bluuebunny/crossref_metadata_2025_split huggingface dataset:
Xanthogranulomatous Pyelonephritis
Authors: Li Li , Parwani Anil V. 
Published: February 2021

Abstract
Xanthogranulomatous pyelonephritis is an uncommon chronic destructive granulomatous process of renal parenchyma in association with long-term urinary tract obstruction and infection. It affects females more often than males, with a wide range of age, from newborn to elderly. Almost all patients are symptomatic and the most common symptoms are flank or abdominal pain, lower urinary tract symptoms, fever, palpable mass, gross hematuria, and weight loss. The common laboratory findings are leukocytosis and anemia. Urine cultures most often reveal Escherichia coli and Proteus mirabilis. Computed tomography is the mainstay of diagnostic imaging for xanthogranulomatous pyelonephritis. Imaging studies may demonstrate diffuse or focal form. Histologically, xanthogranulomatous pyelonephritis presents a granulomatous inflammatory infiltrate composed of neutrophils, lymphocytes, plasma cells, xanthomatous histiocytes, and multinucleated giant cells. The differential diagnosis includes clear cell renal cell carcinoma, papillary renal cell carcinoma, sarcomatoid renal cell carcinoma, leiomyosarcoma, malakoplakia, and megalocytic interstitial nephritis. Both antibiotics and surgery can be treatment options depending on the patient's disease status.
Expression of AIF and HtrA2/Omi in Small Lymphocytic Lymphoma and Diffuse Large B-Cell Lymphoma
Authors: Li Shaoying , Wan Mei , Cao Xu , Ren Yongsheng 
Published: February 2021

Abstract
Context.—The pathogenesis of non-Hodgkin lymphoma may involve deregulation of apoptosis. In response to apoptotic stimuli, several proapoptotic proteins are released into the cytoplasm from the mitochondria, including second mitochondria-derived activator of caspases/direct inhibitor of apoptosis protein binding protein with low pI (Smac/DIABLO), apoptosis-inducing factor (AIF), and high temperature requirement protein A2 (HtrA2/Omi). Apoptosis-inducing factor promotes apoptosis through a caspase-independent pathway, while Smac/DIABLO and HtrA2/Omi do so through both caspase-dependent and caspase-independent pathways. Smac/DIABLO was reported to be strongly positive in diffuse large B-cell lymphoma (DLBCL) and virtually absent in small lymphocytic lymphoma/chronic lymphocytic leukemia (SLL/CLL). Little is known about the expression of AIF and HtrA2/Omi in lymphomas.
Objective.—To evaluate the expression of AIF and HtrA2/Omi in SLL and DLBCL.
Design.—Twenty-three DLBCLs, 20 SLLs/CLLs, and 10 benign lymph nodes were evaluated for AIF and HtrA2/Omi expression by immunohistochemical staining.
Results.—Apoptosis-inducing factor was strongly and diffusely expressed in 19 of 23 (83%) cases of DLBCL with comparable expression pattern between germinal center–like and non-germinal center–like subgroups. Apoptosis-inducing factor was weakly positive in 15 of 20 (75%) cases of SLL/CLL with increased intensity in pseudofollicles. In contrast, HtrA2/Omi was weakly expressed in SLL/CLL (17 of 20; 85%) and DLBCL (18 of 23; 78%).
Conclusions.—The different expression level and pattern of AIF and HtrA2/Omi in SLL/CLL and DLBCL may suggest different apoptotic mechanisms involved in the pathogenesis and prognosis of these diseases. HtrA2/Omi does not appear to be a major player in the regulation of apoptosis of DLBCL and SLL/CLL.
Maintaining Clinical Tissue Archives and Supporting Human Research: Challenges and Solutions
Authors: Giannini Caterina , Oelkers Michael M , Edwards William D , Aubry Marie Christine , Muncil Maureen M , Mohamud Koshin H , Sandleback Sara G , Nowak John M , Bridgeman Andrew , Brown Marie E , Cheville John C 
Published: February 2021

