bluuebunny/crossref_metadata_2025 huggingface dataset:
Hyperchromatic Crowded Groups in Cervical Cytology—Differing Appearances and Interpretations in Conventional and ThinPrep Preparations: A Study From the College of American Pathologists Interlaboratory Comparison Program in Cervicovaginal Cytology
Authors: Renshaw Andrew A. , Mody Dina R. , Wang Edward , Haja Jennifer , Colgan Terence J.
Published: February 2021

Context.—The practice of gynecologic cytology requires that high-grade squamous intraepithelial lesion (HSIL) be precisely recognized. In this regard, hyperchromatic crowded groups are known to be difficult to classify in conventional gynecologic cytology, but whether this is true in ThinPrep specimens is uncertain.

Objective.—To assess whether hyperchromatic crowded groups of cells in challenging HSIL cases are a problem in ThinPrep preparations, and whether these groups differ in appearance from those of conventional smears.

Design.—Sixteen images were taken from both conventional smears and ThinPrep slides that had a reference diagnosis of HSIL in the College of American Pathologists Interlaboratory Comparison Program in Cervicovaginal Cytology, but had performed poorly on subsequent participants' reviews. These 32 representative images were of hyperchromatic crowded groups and were classified by 20 Cytopathology Resource Committee members (17 pathologists and 3 cytotechnologists), who were masked to the reference diagnosis. A consensus classification was derived using the majority opinion of the individual reviewers. Finally, 5 cytologic features were assessed for those images that were interpreted as abnormal by the consensus classification.

Results.—None of the 32 images was uniformly interpreted as either benign, squamous lesion, or glandular lesion on individual review. Only 27% of individual interpretations of conventional smear images and 15% of ThinPrep images were interpreted as HSIL/squamous cell carcinoma (P < .001). Individual interpretations of ThinPrep images as glandular lesions (60%) were more often made than those of conventional smears (44%, P < .001). The consensus interpretation of ThinPrep images was glandular lesion in 75% of cases, whereas fewer than 50% of the consensus interpretations of conventional smear images were in this category. Conventional smear images were characterized by elongate nuclei (43%) and large nuclei (71%), whereas ThinPrep images more often showed rounded smooth edges (53%) and small nuclei (80%), and were recognized as a glandular lesion.

Conclusions.—Hyperchromatic crowded groups of cells are a source of difficulty in challenging HSIL cases for both conventional smears and ThinPrep specimens. In conventional smears, these groups are more likely to be labeled as a squamous lesion, owing to their elongate and large nuclei. In ThinPrep specimens, however, these groups are more likely to be labeled as glandular lesions, owing to their smooth contoured borders and small nuclei.
Measuring Human Complement Activation by HLA Antibodies
Authors: Watanabe Jota , Scornik Juan C.
Published: February 2021

Context.—The clinical significance of HLA antibodies in transplantation depends on their ability to activate complement, which is measured by the standard complement-dependent cytotoxicity test. Recent reports indicate that C3b measurement on target cells may be a better indicator of human complement activation than standard cytotoxicity.

Objective.—To determine the characteristics of the test, the role of other complement components, and the potential influence of the patient's own complement activity.

Design.—The T-cell deposition of multiple complement components triggered by HLA alloantibodies was evaluated by flow cytometry using normal human serum as the source of complement. Complement activity in patients' sera was measured after activation with a standard antibody.

Results.—When HLA antibodies activate complement, C3b deposition is usually highest, followed by that of C4b and C5b. Deposition of C1q, C3d, iC3b, or C5b-9 was low or undetectable in this study. The C5 was activated only when relatively high levels of C3b were present. There was a critical concentration of antibody, unique for each patient, below which activation of C3 declined abruptly. The complement activity in the serum of candidates for liver, heart, and lung transplantation that was tested with a standard antibody was similar to normal serum. In contrast, kidney transplant candidates exhibited higher complement activity. Unexpectedly, serum C3 activity was retained for at least 72 hours after collection.

Conclusions.—Measurement of C3b, and in some instances C4b or C5b, offers a better definition of the ability of HLA antibodies to activate human complement than tests that are in current use. The results provide a necessary baseline to conduct clinical correlation studies.
A Comparison of Glass and Plastic Blood Collection Tubes for Routine and Specialized Coagulation Assays: A Comprehensive Study
Authors: Kratz Alexander , Stanganelli Nancy , Van Cott Elizabeth M.
Published: February 2021

Context.—Blood collection tubes made from plastic are beginning to replace glass tubes. Coagulation test results can be influenced easily by preanalytic factors, including exposure to surfaces that activate the clotting cascade.

Objective.—To compare the effects of the blood collection tube material on 22 coagulation assays performed in clinical laboratories.

Design.—Paired blood samples from 28 healthy volunteers were drawn into BD Vacutainer Glass Citrate Tubes and BD Vacutainer Plus Plastic Citrate Tubes, and the results of coagulation assays were determined in parallel.

Results.—No statistically significant differences were observed between glass and plastic for 14 assays: prothrombin time (and international normalized ratio); activated partial thromboplastin time; activated protein C resistance; antithrombin activity; factors II, V, VIII, and IX; α2-antiplasmin; plasminogen activity; von Willebrand factor antigen; ristocetin cofactor; thrombin time; and reptilase time. Statistically significant differences were found for fibrinogen; chromogenic protein C activity; protein S activity; PTT-LA lupus anticoagulant–sensitive activated partial thromboplastin time; and factors VII, X, XI, and XII. Mean differences ranged from 0.4% to 5.5% and were unlikely to be of clinical significance.

