bluuebunny/crossref_metadata_2025 huggingface dataset:
Pronominale demonstrativer: nye perspektiver fra norsk og svensk
Authors: Kinn Kari , Larsson Ida
Published: February 2021

This paper is concerned with pronominal demonstatives (referred to as psychologically distal demonstratives by Johannessen 2008a, b) in older Norwegian spoken language, and written Swedish from the 19th century and the present-day. We show that pronominal demonstratives can be attested in speakers born in different parts of Norway in the 19th century, and in Swedish texts from the same period. However, the pronominal forms do not seem to be used in precisely the same way in the two languages. In Swedish, han/hon ‘he/she’ do not seem to behave formally like demonstratives. Instead, we propose that they are syntactically reduced pronouns at the edge of the DP, above the position for demonstratives, and that they double features lower down in the noun phrase. In Norwegian, on the other hand, han/hun are used as demonstratives already in the 19th century, in the way described for present-day Norwegian by Johannessen (2008a, b).
The Amyloid Deposit in Calcifying Epithelial Odontogenic Tumor Is Immunoreactive for Cytokeratins
Authors: Aviel-Ronen Sarit , Liokumovich Pavel , Rahima David , Polak-Charcon Sylvie , Goldberg Iris , Horowitz Ada
Published: February 2021

Calcifying epithelial odontogenic tumor, also known as Pindborg tumor, is a rare benign tumor with locally aggressive behavior. It is characterized by squamous epithelial cells, calcifications, and eosinophilic deposits that have been identified as amyloid. We report a case of calcifying epithelial odontogenic tumor and investigate the nature of the amyloid, using histologic, immunohistochemical, and ultrastructural studies. The amyloid was immunohistochemically negative for basement membrane components and positive for all cytokeratin stains performed (cocktail of cytokeratins 1, 5, 6, 8, 13, and 16, and cytokeratins AE1 and AE3). The amyloid stained focally in a glandular-like pattern, reminiscent of the epithelial glandlike structures of the tumor. We conclude that the amyloid is derived from filamentous degeneration of keratin filaments that originate from the tumor squamous epithelium. The keratin degeneration is part of a developmental or aging process that the tumor undergoes.
Spindle Cell Tumor of Urinary Bladder Serosa With Phenotypic and Genotypic Features of Gastrointestinal Stromal Tumor
Authors: Lasota Jerzy , Carlson John A. , Miettinen Markku
Published: February 2021

Most mesenchymal tumors of the gastrointestinal tract are now referred to as gastrointestinal stromal tumors (GISTs). The tumors differ from ordinary leiomyomas and schwannomas in several respects: the GISTs typically express c-kit protein (CD117) and CD34, 30% to 50% of them are (often focally) positive for α-smooth muscle actin, and all are negative for desmin and S100 protein. Recently, mutations in the exon 11 of the c-kit gene have been identified and confirmed as a molecular genetic marker for the subset of GISTs. In this report, we describe a mesenchymal tumor removed from the pelvic cavity of a 52-year-old woman, who is alive without disease 36 months after the surgery. The 5-cm tumor was densely attached to the external aspect of the urinary bladder but was attached to small intestine by only filmy adhesions. The tumor grossly resembled a leiomyoma and was histologically composed of sheets of spindle cells with a dense collagenous background. The mitotic activity was low, less then 1 per 50 high-power fields. Immunohistochemically, the tumor cells were negative for α-smooth muscle actin and desmin and positive for CD117 and CD34. Molecular genetic analysis of the exon 11 of the c-kit gene revealed a point mutation in the region commonly mutated in GISTs. This mutation substituted T for A in the codon 557, leading to the change of amino acid sequence (tryptophan for arginine) of the KIT protein. This case illustrates that tumors phenotypically and genotypically similar to GISTs may present in sites other than the tubular gastrointestinal tract.
Persistent Tuberculosis or Specimen Contamination?
Authors: Trakas Kathy , Stosor Valentina , Dietrich Stephen , Mosher Laura , Warren John R.
Published: February 2021

Cross-contamination during sequential processing of sputum specimens from different patients causes false-positive growth of Mycobacterium tuberculosis in culture. We describe an unusual case of cross-contamination in a 36-year-old man with acquired immunodeficiency syndrome and possible persistent tuberculosis. Culture with 1 of 3 sputum specimens was positive for rifampin-susceptible M tuberculosis. Review of processing revealed that his single culture-positive sputum specimen had followed a sputum specimen from another patient with active pulmonary tuberculosis that was positive in culture for M tuberculosis resistant to rifampin. Molecular strain typing by restriction fragment length polymorphism demonstrated the 2 isolates to be an identical strain of M tuberculosis. Agar proportion susceptibility testing of the rifampin-resistant isolate revealed low numbers of resistant organisms in a range of 1.5% to 3.3%. It was concluded that rifampin-susceptible organisms that constituted approximately 98% of the resistant isolate contaminated sputum from the patient with possible persistent tuberculosis. His culture result was, therefore, considered false positive, not an indication of tuberculosis.
Accuracy of Fine-Needle Aspiration of Thyroid
Authors: Amrikachi Mojghan , Ramzy Ibrahim , Rubenfeld Sheldon , Wheeler Thomas M.
Published: February 2021

Context.—Fine-needle aspiration has become an accepted and cost-effective procedure for rapid diagnosis of thyroid lesions. The routine use of fine-needle aspiration has reduced the rate of unnecessary surgery for thyroid nodules.

