bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparative Analytical Costs of Central Laboratory Glucose and Bedside Glucose Testing: A College of American Pathologists Q-Probes Study
Authors: Howanitz Peter J. , Jones Bruce A.
Published: February 2021

Context.—One of the major attributes of laboratory testing is cost. Although fully automated central laboratory glucose testing and semiautomated bedside glucose testing (BGT) are performed at most institutions, rigorous determinations of interinstitutional comparative costs have not been performed.

Objectives.—To compare interinstitutional analytical costs of central laboratory glucose testing and BGT and to provide suggestions for improvement.

Design.—Participants completed a demographic form about their institutional glucose monitoring practices. They also collected information about the costs of central laboratory glucose testing, BGT at a high-volume testing site, and BGT at a low-volume testing site, including specified cost variables for labor, reagents, and instruments.

Participants.—A total of 445 institutions enrolled in the College of American Pathologists Q-Probes program.

Main Outcome Measure.—Median cost per glucose test at 3 testing sites.

Results.—The median (10th–90th percentile range) costs per glucose test were $1.18 ($5.59–$0.36), $1.96 ($9.51– $0.77), and $4.66 ($27.54–$1.02) for central laboratory, high-volume BGT sites, and low-volume BGT sites, respectively. The largest percentages of the cost per test were for labor (59.3%, 72.7%, and 85.8%), followed by supplies (27.2%, 27.3%, and 13.4%) and equipment (2.1%, 0.0%, and 0.0%) for the 3 sites, respectively. The median number of patient specimens per month at the high-volume BGT sites was 625 compared to 30 at the low-volume BGT sites. Most participants did not include labor, instrument maintenance, competency assessment, or oversight in their BGT estimated costs until required to do so for the study.

Conclusions.—Analytical costs per glucose test were lower for central laboratory glucose testing than for BGT, which, in turn, was highly variable and dependent on volume. Data that would be used for financial justification for BGT were widely aberrant and in need of improvement.
Lipoprotein Lipase Gene Polymorphism and Lipid Profile in Coronary Artery Disease
Authors: Duman Belgin Süsleyici , Türkoğlu Çavlan , Akpınar Belhhan , Güden Mustafa , Vertii Anastassia , Dak Esranur , Çağatay Penbe , Günay Demet , Büyükdevrim A. Sevim
Published: February 2021

Context.—Lipoprotein lipase (LPL) plays a central role in lipid metabolism, hydrolyzing triglyceride in chylomicrons and very-low-density lipoproteins. The PvuII polymorphic variant of LPL gene is common and might affect risk of coronary artery disease (CAD).

Objective.—Our aim was to determine whether LPL– PvuII polymorphism can be considered to be an independent risk factor or a predictor for CAD in Turkish subjects.

Design.—We used polymerase chain reaction and restriction enzyme digestion to determine the distribution of the previously described C→T transition that causes a PvuII polymorphism in intron 6 among healthy blood donors of Turkish origin and among angiographically confirmed CAD patients with comparable ethnic backgrounds.

Results.—For the PvuII genotypes, within the CAD group (n = 80), the +/− genotype was found in 39 individuals (48.8%), whereas 25 (31.3%) carried the +/+ genotype, and 14 (17.5%) carried the −/− genotype. Within the control group (n = 49), the −/− genotype was found in 19 individuals (38.8%), 16 (32.7%) carried the +/− genotype, and 14 (28.6%) carried the +/+ genotype. The genotype frequency distribution was significantly different (P = .049) in the CAD and control study groups. The most frequent genotype among CAD patients was +/−; this genotype was more frequent in patients than in control subjects. However, the −/− genotype was more prevalent in the control group. Lipoprotein lipase–PvuII polymorphism was found to be associated with fasting total cholesterol and low-density lipoprotein cholesterol levels. The +/+ genotype was found to have higher levels of total cholesterol and low-density lipoprotein cholesterol in both the CAD and control groups.

Conclusion.—There was a difference in the distribution of LPL–PvuII genotypes between the healthy subjects and the patients with CAD. Lipoprotein lipase–PvuII polymorphisms were not detected as independent risk factors for CAD in this study group, but had associations with lipid levels.
Pleomorphic Giant Cell Carcinoma of the Prostate
Authors: Lopez-Beltran Antonio , Eble John N. , Bostwick David G.
Published: February 2021

We report the clinical and pathologic features of 2 cases of pleomorphic giant cell carcinoma of the prostate. One case was found at autopsy in a 77-year-old man and was composed of high-grade prostatic adenocarcinoma with prominent anaplastic giant cells. The patient presented with metastases to multiple retroperitoneal lymph nodes, liver, and lumbar vertebrae. The second case occurred in a 45-year-old man who underwent transurethral resection of the prostate and was found to have high-grade prostatic adenocarcinoma with an extensive anaplastic giant cell component. The patient presented with distant metastases and died within 9 months. Both regular adenocarcinoma and anaplastic giant tumor cells displayed cytoplasmic immunoreactivity for prostate-specific antigen, prostatic acid phosphatase, and keratin AE1/AE3; in one case, scattered cells were also positive for chromogranin and epithelial membrane antigen. Pleomorphic giant cell carcinoma is a rare variant of prostatic adenocarcinoma with a poor prognosis that should be considered in the differential diagnosis of prostatic pleomorphic tumors.
Sarcomatoid Renal Cell Carcinoma With Divergent Sarcomatoid Growth Patterns: A Case Report and Review of the Literature
Authors: Li Lin , Teichberg Saul , Steckel Joph , Chen Qiang-hua
Published: February 2021

