bluuebunny/crossref_metadata_2025 huggingface dataset:
Pancreatic Cytopathology: A Practical Approach and Review
Authors: Bellizzi Andrew M. , Stelow Edward B.
Published: February 2021

Context.—Pancreatic cytopathology plays an important role in the diagnosis and management of patients with solid and cystic lesions of the pancreas.

Objective.—To serve as a practical guide to pancreatic cytopathology for the practicing pathologist.

Data Sources.—A comprehensive assessment of the medical literature was performed.

Conclusions.—We review pancreatic cytopathology, with specific discussions of its role in patient management, specimen types and specimen processing, specific diagnostic criteria, and the use of ancillary testing and advanced techniques.
Primary Pulmonary Follicular Dendritic Cell Neoplasm: A Case Report and Review of the Literature
Authors: Denning Krista L. , Olson Peter R. , Maley, Jr Richard H. , Flati Veronica R. , Myers Jeffrey L. , Silverman Jan F.
Published: February 2021

Follicular dendritic cell tumor (FDCT) is an uncommon neoplasm that typically presents as a slow-growing, painless mass without systemic symptoms. Histologically, FDCT is characterized as a proliferation of spindle to ovoid cells having plump eosinophilic cytoplasm with indistinct borders and nuclei with vesicular or granular chromatin and small distinct nucleoli. The immunohistochemical profile of FDCT includes positive staining for CD21, CD23, CD35, vimentin, fascin, HLA-DR, epithelial membrane antigen, clusterin, and D2-40. Follicular dendritic cell tumor occurs primarily in lymphoid tissue; however, involvement of extranodal sites such as the tonsils, spleen, and gastrointestinal tract has been reported. Lung involvement typically represents metastatic disease with, to our knowledge, only 2 prior cases of extranodal primary FDCT of the lung reported. We report the third case of primary pulmonary FDCT arising in a 64-year-old woman.
Perivascular Epithelioid Cell Tumor
Authors: Armah Henry B. , Parwani Anil V.
Published: February 2021

Perivascular epithelioid cell tumors are mesenchymal neoplasms defined by the presence of histologically and immunohistochemically distinctive perivascular epithelioid cells. The perivascular epithelioid cell has no known normal tissue counterpart and coexpresses myoid and melanocytic markers. This tumor family shows marked female predominance and includes angiomyolipoma, clear cell sugar tumor, lymphangioleiomyomatosis, and a group of rare, morphologically and immunophenotypically similar tumors arising at a variety of visceral and soft tissue sites. This latter subset has been collectively termed perivascular epithelioid cell tumors–not otherwise specified. They are usually composed of epithelioid, but occasionally spindled, cells with clear to granular eosinophilic cytoplasm and focal perivascular accentuation. The mainstay of treatment is wide excision. Although most cases are benign, a subset behaves in a malignant fashion. Since few malignant cases have been reported, firm criteria for malignancy have yet to be established. This review focuses on the perivascular epithelioid cell tumors–not otherwise specified subset.
Necrotizing Sialometaplasia: A Practical Approach to the Diagnosis
Authors: Carlson Diane L.
Published: February 2021

Context.—Necrotizing sialometaplasia is a benign, self-limited lesion of both major and minor salivary glands, although more commonly the latter. It can represent a diagnostic dilemma and may be mistaken for a malignant neoplasm, such as mucoepidermoid carcinoma, as well as invasive squamous cell carcinoma. A major causal relationship has been ascribed to ischemia. Bulimia, an eating disorder with increasing prevalence in our society, may also be an underlying underreported cause.

Objective.—To discuss the potential pathogenesis, diagnostic pitfalls, and the application of immunohistochemistry as an aid in the diagnosis of necrotizing sialometaplasia.

Data Sources.—This report uses a previously published case history for illustrative purposes and a review of the current literature.

Conclusions.—The diagnosis of necrotizing sialometaplasia may be difficult and is reliant upon a well-oriented biopsy section and a complete clinical history. Diagnosis may be further supplemented via immunohistochemistry, demonstrating focal to absent immunoreactivity for p53, low immunoreactivity for MIB1 (Ki-67), and the presence of 4A4/p63- and calponin-positive myoepithelial cells. Interpreted in context collectively, these findings may be helpful adjuncts in the diagnosis of necrotizing sialometaplasia; nonetheless, to date, hematoxylin-eosin staining remains the gold standard.
Challenges in the Interpretation of Peritoneal Cytologic Specimens
Authors: Lin Oscar
Published: February 2021

Context.—The presence of malignant cells in peritoneal washings leads to classification as International Federation of Gynecology and Obstetrics stage IC or higher in ovarian carcinomas and at least International Federation of Gynecology and Obstetrics stage IIIA in endometrial carcinomas. Unfortunately, the morphologic examination of cytologic specimens has not proven to be a sensitive or specific diagnostic tool. Malignant cells might be few in number and might be unrecognized among a large population of mesothelial cells and/or macrophages, or reactive mesothelial cells might be misinterpreted as neoplastic cells leading to unnecessary chemotherapy.

Objective.—To evaluate the main pitfalls in the evaluation of peritoneal washings in patients with gynecologic malignancies and analyze the ancillary studies that might be helpful to achieve the correct diagnosis with an emphasis on immunocytochemistry.