Objectives.—To determine the accuracy of fine-needle aspiration biopsy diagnosis and to discuss the possible pitfalls.

Design, Setting, and Participants.—Reports of 6226 fine-needle aspiration biopsies of the thyroid performed during a period of 16 years (1982–1998) were reviewed. Computerized reports of the fine-needle aspiration biopsies were sent to the physicians who performed the procedures, and clinical follow-up information regarding the patients was requested. Twenty-four clinicians participated in the study. Histologic diagnoses were available for 354 cases. The cytopathologic diagnoses were correlated with the histologic findings or clinical outcomes.

Results.—The cytologic diagnoses were as follows: 210 (3.4%) malignant, 450 (7.2%) suspicious, 3731 (60%) benign, and 1845 (29.5%) unsatisfactory. Most of the cases with negative or unsatisfactory aspirates were followed clinically or by repeat fine-needle aspiration. We identified 11 false-negative and 7 false-positive diagnoses. For aspirates considered sufficient for diagnosis, the sensitivity and specificity levels were 93% and 96%, respectively.

Conclusions.—Fine-needle aspiration of the thyroid gland is highly accurate and has a low rate of false-negative and false-positive diagnoses. The major diagnostic problems are caused by diagnosis using a marginally adequate specimen, diagnosis of malignancy based on just 1 or 2 atypical cytologic features, or overlapping cytologic features of follicular neoplasm with those of follicular variant of papillary carcinoma.
Intraneuronal Aβ-Amyloid Precedes Development of Amyloid Plaques in Down Syndrome
Authors: Gyure Kymberly A. , Durham Robert , Stewart Walter F. , Smialek John E. , Troncoso Juan C.
Published: February 2021

Context.—Down syndrome patients who live to middle age invariably develop the neuropathologic features of Alzheimer disease, providing a unique situation in which to study the early and sequential development of these changes.

Objective.—To study the development of amyloid deposits, senile plaques, astrocytic and microglial reactions, and neurofibrillary tangles in the brains of young individuals (<30 years of age) with Down syndrome.

Methods.—Histologic and immunocytochemical study of a series of autopsy brains (n = 14, from subjects aged 11 months to 56 years, with 9 subjects <30 years) examined at the Office of the Chief Medical Examiner of the State of Maryland and The Johns Hopkins Hospital.

Results.—The principal observations included the presence of intraneuronal Aβ immunostaining in the hippocampus and cerebral cortex of very young Down syndrome patients (preceding the extracellular deposition of Aβ) and the formation of senile plaques and neurofibrillary tangles.

Conclusions.—We propose the following sequence of events in the development of neuropathologic changes of Alzheimer disease in Down syndrome: (1) intracellular accumulation of Aβ in neurons and astrocytes, (2) deposition of extracellular Aβ and formation of diffuse plaques, and (3) development of neuritic plaques and neurofibrillary tangles with activation of microglial cells.
Cerebrospinal Fluid Aβ42, Tau, and F2-Isoprostane Concentrations in Patients With Alzheimer Disease, Other Dementias, and in Age-Matched Controls
Authors: Montine Thomas J. , Kaye Jeffery A. , Montine Kathleen S. , McFarland Lynne , Morrow Jason D. , Quinn Joseph F.
Published: February 2021

Objective.—To test the hypothesis that quantification of cerebrospinal fluid (CSF) F2-isoprostanes (F2-IsoPs), in vivo biomarkers of free radical damage, along with CSF Aβ42 and tau levels improves laboratory diagnostic accuracy for Alzheimer disease (AD).

Participants.—Patients with probable AD (n = 19), dementias other than AD (n = 8), and age-matched controls (n = 10).

Main Outcome Measures.—Cerebrospinal fluid concentrations of Aβ42 and tau were determined by a commercially available test (Athena Diagnostics, Worcester, Mass). Cerebrospinal fluid F2-IsoP levels were quantified by gas chromatography/mass spectrometry.

Results.—Individuals were classified as AD or non-AD by a published method using CSF Aβ42 and tau levels (95% sensitivity, 50% specificity), by CSF F2-IsoP levels greater than 25 pg/mL and Aβ42 concentrations less than 1125 pg/mL (90% sensitivity, 83% specificity), and by combined analysis using CSF F2-IsoP, Aβ42, and tau levels (84% sensitivity, 89% specificity).

Conclusion.—Cerebrospinal fluid F2-IsoP quantification may enhance the accuracy of the laboratory diagnosis of AD.
Large Cell Variants of CD5+, CD23− B-Cell Lymphoma/Leukemia
Authors: Dunphy Cherie H. , Perkins Sherrie L.
Published: February 2021

Context.—Mantle cell lymphoma (MCL), and its leukemic phase, constitute a well-studied hematologic malignancy with known overall survival, prognostic indicators, morphologic findings at diagnosis and in bone marrow, and known incidence of the bcl-1 immunoglobulin gene rearrangement. Large cell variants of B-cell lymphoma/leukemia with a mantle cell immunophenotype (CD5+, CD23−), including but not limited to blastic MCL, prolymphocytoid MCL, blastic mantle cell leukemia, and prolymphocytic mantle cell leukemia, are not as well characterized. Although blastic MCL is known to be associated with a shorter overall survival than conventional MCL, the large cell variants of B-cell lymphoma/leukemia with a mantle cell immunophenotype have not been described as fully as conventional MCL.

Objective.—The purpose of the present study was to describe the large cell variants of B-cell lymphoma/leukemia with a mantle cell immunophenotype.