A 71-year-old woman who presented with left abdominal pain was found to have a noncalcified renal mass with a perisplenic extension on imaging studies. Histologically, the tumor showed predominantly malignant spindle cells with extensive osteoid and chondroid matrix production. Various growth patterns resembling rhabdomyosarcoma, malignant fibrous histiocytoma, and fibrosarcoma were also observed. Immunohistochemistry showed positive staining of the neoplastic cells for cytokeratin and focally positive staining for CD10 and CD117 (c-Kit). Electron microscopic examination revealed a poorly differentiated neoplasm with both mesenchymal and epithelial features. The tumor was diagnosed as a sarcomatoid renal cell carcinoma with overgrowth of the sarcomatoid component (World Health Organization: renal cell carcinoma, unclassified). To our knowledge, sarcomatoid renal cell carcinoma with such a broad morphologic phenotype in a single case has not been documented. Furthermore, the CD117 expression in a sarcomatoid renal cell carcinoma that was observed in this case merits further investigation.
Pseudoglandular Elements in Schwannomas
Authors: Robinson Christopher A. , Curry Bernadette , Rewcastle N. Barry
Published: February 2021

Context.—Uncommon examples of schwannomas are seen in which a coexisting glandular component is present. The pseudoglandular schwannoma is a relatively recently described variant in which cystic spaces are lined by pseudocolumnar or cuboidal-like neoplastic Schwann cells exhibiting an epithelial-like appearance.

Objectives.—To determine the incidence of pseudoglandular elements in schwannomas, to describe the variable morphology of the schwannomas that may contain pseudoglandular elements, and to discuss the potential mechanisms of development and biological significance of these elements.

Design.—We screened 202 schwannomas from any anatomic site for the presence of pseudoglandular elements and examined these with light microscopy, immunohistochemistry, and electron microscopy.

Results.—Sixteen (7.9%) of the schwannomas contained pseudoglandular elements, which ranged from poorly to well organized in appearance and which were found in schwannomas exhibiting a wide range of morphologic appearances. The Schwann cell nature of the cells composing these elements was apparent both immunohistochemically and ultrastructurally. The frequency of proliferative activity within these elements was no greater than that observed throughout the remainder of the respective schwannomas.

Conclusions.—Our observations suggest that, rather than representing a distinct phenotypic schwannoma variant, pseudoglandular elements likely arise as a response to a degenerative phenomenon, perhaps reflecting the propensity that the Schwann cell has to palisade formation. Such elements may be found within a variety of schwannoma variants and do not appear to possess a unique growth potential.
Glomangiomyoma (Glomus Tumor) of the Kidney
Authors: Siddiqui Noman H. , Rogalska Agnieszka , Basil Indu S.
Published: February 2021

We report herein a case of glomus tumor arising in the kidney of a 55-year-old woman, which was found incidentally on a computed tomographic scan. Partial nephrectomy revealed a 2-cm encapsulated mass that was architecturally similar to glomus tumor. Immunohistochemistry showed positivity of tumor cells for vimentin and smooth muscle actin. On electron microscopy, cytoplasmic thin filaments and dense bodies were seen, confirming the smooth muscle nature of the tumor. Glomus tumors arising in visceral organs are rare, and those arising in kidney are exceedingly rare.
Surgical Pathology in the Era of the Civil War: The Remarkable Life and Accomplishments of Joseph Janvier Woodward, MD
Authors: Rapkiewicz Amy V. , Hawk Alan , Noe Adrienne , Berman David M.
Published: February 2021

Joseph Janvier Woodward was an assistant surgeon in the US Army during the Civil War, coauthored the definitive works on the mortality and morbidity of that war, attended at the autopsy of President Lincoln, and attended President Garfield after he was shot. He revolutionized the field of photomicroscopy and was one of the first pathologists to use aniline dyes as tissue stains. Yet despite the occasional biographical sketch every few decades, he is largely unknown today. Herein, we review his contributions to surgical pathology and medicine and present modern-day photomicrographs of 140-year-old slides from Woodward's original collection.
Primary Extraneural Myxopapillary Ependymoma of the Broad Ligament
Authors: Whittemore Darren E. , Grondahl Robert E. , Wong Kondi
Published: February 2021

Primary extraneural ependymomas are rare tumors that arise in ectopic sites, including pulmonary, sacrococcygeal region, ovarian, and paraovarian tissues. Four such ependymomas reported in the literature involve the paraovarian tissues, including 2 broad ligament ependymomas. Here we describe a myxopapillary ependymoma of the broad ligament in a 22-year-old woman, which may be the first tumor of this type to be reported in this location. Cytology, histology, cytochemistry, immunohistochemistry, and flow cytometry ploidy analysis are studied and described. Identification of perivascular ependymal rosettes, ependymal canals, vimentin and glial fibrillary acidic protein immunoreactivity, cytochemical staining of blepharoplasts or terminal bars by phosphotungstic acid hematoxylin, and presence of multiple foci of myxoid degeneration among the ependymal rosettes characterized a myxopapillary ependymoma.
Is There a Set of Histologic Changes That Are Invariably Reflux Associated?
Authors: Takubo Kaiyo , Honma Naoko , Aryal Gopi , Sawabe Motoji , Arai Tomio , Tanaka Yasuo , Mafune Ken-ichi , Iwakiri Katsuhiko
Published: February 2021

