia are not fully characterized.

Objective.—To establish a comprehensive immunophenotypic spectrum of normal basophils and to assess the range of immunophenotypic aberrations of basophils in chronic myelogenous leukemia.

Design.—Using 4-color flow cytometry, we compared the immunophenotypic profile of basophils in peripheral blood or bone marrow samples from 20 patients with no evidence of neoplasia to basophils from 15 patients with chronic myelogenous leukemia.

Results.—Basophils in control cases were all positive for CD9, CD13, CD22, CD25 (dim), CD33, CD36, CD38 (bright), CD45 (dimmer than lymphocytes and brighter than myeloblasts), and CD123 (bright), and were negative for CD19, CD34, CD64, CD117, and HLA-DR. Basophils in all chronic myelogenous leukemia patients possessed 1 to 5 immunophenotypic aberrancies. The most common aberrancies were underexpression of CD38, followed by aberrant expression of CD64 and underexpression of CD123. CD34 and CD117 were present in cases with basophilic precursors. Myeloblasts showed a distinct immunophenotypic profile, as they typically expressed CD34 and CD117, showed dimmer expression (compared with basophils) of CD38, CD45, and CD123, and lacked expression of CD22.

Conclusions.—Flow cytometric immunophenotyping can identify immunophenotypic aberrations of basophils in chronic myelogenous leukemia, and discriminate basophils from myeloblasts.
Evidence-Based Pathology and the Pathologic Evaluation of Thymomas: Transcapsular Invasion Is Not a Significant Prognostic Feature
Authors: Gupta Ruta , Marchevsky Alberto M. , McKenna Robert J. , Wick Mark , Moran Cesar , Zakowski Maureen F. , Suster Saul
Published: February 2021

Context.—Evaluation of transcapsular invasion is currently considered very important in the pathologic examination of thymomas. However, recent studies have questioned the prognostic value of stratifying thymoma patients into stage I and II disease. Evidence-based pathology promotes the use of systematic reviews of literature and meta-analysis of data to synthesize the results of multiple publications.

Objective.—To analyze the data in the literature regarding the prognostic importance of transcapsular invasion in thymoma stage I and II.

Design.—A systematic review of the English literature was carried out for “thymoma,” “stage,” and “prognoses.” Case reports, case series with fewer than 10 cases, and studies with follow-up periods shorter than 5 years were excluded. Twenty-one retrospective publications reporting the experience with 2451 thymomas were selected for review, including 1419 stage I and 1032 stage II patients. Meta-analysis was performed, and possible publication bias was studied with funnel plots of precision and various statistics.

Results.—Meta-analysis yielded no significant differences in disease-free or overall survival rates in stage I and II thymoma patients. Funnel plots of precision and statistical tests such as the Egger regression intercept test showed no significant publication bias.

Conclusions.—The lack of significant differences in the prognosis of patients with stages I and II thymoma suggests that evaluation of transcapsular invasion is of no clinical value in tumors that lack invasion of neighboring organs or the pleura. The data regarding the prognosis of stage II thymoma patients is somewhat heterogenous, with only some individuals having been treated with radiation therapy, suggesting the need for future randomized controlled trials.
Alveolar Airspace and Pulmonary Artery Involvement by Extramedullary Hematopoiesis: A Unique Manifestation of Myelofibrosis
Authors: Ozbudak Irem H. , Shilo Konstantin , Hale Sabine , Aguilera Nadine S. , Galvin Jeffrey R. , Franks Teri J.
Published: February 2021

Pulmonary extramedullary hematopoiesis is a rare manifestation of myelofibrosis. We encountered a unique case of pulmonary extramedullary hematopoiesis occurring in a 59-year-old white man, where in addition to the typical foci of interstitial hematopoietic cells, a surgical lung biopsy showed airspace and arterial wall involvement. Airspace foci were associated with acute and organizing alveolar hemorrhage, while within arteries the hematopoietic elements had a striking predilection for the vascular intima. The hematopoietic foci included erythroid precursors, myeloid precursors, and megakaryocytes, which were immunoreactive with hemoglobin, myeloperoxidase, and CD61, respectively. Whether extramedullary hematopoiesis represents in situ embryonic stem cell differentiation or a compensatory seeding of hematopoietic cells from the bone marrow remains to be elucidated. However, familiarity with these findings in the lung could be helpful in uncovering occult hematological disorders accompanied by extramedullary hematopoiesis. Extramedullary hematopoiesis should also be considered as a cause of pulmonary hemorrhage, especially in the setting of myelofibrosis.
Surgical Neuropathology Update: A Review of Changes Introduced by the WHO Classification of Tumours of the Central Nervous System, 4th Edition
Authors: Brat Daniel J. , Parisi Joseph E. , Kleinschmidt-DeMasters Bette K. , Yachnis Anthony T. , Montine Thomas J. , Boyer Philip J. , Powell Suzanne Z. , Prayson Richard A. , McLendon Roger E.
Published: February 2021

