bluuebunny/crossref_metadata_2025 huggingface dataset:
Quality Control of Test Systems Waived by the Clinical Laboratory Improvement Amendments of 1988
Authors: LaBeau Kathleen M. , Simon Marianne , Steindel Steven J.
Published: January 2021

Context.—Recent advances in laboratory testing technology have resulted in a rapidly increasing number of test systems targeted for physician office, point-of-care, and home health care settings. With enhanced error detection mechanisms and unitized reagents, these new systems simplify the testing process and the assessment of analytical test performance. Many also meet the criteria set by the Clinical Laboratory Improvement Amendments of 1988 (CLIA) to qualify as waived test systems, and laboratories using only waived tests are subject to very limited regulatory oversight.

Objective.—To evaluate use patterns and perceptions about quality control requirements with respect to waived testing.

Design and Setting.—Survey of a network of 431 hospital, independent, and physician office laboratories in the US Pacific Northwest.

Results.—Responding laboratories (n = 221) were taking advantage of the availability of waived tests and using them to make definitive diagnoses. We found considerable differences between quality control practices and the laboratories' perceptions of quality control requirements. Most respondents were performing traditional quality control on waived tests, influenced by their interpretation of regulations, the intended use of the test, and the testing personnel employed.

Conclusions.—Technology optimized for alternate quality control can represent an improvement in ease of use while meeting expectations for accuracy and providing relief from regulatory burdens. However, laboratory personnel exhibit confusion in applying new quality control systems.
Abnormal Erythrocyte Anion Exchange in Alzheimer Disease
Authors: Greco Frank A. , Satlin Andrew , Solomon Arthur K.
Published: January 2021

Context.—Several abnormalities have been described in red blood cells of patients with Alzheimer disease (AD), but to date none of these has been confirmed by a second, independent study. Erythrocyte anion exchange has been reported to be abnormal in AD; we have developed a new technique for measuring anion exchange.

Objectives.—To confirm the abnormality of erythrocyte anion exchange in AD and to determine whether the phenomenon has potential for clinical utility.

Design.—Comparison of patients with probable AD to age-matched controls.

Setting.—University hospital and ambulatory clinic.

Methods.—Chloride-bicarbonate exchange was measured in erythrocyte ghosts resealed with a fluorescent probe of chloride concentration.

Results.—Erythrocyte anion exchange is abnormal in AD. This difference appears in citrate but not EDTA anticoagulant. Mahalanobis's generalized distance between the 2 populations is 1.7, and a discriminant function derived from our technique classifies 82% of the study population in accordance with the National Institute of Neurological and Communicative Disorders and Stroke–Alzheimer's Disease and Related Disorders Association criteria. Receiver operating characteristic analysis demonstrates the possibility of choosing cutoffs with high sensitivity and specificity.

Conclusions.—Measurement of red blood cell anion exchange may be useful in classifying patients with AD. The dependence of this phenomenon on anticoagulant suggests the involvement of platelet activation or complement fixation.
Concordance of EndotoxemiaWith Gram-Negative Bacteremia
Authors: Hurley James C.
Published: January 2021

Objective.—To apply meta-analysis to compare the concordance between the results of 2 types of limulus amebocyte lysate (LAL) assay, gelation (GLAL) and chromogenic (CLAL), with the detection of gram-negative bacteremia in patients with suspected bacteremia.

Design.—Meta-analysis using receiver operating characteristic–based analytical method.

Data Sources.—MEDLINE literature search and manual reviews of article bibliographies together with direct approaches to authors of potentially eligible studies.

Study Selection.—The studies that were selected had all included at least 10 patients, of whom at least 2 patients were diagnosed with gram-negative bacteremia, and all had data available for extraction into a contingency table format.

Results.—Fifty-six studies (28 GLAL and 28 CLAL studies) met the inclusion criteria. Studies were stratified by type of test (GLAL vs CLAL). Each analysis was repeated with smaller studies excluded. There was no difference between the 2 types of LAL assays. Among the CLAL studies, there was no difference between studies that did versus those that did not use the sepsis syndrome criteria as a basis for patient inclusion. Among 45 studies for which data on the proportion of non-Enterobacteriaceae were available, there was a trend toward higher concordance as this proportion increased.

Conclusions.—The concordance between the LAL test and the detection of gram-negative bacteremia in patients with suspected bacteremia is no higher with the CLAL assay than with the original GLAL version. However, the concordance is higher among studies with a higher proportion of non-Enterobacteriaceae among the gram-negative bacteremia isolates.
National Inventory of Clinical Laboratory Testing Services (NICLTS)
Authors: Steindel Steven J. , Rauch William J. , Simon Marianne K. , Handsfield James
Published: January 2021

Context.—A statistically valid inventory of the distribution, both geographic and by laboratory type, of clinical and anatomical laboratory testing in the United States is needed to assess the impact of the Clinical Laboratory Improvements Amendments of 1988 and to provide information for other health care and public health policy decisions.

Objective.—To present initial US laboratory testing volume data compiled by the National Inventory of Clinical Laboratory Testing Services.

Design.—Stratified random sample of laboratories performing testing in 1996 with data on the number of laboratory tests performed, identified by method and analyte. Data were collected by field tabulators (moderate- or high-complexity laboratories) or through a mail/telephone survey (waived or provider-performed microscopy laboratories) for each site.

Participants.—Laboratories that were enrolled in the 1996 Online Certification Survey and Reporting System, maintained by the US Health Care Finance Administration, and that performed laboratory testing during 1996.