Abstract
Context.—The increasing number of requests for use of clinically archived tissue in translational research poses unique challenges. Conflicts may arise between pathologists who are responsible for overseeing and preserving the tissues and investigators who need these materials for research purposes.
Objectives.—To evaluate the status of our institution's Tissue Registry Archive and to develop updated written policies and procedures to support a new modern and robust tracking system with features of a library loan system.
Design.—An observational study was performed.
Results.—We found the existing process for managing loans of tissue (slides and paraffin blocks) to be insufficient for the complexity and volume of this task. After extensive customization, a new tracking system was implemented in January 2008. Analysis of the first year of the system's use (2008) showed that of the 206 330 slides and 51 416 blocks loaned out in 2008, 92% and 94%, respectively, were returned by the due date. These rates were markedly improved from those before the new system: 61% and 47%, respectively, in 2005. Material permanently “lost” in 2008 represented only 0.02% of slides and 0.05% of blocks, none of which was the only diagnostic material for the case.
Conclusions.—With expanding needs for archived tissues for clinical care and growing demands for translational research, it is essential that pathology departments at institutions with large tissue-based research endeavors have a tracking and management system in place to meet clinical, educational, and research needs, as well as legal requirements.
Progressive Genetic Alterations of Adenoid Cystic Carcinoma With High-Grade Transformation
Authors: Seethala Raja R. , Cieply Kathleen , Barnes E. Leon , Dacic Sanja 
Published: February 2021

Abstract
Context—Although genome-wide imbalances have been characterized in conventional adenoid cystic carcinoma, other than p53 mutational status, the molecular profile of adenoid cystic carcinoma with high-grade transformation has not been explored.
Objective—To evaluate progressive genetic alterations in adenoid cystic carcinoma with high-grade transformation using array comparative genomic hybridization.
Design—Five adenoid cystic carcinomas with high-grade transformation (4 primary tumors and 1 paired metastasis) were selected and characterized at the DNA level by array comparative genomic hybridization on formalin-fixed paraffin-embedded tissue. Select alterations were validated by fluorescence in situ hybridization.
Results—Chromosomal gains were mostly confined to the areas of high-grade transformation while losses were seen only in the conventional areas. Chromosomal regions with significant gains included 8q24, 17q11.2-q12, 17q23, and 15q11-13. Regions that showed the significant losses included 9q34, 4p16, 1p36.1, and 11q22. Fluorescence in situ hybridization analysis demonstrated increases in C-MYC (8q24.12-q24.13) and a low level increases in ERBB2 (formerly HER2/neu) (17q11.2-q12) in cases showing gains by array comparative genomic hybridization in these regions. However, no tumor showed HER2/neu immunopositivity.
Conclusions—High-grade transformation in adenoid cystic carcinoma is a complex process that is reflected by several chromosomal alterations. Our findings implicate C-MYC amplification in this progression, although the role of HER2/neu is still unclear. Other candidate oncogenes, particularly on chromosome 17q23, warrant investigation in this rare tumor.
Serum Levels of Interleukins 6, 10, and 13 Before and After Treatment of Classic Hodgkin Lymphoma
Authors: Gaiolla Rafael D , Domingues Maria A. C , Niéro-Melo Lígia , de Oliveira Deilson Elgui 
Published: February 2021

Abstract
Context.—Interleukins (ILs) 6, 10, and 13 seem to be important in the pathogenesis of Hodgkin lymphoma (HL), but there is insufficient data on the serum levels of these cytokines in patients with HL.
Objectives.—To evaluate serum levels of IL-6, IL-10, and IL-13 before and after HL treatment and to determine their potential association with clinical and laboratory parameters.
Design.—Serum IL-6, IL-10, and IL-13 levels were quantified in the serum of 27 patients with HL by enzyme-linked immunosorbent assay. Results were evaluated against clinical and laboratory parameters, response to treatment, and presence of infection by the Epstein-Barr virus. As a control group, serum samples from 26 healthy blood donors were evaluated the same way.
Results.—Pretreatment serum levels of IL-6 and IL-10 were significantly higher in patients with HL (P &lt; .001), and a significant decrease was observed after treatment (P &lt; .001). Serum IL-13 was undetectable in both patient and control groups. Serum IL-6 was higher in patients with abdominal involvement (P  =  .02), hepatomegaly (P  =  .03), B symptoms (P  =  .02), and anemia (P  =  .02). Serum IL-10 levels were higher in patients with hypoalbuminemia (P  =  .04). No association with EBV status was observed. Lymphocytopenia and B symptoms were accurate predictors of IL-6 serum levels before treatment, and higher pretreatment levels of IL-6 were observed in patients with treatment failure (P  =  .03).
Conclusions.—Serum levels of IL-6 and IL-10 were frequently elevated in patients with HL and decreased substantially after conventional chemotherapy. The association of elevated IL-6 and IL-10 levels in serum with some clinical and laboratory features suggests those ILs may be useful biomarkers for monitoring the HL disease and its response to chemotherapy.
Epithelial Neoplasms of the Appendix
Authors: Tang Laura H. 
Published: February 2021

