bluuebunny/crossref_metadata_2025 huggingface dataset:
Familial Hypercholesterolemia
Authors: Suárez Bagnasco Mariana
Published: February 2021

Familial hypercholesterolemia is a genetic and metabolic disorder associated with an increased risk of morbidity and mortality. Two main types of familial hypercholesterolemia are distinguished: heterozygous familial hypercholesterolemia and homozygous familial hypercholesterolemia. Homozygous familial hypercholesterolemia progresses much more aggressively with higher levels of LDL-C and higher risk of cardiovascular disease at earlier ages. The prognosis of homozygous familial hypercholesterolemia largely depends on the LDL-C levels. Reducing the LDL-C level is one of the primary goals of treatment patients with familial hypercholesterolemia. Effective control of LDL-C significantly reduces the cardiovascular morbidity and mortality. Understanding the factors likely to affect treatment adherence is paramount. Adherence to treatment can be improve when a genetic etiology is confirmed. Positive genetic test result has beneficial effects on adherence to pharmacotherapy and in achieving LDL-C levels reduction.
The Application of Chitosan-Based Compounds against Metallic Corrosion
Authors: El Ibrahimi Brahim , Guo Lei , Verger Nardeli Jéssica , Oukhrib Rachid
Published: February 2021

Biopolymers-based compounds were used by different manners for metal protection toward corrosion phenomena, namely via inhibiting additive and coating strategies. In the last decade, the application of these compounds or their chemically modified forms as effective replacements for toxic inorganic and organic inhibitors attracts more attention. Additionally to their intrinsic chemical stability, biodegradability, eco-friendly, low cost and renewability, biopolymers set were shown the remarkable effect to control the dissolution of several metallic materials in various corrosive environments. Among a large variety of available biopolymers, chitosan and its functionalized form, as well as its nanoparticle composites, have been reported and widely used as good anti-corrosion compounds for different metal/medium systems. In this context, the current chapter aims to shed more light on this subject.
Hemoglobin Profiles and Hematologic Features of Thalassemic Newborns: Application to Screening of α-Thalassemia 1 and Hemoglobin E
Authors: Tritipsombut Jaruwan , Sanchaisuriya Kanokwan , Fucharoen Supan , Fucharoen Goonnapa , Siriratmanawong Nirut , Pinmuang-ngam Charnchai , Sanchaisuriya Pattara
Published: February 2021

Context.—Thalassemia and hemoglobinopathies are major public health problems worldwide. To establish a cost-effective screening tool for newborns in regions where the incidence of these disorders is significant, study of the hemoglobin and hematologic features of normal and thalassemic newborns is necessary.

Objective.—To study hemoglobin and hematologic characteristics of normal and various thalassemic newborns and to assess the effectiveness of simple screening methods for α-thalassemia 1 and hemoglobin E.

Design.—Study was made of 402 cord blood specimens collected from unrelated Thai individuals. Hematologic parameters and hemoglobin profiles were determined. Thalassemia mutations were identified using polymerase chain reaction–related techniques.

Results.—As many as 178 subjects (44.3%) were found to carry thalassemia genes with 18 different genotypes. All forms of α-thalassemia including double heterozygote for hemoglobin E and α-thalassemia showed significant reduction in hemoglobin, mean corpuscular volume, and mean corpuscular hemoglobin with increasing trend of red blood cell as compared with a non–α-thalassemic group. Although heterozygous hemoglobin E and β-thalassemia showed no hematologic difference from nonthalassemic group, heterozygous α-thalassemia 1 including those with hemoglobin E showed significant increase in hemoglobin Bart level.

Conclusions.—Based on these findings, effective primary screening with 100% accuracy for α-thalassemia 1 and hemoglobin E in newborns in the region could be carried out using mean corpuscular volume less than 95 fL, mean corpuscular hemoglobin less than 30 pg, or hemoglobin Bart greater than 8.0% and hemoglobin E greater than 0.5%, respectively.
Systematic Assessment of Culture Review as a Tool to Assess Errors in the Clinical Microbiology Laboratory
Authors: Goodyear Nancy , Ulness Bruce K. , Prentice Jennifer L. , Cookson Brad T. , Limaye Ajit P.
Published: February 2021

Context.—Daily supervisory review is a common practice in microbiology laboratories; however, there are no publications describing errors corrected by this practice.

Objective.—To determine (1) the correction rates for routinely reviewed positive cultures, (2) the correction rates for negative cultures, and (3) the types of corrections that are found, including the number with potential clinical significance.

Design.—We prospectively assessed errors identified during culture report review for all positive (10-month period) and negative (1-month period) cultures at a single, university-based clinical microbiology laboratory in the United States. Errors were classified using predefined categories, and total and per category error rates were determined. A χ2 test was used to assess significant differences between error rates.

Results.—A total of 112 108 culture reports were examined; 914 reports required a total of 1043 corrections. Of 101 703 positive culture reports, 786 (0.8%) required 900 corrections, 302 (0.3%) of which were potentially clinically significant. Of 10 405 negative culture reports, 128 (1.2%) required 143 corrections, 5 (0.05%) of which were potentially clinically significant. The rate of potentially clinically significant errors was significantly higher among positive versus negative culture reports (P < .001). Errors from positive culture reports most commonly involved susceptibility (374 [42%]), reporting (275 [31%]), and identification workup (217 [24%]). Most potentially significant errors from positive culture reports involved susceptibility testing (n = 253) and specimens from wound or lower respiratory tract (P < .001).