Main Outcome Measure.—Laboratory testing distribution for 1996 in the United States by analyte, method, and specimen type.

Results.—An overall response rate of 79% provided data from 757 moderate- or high-complexity laboratories and 1322 waived or provider-performed microscopy laboratories. The estimated total US testing volume for 1996 was 7.25 ± 1.09 billion tests. Laboratories performing complex testing, defined as greater than 16 method/analyte/specimen type combinations, comprised 16% of the US laboratories by survey site, but performed 80% (95% confidence limits, 43% to 100%) of the testing volume. Glucose analysis was the most frequently performed test. Automated hematology and chemistry analyzers were the most frequently used methods.

Conclusions.—A statistically valid, consistent survey of the distribution of US laboratory testing was obtained. Simple analysis of these data by laboratory type and geographic region can provide insights into where laboratory testing is performed. The study design allows extensions that will facilitate collection of additional data of importance to public health and medical care delivery.
Angiotensin-Converting Enzyme, Transforming Growth Factor β1, and Interleukin 11 in the Osteolytic Lesions of Langerhans Cell Histiocytosis
Authors: Brown Robert E.
Published: January 2021

Objective.—To assess the expression of potential osteoclastogenic and osteolytic factors in osteolytic lesions from patients with Langerhans cell histiocytosis.

Design.—Paraffin-embedded biopsy sections from 5 such archival cases underwent immunohistochemical procedures with antibodies to detect the following antigens: CD1a, S100 protein, interleukin 11, the latency-associated peptide of transforming growth factor β1, and angiotensin-converting enzyme.

Results.—Commonalities noted include (1) the presence of multinucleated osteoclast-like giant cells, (2) the expression of interleukin 11 and latency-associated peptide antigens in lesional Langerhans cells, and (3) plasmalemmal immunoreactivity for angiotensin-converting enzyme antigen on non–Langerhans cell histiocytes and, on occasion, osteoclast-like giant cells and endothelial cells.

Conclusions.—These observations suggest a possible pathogenetic sequence for osteolysis in Langerhans cell histiocytosis that involves angiotensin II formation, leading to the activation of latent transforming growth factor β1 and, in turn, to the enhanced production of interleukin 11, resulting in both osteoclastogenesis and impaired remodeling of bone.
Histopathologic and Immunohistochemical Studies on the Mechanism of Interlobular Fibrosis of the Pancreas
Authors: Suda Koichi , Takase Masaru , Takei Kazuo , Kumasaka Toshio , Suzuki Fujihiko
Published: January 2021

Objective.—To elucidate the mechanism of interlobular fibrosis of the pancreas, which is categorized as chronic alcoholic pancreatitis.

Methods.—Forty pancreatic tissue samples from patients with ampullary carcinomas, which cause various degrees of stricture of the main pancreatic duct, and 20 patients with chronic alcoholic pancreatitis were studied histopathologically and immunohistochemically.

Results.—Fibrosis was observed in 23 of 40 patients with ampullary carcinomas and was classified into 3 categories: mild changes (10 cases), moderate changes (9 cases), and marked changes (4 cases). In the mild change cases, mild fibrosis was diffusely distributed in the interlobular areas, with scant immunoreactivity of anti–α-smooth muscle actin (α-SMA) and an expansive lobular appearance, whereas moderate and marked change cases showed interlobular and intralobular fibrosis with marked anti–α-SMA immunoreactivity and lobular atrophy. By quantitative analysis, the mild change cases showed both higher MIB1-positive and lower apoptotic acinar cell ratios than those of moderate and marked changes. Anti–α-SMA immunoreactivity in the patients with chronic alcoholic pancreatitis was found in interlobular fibrosis. Hence, mild changes in cases of ampullary carcinomas had histologic findings similar to chronic alcoholic pancreatitis, except for excessive fibrosis cases with patchy distribution.

Conclusion.—Incomplete obstruction of the main pancreatic duct caused the beginning of interlobular fibrosis, which is categorized as chronic alcoholic pancreatitis.
Long-Term Experience With an Accelerated Protocol for Diagnosis of Chest Pain
Authors: Caragher Timothy E. , Fernandez Balbino B. , Barr Lawrence A.
Published: January 2021

Context.—More than 6 million patients present annually with chest pain suggestive of acute coronary syndrome. Rapid and accurate diagnosis is essential for best clinical outcomes, for optimal management of hospital resources, and for minimizing medicolegal exposure.

Objective.—To evaluate the clinical and cost outcomes of an accelerated protocol for chest pain triage in a community-based hospital of moderate size.

Methods.—One hundred successive patients with chest pain were diagnosed according to the Traditional Chest Pain Protocol, which included testing of serial blood samples for creatine kinase (CK)-MB and total CK. These patients were also subjected to the Accelerated Chest Pain Protocol under evaluation, which included testing at shortened intervals for myoglobin and cardiac troponin I in addition to CK and CK-MB. Diagnostic sensitivity and specificity were compared versus the final assigned diagnosis. The Accelerated Chest Pain Protocol was implemented for routine use. Follow-up evaluations were conducted at 1 month (test group A, N = 180) and 22 months (test group B, N = 180). Costs for diagnosis and treatment of the 2 test groups were compared with those for the control group.

Results.—The 2 protocols had equivalent specificity values (99%). The sensitivity of the Accelerated Chest Pain Protocol was higher than that of the Traditional Chest Pain Protocol (95% vs 58%). Cost savings of 29% and a reduction in length of stay of 33% were achieved in test group B versus the control group.