Abstract
Context.—The appendix gives rise to an array of epithelial neoplasms showing glandular or neuroendocrine differentiation, and some tumors with elements of both cell types. Although some appendiceal neoplasms resemble their counterparts in the small and large intestines (conventional adenocarcinoma and carcinoid tumor), the appendix also gives rise to relatively unique entities including mucinous neoplasms and goblet cell carcinoid tumors, which present a challenge in pathologic classification and clinical management.
Objective.—To review clinical and diagnostic issues for 3 pathologic types of epithelial neoplasms of the appendix: (1) adenocarcinoma, with specific focus on mucinous neoplasm; (2) goblet cell carcinoid tumor and associated adenocarcinoma; and (3) typical carcinoid tumor.
Data Sources.—Case-derived material and literature review.
Conclusions.—The most important issue in pathologic assessment of epithelial tumors of the appendix is to understand the clinical implications inherent in the diagnosis.
Aberrant CpG Island Hypermethylation in Pediatric Gastric Mucosa in Association With Helicobacter pylori Infection
Authors: Shin So-Hyun , Park Seog-Yun , Ko Jae-Sung , Kim Nayoung , Kang Gyeong Hoon 
Published: February 2021

Abstract
Context.—Helicobacter pylori infection is primarily acquired during childhood and persists throughout life in the absence of eradication with antibiotics. Helicobacter pylori infection induces methylation in the promoter CpG island loci in gastric epithelial cells. Thus, aberrant CpG island hypermethylation in gastric epithelial cells likely occurs early in life, although there are no existing data supporting this notion.
Objectives.—To identify whether aberrant CpG island hypermethylation occurs in pediatric stomach mucosa in association with H pylori infection and to compare methylation profiles of samples from pediatric and adult stomach tissues.
Design.—We analyzed pediatric (n  =  47) and adult (n  =  38) gastric mucosa samples for their methylation status in 12 promoter CpG island loci using the MethyLight assay and compared the number of methylated genes and the methylation levels in individual genes between H pylori–positive and H pylori–negative sample results and between pediatric and adult samples.
Results.—The average number of methylated genes was significantly higher in H pylori–infected pediatric samples than in H pylori–negative pediatric samples (3.4 versus 0.3, P &lt; .001) and in H pylori–infected adult samples than in H pylori–negative adult samples (7.6 versus 0.9, P &lt; .001). Seven genes showed significantly higher methylation levels in H pylori–infected pediatric samples than in H pylori–negative pediatric samples (all values were P &lt; .05).
Conclusions.—These results indicate that CpG island hypermethylation occurs in pediatric gastric mucosa in association with H pylori infection and that the genes affected by H pylori–associated hypermethylation were similar in pediatric and adult samples.
Clinical Implications of Margin Involvement by Pleomorphic Lobular Carcinoma In Situ
Authors: Downs-Kelly Erinn , Bell Diana , Perkins George H. , Sneige Nour , Middleton Lavinia P. 
Published: February 2021

Abstract
Context.—The appropriate treatment for patients with pleomorphic lobular carcinoma in situ (PLCIS) is unknown. When diagnosed on core biopsy, excision is recommended; however, management of PLCIS when it involves margins has not been addressed.
Objective.—To evaluate the significance of PLCIS that is located close to, or at, a resection margin.
Design.—We identified 26 patients with resection specimens containing PLCIS, all of whom were offered chemoprevention and radiation therapy. The margin status in these patients was subdivided as PLCIS cells at the margin without obvious truncation of lesion; PLCIS less than or equal to 1 mm from, but not involving, the margin; PLCIS 1.1 to 2 mm from the margin; and PLCIS at least 2.1 mm from the margin.
Results.—Patient age ranged from 35 to 76 years (mean, 58 years), and length of follow-up ranged from 4 to 108 months (mean, 46 months). Six of the 26 patients (23%) received chemoprevention, 4 of 26 patients (15%) received radiation therapy, and 6 of 26 patients (23%) received both. The remaining 10 patients received no further therapy. Pleomorphic lobular carcinoma in situ was at the margin in 6 of the 26 cases (23%), 1 mm from the margin in 7 of 26 cases (27%), 1.1 to 2 mm from the margin in 4 of 26 cases (15%), and was at least 2.1 mm from the margin in 9 of 26 cases (35%). In 1 of the 26 patients, recurrent PLCIS was identified 18 months after initial surgery, for an overall recurrence rate of 3.8%. All other patients were clinically and radiologically free of disease at last follow-up.
Conclusions.—This is the first series, to our knowledge, that evaluates margin status in patients with PLCIS and documents recurrence. Recurrent PLCIS was identified at a rate similar to low- or intermediate-grade ductal carcinoma in situ. Therefore, known methods of local control, including surgical excision with negative margins (2 mm), may be the appropriate treatment in these patients.
Nodular Lymphocyte Predominant Hodgkin Lymphoma: Diagnostic Pearls and Pitfalls
Authors: Smith Lauren B. 
Published: February 2021