Design.—Nineteen cases of large cell variants of CD5+, CD23− B-cell lymphoma/leukemia are reviewed and described in regard to morphology, bone marrow morphological findings, Cyclin D1 immunostaining, and bcl-1 analysis. Clinical data were not available owing to the varied clinical sources of the specimens.

Setting.—Tertiary-care academic institution.

Results.—Lymph node involvement in blastic CD5+, CD23− B-cell lymphoma was diffuse (100%) with a nodular component (33%) or focal mantle zone pattern (10%). Bone marrow involvement in blastic CD5+, CD23− B-cell lymphoma was seen in only 27% of cases and was composed predominantly of small, slightly irregular lymphocytes. Cyclin D1 was demonstrated in 60% of the 15 cases analyzed and more sensitive in B5–fixed tissue. Bcl-1 (performed in 5 cases) was not detected in the 4 cases of blastic CD5+, CD23− B-cell lymphoma analyzed and was detected in the case of the prolymphocytoid MCL. Cyclin D1 was demonstrated in all 4 bcl-1 negative cases and was negative in the bcl-1 positive prolymphocytoid MCL.

Conclusion.—Careful analysis of clinical data, morphology, immunophenotype, Cyclin D1 expression, and molecular analysis are required to differentiate the unusual large cell variants of MCL from other processes.
One Patient, Two Lymphomas
Authors: Tang Zuoqin , Jing Wen , Lindeman Neal , Harris Nancy Lee , Ferry Judith A.
Published: February 2021

We report the case of a 73-year-old man who presented with a 2- to 3-month history of epigastric discomfort and guaiac-positive stool. An upper gastrointestinal endoscopy revealed a diffuse erythematous nodular mucosa and submucosal thickening in the stomach. Diffuse mucosal nodularity was also found in the second portion of the duodenum. A complete workup with histologic, immunohistochemical, and molecular studies revealed 2 distinct, apparently unrelated lymphomas, namely, a gastric marginal zone B-cell lymphoma (mucosa-associated lymphoid tissue type) in a background of Helicobacter pylori gastritis and a grade 1/3 duodenal follicular lymphoma. The patient was then treated with an H pylori eradication regimen. No therapy was given for his duodenal follicular lymphoma because his symptoms were thought to be due to the gastric disease and because the duodenal lesion was small. A 6-month follow-up with upper gastrointestinal endoscopy revealed only focal biopsy scarring in the stomach and an apparently normal duodenum. The follow-up biopsies revealed significant regression of his mucosa-associated lymphoid tissue lymphoma, but persistence of his duodenal follicular lymphoma. The combination of these 2 lymphomas in the same patient and the different clinical responses to antibiotic treatment make this case unique.
Microdissection Genotyping of Mixed Glial and Primitive Neuroectodermal Central Nervous System Neoplasm
Authors: Mohan Deepak , Rao Gutti R. , Swalsky Patricia A. , Bakker Anke , Martinez A. Julio , Finkelstein Sydney D.
Published: February 2021

A 22-year-old man with previous radiation treatment for childhood astrocytoma underwent resection of a right parietooccipital lesion. Histopathology revealed a malignant neoplasm with areas of astrocytic and primitive neuroectodermal components. To resolve the relationship and cellular origin, representative tissue was microdissected from several targets, obtaining a balanced mixture of each element. Nonneoplastic brain parenchyma was separately microdissected to determine polymorphic marker informativeness and to serve as an internal negative control. Despite the relatively small quantity of tissue removed for each microdissection target, sufficient material was available for reliable, balanced, polymerase chain reaction–format genotyping encompassing a panel of tumor suppressor genes and genetic loci associated with these forms of neoplasia. The findings revealed distinct discordant genotypic profiles for each of the neoplastic components. The efficacy of the approach used for molecular analysis of this complex neoplasm and the implication of the genotypic findings are discussed.
What Is a Picture Worth?: Digital Imaging Applications in Autopsy Reports
Authors: Pritt Bobbi , Gibson Pamela , Cooper Kumarasen , Hardin Nicolas
Published: February 2021

Context.—An image-enhanced report (IER) containing color digital images can serve as an educational tool and document important gross and microscopic findings in anatomic pathology.

Objective.—To determine the clinical impression of IERs on an academic autopsy service.

Design.—Autopsy IERs were initiated at this institution in December 2001. From January 2002 to July 2003, 261 hospital-service autopsies were performed; color images were produced for 39 (15%) of these autopsies. Of these IERs, 29 were distributed to 74 hospital-employed physicians. Each hospital physician recipient was sent a 6-question e-mail survey to evaluate his or her impression of image quality and added value.

Results.—Of the 74 hospital-employed physicians sent an IER, 41 responded to the survey (response rate, 55%). Twenty-one respondents recalled receiving a report with color images. Image quality was uniformly rated as good or excellent. Ninety-five percent thought the images increased their understanding of the report, and 76% thought that the images increased the utility of the report. All respondents stated they would (or did) use the images for educational purposes. Twenty-one percent of all respondents thought the presence of color images would increase their likelihood of requesting a future autopsy.