Conclusions.—Review of culture reports from positive cultures from nonsterile sites with special attention to antimicrobial susceptibility testing and reporting would be most likely to detect potentially significant errors within the clinical microbiology laboratory.
Multiple Gastrointestinal Stromal Tumors and Lipomatosis
Authors: Liu Xiuli , Wilcox Charles Melbern , Nodit Laurentia , Lazenby Audrey J.
Published: February 2021

In this report, we describe a 36-year-old man with the synchronous occurrence of multiple gastric gastrointestinal stromal tumors and multiple intestinal lipomas. Multiple, small, and well-circumscribed gastric gastrointestinal stromal tumors (3 mm to 2 cm) were present within the gastrectomy specimen. The gastrointestinal stromal tumors were composed of epithelioid cells that were strongly positive for CD117 but negative for S100 protein or smooth muscle–specific actin. Also, 17 small submucosal lipomas were identified in the duodenal portion of the gastrectomy specimen. Endoscopic follow-up of the patient revealed more than 20 additional lipomas scattered throughout the intestine. Several large intestinal lipomas were resected endoscopically and histologically confirmed. Although both multicentric gastrointestinal stromal tumor and gastrointestinal lipomatosis have been reported in association with a few genetic syndromes, there has been no report, to our knowledge, of their coexistence. We feel that the coexistence of multiple lesions of these 2 rare diseases in this relatively young patient may represent a novel syndrome.
Resolution of Giant Cell Myocarditis After Extended Ventricular Assistance
Authors: Eid Shaker M. , Schamp David , Halushka Marc K. , Barouch Lili A.
Published: February 2021

Lower recurrence rates and improved long-term outcomes are the goal of treatment for giant cell myocarditis (GCM). We describe a case of GCM in an Asian woman who presented with new onset palpitations and syncope. She initially had normal systolic function by echocardiography with magnetic resonance imaging evidence of infiltrative cardiomyopathy. She underwent implantation of a biventricular assist device (BiVAD) because of rapidly deteriorating hemodynamic status. Giant cell myocarditis was diagnosed at that time by surgical biopsy. She was not treated with immunosuppressive therapy because of low likelihood of recovery and concerns for potential infection with the BiVAD in place. She received a heart transplant 12 months later and had extensive fibrosis but no evidence of active GCM in the heart explant. The role of extended BiVAD support in patients with GCM should be further investigated.
Automatic Failure in Gynecologic Cytology Proficiency Testing
Authors: Moriarty Ann T. , Crothers Barbara A. , Bentz Joel S. , Souers Rhona J. , Fatheree Lisa A. , Wilbur David C.
Published: February 2021

Context.—Automatic failure in gynecologic cytology proficiency testing occurs when a high-grade lesion or carcinoma (HSIL+, Category D) is misinterpreted as negative for intraepithelial lesion or malignancy (Category B).

Objectives.—To document the automatic failure rate in 2006 and 2007 from the College of American Pathologists proficiency testing program (PAP PT) and compare them to projected values from 2004.

Design.—Identify automatic failures from PAP PT in 2006 and 2007 and compare the rates of failure regarding participant and preparation type to validated slides in the College of American Pathologists Interlaboratory Comparison Program in 2004.

Results.—There were 65 264 participant responses for HSIL+ slides included in this analysis from 2006 and 2007. Overall, 1% (666 of 65 264) of the HSIL+ responses were classified as negative, resulting in automatic failure for the participant. There were significantly fewer automatic failures in 2007 as compared with either 2006 or projected from 2004 data (P < .001). Conventional preparations had a lower automatic failure rate than liquid-based preparations but only for 2006. Both pathologists and cytotechnologists interpreting liquid-based preparations faired better than projected from 2004 data.

Conclusions.—The automatic failure rate in PAP PT is lower than expected based on 2004 data from the College of American Pathologists Interlaboratory Comparison Program. Automatic failures are a relatively small component (1% or less) of proficiency testing failures. The rate of automatic failure decreased from 2006 to 2007 and may be due to loss of poor performers in the testing pool, the test-taking environment, or removal of less robust slides from the program.
Carcinoma of the Breast With Medullary-like Features: Diagnostic Challenges and Relationship With BRCA1 and EZH2 Functions
Authors: Kleer Celina G.
Published: February 2021

This case presentation reviews the histologic distinction between pure medullary carcinoma and breast carcinomas with medullary-like features. This particular case prompts us to analyze the relationship among medullary carcinoma, basal-like breast carcinomas and carcinomas associated with germline BRCA1 mutations. In addition to now well-defined features, such as expression of high-molecular-weight cytokeratins and EGFR (epidermal growth factor receptor), basal-like tumors have a deficiency or dysfunction of BRCA1. This association in part explains the histologic features of BRCA1-associated breast cancers. Recent studies in our laboratory demonstrate that BRCA1 protein is regulated by a recently described gene, EZH2. These concepts illustrate the important relationships among histopathologic features; genomic profile; single gene abnormalities, such as BRCA1 and EZH2; and growth regulation in this subset of breast carcinomas.
Mitotic Index of Invasive Breast Carcinoma
Authors: Meyer John S. , Cosatto Eric , Graf Hans Peter
Published: February 2021

Context.—Mitotic figure counts are related to breast cancer behavior but have not been sufficiently reproducible to be accepted for clinical decision-making.