Data Sources.—A comprehensive review of the literature was performed.

Conclusions.—Peritoneal effusions may represent major challenges to the pathologist and can have important clinical implications. Immunostains for epithelial markers such as B72.3, MOC-31, and Ber-EP4 represent the best available markers to identify epithelial cells. Caution is advised to not overdiagnose endometriosis or endosalpingiosis as adenocarcinoma.
The T1799A BRAF Mutation Is Absent in Cribriform-Morular Variant of Papillary Carcinoma
Authors: Schuetze David , Hoschar Aaron P. , Seethala Raja R. , Assaad Adel , Zhang Xiatong , Hunt Jennifer L.
Published: February 2021

Context.—Cribriform-morular variant of papillary thyroid carcinoma (CMVPTC) is one of the rare types of papillary carcinoma. It has been associated with familial adenomatous polyposis, though it can also occur sporadically. The molecular pathogenesis of this tumor is incompletely understood. It appears that there can be molecular contributions from the RET/PTC translocations and from mutations in the APC gene and β-catenin gene, which are both part of the Wnt signaling pathway. However, one of the most common mutations in papillary carcinoma, the BRAF mutation, has not been reported in this variant of papillary carcinoma.

Objective.—To investigate the BRAF mutational status in CMVPTC.

Design.—Four cases of CMVPTC (1 associated with familial adenomatous polyposis and the others apparently sporadic) were identified from the files of 3 large centers. Deoxyribonucleic acid was extracted and successfully amplified from each case. The polymerase chain reaction products were sequenced and evaluated for the T1799A BRAF mutation.

Results.—None of the 4 cases harbored the T1799A BRAF mutation (0/4).

Conclusions.—The T1799A BRAF mutation does not appear to play a role in the tumorigenesis of CMVPTC.
Epithelioid Sarcoma
Authors: Armah Henry B. , Parwani Anil V.
Published: February 2021

Epithelioid sarcomas are rare, mesenchymal tumors of unknown histogenesis and display multidirectional differentiation, which is predominantly epithelial. They have no normal cellular counterpart and differ from both synovial sarcoma and carcinoma. They account for less than 1% of all soft tissue sarcomas and are usually slow growing, with peak incidence in young adult men and occur predominantly in extremities. Histologically, they form nodules, with central necrosis surrounded by bland, polygonal cells with eosinophilic cytoplasm and peripheral spindling. They regularly express vimentin, cytokeratins, epithelial membrane antigen, and CD34, whereas staining is usually negative with S100, desmin, and FLI-1. Ultrastructurally, they display epithelial and mesenchymal features, including myofibroblastic differentiation. They manifest no specific cytogenetic findings, but several cases have displayed chromosomal abnormalities in 22q region. Clinically, they have a high recurrence rate, and up to 50% of epithelioid sarcomas metastasize. Proximal, fibroma-like, and angiomatoid variants have been described. The proximal variant (with larger cells, prominent nucleoli, and rhabdoid changes) is clinically more aggressive.
Flat Ductal Intraepithelial Neoplasia of the Breast: A Review of Diagnostic Criteria, Differential Diagnoses, Molecular-Genetic Findings, and Clinical Relevance—It Is Time to Appreciate the Azzopardi Concept!
Authors: Moinfar Farid
Published: February 2021

Context.—More than 25 years ago, John G. Azzopardi described a distinctive intraepithelial neoplastic breast lesion, which he designated “clinging carcinoma in situ”; he considered it as another variant of ductal carcinoma in situ, an early lesion that can easily be missed because the changes are mainly cytologic rather than architectural. The lesion remained widely unrecognized and/or ignored until recent years when its neoplastic nature was confirmed at the molecular-genetic level.

Objective.—To deal with historical aspects of the evolving concept of “clinging” and to focus on several important issues such as characteristic morphologic features with particular attention to the diagnostic criteria and differential diagnoses, recent molecular-genetic findings, appropriate terminology and classification, as well as the significance of this type of lesion for both surgical pathologists and clinicians.

Data Sources.—A thorough search of the literature was performed and publications using a variety of designations including “clinging carcinoma in situ,” “flat epithelial atypia,” “ductal intraepithelial neoplasia-flat type,” “atypical cystic lobules,” “columnar cell change with atypia,” “columnar cell hyperplasia with or without atypia,” “columnar alteration with prominent apical snouts and secretion,” and so forth were reviewed.

