bluuebunny/crossref_metadata_2025 huggingface dataset:
Malignant Fibrous Histiocytoma: Between the Past and the Present
Authors: Al-Agha Osama M. , Igbokwe Anne A.
Published: February 2021

The precise nature and diagnostic concept of malignant fibrous histiocytoma (MFH) has been debated for years. Currently, a histiocytic lineage of the tumor cells is no longer favored. The nomenclature and classification of MFH and its subtypes have also been changed. The MFH pattern, especially that of storiform-pleomorphic variant, is viewed as a morphologic pattern shared by a number of sarcomas as well as by other nonsarcomas. Therefore, a diagnosis of MFH based solely on morphology is no longer acceptable and identification of a line of differentiation should be sought. A diagnosis of MFH should be made only for pleomorphic sarcomas in which no specific line of differentiation is discerned. Precise categorization of MFH-like tumors may require thorough sampling of the tumor and judicious use of immunohistochemistry and/or electron microscopy. Familiarity with the current terminology and classification of MFH and its subtypes is of paramount significance in the modern practice of pathology.
Primary Peritoneal Anaplastic Giant Cell Carcinoma: Case Report of an Unusual and Highly Malignant Müllerian Neoplasm
Authors: Lu Xian , Zhang Cunxian , Liu Fang , Sung C. James , Steinhoff Margaret M. , Lawrence W. Dwayne
Published: February 2021

Virtually all primary peritoneal carcinomas (PPCs) are of serous papillary type. We report an unusual histologic type of PPC composed of anaplastic giant cells, which exhibited an aggressive clinical course. A 72-year-old woman presented with lower abdominal pain. Computed tomography showed a diffuse omental thickening. The patient underwent an exploratory laparotomy with omentectomy, total hysterectomy, bilateral salpingo-oophorectomy, and appendectomy. Pathologic examination revealed extensive omental replacement by tumor but only superficial surface cortical involvement of both ovaries, a disease distribution consistent with a typical müllerian-derived PPC. However, this neoplasm was composed of diffuse anaplastic tumor giant cells, rather than serous carcinoma, which is the usual histologic type encountered in PPC. The patient died within 1 month after surgery. We report this unusual histologic variant of PPC to raise awareness that anaplastic giant cell carcinoma may arise in the pelvic peritoneum as a primary tumor.
Physician Compliance With Platelet Usage Criteria
Authors: Ang Daphne Chua , Marinescu Luminita , Kuriyan Mercy
Published: February 2021

Context.—Platelet transfusions are used in clinical practice as prophylaxis or to treat bleeding thrombocytopenic patients. This procedure also carries risks and costs and must be allocated appropriately.

Objective.—To evaluate physician compliance with the platelet transfusion criteria in our tertiary care academic institution.

Design.—We evaluated platelet unit releases from the transfusion service for 4 months, and we retrieved pretransfusion platelet counts. Reasons for transfusion were obtained by reviewing patient charts and talking to clinicians. Compliance with hospital criteria for platelet use was determined.

Results.—Platelets were given to 113 patients in 282 transfusion episodes. Criteria were not met for 32 (11%) of 282 platelet transfusions. Justifiable reasons for transfusion at platelet counts of greater than 10 × 103/μL included bleeding risk from oral ulcers, other risks of bleeding in patients who were transfused before discharge, and antiplatelet drug use in cardiac surgery patients. Reasons for transfusion at platelet counts greater than 10 × 103/ μL that were not justified include transfusion at a platelet count of 110 × 103/μL to a lung cancer patient with no platelet dysfunction and transfusion to 4 septic patients with platelet counts of 70 to 90 × 103/μL.

Conclusions.—This study showed 89% physician compliance with hospital platelet transfusion criteria. Transfusion-medicine specialists concurred that strict adherence to hospital blood usage criteria was not applicable for 9.2% of these patients; however, 5 (1.8%) of 282 platelet transfusions were not indicated and could have been prevented by transfusion medicine physician intervention.
Loss of the Y Chromosome: An Age-Related or Clonal Phenomenon in Acute Myelogenous Leukemia/Myelodysplastic Syndrome?
Authors: Wong Anna K. , Fang Belle , Zhang Ling , Guo Xiuqing , Lee Stephen , Schreck Rhona
Published: February 2021

Context.—The clinical association between loss of the Y chromosome and acute myelogenous leukemia and myelodysplastic syndrome (AML/MDS) has been debated because both phenomena are related to aging. A prior publication suggests that loss of the Y chromosome in more than 75% of cells may indicate a clonal phenomenon that could be a marker for hematologic disease.

Objective.—To evaluate the relationship between loss of the Y chromosome and AML/MDS.

Design.—A retrospective review of cytogenetic reports of 2896 male patients ascertained from 1996 to 2007 was performed. Results were stratified based on the percentage of cells missing the Y chromosome and were correlated with patients' ages and bone marrow biopsy reports through logistic regression analysis with adjustment for age.

Results.—Loss of the Y chromosome was found in 142 patients. Of these, 16 patients demonstrated myeloid disease, with 2 cases of AML and 14 cases of MDS. An increased incidence (P < .05) of AML/MDS was seen only in the group composed of 8 patients with complete loss of the Y chromosome in all karyotyped cells (1 case of AML and 7 cases of MDS).