Conclusions.—The Accelerated Chest Pain Protocol improved the accuracy and timeliness of diagnosis of acute coronary syndrome while reducing costs.
Hantavirus Pulmonary Syndrome Is Distinguishable From Acute Interstitial Pneumonia
Authors: Colby Thomas V. , Zaki Sherif R. , Feddersen Richard M. , Nolte Kurt B.
Published: January 2021

Context.—Hantavirus pulmonary syndrome (HPS) and acute interstitial pneumonia (AIP) can share similar clinical presentations. AIP is an acute, diffuse lung disease that has some clinical features suggesting a viral infection, although causative agent(s) have not been identified.

Objective.—To clinically, histologically, and immunohistochemically compare cases of HPS to cases of AIP and to determine if any cases of AIP were actually examples of HPS.

Design.—Seven cases of HPS and 9 cases of AIP were compared clinically and histologically by semiquantitative grading of features in lung tissue. The cases were also evaluated immunohistochemically for the presence of hantaviral antigens.

Results.—Hantavirus pulmonary syndrome had a shorter clinical duration and more acute changes histopathologically; AIP was of longer clinical duration and was usually accompanied by histologic evidence of organization. Hantavirus pulmonary syndrome was distinguished by the presence of immature leukocytes in the pulmonary vasculature. No hantaviral antigens were identified immunohistochemically in the 9 case of AIP. Hantaviral antigens were identified in all 7 cases of HPS.

Conclusion.—Cases of AIP and fatal cases of HPS can generally be distinguished on clinical and histologic grounds, and this distinction can be further confirmed immunohistochemically.
Estrogen and Progesterone Receptors in Non–Small Cell Lung Cancer in 248 Consecutive Patients Who Underwent Surgical Resection
Authors: Nunno Lucio Di , Larsson Lisbeth G. , Rinehart John J. , Beissner Robert S.
Published: January 2021

Context.—Different authors have reported estrogen receptor (ER) expression between 0% and 96.8% and progesterone receptor (PR) expression between 21.8% and 34.7%.

Objective.—To examine the discrepancies in the literature regarding the expression of ERs and PRs in non–small cell lung cancer.

Design.—Retrospective analysis.

Setting.—A referral tertiary care center.

Patients.—We reviewed 248 consecutive cases of stage I and II non–small cell lung cancers.

Methods and Results.—Sections of formalin-fixed and paraffin-embedded tumor tissue were stained with ER and PR monoclonal antibodies using the avidin-biotin complex detection system with antigen retrieval. Men represented 66.1% of the patients, and women represented 33.9%. Large cell (undifferentiated) carcinoma constituted 10.4% of the entire population; squamous cell carcinoma, 39.1%; adenocarcinoma, 33.0%; and bronchoalveolar carcinoma, 17.3%. Patients with stage I disease represented 77.0% of the population. In this patient population, we found no nuclear or cytoplasmic expression of either ERs or PRs (95% confidence interval, 0%–1.2%).

Conclusions.—The absence of expression of ERs and PRs differs from previous articles, which use a variety of techniques, impairing a meaningful comparison of data. In addition, the presence of ER and PR expression in a lung carcinoma is supportive of a nonpulmonary primary tumor metastatic to the lung. The absence of their expression in non–small cell lung cancer does not support a role of these transcription factors in initiating and maintaining this neoplastic process.
Actinomyces and Actinobacillus actinomycetemcomitans-Actinomyces–Associated Lymphadenopathy Mimicking Lymphoma
Authors: Amrikachi Mojghan , Krishnan Bhuvaneswari , Finch Christie J. , Shahab Imran
Published: January 2021

We present 2 unusual cases of long-standing, extensive reactive lymphadenopathy secondary to Actinomyces infection, 1 of which was also accompanied by Actinobacillus actinomycetemcomitans-Actinomyces complex infection. To our knowledge, histologic features of lymph node involvement by these organisms have not been previously reported in the literature. One patient had extensive cervical, posterior mediastinal, and abdominal lymphadenopathy. The second patient presented with a submandibular mass and cervical lymphadenopathy. Clinical features strongly suggested lymphoma. The histologic examination of the lymph nodes from both patients revealed reactive follicular hyperplasia, marked interfollicular and capsular fibrosis, and multiple interfollicular microabscesses. Characteristic Actinomyces colonies were identified at the center of the microabscesses in deep sections. Cultures were obtained from the lymph nodes of 1 patient, and were positive for A actinomycetemcomitans. Both patients had poor dental hygiene. Lymphadenopathy subsided with antibiotic therapy and appropriate dental care.
Granulosa Cell Tumor of the Adult Type
Authors: Al-Bozom Issam A. , El-Faqih Salah R. , Hassan Salaheldin H. , El-Tiraifi Abdelmoniem E. , Talic Riyadh F.
Published: January 2021

We report a case of testicular granulosa cell tumor of the adult type in a 48-year-old man. Microscopically, the tumor consisted of round to ovoid cells with grooved nuclei that were arranged in several patterns, including microfollicular, macrofollicular, insular, trabecular, gyriform, solid, and pseudosarcomatous. These cells demonstrated strong immunopositivity with MIC2 (O13) antibody, vimentin, and smooth muscle actin and focal positivity with cytokeratin. Although this type of sex cord–stromal tumor is relatively common in the ovaries, it is still extremely unusual in the testis, and it probably represents the rarest type of testicular sex cord–stromal tumor.
C282Y Mutation and Hepatic Iron Status in Hepatitis C and Cryptogenic Cirrhosis
Authors: Lal Priti , Fernandes Helen , Koneru Baburao , Albanese Ernest , Hameed Meera
Published: January 2021

Background.—Increased iron deposition in liver is seen in both primary and secondary hemochromatosis. However, it is not uncommon to see significant iron deposition in a liver biopsy, explant, or autopsy specimen without any significant clinical risk factor. Because of the discovery of the candidate gene (HFE) for hereditary hemochromatosis, we may now be able to screen high-risk patient populations for the abnormal mutation (C282Y).