Many histologic changes have been described in the esophageal squamous mucosa in patients with gastroesophageal reflux disease (GERD), including dilated intercellular spaces, balloon cells, intrapapillary vessel dilation, elongated papillae, basal cell hyperplasia, acanthosis, intraepithelial eosinophils, Langerhans cells, and p53 protein overexpression. To define a set of histologic changes that are invariably reflux associated, we examined the histologic changes in esophageal specimens from normal controls, patients with GERD, patients without GERD but with a suspicion of other pathology, and patients with esophageal carcinoma. We also examined biopsy specimens from sites with differing endoscopic features, including cloudy white and reddened mucosa. A definitive set of reflux-associated histologic changes could not be defined from the small number of biopsy specimens examined in the present study. Histologic changes indicative of GERD are likely to be found somewhere in the esophagus in all patients with GERD, but these changes are nonspecific. A set of histologic changes that are invariably reflux associated may exist, but these changes are nonspecific. To develop a set of characteristic reflux-associated features, endoscopists may perform targeted biopsies from several sites with various endoscopic features and at different stages of disease.
Frozen Section Examination of Liver, Gallbladder, and Pancreas
Authors: Lechago Juan
Published: February 2021

Context.—Frozen section of the liver is a comparatively frequent request that most often applies to a relatively limited number of situations. The only indication for frozen tissue examination of a gallbladder with any frequency is the presence of a polypoid mucosal lesion or a suspicious thickening of the gallbladder wall. A variety of intraoperative consultations may be applicable during surgery of the pancreas.

Objective.—To examine the indications and pitfalls regarding the gross examination and frozen section performance for liver, gallbladder, and pancreas.

Data Sources.—Author experience and review of the pertinent literature.

Conclusions.—Although indications are relatively straightforward for frozen section of liver and gallbladder, handling of the pancreas specimens for frozen tissue examination is often a cause for a certain degree of anxiety. This situation is the result of a relative rarity of such specimens outside large tertiary referral medical centers coupled with a variety of confounding factors, including the presence of chronic pancreatitis with distortion of the normal structures and the frequent presence of variable degrees of dysplasia. The suboptimal preservation of the frozen tissue adds further angst to the scenario. In this article, the main issues are critically examined in light of the experience of the author and others.
Is There a Way for Pathologists to Decrease Interobserver Variability in the Diagnosis of Dysplasia?
Authors: Montgomery Elizabeth
Published: February 2021

Many obstacles interfere with our efforts to screen patients with Barrett esophagus. Probably the largest is choosing the appropriate patient group for screening. Beyond this problem, sampling error on the part of endoscopists is probably more serious a problem than observer variation among pathologists reviewing patient samples. Pathologists agree well on lesions that merit close follow-up or other intervention (high-grade dysplasia and invasive carcinoma), although interobserver agreement between pathologists interpreting lesser lesions is not good. This lack of agreement is not likely to improve substantially, and many adjunct markers are being sought in an attempt to identify patients with lesions of lower grades that are most likely to progress, allowing doctors to identify patients who would benefit from upgraded surveillance.
Cytologic Features of Low-Grade Squamous Intraepithelial Lesion in ThinPrep Papanicolaou Test Slides and Conventional Smears: Comparison of Cases That Performed Poorly With Those That Performed Well in the College of American Pathologists Interlaboratory Comparison Program in Cervicovaginal Cytology
Authors: Renshaw Andrew A. , Dubray-Benstein Barbara , Haja Jennifer , Hughes Jonathan H.
Published: February 2021

Context.—Both conventional and ThinPrep Papanicolaou smears with high-grade squamous intraepithelial lesions that are frequently missed are known to have relatively few abnormal cells. Whether this is also true of cases of low-grade squamous intraepithelial lesion is not known.

Objective.—To compare the cytologic features of cases of low-grade squamous intraepithelial lesion that perform poorly with the features of cases that perform well.

Design.—The cytologic features of 10 ThinPrep Pap Test and conventional smear cases of low-grade squamous intraepithelial lesion that performed poorly in the College of American Pathologists Interlaboratory Comparison Program were compared with 46 ThinPrep Pap Test and conventional smear cases that performed extremely well. The numbers of abnormal cells were categorized into less than 50, 51 to 100, 101 to 250, 251 to 500, and more than 500.

Results.—The median number of abnormal cells for cases that performed poorly was less than 50, whereas the median number of abnormal cells for cases that performed well was between 101 and 250. Overall, cases that performed poorly were significantly more likely to have less than 50, less than 100, and less than 250 abnormal cells than cases that performed well (P < .001, P < .001, and P = .009, respectively). A minority of cases performed well even with very few abnormal cells and groups. The same findings were present when conventional smears and ThinPrep specimens were analyzed separately.

Conclusions.—ThinPrep Pap Test cases and conventional smears with a diagnosis of low-grade squamous intraepithelial lesion that perform poorly in this program have significantly fewer abnormal cells than those that perform well. The median number of abnormal cells in cases that performed well is lower than that of comparable high-grade cases in the program.
High-Grade Pelvic Osteosarcoma With Intravascular Extension to the Right Side of the Heart: A Case Report and Review of the Literature
Authors: Jani Jigna C. , Massad Malek , Kpodonu Jacques , Alagiozian-Angelova Victoria , Guzman Grace
Published: February 2021

We describe a rare case of high-grade osteosarcoma with intravascular extension to the right atrium and right ventricle in a 23-year-old woman. Osteosarcomas rarely metastasize to the heart, and only a few cases have been reported in the literature thus far. Diagnoses in some of these cases were made during investigation for severe cardiac failure and in most of these cases at autopsy. We describe a unique case of intravascular extension of the tumor embolus in a cordlike fashion from the left femoral vein to the right side of the heart that morphologically resembled a chondrosarcoma.
Creatinine Measurement: State of the Art in Accuracy and Interlaboratory Harmonization
Authors: Greg Miller W. , Myers Gary L. , Ashwood Edward R. , Killeen Anthony A. , Wang Edward , Thienpont Linda M. , Siekmann Lothar
Published: February 2021

Context.—The National Kidney Disease Education Program recommends calculating glomerular filtration rate from serum creatinine concentration. Accurate creatinine measurements are necessary for this calculation.

