bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of Ataxia-Telangiectasia Mutated Protein Expression in Diffuse Large B-Cell Lymphomas of Primary Central Nervous System and Non–Central Nervous System Origin
Authors: Kim Se Hoon , Cheong June-Won , Park Kwang Hwa , Kim Tai Seung , Yang Woo-Ick
Published: February 2021

Context.—The ataxia-telangiectasia mutated (ATM) gene encodes a nuclear 370-kd phosphoprotein known to be associated with chromosomal regions containing double-strand breaks. The mutations in the ATM gene may be involved in the development of some subtypes of sporadic lymphomas and leukemias. In primary central nervous system diffuse large B-cell lymphomas (PCNS DLBCLs), the pathogenetic role of ATM mutation has not been investigated.

Objective.—To investigate ATM protein expression in PCNS DLBCLs, in comparison with that in non–central nervous system (non-CNS) DLBCLs and to study the relationship of ATM protein loss with several clinicopathologic parameters.

Design.—This study included 42 cases of PCNS DLBCL and 33 cases of non-CNS DLBCL from immunocompetent patients. The ATM protein loss was analyzed by immunohistochemical staining. For the subclassification of DLBCL and analysis of the relationship between ATM and other prognostic markers, we performed immunohistochemical evaluation to detect the following markers: Bcl-6, CD10, multiple myeloma-1, CD138, Bcl-2, Ki-67, and p53.

Results.—The loss of ATM expression was statistically more frequent in PCNS DLBCLs (21/42 cases [50.0%]) than in non-CNS DLBCLs (0/33 cases [0.0%]; P < .001). The loss of ATM expression was not a prognostic marker in PCNS DLBCLs (P = .64). The loss of ATM expression had a strong correlation with the germinal center B-cell–like subtype (P = .01), a low Ki-67 labeling index (P = .03), and low Bcl-2 expression (P = .01) among several clinicopathologic parameters.

Conclusions.—Our results suggest that the ATM protein is more strongly correlated with PCNS DLBCL lymphomagenesis than with non-CNS DLBCLs, especially in germinal center B-cell–like subtypes demonstrating low Ki-67 labeling indexes and low Bcl-2 expression.
Hemangiomas and Angiosarcomas of the Breast: Diagnostic Utility of Cell Cycle Markers With Emphasis on Ki-67
Authors: Shin Sandra J. , Lesser Martin , Rosen Paul Peter
Published: February 2021

Context.—Vascular tumors comprise a minor subgroup of tumors arising in the breast and represent variants of hemangiomas and angiosarcomas. Diagnostic challenges may arise when differentiating hemangiomas from types I and II angiosarcomas. Ki-67 expression has been used as an adjunct to distinguish between benign and malignant lesions exhibiting histologic overlap at various anatomic sites.

Objective.—To investigate the utility of Ki-67 and other cell cycle regulatory proteins (S-phase kinase-associated protein 2 [Skp2], p27, and cyclin D1) in the differential diagnosis of mammary vascular lesions.

Design.—Thirty-four vascular tumors (21 hemangiomas and 13 angiosarcomas) of the breast were studied. The Ki-67 index and immunoreactivity for Skp2, p27, and cyclin D1 were determined in each case. Appropriate statistical methods were used.

Results.—The mean value of Ki-67 index was statistically different when comparing hemangiomas and angiosarcomas (P < .001). Angiosarcomas were typically positive for Skp2, whereas hemangiomas were negative (P < .001). Sensitivity and specificity cutoffs for Ki-67 index to distinguish hemangiomas from angiosarcomas showed a candidate cutoff point of 175. The mean values of Ki-67 of low-grade angiosarcomas were significantly different from all hemangiomas (P < .001) and also different from the subset of atypical hemangiomas (P = .02). Sensitivity and specificity cutoffs for Ki-67 index to distinguish all hemangiomas from low-grade angiosarcomas showed a candidate cutoff point between 150 and 175. Among angiosarcomas, positivity for Ki-67 was inversely related to that of p27 but not to Skp2 or cyclin D1. This was also true among hemangiomas.

Conclusions.—Ki-67 index can be used as a diagnostic tool to distinguish between benign and malignant vascular lesions of the breast. This can be particularly helpful in cases of histologic overlap such as low-grade angiosarcoma and hemangioma.
Thyroid Transcription Factor 1 Immunohistochemistry as an Intraoperative Diagnostic Tool at Frozen Section for Distinction Between Primary and Secondary Lung Tumors
Authors: Butcher David N. , Goldstraw Peter , Ladas George , Dusmet Michael E. , Sheppard Mary N. , Nicholson Andrew G.
Published: February 2021

Context.—Intraoperative distinction between primary and metastatic carcinomas in the lung at frozen section remains problematic.

Objective.—To assess the value and practicality of immunohistochemistry for thyroid transcription factor 1 at the time of intraoperative frozen section.

Design.—Thirty-three patients presented with either a solitary pulmonary mass or 2 pulmonary masses and a history of carcinoma in a different organ. In addition to routine frozen section for assessment of tumor type, we looked for expression of thyroid transcription factor 1, using the EnVision system with abridged methodology.