Context.—The World Health Organization (WHO) recently published its 4th edition of the classification of tumors of the central nervous system, incorporating a substantial number of important changes to the previous version (WHO 2000). The new WHO classification introduces 7 changes in the grading of central nervous system neoplasms, ranging in significance from minor to major, in categories of anaplastic oligoastrocytomas, meningiomas, choroid plexus tumors, pineal parenchymal tumors, ganglioglioma, cerebellar liponeurocytoma, and hemangiopericytomas. The 4th edition also introduces 10 newly codified entities, variants, and patterns, as well as 1 new genetic syndrome. A number of established brain tumors are reorganized, including medulloblastomas and primitive neuroectodermal tumors, in an attempt to more closely align classification with current understanding of central nervous system neoplasia.

Objective.—To summarize and discuss the most significant updates in the 4th edition for the practicing surgical pathologist, including (1) changes in grading among established entities; (2) newly codified tumor entities, variants, patterns, and syndromes; and (3) changes in the classification of existing brain tumors.

Data Sources.—The primary source for this review is the WHO Classification of Tumours of the Central Nervous System, 4th edition. Other important sources include the 3rd edition of this book and the primary literature that supported changes in the 4th edition.

Conclusions.—The new edition of the WHO blue book reflects advancements in the understanding of brain tumors in terms of classification, grading, and new entities. The changes introduced are substantial and will have an impact on the practice of general surgical pathologists and neuropathologists.
Podoplanin Expression in Cancerous Stroma Induces Lymphangiogenesis and Predicts Lymphatic Spread and Patient Survival
Authors: Kitano Haruhisa , Kageyama Shun-Ichiro , Hewitt Stephen M. , Hayashi Ryuji , Doki Yoshinori , Ozaki Yoshitomo , Fujino Shozo , Takikita Mikiko , Kubo Hajime , Fukuoka Junya
Published: February 2021

Context.—Podoplanin is a mucin-type glycoprotein and a lymphatic endothelial marker. Immunohistochemical staining for podoplanin is currently used as a routine pathologic diagnosis tool in Japan to identify lymphatic invasion of cancer cells. Recent reports suggest that podoplanin and other proangiogenic molecules are expressed in stromal fibroblasts and myofibroblasts.

Objective.—To analyze the distribution of podoplanin expression in tumor stroma and its clinical and biologic significance.

Design.—We performed immunohistochemistry for podoplanin on tissue microarrays from 1350 cases of 14 common cancer types.

Results.—Two hundred eighty-seven of 662 cases (43%) showed podoplanin expression in the stromal cells within cancer nests. Stromal podoplanin expression in 14 common cancer types was significantly associated with tumor stage (P < .001), lymph node metastases (P < .001), lymphatic invasion (P  =  .02), and venous invasion (P < .001). The stromal cells positive for podoplanin were also positive for α-smooth muscle actin but negative for desmin, confirming a myofibroblasts phenotype. In contrast, myofibroblasts in inflammatory fibrotic lung diseases were podoplanin negative. Lymphatic vessel density was greater in the stromas with podoplanin expression than in the stroma lacking podoplanin-expressing stromal cells (P  =  .01). Survival data were available for non–small cell lung cancer. Stromal podoplanin expression was associated with poorer prognosis in adenocarcinoma (P < .001) and remains statistically significant after adjustment for sex, age, and stage (P  =  .01).