Conclusions.—Color digital images are perceived as a valuable addition to the autopsy report. Although clinicians did not consider color images a strong motivator to request a future autopsy, most thought that the images enhanced their understanding and the utility of the report. All respondents stated they would use the images to educate themselves, medical students, residents, and/or the patient's family.
False-Positive D-Dimer Result in a Patient With Castleman Disease
Authors: Mugler Kimberly , Lefkowitz Jerry B.
Published: February 2021

In suspected cases of disseminated intravascular coagulation, concurrent elevation of both fibrin(ogen) degradation products (FDPs) and D-dimer levels aids in confirming the diagnosis. This pattern of results reflects the action of plasmin proteolysis of cross-linked fibrin polymers as well as fibrinogen. We report the case of a patient with human immunodeficiency virus (HIV) and Castleman disease who presented with a high-positive D-dimer level and a negative FDP level in the course of a workup for disseminated intravascular coagulation. This finding suggested the possibility of either a false-positive D-dimer or a false-negative FDP level. To investigate the former, a Western blot was performed on the patient's serum to determine the presence of the D-dimer. No D-dimer band was visualized on the Western blot, confirming the false-positive nature of the D-dimer result. Insufficient quantity of patient serum, however, prevented further investigation into the etiology of this result. The false-positive D-dimer result is likely attributable to interference caused by the patient's Castleman disease–associated monoclonal gammopathy, a phenomenon that has been reported in other immunoassays. As the development of lymphoproliferative disorders is especially common within the HIV population, and hypergammaglobulinemia in Castleman disease is particularly common, clinicians should be aware of this phenomenon when the laboratory findings do not fit the clinical picture. Although it is rare, recognition of potential paraprotein interference in immunoassays will help avoid undertreatment or overtreatment of patients based on erroneous laboratory results.
How Sensitive Is a Prostate-Specific Antigen Measurement?: How Sensitive Does It Need to Be?
Authors: Bock Jay L. , Klee George G.
Published: February 2021

Assays are now available that can measure very low concentrations of prostate-specific antigen (PSA), but their analytic performance and clinical utility are not well defined. This brief article highlights some of the clinical issues related to the limited prognostic significance of small changes in PSA concentrations in men with prostate cancer who have been treated with prostate ablation therapy. College of American Pathologists proficiency survey data are presented, illustrating the performance of commercial PSA assays with low PSA concentration survey samples tested between 1998 and 2002. The performance of the assays appears to be improving, but many of the currently used assays have intralaboratory coefficients of variation greater than 20% for PSA concentrations less than 0.4 ng/mL. Also, there are major differences in the level of PSA reported by various assays in these low concentration samples. These level differences (if they are also seen in clinical samples) may cause clinical problems when fixed serum PSA thresholds (eg, 0.2 ng/mL) are used to make clinical decisions related to prostate tumor recurrence.
Zero-Check: A Zero-Knowledge Protocol for Reconciling Patient Identities Across Institutions
Authors: Berman Jules J.
Published: February 2021

Context.—Large, multi-institutional studies often involve merging data records that have been de-identified to protect patient privacy. Unless patient identities can be reconciled across institutions, individuals with records held in different institutions will be falsely “counted” as multiple persons when databases are merged.

Objective.—The purpose of this article is to describe a protocol that can reconcile individuals with records in multiple institutions.

Design.—Institution A and Institution B each create a random character string and send it to the other institution. Each institution receives the random string from the other institution and sums it with their own random string, producing a random string common to both institutions (RandA+B). Each institution takes a unique patient identifier and sums it with RandA+B. The product is a random character string that is identical across institutions when the patient is identical in both institutions. A comparison protocol can be implemented as a zero-knowledge transaction, ensuring that neither institution obtains any knowledge of its own patient or of the patient compared at another institution.

Results.—The protocol can be executed at high computational speed. No encryption algorithm or 1-way hash algorithm is employed, and there is no need to protect the protocol from discovery.

Conclusion.—A zero-knowledge protocol for reconciling patients across institutions is described. This protocol is one of many computational tools that permit pathologists to safely share clinical and research data.
Evaluation of Linearity in the Clinical Laboratory
Authors: Jhang Jeffrey S. , Chang Chung-Che , Fink Daniel J. , Kroll Martin H.
Published: February 2021

Context.—Clinical laboratory assessment of test linearity is often limited to satisfying regulatory requirements rather than integrating this tool into the laboratory quality assurance program. Although an important part of quality control and method validation for clinical laboratories, linearity of clinical tests does not get the attention it deserves.

Objective.—This article evaluates the concepts and importance of linearity evaluations for clinical tests.

Design.—We describe the theory and procedural steps of each linearity evaluation. We then evaluate the statistical methods for each procedure.

Results.—Visual assessment, although simple, is subjective. The lack-of-fit error and the 1986 NCCLS EP6-P G test are sensitive to imprecision and assume that the data are first order. Regression analysis, as developed as the polynomial method, is partly based on the experiences of the College of American Pathologists Instrumentation Resource Committee and has proved to be a robust statistical method.

Conclusions.—We provide general guidelines for handling non-linear results from a linearity evaluation. Handling linearity data in an objective manner will aid clinical laboratorians whose goal is to improve the quality of the tests they perform.
Inlet Patch: Prevalence, Histologic Type, and Association With Esophagitis, Barrett Esophagus, and Antritis
Authors: Tang Ping , McKinley Matthew J. , Sporrer Maria , Kahn Ellen
Published: February 2021

Context.—Inlet patch is a congenital anomaly of the cervical esophagus consisting of gastric mucosa. Case reports have documented the histologic type and its associated complications.

Objective.—To report the prevalence and histologic types of inlet patch as well as its association with Barrett esophagus and Helicobacter pylori–associated gastritis.