Results.—Ten cases were positive for thyroid transcription factor 1, which was confirmed on subsequent paraffin sections. Nine of these were confirmed as primary pulmonary adenocarcinomas, but 1 case proved to be a rare false-positive metastatic colonic carcinoma. Twenty-three cases were negative on frozen section and reported as favoring metastatic disease. In all cases, additional immunohistochemical data increased diagnostic confidence, but particularly in cases of positive primary pulmonary tumors and in cases with disease metastatic from sites other than the large bowel. The average time in addition to that of the basic frozen section was 24 minutes per test with a cost of £32 (US$57).

Conclusions.—Frozen section immunohistochemistry for thyroid transcription factor 1 shows specificity and sensitivity similar to those seen for formalin-fixed tissues and is feasible within the time frame of a thoracotomy. Diagnostic confidence is increased, especially with positive primary pulmonary tumors. However, its practice should be properly planned within an operative procedure as liberal usage will likely have significant staff and cost implications.
Low Smooth Muscle Cell Densities Characterize Sites With Isolated Interstitial Lipid in Coronary Artery Intima
Authors: Tracy Richard E.
Published: February 2021

Context.—The initial step in the development of atherosclerotic lesions is suggested to be the retention of low-density lipoprotein. This suggestion would seem to imply that some interval of time ought to intervene between the initial retention of interstitial lipid and subsequent influx of fatty streak cellular elements. Yet no evidence for such a waiting interval has been offered.

Objective.—To describe findings from application to coronary arteries from forensic autopsy specimens of a new method for staining lipids in paraffin sections.

Design.—Isolated interstitial lipid (IIL) (extracellular lipid pools accompanied by no perceptible intracellular lipid or other fatty streak elements at the affected sites) was identified in various intimal compartments, and smooth muscle cell (SMC) numbers were counted at these sites.

Results.—Isolated interstitial lipid was a surprisingly frequent finding after age 35 years, seen in 87 (84%) of 104 cases. The number of SMCs per unit area of sectioned intima was high in specimens lacking IIL (15.5 SMCs/[100 μm]2), lowest at sites displaying IIL (8.3 SMCs/[100 μm]2), and intermediate at sites lacking IIL in specimens that do contain IIL at some other location (12.6 SMCs/[100 μm]2).

Conclusions.—These findings plus other evidence support the proposal that retention of lipid most often happens, in aging arteries, at sites where the architecture was previously altered by diluting of constant SMC numbers by expanding collagenous matrix, thereby lowering SMC densities.
Type IV Collagen Immunostaining Is a Simple, Reliable Diagnostic Tool for Distinguishing Between Adenomatous and Normal Pituitary Glands
Authors: Jarzembowski Jason , Lloyd Ricardo , McKeever Paul
Published: February 2021

Context.—Pituitary adenomas are clinically diagnosed based on radiologic studies and/or secondary effects of hormone production. Definitive pathologic identification relies on immunohistochemical detection of a clonal population of hormone-producing cells. However, not all adenomas secrete hormones, so performing a battery of stains is inefficient. Reports have shown decreased type IV collagen in the stroma of other epithelial tumors.

Objective.—To validate type IV collagen immunohistochemistry as a diagnostic method.

Design.—We immunostained 27 adenomas and 19 normal pituitaries. The areas with the sparsest type IV collagen fibers were viewed at 3 magnifications (×10, ×20, and ×40 objectives), counting 1, 3, or 10 microscopic fields. A field was scored as “traversable” if a path existed from any point on the periphery of the field to a point on the approximately opposite periphery that did not cross any stained fibers. Results were compared with reticulin staining and to the existing diagnosis previously determined by histology, hormone immunostaining, and clinical correlation.

Results.—Adenomas have less type IV collagen in their basement membranes, leading to sparser, trabecular staining in neoplasms versus a more rigid meshwork pattern in normal glands. One might envision the stained fibers as maze walls—one can traverse medium-powered fields in an adenoma, but one hits dead ends and gets trapped in those of a normal gland. Finding a single representative ×10 field to be traversable was 97.5% sensitive and 96.5% specific for an adenoma. Reticulin staining yielded identical results.

Conclusions.—Type IV collagen immunostaining is a simple and reliable method of diagnosing pituitary adenomas.
Quantitative Assessment of the BCR-ABL Transcript Using the Cepheid Xpert BCR-ABL Monitor Assay
Authors: Dufresne Scott D. , Belloni Dorothy R. , Levy Norman B. , Tsongalis Gregory J.
Published: February 2021

Context.—Chronic myelogenous leukemia (CML) and the assessment of the BCR-ABL transcript has become a new paradigm. Novel tyrosine kinase inhibitors as mainstream therapeutic options for the CML patient warrant routine quantification of the BCR-ABL transcript. The Xpert BCR-ABL Monitor assay is a nested reverse transcriptase polymerase chain reaction that greatly reduces technical time by using a single cartridge to isolate RNA and run a quantitative reverse transcriptase polymerase chain reaction.

Objective.—To evaluate the Xpert BCR-ABL Monitor assay for quantitative assessment of the BCR-ABL transcript in CML patients.

Design.—A standard curve of K-562 cells diluted in normal peripheral blood was used to test the sensitivity, linearity, and percent coefficient of variation of the assay. Specimen stability was tested by running standard curves immediately and after 24 hours or 96 hours of storage at 4°C. Specimens from normal controls, patients known to have CML, or patients suspected of having CML were also tested.

Results.—The sensitivity of the assay was sufficient to detect 1 K-562 cell in 105 normal cells. The R2 of the standard curve was 0.98 and the percent coefficient of variation for each data point was 15% to 24%. Eleven of 14 patients with known CML on imatinib treatment tested positive for the BCR-ABL transcript, whereas 10 normal controls tested negative.