Objective.—To improve reproducibility and accuracy of the mitotic count.

Design.—Mitotic index (MI) was defined as the mitotic cell count per 10 high-power fields (HPFs), an area 0.183 mm2. Two to 6 replicate sets of 10 HPFs were counted from 328 invasive breast carcinomas. Standard errors and coefficients of variation for mean MI were compared with expected results predicted by the binomial distribution.

Results.—The boundaries for MI that separated the data into equal thirds (tertials) were 1.14 and 5.33. Standard errors and coefficients of variation for MI followed distributions predicted by binomial probability. Mean coefficient of variation was 147% for the low tertial, 72% for the midtertial, and 34.6% for the upper tertial.

Conclusions.—Standard errors for MI based on a single count of 10 HPFs are too broad and coefficients of variation too large to be acceptable for clinical use. This is explained as a binomial probability effect, possibly with a contribution from tumor heterogeneity. Errors can be reduced in proportion to the square root of the number of sets of 10 HPFs counted. Tertial cutoffs of MI of the Nottingham system currently used in breast carcinoma grading are too high to be applicable to the population we studied. We recommend validation of cutoffs before they are applied to a particular population of breast carcinomas. Counting 5 sets of 10 HPFs is necessary to accurately rank carcinomas with low MIs.
Diagnosing Nonneoplastic Lesions in Nephrectomy Specimens
Authors: Truong Luan D. , Shen Steven S. , Park Moon-Hyang , Krishnan Bhuvaneswari
Published: February 2021

Context.—Nonneoplastic changes are often identified in nephrectomy specimens removed for renal neoplasms. Although they may be of prognostic or therapeutic importance, they are often overlooked. Nephrectomy is also performed for nonneoplastic lesions, the most frequent of which are urinary obstruction and end-stage renal disease, but the tissue diagnosis of these conditions and the implicated clinicopathologic correlation may not be well appreciated.

Objective.—To outline these nonneoplastic lesions with special attention to important diagnostic caveats and clinicopathologic correlations.

Data Sources.—The presented information was derived from literature, personal experience, and review of case materials at the authors' institutions.

Results.—Nonneoplastic lesions are seen in most (90%) nephrectomy specimens removed for renal neoplasms. Although these lesions span the spectrum of “medical” kidney diseases, the most frequent of them are hypertensive nephrosclerosis and diabetic nephropathy. Recognition of these diseases is important because they are often first diagnosed and later confirmed clinically. Furthermore, the severity of these lesions may predicate both short- and long-term renal function and thus help guide treatment. Among conditions that necessitate nephrectomy, advanced urinary obstruction, end-stage renal disease, and end-stage renal disease with acquired cystic changes are probably the most frequent. These conditions have characteristic morphologic features, but they may be associated with superimposing lesions previously not well described. These superimposing lesions may create diagnostic confusion; yet, some of them are the reason for nephrectomy. Thus, acute bacterial infection, urine polyp, granulomatous pyelitis, papillary necrosis, massive bleeding, and renal dysplasia can develop against the background of obstructive nephropathy. Renal neoplasms may develop from the background of end-stage renal disease without cystic changes. A renal neoplasm or massive bleeding with or without neoplasm is usually the reason for nephrectomy in kidney with acquired cystic kidney diseases. Thus, while nonneoplastic changes are frequent in nephrectomy specimens, they are often unrecognized. Awareness of these conditions and a familiarity with their diagnostic features as well as the implicated clinicopathologic correlation should help obviate this diagnostic problem.
Focal Segmental Glomerulosclerosis: A Morphologic Diagnosis in Evolution
Authors: Thomas David B.
Published: February 2021

Context.—The diagnosis of focal segmental glomerulosclerosis (FSGS) is a descriptive pathologic diagnosis that in certain clinical situations (ie, primary or idiopathic) becomes its own disease. The clinical diversity, varied histology, and nonspecific morphologic features of FSGS all contribute to the complexity and problematic nature in making a pathologic diagnosis of FSGS. The definitions of the disease and of the morphologic features have evolved during the last century.

Objective.—To review historic and morphologic features of FSGS in order to demonstrate a practical approach in achieving a pathologic diagnosis of FSGS on kidney tissue.

Data Sources.—In 2004 a working proposal on the pathologic (morphologic) classification of FSGS was published in an attempt to unify the complexity of diagnosing FSGS, and it has shown to be both reproducible and with unique clinical implications for each defined FSGS variant.

Conclusions.—An accurate diagnosis of FSGS can be challenging. During the last few decades, numerous new scientific discoveries have enriched our knowledge of pathogenetic mechanisms of nephrotic syndrome. Thus, it is expected there will be a need for a further modification to a morphologic classification and that the pathologist's role in diagnosing FSGS will remain in evolution. This review recapitulates the history of the pathologic diagnosis of FSGS and a current morphologic classification, hopefully opening up a discussion for further modifications that reflect the status of knowledge evolving in the 21st century.
The Pathology and Genetics of Metastatic Pancreatic Cancer
Authors: Yachida Shinichi , Iacobuzio-Donahue Christine A.
Published: February 2021

Context.—Metastatic disease is the most critical determinant of resectability of pancreatic cancer and accounts for the poor outcome of patients with this disease. Thus, a better understanding of metastatic pancreatic cancer will afford new opportunities for therapeutic intervention.