Conclusions.—The results of this study suggest that plastic tubes can be used in place of glass tubes for a wide variety of coagulation assays.
Fine-Needle Aspiration of Papillary Thyroid Carcinoma: Distinguishing Between Cases That Performed Well and Those That Performed Poorly in the College of American Pathologists Nongynecologic Cytology Program
Authors: Renshaw Andrew A. , Wang Edward , Haja Jennifer , Wilbur David , Henry Michael R. , Hughes Jonathan H.
Published: February 2021

Context.—Although the cytologic features of papillary thyroid carcinoma in fine-needle aspiration specimens are well known, the correlation of these features with the ability of cytologists to identify this tumor has not been well studied.

Objective.—To compare the cytologic features of cases of papillary thyroid carcinoma that performed poorly with those of cases that performed well.

Design.—The cytologic features of 13 cases of papillary thyroid carcinoma from the College of American Pathologists Nongynecologic Cytology Program that performed poorly were compared with those of 15 cases that performed well.

Results.—Compared with cases that performed well, cases that performed poorly were significantly more likely to lack marked nuclear enlargement (38% vs 100%, P < .001), lack pale chromatin (8% vs 47%, P = .04), and lack intranuclear inclusions (8% vs 53%, P = .02). The differences between the 2 groups in staining, type of preparation, nuclear grooves, nuclear crowding, colloid, cellularity, nuclear pleomorphism, and Hurthle cell change were not significant.

Conclusions.—Cases of papillary thyroid carcinoma that lack marked nuclear enlargement, pale chromatin, and intranuclear inclusions are significantly more difficult to recognize than cases that have these features. Increased awareness of these types of cases might improve the performance of thyroid fine-needle aspiration in clinical practice.
Tumoral Calcinosis of the Hand: Three Unusual Cases With Painful Swelling of Small Joints
Authors: Kim Han-Seong , Suh Jin Su , Kim Yong Hoon , Park Sung-Hye
Published: February 2021

Tumoral calcinosis is a rare ectopic calcification syndrome characterized by irregular soft tissue masses originally described as being found mainly in large joints. We report 3 cases of tumoral calcinosis that occurred in unusual locations, the metacarpophalageal and proximal interphalangeal joints of the hand. The patients were women who ranged in age from 26 to 44; all presented with complaints of painful swelling of the joints. Laboratory tests demonstrated normal serum phosphate and calcium levels. Radiologic examination disclosed para-articular calcified masses. On surgical excision, the deep-seated calcified masses were attached to collateral ligaments of the joints. Milky and chalklike fluid was released during surgery. The masses measured 1.5, 0.9, and 0.8 cm in length and had irregular surfaces. Microscopically, the masses had fibrous capsule and the inner small cystic spaces that contained granular, calcified material. These cysts contained proliferating capillaries, mononuclear lymph plasma cells, and giant cells. No recurrences were found in any of the patients during the follow-up periods.
Esophageal Melanocytosis Morphologic Features and Review of the Literature
Authors: Chang Fuju , Deere Harriet
Published: February 2021

Endoscopic or macroscopic esophageal melanocytosis is a benign clinicopathologic entity characterized by melanocytic proliferation in esophageal squamous epithelium and melanin deposition in the mucosa. Little is known about the etiology and natural course of this condition, although it has been suggested to be a precursor of primary esophageal melanoma by some authors. Following a search of the bibliographic databases (PubMed and Medline) regarding esophageal melanocytosis and melanosis, thirty-four cases of isolated esophageal melanocytosis (including one unpublished case from us) were found. The histopathologic features of esophageal melanocytosis are reviewed and its differential diagnosis with other pigmented esophageal lesions is discussed.
Pediatric Surgical Pathology: Pitfalls and Strategies for Error Prevention
Authors: Coffin Cheryl M.
Published: February 2021

Context.—Few data exist regarding quality measures for pediatric surgical pathology, types of errors, or how error-prone situations and diagnostic pitfalls can be minimized.

Objective.—This review reports on survey findings regarding methodology for quality assurance and error detection measurement and classification in pediatric surgical pathology. It presents information regarding, and quality aspects of, intraoperative consultations in pediatric surgical pathology. General strategies for identifying diagnostic pitfalls in pediatric surgical pathology are briefly discussed.

Data Sources.—A survey of children's hospitals based on a survey created by the Association of Directors of Anatomic and Surgical Pathology, literature review, and institutional quality assurance records provided information for this review.

Conclusions.—Approaches to quality assurance and error reduction in pediatric surgical pathology are similar to those used in general surgical pathology. The children's hospitals that were surveyed used a variety of standard quality assurance measures. Because of differences in data collection, classification, and reporting, it is not possible to provide a detailed analysis of the types of diagnostic error across institutions at this time. Intraoperative consultations are a potential source of error. Pediatric neoplasms and Hirschsprung disease account for the majority of intraoperative consultations in the pediatric setting. Further considerations include the unique aspects of pediatric medical and neoplastic disorders and special diagnostic criteria, classification, grading, and staging requirements.
Error Reduction in Surgical Pathology
Authors: Nakhleh Raouf E.
Published: February 2021

Context.—Because of its complex nature, surgical pathology practice is inherently error prone. Currently, there is pressure to reduce errors in medicine, including pathology.