Materials and Methods.—In this study we analyzed the livers of 50 transplant patients with a diagnosis of either hepatitis C cirrhosis or cryptogenic cirrhosis for the prevalence of the more common C282Y mutation of the HFE gene and correlated the findings to hepatic iron concentration.

Results.—Of the 26 cases of hepatitis C cirrhosis, 3 were found to be heterozygous for the C282Y mutation. Of the 22 cases of cryptogenic cirrhosis, 1 was found to be heterozygous for the C282Y mutation. Stainable iron was increased in hepatitis C cirrhosis (76.9%) as compared to cryptogenic cirrhosis (50%) (P = .05). Of the 3 heterozygotes with hepatitis C cirrhosis, 2 showed hepatic iron concentrations of 3+ and 4+, and 1 showed 1+.

Conclusions.—We conclude that patients with hepatitis C have an increased tendency to accumulate iron in the liver, and mutations in the HFE gene play a minor role in hepatic accumulation of iron in these patients.
Malignant Giant Cell Tumor of Synovium (Malignant Pigmented Villonodular Synovitis)
Authors: Layfield Lester J. , Meloni-Ehrig Aurelia , Liu Katharine , Shepard Rebecca , Harrelson John M.
Published: January 2021

Context.—Pigmented villonodular synovitis (PVNS) is a well-recognized entity that has the potential for extensive local destruction, even though it rarely metastasizes. Rare reports of malignant forms are recorded in the literature. We observed 2 patients in whom examples of PVNS followed an aggressive course with multiple recurrences, metastasis, or degeneration to an appearance resembling malignant fibrous histiocytoma.

Objective.—We studied the occurrence and persistence of aneuploidy for chromosomes 5 and 7 in 2 patients with clinically aggressive PVNS.

Design.—Fluorescence in situ hybridization was performed for the detection of chromosomes 5 and 7 in the primary lesions, recurrences, and metastases in 2 examples of PVNS.

Results.—Fluorescence in situ hybridization demonstrated small but significant numbers of cells with trisomies for chromosomes 7 and/or 5 in both the primary and recurrent lesions of both patients.

Conclusions.—The presence of consistent chromosomal trisomies (5 and 7) in both patients' examples of PVNS suggests a neoplastic nature for this lesion. The persistence of these trisomies in the primary lesions, recurrences, and metastases supports a molecular link between the primaries, recurrences, and metastases despite changes in morphologic features. The presence of persistent trisomies in the recurrent and metastatic lesions supports the concept of malignant PVNS.
Vulvar Hypertrophy With Lymphedema
Authors: Vang Russell , Connelly John H. , Hammill Hunter A. , Shannon Rhonda L.
Published: January 2021

We report the case of a 43-year-old quadriplegic woman with bilateral vulvar enlargement. The clinical impression was labial hypertrophy, but the microscopic features mimicked aggressive angiomyxoma because of the location, hypocellular proliferation of fibroblastic cells in an edematous-myxoid stroma, and vessels with perivascular collagen deposition, which simulated the thick-walled vessels of aggressive angiomyxoma. Since the lesion lacked true thick-walled vessels and contained ectatic tortuous lymphatics, the pathologic interpretation was lymphedema. This vulvar lesion should be recognized to prevent the misdiagnosis of aggressive angiomyxoma.
Herpes Simplex Encephalitis Occurring After Chemotherapy, Surgery, and Stereotactic Radiotherapy for Medulloblastoma
Authors: Molloy S. , Allcutt D. , Brennan P. , Farrell M. A. , Perryman R. , Brett F. M.
Published: January 2021

Reactivation of latent herpes simplex virus (HSV) in the trigeminal ganglion most commonly gives rise to recurrent herpes labialis and rarely to herpes simplex encephalitis. The mechanisms underlying reactivation of latent trigeminal HSV are complex. Here we report the case history of a 25-year-old woman who developed a fatal, bilateral necrotizing destructive temporal lobe lesion following surgical removal of a cerebellar medulloblastoma and combined radiotherapy and chemotherapy for recurrent tumor. Neuropathologic examination of the brain revealed minimal inflammatory changes, but immunohistochemistry was positive for HSV protein, and HSV deoxyribonucleic acid (DNA) was recovered from formalin-fixed paraffin-embedded brain tissue. The temporal proximity of the surgery, chemotherapy, and radiotherapy to the onset of disease suggests that these factors may have acted as triggers that precipitated conversion of latent HSV to overt HSV.
Laryngeal Metastasis 7 Years After Radical Nephrectomy
Authors: Dee Simpson L. , Eshghi Majid , Otto Clifton S.
Published: January 2021