Design.—We reviewed 1821 consecutive pathology reports from endoscopies of the upper gastrointestinal tract between 1995 and 2002 and identified 20 patients with inlet patch. The patients' ages ranged from 16 to 75 years (mean, 55 years). We examined biopsies from these patients of the cervical esophagus, distal esophagus, and antrum that had been stained with hematoxylin-eosin and the Steiner stain. Biopsies from the cervical esophagus composed of nonoxyntic gastric mucosa were also stained for gastrin-producing cells.

Results.—In our patient population, inlet patch occurred in 1.1% of all patients in whom an inlet patch had been searched for endoscopically and a biopsy performed. In the inlet patch, oxyntic mucosa was the most common histologic type (11/20), followed by cardiac mucosa (5/20). Four specimens of the inlet patch contained only foveolar epithelium and were therefore considered too superficial to be classified. Twelve of 20 biopsies of the inlet patch were inflamed, and 1 of them was associated with H pylori. Pancreatic acinar tissue was noted in 2 patients; no intestinal metaplasia was found. In the distal esophagus, 4 patients with inlet patch had distal esophagitis, 4 had Barrett esophagus, 5 had oxyntic mucosa, 3 had pancreatic acinar tissue (1 coexisting with oxyntic mucosa), and 5 presented with only unremarkable esophageal squamous mucosa. Antral gastritis was seen in 2 patients, 1 of them with H pylori. The same patient also had H pylori in the inlet patch.

Conclusion.—Inlet patch occurred in about 1% of our study population. Oxyntic mucosa constituted the most common histologic type; inflammation was common. The H pylori infection of the inlet patch correlated with that of the antrum. None of the inlet patch biopsies showed intestinal metaplasia. Pancreatic acinar tissue occurred with similar frequency in the inlet patch and distal esophagus. Esophagitis was noted in 25% of the patients with inlet patch, and Barrett esophagus was noted in 20%.
Macrofollicular Variant of Papillary Carcinoma of the Thyroid
Authors: Lugli Alessandro , Terracciano Luigi Maria , Oberholzer Martin , Bubendorf Lukas , Tornillo Luigi
Published: February 2021

Context.—The macrofollicular variant of papillary carcinoma of the thyroid is a rare entity described by J. Albores-Saavedra and colleagues in 1991. It is characterized histologically by a predominance of macrofollicles and clinically by a low incidence of metastasis. This entity may represent a source of diagnostic error, since it can be easily misinterpreted as a macrofollicular adenoma or nodular goiter.

Design.—In this study, we describe 3 cases of papillary carcinoma of the thyroid with a macrofollicular growth pattern and review the literature.

Results.—The fine-needle aspiration biopsies in 2 cases showed large cells with optically clear nuclei and nuclear grooves, suggestive of papillary carcinoma of the thyroid. In one case, the cytology showed no signs of malignancy. In all cases, the tumors showed a combination of the conventional follicular variant of papillary carcinoma of the thyroid and macrofollicles (diameter, >250 μm) occupying more than 50% of the cross-sectional area. Cytologic features were large, cuboidal cells with optically clear, ground-glass nuclei with smooth outlines, a fine chromatin pattern, nuclear grooves, and pseudoinclusions. The colloid was dense and more eosinophilic than in adjacent normal follicles. In 2 cases, there was capsular or blood vessel infiltration, and one tumor had metastasized to a cervical lymph node. One tumor recurred 1 year later as an anaplastic carcinoma. Immunohistochemical staining showed a positivity of the tumor cells for cytokeratins 7, 17, and 19, thyroid transcription factor-1, and galectin-3 and a negativity for cytokeratin 20 and p53.

Conclusions.—Although it has been suggested that this tumor is a highly differentiated variant with a favorable prognosis, our study shows that its biologic behavior is not conclusive because metastases and recurrences with dedifferentiation may occur.
Cytologic Features of High-Grade Squamous Intraepithelial Lesion in ThinPrep Papanicolaou Test Slides: Comparison of Cases That Performed Poorly With Those That Performed Well in the College of American Pathologists Interlaboratory Comparison Program in Cervicovaginal Cytology
Authors: Renshaw Andrew A. , Schulte Michael A. , Plott Elizabeth , Dubray-Benstein Barbara , Cobb Camilla J. , Lozano Richard L. , Neal Margaret H. , Hughes Jonathan H. , Young Nancy A. , Prey Marianne
Published: February 2021

Context.—Conventional Papanicolaou (Pap) test slides of high-grade squamous intraepithelial lesions (HSILs) that are frequently misdiagnosed are known to have relatively few dysplastic cells. Whether this is true of cases of HSIL in ThinPrep Pap Test specimens is not known.

Objective.—To determine if cases of HSIL in ThinPrep specimens that are frequently missed have relatively few dysplastic cells.

Design.—The cytologic features of 16 ThinPrep cases of HSIL that performed poorly in the College of American Pathologists Interlaboratory Comparison Program were compared with 22 ThinPrep Pap Test cases that performed extremely well.

Results.—Significantly more cases that performed poorly had fewer than 250 dysplastic cells (13/16) than cases that performed well (3/22) (P < .001).