Conclusion.—Loss of the Y chromosome appears to be primarily an age-related phenomenon. However, in individuals in which all cells on cytogenetic analysis showed loss of the Y chromosome, there was a statistically significant increase in AML/MDS, suggesting that the absence of any normal-dividing cells in a bone marrow analysis may be indicative of AML/MDS.
Practical Detection of t(14;18)(IgH/BCL2) in Follicular Lymphoma
Authors: Gu Keni , Chan Wing C. , Hawley Robert C.
Published: February 2021

The t(14;18)(q32;q21) translocation is the genetic hallmark of follicular lymphoma. Detection of this translocation can facilitate the diagnosis of follicular lymphoma and can be used to monitor response to therapy and level of residual disease. We herein review and compare practical techniques for detecting t(14;18)(q32;q21), including conventional cytogenetics, fluorescence in situ hybridization, Southern blot analysis, and polymerase chain reaction–based assay. Emphasis is placed on fluorescence in situ hybridization and polymerase chain reaction–based assay, given the applicability of these techniques to fixed, paraffin-embedded tissue.
Specimen Labeling Errors: A Q-Probes Analysis of 147 Clinical Laboratories
Authors: Wagar Elizabeth A. , Stankovic Ana K. , Raab Stephen , Nakhleh Raouf E. , Walsh Molly K.
Published: February 2021

Context.—Accurate specimen identification is critical for quality patient care. Improperly identified specimens can result in delayed diagnosis, additional laboratory testing, treatment of the wrong patient for the wrong disease, and severe transfusion reactions. Specimen identification errors have been reported to occur at rates of 0.1% to 5%.

Objective.—To determine the frequency of labeling errors in a multi-institutional survey.

Design.—Labeling errors were categorized as: (1) mislabeled, (2) unlabeled, (3) partially labeled, (4) incompletely labeled, and (5) illegible label. Blood specimens for routine or stat chemistry, hematology, and coagulation testing were included. Labeling error rates were calculated for each participant and tested for associations with institutional demographic and practice variable information.

Results.—More than 3.3 million specimen labels were reviewed by 147 laboratories. Labeling errors were identified at a rate of 0.92 per 1000 labels. Two variables were statistically associated with lower labeling error rates: (1) laboratories with current, ongoing quality monitors for specimen identification (P = .008) and (2) institutions with 24/7 phlebotomy services for inpatients (P = .02). Most institutions had written policies for specimen labeling at the bedside or in outpatient phlebotomy areas (96% and 98%, respectively). Allowance of relabeling of blood specimens by primary collecting personnel was reported by 42% of institutions.

Conclusions.—Laboratories actively engaged in ongoing specimen labeling quality monitors had fewer specimen labeling errors. Also, 24/7 phlebotomy services were associated with lower specimen error rates. Establishing quality metrics for specimen labeling and deploying 24/7 phlebotomy operations may contribute to improving the accuracy of specimen labeling for the clinical laboratory.
ProEx C Immunocytochemistry and High-Risk Human Papillomavirus DNA Testing in Papanicolaou Tests With Atypical Squamous Cell (ASC-US) Cytology: Correlation Study With Histologic Biopsy
Authors: Siddiqui Momin T. , Hornaman Kelly , Cohen Cynthia , Nassar Aziza
Published: February 2021

Context.—Papanicolaou tests with atypical squamous cells of undetermined significance (ASC-US) cytology and adjunct testing for high-risk human papillomaviruses (hr-HPV) are helpful in detecting high-grade disease. Detection of disease may be further improved with molecular markers known to be overexpressed in cervical carcinoma. ProEx C detects 2 such molecular markers, minichromosome maintenance protein 2 and topoisomerase II, which are associated with abnormal cell cycle regulation.

Objective.—To determine the utility of ProEx C as a marker for high-grade cervical intraepithelial neoplasia 2+ disease when compared with hr-HPV status in Papanicolaou tests with ASC-US cytology.

Design.—A SurePath slide was prepared on all ASC-US cases from the residual SurePath vial pellet and stained using the ProEx C reagent prediluted with water-bath antigen retrieval, using a Dako autostainer. Nuclear staining of cytologically atypical squamous cells was considered a positive result. Adjunct testing for hr-HPV used Digene Hybrid Capture 2. Follow-up biopsy results were available for review following the Papanicolaou test.

Results.—Two hundred patients with ASC-US diagnoses were part of this study. The sensitivities of ProEx C and hr-HPV testing in detecting high-grade cervical intraepithelial neoplasia 2+ disease were 98.04% and 82.35%, respectively, whereas the specificity for detecting high-grade disease was 74.50% and 73.15%, respectively.

Conclusions.—ProEx C staining is a more sensitive and specific biomarker for detecting cervical disease than adjunct testing for hr-HPV status in Papanicolaou tests with ASC-US.
Primary Malignant Melanoma of the Esophagus With Separate Foci of Melanoma In Situ and Atypical Melanocytic Hyperplasia in a Patient Positive for Human Immunodeficiency Virus: A Case Report and Review of the Literature
Authors: Fredricks Jennifer Rose Chapman , Bejarano Pablo A.
Published: February 2021

Primary malignant melanoma of the esophagus (PMME) is a rare neoplasm. The primary nature of esophageal melanoma has been questioned in the past because most reported cases have not been able to demonstrate local tumorigenesis or evolution of the malignancy from a preceding benign lesion or cell. In addition, the occurrence of metastatic melanoma to the esophagus is much more common than PMME. We report a case of PMME with separate foci of melanoma in situ and atypical melanocytic hyperplasia in a patient with human immunodeficiency virus infection. To our knowledge, this is the first reported case of PMME in a patient with a previous diagnosis of human immunodeficiency virus infection. In addition to adding data to the limited literature on this subject, we also provide histologic evidence that demonstrates the primary nature of some esophageal melanomas. This case also documents the occurrence of PMME in a patient positive for human immunodeficiency virus. We also provide a review of the relevant literature.
Hypersensitivity Pneumonitis: Clinical Perspectives
Authors: Madison J. Mark
Published: February 2021

Context.—The clinical course of hypersensitivity pneumonitis (HSP) is highly variable and its diagnosis clinically challenging.