Metastasis of renal cell carcinoma to the head and neck, especially the larynx, is an extremely rare event. Most previously reported cases have involved a presenting laryngeal lesion that lead to the discovery of an underlying primary renal cell carcinoma. Even more unusual is the occurrence of an isolated laryngeal metastasis revealing itself years after nephrectomy, with an interim of undetected recurrence. We believe this case to be the first reported example of an isolated supraglottic laryngeal renal cell carcinoma metastasis occurring 7 years after radical nephrectomy. Local excision of such isolated lesions seems to offer a favorable prognosis.
The Changing Concepts of Amyloid
Authors: Picken Maria M.
Published: January 2021

The first issue of the Archives of Pathology & Laboratory Medicine, published 75 years ago, contained an article by Richard Jaffé on the experimental induction of amyloidosis in mice. This publication was one of a series of milestones that have marked our ongoing and evolving concept of amyloidosis, beginning with the first description by Virchow more than a century ago. Since that time, scientific understanding of amyloidogenesis has expanded through the involvement of newly developed techniques, such as biochemical analysis, electron microscopy, and molecular genetics. As a result of these investigations, it is now known that amyloidoses comprise an entire family of sporadic, familial and/or inherited, degenerative, and infectious disease processes, linked by the common theme of abnormal protein folding and deposition. This article seeks to provide a synopsis of the present state of our knowledge with regard to these disorders, including current terminology, classification, major clinical syndromes, and diagnosis.
DNA Technology, the Clinical Laboratory, and the Future
Authors: Kiechle Frederick L.
Published: January 2021

Objective.—To review the advances in clinically useful molecular biological techniques and their applications in clinical practice as presented at the Ninth Annual William Beaumont Hospital DNA Symposium.

Data Sources.—The 10 manuscripts submitted were reviewed and their major findings were compared with literature on the same topic.

Study Selection.—One manuscript reviewed the development of pharmacogenetics, 3 described analytic approaches to detect aneuploidy or cancer, 1 described transcription factor E2F-1 increase during apoptosis, 2 reported on genetic and pharmacologic factors that influence platelet aggregation, 2 described molecular methods for detecting long QT syndrome or mycobacteria, and 1 reported a modification in collection of buccal DNA.

Data Synthesis.—Genomic and proteomic approaches to develop clinically useful assays have been successful. Aneuploidy can be easily detected by comparative genomic hybridization, which does not require cell culture like cytogenetics. Mutations have been characterized for a variety of hereditary cancer syndromes, 2 inherited long QT syndromes, and thromboembolism. PlA1 and PlA2 polymorphisms in platelets are associated with a difference in aggregation inhibition by estrogen, another example of genotypic pharmacogenetics. Protein expression differences may define colorectal cancer stage and explain apoptotic signal transduction. Mycobacterial detection by nucleic acid amplification and simplified buccal DNA collection demonstrate cost-effective strategies.

Conclusion.—The working draft of the Human Genome Project is completed and the number of clinically useful molecular pathologic techniques and assays will expand as additional disease-associated mutations are defined. Expanded use of database software for genomic and proteomic screening should increase the efficiency of clinical useful assay development.
Combined Factor V Leiden and Prothrombin Genotyping in Patients Presenting With Thromboembolic Episodes
Authors: Friedline John A. , Ahmad Ejaz , Garcia Diana , Blue Deborah , Ceniza Noel , Mattson Joan C. , Crisan Domnita
Published: January 2021

Background.—Several genetic defects are associated with increased risk of venous thrombosis. The factor V Leiden (FVL) and prothrombin G20210A mutations are the most frequent causes of inherited thrombophilia.

Objectives.—To evaluate combined genotyping for these 2 mutations in patients presenting with thromboembolic episodes and to correlate genotypic findings with clinical characteristics.

Results.—Blood specimens were collected from 401 patients presenting with thromboembolic disease between January 1998 and September 1998, and genotyping for both FVL and prothrombin mutations was performed. Thirty-two patients (8%) were heterozygous for FVL, 4 (1%) were homozygous for FVL, and 20 (5%) were heterozygous for the prothrombin mutation. Two cases (0.5%) were identified with combined FVL and prothrombin mutations. The most common clinical presentation was lower-extremity deep vein thrombosis with or without pulmonary embolism. Arterial events were rare. The thromboembolic episodes were often precipitated by additional risk factors. Recurrent disease was found in 73.9% of FVL carriers and 52.9% of prothrombin mutation carriers; 52% of the patients with FVL and 50% of prothrombin mutation carriers had a first thrombotic episode before age 45 years. The 2 cases with combined genetic defects demonstrate amplified thrombotic risk. In the first case this was effected in thrombosis at a young age, and recurrence of thrombotic events even in the absence of precipitating factors. A complex interplay between genetic and additional risk factors was seen in the second case.

Conclusions.—Identification of both FVL and prothrombin mutations is important in the overall assessment and management of patients with thrombophilia. Detection of these mutations can identify patients at high risk and help evaluate the interaction of genetic and acquired risk factors.
Histologic and Histochemical Characterization of Seminal Vesicle Intraluminal Secretions
Authors: Shah Rajal B. , Lee Min W. , Giraldo Alvaro A. , Amin Mahul B.
Published: January 2021

Context.—We have observed intraluminal crystalloid morphology in seminal vesicles that is superficially similar to that seen in prostate neoplasia, but found little information on such morphology in the literature.