Conclusions.—The Xpert BCR-ABL Monitor assay is a rapid, sensitive method for monitoring the presence of the BCR-ABL transcript in CML patients. The single-use cartridge minimizes hands-on technical time, minimizes the potential for contamination, and allows quantitative BCR-ABL testing to be performed in a random access fashion.
Relevance of Parvovirus B19, Herpes Simplex Virus 2, and Cytomegalovirus Virologic Markers in Maternal Serum for Diagnosis of Unexplained Recurrent Abortions
Authors: Zaki Maysaa El-Sayed , Goda Hossam
Published: February 2021

Context.—The impact of viral infections during pregnancy on adverse pregnancy outcomes is not understood fully.

Objective.—To assess the frequency of parvovirus B19, herpes simplex 2, and cytomegalovirus infections in relation to late abortions, in sera from Egyptian pregnant women to establish basic knowledge for future pregnancy care. In addition, to study the diagnostic value of specific immunoglobulin M (IgM) against those viruses compared with their genomes detection by polymerase chain reaction in maternal serum as a noninvasive method of laboratory diagnosis.

Design.—Patients were recruited at the Women's Clinic, Mansoura University. One group of patients with recurrent spontaneous abortions (RSA) and a second group of pregnant women without a history of RSA were evaluated including demographic, medical, and clinical data. Virologic markers were evaluated for specific IgM and for viral DNA to cytomegalovirus, herpes simplex virus 2, and parvovirus B19.

Results.—There was a statistically significant difference between the RSA group and the pregnant women without RSA group in frequency of parvovirus IgM (84% and 16.7%, respectively) (P < .001) and herpes simplex IgM (40% for RSA) (P = .001). Parvovirus B19 viremia was positive in 48% RSA, herpes simplex virus 2 was positive in 32% RSA, and cytomegalovirus was positive in 12% RSA patients. For RSA patients with parvovirus viremia, the mean ± SD of IgM value was 78.5 ± 30.12 IU/mL, and for RSA patients with negative viremia it was 30.02 ± 17.64 IU/mL with statistically significant difference between both levels (P < .001).

Conclusions.—From this study, we conclude that viral infections with parvovirus B19 and herpes simplex 2 were frequently associated with recurrent abortions, and careful investigation for this condition must include evaluating these patients for the previously mentioned viruses. Serologic study by specific IgM for parvovirus and herpes simplex seem to be reliable as screening tests for high-risk pregnancy.
Occult Primary Parotid Gland Acinic Cell Adenocarcinoma Presenting With Extensive Lung Metastasis
Authors: Tavora Fabio , Rassaei Negar , Shilo Konstantin , Foss Robert D. , Galvin Jeffrey R. , Travis William D. , Franks Teri J.
Published: February 2021

Acinic cell adenocarcinoma is a malignant salivary gland neoplasm with a relatively low rate of lymphangitic spread to regional lymph nodes. Distant metastases are rare and their occurrence typically indicates an unfavorable outcome. We encountered an unusual example of acinic cell adenocarcinoma that initially presented in the lung, whereas the primary parotid carcinoma, despite extensive clinical evaluation, only became apparent 1 year after initial diagnosis. The histologic, immunohistochemical, and ultrastructural features of the tumor in the parotid gland and lung were similar. The tumor displayed an aggressive behavior resulting in death within 2 years of the initial presentation. This presentation is unique, showing that peripheral lung tumors of salivary gland type are likely to be metastatic, and careful clinical evaluation is warranted in establishing their primary site of origin.
Molecular Pathology of Lymphangioleiomyomatosis and Other Perivascular Epithelioid Cell Tumors
Authors: Martignoni Guido , Pea Maurizio , Reghellin Daniela , Gobbo Stefano , Zamboni Giuseppe , Chilosi Marco , Bonetti Franco
Published: February 2021

Context.

Lymphangioleiomyomatosis (LAM) is a cystic lung disease that can be included in the wide group of proliferative lesions named PEComas (perivascular epithelioid cell tumors). These proliferative tumors are characterized by the coexpression of myogenic and melanogenesis-related markers. In all these lesions, genetic alterations related to the tuberous sclerosis complex (TSC) have been demonstrated. Striking improvements in the understanding of the genetic basis of this autosomal dominant genetic disease are coupled to the understanding of the mechanisms that link the loss of TSC1 (9q34) or TSC2 (16p13.3) genes with the regulation of the Rheb/m-TOR/p70S6K pathway. These data have opened a new era in the comprehension of the pathogenesis of LAM and have also suggested new therapeutic strategies for this potentially lethal disease.

Objective.

To present and discuss the pathologic and molecular features of LAM within the spectrum of PEComas, providing a rational approach to their diagnosis.

Data Sources.

The published literature and personal experience.

Conclusions.