Objective.—To provide a concise review of major clinical, radiographic, and laboratory findings that permits diagnosis of HSP from the standpoint of a clinician/pulmonologist.

Data Sources.—Review of major contemporary and historical literature in combination with the author's experience and viewpoints.

Conclusions.—The approach to the diagnosis of HSP is multidisciplinary. For patients being evaluated for unexplained dyspnea and cough and an unknown interstitial disease process, the initial evaluation should include detailed environmental and occupational histories with ancillary testing such as serology, chest imaging, inhalation challenges, and bronchoalveolar lavage, as indicated. In uncertain cases, lung biopsy is recommended.
Hypersensitivity Pneumonitis: Histopathology
Authors: Barrios Roberto J.
Published: February 2021

Context.—The classic histopathology of hypersensitivity pneumonitis (HSP) is well known but variations do occur and at times the diagnosis can be difficult. This is particularly true in the chronic stage of the disease.

Objective.—To review the wide variety of histopathologic changes that can be seen in HSP and to offer a practical approach to diagnosis, including the diagnosis of recently described variants of HSP such as the so-called hot tub lung.

Data Sources.—This review draws from the author's own experience and a concurrent search of national and international literature.

Conclusions.—The diagnosis of HSP can be made with confidence only in light of clinical, serologic, and radiographic data. A particular challenge for pathologists is the recognition of the disease in its chronic stage. In this stage, the identification of poorly formed granulomas in association with (1) a pattern of homogeneous linear fibrosis and (2) irregular fibrosis in a partially peribronchiolar distribution would facilitate the diagnosis.
Hypersensitivity Pneumonitis: An Immunopathology Review
Authors: Woda Bruce A.
Published: February 2021

Context.—Hypersensitivity pneumonitis (HSP) is an immunologically mediated alveolar and interstitial lung disease caused by repeated inhalation of organic dusts and some occupational agents.

Objective.—The pathogenesis of HSP is uncertain. A number of unexplained features of HSP remain, namely (1) why do so few exposed individuals develop clinical HSP, (2) what triggers an acute episode after prolonged periods of previous sensitization, and (3) what leads to disease progression. This article considers these issues and aims to discuss and clarify current concepts in pathogenesis.

Data Sources.—Pertinent literature review in conjunction with the author's personal interpretive opinion.

Conclusions.—Current data suggest that individuals with a TH1 dominant response are likely to develop clinical disease. There is also some evidence that genetic factors such as polymorphisms in the major histocompatibility complex, tumor necrosis factor α, and tissue inhibitor of metalloproteinase 3 are associated with the development of or resistance to the disease.
Application of Immunohistochemistry to Thyroid Neoplasms
Authors: Fischer Sandra , Asa Sylvia L.
Published: February 2021

Context.—Thyroid lesions with nodular architecture and follicular pattern of growth often pose difficulties in accurate diagnosis during the assessment of cytologic and histologic specimens. The diagnosis of follicular neoplasm on cytology or of follicular tumor of uncertain malignant potential on histology is likely to cause confusion among clinicians and delay effective management of these lesions. Occasionally, thyroid tumors represent unusual or metastatic lesions and their accurate diagnosis requires immunohistochemical confirmation.

Objective.—To review the literature on the applications of immunohistochemistry in the differential diagnosis of thyroid tumors.

Data Sources.—Relevant articles indexed in PubMed (National Library of Medicine) between 1976 and 2006.

Conclusions.—Our review supports the use of ancillary techniques involving a panel of antibodies suitable for immunohistochemistry and molecular analysis in the assessment of thyroid nodules. These tools can improve diagnostic accuracy when combined with standard morphologic criteria.
Application of Immunohistochemistry in the Diagnosis of Non-Hodgkin and Hodgkin Lymphoma
Authors: Higgins Russell A. , Blankenship Jennifer E. , Kinney Marsha C.
Published: February 2021

Context.—Beginning with the immunologic classifications of Lukes and Collins and Kiel and culminating in the Revised European-American Lymphoma and World Health Organization classifications, the diagnosis of lymphoid tumors relies heavily on the determination of cell lineage, maturation, and function, based on antigen expression in addition to morphology and clinical features. Technologic advances in immunology, antibody production, genetic analysis, cloning, and the identification of new genes and proteins by microarray and proteomics have provided pathologists with many antibodies to use in routine diagnosis.

Objective.—To provide guidance to the practicing pathologist in the appropriate selection of an antibody panel for the diagnosis of lymphoma based on morphology and relevant clinical data and to avoid pitfalls in the interpretation of immunohistochemical data. Attention is given to some of the newer antibodies, particularly against transcription factors, that are diagnostically and prognostically useful.