Objective.—To review factors that contribute to errors and to discuss error-reduction strategies.

Design.—Literature review.

Results.—Multiple factors contribute to errors in medicine, including variable input, complexity, inconsistency, tight coupling, human intervention, time constraints, and a hierarchical culture. Strategies that may reduce errors include reducing reliance on memory, improving information access, error-proofing processes, decreasing reliance on vigilance, standardizing tasks and language, reducing the number of handoffs, simplifying processes, adjusting work schedules and environment, providing adequate training, and placing the correct people in the correct jobs.

Conclusions.—Surgical pathology is a complex system with ample opportunity for error. Significant error reduction is unlikely to occur without a sustained comprehensive program of quality control and quality assurance. Incremental adoption of information technology and automation along with improved training in patient safety and quality management can help reduce errors.
Improving Patient Safety Through Quality Assurance
Authors: Raab Stephen S.
Published: February 2021

Context.—Anatomic pathology laboratories use several quality assurance tools to detect errors and to improve patient safety.

Objective.—To review some of the anatomic pathology laboratory patient safety quality assurance practices.

Design.—Different standards and measures in anatomic pathology quality assurance and patient safety were reviewed.

Main Outcome Measures.—Frequency of anatomic pathology laboratory error, variability in the use of specific quality assurance practices, and use of data for error reduction initiatives.

Results.—Anatomic pathology error frequencies vary according to the detection method used. Based on secondary review, a College of American Pathologists Q-Probes study showed that the mean laboratory error frequency was 6.7%. A College of American Pathologists Q-Tracks study measuring frozen section discrepancy found that laboratories improved the longer they monitored and shared data. There is a lack of standardization across laboratories even for governmentally mandated quality assurance practices, such as cytologic-histologic correlation. The National Institutes of Health funded a consortium of laboratories to benchmark laboratory error frequencies, perform root cause analysis, and design error reduction initiatives, using quality assurance data. Based on the cytologic-histologic correlation process, these laboratories found an aggregate nongynecologic error frequency of 10.8%. Based on gynecologic error data, the laboratory at my institution used Toyota production system processes to lower gynecologic error frequencies and to improve Papanicolaou test metrics.

Conclusion.—Laboratory quality assurance practices have been used to track error rates, and laboratories are starting to use these data for error reduction initiatives.
Critical Values in Anatomic Pathology
Authors: Silverman Jan F. , Pereira Telma C.
Published: February 2021

Similar to critical values (CVs) in clinical pathology, occasional diagnoses in surgical pathology and cytology could require immediate notification of the physician to rapidly initiate treatment. However, there are no established CV guidelines in anatomic pathology. A retrospective review of surgical pathology reports was recently conducted to study the incidence of CVs in surgical pathology and to survey the perceptions of pathologists and clinicians about CVs in surgical pathology, with a similar analysis of CVs performed in cytology. The results indicated that CVs in surgical pathology and cytology are uncommon but not rare and that there is a wide range of opinion among pathologists and between pathologists and clinicians about the need for an immediate telephone call and about the degree of urgency. It was obvious from the study that there is a lack of consensus in identifying what constitutes surgical pathology and cytology CV cases. Since the Institute of Medicine's report on medical errors, there has been an increasing number of initiatives to improve patient safety. Having guidelines for anatomic pathology CVs could enhance patient safety, in contrast to the current practice in which CV cases are managed based on common sense and on personal experience. Therefore, a discussion involving the pathology community might prove useful in an attempt to establish anatomic pathology CV guidelines that could represent a practice improvement.
Determining Customer Satisfaction in Anatomic Pathology
Authors: Zarbo Richard J.
Published: February 2021

Context.—Measurement of physicians' and patients' satisfaction with laboratory services has become a standard practice in the United States, prompted by national accreditation requirements. Unlike other surveys of hospital-, outpatient care–, or physician-related activities, no ongoing, comprehensive customer satisfaction survey of anatomic pathology services is available for subscription that would allow continual benchmarking against peer laboratories. Pathologists, therefore, must often design their own local assessment tools to determine physician satisfaction in anatomic pathology.

Objective.—To describe satisfaction survey design that would elicit specific information from physician customers about key elements of anatomic pathology services.

Design.—The author shares his experience in biannually assessing customer satisfaction in anatomic pathology with survey tools designed at the Henry Ford Hospital, Detroit, Mich. Benchmarks for physician satisfaction, opportunities for improvement, and characteristics that correlated with a high level of physician satisfaction were identified nationally from a standardized survey tool used by 94 laboratories in the 2001 College of American Pathologists Q-Probes quality improvement program.

Results.—In general, physicians are most satisfied with professional diagnostic services and least satisfied with pathology services related to poor communication.

Conclusions.—A well-designed and conducted customer satisfaction survey is an opportunity for pathologists to periodically educate physician customers about services offered, manage unrealistic expectations, and understand the evolving needs of the physician customer. Armed with current information from physician customers, the pathologist is better able to strategically plan for resources that facilitate performance improvements in anatomic pathology laboratory services that align with evolving clinical needs in health care delivery.
Manual Exfoliation Plus Immunomagnetic Bead Separation as an Initial Step Toward Translational Research
Authors: Mojica Wilfrido D. , Arshad Ayesha , Sharma Sanjay , Brooks Stephen P.
Published: February 2021

Context.—The development of biotechnologic platforms capable of high throughput analysis has ushered in a promising new era of translational medicine. However, most studies to date are based on in vitro cell lines or substitute models for human disease. Although these model systems have proven insightful, it is readily becoming apparent that human clinical tissue must be studied in order to fully understand all the nuances of human disease. Studies that are based on human tissue, however, are limited by qualitative and quantitative issues, factors often precluding their use in high throughput studies.