The inclusion of LAM within the PEComa category is supported by a variety of biologic data and can significantly help in providing a comprehensive view of this interesting and clinically relevant group of lesions. The demonstration of molecular alterations of the mTOR pathway in LAM and other PEComas represents a rational basis for innovative therapeutic approaches with inhibitors of mTOR signaling.
Neurocysticercosis
Authors: Moskowitz Jack , Mendelsohn Geoffrey
Published: February 2021

Neurocysticercosis is a significant public health issue within the United States. Although cysticercosis was once thought to have been eradicated in the United States, the number of documented cases is rising and immigrants from endemic areas are at the highest risk for acquiring and developing this disease. The clinical presentation of neurocysticercosis is variable and vague neurologic symptoms or sudden unexplained death in individuals with risk factors may be the only available information warranting a consideration of neurocysticercosis. Radiologic and laboratory findings can help guide medical and surgical interventions, while histologic confirmation establishes a more definitive diagnosis. Encysted larvae can be found throughout the central nervous system and undergo progressive stages of decay. Degenerating vesicles elicit an inflammatory response, involving surrounding structures, and cause the major clinical symptomatology.
Precursor Lymphoblastic Lymphoma Reoccurring as a Donor-Derived Neoplasm: A Case Report and Review of the Literature
Authors: Dickson Brendan C. , Chung Catherine T-S. , Patterson Bruce J. , Riddell Robert H. , Kamel-Reid Suzanne , Messner Hans A. , Lipton Jeffrey H.
Published: February 2021

Precursor lymphoblastic lymphoma is an uncommon neoplasm. We report the case of a man who presented with precursor T lymphoblastic lymphoma and ultimately received an allogeneic bone marrow transplant from his human leukocyte antigen–identical sister. Four years later he developed recurrent disease. By means of DNA probing for the amelogenin locus and fluorescence in situ hybridization, the neoplastic cells of the recurrent lesion were found to be of donor origin. We offer the report of a patient with an unusual lymphoblastic lymphoma who, after successful bone marrow transplantation, developed the same disease of donor cell origin; further, we offer a literature review on donor cell lymphoma.
Improving the Quality of Surgical Pathology Reports for Breast Cancer: A Centralized Audit With Feedback
Authors: Onerheim Ronald , Racette Pierre , Jacques André , Gagnon Robert
Published: February 2021

Context.—Good communication of pathologic characteristics of a malignancy is crucial to therapy choices and accurate prognostication. The information must be easily retrieved from a surgical pathology report.

Objectives.—To evaluate, first in 1999, the quality of surgical pathology reports for segmental breast resections for cancer in Quebec hospitals. Subsequently, to reevaluate, in 2003, the same indicators to determine if the first surveillance, with feedback, was associated with an improvement in the quality of the reports.

Design.—All Quebec hospitals performing the preset number of 20 or more segmental breast resections for cancer in 1999 and 2003 participated. A committee of pathologists, after review of the literature, chose 7 diagnostic elements deemed vital to a surgical pathology report for conservative breast cancer surgery. Medical archivists in each institution were instructed on how to retrieve the data. The main outcome measure was the presence or absence of the diagnostic information clearly presented on the surgical pathology report.

Results.—Fifty-one hospitals participated in 1999 and 50 in 2003. Overall, conformity improved from 85.0% in 1999 for the first evaluation to 92.5% in 2003 for the second evaluation (P < .001). Six of the 7 indicators showed an improvement in the level of conformity between the first and second evaluations. Conformity was weakest for recording the distance between the tumor and the resection margin (68.2%) and vascular/lymphatic invasion (61.4%) in 1999.

Conclusions.—Surveillance of quality of surgical pathology reports, with feedback, is significantly associated with an improvement in the quality of reports.
Use of In Situ Hybridization to Detect Human Papillomavirus in Head and Neck Squamous Cell Carcinoma Patients Without a History of Alcohol or Tobacco Use
Authors: Lee Walter T. , Tubbs Raymond R. , Teker Aysenur M. , Scharpf Joseph , Strome Marshall , Wood Benjamin , Lorenz Robert R. , Hunt Jennifer
Published: February 2021

Context.—Head and neck squamous cell carcinoma is commonly associated with tobacco and alcohol use. There are, however, a group of patients without a significant history of tobacco or alcohol use, and the etiology of these tumors is incompletely understood.

Objective.—To examine tumors in this subpopulation for association with human papillomavirus (HPV) using newly available in situ hybridization probes.

Design.—Between October 2004 and October 2005, 22 patients who did not use alcohol or tobacco were included. Formalin-fixed, paraffin-embedded tissue sections were used to perform in situ hybridization using newly available probe sets (Ventana Medical Systems, Tucson, Ariz). The slides were examined for the presence of integrated HPV using light microscopy. Positive and negative xenograft controls were run with the assay.

Results.—The mean age of the patients was 64 years. There were 14 men and 8 women. The most common anatomic sites included tongue (n = 8), tonsil (n = 7), and larynx (n = 7). All cases and controls were successfully stained. Only 2 cases were positive for high-risk HPV, and both demonstrated an integrated pattern. Both cases were tumors of the tonsil. No cases were positive for low-risk HPV.

Conclusions.—These results demonstrate that the new probe sets for HPV can be used very efficiently in clinical pathology material of head and neck squamous cell carcinoma. Our data show that high-risk HPV is an uncommon finding in head and neck squamous cell carcinoma from patients who do not have a history of tobacco or alcohol use; low-risk HPV was not seen in any case.
Patient Safety and Error Reduction in Surgical Pathology
Authors: Nakhleh Raouf E.
Published: February 2021

Context.—National patient safety goals and error reduction efforts should be addressed by each surgical pathology laboratory.

Objective.—To review issues relevant to patient safety and error reduction in surgical pathology in the context of continuous quality improvement.

Data Sources.—The literature is reviewed.