Data Sources.—The information presented in this article is based on review of the literature using the OVID database (Ovid MEDLINE 1950 to present with daily update) and 20 years of experience in diagnostic hematopathology.

Conclusions.—Immunophenotyping is required for the diagnosis and classification of lymphoid malignancies. Many paraffin-reactive antibodies are available to the pathologist but most are not specific. To avoid diagnostic pitfalls, interpretation of marker studies must be based on a panel and knowledge of a particular antigen's expression in normal, reactive, and neoplastic conditions.
The Impact of the Distribution of Human Papillomavirus Types and Associated High-Risk Lesions in a Colposcopy Population for Monitoring Vaccine Efficacy
Authors: Antonishyn Nick A. , Horsman Greg B. , Kelln Rod A. , Saggar Jasdeep , Severini Alberto
Published: February 2021

Context.—Impact studies of the new human papillomavirus (HPV) vaccines will be biased unless local baseline distribution studies are conducted. Vaccine cross protection for other important oncogenic HPV types and the emergence of potential genotype replacements require the knowledge of the prevaccine epidemiology of HPV.

Objective.—To determine the prevaccine distribution of HPV types in Saskatchewan, using a subpopulation of women referred to a colposcopy clinic.

Design.—One thousand three hundred fifty-five specimens obtained during colposcopic examination were typed for HPV using L1 or E1 gene polymerase chain reaction and direct sequencing. HPV-16 and HPV-31 infections were confirmed with real-time E6 polymerase chain reaction. Indeterminate samples were analyzed using Luminex technology. Correlations of the HPV type and histology were examined for statistical significance.

Results.—The most commonly identified genotype in patients with cervical intraepithelial neoplasia grade 2 or worse was HPV-16 (46.7%) followed by HPV-31 (14.7%) and then HPV-18 (3.9%). Fifteen of 330 specimens that were positive for HPV-16 or HPV-31 were further resolved to be mixed HPV-16/HPV-31 infections by real-time polymerase chain reaction. The risk of cervical intraepithelial neoplasia associated with HPV-18 infection (0.4–1.7) is substantially lower than with either HPV-16 (3.6–11.0) or HPV-31 (1.8–12.6).

Conclusions.—HPV-31 is contributing significantly to the proportion of women with cervical intraepithelial neoplasia in our population and shows a higher prevalence than HPV-18 in high-grade lesions. The clinical significance of HPV-31 may be underestimated and its continued significance will depend on the level of cross protection offered by the new vaccines.
Pseudosarcomas of Soft Tissue
Authors: Rosenberg Andrew E.
Published: February 2021

One of the most common and important pitfalls in soft tissue pathology are the so-called pseudosarcomas. These lesions are nonneoplastic; however, their rapid growth, hypercellularity, cytologic atypia, and mitotic activity makes them prone to be misinterpreted as sarcoma. The most common of these lesions are fibroblastic/myofibroblastic and matrix-forming proliferations, including nodular fasciitis, proliferative fasciitis and myositis, ischemic fasciitis, massive localized edema, myositis ossificans, and bizarre parosteal osteochondromatous proliferation and related entities. Most of these lesions rarely recur following simple excision; therefore, their accurate recognition helps prevent excessive therapy.
Placental Pathology, a Survival Guide
Authors: Roberts Drucilla J.
Published: February 2021

Placental pathology continues to be an underutilized, undertaught, and inadequately handled surgical subspecialty. The requests for placental pathology are soaring, due partly to demands from obstetricians and to the litigious environment in which they practice, and to improved obstetrical care leading to pregnancies in medically challenging situations. Evaluation of the placenta requires a good understanding of the questions and issues concerning both the fetus/infant and the mother. Information from placental pathology can be critical in early neonatal care and in reproductive planning for the family, and it can provide risk assessment for neurologic outcome of the infant. A comfortable interaction among the obstetric staff, mothers, and pathologists often obviates need for legal intervention in unexpected pregnancy outcomes. Some critical pathologic features that involve maternal and fetal management are illustrated herein. A template for gross examination and a few critical histopathologic diagnostic features with clincopathologic correlation are included.
Proteomic Comparison of Nasopharyngeal Cancer Cell Lines C666-1 and NP69 Identifies Down-Regulation of Annexin II and β2-Tubulin for Nasopharyngeal Carcinoma
Authors: Chan Charles M. L. , Wong S. C. Cesar , Lam Money Y. Y. , Hui Edwin P. , Chan John K. C. , Lo Elena S. F. , Cheuk W. , Wong Manson C. K. , Tsao S. W. , Chan Anthony T. C.
Published: February 2021

Context.—Nasopharyngeal carcinoma (NPC), common in southern China and North Africa, has a complex etiology involving interplay between viral, environmental, and hereditary factors and is almost constantly associated with the Epstein-Barr virus. Since the prognosis of locally advanced and metastatic diseases is poor, increased understanding of the pathogenesis of NPC would be important for discovering novel markers for patients' management.

Objectives.—To compare the proteomic expression profile between an Epstein-Barr virus–associated NPC cell line (C666-1) and a normal NP cell line (NP69). The proteins with differential expression were analyzed in 40 undifferentiated NPC paraffin-embedded specimens.

Design.—Differentially expressed proteins discovered between the two cell lines were identified by mass spectrometry. After confirmation by immunocytochemical staining, their expression in patient samples was measured using 40 pairs of undifferentiated NPCs together with their adjacent normal epithelia.