Conclusions.—This distinctive lesion represents one of the earliest morphologically recognizable neoplastic alterations of the breast that is commonly associated with mammographically suspicious microcalcifications. It is characterized by mildly to severely atypical cells simply replacing the single layer of native epithelial cells in a flat fashion without appreciable proliferation; tufting, intraluminal bridging, micropapillary structures, and so forth are typically absent or very focal and minimal, if present at all. Based on the degree of cytologic atypia, low- and high-grade flat ductal intraepithelial neoplasia need to be separated. Although additional studies are needed to better understand the clinical significance of flat ductal intraepithelial neoplasia, several lines of evidence strongly support the concept of clinging. Indeed, as pointed out by Azzopardi, surgical pathologists need to pay more attention to the cytologic alterations of the breast lesions by analyzing the involved cell populations using high-power magnification.
Safety and Efficiency Considerations for the Introduction of Electronic Ordering in a Blood Bank
Authors: Georgiou Andrew , Greenfield Tony , Callen Joanne , Westbrook Johanna I.
Published: February 2021

The introduction of computerized provider order entry (CPOE) systems is associated with major changes in work processes. Implementation strategies need to consider how the technology will affect and be affected by the organization in which it is being installed. The aim of this study was to examine the potential effect of the introduction of a CPOE system on key work processes in a hospital blood bank by using qualitative data from focus groups, interviews, and participant observation and quantitative data of telephone communication. We found that work practices in the blood bank are made up of a mosaic of collaborative processes underpinned by communication channels to facilitate safe and efficient work practices. The introduction of CPOE systems requires consideration of these channels and of the ways that CPOE may disrupt existing communication processes. There needs to be high levels of staff preparedness to minimize patient risk and optimize performance.
Laboratory Sanctions for Proficiency Testing Sample Referral and Result Communication: A Review of Actions From 1993–2006
Authors: Killeen Anthony A.
Published: February 2021

Context.—The Clinical Laboratory Improvement Amendments of 1988 (CLIA) regulations for proficiency testing (PT) include prohibitions against intentional PT sample referral or result communication, and specify sanctions against laboratories that violate these regulations. There has been little published analysis of sanctions against clinical laboratories because of PT violations.

Objective.—To examine the application of principal sanctions as reported by the Centers for Medicare and Medicaid Services annually in the Laboratory Registry and to examine relevant aspects of judicial hearings and appeals in these cases.

Design.—The Laboratory Registry was examined for all available years (1993–2006) to determine the incidence of application of principal sanctions for PT violations. In addition, the decisions from the US Department of Health and Human Services hearings and appeals were reviewed to better understand the judicial disposition of these cases.

Results.—During the 14-year period examined, 78 laboratories received a principal sanction for a PT violation involving sample referral or result communication. During the same period, the number of laboratories in nonexempt states that would be expected to have participated in PT averaged 45 983. The interpretive meaning of the key terms intentional and referral, and the implications for sanctioned laboratories and their owners and operators are discussed.

Conclusions.—Applications of a principal sanction for a PT violation were rare during the period of this study. However, the consequences of the imposition of such a sanction are severe. Suggestions are offered on policies and practices to minimize the risk of a PT sample referral or result communication.
Update on Immunohistochemical Methods Relevant to Dermatopathology
Authors: Wasserman Justin , Maddox Jessica , Racz Mark , Petronic-Rosic Vesna
Published: February 2021

Context.—Dermatopathology covers a large variety of entities, some having very similar histologic appearances. Immunohistochemistry is an incredibly helpful tool that is useful in diagnosis as well as prognosis of selected skin tumors.

Objective.—To provide a comprehensive review of recent trends and immunohistochemical stains used by dermatopathologists. Emphasis is placed on new stains as well as novel uses of existing stains.

Data Sources.—All data were gathered from published journal articles available through the National Center for Biotechnology Information PubMed database.

Conclusions.—New immunohistochemical targets are continually being found, contributing to more accurate diagnosis and classification of skin tumors. The presence of specific markers can be used to determine the aggressiveness of malignanicies and design treatment strategies. In addition, application of existing stains can help determine intravascular spread of malignancy in primary cutaneous lesions. And use of rapid immunohistochemical staining techniques on frozen sections can assist in more complete excision of tumor margins. Immunohistochemistry is a highly versatile and growing tool of dermatopathologists.
Update on Esophagitis: Controversial and Underdiagnosed Causes
Authors: Noffsinger Amy E.
Published: February 2021

Context.—Esophagitis is a common cause of symptoms for which patients seek the advice of a physician. Esophagitis of differing etiologies often demonstrate overlapping histopathologic features, making their distinction difficult. This is especially true in esophageal disorders associated with increased numbers of intraepithelial eosinophils, some of which have just recently been recognized.

Objective.—This review discusses the important clinical and pathologic features of the 2 most common disorders associated with esophageal eosinophilic infiltrates—reflux esophagitis and eosinophilic esophagitis—with special emphasis on features that allow the surgical pathologist to distinguish between these disorders. The various forms of drug-induced esophagitis are also discussed because these are frequently underrecognized by pathologists.

Data Sources.—Data were extracted from articles identified through PubMed-based research. Histologic figures have been taken from the personal case collection of the author.

Conclusions.—Reflux and eosinophilic esophagitis demonstrate overlapping histologic features, which may make their distinction difficult. Drug-induced esophagitis is probably a common phenomenon but is underrecognized by pathologists.
Update in Neoplastic Lung Diseases and Mesothelioma
Authors: Gordon Ilyssa O. , Sitterding Stephanie , Mackinnon A. Craig , Husain Aliya N.
Published: February 2021

Context.—Lung cancer is a common disease frequently seen by the surgical pathologist. Although secondary to improvements in screening and radiologic techniques and aggressive resection of small pulmonary nodules, the diagnosis of preneoplastic lesions is increasing in frequency and importance. Consequently, a greater understanding of their role in the development of lung carcinoma is needed for optimal patient care. Two lesions often encountered as small pulmonary nodules are bronchioloalveolar carcinoma and adenocarcinoma, which can be challenging to distinguish. Recently, updates to the TNM classification of non–small cell lung carcinoma have been reported that directly impact prognosis and treatment algorithms. Identification of new molecular targets in pleural mesothelioma and in preneoplastic lesions may lead to improved therapeutic strategies.