Conclusions.—Patient safety goals can and should be addressed within the context of a quality improvement plan. Multiple factors that contribute to errors in surgical pathology are discussed. The current literature defines the extent of these problems within specific segments of the test cycle (preanalytic, analytic, and postanalytic). Potential solutions are presented that may reduce or avoid errors. In addition, general principles are outlined that enhance the laboratory's ability to successfully and continuously address patient safety and error reduction.
Lymphoepithelial Carcinoma of the Parotid Glands and Its Relationship With Benign Lymphoepithelial Lesions
Authors: Schneider Manuela , Rizzardi Clara
Published: February 2021

The salivary glands, despite their relatively simple morphology, give rise to more than 30 histologically distinct benign and malignant tumors. Salivary gland neoplasms comprise less than 2% of all tumors in humans and 3% of all head and neck tumors. They arise in the parotid gland in 80% of cases, and approximately 80% are benign and 20% are malignant. Among them are lymphoepithelial lesions, rare lesions of the salivary glands and especially of the parotid gland that are characterized by lymphocytic infiltration associated with an epithelial proliferation. They are divided into benign, which is considered as a tumorlike condition, and malignant, which is a rare carcinoma of the salivary glands. This article provides a review of the current knowledge on lymphoepithelial carcinoma with a look at its association with benign lesions and on the importance of making the correct diagnosis for the appropriate treatment.
Application of Immunohistochemistry to Cytology
Authors: Fowler Larry J. , Lachar Whitney A.
Published: February 2021

Context.—The uses of monoclonal antibodies via immunochemistry have been reported frequently within the literature using various methodologies with applications to cytology specimens. The direct application of immunochemistry to cytology may have a variety of pitfalls that the general pathologist familiar with its application to histology may be unaware of when applying it prospectively to patient specimens.

Objective.—To review common pitfalls when applying immunochemistry to cytology specimens and to suggest approaches to the more common differential dilemmas that apply to a variety of cytology specimens that could be seen in a general pathology practice.

Data Sources.—The authors' own experiences of applying immunochemistry to cytopathology specimens within an academic setting along with supportive data from the literature.

Conclusions.—Immunochemistry can be used to increase the predictability of a cytology diagnosis if care is taken with the cytology sample preparation methodology and there is judicious use of select monoclonal antibody panels to support a specific cytology diagnosis. Up-to-date evidence-based antibody databases should be used when selecting antibody panels.
Application of Immunohistochemistry to the Diagnosis of Malignant Mesothelioma
Authors: Marchevsky Alberto M.
Published: February 2021

Context.—The diagnosis of malignant mesothelioma (MM) is rendered with the aid of immunohistochemistry to demonstrate the presence of “mesothelial,” “epithelial,” or “sarcomatous” differentiation. Antibody panels that have been proposed for the distinction between MM and other neoplasms usually include 2 or more epithelial markers used to exclude the diagnosis of a carcinoma, such as monoclonal and polyclonal carcinoembryonic antigen, Ber-EP4, B72.3, CD15, MOC-31, thyroid transcription factor 1, BG8, and others, and 2 or more mesothelial markers used to confirm the diagnosis of MM, such as cytokeratin 5/6, calretinin, HBME-1, thrombomodulin, WT-1, mesothelin, D2-40, and podoplanin. In general, most antibody panels provide excellent sensitivity and specificity for the differential diagnosis between MM epithelial variant and adenocarcinoma, particularly of lung origin. However, the accuracy of these markers is lower for the diagnosis of sarcomatous MM and for the differential diagnosis between MM and squamous cell carcinoma and carcinomas of renal, ovarian, and other origin.

Objective.—To identify optimal antibody panels for the diagnosis of MM.

Data Sources.—Literature review to determine how many and which mesothelial and epithelial markers need to be included in differential diagnosis antibody panels.

Conclusions.—Various antibody panels have been recommended for the diagnosis of MM, with no overall consensus about how many and which markers should be used. A recent study with Bayesian statistics has demonstrated that the use of many markers does not provide higher diagnostic accuracy than the use of selected single antibodies or various combinations of only 2 markers. There is a need for the development of evidence-based or consensus-based guidelines for the diagnosis of MM in different differential diagnosis situations.
Application of Immunohistochemistry to Infections
Authors: Eyzaguirre Eduardo , Haque Abida K.
Published: February 2021

Context.—Pathologists play an important role in the diagnosis or exclusion of infectious diseases. Traditionally, the diagnosis of infectious diseases rely on serologic assays and cultures. Serologic results may be difficult to interpret in the setting of immunosuppression, fresh tissue is not always available for culture, and culture of fastidious pathogens can be difficult and may take weeks or months to yield a result. Although some microorganisms or their cytopathic effects may be readily identifiable on routine and/ or histochemical stains, often these changes are not specific or are sparse in the sample evaluated. In these cases, additional immunohistochemical stains are often needed to establish the diagnosis of infection.

Objective.—To review the current value and limitations of the use of immunohistochemistry in the diagnosis of infectious diseases in formalin-fixed tissue samples.

