bluuebunny/crossref_metadata_2025 huggingface dataset:
Leadership and Management Training for Residents and Fellows: A Curriculum for Future Medical Directors
Authors: Hemmer Patrick R. , Karon Brad S. , Hernandez James S. , Cuthbert Carla , Fidler Mary E. , Tazelaar Henry D.
Published: February 2021

Context.—Management of laboratories and pathology practices is increasingly complex. Residents and fellows in laboratory medicine and pathology need more structured curricula in leadership and management (L&M) training to function as medical and laboratory directors.

Objective.—To define a curriculum that provides basic competency in L&M for residents and fellows in pathology.

Design.—A year-long formal L&M course included didactic lectures, interactive sessions, case scenarios, team-building exercises, formal team presentations (capstone project), and precourse and postcourse assessment of L&M knowledge. The curriculum meets requirements of American College of Graduate Medical Education and supports goals for leadership training of the College of American Pathologists. Participants evaluated (5-point scale) the content and speakers of all sessions. Trainees were evaluated after considering postcourse examination results, quality of the capstone presentation, and a global assessment.

Results.—The 5 non-capstone sessions received evaluation scores ranging from 4.4 (informatics) to 5 (L&M basics). Postcourse test scores showed significant improvement when compared with the pretest scores for the 2003– 2004 and 2004–2005 trainee cohorts.

Conclusions.—Short-term results indicate that the course described improves trainee knowledge of L&M issues.
Interference of Asian, American, and Indian (Ashwagandha) Ginsengs in Serum Digoxin Measurements by a Fluorescence Polarization Immunoassay Can Be Minimized by Using a New Enzyme-Linked Chemiluminescent Immunosorbent or Turbidimetric Assay
Authors: Dasgupta Amitava , Kang Edward , Olsen Margaret , Actor Jeffrey K. , Datta Pradip
Published: February 2021

Context.—Ginsengs are widely used by the general population. These herbs interfere with serum digoxin measurement using the fluorescence polarization immunoassay.

Objective.—To assess potential interference of different ginsengs (Asian, American, and Indian, also known as Ashwagandha) in vitro and in vivo in a mouse model by using a new enzyme-linked chemiluminescent immunosorbent digoxin assay and an existing turbidimetric assay. Comparisons were made with the fluorescence polarization immunoassay.

Design.—Aliquots of drug-free serum pools were supplemented with ginseng and apparent digoxin concentrations were measured using enzyme-linked chemiluminescent immunosorbent digoxin assay, turbidimetric assay, and fluorescence polarization immunoassay digoxin assays. Mice were fed with different ginseng preparations and apparent digoxin concentrations were measured 1 and 3 hours later. In a separate experiment, aliquots of serum digoxin pools were further supplemented with ginsengs and the serum digoxin concentrations were measured again.

Results.—A significant apparent digoxin concentration was observed both in vitro and in vivo using the fluorescence polarization immunoassay, but no apparent digoxin concentration was observed using enzyme-linked chemiluminescent immunosorbent digoxin assay and turbidimetric assay. No interference was observed with enzyme-linked chemiluminescent immunosorbent digoxin assay and turbidimetric assay when digoxin serum pools were further supplemented with various ginsengs.

Conclusions.—It was concluded that both enzyme-linked chemiluminescent immunosorbent and turbidimetric digoxin assays are free from ginseng interferences.
Blood Management
Authors: Goodnough Lawrence T. , Shander Aryeh
Published: February 2021

Context.—We provide an overview of the principles of blood management: the appropriate use of blood and blood components, with a goal of minimizing their use.

Objective.—To review the strategies that exploit combinations of surgical and medical techniques, technologic devices, and pharmaceuticals, along with an interdisciplinary team approach that combines specialists who are expert at minimizing allogeneic blood transfusion.

Data Sources.—A search on Medline and PubMed for the terms English and humans used in articles published within the last 20 years.