Results.—Proteomic findings indicated that adenosine triphosphate synthase α chain was up-regulated, whereas annexin II, annexin V, β2-tubulin, and profilin 1 were down-regulated. After confirming the results in agar-processed cell lines, annexin II and β2-tubulin expression were found to be lower in tumor cells than in adjacent normal epithelial cells in 100% and 90% of the patients' specimens, respectively. Finally, annexin II down-regulation was positively associated with lymph node metastasis, suggesting that it may be a prognostic factor in NPC.

Conclusions.—The results suggest that annexin II and β2-tubulin down-regulation is important in NPC formation and may represent potential targets for further investigations.
Urine Culture Contamination: A College of American Pathologists Q-Probes Study of 127 Laboratories
Authors: Bekeris Leonas G. , Jones Bruce Allen , Walsh Molly K. , Wagar Elizabeth A.
Published: February 2021

Context.—While urine culture contamination may not be completely avoidable, some laboratories have lower contamination rates than others. A College of American Pathologists (CAP) 1998 Q-Probes study showed that many interventions commonly assumed to reduce contamination were not demonstrably effective. This article revisits the issue.

Objective.—To examine the frequency of urine culture contamination, review current laboratory practices in the collection of urine culture specimens, and determine practice characteristics that may be associated with the contamination rate.

Design.—Laboratories participating in a CAP Q-Probes study were required to prospectively collect data on 120 consecutive urine culture specimens and provide information on the patient's demographics (age and sex), the location where the specimen was collected, how the specimen was handled, the number of isolates in quantities greater than or equal to 10 000 colony-forming units (CFU)/mL, and whether the laboratory considered the specimen to be contaminated. Specific inclusion and exclusion criteria were provided to the participants. Each laboratory completed a supplemental questionnaire that probed for specific laboratory urine culture collection practices.

Results.—One hundred twenty-seven laboratories participated in the study. Results from a total of 14 739 urine specimens were received. For the purpose of this study, a urine specimen was determined to be contaminated if the culture yielded more than 2 isolates in quantities greater than or equal to 10 000 CFU/mL. Using these criteria the median institution had a contamination rate of 15.0%. Laboratories in the 10th percentile (low performance) had an average contamination rate of 41.7%, while laboratories in the 90th percentile had an average rate of 0.8%. The collection site had no influence on the contamination rate, but postcollection processing, especially refrigeration of the specimen, had a substantial effect. Providing instruction to patients produced a statistically significant lowering of contamination rates for specimens from male patients (P = .006) but not for female patients, except when written instructions were provided in the emergency room, in which case specimen contamination rates for both male and female patients dropped (P = .01).

Conclusions.—The median contamination rates remain at a level comparable to the results seen in a previous Q-Probes study, and some laboratories have very high contamination rates. Specimen refrigeration is associated with lower overall urine culture specimen contamination rate. Providing patient instruction is also associated with lower contamination rates under specific circumstances.
Longitudinal Clinical Evaluation of a Novel Antibody Cocktail for Detection of High-Grade Squamous Intraepithelial Lesions on Cervical Cytology Specimens
Authors: Tambouret Rosemary H. , Misdraji Joseph , Wilbur David C.
Published: February 2021

Context.—Although cervical cancer screening by cytology is successful, the test continues to show relatively poor operating characteristics. Cell cycle markers may enhance detection of high-grade squamous intraepithelial lesions.

Objective.—To determine the clinical usefulness of ProExC, an immunocytochemical assay for cell cycle components, performed on routine cervical cytology samples.

Design.—Cervical cytology samples were collected using the SurePath method. Residual cells remaining after preparation of the Papanicolaou-stained slide were used to make a second slide for ProExC staining using an indirect polymer-based immunoperoxidase method. Only adequately cellular slides were evaluated for the presence of nuclear staining within cytologically abnormal epithelial cells. Results were correlated with clinical follow-up.

Results.—Six hundred twenty-four samples were satisfactorily cellular and stained. Correlation with clinical follow-up for subsequent cervical intraepithelial neoplasia 2+ on biopsy/high-grade squamous intraepithelial lesion on cytology (CIN 2+/HSIL) showed that 434 results were true negative, 78 true positive, 18 false-negative, and 94 false-positive, resulting in a sensitivity/specificity of 81%/82%. When ProExC results were combined with any level of cytologic atypia, sensitivity for CIN 2+/HSIL was 92% and specificity was 84%.

Conclusions.—ProExC shows promise as an aid in enhancing the sensitivity and specificity of cervical cytology for subsequent CIN 2+/HSIL and may be useful in identifying those cervical lesions most apt to progress.
Touch Imprint Cytology in Tumor Tissue Banks for the Confirmation of Neoplastic Cellularity and for DNA Extraction
Authors: Mangia Anita , Chiriatti Annalisa , Chiarappa Patrizia , Incalza Maria Angela , Antonaci Giovanni , Pilato Brunella , Simone Giovanni , Tommasi Stefania , Paradiso Angelo
Published: February 2021

Context.—Learning the characteristics of frozen tissue samples stored in tumor banks for biological studies remains a problem.

Objective.—To assess the use of touch imprint cytology on fresh tissue samples as a rapid and reliable method of determining the presence and quantity of neoplastic cells before freezing.

Design.—Touch imprint cytology was performed on 259 specimens of operable breast cancer. Touch imprints were prepared from fresh tissue specimens before freezing samples for storage. Each tumor sample was imprinted on a glass slide and stained with hematoxylin-eosin. Tumor cellularity was quantified as negative, poor, moderate, or rich.