Conclusion.—Our data indicate that podoplanin expression in stromal myofibroblasts may function as a proangiogenic biomarker and may serve as a predictive marker of lymphatic/vascular spread of cancer cells and a prognostic marker of patient survival.
A Practical Approach to Testicular Biopsy Interpretation for Male Infertility
Authors: Cerilli Lisa A. , Kuang Wayne , Rogers David
Published: February 2021

Context.—The combination of testicular biopsy and clinical evaluation for male infertility is becoming progressively more important because new technologies allow men previously considered infertile to father children. Although most general pathologists are experienced with normal, neoplastic, and cryptorchid testicular specimens, the testicular biopsy for infertility requires understanding of a different set of diagnostic categories not otherwise commonly encountered.

Objective.—To highlight a standardized nomenclature for germ cell abnormalities allowing for effective communication with the urologist and maximal clinical benefit from the biopsy.

Data Sources.—Previously published consensus statements, review articles, peer-reviewed research publications, and abstracts.

Conclusions.—A practical approach to evaluating testicular biopsies for fertility and the clinical implications for each abnormality are herein outlined.
Adequacy of Surgical Pathology Reporting of Cancer: A College of American Pathologists Q-Probes Study of 86 Institutions
Authors: Idowu Michael O. , Bekeris Leonas G. , Raab Stephen , Ruby Stephen G. , Nakhleh Raouf E.
Published: February 2021

Context.—Inclusion of all scientifically validated elements in surgical pathology cancer reports is needed for optimal patient care.

Objective.—To evaluate the frequency with which surgical pathology cancer reports contain all the scientifically validated elements required by the American College of Surgery (ACS) Commission on Cancer (CoC), the extent to which checklists are used, and the effects that the use of checklists have on the completeness of cancer reports.

Design.—Participants in the College of American Pathologists voluntary Q-Probes program reviewed 25 consecutive surgical pathology reports to include cancer reports from breast, colon, rectum, and prostate cancer specimens. For each report, the type and total number of missing required elements, deemed essential by the ACS CoC, was recorded.

Results.—A total of 2125 cancer reports were reviewed in 86 institutions; 68.8% of all surgical pathology cancer reports included all the required elements. Institutions in which checklists were routinely used reported all required elements at a higher rate than those that did not use checklists (88% versus 34%), and institutions that had a system in place to track errors also reported all required elements at a higher rate when compared to those that did not have such a system in place (88% versus 68%). The missing mandated elements, common to cancer reports of all tumor types, were extent of invasion and status of the resection margin.

Conclusions.—This study demonstrates that about 30% of cancer reports do not have all the scientifically validated elements required by the ACS CoC. Pathology departments in which checklists are not routinely used have a substantially lower rate of reports that include all the required elements.
Hypomethylation of the DNMT3L Promoter in Ocular Surface Squamous Neoplasia
Authors: Manderwad Guru Prasad , Gokul Gopinathan , Kannabiran Chitra , Honavar Santosh G. , Khosla Sanjeev , Vemuganti Geeta K.
Published: February 2021

Context.—Cancer is known to have epigenetic inputs, with events like genomewide hypomethylation and gene-specific hypermethylation of DNA. The DNA methyltransferase enzymes act as effectors of this reprogramming. A previous study revealed that hypomethylation at the DNA methyltransferase 3-like (DNMT3L) promoter could be a potential biomarker in cervical tumors. Because the pathobiology of ocular surface squamous neoplasia (OSSN) is similar to that of cervical tumors, we wanted to determine whether similar changes occur in the methylation pattern at the DNMT3L promoter in OSSN.

Objective.—To evaluate the methylation status of the DNMT3L promoter in OSSN compared with healthy conjunctiva.

Design.—We evaluated DNA methylation at the DNMT3L promoter in the tumor tissues of 6 patients with histologically proven OSSN and in healthy conjunctiva tissue from 7 individuals for controls using the sodium bisulfite–assisted conversion of genomic DNA. Extracted genomic DNA was treated with sodium bisulfite and amplified with specific primers for the DNMT3L promoter region. The specific polymerase chain reaction products were cloned and sequenced.

Results.—The mean age of these patients was 50.2 years (range, 35–65 years). Histologically, 4 OSSN cases were invasive; 2 were intraepithelial. Healthy conjunctival tissues exhibited a methylated promoter region, whereas a variable loss of methylation was observed in all 6 OSSN cases.

Conclusions.—We have, for the first time to our knowledge, identified loss of methylation at the DNMT3L promoter in OSSN cases, but its physiologic significance is yet to be understood. Further studies are warranted to substantiate our results.