Conclusions.—Blood management is most successful when multidisciplinary, proactive programs are in place so that these strategies can be individualized to specific patients.
Emerging Eosinophilic (Allergic) Esophagitis: Increased Incidence or Increased Recognition?
Authors: Vanderheyden Andrew D. , Petras Robert E. , DeYoung Barry R. , Mitros Frank A.
Published: February 2021

Context.—Eosinophilic esophagitis is a disease of the esophagus with distinct histologic features (prominent intraepithelial eosinophils, particularly superficial with clustering) and characteristic endoscopic features (trachealization, white plaques). The presence of intraepithelial eosinophils had been recognized since 1982 as indicative of reflux esophagitis but little attention was initially paid to their numbers or location. Eosinophilic esophagitis has been recently described and there have been a number of reports that its incidence is on the rise. It had been our impression that eosinophilic esophagitis was being seen more frequently, perhaps resulting from some environmental change.

Objective.—To investigate the increased prevalence of eosinophilic esophagitis.

Design.—We analyzed a similar group of cases from 2005 (n = 150) as compared with 1990 (n = 115). Consecutive patients with mucosal esophageal biopsies from May through June of the respective years were included in the analysis. Patients with Barrett metaplasia or with carcinoma were excluded. The highest density of intraepithelial eosinophils for each patient was recorded as the number of intraepithelial eosinophils per single high-power field. The patients were categorized by the number of intraepithelial eosinophils per high-power field with those cases with greater than 20 intraepithelial eosinophils per high-power field representing eosinophilic esophagitis.

Results.—There was no difference in the incidence of eosinophilic esophagitis between 1990 and 2005.

Conclusions.—The apparent increased incidence of eosinophilic esophagitis is largely a result of an increase in recognition rather than an increase in disease resulting from an environmental factor.
Primary Osteosarcoma of the Breast: Report of 2 Cases
Authors: Bahrami Armita , Resetkova Erika , Ro Jae Y. , Ibañez Joe D. , Ayala Alberto G.
Published: February 2021

Two distinct histologic variants of primary breast osteosarcoma in 2 elderly women are described. The first patient was an 88-year-old woman with a long-standing, slow-growing, 18-cm mass in her right breast. The second patient was a 96-year-old woman with a recently self-detected, painless, 7.5-cm lump in her left breast. Clinically, there was no evidence of metastasis, and both women underwent simple mastectomy. Histologic features of both specimens were those of high-grade primary breast osteosarcoma. The first patient's tumor was classified as a chondroblastic variant, and the second as an osteoblastic variant of osteosarcoma. The patients were alive without evidence of local recurrence or hematogenous spread at a 16- and 4-month follow-up, respectively. Primary mammary osteosarcoma should be distinguished from metaplastic/ sarcomatoid carcinoma with heterologous osseous/cartilaginous differentiation or malignant phyllodes tumor because it has a different biological behavior and requires a different treatment approach.
Breast Carcinoma in Uganda: Microscopic Study and Receptor Profile of 45 Cases
Authors: Roy Indrojit , Othieno Emmanuel
Published: February 2021

Context.—Histologic and receptor data on breast carcinoma in Uganda are scarce. Estrogen receptor status is not routinely available. Breast cancer blocks from Uganda were studied in Montreal, Canada, and clinical correlations subsequently discussed in Kampala, Uganda.

Objective.—To correlate histologic features (tumor type, histologic grade), receptor profile (estrogen receptor, progesterone receptor, and HER2/neu), and age in Ugandan women.

Design.—Pathology reports for 2000–2004 from Nsambya Hospital, reporting invasive breast carcinoma, provided 45 microscopically confirmed cases.

Results.—Seventy-three percent of patients were 50 years or younger. Histologic types were invasive ductal carcinoma (78%) and “good” prognosis types (11%). Overall 40% were grade 3, but 48% of invasive ductal carcinomas were grade 3. Estrogen receptor was positive in 60% overall and in 51% of invasive ductal carcinomas. HER2/neu was overexpressed in 11%; 36% were “triple” negative (estrogen receptor, progesterone receptor, HER2/neu negative).