Objective.—To summarize and discuss the current understanding of the clinical and molecular features of metastatic pancreatic cancer.

Data Sources.—Published literature on advanced stage pancreatic cancer, pancreatic cancer metastasis, and autopsy findings in patients with pancreatic cancer.

Conclusions.—In the clinical setting, it can be difficult to distinguish a metastatic pancreatic carcinoma from primary neoplasms in the liver, lung, or ovary. However, immunolabeling for DPC4 protein as part of a diagnostic panel is useful for making this distinction. Emerging data from a variety of investigators now indicate that overexpression of EphA2, loss of DPC4 and MKK4, and aberrant activation of the Hedgehog signaling pathway are associated with metastatic propensity of pancreatic cancers, providing novel therapeutic targets for the most lethal stage of this disease.
Morphologic Features of Adenocarcinoma of the Lung Predictive of Response to the Epidermal Growth Factor Receptor Kinase Inhibitors Erlotinib and Gefitinib
Authors: Zakowski Maureen F. , Hussain Sanaa , Pao William , Ladanyi Marc , Ginsberg Michelle S. , Heelan Robert , Miller Vincent A. , Rusch Valerie W. , Kris Mark G.
Published: February 2021

Context.—A subset of lung adenocarcinomas appears preferentially sensitive to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). EGFR-activating mutations and never smoking are associated with response to TKIs.

Objectives.—To describe the morphology of adenocarcinomas responsive to TKIs, compare it to tumors in nonresponding patients, and correlate findings with EGFR mutations, gene copy number, and protein expression.

Design.—Material from 52 EGFR TKI-treated patients was studied: 29 responders and 23 nonresponders. Adenocarcinoma subtypes and morphologic features were defined in histologic and cytologic material. EGFR mutations were detected by sequencing, copy number by chromogenic in situ hybridization, and expression by immunohistochemistry.

Results.—Tumors from TKI responders tended to be better-differentiated adenocarcinomas with bronchioloalveolar carcinoma components. Nonresponders showed more heterogeneous morphology, higher grade, and more subtypes, and were more likely to show solid growth. In nonresponders, the only pure bronchioloalveolar carcinoma was mucinous, a subtype known to be negative for EGFR mutations. Using World Health Organization criteria, all tumors in both groups other than pure bronchioloalveolar carcinomas would be classified as adenocarcinomas, mixed subtype, thereby obscuring some of these distinctions. EGFR mutations were significantly more common in responders (22/29 vs 0/23; P < .001). Immunohistochemistry and chromogenic in situ hybridization results were not significantly correlated with EGFR mutations or response to TKIs in this study.

Conclusions.—Overall, histologic differences exist between tumors that respond to TKIs and those that do not, although sampling affects classification, and there is significant histologic overlap between the 2 groups. Response is strongly associated with EGFR mutations.
College of American Pathologists Considerations for the Delineation of Pathology Clinical Privileges
Authors: Catalano Jr Edward W. , Ruby Stephen Gerard , Talbert Michael L. , Knapman Douglas G.
Published: February 2021

Context.—The Joint Commission (JC) established new medical staff privileging requirements effective January 2008. The new requirements include the development of ongoing professional practice evaluation (OPPE) and focused professional practice evaluation (FPPE) processes and incorporate the general competencies of patient care, medical knowledge, practice-based learning and improvement, interpersonal and communication skills, professionalism and systems-based practice jointly developed by the Accreditation Council for Graduate Medical Education (ACGME) and the American Board of Medical Specialties (ABMS). The College of American Pathologists makes resources available to assist members and their facilities in implementing the new requirements and improving patient care.

Objectives.—To review the general requirements for privileging and identify how they may apply to pathologists, to identify currently available activities and metrics that may be useful in addressing these requirements, and to present identified concepts, activities, and metrics for consideration by pathologists and hospitals for their adaptation into the policies and procedures that address the new JC physician privileging requirements.

Design.—Review available pathology privileging documentation that addressed the previous JC requirements, review the new requirements, and search for and review available and applicable resources, activities, and metrics.

Results.—Common pathology activities and metrics can be incorporated into the privileging processes. Current and new activities and metrics can be incorporated or developed to address the 6 ACGME/ABMS “General Competencies.”

Conclusion.—Each hospital has unique privileging and physician evaluation requirements. Providing concepts, activities, and metrics for pathologists and hospitals to consider in pathology privileging will help implement the OPPE and FPPE processes and meet medical staff privileging requirements.
Undifferentiated Malignant Neoplasms of the Sinonasal Tract
Authors: Wenig Bruce M.
Published: February 2021

Context.—The most commonly encountered malignant neoplasms of the sinonasal tract are the keratinizing and nonkeratinizing types of squamous cell carcinoma. However, this complex anatomic region may represent the site of aggressive, non–squamous cell epithelial and nonepithelial malignant neoplasms of varying histogenesis, which are grouped under the term undifferentiated malignant neoplasms. Frequently, these undifferentiated malignancies share clinical and light microscopic features, which makes differentiation of one from the other virtually impossible without the use of adjunct analyses (eg, immunohistochemistry, electron microscopy, or molecular biologic studies). These tumors often are clinically aggressive and usually fatal, despite all attempts at controlling disease. Nevertheless, differentiating these tumors has clinical import because advances in therapeutic intervention may increase survival with good quality of life, and in some instances may achieve a cure.