Objective.—To present recent advances in our understanding of neoplastic lung diseases and mesothelioma and to describe how these advances relate to the current practice of pulmonary pathology.

Data Sources.—Published literature from PubMed (National Library of Medicine) and primary material from the authors' institution.

Conclusions.—It is important for the surgical pathologist to understand current diagnostic classifications of non– small cell lung cancer and to be aware of the range of preneoplastic lesions, as well as the features useful for distinguishing bronchioloalveolar carcinoma from adenocarcinoma in small pulmonary nodules. Although pleural mesothelioma has distinct features, it can also overlap histologically with adenocarcinoma, and immunohistochemistry can greatly aid in accurate diagnosis. New therapies targeting molecular markers in both non–small cell lung cancer and mesothelioma rely on accurate histopathologic diagnosis of these entities.
Guidelines for Pathologic Diagnosis of Malignant Mesothelioma: A Consensus Statement from the International Mesothelioma Interest Group
Authors: Husain Aliya N. , Colby Thomas V. , Ordóñez Nelson G. , Krausz Thomas , Borczuk Alain , Cagle Philip T. , Chirieac Lucian R. , Churg Andrew , Galateau-Salle Francoise , Gibbs Allen R. , Gown Allen M. , Hammar Samuel P. , Litzky Leslie A. , Roggli Victor L. , Travis William D. , Wick Mark R.
Published: February 2021

Context.—Malignant mesothelioma (MM) is an uncommon tumor that can be difficult to diagnose.

Objective.—To develop practical guidelines for the pathologic diagnosis of MM.

Data Sources.—A pathology panel was convened at the International Mesothelioma Interest Group biennial meeting (October 2006). Pathologists with an interest in the field also contributed after the meeting.

Conclusions.—There was consensus opinion regarding (1) distinguishing benign from malignant mesothelial proliferations (both epithelioid and spindle cell lesions), (2) cytologic diagnosis of MM, (3) key histologic features of pleural and peritoneal MM, (4) use of histochemical and immunohistochemical stains in the diagnosis and differential diagnosis of MM, (5) differentiating epithelioid MM from various carcinomas (lung, breast, ovarian, and colonic adenocarcinomas and squamous cell and renal cell carcinomas), (6) diagnosis of sarcomatoid mesothelioma, (7) use of molecular markers in the differential diagnosis of MM, (8) electron microscopy in the diagnosis of MM, and (9) some caveats and pitfalls in the diagnosis of MM. Immunohistochemical panels are integral to the diagnosis of MM, but the exact makeup of panels used is dependent on the differential diagnosis and on the antibodies available in a given laboratory. Immunohistochemical panels should contain both positive and negative markers. The International Mesothelioma Interest Group recommends that markers have either sensitivity or specificity greater than 80% for the lesions in question. Interpretation of positivity generally should take into account the localization of the stain (eg, nuclear versus cytoplasmic) and the percentage of cells staining (>10% is suggested for cytoplasmic membranous markers). These guidelines are meant to be a practical reference for the pathologist.
Lymph Node Melanosis in a Patient With Metastatic Melanoma of Unknown Primary
Authors: Malafronte Patrick , Sorrells Timothy
Published: February 2021

Tumoral or nodular melanosis in the skin is considered a variation of completely regressed melanoma, presenting clinically as a suspicious pigmented papule or nodule. Microscopically, the lesion consists of a nodular accumulation of heavily pigmented melanophages in the dermis, staining positive for immunohistochemical markers of histiocytic lineage (CD68) and negative for those of melanocytic lineage (S100, HMB-45, Melan-A). This process is rarely described in lymph nodes. We present a report of a patient with melanosis involving multiple lymph nodes of an axillary dissection, done for metastatic melanoma with an unknown primary, and discuss possible prognostic and treatment factors.
Best Practices in Diagnostic Immunohistochemistry: Spindle Cell Neoplasms of the Gastrointestinal Tract
Authors: Turner Matthew S. , Goldsmith Jeffrey D.
Published: February 2021

Context.—The proper classification of spindle cell neoplasms of the gastrointestinal tract frequently requires the use of immunohistochemistry, as the histologic appearance of these lesions often overlaps.

Objective.—To review the antibodies used in the diagnosis of spindle cell neoplasms of the gastrointestinal tract, and to outline an approach to the evaluation of these lesions by using immunohistochemistry.

Data Sources.—The authors' experience and a review of the English literature from 1976 to 2008.