Objective.—To evaluate the state of the art in measuring serum creatinine, as well as the ability of a proficiency testing program to measure bias for individual laboratories and method peer groups.

Design.—A fresh-frozen, off-the-clot pooled serum specimen plus 4 conventional specimens were sent to participants in the College of American Pathologists Chemistry Survey for assay of creatinine. Creatinine concentrations were assigned by isotope dilution mass spectrometry reference measurement procedures.

Participants.—Clinical laboratories with an acceptable result for all 5 survey specimens (n = 5624).

Results.—The fresh frozen serum (FFS) specimen had a creatinine concentration of 0.902 mg/dL (79.7 μmol/L). Mean bias for 50 instrument-method peer groups varied from −0.06 to 0.31 mg/dL (−5.3 to 27.4 μmol/L), with 30 (60%) of 50 peer groups having significant bias (P < .001). The bias variability was related to instrument manufacturer (P ≤ .001) rather than method type (P = .02) with 24 (63%) of 38 alkaline picric acid methods and with 6 (50%) of 12 enzymatic methods having significant biases. Two conventional specimens had creatinine concentrations of 0.795 and 2.205 mg/dL (70.3 and 194.9 μmol/L) and had apparent survey biases significantly different (P < .001) from that of the FFS specimen for 34 (68%) and 35 (70%) of 50 peer groups, respectively.

Conclusions.—Thirty of 50 peer groups had significant bias for creatinine. Bias was primarily associated with instrument manufacturer, not with type of method used. Proficiency testing using a commutable specimen measured participant bias versus a reference measurement procedure and provided trueness surveillance of instrument-method peer groups.
Myeloid Sarcoma Involving the Breast
Authors: Valbuena Jose R. , Admirand Joan H. , Gualco Gabriela , Medeiros L. Jeffrey
Published: February 2021

Context.—Myeloid sarcoma is a neoplasm of myeloid cells that can arise before, concurrent with, or following acute myeloid leukemia. Rarely, it can also occur as an isolated mass.

Objective.—To describe the clinicopathologic features of 6 patients with myeloid sarcoma involving the breast.

Design.—Clinical information for all 6 patients was obtained from the medical record. Routine hematoxylin-eosin–stained slides; naphthol AS-D chloroacetate stain; and immunohistochemical stains for myeloid, B-cell, and T-cell antigens were prepared.

Results.—There were 6 women with a median age of 52 years (range, 31–73 years). Two patients presented with isolated tumors of the breast, with no history or subsequent development of acute myeloid leukemia. In 3 patients, the breast tumors represented relapse of acute myeloid leukemia. One patient who presented initially with myeloid sarcoma involving the breast, skin, and spleen was lost to follow-up. Histologically, these tumors were classified as well differentiated (n = 3), poorly differentiated (n = 2), and blastic (n = 1). Naphthol AS-D chloroacetate esterase was positive in all 3 cases assessed. Immunohistochemistry showed that myeloperoxidase (n = 5) and CD43 (n = 3) were positive, and CD3 (n = 5) and CD20 (n = 5) were negative in all cases assessed. Lysozyme was positive in 4 (80%) of 5; CD117 was positive in 2 (67%) of 3; and single cases were positive for CD45 (1/3), TdT (1/2), CD79a, and the PAX5 gene product.

Conclusions.—Myeloid sarcoma involving the breast is uncommon. In the literature, as in this study, these tumors most often represent relapse or the initial presentation of acute myeloid leukemia. However, 2 of the cases we report presented with isolated masses, without a history or subsequent development of acute myeloid leukemia at last follow-up. Immunohistochemical studies are extremely helpful for recognizing isolated myeloid sarcoma.
Malignant Deciduoid Mesothelioma: A Diagnostic Challenge
Authors: Mourra Najat , Chaisemartin Cecilede , Goubin-Versini Isabelle , Parc Rolland , Flejou Jean-Francois
Published: February 2021

Malignant deciduoid mesothelioma, a rare phenotype of epithelioid mesothelioma, arises more commonly from the peritoneum of young women, but it is also reported in the pleura of elderly people. We report a case of malignant deciduoid mesothelioma that occurred in a 41-year-old woman after cesarean section and was initially misdiagnosed as pseudotumoral deciduosis. Microscopically, the tumor was entirely composed of deciduoid areas, and only scattered tumor cells were positive for calretinin and keratin 5/6. The patient died 14 months after the first operation. This observation confirms the poor prognosis of this entity and the importance of the differential diagnosis of pseudotumoral deciduosis.
Association of Mild Transient Elevation of Troponin I Levels With Increased Mortality and Major Cardiovascular Events in the General Patient Population
Authors: Gudmundsson G. Steinar , Kahn Stephen E. , Moran John F.
Published: February 2021

Context.—The prognostic value of mild elevation of cardiac-specific troponin I (cTnI) levels is poorly defined, which can make interpretation of such an elevation difficult.

Objective.—To study the prognostic value of transient mild elevation of cTnI levels in the hospitalized patient population.