Objective.—To compare and contrast the clinical, light microscopic, and immunohistochemical features of sinonasal undifferentiated malignant neoplasms.

Data Sources.—Case-derived material and literature review.

Conclusions.—A variety of undifferentiated malignant neoplasms occur in the sinonasal tract with overlapping clinical and pathologic findings. In limited biopsy material, differentiation of these tumor types can be challenging. The pathologist plays a primary role in establishing the correct diagnosis, which often necessitates the use of adjunct studies that allow for differentiating among these neoplasms.
Pulmonary Site Bioprostheses: Morphologic Findings in 40 Cases
Authors: Soor Gursharan S. , Leong Shaun W. , Butany Jagdish , Shapero Jonathan L. , Williams William G.
Published: February 2021

Context.—From January 1995 to June 2003, there were 514 patients who underwent pulmonary valve replacements at either the Hospital for Sick Children or Toronto General Hospital. Fifty-four (10.5%) of these adults returned for replacement of their prostheses because of failure. Forty (74.1%) of the 54 explants were bioprostheses, and 14 (25.9%) were homografts.

Objective.—To present the morphologic findings from this consecutive series of 40 pulmonary-site bioprostheses.

Design.—Data were obtained by review of pathologic, clinical, and surgical records for all 40 patients with bioprosthetic pulmonary valves explanted from 1995 to June of 2003.

Results.—The mean duration of valve implantation was 14.3 ± 5.2 years (2–26 years). Median age at implantation was 16.7 ± 10.3 years (range, 3 months to 53 years). Structural valve deterioration was found in 39 (97.5%) of the valves. Morphologic evidence of stenosis was found in all valves, whereas incompetence was found in 28 (70.0%). Calcification was present in 32 (80.0%) of the valves and was severe and diffuse in 22 (55.0%). Host tissue overgrowth, or pannus, was present on 39 (97.5%) of the valves and was severe in 35 (87.5%). Tears were present in 19 (47.5%) of the valves.

Conclusions.—Explanted bioprostheses showed a high degree of calcification and pannus, which together led to stenosis. Cusp immobilization, involving all 3 cusps, was frequent and was more common in patients younger than 30 years of age at explantation (P < .001). Host-tissue overgrowth is a significant problem with bioprostheses, and pulmonary-site bioprostheses are no exception.
Gene Expression–Based Prognostic and Predictive Markers for Breast Cancer: A Primer for Practicing Pathologists
Authors: Kim Chungyeul , Taniyama Yusuke , Paik Soonmyung
Published: February 2021

Context.—Gene expression–based prognostic assays for breast cancer are now available as commercial reference laboratory tests covered by insurance.

Objective.—To provide practicing pathologists with information about the nature of these assays, differences among them, and their use by clinical oncologists in the management of patients diagnosed with breast cancer.

Data Sources.—Review of literature and unpublished data from the National Surgical Adjuvant Breast and Bowel Project. This review focused on a general conceptual description of the technology behind these assays and differences among them to aid understanding by pathologists in practice.

Conclusions.—While these assays are clinically useful, they are still evolving. The future development of gene expression–based markers will need to be more clinical-context–specific to be clinically useful.
Pathology's Contributions to Disease Surveillance: Sending Our Data to Public Health Officials and Encouraging Our Clinical Colleagues to Do So
Authors: Aller Raymond D.
Published: February 2021

Pathology and clinical laboratories produce many types of data and information that are of relevance in protecting the health of the public. Electronic linkages between laboratory/pathology information systems and public health surveillance databases help ensure that these data reach the appropriate responder rapidly, completely, and accurately. Many efforts are underway to facilitate the flow of data from laboratory/pathology data sources to public health systems. Likewise, pathologists can encourage the contribution of clinical data from other parts of the health care enterprise. Chief complaint data from the emergency department and usage of over-the-counter medications from the retail pharmacy are useful for real-time population health surveillance. Having directly advocated transmission of data from our laboratories and facilitated other departments' participation in the public health surveillance network, we can also serve the public's health in other ways. Public health jurisdictions have a great need for staff with the skill sets of an experienced laboratorian. So, plan to contribute: data and talent.
Insights Into Selected Genetic Diseases Affecting the Female Reproductive Tract and Their Implication for Pathologic Evaluation of Gynecologic Specimens
Authors: Gwin Katja , Wilcox Rebecca , Montag Anthony
Published: February 2021

Context.—Recent advances in the understanding of genetic conditions involving the female genital tract and mechanisms of carcinogenesis in this setting affect patient management and thus necessitate appropriate pathologic evaluation of specimens. In the past, specimens from prophylactic surgery were a rarity; however, they are now more frequently encountered and often require a significant variation from routine processing methods. Pathologists also receive more specimens requiring prospective workup for possible underlying genetic conditions such as microsatellite instability.

Objective.—To summarize the current knowledge of important genetic and hereditary conditions affecting the female reproductive organs while highlighting the resulting practical significance for specimen handling, “grossing,” and microscopic evaluation in gynecologic pathology.

Data Sources.—This update is based on a review of recent peer-reviewed literature and the experience with cases at the parent institutions.