Objective.—To develop a simple and rapid tissue procurement protocol for use in obtaining a homogeneous epithelial cell population from clinical tissue and the recovery of nucleic acids and proteins of high quality and quantity. Also, to determine if the technique preserves tissue, thereby allowing morphologic correlation with molecular findings.

Design.—Performance of manual exfoliation to procure cells from clinical resection specimens and use of immunomagnetic beads embedded with the antibody ber-Ep4 for the positive enrichment of a homogeneous epithelial cell population. Nucleic acids and proteins are then separated using a phenol plus guanidine thiocyante solution. Nucleic acids and proteins are quantitated and qualitatively analyzed using standard laboratory techniques.

Results.—Nucleic acids and proteins of high quality and quantity were recovered following manual exfoliation and immunomagnetic bead separation. Tissue architecture was not destroyed, thus permitting histologic and molecular correlation.

Conclusions.—A simple and reproducible protocol is presented that may enable the molecular profiling of clinically resected tissue. Although the technique is currently limited to certain tissue and tumor types, further research will broaden its overall application.
Mixed Epithelial and Stromal Tumor of the Kidney and Cystic Nephroma Share Overlapping Features: Reappraisal of 15 Lesions
Authors: Antic Tatjana , Perry Kent T. , Harrison Kathleen , Zaytsev Polina , Pins Michael , Campbell Steven C. , Picken Maria M.
Published: February 2021

Context.—Cystic nephroma is a rare cystic tumor, which only recently has been recognized as an exclusively adult lesion. Mixed epithelial and stromal tumor of the kidney is also a rare, recently recognized, biphasic tumor composed of tubular and cystic elements embedded in grossly recognizable spindle cell stroma. The histogenesis of both lesions is unclear.

Objectives.—To compare clinical phenotype, morphology, and immunohistochemistry in mixed epithelial and stromal tumor of the kidney and cystic nephroma in order to explore the relationship between these 2 lesions.

Design.—Fifteen biphasic lesions (8 mixed epithelial and stromal tumors of the kidney and 7 cystic nephromas) were studied. All cases were reviewed and subjected to detailed pathologic studies, and the results were correlated with clinical findings.

Results.—Mixed epithelial and stromal tumor of the kidney occurred exclusively in women aged 36 to 80 years (mean, 49.7 years), all of whom had a history of estrogen therapy and/or obesity. Cystic nephroma occurred in both sexes; patients were aged 22 to 71 years (mean, 50.4 years), and a history of hormonal therapy was present on occasion. All 15 lesions were benign. Lesions varied by size, the proportion of cystic component, and the amount and cellularity of stroma. However, in all lesions tested, the stroma was diffusely positive for smooth muscle actin, and smooth muscle differentiation was confirmed by electron microscopy. In mixed epithelial and stromal tumors of the kidney, the stroma was positive for estrogen and progesterone receptors in 4 of 5 lesions tested. In cystic nephroma, focal positivity for hormone receptors was seen in 2 of 7 tumors tested; both positive lesions were from women. The epithelial lining in both mixed epithelial and stromal tumor of the kidney and cystic nephroma lesions was variable with regard to shape, cytoplasmic appearance, and immunophenotype (with focal positivity for CD10, cytokeratin 7, high-molecular-weight keratin, and Ulex europaeus detectable in both lesions). This pattern suggests variable differentiation, which was confirmed by electron microscopic studies (performed in 1 case).

Conclusions.—While mixed epithelial and stromal tumor of the kidney has a strong association with the female sex and hormonal milieu, cystic nephroma can affect both sexes and, on occasion, may also have hormonal associations. Morphologically, there is considerable overlap between both lesions, which suggests that they may represent opposite ends of the spectrum of the same process. Our studies also suggest that the tubules may be entrapped rather than comprising an intrinsic component of the tumor. However, further studies, including molecular studies, are needed to support this hypothesis.
Expression of Renal Cell Carcinoma–Associated Markers Erythropoietin, CD10, and Renal Cell Carcinoma Marker in Diffuse Malignant Mesothelioma and Metastatic Renal Cell Carcinoma
Authors: Butnor Kelly J. , Nicholson Andrew G. , Allred D. Craig , Zander Dani S. , Henderson Douglas W. , Barrios Roberto , Haque Abida K. , Allen Timothy C. , Killen Deanna E. , Cagle Philip T.
Published: February 2021

Context.—Metastatic renal cell carcinoma (MRCC) involving the thorax can be difficult to distinguish from diffuse malignant mesothelioma (DMM) using traditional morphologic approaches. Standard panels of immunohistochemical markers are of limited benefit.

Objective.—To investigate several antibodies to renal cell carcinoma–associated proteins for differentiating MRCC from DMM.

Design.—One hundred DMMs and 20 MRCCs were evaluated for immunoexpression of erythropoietin. The same cases and an additional 45 DMMs were evaluated for CD10 and renal cell carcinoma marker (RCCMa) immunoreactivity.