Conclusion.—ThinPrep Pap Test cases with a diagnosis of HSIL that performed poorly in this program had significantly fewer dysplastic cells than those that performed well.
Textiloma (Gossypiboma) Mimicking Recurrent Intracranial Tumor
Authors: Ribalta Teresa , McCutcheon Ian E. , Neto Antonio G. , Gupta Deepali , Kumar A. J. , Biddle David A. , Langford Lauren A. , Bruner Janet M. , Leeds Norman E. , Fuller Gregory N.
Published: February 2021

Context.—Resorbable substances used to achieve hemostasis during neurosurgical procedures comprise 3 principal classes based on chemical composition: (1) gelatin sponge, (2) oxidized cellulose, and (3) microfibrillar collagen. Nonresorbable hemostatic aides include various forms of cotton and rayon-based hemostats (cottonoids and kites). Resorbable and nonresorbable hemostatic agents have been reported to cause symptomatic mass lesions, most commonly following intra-abdominal surgery. Histologic examination typically shows a core of degenerating hemostatic agent surrounded by an inflammatory reaction. Each agent exhibits distinctive morphologic features that often permit specific identification. Hemostat-associated mass lesions have been variously referred to as textilomas, gossypibomas, gauzomas, or muslinomas.

Objectives.—The aims of this study were to (1) identify cases of histologically proven cases of textiloma in neurosurgical operations, (2) characterize the specific hemostatic agent associated with textiloma formation, and (3) characterize the preoperative magnetic resonance imaging appearance of textiloma.

Design.—Cases in which a textiloma constituted the sole finding on repeat surgery for recurrent brain tumor, or was a clinically significant component of a radiologically identified mass lesion together with residual tumor, constituted the study set.

Results.—Five textilomas were identified and evaluated. The primary neoplasm was different in each case and included pituitary adenoma, tanycytic ependymoma, anaplastic astrocytoma, gliosarcoma, and oligodendroglioma. In all cases, preoperative magnetic resonance imaging suggested recurrent tumor. Textilomas included all categories of resorbable hemostatic agent. Other foreign bodies were present in some cases; the origin of these foreign bodies was traced to fibers shed from nonresorbable hemostatic material placed temporarily during surgery and removed before closure (cottonoids and kites). Inflammatory reactions included giant cells, granulomas, and fibroblastic proliferation. Microfibrillar collagen (Avitene) textilomas were associated with a striking eosinophil infiltration that was not seen with any other hemostatic agent.

Conclusions.—Hemostatic agents may produce clinically symptomatic, radiologically apparent mass lesions. When considering a mass lesion arising after intracranial surgery, the differential diagnosis should include textiloma along with recurrent tumor and radiation necrosis.
Minimal (≤0.1 cm) Invasive Carcinoma in Breast Core Needle Biopsies
Authors: Renshaw Andrew A.
Published: February 2021

Context.—Although minimally invasive (microinvasive) carcinoma (≤0.1 cm) of the breast is a well-known and well-characterized entity in excision specimens, the significance of small foci of invasion in breast core needle biopsies has not been well described.

Objective.—To define the significance of minimally invasive carcinoma in breast core needle biopsies.

Design.—Review of a large series of core needle biopsies for invasive carcinomas measuring 0.1 cm or less and correlation of the results with those of subsequent excision.

Setting.—Large community hospital.

Results.—From approximately 8500 biopsies, a total of 18 cases of minimally invasive carcinoma from 16 women aged 42 to 80 years were identified. All were present on only 1 of 8 slides made from the block. Overall, the incidence was approximately 0.1% of all biopsies and 1% of all invasive carcinomas. Six cases were invasive lobular carcinomas, 1 was tubulolobular carcinoma, 3 were tubular carcinomas, and the remaining 8 were ductal carcinomas. Eight cases were associated with high-grade comedo ductal carcinomas, 2 with low-grade ductal carcinoma in situ, 3 with atypical ductal hyperplasia, 3 with atypical ductal hyperplasia and lobular carcinoma in situ, and 2 with no other lesion. From a total of 8 sections done entirely through the block, the lesion was present on the first level in 4 cases and the fifth level in 5 cases. No cases were identified in the last 3 levels. Subsequent pathology was available for 16 of the 18 cases. Invasive carcinomas measuring more than 1 cm were present in 9 cases (64%; along with 2 positive lymph nodes), invasive carcinomas less than 1 cm in 2 cases (14%), ductal carcinoma alone in 4 cases (29%), and no carcinoma in 1 case (7%). No pathologic or radiologic features were associated with the finding of invasive carcinoma at excision.

Conclusion.—Invasive carcinoma measuring 0.1 cm or less is a rare finding in breast core needle biopsies, is commonly associated with in situ carcinomas and atypical hyperplasias, and is often associated with larger invasive foci at excision. However, invasive carcinomas smaller than 0.1 cm can occur without any other significant findings and may require relatively extensive sampling to identify.
Splenic Pregnancy: A Case Report and Review of the Literature
Authors: Kalof Alexandra N. , Fuller Bradbury , Harmon Maureen
Published: February 2021

Primary splenic pregnancy is the least common form of extrauterine pregnancy. We report a case of splenic pregnancy occurring in a 29-year-old woman presenting with acute abdomen and hemoperitoneum. Recognition of this rare form of gestation is of critical importance, owing to the risk of exsanguination and death, and should be considered in the differential diagnosis of acute abdomen in women of reproductive age.
Errors in Laboratory Medicine: Practical Lessons to Improve Patient Safety
Authors: Howanitz Peter J.
Published: February 2021

Context.—Patient safety is influenced by the frequency and seriousness of errors that occur in the health care system. Error rates in laboratory practices are collected routinely for a variety of performance measures in all clinical pathology laboratories in the United States, but a list of critical performance measures has not yet been recommended. The most extensive databases describing error rates in pathology were developed and are maintained by the College of American Pathologists (CAP). These databases include the CAP's Q-Probes and Q-Tracks programs, which provide information on error rates from more than 130 interlaboratory studies.