Design.—We performed a case-control study that compared the outcome of patients hospitalized for any cause with at least 2 subsequent transient cTnI measurements of 0.1 ng/mL or higher and less than 1.5 ng/mL with matched controls with cTnI levels less than 0.1 ng/mL. A cohort of 118 patients (mean ± SD age, 67.4 ± 14.0 years; 35.6% men) was followed up for an average ± SD of 11.9 ± 7.9 months. Seventy-one cases were matched with 37 controls in terms of demographics, coronary artery disease risk factors, and reason for admission. End points were all-cause mortality and major cardiovascular end points, including cardiovascular mortality, myocardial infarction, and revascularization.

Results.—The total event rate was significantly increased in the case group compared with the control group at 12, 6, and 3 months (62.0% vs 24.3%, 59.2% vs 16.2%, and 47.9% vs 5.4%, respectively; P < .001). At 12, 6, and 3 months, the cases had a significant increase in all-cause mortality (43.7% vs 16.2%, 40.8% vs 8.1%, and 33.8% vs 0.0%, respectively; P = .005) and major cardiovascular end points (26.8% vs 8.1%, 26.8% vs 8.1%, and 21.1% vs 5.4%, respectively; P = .02) compared with controls.

Conclusion.—Transient mild elevation of cTnI levels in hospitalized patients is associated with an increase in all-cause mortality and major cardiovascular complications. Such elevations of cTnI levels can be considered a marker for both all-cause and cardiovascular morbidity and mortality.
Regulators of Apoptosis in Cholangiocarcinoma
Authors: Jhala Nirag C. , Vickers Selwyn M. , Argani Pedram , McDonald Jay M.
Published: February 2021

Context.—Dysregulation of mediators of apoptosis is associated with carcinogenesis. For biliary duct cancers, p53 gene mutation is an important contributor to carcinogenesis. Mutations in the p53 gene affect transcription of the Fas gene, resulting in lack of Fas expression on cell membrane. It has been previously shown that cloned Fas-negative but not Fas-positive human cholangiocarcinoma cells are resistant to anti–Fas-mediated apoptosis and develop tumors in nude mice. In addition, interferon gamma induces Fas expression in Fas-negative cholangiocarcinoma cells and makes them susceptible to apoptosis. Therefore, it becomes important to characterize immunophenotypic expression of p53 and Fas in normal and neoplastic human tissues of the biliary tract to further understand the pathogenesis of the disease. To date, human studies to characterize differences in immunophenotypic expression of the Fas protein between intrahepatic and extrahepatic biliary duct cancers and in their precursor lesions have not been performed.

Objective.—To report the immunophenotypic expression of p53 and Fas expression in various stages in the development of bile duct cancers (intrahepatic and extrahepatic tumor location) and their association with tumor differentiation.

Design.—Thirty bile duct cancer samples (13 intrahepatic and 17 extrahepatic) from 18 men and 12 women who ranged in age from 44 to 77 years (mean age, 65.6 years) were retrieved from the surgical pathology files. Hematoxylin-eosin–stained slides were evaluated for the type and grade of tumor and dysplastic changes in the biliary tract epithelium. Additional slides were immunohistochemically stained with p53 and anti–Fas mouse monoclonal antibody. The pattern of Fas distribution and percentage of cells positive for p53 and Fas expression were determined.

Results.—The percentage of Fas-expressing cells is significantly (P = .01) more frequently noted in extrahepatic tumors compared with intrahepatic tumors. Furthermore, Fas expression decreased from dysplastic epithelium to cholangiocarcinoma (P = .01), and this decreasing trend continued from well to poorly differentiated tumors. Nuclear p53 expression was not identified in normal and dysplastic epithelium but was noted in 30% of carcinomas (P = .02).

Conclusion.—Fas expression is an early event in pathogenesis of bile duct cancers. Immunophenotypic expression of Fas is associated with well to moderately differentiated tumors but not with poor tumor differentiation.
Renal Neoplasms in Younger Adults: Analysis of 112 Tumors From a Single Institution According to the New 2004 World Health Organization Classification and 2002 American Joint Committee on Cancer Staging System
Authors: Cao Ying , Paner Gladell P. , Perry Kent T. , Flanigan Robert C. , Campbell Steven C. , Picken Maria M.
Published: February 2021

Context.—Adult renal neoplasms have a predilection for older patients and are clinically and morphologically distinct from renal neoplasms found in pediatric age groups. Relatively rare tumors occur in younger adults (18–45 years of age). Whether these renal tumors are morphologically and clinically distinct from those of older adults has been the subject of controversy. Recent modification of the World Health Organization histologic classification and the American Joint Committee on Cancer staging system of adult renal tumors further highlighted the need for case analysis in this age group.

Objective.—To analyze renal tumors in younger adults based on a large surgical series from a single institution.

Design.—Of 780 renal mass nephrectomy (partial, total, or radical) specimens that were available for evaluation and had been obtained between 1986 and 2004 at Loyola University Medical Center, 112 specimens were from patients between 18 and 45 years of age. The tumors were reevaluated according to the 2004 World Health Organization classification and the 2002 American Joint Committee on Cancer staging system.

Results.—The likelihood of clear cell renal cell carcinoma was significantly reduced from 65% in older adults to 53% in younger adults (18–45 years, P = .04). The reduction trend was more significant when comparing an even younger age group. The majority (64%) of clear cell renal cell carcinoma in younger adults was low stage, T1a. Seventeen percent of these tumors had multilocular cystic features involving more than 50% of the tumor volume (55%–85%). The number of oncocytomas was also significantly lower in younger adults than in older adults (2% vs 11%, P < .001), and this presumably age-related benign neoplasm was not identified in patients younger than 40 years in this study. In contrast, the miscellaneous tumor category showed a remarkable increase, from 4% in older adults to 26% in younger adults (P < .001). The youngest patient group (18–35 years) had a higher incidence of miscellaneous tumors, 37%. Younger female adults tended to have more benign miscellaneous neoplasms than did their male counterparts (64% vs 36%, P < .001). Clear cell and chromophobe renal cell carcinoma occurred more frequently in younger male adults than in female adults (2:1 and 8:1, respectively).