Design.—Two hundred fifty-three prostate specimens (163 needle biopsies, 75 radical prostatectomies with prostate carcinoma, 11 prostates from autopsy, and 4 cystoprostatectomies without prostate carcinoma) were examined for seminal vesicle secretions, which were categorized as (a) dense platelike inspissated, (b) fluidlike, (c) crystalloid morphology, and (d) absent. Histochemical stains (periodic acid–Schiff with and without diastase, Alcian blue at pH 2.5, and mucicarmine) were performed to characterize the nature of secretions.

Results.—Proteinaceous secretions were identified in 82% of seminal vesicles examined. Of these, 61% had predominantly dense, platelike, inspissated secretions, 15% had predominantly fluidlike secretions, and 24% had predominantly crystalloid morphology. Although in some cases the crystalloid morphology resembled that of prostatic intraluminal crystalloids, the seminal vesicle crystalloids differed in that they were invariably multiple, had curved edges, and had varied forms (elliptical, cylindrical, rodlike, and rectangular). Seventy-one percent of seminal vesicle crystalloids were associated with dense, platelike, inspissated secretions and appeared to be created by fracturing within platelike secretions. There was no relationship between seminal vesicle crystalloid morphology and associated malignancy in the prostate gland, as it was seen in 24% of cases with prostate carcinoma and 25% of cases without prostate carcinoma (P = 1.0000). Fluidlike secretions were positive for Alcian blue (pH 2.5) and mucicarmine, whereas dense platelike secretions and crystalloid morphology were negative for Alcian blue (pH 2.5) and mucicarmine.

Conclusions.—Seminal vesicle secretions are fairly common and, when fluidlike, are composed of acid mucopolysaccharides. Inspissation of secretions appears to be associated with loss of acidity, presumably resulting in dense platelike secretions and crystallization. Awareness of both the crystalloid morphology in seminal vesicle tissue and the distinguishing features from prostatic crystalloids may be important while interpreting prostate needle biopsies in which seminal vesicle epithelium may be confused for prostate carcinoma because of a small acinar morphology with accompanying cytologic atypia and crystalloid morphology.
Anabolic Steroid Abuse and Cardiac Sudden Death
Authors: Fineschi Vittorio , Baroldi Giorgio , Monciotti Floriana , Reattelli Laura Paglicci , Turillazzi Emanuela
Published: January 2021

Context.—Androgenic anabolic steroids (AAS) used for improving physical performance have been considered responsible for acute myocardial infarction and sudden cardiac death.

Objective.—To establish the relationship between AAS and cardiac death.

Design.—Case report.

Patients.—Two young, healthy, male bodybuilders using AAS.

Main Outcome Measures.—Pathologic cardiac findings associated with AAS ingestion.

Results.—The autopsy revealed normal coronary arteries. In one case, we documented a typical infarct with a histologic age of 2 weeks. A segmentation of myocardial cells at the intercalated disc level was observed in the noninfarcted region. This segmentation was the only anomaly detected in the second case. No other pathologic findings in the heart or other organs were found. Urine in both subjects contained the metabolites of nortestosterone and stanozolol.

Comment.—A myocardial infarct without vascular lesions is rare. To our knowledge, its association with AAS use, bodybuilding, or both lacks any evidence of a cause-effect relationship. The histologic findings in our 2 cases and in the few others reported in medical literature are nonspecific and do not prove the cardiac toxicity of AAS. A better understanding of AAS action on the neurogenic control of the cardiac function in relation to regional myocardial contraction and vascular regulation is required.
Primary Malignant Melanoma of the Larynx
Authors: Amin Hesham M. , Petruzzelli Guy J. , Husain Aliya N. , Nickoloff Brian J.
Published: January 2021

Primary malignant melanoma of the larynx is a rare clinical entity. Only 53 cases have been reported in the medical literature to date. This report describes a case of primary malignant melanoma arising in the larynx and diagnosed by histologic examination of an excisional biopsy specimen. The patient was a 53-year-old man with a history of smoking and hoarseness. There was no clinical evidence of other primary malignant melanocytic lesions. Microscopically, the tumor consisted of polygonal-epithelioid cells admixed with more elongated, spindle-shaped cells. The majority of the cells demonstrated dark brown cytoplasmic and nuclear melanin. Marked pleomorphism and abnormal mitoses were also identified. Despite significant ulceration and disruption of the epithelium, in situ malignant melanocytes were recognized within the remaining portion of the epithelium. Immunohistochemical studies were positive for S100, HMB-45, and vimentin, while cytokeratin and iron stains were negative. Based on the clinical and histologic findings, a diagnosis of primary malignant melanoma of the larynx was established.
Carcinosarcoma of the Tongue With Cyclin D1 Gene Amplification
Authors: Suzuki Hiroaki , Yamashiro Katsushige , Yoshida Chikako , Fujioka Yasunori
Published: January 2021

Carcinosarcoma of the tongue is a rare malignancy and its molecular aspect is unclear. A case of carcinosarcoma of the tongue in a 51-year-old man is presented. A polypoid tumor of the tongue, measuring 12 × 12 × 6 mm, was resected. Histologically, the tumor was composed of a squamous cell carcinoma and a spindle cell sarcomatous component. We previously showed that one cell-cycle regulator, the cyclin D1 gene, was frequently amplified in esophageal carcinosarcoma, which shows the same morphologic features as carcinosarcoma of the tongue. In this case, we examined whether the cyclin D1 gene is amplified in carcinosarcoma of the tongue as well. Fluorescence in situ hybridization analysis revealed that the cyclin D1 gene was amplified in both components of carcinosarcoma of the tongue. The cyclin D1 protein was also detected by immunostaining in both components. Our results suggest that the amplification of cyclin D1 gene plays a role in the molecular pathogenesis of carcinosarcoma of the tongue, at least in some cases.
A Unique, Complex Variant Philadelphia Chromosome Translocation in a Patient With Typical Chronic Myelogenous Leukemia
Authors: Oudat Raida , Khan Zebunnisa , Glassman Armand B.
Published: January 2021