Results.—A significant correlation was found between samples with a tumor size greater than 2 cm and high tumor cellularity (P = .03; χ2 test). Furthermore, 35% of ductal tumors showed higher tumor cellularity compared with lobular tumors (P < .001; χ2 test). No association was found between lymph node status and tumor grade. When samples for which more than 2 imprints were available were examined, tumor cellularity among imprints of the same sample showed an overall agreement of 0.67 (P < .001; κ statistic). It was also determined that the higher the cellularity, the higher the agreement. Our data also showed concordance of 0.87 (P < .001; κ statistic) between touch imprint cytology imprints and histologic sections from contiguous tumor. Moreover, 11 randomly selected samples underwent DNA extraction, polymerase chain reaction, and sequencing to verify the feasibility of DNA analyses. We found that DNA from touch imprint cytology was amplifiable and suitable for direct sequencing.

Conclusions.—Touch imprint cytology may represent an important step in the quality control of tumor cellularity of breast cancer specimens designed to be stored in tumor biobanks and a valid method for assessing the suitability of such tissue for further biomorphologic and biomolecular applications.
Myelodysplastic Syndromes Arising in Patients With Germline TP53 Mutation and Li-Fraumeni Syndrome
Authors: Talwalkar Sameer S. , Cameron Yin C. , Naeem Rizwan C. , John Hicks M. , Strong Louise C. , Abruzzo Lynne V.
Published: February 2021

Context.—Li-Fraumeni syndrome (LFS), characterized by predisposition to early onset of a variety of malignancies, is usually associated with germline mutation of the tumor-suppressor gene, TP53. Mutation carriers are at increased risk of multiple primary tumors, many of which arise in previous radiation-therapy sites. In patients with LFS, acute myeloid leukemia is uncommon and myelodysplastic syndrome (MDS) is rare.

Objective.—To evaluate the morphologic, cytogenetic, and molecular diagnostic findings of 3 unique cases of MDS arising in patients with germline TP53 mutation, 2 with classic LFS.

Design.—We searched the Li-Fraumeni Syndrome Registry in the Department of Genetics at the University of Texas M. D. Anderson Cancer Center (Houston, Texas) and identified 3 patients with documented germline TP53 mutations or LFS who had developed MDS during a period of 6 years (2000–2005). The clinical, cytogenetic, and molecular diagnostic data and bone marrow aspirate smears and biopsies on all patients were reviewed. Immunohistochemical staining with antibody to p53 was also performed.

Results.—Two patients met the criteria for classic LFS; one had no history of malignancy in first-degree relatives. The MDS followed chemotherapy and radiation therapy and progressed to acute myeloid leukemia in 2 patients. Cytogenetic analysis demonstrated chromosome 5 abnormalities in a complex karyotype in all cases. Two patients died, one of acute myeloid leukemia and one with glioblastoma multiforme, MDS, and persistent pancytopenia.

Conclusions.—Patients with LFS may develop MDS, which is most likely therapy-related and is associated with cytogenetic markers of poor prognosis.
Clinicopathologic Analysis of Cutaneous Lymphoma in Taiwan: A High Frequency of Extranodal Natural Killer/T-Cell Lymphoma, Nasal Type, With an Extremely Poor Prognosis
Authors: Liao Jia-Bin , Chuang Shih-Sung , Chen Hsiu-Chiung , Tseng Hui-Hwa , Wang Jyh-Seng , Hsieh Pin-Pen
Published: February 2021

Context.—Primary cutaneous lymphoma is an uncommon, extranodal lymphoma, and it is usually more indolent with a better prognosis than its histologically similar systemic counterpart is.

Objectives.—To illustrate the clinicopathologic features of cutaneous lymphomas in Taiwan and to compare the relative frequencies of subtypes of cutaneous lymphoma among different geographic areas.

Design.—A total of 56 patients with cutaneous lymphomas were retrospectively collected and were reclassified according to the 2005 World Health Organization and the European Organization for Research and Treatment of Cancer and the 2008 World Health Organization classifications. The data were compared with those from other studies for different geographic areas.

Results.—Thirty-one (55%) tumors were primary cutaneous lymphomas, and twenty-five (45%) tumors were secondary or concurrent cutaneous lymphomas. Among primary cutaneous lymphomas, 23 cases (74%) were T-cell or natural killer–cell lymphomas, and 8 cases (26%) were B-cell lymphomas. The most common types were extranodal natural killer/T-cell lymphoma, nasal type, and primary cutaneous peripheral T-cell lymphoma, unspecified (5 cases each; 16%). In contrast with other primary cutaneous B-cell and T-cell lymphomas, either primary or secondary extranodal cutaneous natural killer/T-cell lymphomas, nasal type, had extremely poor prognoses (1-year overall survival, 0%).