Objectives.—To define critical performance measures in laboratory medicine, describe error rates of these measures, and provide suggestions to decrease these errors, thereby ultimately improving patient safety.

Setting.—A review of experiences from Q-Probes and Q-Tracks studies supplemented with other studies cited in the literature.

Design.—Q-Probes studies are carried out as time-limited studies lasting 1 to 4 months and have been conducted since 1989. In contrast, Q-Tracks investigations are ongoing studies performed on a yearly basis and have been conducted only since 1998. Participants from institutions throughout the world simultaneously conducted these studies according to specified scientific designs. The CAP has collected and summarized data for participants about these performance measures, including the significance of errors, the magnitude of error rates, tactics for error reduction, and willingness to implement each of these performance measures.

Main Outcome Measures.—A list of recommended performance measures, the frequency of errors when these performance measures were studied, and suggestions to improve patient safety by reducing these errors.

Results.—Error rates for preanalytic and postanalytic performance measures were higher than for analytic measures. Eight performance measures were identified, including customer satisfaction, test turnaround times, patient identification, specimen acceptability, proficiency testing, critical value reporting, blood product wastage, and blood culture contamination. Error rate benchmarks for these performance measures were cited and recommendations for improving patient safety presented.

Conclusions.—Not only has each of the 8 performance measures proven practical, useful, and important for patient care, taken together, they also fulfill regulatory requirements. All laboratories should consider implementing these performance measures and standardizing their own scientific designs, data analysis, and error reduction strategies according to findings from these published studies.
Granulosa Cell Tumor–like Variant of Endometrioid Carcinoma of the Ovary Exhibiting Nuclear Clearing With Biotin Activity: A Subtype Showing Close Macroscopic, Cytologic, and Histologic Similarity to Adult Granulosa Cell Tumor
Authors: Fujibayashi Mariko , Aiba Motohiko , Iizuka Eiji , Igarashi Akiyoshi , Okamura Mitsue , Takagi Koichiro
Published: February 2021

Context.—The sex cord–like variant of endometrioid carcinoma of the ovary shows many similarities to Sertoli-Leydig cell tumor and granulosa cell tumor. However, few cases of the granulosa cell tumor–like variant have been reported, suggesting this tumor might often be hidden under the diagnosis of granulosa cell tumor.

Objective.—To investigate the similarities and differences between the granulosa cell tumor–like variant of endometrioid carcinoma and granulosa cell tumor of the ovary and to evaluate a newly observed feature, namely, nuclear clearing (or optically clear nuclei), in this variant tumor.

Design.—A comparative macroscopic, cytologic, histopathologic, and immunohistochemical study in specimens obtained from the following patients: 1 patient with granulosa cell tumor–like variant of endometrioid carcinoma diagnosed by frozen section examination, 3 patients with granulosa cell tumor, and 6 patients with classic endometrioid carcinoma.

Results.—The granulosa cell tumor–like variant showed close macroscopic, cytologic, and microscopic similarities to granulosa cell tumor. However, the 2 tumors could be differentiated immunohistochemically. The former also showed intense staining for progesterone receptors and contained nonmorular nests that exhibited the so-called nuclear clearing with biotin activity.

Conclusion.—Because the granulosa cell tumor–like variant is pathologically similar to granulosa cell tumor, showing only some dissimilarities to the latter, it can easily be misdiagnosed if the possibility of this variant is not kept in mind. Identification of the typical endometrioid histologic features or related lesions or immunohistochemistry may lead to a proper diagnosis. The observation of nuclear clearing with biotin activity in nonmorular nests suggests that this tumor has endometrioid epithelial characteristics.
Sudden Unexpected Death in a 31-Year-Old Man Caused by Arrhythmogenic Right Ventricular Cardiomyopathy
Authors: Ye Dongjiu , Edwards William D. , Rizkalla Waheeb
Published: February 2021

A 31-year-old white man collapsed suddenly at a graduation ceremony and was pronounced dead after attempted resuscitation. He had no pertinent medical or familial history. Postmortem toxicologic studies showed negative results. A complete autopsy revealed a cardiac cause of death. Grossly, the right ventricular chamber was moderately to markedly dilated, and its free wall showed extensive myocardial adiposity. Microscopically, the right ventricular free wall consisted predominantly of adipose tissue, with only small subendocardial islands of hypertrophied myocytes and interstitial fibrosis. These features are characteristic of arrhythmogenic right ventricular cardiomyopathy. Moreover, Purkinje-like cells were observed among right ventricular myocytes and may have increased the likelihood of developing an arrhythmia. To our knowledge, this finding has not been previously emphasized. Because arrhythmogenic right ventricular cardiomyopathy accounts for 10% of cases of sudden unexpected cardiac death, recognition of this disease by pathologists is important, especially in cases of otherwise unexplained death in young persons.
Performance of the Revised Bethesda Guidelines for Identification of Colorectal Carcinomas With a High Level of Microsatellite Instability
Authors: Gologan Adrian , Krasinskas Alyssa , Hunt Jennifer , Thull Darcy L. , Farkas Linda , Sepulveda Antonia R.
Published: February 2021

Context.—Criteria for microsatellite instability (MSI) testing to rule out hereditary nonpolyposis colorectal cancer were recently revised and include parameters such as age and specific histologic features that can be identified by the pathologist, triggering reflex MSI testing.