Conclusions.—Breast carcinoma in Ugandan women presents at a younger age and is histologically and by receptor profile more aggressive than carcinoma in Caucasian women.
Postmortem Whole-Body Computed Tomography Angiography Visualizing Vascular Rupture in a Case of Fatal Car Crash
Authors: Flach Patricia M. , Ross Steffen G. , Bolliger Stephan A. , Preiss Ulrich S. , Thali Michael J. , Spendlove Danny
Published: February 2021

In addition to the increasingly significant role of multislice computed tomography in forensic pathology, the performance of whole-body computed tomography angiography provides outstanding results. In this case, we were able to detect multiple injuries of the parenchymal organs in the upper abdomen as well as lesions of the brain parenchyma and vasculature of the neck. The radiologic findings showed complete concordance with the autopsy and even supplemented the autopsy findings in areas that are difficult to access via a manual dissection (such as the vasculature of the neck). This case shows how minimally invasive computed tomography angiography can serve as an invaluable adjunct to the classic autopsy procedure.
Intradural Extramedullary Leptomeningeal Hemangioblastomatosis and Paraneoplastic Limbic Encephalitis Diagnosed at Autopsy: An Unlikely Pair
Authors: Ramachandran Rageshree , Lee Han Sung , Matthews Brandy , Shatzel Alan , Tihan Tarik
Published: February 2021

Typical cerebellar or spinal cord hemangioblastoma is often solitary and has a benign clinical course, whereas disseminated hemangioblastomatosis is extremely rare. We report a 75-year-old man with disseminated “leptomeningeal” hemangioblastomatosis and concurrent paraneoplastic limbic encephalitis who died of this disease. The patient presented with gait problems and cognitive deficits, and was diagnosed with a cervical spinal tumor. Surgical resection achieved an apparent gross total resection, but later the patient began experiencing severe cognitive decline. His condition progressively deteriorated during the next few months, and he died 15 months after his initial surgery. Autopsy revealed disseminated extramedullary intradural hemangioblastomatosis with extensive leptomeningeal nodules involving the entire spinal cord, medulla, pons, and midbrain, as well as histologic features of limbic encephalitis. There was no evidence of von Hippel–Lindau disease, and no specific etiology was identified for the dementia. To the best of our knowledge, this is the first case of limbic encephalitis occurring in the setting of disseminated hemangioblastomatosis.
A Unique Case of Mantle Cell Lymphoma With an Aberrant CD5−/CD10+ Immunophenotype and Typical Morphology
Authors: Sriganeshan Vathany , Blom Thomas R. , Weissmann David J.
Published: February 2021

Mantle cell lymphoma (MCL) is a non-Hodgkin lymphoma with a poor prognosis that may be confused with less aggressive diseases, such as small lymphocytic lymphoma and follicular lymphoma. In many cases immunophenotyping, particularly analysis of reactivity for CD5 and CD10, is an important adjunct to morphology that usually distinguishes MCL from follicular lymphoma; the former is CD5+/CD10−, whereas follicular lymphoma is the reverse. We report a case of MCL, initially diagnosed as follicular lymphoma, that at presentation expressed neither CD5 nor CD10. At relapse, it was still CD5−, but CD10 was now detected. Studies for a t(11;14) translocation and CYCLIN D1 protein expression, however, permitted a revised diagnosis of MCL. An MCL with this immunophenotype and classical morphology has not been previously reported.
Morphologic Features of 115 Lymphomas of the Orbit and Ocular Adnexa Categorized According to the World Health Organization Classification: Are Marginal Zone Lymphomas in the Orbit Mucosa-Associated Lymphoid Tissue–Type Lymphomas?
Authors: Lagoo Anand S. , Haggerty Christopher , Kim Young , Hammons Matthew , Neufeld Kenneth , Redher Catherine , Woodward Julie , Klintworth Gordon K.
Published: February 2021

Context.—Marginal zone lymphomas (MZLs) are the most common lymphomas encountered in the orbit and ocular adnexa. The accurate categorization of these lymphomas is critical to avoid undertreatment or overtreatment.

Objective.—To identify features of orbital MZLs that distinguish them from other lymphomas and reactive lymphoid infiltrates and support the categorization of orbital MZL as mucosa-associated lymphoid tissue (MALT)–type MZLs.

Design.—Biopsies from 149 patients with lymphoid lesions of ocular adnexa were examined. Additional immunohistochemical stains and fluorescence in situ hybridization study for the MALT1 locus were performed in selected cases, and patient charts were reviewed.

Results.—A total of 115 lymphomas and 34 reactive infiltrates were identified, of which B-cell lymphomas constituted 92% and MZLs constituted 54% of all lymphomas. Certain clinical features (young age, race, bilaterality) favored a reactive infiltrate, but none were diagnostic. Histologic features, such as infiltrative lesions, reactive B-cell follicles, and lymphoepithelial lesions, overlapped between reactive infiltrates and conjunctival MZL. In contrast to conjuctival MZL, orbital MZL infrequently showed reactive follicles, rarely showed epithelial tissue, and did not show lymphoepithelial lesions. Cytogenetic abnormality involving the MALT1 locus was demonstrated in only 15% of ocular adnexal MZLs.