Conclusions.—This study showed that the frequency of subtypes of primary cutaneous lymphoma varied in different geographic areas. Compared with the Western countries, there was a higher frequency of extranodal natural killer/T-cell lymphoma, nasal type, and a lower frequency of mycosis fungoides in Taiwan. Extranodal natural killer/T-cell lymphoma, nasal type, also had an extremely poor prognosis compared with other lymphomas.
Intrapulmonary Ectopic Liver After Orthotopic Heart Transplantation
Authors: Mehta Rupal I. , Lai Chi K. , Kee Stephen , Fishbein Michael C.
Published: February 2021

We report a case of a 54-year-old woman who was found to have multiple intrapulmonary nodules detected on imaging 33 months after orthotopic heart transplantation. Needle biopsy of 2 discrete nodules showed benign hepatic tissue, consistent with intrapulmonary foci of ectopic liver. In this report, the clinical, radiologic, microscopic, and fluorescent in situ hybridization results of 2 biopsied nodules are described. A brief review of the published information on ectopic liver is also presented. To our knowledge, multiple ectopic foci of the liver have never been reported at any site. Furthermore, this is the first reported case that involves a transplant recipient, thereby introducing additional, unique ramifications to this rare but intriguing entity.
Merkel Cell Carcinoma
Authors: Wong Hannah H. , Wang Jun
Published: February 2021

Merkel cell carcinoma is a rare, highly aggressive neuroendocrine cutaneous neoplasm with a variable clinical presentation. Histologically, it is a predominantly dermal-based lesion composed of monotonous small round cells with scanty cytoplasm, often difficult to differentiate from small round cell tumors, metastatic small cell carcinoma, blastic hematologic malignancies, and melanoma. The malignant cells express both epithelial and neuroendocrine immunohistochemical markers, a unique feature that helps differentiate this neoplasm from other entities. The pathogenesis of Merkel cell carcinoma has remained a mystery despite its association with various chromosomal abnormalities and with growth signaling and apoptotic pathways. The discovery of the Merkel cell polyomavirus suggests another clue to its pathogenesis. This virus integrates into band 3p14 and promotes carcinogenesis by altering the activity of tumor suppressor and cell cycle regulatory proteins. This discovery of the Merkel cell polyomavirus may greatly enhance our understanding of this rare aggressive neoplasm and allow further advancements in treatment.
Comparison of ThinPrep Preparations to Other Preparation Types in Gastrointestinal Cytology: Observations From the College of American Pathologists Interlaboratory Comparison Program in Nongynecologic Cytology
Authors: Clayton Amy C. , Bentz Joel S. , Wasserman Patricia G. , Schwartz Mary R. , Souers Rhona J. , Chmara Beth Anne , Laucirica Rodolfo , Clary Karen M. , Moriarty Ann T. ,   for the College of American Pathologists Cytopathology Resource Committee
Published: February 2021

Context.—Differences in participant responses for ThinPrep (TP) and non-ThinPrep (NTP) preparations for gastrointestinal cytology challenges, which circulated in the College of American Pathologists Interlaboratory Comparison Program in Nongynecologic Cytology (CAP NGC), may help to identify performance variations between preparation types.

Objective.—To compare the performance of TP-prepared slides of gastrointestinal exfoliative cytology specimens to that of NTP preparations in the CAP NGC program.

Design.—Participant responses between 2000 and 2007 were evaluated for esophageal wash/brush, gastric wash/brush, and biliary tract brush specimens with a reference diagnosis of adenocarcinoma, squamous cell carcinoma, carcinoid, or spindle cell neoplasm. ThinPrep challenges were compared with NTP preparations (conventional smears, cytospins) for discordant responses.

Results.—In all, 6023 pathologist responses and 3825 cytotechnologist responses were reviewed. Non-ThinPrep preparations comprised 93% (n  =  11 588) of the challenges, while 7% (n  =  912) were TP material. A match for a “positive/suspicious” diagnosis was seen in 88.5% of NTP and 95.9% of TP preparations (P < .001). These results were statistically significant when the specific reference diagnosis was adenocarcinoma (P < .001). Overall performance of cytotechnologists was not different from that of pathologists (89.2% versus 89.0%; P  =  .75). Cytotechnologists had better performance for detecting squamous cell carcinoma (96.3% versus 92.6%; P < .001), while pathologists had better performance for detecting spindle cell neoplasm (79.7% versus 42.9%; P < .001).

Conclusions.—ThinPrep preparations performed significantly better than NTP preparations in gastrointestinal cytology specimens circulated in an interlaboratory comparison program. Performance varied by reference interpretation, with the best performance for the interpretation of adenocarcinoma. Cytotechnologists and pathologists performed at the same level overall, but with differences for the diagnosis of spindle cell neoplasm and squamous carcinoma.
Acute Erythroid Leukemia
Authors: Zuo Zhuang , Polski Jacek M. , Kasyan Armen , Medeiros L. Jeffrey
Published: February 2021

Context.—Acute erythroid leukemia (AEL) is an uncommon type of acute myeloid leukemia (AML), representing less than 5% of all cases. Acute erythroid leukemia is characterized by a predominant erythroid proliferation, and in the current World Health Organization (WHO) classification scheme there are 2 subtypes: erythroleukemia (erythroid/myeloid leukemia) and pure erythroid leukemia. Morphologic findings are most important for establishing the diagnosis. The erythroleukemia subtype, which is most common, is defined as the presence of 50% or more erythroid precursors and 20% or more blasts in the nonerythroid component. The pure erythroid leukemia subtype is composed of 80% or more immature erythroblasts. Although these morphologic criteria appear straightforward, AEL overlaps with other types of AML and myelodysplastic syndrome that are erythroid rich.

Objective.—To provide an update of AEL, including clinical presentation, morphologic features, immunophenotype, and cytogenetic and molecular data. As the erythroleukemia subtype is most common, the literature and this review are biased towards this subtype of AEL.