Abstract
Context.—The diagnosis of nodular lymphocyte predominant Hodgkin lymphoma involves key histopathologic and immunophenotypic findings. Appropriate classification is essential owing to the unique therapeutic and prognostic implications of this diagnosis.
Objective.—To define the histologic and immunophenotypic features useful in diagnosing nodular lymphocyte predominant Hodgkin lymphoma and to identify the important differential diagnostic considerations. Diagnostic difficulty can arise in differentiating nodular lymphocyte predominant Hodgkin lymphoma from classical Hodgkin lymphoma, T-cell/histiocyte-rich large B-cell lymphoma, follicular lymphoma (floral variant), and follicular hyperplasia with progressive transformation of germinal centers.
Design.—Discussion of illustrative cases including morphologic and immunophenotypic findings.
Results.—With the morphologic and immunophenotypic methods described, a diagnosis of nodular lymphocyte predominant Hodgkin lymphoma can be made on excisional biopsies.
Conclusion.—Clinical, histologic, and immunophenotypic features are invaluable in reaching an accurate diagnosis.
Bronchioloalveolar Carcinoma and the Significance of Invasion: Predicting Biologic Behavior
Authors: Schmidt Lindsay , Myers Jeffrey 
Published: February 2021

Abstract
A resected adenocarcinoma illustrates challenges in diagnosing bronchioloalveolar carcinoma (BAC). Bronchioloalveolar carcinoma is defined by lack of invasion, something that may be difficult to assess in scars. Small (≤0.5 cm) invasive foci have little impact on the good prognosis associated with low-stage tumors. The term microinvasive adenocarcinoma or minimally invasive adenocarcinoma has been proposed for otherwise typical BACs and small invasive foci measuring 0.5 cm or less. Larger areas of invasion are associated with a more aggressive course and more reliably distinguish BAC from other variants of adenocarcinoma. Separating BAC from other forms of adenocarcinoma is important owing to differences in prognosis and emerging therapeutic strategies.
Acral Junctional Nevus Versus Acral Lentiginous Melanoma In Situ: A Differential Diagnosis That Should Be Based on Clinicopathologic Correlation
Authors: Puccio Francisco Bravo , Chian Cesar 
Published: February 2021

Abstract
Context.—Acral lentiginous melanoma is the most prevalent clinical presentation of melanoma in ethnic groups other than whites and also occurs in significant numbers in North America and Europe. Despite a clear-cut clinical picture, histologic findings seen in partial biopsies may be too subtle and deceive pathologists dealing with such cases.
Objectives.—To make pathologists aware of the histologic findings during early phases of acral lentiginous melanoma (including the in situ phase), to compare those findings with what is seen in acral junctional nevus, and to highlight their similarities and differences. This review will also emphasize the important clinical and dermatoscopic findings to be considered when diagnosing acral lentiginous melanoma.
Data Sources.—Review of published articles on the epidemiology; the clinical, dermatoscopic, and histopathologic findings; and the molecular biology of acral lentiginous melanoma as well as the personal experience of the authors when dealing with such cases.
Conclusions.—Acral lentiginous melanoma is a clinicopathologic entity with a clear-cut clinical picture: a diameter larger than 0.7 mm; ill-defined, darkly pigmented, flat lesion with irregular borders on acral locations; and the presence of mostly single-cell proliferations of melanocytes along the dermo-epidermal junction. Along with a few additional criteria, these findings should be sufficient to allow the pathologist to make the diagnosis and to recommend complete excision. Fluent communication between clinician and pathologist will facilitate a correct diagnosis.
Mitochondrial Disorders of DNA Polymerase γ Dysfunction: From Anatomic to Molecular Pathology Diagnosis
Authors: Zhang Linsheng , Chan Sherine S. L. , Wolff Daynna J. 
Published: February 2021