Conclusion.—Many MZLs of orbital soft tissue lack key features associated with MALT-type MZL, and the designation MALT lymphoma should be avoided in their diagnosis.
Targeted Therapy in Non–Small Cell Lung Cancer: A Commentary
Authors: Murer Bruno
Published: February 2021

Context.—The development of targeted therapy provides an exciting prospect for treatment of advanced non–small cell lung cancer. In the last few years the epithelial growth factor receptor has emerged as one of the most important targets in very selected patients.

Objective.—To review current data on the role of the targeted therapy in advanced non–small cell lung cancer and offer some perspectives for the practitioner.

Data Sources.—This review is drawn from pertinent literature and the author's experience.

Conclusions.—Despite the remarkable development of targeted therapies in advanced non–small cell lung cancer, there is not yet a real improvement in overall survival. This might be due to (1) the development of primary or secondary resistance to therapy, (2) the biologic method used to select the population to treat, or (3) the molecular status of epithelial growth factor receptor may not be the most important predictor for targeted therapy. The understanding of interactions between epithelial growth factor receptor inhibitors and other molecules will be essential in the development of more effective treatment strategies.
Clinical Evaluation of Gen-Probe's Amplified Mycobacterium Tuberculosis Direct Test for Rapid Diagnosis of Mycobacterium tuberculosis in Egyptian Children at Risk for Infection
Authors: Zaki Maysaa El-Sayed , Hassan Samir Abou-El
Published: February 2021

Context.—Diagnostic detection of tuberculosis (TB) has improved considerably. Available, standardized, nucleic acid–based amplification techniques have been shown to yield reliable results within 4 to 7 hours of sample processing.

Objective.—To study the diagnostic performance of Gen-Probe's technique for direct detection of Mycobacterium tuberculosis in comparison with BACTEC 460 TB culture for both positive and negative Ziehl-Neelsen smears in Egyptian children at risk for TB infection.

Design.—We prospectively evaluated 50 children from families with a positive history of TB. All patients were referred from outpatient clinics of the Mansoura University Children's Hospital, Egypt. The children had a positive tuberculin skin test with an induration diameter of more than 10 mm and had scars from a bacille Calmette-Guérin vaccination within the past 2 years. Three consecutive sputum samples were taken from each patient. The samples were examined to detect M tuberculosis by means of the Gen-Probe technique, direct smear microscopy, and bacterial culture by BACTEC 460 TB.

Results.—Of the 50 cases, 30 (60%) had sputum samples that were positive for TB by BACTEC 460 TB culture, and 29 cases (58%) were positive by the Gen-Probe technique. Sensitivity and specificity of Ziehl-Neelsen smears was 83.3% and 100%, respectively, with overall accuracy of 90%. Sensitivity and specificity of the Gen-Probe technique were 96.7% and 100%, respectively, with overall accuracy of 98%.

Conclusions.—The results of this study suggest that the Gen-Probe technique is an accurate method for rapid detection of M tuberculosis complexes in respiratory samples from children at risk for TB. It can be used for diagnosis of smear-negative cases that are suspect for TB.
Molecular Pathology in Anatomic Pathology Practice: A Review of Basic Principles
Authors: Hunt Jennifer L.
Published: February 2021

Molecular testing in pathology emerged shortly after polymerase chain reaction became a standard molecular biology assay.1 Testing efforts began in the clinical laboratories primarily with assays for genetically inherited diseases and assays for clonality in hematologic malignancies.12 Today, the field has evolved into “molecular diagnostics,” which encompasses testing in almost every area of anatomic pathology.3 Molecular testing is now even making its way definitively into both surgical pathology and cytopathology, although molecular anatomic pathology is still young with few standard tissue-based molecular assays. As more clinically valuable information is gained from molecular pathology testing of tissues, unique challenges are also becoming apparent at the intersection between tissue diagnosis and DNA diagnosis. This review focuses on basic molecular pathology concepts, with particular emphasis on the challenge of tissue-based testing in anatomic pathology.
Iris Melanoma
Authors: Henderson Evita , Margo Curtis E.
Published: February 2021