Conclusions.—The most common spindle cell neoplasm of the gastrointestinal tract is gastrointestinal stromal tumor; this lesion is readily diagnosed with c-kit immunohistochemistry in most cases. Other stains, such as smooth muscle actin, desmin, S100 protein, and β-catenin, are also useful in the diagnosis of smooth muscle tumors, schwannomas, desmoid-type fibromatoses, and metastatic melanoma.
Performance of Herpes Simplex Challenges in Proficiency Testing: Observations From the College of American Pathologists Proficiency Testing Program
Authors: Moriarty Ann T. , Darragh Teresa M. , Souers Rhona , Fatheree Lisa A. , Wilbur David C.
Published: February 2021

Context.—Herpes simplex virus (HSV) is a common sexually transmitted disease that is decreasing in prevalence. Herpes simplex virus challenge cases have performed well in the educational College of American Pathologists Interlaboratory Comparison Program in Cervicovaginal Cytology. However, since gynecologic cytology proficiency testing (PT) was instituted, performance of HSV challenge cases has worsened.

Objective.—To determine if the decrease in performance for HSV challenges is due to inexperience in identifying herpes virus or “gaming” of PT.

Design.—We compare graded (field-validated) and ungraded (educational) slides with HSV prior to PT (1991– 2005) and after PT (2006 and 2007) in an attempt to characterize changes in performance of slides demonstrating purely HSV cellular features. All HSV slides were negative for intraepithelial lesion with the specific reference interpretation of HSV. Slides were excluded from analysis if they demonstrated more than one diagnostic category or had squamous intraepithelial lesion in addition to HSV changes.

Results.—A total of 40 634 HSV responses were evaluated. A significant difference existed in the diagnosis of HSV in PT compared with graded challenges prior to PT (96.6 versus 98.6; P < .001). No difference was seen in educational challenges pre-PT and post-PT (P = .14). No difference was present between slide preparation type; however, a difference was seen between cytotechnologist and pathologist response.

Conclusions.—There is a change in the performance of slide challenges demonstrating the cellular features of HSV in PT, most likely due to testing strategies of participants, rather than lack of recognition of HSV secondary to decreased prevalence.
Fellowship Trends of Pathology Residents
Authors: Lagwinski Nikolaj , Hunt Jennifer L.
Published: February 2021

Context.—Recent changes in pathology residency education have included a decrease in the program length (from 5 years to 4 years for combined anatomic and clinical pathology training) and a national mandate for programs to assess 6 general competencies of trainees. These have undoubtedly led to changes in program curricula and in residents' desires to seek fellowship training.

Objective.—This study was designed to gather information about what residents are seeking from fellowship training programs.

Design.—This study used an online survey to assess attitudes of residents in training programs toward fellowship training. The survey instrument had 26 questions pertaining to fellowship choices, motivations for pursuing fellowships, expectations of the fellowships, and postresidency concerns.

Results.—There were 213 respondents from a mix of program types and representing each postgraduate year. Most residents will seek at least 1 or 2 fellowships after residency training. The most popular first-choice fellowship was surgical pathology (26%), followed by cytopathology (16%), hematopathology (15%), gastrointestinal pathology (10%), dermatopathology (8%), and forensic pathology (5%). The most common reasons for pursuing fellowship training were to “increase marketability” (43%) or to “become an expert in a particular area” (33%). Most trainees got their information about fellowship training programs from Internet sources.

Conclusions.—Fellowship programs will benefit from an optimally designed Web site because residents seek information predominantly from the Internet. Residents seeking fellowships are particularly concerned with selecting programs that provide job connections, an increase in their marketability, and the opportunity to develop diagnostic expertise.
Racial Differences in Motivators and Barriers to Blood Donation Among Blood Donors
Authors: Shaz Beth H. , Demmons Derrick G. , Hillyer Krista L. , Jones Robert E. , Hillyer Christopher D.
Published: February 2021

Context.—Nationally, African Americans are underrepresented in community blood donation programs. To increase blood donation by African Americans, differences between motivators and barriers to blood donation between races should be investigated.

Objective.—To investigate motivators and barriers to blood donation in African American and white blood donors.

Design.—An 18-item, anonymous, self-administered questionnaire regarding demographics and motivators and barriers to donation was completed by blood donors at a predominately African American and a predominately white fixed donation site.

Results.—A total of 599 participants (20% African American, 75% white, and 5% other) completed the survey. The most commonly reported reasons to donate included: “because it is the right thing to do” (45% African Americans and 62% white) and “because I want to help save a life” (63% African Americans and 47% white). Unpleasant experiences did not differ as a barrier to continue donation between African Americans and whites. African Americans placed more importance on donating blood to someone with sickle cell disease, convenience of blood donation, treatment of donor center staff, and level of privacy during the screening process.

Conclusions.—These data suggest that in a large metropolitan area, reasons for donation among African American and white donors differ. To retain and increase donation frequency of African American donors, these factors should be considered in creating an African American donor recruitment and retention program.
Grover Disease (Transient Acantholytic Dermatosis)
Authors: Weaver Joshua , Bergfeld Wilma F.
Published: February 2021