The Philadelphia (Ph) chromosome [der(22) t(9;22)(q34;q11)] is the characteristic chromosomal abnormality found in chronic myelogenous leukemia (CML). This chromosome has been reported in patients with other chromosomal abnormalities. In this study, we describe a patient with hematologically typical chronic-phase CML with an unusual and complex translocation involving chromosomes 9, 11, and 22. These complex translocations were identified by G-banded conventional cytogenetics and confirmed by fluorescence in situ hybridization (FISH) using whole chromosome painting probes (wcp). To the best of our knowledge, these are unique translocations involving the short and the long arms of chromosome 9 in 4 different translocations with the short arm of chromosome 11 and the long arm of chromosome 22.
Extranodal Lymphoplasmacytoid Lymphoma (Immunocytoma) Presenting as Small Intestinal Obstruction
Authors: Recine Monica A. , Perez Maria T. , Cabello-Inchausti Beria , Lilenbaum Rogerio C. , Robinson Morton J.
Published: January 2021

A 57-year-old woman presented with intermittent symptoms of intestinal obstruction. Workup provided nondiagnostic radiologic studies. An exploratory laparotomy revealed a segmental dilatation in the proximal ileum, which showed diffuse thickening of the intestinal wall. Microscopic examination of the affected area disclosed a diffuse transmural infiltrate composed of small lymphocytes, mature plasma cells, and lymphoplasmacytoid cells in different stages of maturation associated with extracellular periodic acid-Schiff–positive material. In addition, serum protein electrophoresis showed a monoclonal immunoglobulin M κ paraprotein. Postoperative workup did not demonstrate evidence of systemic involvement. The morphologic features and immunohistochemical and molecular analyses were consistent with lymphoplasmacytoid lymphoma (immunocytoma). We report an unusual case of primary extranodal immunocytoma involving the small intestine and discuss its clinicopathologic features.
An Evaluation of Analytic Goals for Assays of Drugs
Authors: Steele Bernard W. , Wang Edward , Palomaki Glenn E. , Klee George G. , Elin Ronald J. , Soldin Steven J. , Witte David L.
Published: January 2021

Objective.—To determine if the levels of imprecision of the commonly used analytic methods for drug measurements are suitable for long-term therapeutic drug monitoring.

Design.—In 1996, 4 identical lyophilized samples (2 in the first mailing and 2 in the second mailing 4 months later) were sent to laboratories participating in a nationwide proficiency testing program. Similarly, in 1999, replicates from a liquid pool of spiked sera were mailed 3 times, 4 months apart, to participating laboratories. For each of 11 drugs regulated under the Clinical Laboratory Improvement Amendments of 1988 and 1 metabolite, the total variance for each method was partitioned into within- and between-laboratory components. The total within-laboratory and the total survey coefficients of variation (CVs) for each method were then compared with the “acceptable” precision criteria of Glick, Burnett, and Fraser for each drug.

Setting.—The first 2 mailings of the College of American Pathologists Therapeutic Drug Monitoring surveys for 1996, sets Z and ZM, and the 3 mailings of 1999, sets ZM, Z, and Z2.

Main Outcome Measures.—For each drug studied, the CV of each method was compared with the various imprecision criteria, and if greater than any of the criteria, the method was then tabulated as not meeting that specific criterion.

Participants.—The approximately 5000 participants of the survey.

Results.—The number of methods deemed as not having acceptable total long-term within-laboratory precision by the various criteria ranged from 35% to 88% in 1996 and from 22% to 77% in 1999.

Conclusion.—The number of failures possibly indicates that many of the reagent assays being utilized are not precise enough for long-term therapeutic drug monitoring of chronically administered drugs or that the published criteria used to evaluate the data in this study are too stringent.
Comparison of Immunoperoxidase Staining of 3 Different Types of CD5 Antibodies in a Spectrum of Breast Lesions
Authors: Walsh Rebecca , Peston David , Shousha Sami
Published: January 2021

Context.—We recently described a patient with chronic lymphocytic leukemia who presented with a breast carcinoma that stained positive for CD5 using a commercially available antibody (CD5-4C7, Novocastra, Newcastle upon Tyne, UK).

Objectives.—To study the distribution of CD5 immunoreactivity in tissue sections of a variety of benign and malignant breast lesions using the antibody CD5-4C7 and to compare the results with those obtained with 2 other commercially available CD5 antibodies (CD5/54/F6, Dako, Ely, Cambridgeshire, UK, and CD5/54/B4, Novocastra).

Design.—Paraffin sections of 102 breast biopsy specimens with various diagnoses were examined using the avidin-biotin immunoperoxidase complex technique.

Setting.—The histopathology department of a tertiary referral teaching hospital.