Conclusions.—Renal neoplasms are more heterogeneous in younger adults and have a different distribution pattern compared with that in older adults. Malignant and benign renal neoplasms tend to have a contrasting sex distribution in younger adults.
Comparison of Relative Value of Bone Marrow Aspirates and Bone Marrow Trephine Biopsies in the Diagnosis of Solid Tumor Metastasis and Hodgkin Lymphoma: Institutional Experience and Literature Review
Authors: Moid Farah , DePalma Louis
Published: February 2021

Context.—Bone marrow aspirates as well as bone marrow trephine biopsies are frequently performed to assess whether there is marrow involvement by a malignancy. Numerous reports differ in the relative value of these 2 procedures and fail to provide concise guidelines that can help choose the appropriate technique in this clinical situation.

Objective.—To compare the relative value of aspirates and trephine biopsies in the diagnosis of solid tumor metastasis and Hodgkin lymphoma. In addition, we correlate our findings with those of the literature to provide a concise practice guideline.

Design.—Sixty-six cases showing bone marrow involvement by solid tumor and Hodgkin lymphoma in bone marrow aspirates, bone marrow trephine biopsies, or both were included in the study. The diagnosis and findings made on aspirates were compared with those made on trephine biopsies in each case.

Results.—In those cases where both aspirate and trephine biopsy were available for evaluation, there was a 22% positive correlation in the findings on aspirates and trephine biopsies. The correlation between aspirates and trephine biopsies was highest in cases of small cell carcinoma of the lung (3/11, or 36.3%) followed by breast carcinoma (7/20, or 35%), prostate carcinoma (1/9, or 11.1%), and Hodgkin lymphoma (1/20, or 5%). Two of 5 cases from the miscellaneous category demonstrated simultaneous involvement of aspirate and trephine biopsy by a gastric carcinoma as well as an adrenal gland carcinoma.

Conclusions.—Bone marrow aspirate and bone marrow trephine biopsy should both be performed in patients with proven or suspected malignancies where staging may affect management. However, bone marrow aspirate has only a minimal role, if any, in detecting bone marrow involvement by Hodgkin lymphoma. In cases of breast carcinoma, small cell carcinoma of lung, and prostate carcinoma, aspirate evaluation may confirm trephine biopsy results or, more rarely, provide the sole confirmation of the malignancy.
Screening for Giardia/Cryptosporidium Infections Using an Enzyme Immunoassay in a Centralized Regional Microbiology Laboratory
Authors: Church Deirdre , Miller Karena , Lichtenfeld Angelika , Semeniuk Heather , Kirkham Brenda , Laupland Kevin , Elsayed Sameer
Published: February 2021

Context.—Stool parasitologic testing for Giardia and Cryptosporidium (G/C) previously relied on staining (ie, modified iron hematoxylin-kinyoun), ethyl acetate concentration procedures, and microscopy (the stool ova and parasite method). In April 1999, a microplate enzyme immunoassay (EIA) (ProSpecT G/C, Remel, Inc, Lenexa, Kan) for routine screening of all stool specimens was implemented.

Objective.—To determine the clinical and laboratory impact of this service change.

Design.—Changes were made to the regional microbiology requisition so that physicians could order either a G/ C EIA screen or stool ova and parasite examination. During a 3-year period (May 1999 through April 2002), changes in physician ordering practice, the rate of detection of G/ C infections, and test turnaround times were monitored. The economic outcomes have also been studied and compared annually since implementation and up to the current fiscal year (2004).

Results.—The following effects have been noted since G/ C EIA screening was implemented: (1) 70% of all stool parasite tests ordered were converted to G/C EIA screens versus stool ova and parasite tests, (2) stool parasitologic volumes decreased by up to 30% because of physicians ordering a single test per patient, (3) most stool parasite results (70%–80%) were reported within 24 hours of specimen receipt, and (4) the screening assay has improved detection of cryptosporidiosis cases. Although the G/C EIA tests cost more than stool ova and parasite examination, the equivalent of 1.8 full-time employees have been freed up to perform other duties.

Conclusions.—Routine stool G/C EIA screening in our region is not only clinically relevant but also improves the timeliness and efficiency of detection of these important enteric parasite infections.
Hemangioma Versus Vascular Malformation: Presence of Nerve Bundle Is a Diagnostic Clue for Vascular Malformation
Authors: Adegboyega Patrick A. , Qiu Suimin
Published: February 2021

Context.—Arteriovenous vascular malformations and hemangiomas are benign vascular lesions that are difficult to distinguish from one another clinically. Also, they may be confused with each other at histopathology. Therefore, histochemical stains for the presence of an artery are frequently used to distinguish between the two.

Objective.—Because it is clinically relevant to differentiate between arteriovenous vascular malformations and hemangiomas, this study was carried out to explore additional diagnostic clues that may help in the diagnosis and differentiation of these lesions.