Grover disease, also known as transient acantholytic dermatosis, is a papulovesicular rash of the upper trunk, generally among older white males; it is usually pruritic but temporary. Grover disease is characterized by 4 different acantholytic histologic patterns, and it has been associated with numerous disorders, including hematologic malignancies. Follow-up and treatment are often difficult to evaluate secondary to the spontaneous remittance and occasional fluctuant course of the disease. Our objective will be to discuss the diagnostic considerations of Grover disease and focus on the postulated pathogenesis, including concurrent disorders and the role of the pathologist in examining skin biopsies of this nonhereditary vesicobullous disorder. Although recognized as a common condition, Grover disease's pathogenesis still remains unknown. Because Grover disease has been associated frequently with other dermatologic and nondermatologic skin conditions, inspection for other pathologic processes within the skin biopsy is essential to rule out other concomitant disorders, including hematopoietic malignancies.
Respiratory Bronchiolitis/Interstitial Lung Disease: Fibrosis, Pulmonary Function, and Evolving Concepts
Authors: Churg Andrew , Müller Nestor L. , Wright Joanne L.
Published: February 2021

Context.—The concept of respiratory bronchiolitis/interstitial lung disease (RBILD) was introduced to explain the presence of interstitial lung disease in individuals whose only finding on surgical lung biopsy was smoker's respiratory bronchiolitis (RB). Over time, the diagnostic criteria for RBILD have become progressively more confused.

Objective.—To review the diagnostic criteria for RBILD.

Design.—The review was based on the literature and personal experience.

Conclusions.—The concept of RBILD has changed over time with the recognition that, histologically and radiologically, RB and RBILD are usually indistinguishable. Most authors accept mild alveolar wall fibrosis extending away from the respiratory bronchioles as a part of both RB and RBILD, and occasional cases show quite marked, but probably localized, interstitial fibrosis. What has not been appreciated is that RB is not only an extremely common disease in cigarette smokers but also is ordinarily associated with airflow obstruction. Further, interstitial fibrosis is sometimes found in centrilobular emphysema, and this phenomenon has probably lead to some cases of centrilobular emphysema being misclassified as RB or RBILD. Despite the presence of fibrosis, centrilobular emphysema is still associated with airflow obstruction. We suggest that RBILD be restricted to the clinical setting in which cigarette smokers have a restrictive or mixed obstructive and restrictive functional abnormality, have a marked decrease in diffusing capacity with minimal evidence of airflow obstruction, or have imaging studies showing ground glass opacities/centrilobular nodules plus reticulation and no other lesion besides RB on biopsy to account for these changes. In this setting, the presence of RB-associated interstitial fibrosis probably causes the functional changes.
Diagnosis of Metastatic Neoplasms: An Immunohistochemical Approach
Authors: Krishna Murli
Published: February 2021

Context.—It is important to determine the type and/or site of origin of metastatic tumors for optimal clinical management.

Objective.—To summarize the use of currently available immunohistochemical markers in the evaluation of metastatic tumors.

Data Sources.—Review of relevant literature on immunohistochemical evaluation of tumors and the author's personal experience.

Conclusions.—Immunohistochemistry is an important ancillary technique for evaluation of metastatic tumors and should be used in the context of routine morphology and clinical information. While a single marker may be used to support a known or suspected site of origin, a carefully constructed panel is strongly recommended, particularly for tumors of morphologically uncertain lineage or origin.
The Utility of C4d, C9, and Troponin T Immunohistochemistry in Acute Myocardial Infarction
Authors: Jenkins Crystal P. , Cardona Diana M. , Bowers Jennifer N. , Oliai Bahram R. , Allan Robert W. , Normann Sigurd J.
Published: February 2021

Context.—Full activation and involvement of the complement pathway follows acute myocardial infarction. Complement fragment C4d is a stable, covalently bound marker of complement activation. Troponin T is specific for cardiomyocytes.

Objectives.—To determine the specificity of C4d, C9, and troponin T immunoreactivity in necrotic myocytes and to establish whether they can be used to delineate acute myocardial infarction.

Design.—Twenty-six autopsy cases with a total of 54 myocardium areas of infarction were reviewed retrospectively. Immunohistochemistry for C4d, C9, and troponin T was used on paraffin sections of formalin-fixed tissue. Controls consisted of 5 cases without evidence of infarction, and histologically normal myocardium functioned as an internal control.

Results.—C4d and C9 antibodies reacted strongly and diffusely with necrotic myocytes in all samples of infarctions for up to 2 days (19 of 19; 100%). Adjacent histologically normal myocytes were nonreactive, resulting in a clear delineation between damaged and viable myocardium. Reactivity declined with increased duration and was absent in scars. Troponin T showed loss of staining in preinflammatory lesions (8 of 13; 62%); however, nonspecific patchy loss of staining was present in negative controls and in viable myocardium. Immunostains provided new diagnoses in 2 cases, including evidence of reinfarction and a newly diagnosed acute myocardial infarction.

Conclusions.—C4d and C9 have comparable reactivity and specificity for necrotic myocytes. C4d and C9 staining of necrotic myocytes is apparent before the influx of inflammatory cells, demonstrating utility in early myocardial infarction. Patchy loss of Troponin T in some cases of histologically normal myocardium limited its usefulness as a sole marker of infarction.
Small Intestinal Bacterial Overgrowth: Histopathologic Features and Clinical Correlates in an Underrecognized Entity
Authors: Lappinga Paul J. , Abraham Susan C. , Murray Joseph A. , Vetter Emily A. , Patel Robin , Wu Tsung-Teh
Published: February 2021

Context

Small intestinal bacterial overgrowth (SIBO) is a common cause of chronic diarrhea and malabsorption. Morphologic changes associated with this condition have not, to our knowledge, been studied in detail.