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

Conclusions.—Immunohistochemistry has proven to be a useful tool in the diagnosis of infectious diseases in tissue samples. Immunohistochemistry is especially useful in the identification of microorganisms that are present in low numbers, stain poorly, are fastidious to grow, are noncultivable, or exhibit an atypical morphology. Finally, it is important to remember that there may be widespread occurrence of common antigens among bacteria and pathogenic fungi and both monoclonal and polyclonal antibodies must be tested for possible cross-reactivity with other organisms.
Application of Immunohistochemistry to Soft Tissue Neoplasms
Authors: Heim-Hall Josefine , Yohe Sophia L.
Published: February 2021

Context.—Soft tissue tumors are composed of numerous and complex diagnostic entities. Because of this complexity and the recognition of an intermediate malignancy category including some tumors with a deceptively bland histologic appearance, soft tissue tumors may represent a major diagnostic challenge to the general practicing pathologist.

Objective.—To correctly diagnose soft tissue tumors with the ancillary use of immunohistochemistry.

Data Sources.—Review of the current literature with emphasis on those tumors for which immunohistochemistry has proven to be particularly useful.

Conclusions.—Immunohistochemistry plays an important role in the diagnosis of soft tissue tumors. One of its major utilities is to correctly identify a tumor as being of mesenchymal or nonmesenchymal origin. Once mesenchymal origin has been established, histologic subtyping according to specific cell lineage may be achieved with the use of lineage-specific markers. Tumors of uncertain cell lineage and tumors with primitive small round cell morphology are often characterized by a unique immunohistochemical phenotype. In this group of tumors, immunohistochemistry is most widely applied and is of greatest value. Despite the rapid development of molecular genetic techniques, immunohistochemistry still remains the most important diagnostic tool in the diagnosis of soft tissue tumors aside from recognition of morphologic features and clinical correlation.
Formatting Pathology Reports: Applying Four Design Principles to Improve Communication and Patient Safety
Authors: Valenstein Paul N.
Published: February 2021

Context.—Eighty-two million surgical pathology and cytology reports were issued in the United States during 2007; a subset of these reports will be misunderstood by readers. Recent attention has focused on standardizing the content of pathology reports, particularly for common malignancies, to facilitate transmission of required information. Comparatively little attention has been focused on the format of reports—the arrangement of headlines, text blocks, and other report elements to optimize communication.

Objective.—To provide guidance to report designers and authors about how to format reports to maximize the speed, fidelity, and ease of information transfer.

Data Sources.—Review of relevant literature from commercial publishing and aviation and the fields of cognitive psychology and pathology, supplemented with an analysis of 10 000 pathology reports and the author's personal experience as a practicing pathologist.

Conclusions.—Four evidence-based and time-tested principles can help pathologists format information to communicate more effectively: (1) use of diagnostic headlines to emphasize key points, (2) maintenance of layout continuity with other reports and over time, (3) optimization of information density for readers, and (4) reduction of extraneous information or “clutter.” Practical advice is also provided to help pathologists minimize corruption of formatting as reports are transmitted electronically between medical information systems.
Gaucher Disease: Review of the Literature
Authors: Chen Mingyi , Wang Jun
Published: February 2021

We present a brief review of Gaucher disease, the most common lysosomal storage disease. Gaucher disease is a rare autosomal recessive disorder characterized by defective function of the catabolic enzyme β-glucocerebrosidase, leading to an accumulation of its substrate, glucocerebroside, in the mononuclear phagocyte system, especially histiocytes in the spleen, lymph nodes, and bone marrow; Kupffer cells in the liver; osteoclasts in bone; microglia in the central nervous system; alveolar macrophages in the lungs; and histiocytes in the gastrointestinal tracts, genitourinary tracts, and the peritoneum. Clinical signs and symptoms include neurologic dysfunctions, bone infarcts and malformations, hepatosplenomegaly and hypersplenism leading to anemia, neutropenia, and thrombocytopenia. Enzyme replacement therapy with recombinant glucocerebrosidase is the mainstay of treatment for Gaucher disease, which became the first successfully managed lipid storage disease. Future treatments may include oral enzyme replacement and/or gene therapy interventions.
The Informed Consent Process in Whole Blood Donation
Authors: Alaishuski Lindsay A. , Grim Rodney D. , Domen Ronald E.
Published: February 2021

Context.—Informed consent in transfusion medicine has been an area lacking of significant research and it is unknown if donors fully comprehend the risks associated with whole blood donation.

Objective.—To assess the adequacy of the informed consent process in whole blood donation.

Design.—A brief questionnaire was constructed and distributed to whole blood donors visiting various fixed and mobile donor sites of the Central Pennsylvania Blood Bank. Questions consisted of demographic information; donor opinions of information content, length, and comprehension; and a short quiz pertaining to donor risks and eligibility.

Results.—Analysis of 849 surveys demonstrated that donors comprehended a mean of 73.5% of the various donor eligibility and risks that were surveyed. Female and younger donors scored statistically higher on comprehension questions compared with male and older counterparts. Donors were most aware of (1) donor eligibility requirements related to acquired immunodeficiency syndrome comprehension, (2) the risk of dizziness postdonation, and (3) having lived in a certain country (93.7%–95.6% comprehension, respectively). Donors were least aware of (1) the risk of a possible referral to a physician for outstanding medical conditions or positive test results, (2) the risk of a positive test result, and (3) West Nile virus testing information (22.4%–49.3% comprehension, respectively).