Results.—Erythropoietin was expressed in 100% of DMMs and MRCCs. Staining for CD10 was observed in 54% of DMMs and 100% of MRCCs. RCCMa stained 26% of DMMs and 55% of MRCCs. Although erythropoietin staining was similarly strong and diffuse in both DMM and MRC, patterns of staining for RCCMa and CD10 differed between MRCC and DMM. Immunoreactivity was strong and diffuse for both RCCMa and CD10 in most MRCCs. Of CD10-positive DMMs, nearly half showed staining in less than 50% of tumor cells and about one fourth of positive cases exhibited only weak to moderately intense staining. Only half of RCCMa-positive DMMs showed staining in more than 49% of tumor cells and staining was only weak to moderately intense in most cases.

Conclusions.—Given the overlap in the expression of renal cell carcinoma markers in MRCC and DMM, results with these markers must be interpreted cautiously and should be used in conjunction with mesothelium-associated markers. Differences in expression may potentially help distinguish MRCC from DMM inasmuch as strong and diffuse expression of RCCMa and CD10 supports a diagnosis of MRCC over DMM.
Low-Grade Mucosa-Associated Lymphoid Tissue Lymphoma Involving the Kidney: Report of 3 Cases and Review of the Literature
Authors: Qiu Libo , Unger Pamela D. , Dillon Robert W. , Strauchen James A.
Published: February 2021

Low-grade B-cell lymphoma of mucosa-associated lymphoid tissue involving the kidney is rare. We report a series of 3 cases. The first case occurred in an 83-year-old woman who presented with back pain. The second case was a 53-year-old man with a history of sarcoidosis who was found, in the course of evaluation of sarcoidosis, to have a right renal mass. The third case occurred in a 72-year-old man who had a history of periorbital mucosa–associated lymphoid tissue lymphoma and had been treated with surgery and radiation 1 year prior to this presentation. Histologically, all 3 patients showed infiltrate of uniform small-to-medium–sized lymphocytes with irregular nuclear contours and abundant cytoplasm resembling centrocytes or monocytoid lymphoid cells. The first patient received chemotherapy without complications. The second patient underwent a partial nephrectomy and was asymptomatic at the subsequent follow-up. The third patient developed a pulmonary embolism following nephrectomy, and further follow-up is not available.
Human Leukocyte Antigen Alleles and Haplotypes Associated With Chronicity of Hepatitis B Virus Infection in Koreans
Authors: Hwang Sang-Hyun , Sohn Yong-Hak , Oh Heung-Bum , Hwang Chang Yun , Lee Soong-Hwan , Shin Eun-Soon , Lee Kwan Jeh
Published: February 2021

Context.—Chronic hepatitis B infection is the leading cause of cirrhosis and hepatocellular carcinoma. Human leukocyte antigen may be involved in the chronicity of hepatitis B virus (HBV) infection.

Objective.—To analyze the association between HBV chronicity and human leukocyte antigen alleles and haplotypes of 636 organ donors and recipients.

Design.—Subjects were categorized into 2 groups according to their clinical and serologic profiles, specifically, an HBV natural convalescent group and an HBV chronic carrier (CC) group.

Results.—Hepatitis B chronicity was positively associated with A33 (P = .004, odds ratio [OR] = 1.59) and DR7 (P < .001, OR = 2.58), and negatively associated with HLA-DR13 (P < .001, OR = 0.40). Coexpression of A33 and DR7 was significantly higher in the CC group (OR = 3.63), compared with that of either allele alone (OR = 1.76 in A33; OR = 2.53 in DR7). The statistically significant haplotypes were B44-DR7 (P < .001, OR = 5.44), A33-DR7 (P < .001, OR = 4.47), and A33-B44-DR7 (P < .001, OR = 7.31) in the CC group.

Conclusions.—Our results indicate that alleles of A33, DR7, and haplotypes containing DR7 are associated with HBV chronicity among Koreans. Moreover, the 2 antigens had an additive effect on chronicity. These findings support the theory that human leukocyte antigen class I–restricted cytotoxic T cells and human leukocyte antigen class II– restricted helper T cells play an important role in HBV chronicity.
Nephrogenic Systemic Fibrosis Mimicking Inflammatory Breast Carcinoma
Authors: Solomon Garron J. , Wu Elizabeth , Rosen Paul Peter
Published: February 2021

Nephrogenic systemic fibrosis, previously known as nephrogenic fibrosing dermopathy, is a newly recognized systemic fibrosing disorder primarily affecting patients with chronic renal failure. Patients with skin involvement often develop papules and plaques with peau d'orange surface changes. The lower extremities and trunk are most commonly affected. The most important histologic differential diagnosis is with scleromyxedema. To our knowledge, we report the first case of nephrogenic systemic fibrosis involving the breasts of a 61-year-old woman with end-stage renal disease, clinically mimicking inflammatory breast carcinoma. We propose that nephrogenic systemic fibrosis be considered in the differential diagnosis as a rare possibility when cutaneous changes in the breast suggest inflammatory breast carcinoma in a patient with renal failure.
Clear Cell Sarcoma of Tendons and Aponeuroses: A Review
Authors: Dim Daniel C. , Cooley Linda D. , Miranda Roberto N.
Published: February 2021