Design.—A total of 167 cases of benign extracranial vascular lesions were retrieved from the anatomic pathology file of our institution. These comprised 66 cases diagnosed as arteriovenous vascular malformations and 101 cases previously diagnosed as hemangiomas. The hematoxylin-eosin–stained glass slides were reviewed, Movat pentichrome histochemical stain was used to identify elastic vessels (arteries/arterioles), and S100 immunostain was used to identify nerves within these vascular lesions. For immunohistochemistry, the avidin-biotin detection method was used.

Results.—With Movat stain, the presence of thick-walled elastic arteries was detected in 12 of the 101 cases previously diagnosed as hemangiomas, and these cases were therefore reclassified as vascular malformations. Using the same criterion, 2 of the 66 cases originally diagnosed as arteriovenous vascular malformations were reclassified as hemangiomas because they lacked arterial structures. Thus, with this strict criterion, we ended up with 91 cases of hemangiomas and 76 cases of arteriovenous vascular malformations. Intralesional nerves were identified in 91% (69/76) of cases of arteriovenous vascular malformations, including all the 12 arteriovenous vascular malformations previously diagnosed as hemangiomas. In contrast, no intralesional nerve was detected in any of the 91 hemangiomas.

Conclusions.—These results show that nerve bundles are consistently present in vascular malformations and absent in hemangiomas and so can be used as a diagnostic clue to differentiate between these lesions. Also, in addition to describing a previously unreported component of vascular malformations, these data further confirm the hamartomatous nature of these lesions.
Validation of a Rapid Diagnostic Strategy for Determination of Significant Bacterial Counts in Bronchoalveolar Lavage Samples
Authors: Laupland Kevin B. , Church Deirdre L. , Gregson Daniel B.
Published: February 2021

Context.—Bacterial cultures of bronchoscopic samples require 1 to 2 days for results to be available for use in clinical decisions. We developed a rapid diagnostic testing strategy that is highly sensitive for screening bacteria in bronchoalveolar lavage (BAL) samples, with results available within hours of collection.

Objective.—To validate the ability of a bacterial adenosine triphosphate (ATP) assay and routine Gram stain microscopy to detect significant bacterial counts in BAL samples.

Design.—Four hundred seventy-seven BAL samples from 319 patients suspected of having pneumonia were tested using a rapid diagnostic strategy, consisting of Gram stain and a bacterial ATP assay. Rapid results were compared with quantitative cultures with a positive cutoff of 104 CFU/mL or higher.

Results.—Significant bacterial counts were identified in 107 samples (22%). The most common etiologic agents were Staphylococcus aureus (25%), Haemophilus influenzae (17%), and Streptococcus pneumoniae (12%). The rapid test results were false negative in 5 cases (S aureus in 2, both Klebsiella pneumoniae and S aureus in 1, and Stenotrophomonas maltophilia and S pneumoniae in 1 case each). The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of the rapid diagnostic strategy were 95.3%, 54.9%, 37.9%, 97.6%, and 63.9%, respectively.

Conclusion.—A negative result with this rapid diagnostic testing strategy rules out significant bacterial counts in BAL samples with a high degree of certainty and may allow use of narrow-spectrum antimicrobial agents or withholding of empiric antimicrobial therapy in patients suspected of having ventilator-associated pneumonia.
Incidental Stromal-Predominant Mixed Epithelial-Stromal Tumors of the Kidney: A Mimic of Intraparenchymal Renal Leiomyoma
Authors: Parikh Parin , Chan Theresa Y. , Epstein Jonathan I. , Argani Pedram
Published: February 2021

Context.—Mixed epithelial-stromal tumor of the kidney is a recently recognized benign renal tumor that usually occurs in adult women and typically forms a sizable lesion with solid and cystic areas. The recognized morphologic spectrum of this recently described entity is evolving.

Objective.—To review the clinicopathologic features of 3 small mixed epithelial-stromal tumors of the kidney that were incidental findings in kidneys removed for other reasons.

Design.—The clinical presentation and morphologic findings of the 3 cases were reviewed. A panel of immunohistochemical stains was performed.

Setting.—Academic medical center.

Results.—All 3 lesions contained predominantly fascicles of smooth muscle mimicking leiomyoma, but they also had cellular subpopulations of smaller, müllerian-appearing stromal cells. Tubules present within the lesion were most abundant at the periphery, suggesting that they might be entrapped. Although only the spindled smooth muscle cells were immunoreactive for muscle markers desmin and actin, both the spindled smooth muscle cells and the cellular müllerian-appearing stromal cells demonstrated diffuse nuclear labeling for estrogen and progesterone receptors.

Conclusions.—Mixed epithelial-stromal tumor of the kidney may present as an incidental stromal-predominant lesion within the kidney. Such lesions are easily confused with leiomyomas or stromal-predominant angiomyolipomas.
Whipple Disease: A Case Report and Review of the Literature
Authors: Muir-Padilla M. A. J. Jeannie , Myers C. O. L. Jerome B.
Published: February 2021

Whipple disease is a chronic, relapsing, and multisystem disease. It presents a diagnostic challenge for both clinicians and pathologists. Recent advances in isolation and culture have identified the organism responsible for the disease to be a member of the order Actinomycetes designated Tropheryma whipplei. Several immune system changes have been noted in patients with Whipple disease, but whether these are primary or secondary is as yet undetermined. Long-term antibiotic therapy is required, and relapses are common, especially with central nervous system involvement.
Increased Blasts Mimicking Acute Leukemia in a Patient With Polysubstance Abuse
Authors: Bianco Michelle , Turner John , Rosenthal Nancy
Published: February 2021