Conclusions.—Whole blood donors believed that they were giving informed consent, but a significant percentage of donors were unaware of several of the risks associated with blood donation, including participation in West Nile virus research testing. Our data suggest that donors do not fully comprehend the risks of whole blood donation and that repetition of information to the donor, and in multiple formats, strengthens the level of comprehension and thus the informed consent process.
Ovarian Frozen Section Diagnosis: Use of Whole-Slide Imaging Shows Excellent Correlation Between Virtual Slide and Original Interpretations in a Large Series of Cases
Authors: Fallon Margaret A. , Wilbur David C. , Prasad Manju
Published: February 2021

Context.—Whole-slide images (WSI) are a tool for remote interpretation, archiving, and teaching. Ovarian frozen sections (FS) are common and hence determination of the operating characteristics of the interpretation of these specimens using WSI is important.

Objectives.—To test the reproducibility and accuracy of ovarian FS interpretation using WSI, as compared with routine analog interpretation, to understand the technology limits and unique interpretive pitfalls.

Design.—A sequential series of ovarian FS slides, representative of routine practice, were converted to WSI. Whole-slide images were examined by 2 pathologists, masked to all prior results. Correlation characteristics among the WSI, the original, and the final interpretations were analyzed.

Results.—A total of 52 cases, consisting of 71 FS slides, were included; 34 cases (65%) were benign, and 18 cases (35%) were malignant, borderline, and of uncertain potential (9 [17%], 7 [13%], and 2 [4%] of 52 cases, respectively). The correlation between WSI and FS interpretations was 96% (50 of 52) for each pathologist for benign versus malignant, borderline, and uncertain entities. Each pathologist undercalled 2 borderline malignant cases (4%) as benign cysts on WSI. There were no overcalls of benign cases. Specific issues within the benign and malignant groups involved endometriosis versus hemorrhagic corpora lutea, and granulosa cell tumor versus carcinoma, respectively.

Conclusions.—The correlation between original FS and WSI interpretations was very high. The few discordant cases represent recognized differential diagnostic issues. Ability to examine gross pathology and real-time consultation with surgeons might be expected to improve performance. Ovarian FS diagnosis by WSI is accurate and reproducible, and thus, remote interpretation, teaching, and digital archiving of ovarian FS specimens by this method can be reliable.
Limiting the Use of Atypical/Inconclusive as a Category in Nongynecologic Cytology Specimens
Authors: Koen Tracie M. , Mody Dina R. , Scheiber-Pacht Miriam , Fairley Todd , Thrall Michael J.
Published: February 2021

Context.—Atypical has served as a descriptive term in cytology since the birth of the specialty by Dr Papanicolaou. This indeterminate diagnosis often results in repeat biopsies or additional tissue sampling and a needless delay in patient care if used inappropriately. Because of the definitional ambiguity of this term and the associated physician frustration, we have made a concerted effort at Methodist Hospital since 1995 to minimize the use of atypical as a diagnostic category.

Objective.—To evaluate whether the dissolution of the atypical category has increased our cytologic-histologic discordance rate to more than the published reference range.

Design.—From March 3, 2006, through December 31, 2008, all nongynecologic cases with atypical/indeterminate listed as the general diagnostic category were identified and retrieved from our laboratory data files. We then assessed the cytologic-histologic correlation rate during the corresponding time frame.

Results.—A total of 48 atypical cases (0.2%) from 19 347 nongynecologic specimens were identified. Of the atypical cases, 52% (25 of 48) had intradepartmental consultation, 58% (28 of 48) had additional preparations examined, and 29% (14 of 48) documented limitations because of poor preservation. Our cytologic-histologic discrepancy rate for the period was 5.5% (214 of 3912 cases), with 89.3% (191 of 214 cases) resulting from sampling issues. On review of the small percentage of cytologic interpretative discrepancies, only one case was unhampered by less than 10% tumor cellularity or poor preservation.

Conclusions.—Not using atypical as a diagnostic category, unless defined by Bethesda guidelines, has not affected our cytologic-histologic correlation rate.
The Immunohistochemistry Laboratory: Looking at Molecules and Preparing for Tomorrow
Authors: Teruya-Feldstein Julie
Published: February 2021

Context.—Surgical and subspecialty pathologists rely heavily on the patient's clinical context, imaging studies, morphology, and on ancillary studies such as immunohistochemistry (IHC), cytogenetics, and molecular diagnostics in arriving at accurate, contemporary diagnoses. Lymphoma/leukemia classification has led the way in the number of antibodies used in IHC algorithmic diagnostic approaches to distinguish more than 40 diseases. As the era of genomics, transcriptomics, proteomics, and targeted pathway therapeutics unfolds—and as infusion of federal funds to programs such as Accelerating Clinical Trials of Novel Oncologic PathWays (ACTNOW) requires that correlative biomarker assays be performed in Clinical Laboratory Improvement Amendments of 1988 (CLIA)–certified IHC laboratories—we face changes and challenges for the future.

Objective.—To discuss the laboratory, pertinent daily diagnostic, prognostic, and therapeutic uses of IHC, and future directions and challenges.

Data Sources.—Recent literature review and ongoing current activities in our laboratory and institution.