Objective

To better characterize the histopathologic changes associated with SIBO by comparing the clinicopathologic features of patients with SIBO (duodenal aspirate cultures with ≥105 colony-forming units [CFUs]/mL) to controls with cultures found to be negative (<105 CFUs/mL).

Design

We included 67 consecutive patients with SIBO and 55 controls in the series. Each duodenal biopsy was assessed for the following features: villous to crypt ratio, intraepithelial lymphocytosis, crypt apoptoses, basal plasmacytosis, cryptitis/villitis, peptic duodenitis, erosions/ulcers, eosinophilia, and absence of goblet and Paneth cells; and correlated with clinical features and culture results.

Results

Decreased villous to crypt ratio (<3∶1) was more frequent in SIBO than controls (24% versus 7%; P  =  .01). Duodenal biopsies from patients with SIBO were slightly less likely to be judged within reference range than were controls (52% versus 64%; P  =  .27). There were no significant differences in any of the other histologic features. Clinically, patients in the SIBO group were older than the age of controls (mean, 60 years versus 52 years; P  =  .02), and they were more likely to have one of the known predisposing factors for bacterial overgrowth (66% versus 36%; P  =  .002). Other clinical features, including presenting symptoms, were similar.

Conclusions

Villous blunting is the only feature more common to SIBO than to controls. More than half of biopsies from SIBO patients are histologically unremarkable. Therefore, SIBO needs to be considered as a potential etiology for gastrointestinal symptoms even when duodenal biopsies are found to be normal.
Pseudoneoplastic Mimics of Prostate and Bladder Carcinomas
Authors: Hameed Omar , Humphrey Peter A.
Published: February 2021

Context.—The differential diagnoses of prostatic carcinoma and bladder epithelial neoplasms include several histologic mimics that should be known to avoid misdiagnosis.

Objective.—To discuss pseudoneoplastic lesions of the prostate and bladder that could potentially be confused with prostatic carcinoma and bladder epithelial neoplasms, respectively, with specific focus on their distinguishing histopathologic features.

Data Sources.—Relevant published literature and authors' experience.

Conclusions.—Pseudoneoplastic lesions in the prostate include those of prostatic epithelial origin, the most common being atrophy, adenosis (atypical adenomatous hyperplasia), basal cell hyperplasia, and crowded benign glands, as well as those of nonprostatic origin, such as seminal vesicle epithelium. Such lesions often mimic lower-grade prostatic adenocarcinoma, whereas others, such as clear cell cribriform hyperplasia and granulomatous prostatitis, for example, are in the differential diagnosis of Gleason adenocarcinoma, Gleason grade 4 or 5. Pseudoneoplastic lesions of the urinary bladder include lesions that could potentially be confused with urothelial carcinoma in situ, such as reactive urothelial atypia, and others, such as polypoid/papillary cystitis, where papillary urothelial neoplasms are the main differential diagnostic concern. Several lesions can mimic invasive urothelial carcinoma, including pseudocarcinomatous hyperplasia, von Brunn nests, and nephrogenic adenoma. Diagnostic awareness of the salient histomorphologic and relevant immunohistochemical features of these prostatic and urinary bladder pseudoneoplasms is critical to avoid rendering false-positive diagnoses of malignancy.
Renal Diseases With Organized Deposits: An Algorithmic Approach to Classification and Clinicopathologic Diagnosis
Authors: Herrera Guillermo A. , Turbat-Herrera Elba A.
Published: February 2021

Context.—Most renal diseases with organized deposits are relatively uncommon conditions, and proper pathologic characterization determines the specific diagnosis. Different entities with specific clinical correlates have been recognized, and their correct diagnosis has an impact on patient management, treatment options, and determination of prognosis.

Objective.—The diagnosis of these conditions depends on careful evaluation of the findings by light microscopy together with immunofluorescence and electron microscopy. The objective of this manuscript is to delineate an algorithmic approach helpful in the pathologic assessment of these conditions at the light microscopic level. In some diseases, the immunomorphologic parameters short of electron microscopy provide solid information to suggest or make a definitive diagnosis. Nevertheless, electron microscopy plays a crucial role, because the criteria to separate these entities often are heavily influenced by the electron microscopic findings. Accepted diagnostic criteria for each of these conditions are discussed.

Design.—Information used for this manuscript is gathered from published data and the authors' experience.

Results.—The most common of these conditions is amyloidosis, which may account for as many as 5% to 8% of all renal biopsies in some renal pathology practices. Fibrillary, immunotactoid, and cryoglobulinemic glomerulopathies together represent, at most, 1% of all renal biopsies performed for medical renal diseases. Diabetic fibrillosis also is uncommon. Glomerulopathies associated with fibronectin deposits and collagenofibrotic glomerulopathy are extremely rare.