Objective.—To review the performance of the revised Bethesda guidelines to identify MSI-positive colorectal cancers.

Design.—Seventy-five patients with colorectal cancer were included; 68 patients younger than 50 years and 7 patients between 50 and 60 years were selected based on histopathologic criteria. Microsatellite instability testing with the National Cancer Institute–recommended panel and immunohistochemistry for hMLH1 and hMSH2 were performed. Tumors were classified into microsatellite instability high (MSI-H), low (MSI-L), or stable (MSS) categories.

Results.—Overall, 17 (23%) of 75 colorectal cancer cases were classified as MSI-H, including 13 patients younger than 50 years and 4 patients between 50 and 60 years. Among the MSI-H tumors, 10 (59%) were characterized by loss of hMLH1 and 6 (35%) were hMSH2 negative. Histologic features suggestive of MSI-H phenotype were present in 80% of MSI-H and 35% of MSS/MSI-L tumors. The number of positive lymph nodes was higher in MSS/MSI-L adenocarcinomas (P = .04).

Conclusions.—By selecting for age and histologic features, we detected MSI-H tumors in approximately one quarter of colorectal cancer cases meeting the revised Bethesda guidelines and identified 17 MSI-H cases, whereas only 8 would have been recognized by the prior guidelines. These data indicate that reflex testing requested by pathologists based on the revised Bethesda guidelines increases the detection of MSI-H and potential hereditary nonpolyposis colorectal cancer cases.
Epithelial Displacement in Breast Lesions: A Papillary Phenomenon
Authors: Nagi Chandandeep , Bleiweiss Ira , Jaffer Shabnam
Published: February 2021

Context.—Displacement of epithelial cells (DE) in the breast may occur after various types of needling procedures.

Objective.—To determine if specific lesions or entities in the breast are more prone to displacement than others.

Design.—A review of our computer files from January 1994 to June 2004 yielded 53 cases with DE. Clinical information, including the age of the patient, specific reason for the biopsy, and type of biopsy, was gathered. Histologic review of all hematoxylin-eosin–stained slides (core biopsies and excisions) was performed.

Results.—Needling procedures included 1 or more of the following: ultrasound-guided core biopsy (24 cases), mammotome core biopsies (16), fine-needle aspiration (8), anesthetic injection (3), suture placement (5), and wire localization (1). Procedures were performed in order to investigate a mass (34 cases), calcifications (15), both (3), or nipple discharge (1). The time from needling to surgical procedure yielding a specimen with DE ranged from minutes to 47 days. Displacement of epithelial cells occurred in the following sites: biopsy tract (42 cases), lymphatic channels (5), both biopsy tract and lymphatic channels (4), and breast stroma (2). The diagnoses included intraductal papilloma (6 cases) and intraductal carcinoma (DCIS) (45; 15 with invasive carcinoma). The remaining 2 cases were invasive carcinoma (colloid and papillary types) devoid of DCIS. Of the DCIS cases, either pure or with invasive carcinoma, the pattern was micropapillary in 23, intraductal papilloma involved by DCIS in 32, and both features in 12. The remaining 2 cases of DCIS included comedo DCIS and cribriform DCIS involving a cyst.

Conclusions.—With the exception of 3 cases, DE was associated with 1 or more underlying papillary lesions, including pure intraductal papilloma, DCIS involving intraductal papilloma, micropapillary DCIS, and invasive carcinoma. Other etiologies included mucinous carcinoma and cystic lesions, with only 1 case in which a mechanism for DE could not be postulated.
Sodium Status of Collapsed Marathon Runners
Authors: Kratz Alexander , Siegel Arthur J. , Verbalis Joseph G. , Adner Marvin M. , Shirey Terry , Lee-Lewandrowski Elizabeth , Lewandrowski Kent B.
Published: February 2021

Context.—Recommendations for prevention and treatment of medical emergencies in participants in marathon races center on maintenance of adequate hydration status and administration of fluids. Recently, new recommendations for fluid replacement for marathon runners were promulgated by medical and athletic societies. These new guidelines encourage runners to drink ad libitum between 400 and 800 mL/h as opposed to the previous “as much as possible” advice.

Objective.—To assess the sodium and hydration (plasma osmolality) status of collapsed marathon runners after the promulgation of new hydration guidelines.

Design.—Plasma sodium and osmolality values of runners who presented to the medical tent at the finish line of the 2003 Boston Marathon were measured.

Results.—Using reference ranges derived from the general population, of 140 collapsed runners, 35 (25%) were hypernatremic (sodium, >146 mEq/L) and 6 (12%) were hyperosmolar (osmolality, >296 mOsm/kg H2O), whereas 9 (6%) were hyponatremic (sodium, <135 mEq/L) and 8 (16%) were hypo-osmolar (osmolality, <280 mOsm/kg H2O). Compared with a population of marathon runners who had experienced no medical difficulties, 9% of the runners were hypernatremic, 5% were hyponatremic, 8% were hypo-osmolar, and none were hyperosmolar.

Conclusions.—Our findings indicate a significant incidence of hypernatremia with hyperosmolality and hyponatremia with hypo-osmolality among collapsed runners despite the new fluid intake recommendations, suggesting that either further educational measures are required or that the new guidelines are not entirely adequate to prevent abnormalities in fluid balance. Furthermore, the immediate medical management of hypernatremia and hyponatremia is different. Administration of fluids to severely hyponatremic patients may result in fatal cerebral edema. Our findings caution against institution of treatment until laboratory tests determine the patient's sodium status.