Results.—The staining results obtained with CD5-4C7 were different from those obtained with the other 2 antibodies. With 4C7, the normal and benign biopsy specimens showed varying numbers of positive epithelial cells and lymphocytes. Heterogeneous positive staining was also present in 47 (78%) of 60 invasive female breast carcinomas and in all 3 male breast carcinomas examined. A statistically significant correlation was found between CD5 positivity and tumor grade, with grade 3 tumors being less likely to be CD5 positive than grades 1 and 2 (P = .0035). No correlation was found between CD5 positivity and patient's age, tumor histologic type, axillary lymph node status, or progesterone receptors. On the other hand, the CD5/54/F6 and CD5/54/B4 antibodies only stained lymphocytes and occasional normal breast ducts, mostly those showing apocrine metaplasia. All other normal benign and malignant epithelial cells were negative.

Conclusions.—Positive staining for CD5 using the antibody 4C7 is seen in normal and benign breast tissue and 78% of invasive breast carcinomas. The positivity is more common in low-grade tumors. No significant staining was seen with the 2 other CD5 clones used in this study. The significance of the positive staining obtained with CD5-4C7 is not obvious, but this clone may be more sensitive than the others, or it may be recognizing an epitope shared by another antigen.
Computerized Image Analysis of p53 and Proliferating Cell Nuclear Antigen Expression in Benign, Hyperplastic, and Malignant Endometrium
Authors: Elhafey Ahmed S. , Papadimitriou John C. , El-Hakim Mohamed S. , El-Said Ahmed I. , Ghannam Bahaa B. , Silverberg Steven G.
Published: January 2021

Context.—The endometrium is an intrinsically dynamic tissue with great capability for regeneration and proliferation; consequently, there is some overlap between features seen in benign, premalignant, and malignant lesions. This leads to marked intrabiopsy, interbiopsy, and interobserver variability.

Objective.—We studied the specificity and sensitivity of computerized image analysis of molecular markers to evaluate its potential use as a diagnostic tool.

Design.—Specimens from 100 patients were examined and the following histologic diagnoses were assigned: proliferative endometrium (n = 10), secretory endometrium (n = 10), endometrial hyperplasia (n = 40; 30 with no atypia, 10 with atypia), and carcinoma (n = 40; 20 endometrioid, 10 serous, and 10 clear cell). All cases were evaluated immunohistochemically for p53 and proliferating cell nuclear antigen (PCNA) expression. Computerized image analysis was performed with a CAS 200 digital analyzer.

Results.—Expression of p53 was found only in carcinomas (65%) and endometrial hyperplasia with atypia (30%). Expression of p53 was higher in the poor prognostic categories (serous carcinoma and clear cell carcinoma) than in endometrioid carcinoma. In endometrioid carcinoma, p53 expression correlated with grade. Proliferating cell nuclear antigen showed a similar pattern of results to p53 in the various carcinoma subtypes and endometrioid carcinoma grades. Endometrial hyperplasia PCNA values were the lowest among all the groups. Both carcinomas and proliferative endometrium showed higher glandular and stromal PCNA values, significantly different from endometrial hyperplasia with atypia. In proliferative endometrium, stromal PCNA was the highest among all of the groups. The p53 and PCNA results correlated with each other for carcinoma.

Conclusions.—Computerized image analysis correlates well with the established morphologic groups of endometrial pathology and yields results consistent with previous studies. Owing to its higher degree of sensitivity, computerized image analysis is of potential use in cases of diagnostic dilemmas and can help objectively allocate the case in the correct category (eg, proliferative endometrium vs endometrial hyperplasia, endometrial hyperplasia with atypia vs endometrioid carcinoma). It is particularly useful in the evaluation of stromal changes.
CD79a+ T-Cell Lymphoblastic Lymphoma With Coexisting Langerhans Cell Histiocytosis
Authors: Li Shiyong , Borowitz Michael J.
Published: January 2021

Although there is a close association between Langerhans cell histiocytosis and malignant neoplasms, simultaneous occurrence of lymphoblastic lymphoma and Langerhans cell histiocytosis in the same lymph node is an extremely rare finding. Herein, we describe such a case in a 26-year-old woman who presented with progressive cervical lymphadenopathy. The lymphoma cells have an immature T-cell phenotype (terminal deoxynucleotidyl transferase+, HLA-DR+, CD34+, CD38+, and CD7+) with expression of both CD3 and CD79a on immunohistochemical stain. The Langerhans cells are present focally with the characteristic morphologic features and immunophenotype (CD1a+ and S100+). The significance of CD79a coexpression in T-cell lymphoblastic lymphoma and the association between lymphoblastic lymphoma and Langerhans cell histiocytosis are discussed.
Nasopharyngeal Gangliocytic Paraganglioma
Authors: Sinkre Prasanna , Lindberg Guy , Albores-Saavedra Jorge
Published: January 2021

Gangliocytic paraganglioma (GP) is a rare neoplasm described almost exclusively in the gastrointestinal tract, especially the periampullary region. However, several examples have been reported at various sites, including the stomach, jejunum, and appendix. Herein we report a case of GP involving the nasopharynx. To our knowledge, this is the first report of GP at this site. A 44-year-old woman presented with headaches and symptoms of fullness and pressure related to mass effect. An initial endoscopic biopsy was followed by surgical excision of the nasopharyngeal mass. The triphasic tumor fulfilled the morphologic and immunohistochemical criteria for GP. The histogenesis of GP is uncertain, and the current belief is that it arises from the embryonic ventral pancreas. This concept is based largely on the location of most cases, which is along the embryologic migration route of the ventral pancreas, as well as the expression of pancreatic polypeptide by the tumor. The nasopharyngeal location of our case clearly refutes the pancreatic origin of GP. We propose that the tumor probably arises from totipotential adult stem cells, which in the right microenvironment differentiate along nonnative cell lineages.