Clear cell sarcoma of tendons and aponeuroses, also referred to as malignant melanoma of soft parts, is a rare malignancy derived from neural crest cells. It usually presents in the distal lower extremities of young adults, frequently attached to tendons or aponeuroses. It behaves like a high-grade soft tissue sarcoma and is associated with poor overall survival. Magnetic resonance imaging studies of the lesion reveal T1 hypointensity, T2 hyperintensity, and gadolinium uptake. Grossly, the tumor is usually circumscribed with a histologic pattern of uniform polygonal to fusiform cells with clear to pale eosinophilic cytoplasm divided into variably sized clusters by fibrous septa. Immunohistochemical studies in most cases show that the neoplastic cells are positive with HMB-45 and react with antibody against S100 protein. Most cases show a reciprocal cytogenetic translocation t(12;22)(q13;q12) that creates a unique chimeric fusion EWSR1/ATF1 gene transcript. Metastasis occurs mainly to regional lymph nodes and lungs. Poor prognostic indicators include a tumor size equal to or more than 5 cm, presence of metastasis, and necrosis. The mainstay of treatment is wide excision of the tumor. The use of sentinel lymph node biopsy may become an important procedure in detecting occult regional metastasis and guiding the extent of surgery. The beneficial effects of adjuvant chemotherapy and radiotherapy have not been fully evaluated. This article provides a short overview of the current knowledge of clear cell sarcoma of tendons and aponeuroses.
A Case of Fatal DisseminatedBartonella henselaeInfection (Cat-Scratch Disease) With Encephalitis
Authors: Fouch Brandy , Coventry Susan
Published: February 2021

Cat-scratch disease resulting from Bartonella henselae infection is usually a benign, self-limited process in immunocompetent children. Even the rare cases associated with neurologic manifestations are not generally fatal. We report a case of a previously healthy 6-year-old boy with cat-scratch disease, systemic dissemination, and encephalitis that led to his death. Autopsy revealed perivascular lymphocytic infiltrates and microglial nodules in the brain. To our knowledge, this finding has not been previously reported in B henselae infection, possibly because of the paucity of material available for complete neuropathologic evaluation. This case illustrates the extreme severity of the spectrum with which cat-scratch disease can present and provides evidence of brain histopathology that may be representative of the disease.
Adnexal Clear Cell Carcinoma With Comedonecrosis: Clinicopathologic Analysis of 12 Cases
Authors: Chaudhry Iskander H. , Zembowicz Artur
Published: February 2021

Context.—Cutaneous clear cell tumors can pose a diagnostic challenge even to the experienced dermatopathologist; this is partly because of limitations of existing diagnostic categories.

Objective.—To describe a previously unrecognized, distinctive cutaneous adnexal carcinoma capable of an aggressive clinical course.

Design.—Clinicopathologic analysis of a series of 12 cases.

Results.—The patients were older individuals (median age, 71 years) with equal gender frequency. The lesions showed wide anatomic distribution with predilection for the head and neck area, especially the scalp. The lesions presented as rapidly growing, erythematous to flesh-colored, solitary papules/nodules that were capable of quickly reaching a size of several centimeters. Histologically, adnexal clear cell carcinoma with comedonecrosis was characterized by dermal proliferation of nests of epithelial cells showing distinctive zonal arrangement. The periphery of the tumor nests was formed by squamoid cells merging with centrally located clear cell areas containing foci of comedonecrosis. The lesions often showed multilobular or trabecular growth pattern and infiltrating border. Nuclear pleomorphism was variable; mitotic count ranged from 2 to 32/mm2 (median, 8/mm2). No ductal, cuticular, or apocrine differentiation was seen. All cases showed expression of epithelial membrane antigen and cytokeratin 17 in clear cells, with focal carcinoembryonic antigen expression in some cases. Follow-up (average, 37 months) revealed local recurrence (4 cases) and regional and distant metastases (2 cases).

Conclusions.—Adnexal clear cell carcinoma with comedonecrosis appears to be a distinctive adnexal neoplasm that has to be distinguished from more indolent squamous cell and tricholemmal carcinomas.
Hepatic Stellate Cells and Liver Fibrosis
Authors: Moreira Roger Klein
Published: February 2021

Substantial evidence now exists to recognize hepatic stellate cells (HSCs) as the main matrix-producing cells in the process of liver fibrosis. Liver injury of any etiology will ultimately lead to activation of HSCs, which undergo transdifferentiation to fibrogenic myofibroblast-like cells. Quantitative analysis of HSC activation by immunohistochemistry has been shown to be useful in predicting the rate of progression of liver fibrosis in some clinical situations. In the activation process, transforming growth factor β is thought to be the main mediator of fibrogenesis and platelet-derived growth factor is the major inducer of HSC proliferation. Different platelet-derived growth factor and transforming growth factor β inhibitors have been shown to effectively prevent liver fibrosis in animal models and represent promising therapeutic agents for humans.
American Society of Clinical Oncology/College of American Pathologists Guideline Recommendations for Human Epidermal Growth Factor Receptor 2 Testing in Breast Cancer
Authors: Wolff Antonio C. , Hammond M. Elizabeth H. , Schwartz Jared N. , Hagerty Karen L. , Allred D. Craig , Cote Richard J. , Dowsett Mitchell , Fitzgibbons Patrick L. , Hanna Wedad M. , Langer Amy , McShane Lisa M. , Paik Soonmyung , Pegram Mark D. , Perez Edith A. , Press Michael F. , Rhodes Anthony , Sturgeon Catharine , Taube Sheila E. , Tubbs Raymond , Vance Gail H. , van de Vijver Marc , Wheeler Thomas M. , Hayes Daniel F.
Published: February 2021

Purpose.—To develop a guideline to improve the accuracy of human epidermal growth factor receptor 2 (HER2) testing in invasive breast cancer and its utility as a predictive marker.