Conclusions.—Gynecologic specimens received from patients with certain genetic conditions require specific clinicopathologic knowledge for appropriate pathologic examination. The evaluation of prophylactic resection specimens focuses on the detection of cancer precursors and possible occult disease, which may require a more thorough and detailed examination than an obvious carcinoma. Standardized protocols for handling prophylactic gynecologic resection specimens are available for some, but not all, types of specimens. The prospective evaluation of a gynecologic pathology specimen for potential genetic conditions such as microsatellite instability is a very recent subject. Currently, well-established protocols are not available; however, as clinical and prognostic significance has become more clearly elucidated, familiarity with this evolving field is increasingly important to properly assess these pathologic specimens.
Lobular Neoplasia of the Breast: An Update
Authors: Contreras Alejandro , Sattar Husain
Published: February 2021

Context.—Lobular neoplasias (LNs) of the breast include atypical lobular neoplasia and lobular carcinoma in situ. Recent evidence suggests that LN is not only a risk factor for invasive lobular carcinoma, but is also a nonobligate precursor. Pleomorphic lobular carcinoma in situ (PLCIS) is a subtype of LN that has high-grade nuclei and other features that may mimic high-grade ductal carcinoma in situ. The management and follow-up of patients diagnosed with LN on core biopsy is a current issue of debate. However, recent genomic and molecular studies have identified candidate genes that may be important in understanding the pathogenesis of atypical lobular neoplasia and lobular carcinoma in situ, and thus may lead to other therapeutic interventions.

Objective.—To review the literature on LN of the breast and discuss current issues in the diagnosis and management of this entity, with particular attention to the relatively newly recognized lesion PLCIS. Because the management of PLCIS varies from the other LN lesions, the recognition of PLCIS by the pathologist is necessary. Current issues in the molecular pathogenesis of LN are also presented.

Data Sources.—Extensive review of the literature. Hematoxylin-eosin–stained and immunohistochemical-stained tissue from the author's personal collection.

Conclusions.—Although morphology and immunohistochemical stains, such as E-cadherin, are important in the diagnosis and understanding of LN, genomic and molecular studies may guide the way these lesions are handled in the future. Recognizing PLCIS is important both for patient management and for our future understanding of LN pathogenesis.
Anterior Diffuse Retinoblastoma: Mutational Analysis and Immunofluorescence Staining
Authors: Crosby Michelle B. , Hubbard G. Baker , Gallie Brenda L. , Grossniklaus Hans E.
Published: February 2021

Retinoblastoma is the most common primary intraocular tumor of childhood and may be heritable or occur sporadically. Anterior diffuse retinoblastoma is an uncommon variant that is thought to be sporadic. We describe a child with anterior diffuse retinoblastoma who presented with a pseudohypopyon. Genetic analysis showed a germline mutation of the RB1 allele that is potentially heritable. Immunofluorescence staining was positive for transforming growth factor β and for vascular endothelial growth factor and negative for inducible nitric oxide synthase and for hypoxia inducible factor α in the tumor seeds, indicating acquisition of nonischemia-mediated survival factors of the tumor seeds in the aqueous humor.
Pseudomyxoma Peritonei Associated With Primary Mucinous Borderline Tumor of the Renal Pelvicalyceal System
Authors: Rao Priya , Pinheiro Jr Nathanael , Franco Marcello , Ra Seong , Costa Henrique , Manzano João , Paner Gladell P. , Silva Elvio G. , Amin Mahul B.
Published: February 2021

Primary mucinous cystic neoplasms are extraordinarily rare tumors of the kidney. Herein, we present a case of a 52-year-old man who presented with painless hematuria and mucusuria. The nephrectomy showed a markedly enlarged kidney replaced by a large cystic mass filled with mucin and with almost complete destruction of the renal parenchyma. Histologically, the mass was lined primarily by simple mucinous epithelium and showed foci of adenomatous (borderline) change with focal areas exhibiting intraepithelial carcinoma. No invasion was documented after extensive sampling of the tumor. A pathologic diagnosis of intraepithelial carcinoma arising in a mucinous neoplasm of borderline malignancy was rendered. One year later, the patient presented with pseudomyxoma peritonei. This case illustrates that, in a patient with pseudomyxoma peritonei, the absence of an appendiceal, gastrointestinal, or ovarian primary tumor raises the possibility of a primary neoplasm at an unusual site such as the kidney.
Infiltrating Syringomatous Adenoma of the Nipple: Clinical Presentation and Literature Review
Authors: Oo Khine Z. , Xiao Philip Q.
Published: February 2021

Infiltrating syringomatous adenoma of the nipple is a rare neoplasm of the breast. Syringomatous adenoma of the nipple is often misdiagnosed because clinical examination and mammographic findings of syringomatous adenoma of the nipple mimic carcinoma. Despite its benign behavior, syringomatous adenoma of the nipple usually shows infiltrative expansile proliferation into adjacent tissue and underlying breast tissue. Up until now, to our knowledge, there has been no reported case of regional or distant metastasis. Histologically and clinically, syringomatous adenoma of the nipple is often confused with tubular carcinoma as well as low-grade adenosquamous carcinoma of the breast. Special attention given to this tumor by pathologists and clinicians can avoid misdiagnosis and unnecessary treatment.
Fatal Parasitic Meningoencephalomyelitis Caused ByHalicephalobus deletrix: A Case Report and Review of the Literature
Authors: Ondrejka Sarah L. , Procop Gary W. , Lai Keith K. , Prayson Richard A.
Published: February 2021