Toxic insult to the bone marrow may result in partial or complete suppression, with or without reactive changes, and probable eventual regeneration of hematopoietic elements. During the regenerative process, increased blasts may be observed. Distinguishing these changes from an acute leukemic process can be difficult. In particular, the diagnosis of hypocellular bone marrow with increased blasts, also known as hypocellular or hypoplastic acute leukemia, presents a diagnostic dilemma for pathologists. We report a case of hypocellular marrow with increased blasts in a 50-year-old man with an extensive history of alcohol and drug abuse in whom chemotherapy was deferred. Recovery of peripheral blood cell counts and reticulocytosis occurred with withdrawal of the offending agents, and he remains alive and well 1 year later.
Nectin-1 Expression in the Normal and Neoplastic Human Uterine Cervix
Authors: Guzman Grace , Oh Stephen , Shukla Deepak , Valyi-Nagy Tibor
Published: February 2021

Context.—Nectin-1 is an immunoglobulin-like adhesion molecule that is widely expressed in epithelial tissues and participates in the formation of adherens junctions. Reduced expression of nectin-1 has been reported in invasive carcinomas of the human skin.

Objective.—To determine the pattern of nectin-1 expression in the normal, dysplastic, and neoplastic human uterine cervix.

Design.—This retrospective study was performed using immunohistochemistry of specimens of normal mucosa (n = 18) and preneoplastic and neoplastic conditions of the human uterine cervix including squamous dysplasia and invasive uterine cervical squamous carcinoma (n = 23). All specimens were graded according to intensity of cytoplasmic staining (0 = no staining; 4 = strongest intensity).

Results.—Strong widespread cytoplasmic nectin-1 reactivity was found in normal uterine cervical squamous and endocervical mucosa (mean grade = 2.63). In contrast, uterine cervical and endocervical stroma showed minimal to absent staining (mean grade = 0.58). There was a significant difference in staining intensity between normal mucosa versus stroma (P < .001, Wilcoxon matched pairs– signed ranks test). All squamous dysplasia and carcinoma specimens displayed strong cytoplasmic nectin-1 staining (mean grade = 3.08). The advancing edge of these carcinomas demonstrated significantly decreased or absent expression of nectin-1 (mean grade = 1.39) with significant difference in staining intensity at the center of invasive tumors versus the advancing edge (P = .004, Wilcoxon matched pairs–signed ranks test).

Conclusions.—Normal squamous mucosa, dysplasia, and invasive carcinomas of the human uterine cervix stain strongly with nectin-1, and this staining is reduced or absent in the advancing edge of invasive tumors. These findings suggest that down-regulation of nectin-1 may be associated with the loss of cell-to-cell adhesion at the advancing edge of invasive squamous carcinomas of the human uterine cervix.
Review of Pineal Anlage Tumor With Divergent Histology
Authors: Berns Stephen , Pearl Gary
Published: February 2021

Pineal anlage tumor is an extremely rare tumor that is not listed in the 2000 World Health Organization Classification of nervous system tumors. It has been defined as a primary pineal tumor with both neuroepithelial and ectomesenchymal differentiation and without endodermal differentiation. We review the literature on this tumor, including the clinical presentation, gross pathology, histopathology, immunohistochemistry, differential diagnosis, and prognosis.
Gastrointestinal Stromal Tumors: Review on Morphology, Molecular Pathology, Prognosis, and Differential Diagnosis
Authors: Miettinen Markku , Lasota Jerzy
Published: February 2021

Context.—Gastrointestinal stromal tumors (GISTs) are specific, generally Kit (CD117)-positive, mesenchymal tumors of the gastrointestinal tract encompassing a majority of tumors previously considered gastrointestinal smooth muscle tumors. They are believed to originate from interstitial cells of Cajal or related stem cells.

Objective.—To review current clinicopathologically relevant information on GIST.

Data Sources.—Literature in Medline and authors' own experience.

Conclusions.—GISTs usually occur in older adults (median age 55–60 years) and rarely in children in the second decade (<1%) throughout the gastrointestinal tract: 60% in stomach, 35% in small intestine, and less than 5% in rectum, esophagus, omentum, and mesentery; most GISTs in the latter 2 sites are metastatic. Five percent of GISTs occur in patients with neurofibromatosis type 1 syndrome (multiple small intestinal tumors) and in Carney triad (gastric epithelioid GISTs in young females). Familial GISTs occur in patients with inheritable germline Kit or platelet-derived growth factor receptor alpha (PDGFRA) mutations. Histologically GISTs vary from spindle cell tumors to epithelioid and pleomorphic tumors. Most GISTs (95%) express Kit (CD117), CD34 (70%), and heavy caldesmon (80%), whereas 25% are positive for smooth muscle actin and less than 5% for desmin. Tumor size and mitotic activity are best predictive prognostic features; small intestinal tumors behave more aggressively than gastric tumors with similar parameters. Mutually exclusive gain-of-function Kit or PDGFRA mutations occur in a majority of GISTs representing in-frame deletions, point mutations, duplications and insertions. Mutations in Kit juxtamembrane domain (exon 11) are the most common in GISTs of all sites, whereas rare Kit extracellular domain (exon 9) Ala502-Tyr503 duplication is specific for intestinal GISTs. Mutations in PDGFRA have been identified in juxtamembrane (exon 12) and tyrosine kinase domains (exons 14 and 18), nearly exclusively in gastric GISTs, mostly in epithelioid variants. Some Kit and PDGFRA mutations have a prognostic value. Kit/PDGFRA tyrosine kinase inhibitor imatinib has been successfully used in the treatment of metastatic GISTs for more than 5 years. However, primary and acquired secondary resistance linked to certain types of Kit and PDGFRA mutations is limiting long-term success necessitating the use of alternative treatments.