Methods.—The American Society of Clinical Oncology and the College of American Pathologists (CAP) convened an expert panel, which conducted a systematic review of the literature and developed recommendations for optimal HER2 testing performance. The guideline was reviewed by selected experts and approved by the board of directors for both organizations.

Results.—Approximately 20% of current HER2 testing may be inaccurate. When carefully validated testing is performed, available data do not clearly demonstrate the superiority of either immunohistochemistry (IHC) or in situ hybridization (ISH) as a predictor of benefit from anti-HER2 therapy.

Recommendations.—The panel recommends that HER2 status should be determined for all invasive breast cancer. A testing algorithm that relies on accurate, reproducible assay performance, including newly available types of brightfield ISH, is proposed. Elements to reliably reduce assay variation (for example, specimen handling, assay exclusion, and reporting criteria) are specified. An algorithm defining positive, equivocal, and negative values for both HER2 protein expression and gene amplification is recommended: a positive HER2 result is IHC staining of 3+ (uniform, intense membrane staining of > 30% of invasive tumor cells), a fluorescent in situ hybridization (FISH) result of more than 6 HER2 gene copies per nucleus, or a FISH ratio (HER2 gene signals to chromosome 17 signals) of more than 2.2; a negative result is an IHC staining of 0 or 1+, a FISH result of less than 4.0 HER2 gene copies per nucleus, or a FISH ratio of less than 1.8. Equivocal results require additional action for final determination. It is recommended that to perform HER2 testing, laboratories show 95% concordance with another validated test for positive and negative assay values. The panel strongly recommends validation of laboratory assay or modifications, use of standardized operating procedures, and compliance with new testing criteria to be monitored with the use of stringent laboratory accreditation standards, proficiency testing, and competency assessment. The panel recommends that HER2 testing be done in a CAP-accredited laboratory or in a laboratory that meets the accreditation and proficiency testing requirements set out by this document.
Sclerosing Epithelioid Fibrosarcoma of the Cecum: A Radiation-Associated Tumor in a Previously Unreported Site
Authors: Frattini Jared C. , Sosa Julie Ann , Carmack Susanne , Robert Marie E.
Published: February 2021

Data from the nuclear reactor explosion in Chernobyl and the atomic bomb detonations in Hiroshima and Nagasaki demonstrated an association between ionizing radiation and tumoriogenesis. There is a significant association between external beam radiation and radiation-induced sarcoma. Sclerosing epithelioid fibrosarcoma is a rare form of malignant fibrosarcoma that is low grade and indolent with distinct immunohistopathologic characteristics that usually occurs in the soft tissues of the extremities. A 62-year-old man from Kiev who aided in the cleanup at Chernobyl presented with crampy abdominal pain, nausea, and vomiting. His workup revealed a cecal mass, and the final pathology from his laparotomy confirmed sclerosing epithelioid fibrosarcoma with metastasis to the liver. In addition to a review of the literature, we report the first case of sclerosing epithelioid fibrosarcoma arising from the large bowel. Exposure to ionizing radiation from Chernobyl could have played a role in the development of his tumor.
High Incidence of Chromosome 1 Abnormalities in a Series of 27 Renal Oncocytomas: Cytogenetic and Fluorescence In Situ Hybridization Studies
Authors: Paner Gladell P. , Lindgren Valerie , Jacobson Kris , Harrison Kathleen , Cao Ying , Campbell Steve C. , Flanigan Robert C. , Picken Maria M.
Published: February 2021

Context.—It has recently been shown by cytogenetics that there is a high incidence of chromosome 1 abnormalities in renal oncocytomas.

Objective.—To confirm the cytogenetic results by fluorescence in situ hybridization (FISH) analysis.

Design.—Nine additional cytogenetic analyses were added to those reported in our recent study, with a total of 27 tumors studied, which makes it the largest series of renal oncocytomas studied to date by cytogenetics and/or FISH. We used the LSI 1p36/LSI 1q25 Dual Color Probe Set to make the analyses.

Results.—In this study, combined cytogenetics and FISH showed loss of chromosome arm 1p1 in 48% of renal oncocytomas. By FISH, deletion of 1p36.3 was observed in 59% of renal oncocytomas, whereas by cytogenetics, abnormality in chromosome 1 was seen in 32% of tumors. However, the incidence of chromosome 1 abnormalities among 9 bilateral tumors was much higher than in single tumors (88% vs 28%, respectively). Loss of only the 1p36.3 site occurred in 2 renal oncocytomas with translocation of chromosome 1, as shown by cytogenetics. Concordance between the 2 techniques, when they were used simultaneously to detect chromosome 1p1 abnormality, was 82%.