Infection with the saprophagous nematode Halicephalobus species is uncommon but has been reported in horses worldwide. Only 3 human cases have been previously described, all of which have been fatal. We report a fourth fatal case, which occurred in a 39-year-old woman who presented with meningeal signs, altered mental status, and a prodromal pruritic rash. Diagnostic evaluation included an open brain biopsy, which was diagnosed as granulomatous vasculitis. The patient subsequently died after a course of steroids and cyclophosphamide. At autopsy, a robust perivascular mixed inflammatory infiltration of the brain parenchyma, meninges, and ventricular system was present with larval forms and mature nematodes morphologically consistent with Halicephalobus deletrix. Although extremely rare, this organism needs to be considered in the differential diagnosis of human helminthic infection of the central nervous system.
Immunohistochemistry and Quantitative Analysis of Protein Expression
Authors: Cregger Melissa , Berger Aaron J. , Rimm David L.
Published: February 2021

Context.—Immunohistochemistry has taken a central role in the field of pathology, and its role is destined to increase as companion diagnostics analogous to the HercepTest are required for new targeted therapeutics. However, the inherent subjectivity of the assessment of an objective value (the in situ protein concentration) suggests that new technologies to measure the protein concentration may be required to achieve the accuracy required for companion diagnostics.

Objective.—This article discusses the state of immunohistochemistry and reviews the currently available devices for quantitative in situ assessment of protein expression.

Data Sources.—Data for this work were collected from the published literature, the Internet, and from information provided by device vendors.

Conclusions.—Although there is a long history of efforts to quantify immunohistochemistry, there has been a lack of broad acceptance because the resultant objective accuracy has not significantly improved outcome measures compared with the traditional, conventional analysis by eye. As the demand grows for companion diagnostics with complex assessment requirements, we are likely to see increased usage of quantitative platforms, especially those with the capacity to do multiplexed analysis. This most likely will be driven by a requirement for outcomes that cannot be achieved by traditional methods.
Middle Ear Adenoma
Authors: Berns Stephen , Pearl Gary
Published: February 2021

Middle ear adenoma is a benign tumor of the middle ear that can have exocrine (mucinous) and/or neuroendocrine differentiation. Early authors described a separate tumor with predominantly neuroendocrine differentiation as a middle ear carcinoid tumor, but these are now known to be the same tumor. We review the literature of this tumor, including the clinical presentation, gross pathology, histopathology, immunohistochemistry, differential diagnosis, and prognosis.
Cytogenetic Heteromorphisms: Survey Results and Reporting Practices of Giemsa-Band Regions That We Have Pondered for Years
Authors: Brothman Arthur R. , Schneider Nancy R. , Saikevych Irene , Cooley Linda D. , Butler Merlin G. , Patil Shivanand , Mascarello James T. , Rao Kathleen W. , Dewald Gordon W. , Park Jonathan P. , Persons Diane L. , Wolff Daynna J. , Vance Gail H.
Published: February 2021

Context.—Cytogenetic heteromorphisms (normal variants) pose diagnostic dilemmas. Common Giemsa-band heteromorphisms are not described in the literature, although Giemsa-banding is the method most frequently used in cytogenetic laboratories.

Objective.—To summarize the responses from more than 200 cytogeneticists concerning the definition and reporting of cytogenetic heteromorphisms, to offer these responses as a reference for use in clinical interpretations, and to provide guidance for interpretation of newly defined molecular cytogenetic heteromorphisms.

Design.—The Cytogenetics Resource Committee of the College of American Pathologists and the American College of Medical Genetics administered a proficiency testing survey in 1997 to 226 participant cytogenetic laboratories. Supplemental questions asked whether participants considered particular Giemsa-banded chromosomal features to be heteromorphisms and if these would be described in a cytogenetic clinical report.

Results.—Responses were obtained from 99% of participants; 61% stated they would include selected heteromorphism data in a clinical report. More than 90% considered prominent short arms, large or double satellites, or increased stalk length on acrocentric chromosomes to be heteromorphisms; 24% to 36% stated that they would include these in a clinical report. Heterochromatic regions on chromosomes 1, 9, 16, and Y were considered heteromorphisms by 97% of participants, and 24% indicated they would report these findings. Pericentric inversions of chromosomes 1, 2, 3, 5, 9, 10, 16, and Y were considered heteromorphisms with more than 75% of respondents indicating they would report these findings.

Conclusions.—Responses were not unanimous, but a clear consensus is presented describing which Giemsa-band regions were considered heteromorphisms and which would be reported.
Bilateral Presentation of Fibroadenoma With Digital Fibroma–like Inclusions in the Male Breast
Authors: Shin Sandra J. , Rosen Paul Peter
Published: February 2021

Fibroepithelial lesions are uncommon in the male breast. Most published reports describe phyllodes tumors. Fibroadenomas are very common in female breasts, but are exceedingly rare in the male breast. Gynecomastia and/or lobular differentiation have been known to coexist in both types of fibroepithelial lesions in men. We report an exceptional case of recurrent, bilateral fibroadenomas in a man under treatment for prostatic carcinoma. Intracytoplasmic inclusion bodies in stromal cells identical to those seen in infantile digital fibromatosis were identified in one fibroadenoma. To the best of our knowledge, this is the first reported case of bilaterally occurring fibroadenomas in the male breast, one of which also contained digital fibroma– like inclusions, a second unreported phenomenon.
Small Lymphoid Proliferations in Extranodal Locations
Authors: Rao Dinesh S. , Said Jonathan W.
Published: February 2021

Context.—Low-grade non-Hodgkin lymphomas frequently involve extranodal sites including the gastrointestinal tract, skin, and lung, either selectively or as part of widespread dissemination. Differentiation from inflammatory or infectious conditions requires knowledge of specific histologic characteristics of the various entities as well as ancillary techniques.