Abstract
Context.—Primary mitochondrial dysfunction is one of the most common causes of inherited disorders predominantly involving the neuromuscular system. Advances in the molecular study of mitochondrial DNA have changed our vision and our approach to primary mitochondrial disorders. Many of the mitochondrial disorders are caused by mutations in nuclear genes and are inherited in an autosomal recessive pattern. Among the autosomal inherited mitochondrial disorders, those related to DNA polymerase γ dysfunction are the most common and the best studied. Understanding the molecular mechanisms and being familiar with the recent advances in laboratory diagnosis of this group of mitochondrial disorders are essential for pathologists to interpret abnormal histopathology and laboratory results and to suggest further studies for a definitive diagnosis.
Objectives.—To help pathologists better understand the common clinical syndromes originating from mutations in DNA polymerase γ and its associated proteins and use the stepwise approach of clinical, laboratory, and pathologic diagnosis of these syndromes.
Data Sources.—Review of pertinent published literature and relevant Internet databases.
Conclusions.—Mitochondrial disorders are now better recognized with the development of molecular tests for clinical diagnosis. A cooperative effort among primary physicians, diagnostic pathologists, geneticists, and molecular biologists with expertise in mitochondrial disorders is required to reach a definitive diagnosis.
Recurrence Risk and Margin Status in Granular Cell Tumors of the Breast: A Clinicopathologic Study of 13 Patients
Authors: Papalas John A. , Wylie John D. , Dash Rajesh C. 
Published: February 2021

AbstractContext.—Granular cell tumors (GCTs) of the breast are rare neoplasms that mimic epithelial malignancy clinically and rarely occur in association with it. Granular cell tumors of the breast are not infrequently excised with positive margins. Reports describing risk of recurrence including data on margin status and follow-up are lacking.Objective.—To review our series of GCTs of the breast to determine the risk of recurrence if excised with positive or close margins.Design.—Cases of GCT of the breast were reviewed. Margin status of specimens was recorded as positive, close (&lt;1 mm), and negative.Results.—Thirteen female patients with GCT of the breast were identified. Mean patient age at presentation was 45 years. Seventy-seven percent of patients were African American and 23% were white. African American patients presented on average 13 years earlier than white patients. Average tumor size was 1.22 cm. Fifteen percent of lesions had positive margins on excisional biopsy or lumpectomy and 31% had tumor cells within 1 mm of the margin. One of 13 patients (8%) had coexistent invasive ductal carcinoma. Average follow-up for the entire group was 77 months. Patients with positive margins remained free of tumor progression or recurrence for 89 months and patients with close margins also remained disease free during a 64-month follow-up period. No tumors recurred out of the entire group.Conclusion.—Granular cell tumors of the breast have little long-term risk for recurrence, even when excised with positive margins. Surgical evaluation after nonexcisional biopsy may still be indicated to assess for the possible association of colocalized carcinoma.
Revolution in Lung Cancer: New Challenges for the Surgical Pathologist
Authors: Cagle Philip T. , Allen Timothy C. , Dacic Sanja , Beasley Mary Beth , Borczuk Alain C. , Chirieac Lucian R. , Laucirica Rodolfo , Ro Jae Y. , Kerr Keith M. 
Published: February 2021

Abstract
Context—Traditionally, lung cancer has been viewed as an aggressive, relentlessly progressive disease with few treatment options and poor survival. The traditional role of the pathologist has been primarily to differentiate small cell carcinoma from non–small cell carcinoma on biopsy and cytology specimens and to stage non–small cell carcinomas that underwent resection. In recent years, our concepts of lung cancer have undergone a revolution, including (1) the advent of successful, new, molecular-targeted therapies for lung cancer, many of which are associated with specific histologic cell types and subtypes; (2) new observations on the natural history of lung cancer derived from ongoing high-resolution computed tomography screening studies and recent histologic findings; and (3) proposals to revise the classification of lung cancers, particularly adenocarcinomas, in part because of the first 2 developments.
Objective—To summarize the important, new developments in lung cancer, emphasizing the role of the surgical pathologist in personalized care for patients with lung cancer.
Data Sources—Information about the new developments in lung cancer was obtained from the peer-review medical literature and the authors' experiences.
Conclusions—For decades, we have perceived lung cancer as a relentlessly aggressive and mostly incurable disease for which the surgical pathologist had a limited role. Today, surgical pathologists have an important and expanding role in the diagnosis and treatment of lung cancer, and it is essential to keep informed of new advances.