Conclusions.—This study further confirmed our prior results demonstrating the widespread occurrence of chromosome 1 abnormalities in renal oncocytomas. Although no abnormalities in chromosome 1 in tumors with normal karyotypes were detected by FISH using the current set of probes, a much higher incidence of such abnormalities was found in bilateral tumors, suggesting that genetic alterations related to the development of renal oncocytoma reside in this region.
The Heterogeneous Distribution of Monosomy 3 in Uveal Melanomas: Implications for Prognostication Based on Fine-Needle Aspiration Biopsies
Authors: Maat Willem , Jordanova Ekaterina S. , van Zelderen-Bhola Shama L. , Barthen Ed R. , Wessels Hans W. , Schalij-Delfos Nicoline E. , Jager Martine J.
Published: February 2021

Context.—The detection of monosomy 3 in uveal melanomas has repeatedly been associated with adverse outcome. Fine-needle aspiration biopsy is being used to detect monosomy 3 in these tumors, based on the assumption that this chromosomal abnormality is distributed homogeneously throughout the tumor.

Objective.—To study the distribution of monosomy 3 in primary uveal melanoma by fluorescence in situ hybridization (FISH).

Design.—We studied 50 enucleated eyes with uveal melanoma. In all 50 tumors we performed cytogenetic analysis and FISH using a DNA-specific probe for the centromere region of chromosome 3 on cultured tumor cells. In addition, the percentage of tumor cells with monosomy 3 was assessed by FISH on nuclei, isolated from paraffin-embedded tissue and compared to results of FISH on regular histology sections of the paraffin-embedded tissue.

Results.—Combining karyotyping and FISH on cultured cells identified monosomy 3 in 19 (38%) of 50 tumors, whereas FISH on nuclei isolated from paraffin-embedded tissue showed 31 (62%) of 50 as having monosomy for chromosome 3. FISH analysis on paraffin sections showed tumor heterogeneity for copy number of chromosome 3 in at least 7 cases.

Conclusions.—FISH analysis on paraffin sections shows that heterogeneity of monosomy of chromosome 3 is a frequent phenomenon in uveal melanoma. FISH on nuclei isolated from paraffin-embedded tissue identifies a higher frequency of monosomy 3 than the traditional combination of karyotyping and FISH on cultured uveal melanoma cells. The practice of assigning patients to risk categories based on fine-needle aspiration biopsy samples from primary uveal melanoma may be subject to error based on the heterogeneous distribution of monosomy 3 in these tumors.
Presentación
Authors: Serrano de Haro Agustín
Published: February 2021

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Jan Patočka’s Transcendence to the World
Authors: Gubser Michael
Published: February 2021

This essay examines Czech philosopher Jan Patočka’s phenomenology as a philosophy of freedom. It shows how Patočka’s phenomenological concept of worldliness, initially cast within a largely philosophical framework as the domain of human action and transcendence, turned toward a philosophical history of the modern age, viewed as increasingly post-European. Patočka hoped for the moral renewal of a fallen modernity, led first by non-Europeans after the era of decolonization and then by a “solidarity of the shaken” during the dark 1970s of Czechoslovak normalization. The essay starts and concludes by considering the relation between his thought and his dissi-dence, a link that is more tenuous and indirect than some commentators suggest.Este ensayo examina la fenomenología del filósofo checo Jan Patočka como una filosofía de la libertad. Muestra cómo el concepto patočkiano de mundanidad, modelado inicialmente en un marco básicamente filosófico como el dominio de la acción humana y de su trascendencia, giró hacia una historia filosófica de la Modernidad, considerada crecientemente como post-europea. Patočka confiaba en la renovación moral de una Modernidad caída, liderada en un primer momento, tras la era de la descolonización, por no-europeos y, después, por una “solidaridad de los conmovidos” a lo largo de la oscura década de normalización checoslovaca en los 70. El ensayo arranca y concluye considerando la relación entre su pensamiento y su disidencia, un vínculo que es más tenue e indirecto de lo que algunos comentadores sugieren.
La noción de “Mundo de la vida” en el proyecto de Alfred Schutz para una fundamentación fenomenológica de las ciencias sociales
Authors: López Daniela Griselda
Published: February 2021

El tema de la prioridad conceptual del mundo de la vida con relación a cualquier especulación científica abstracta es el tema recurrente en los escritos tempranos de Alfred Schutz. En ellos, la reflexión en torno al mundo de la vida se constituye como la base y el fundamento para la posterior formación de conceptos en ciencias sociales. Particularmente inten-tamos recuperar lo puede denominarse como “reivindicación epistémica” (epistemic claim) de una sociología del mundo de la vida. Esa reivindicación se enmarca en el proyecto schutziano de fundamentación fenomenológica de las ciencias sociales, cuyos orígenes pueden rastrearse en las discusiones entabladas en el marco de la Escuela Austríaca de Economía. La reconstrucción de este debate nos permitió pensar el vínculo entre mundo de la vida y razón científica, de modo tal de evitar la sustitución de la realidad social por las idealidades y abstraccio-nes creadas por la ciencia.The question of conceptual priority of the life-world in relation to any abstract scientific speculation is a recurrent topic in Alfred Schutz´s early writings. There, the reflection on the life- world is constituted as the basis and the foundation for the posterior formation of concepts in social sciences. In particular, we will try to regain something that we could name “an epistemic claim” of a sociology of the life-world. This claim is part of Schutz’s project of phenomenological foundation of social sciences, which origins can be found in discussions among the members of Austrian School of Economics. The reconstruction of this debate has enabled us to think the link between the life-world and the scientific reason, in order to avoid the substitution of social reality by idealizations and abstractions created by the science.