Conclusions.—A systematic, algorithmic approach to the evaluation of the renal biopsies from patients with these disorders is very helpful to rule out certain conditions in the early stages of the evaluation of the biopsies. However, it is not uncommon for the final definitive diagnosis to be reached only after electron microscopic evaluation.
Laboratory Compliance With the American Society of Clinical Oncology/College of American Pathologists Guidelines for Human Epidermal Growth Factor Receptor 2 Testing: A College of American Pathologists Survey of 757 Laboratories
Authors: Nakhleh Raouf E. , Grimm Erin E. , Idowu Michael O. , Souers Rhona J. , Fitzgibbons Patrick L.
Published: February 2021

Context.—To ensure quality human epidermal growth receptor 2 (HER2) testing in breast cancer, the American Society of Clinical Oncology/College of American Pathologists guidelines were introduced with expected compliance by 2008.

Objective.—To assess the effect these guidelines have had on pathology laboratories and their ability to address key components.

Design.—In late 2008, a survey was distributed with the HER2 immunohistochemistry (IHC) proficiency testing program. It included questions regarding pathology practice characteristics and assay validation using fluorescence in situ hybridization or another IHC laboratory assay and assessed pathologist HER2 scoring competency.

Results.—Of the 907 surveys sent, 757 (83.5%) were returned. The median laboratory accessioned 15 000 cases and performed 190 HER2 tests annually. Quantitative computer image analysis was used by 33% of laboratories. In-house fluorescence in situ hybridization was performed in 23% of laboratories, and 60% of laboratories addressed the 6- to 48-hour tissue fixation requirement by embedding tissue on the weekend. HER2 testing was performed on the initial biopsy in 40%, on the resection specimen in 6%, and on either in 56% of laboratories. Testing was validated with only fluorescence in situ hybridization in 47% of laboratories, whereas 10% of laboratories used another IHC assay only; 13% used both assays, and 12% and 15% of laboratories had not validated their assays or chose “not applicable” on the survey question, respectively. The 90% concordance rate with fluorescence in situ hybridization results was achieved by 88% of laboratories for IHC-negative findings and by 81% of laboratories for IHC-positive cases. The 90% concordance rate for laboratories using another IHC assay was achieved by 80% for negative findings and 75% for positive cases. About 91% of laboratories had a pathologist competency assessment program.

Conclusions.—This survey demonstrates the extent and characteristics of HER2 testing. Although some American Society of Clinical Oncology/College of American Pathologists guidelines have been implemented, gaps remain in validation of HER2 IHC testing.
Preventing Platelet-Derived Microparticle Formation—and Possible Side Effects—With Prestorage Leukofiltration of Whole Blood
Authors: Sugawara Akiko , Nollet Kenneth E. , Yajima Kentaro , Saito Shunnichi , Ohto Hitoshi
Published: February 2021

Context.—Platelet-derived microparticles (PDMPs) probably function in hemostasis, thrombosis, inflammation, and transfusion-related immunomodulation.

Objective.—To compare PDMP levels of leukocyte-filtered and unfiltered whole blood during storage.

Design.—Ten whole blood donations were collected and processed. Half of each collection was filtered, half remained unfiltered, and both halves were measured for red cell, white cell, and platelet (PLT) content before storage. Samples were drawn on days 0, 1, 2, 3, 5, 7, 14, 21, 28, and 35 and analyzed by flow cytometry.

Results.—Leukocyte filtration lowered prestorage PDMP and PLT counts by an average of 72% and 99%, respectively. Prestorage PDMP counts were 123 ± 51/µL in unfiltered whole blood supernatant versus 34 ± 18/µL after filtration. Prestorage PLT counts were 190 ± 49/µL in unfiltered whole blood supernatant versus 2 ± 4/µL after filtration. Moreover, PDMP and PLT counts in filtered whole blood remained low throughout storage, typically below 100/µL. In contrast, unfiltered whole blood PDMP- and PLT-gated events increased approximately 2 log during storage, with the peak number of PLT-gated events tending to coincide with the peak number of PDMP-gated events (4 donors) or to come after the peak number of PDMP-gated events (6 donors).

Conclusions.—Leukocyte filtration of whole blood lowers prestorage PDMP and PLT counts. Platelet-derived microparticle and PLT counts remain low throughout 35 days of storage. In contrast, PDMP- and PLT-gated events increase significantly in unfiltered whole blood. The nature of PLT-gated events in stored blood warrants further investigation.
Endocrine Tumors of the Appendix: A Pathologic Review
Authors: Deschamps Lydia , Couvelard Anne
Published: February 2021

Context.—Although rare, appendiceal endocrine tumors are the most common neoplasms of the appendix. Pathologic analysis is important for guiding the management of patients.

Objective.—To provide recent data that focus on the pathology of endocrine tumors of the appendix including classifications and guidelines for patient management.

Data Sources.—A review of the recent literature including TNM classifications and patient management guidelines.

Conclusions.—Appendiceal endocrine tumors are separated into 2 main groups: classic endocrine tumors and goblet cell carcinoids. They can be classified according to World Health Organization and TNM classifications. Evaluation of their prognoses and risks of malignancy, according to these classifications, depends on several parameters including tumor size, proliferation rate, and infiltration of appendiceal wall and mesoappendix. Most patients with classic endocrine tumors of the appendix have a favorable prognosis. Indications for postappendectomy, complementary surgery, which are still controversial, especially for tumors between 1 and 2 cm, are presented and discussed. In contrast, in patients presenting with a goblet cell carcinoid, a right hemicolectomy after the initial appendectomy is considered the standard surgical intervention.