Conclusions.—Meticulous attention at the microscope by expert subspecialty pathologists using ancillary methods is important in making correct diagnoses. Awareness of the literature and interactions with our research colleagues, including clinical, basic, and translational scientists, continue to expand our insights into and understanding of complex diseases; this will ultimately provide prognostic information to assist in appropriate clinical management of our patients and development of new targeted or combination therapies. Multimodality correlations will continue, with morphology, imaging data, immunophenotyping, and genetics as well as steadily increasing integration of pathway signaling, genome, sequenome, transcriptome, and proteome data used in clinical settings.
Modified Alcian Blue Enhances the Intraoperative Diagnosis of Sentinel Lymph Node Metastasis in Invasive Lobular Carcinoma: A Prospective Study
Authors: Khoury Thaer , Malik Deborah , Fan Cathy , Tan Dongfeng , Kulkarni Swati
Published: February 2021

Context.—The sensitivity of an intraoperative diagnosis of sentinel lymph node metastasis of invasive lobular carcinoma using conventional staining is low.

Objective.—To develop a fast, modified, Alcian blue stain to decrease the intraoperative false-negative results in testing for metastatic invasive lobular carcinoma.

Design.—Modified Alcian blue was optimized. Patients who had invasive lobular carcinoma on needle biopsy were candidates for this study. Touch preparations from every sentinel lymph node were prospectively prepared in the same manner, one stained with modified Alcian blue and one with conventional staining. These slides were independently interpreted.

Results.—A total of 121 sentinel lymph nodes from 31 patients with invasive lobular carcinoma were studied. There were 11 patients (35.5%) who had at least one positive lymph node test result. There were a total of 18 positive lymph node results (14.9%). Although 10 sentinel lymph nodes with abnormalities were detected in 7 patients with conventional staining, modified Alcian blue detected 15 sentinel lymph node abnormalities in 10 patients. Modified Alcian blue increased the sensitivity compared with conventional staining from 63.6% to 90.9% (calculated based on the number of patients) and from 55.6% to 83.3% (calculated based on number of sentinel lymph nodes). The staining process takes approximately 11 minutes.

Conclusions.—Modified Alcian blue stain is a relatively rapid, cheap, highly sensitive, and specific method of detecting metastatic invasive lobular carcinoma. This method can be used in conjunction with conventional staining methods used intraoperatively.
Sarcomatoid Neoplasms of the Lung and Pleura
Authors: Travis William D.
Published: February 2021

Sarcomatoid neoplasms of the lung and pleura are rare tumors that present a complex differential diagnosis, making them challenging for surgical pathologists. In the lung, the main tumors are the sarcomatoid carcinomas, including pleomorphic carcinoma, spindle cell carcinoma, giant cell carcinoma, carcinosarcoma, and pulmonary blastoma. They are characterized by histologic heterogeneity; molecular data support their origin from a pluripotent stem cell that undergoes neoplastic transformation with divergent epithelial and sarcomatous differentiation. Diagnosis is difficult in small biopsy specimens and typically requires a resection specimen. Despite the presence of sarcomatoid features, these tumors are classified as lung carcinomas. Pulmonary blastomas must be distinguished from pleuropulmonary blastomas, which are a unique type of thoracic sarcoma typically occurring in young children. In the pleura, the main tumors to consider are the sarcomatoid and desmoplastic types of malignant mesothelioma, solitary fibrous tumor, and desmoid tumor. While light microscopy is sufficient to diagnose most of these tumors, immunohistochemistry can be useful in selected settings. In particular, it can aid to confirm epithelial differentiation in spindle cell carcinomas and the presence of rhabdomyosarcoma in sarcomatoid carcinomas, mesotheliomas, or pleuropulmonary blastomas. For sarcomatoid and desmoplastic mesothelioma, keratin is the most useful stain because it can highlight invasive growth and mesothelial markers are positive in only the minority of cases. Clinical and radiologic correlation is needed to separate some pleomorphic carcinomas with pleural involvement from sarcomatoid malignant mesothelioma, since these poorly differentiated tumors may not express the usual immunohistochemical markers for carcinoma or mesothelioma.
International Internet-Based Assessment of Observer Variability for Diagnostically Challenging Endometrial Biopsies
Authors: Marotti Jonathan D , Glatz Katharina , Parkash Vinita , Hecht Jonathan L
Published: February 2021

Context.—Endometrial carcinoma of endometrioid histology is frequently preceded by endometrial hyperplasia, from which localized, premalignant lesions called endometrial intraepithelial neoplasia (EIN) emerge. Diagnostic criteria for EIN have been developed by histopathologic correlation with clinical outcome, molecular changes, and objective computerized histomorphometry. However, several benign mimics of EIN continue to cause diagnostic confusion.

Objective.—To better understand the diagnostic pitfalls of EIN.

Design.—An online quiz of 18 endometrial biopsies considered difficult by a gynecologic pathologist was constructed. Each case contained clinical history and at least 2 microscopic images. Answer choices included the following: (1) EIN, (2) polyp, (3) benign endometrium (proliferative, secretory, disordered, tubal metaplasia, and lower uterine segment), and (4) adenocarcinoma. Online tutorials were offered at the start, and the authors' diagnosis and clinical follow-up were provided at the end.

Results.—The quiz was completed by 78 participants from 13 countries. Agreement with the authors ranged from 17% to 100% (mean, 55%). For analysis, polyp and benign responses were grouped. The mean percentage of agreement was highest in cases of polyp with no special features (88%), tubal metaplasia (87%), and secretory change (75%). Poorer agreement was seen with cases containing mucinous metaplasia (38%), extensive morular metaplasia (28%), and EIN arising in a polyp (53%). The mean percentage of agreement for EIN without these features was 63%.

Conclusions.—Although the reproducibility of EIN criteria was good, a subset of biopsies with morular metaplasia and EIN in polyps was problematic and likely required consensus review.