Objective.—To describe the key features and provide diagnostic clues to the identification of specific extranodal low-grade lymphomas of T-cell and B-cell types including small lymphocytic lymphoma, follicular lymphoma, mantle cell lymphoma, extranodal marginal zone B-cell lymphomas of mucosal-associated lymphoid tissue, and hairy cell leukemia. Histologic and cytologic features are highlighted, as well as appropriate integration of results of ancillary diagnostic studies including flow cytometry, immunohistochemistry, molecular features, and cytogenetics.

Data Sources.—The published literature as well as personal experience from a specialized hematopathology practice at a large university medical center.

Conclusions.—Correct identification of extranodal low-grade lymphomas and differentiation from hyperplastic and inflammatory or infectious processes require the ability to distinguish each of the specific entities discussed. Ancillary studies are often indispensable in reaching a correct diagnosis.
Serum Levels of Matrix Metalloproteinase 3 (Stromelysin 1) for Monitoring Synovitis in Rheumatoid Arthritis
Authors: Kobayashi Ari , Naito Satoko , Enomoto Hiroyuki , Shiomoi Takayuki , Kimura Tokuhiro , Obata Ken'ichi , Inoue Kazuhiko , Okada Yasunori
Published: February 2021

Context.—Matrix metalloproteinase 3 (MMP-3) is expressed in synovial tissues and involved in cartilage destruction in rheumatoid arthritis and osteoarthritis.

Objective.—To study whether measurement of MMP-3 serum concentrations is useful to monitor the activity of rheumatoid synovitis.

Design.—Levels of MMP-3 in serum and synovial tissue samples obtained from 29 rheumatoid arthritis patients and 20 osteoarthritis patients were measured by the 1-step sandwich enzyme immunoassay system.

Results.—Levels of MMP-3 in the serum and synovial samples were significantly higher in rheumatoid arthritis than in osteoarthritis (P < .001), and the levels correlated directly with each other (r = 0.712, P < .001; N = 49). Immunohistochemistry demonstrated almost exclusive localization of MMP-3 to the lining cells in rheumatoid synovium. The immunoreactivity correlated directly with the scores of synovial inflammatory cell infiltration (r = 0.606, P < .001; n = 29) and the MMP-3 levels in the synovial tissues (r = 0.564, P = .001; n = 29) and those in the serum samples (r = 0.529, P = .003; n = 29) in rheumatoid arthritis. Levels of MMP-3 in rheumatoid serum samples dropped to low values at 1 and 2 weeks after total knee arthroplasty, while the levels of C-reactive protein increased at 1 week and the erythrocyte sedimentation rate and counts of white blood cells and platelets were unchanged at 1 and 2 weeks postoperative.

Conclusions.—Our results demonstrate that MMP-3 levels in the serum of rheumatoid arthritis patients correlate with the levels produced by the synovial lining cells and suggest that the activity of rheumatoid synovitis can be monitored by measuring serum levels of MMP-3.
Distinguishing Prostatic From Colorectal Adenocarcinoma on Biopsy Samples: The Role of Morphology and Immunohistochemistry
Authors: Owens Christopher L. , Epstein Jonathan I. , Netto George J.
Published: February 2021

Context.—Poorly differentiated carcinoma on prostate or colorectal biopsy can occasionally present a diagnostic challenge in determining tumor source especially in locally advanced colorectal carcinoma (CRCa) or prostate carcinoma (PCa). Such determination can affect prognosis and therapy.

Objective.—To evaluate the role of morphology and immunohistochemistry in the previously mentioned setting.

Design.—Surgical pathology and consultation records. Hematoxylin-eosin sections were reviewed in 16 cases (11 PCa, 5 CRCa). Immunohistochemistry for 9 markers was performed in 15 cases.

Results.—Dirty necrosis, seen in 5 (100%) of 5 CRCa and 2 (18%) of 11 PCa cases, and the presence of columnar cells with basal nuclei, seen in 5 (100%) of 5 CRCa and 1 (9%) of 11 PCa cases, appear to be the most useful morphologic parameters. Immunohistochemistry confirmed the value of prostate-specific antigen (PSA), CDX2, cytokeratin (CK) 20, and β-catenin in the differential of CRCa (0% PSA+, 60% CDX2+, 80% CK20+, and 100% β-catenin+) versus PCa (80% PSA+, 0% CDX2+, 10% CK20+, and 0% β-catenin+). P501S had a similar sensitivity as PSA in detecting PCa (80%). Two (20%) of 10 PCa cases were positive for 1 of the 2 markers but not the other. P501S was negative in all 5 cases of CRCa.

Conclusions.—P501S is a useful marker in this setting when included together with PSA, CDX2, CK20, and β-catenin. P501S labels a subset of PCa cases that are negative for PSA. Dirty necrosis and/or columnar cells with basal nuclei could also be of help.