Data Sources.—Clinicopathologic, cytogenetic, and molecular information were extracted from our review of pertinent literature and a subset of AEL cases in the files of The University of Texas M. D. Anderson Cancer Center (Houston) and University of South Alabama (Mobile).

Conclusions.—The current WHO criteria for establishing the diagnosis of AEL reduce the frequency of this entity, as cases once classified as the erythroleukemia subtype are now reclassified as other types of AML, particularly AML with myelodysplasia-related changes and therapy-related AML. This reclassification also may have prognostic significance for patients with the erythroleukemia subtype of AEL. In contrast, the current WHO criteria appear to have little impact on the frequency and poor prognosis of patients with the pure erythroid leukemia subtype of AEL. Molecular studies, preferably using high-throughput methods, are needed for a better understanding of the pathogenesis of AEL, and for developing diagnostic and prognostic markers.
Challenges and Opportunities in the Adoption of College of American Pathologists Checklists in Electronic Format: Perspectives and Experience of Reporting Pathology Protocols Project (RPP2) Participant Laboratories
Authors: Hassell Lewis A. , Parwani Anil V. , Weiss Lawrence , Jones Michael A. , Ye Jay
Published: February 2021

Context.—The site-specific cancer checklists developed by the College of American Pathologists have the potential to improve the quality of data derived from pathology reports and incorporated into cancer registry databases and are now mandated report elements by various accrediting bodies. A pilot project, funded by the Centers for Disease Control National Project for Cancer Registries in 2004, brought 4 pathology services in 3 states, with differing baseline implementations of the checklists, the opportunity to partner with their state National Project for Cancer Registry and their laboratory information system vendors to evaluate the feasibility of using electronically encoded College of American Pathologists cancer checklists for melanoma and tumors of the breast and prostate.

Objectives.—To identify existing and potential barriers to adoption of electronically encoded checklists and to also identify unique benefits not associated with text-only uses of the checklists.

Design.—Participants mapped an implementation process from their current state to an electronic checklist–capable state. For a sample of cases of melanoma, prostate, and breast cancers, the checklist elements were captured and transmitted to the registry using Health Level 7 (version 2.3.1). Process assessments with adoption of electronic checklists were conducted to assess pathologist effect and other potential barriers. An evaluation of the utility and usefulness of electronic checklists was performed after the project.

Results.—All 4 laboratories successfully performed the capture of individual data elements from the College of American Pathologists checklist into a discrete format suitable for electronic transmission. The effect on pathologist performance and laboratory workflow was neutral. Points of resistance were identified in the checklists and in individual users. Specific challenges in individual laboratories varied according to the personnel and the baseline system in use. Clinical responses to implemented changes were generally positive. Analysis of the postproject experiences of the laboratories showed expansion of use and additional utility in some, but not all, laboratories.

Conclusions.—Pathology laboratory adoption of the College of American Pathologists cancer checklists in an electronic format suited to direct transmission to cancer registries poses business case, information technology, and human resource challenges. Laboratory information system vendor readiness to upgrade systems to facilitate this process helps to reduce some of these challenges. Personalities and preferences in practices may yet pose barriers to widespread adoption.
Interference of Hawthorn on Serum Digoxin Measurements by Immunoassays and Pharmacodynamic Interaction With Digoxin
Authors: Dasgupta Amitava , Kidd Laura , Poindexter Brian J. , Bick Roger J.
Published: February 2021

Context.—Hawthorn is an herb indicated for treating cardiac illness. Because a patient taking digoxin may also take hawthorn, we investigated potential interference of hawthorn in serum digoxin measurements using immunoassays as well as pharmacodynamic interaction between hawthorn and digoxin. Hawthorn contains alkaloids that are structurally similar to digoxin and may interfere with serum digoxin measurement using immunoassays. In addition, hawthorn has cardioactive properties similar to digoxin.

Objective.—To study potential pharmacodynamic interaction between hawthorn and digoxin.

Design.—The effects of hawthorn extract on serum digoxin measurements using Digoxin III (Abbott Laboratories, Abbott Park, Illinois) and the Tina-Quant digoxin assay (Roche Diagnostics, Indianapolis, Indiana) were investigated using 2 different brands of extract. To study the pharmacodynamic interaction between hawthorn and digoxin, we used an isolated adult rat cardiomyocyte system, measuring calcium transients by real-time fluorescence spectrophotometry.

Results.—Hawthorn interfered only with the Digoxin III immunoassay but had no effect on the Tina-Quant assay. Both hawthorn extracts increased intracellular calcium levels, but the lack of additive response with digoxin suggests both may bind to the same site of Na, K adenosine triphosphatase.

Conclusion.—Because of interference of hawthorn with a digoxin immunoassay and pharmacodynamic interaction with digoxin, a patient receiving digoxin should avoid hawthorn.
Molecular Pathogenesis of Sporadic Melanoma and Melanoma-Initiating Cells
Authors: Kong Yunyi , Kumar Suresh M. , Xu Xiaowei
Published: February 2021

Recent advances in molecular genetics and cancer stem cell biology have shed some light on the molecular basis of melanomagenesis. In this review, we will focus on major genetic alterations in the melanoma, particularly pathways involved in cell proliferation, apoptosis, and tumor suppression. The potential role of melanoma-initiating cells during melanomagenesis and progression will also be discussed. Understanding pathogenesis of melanoma may uncover new diagnostic clues and therapeutic targets for this increasingly prevalent disease.