The iris is the least common site of primary uveal melanoma. The prognosis of iris melanoma is better than that of melanoma of the ciliary body and choroid, but the reason for this difference is unclear. One possible explanation is that iris melanoma is smaller than its posterior segment counterparts at the time of diagnosis. Most iris melanomas are spindle cell types, according to a modified Callender classification system. There is evidence that the proliferation of melanocytes of the anterior iris surface (iris plaque) and diffuse stromal invasion may be risk factors for local recurrence and metastasis, respectively.
Angiomatoid Fibrous Histiocytoma: A Review With Recent Genetic Findings
Authors: Thway Khin
Published: February 2021

Angiomatoid fibrous histiocytoma is a neoplasm of intermediate biologic potential most often arising in the extremities of children and young adults. Its rarity may lead to misdiagnosis as either a reactive lesion or a benign or higher-grade tumor. Originally described as a type of malignant fibrous histiocytoma, its differentiation remains enigmatic, with precise histogenesis still only hypothesized. Its morphology is distinct, as a circumscribed lesion with sheets of bland spindle to ovoid cells, peripheral lymphoplasmacytic infiltrate, and blood-filled cystic cavities, and half of the cases show strong desmin expression. Cytogenetically, 2 specific translocations, t(12:16)(q13:p11) and more recently t(12:22)(q13:q12), have been characterized. The literature on angiomatoid fibrous histiocytoma is reviewed, particularly with regard to recent molecular genetic developments and differentiation, and its morphology, immunohistochemistry, and differential diagnosis are summarized.
Serum Immunoglobulin G Fraction 4 Levels in Pancreatic Cancer: Elevations Not Associated With Autoimmune Pancreatitis
Authors: Raina Amit , Krasinskas Alyssa M. , Greer Julia B. , Lamb Janette , Fink Erin , Moser A. James , Zeh III Herbert J. , Slivka Adam , Whitcomb David C.
Published: February 2021

Context.—Autoimmune pancreatitis is an uncommon, inflammatory disease of the pancreas that presents with clinical features, such as painless jaundice and a pancreatic mass, similar to those caused by pancreatic cancer. Patients with autoimmune pancreatitis frequently have elevated serum immunoglobulin G fraction 4 (IgG4) levels, and their pancreatic tissue may show IgG4-positive plasma cell infiltration. It is imperative to differentiate autoimmune pancreatitis from pancreatic cancer because autoimmune pancreatitis typically responds to corticosteroid treatment. A previous Japanese study reported that serum IgG4 greater than 135 mg/dL was 97% specific and 95% sensitive in predicting autoimmune pancreatitis.

Objective.—To prospectively measure serum IgG4 levels in pancreatic cancer patients to ascertain whether increased levels might be present in this North American population.

Design.—We collected blood samples and phenotypic information on 71 consecutive pancreatic cancer patients and 103 healthy controls who visited our clinics between October 2004 and April 2006. IgG4 levels were determined using a single radial immunodiffusion assay. A serum IgG4 level greater than 135 mg/dL was considered elevated.

Results.—Five cancer patients had IgG4 elevation, with a mean serum IgG4 level of 160.8 mg/dL. None of our cancer patients with plasma IgG4 elevation demonstrated evidence of autoimmune pancreatitis. One control subject demonstrated elevated serum IgG4 unrelated to identified etiology.

Conclusions.—As many as 7% of patients with pancreatic cancer have serum IgG4 levels above 135 mg/dL. In patients with pancreatic mass lesions and suspicion of cancer, an IgG4 level measuring between 135 and 200 mg/dL should be interpreted cautiously and not accepted as diagnostic of autoimmune pancreatitis without further evaluation.
Application of Immunohistochemistry to Liver and Gastrointestinal Neoplasms: Liver, Stomach, Colon, and Pancreas
Authors: Geller Stephen A. , Dhall Deepti , Alsabeh Randa
Published: February 2021

Context.—Immunohistochemistry has become an integral component of the practice of pathology. Newer antibodies allow for increasingly precise diagnoses for tumors that previously could not be easily identified. Recently, immunohistochemical evaluations have begun to allow pathologists to actively assist in determining prognosis and even in selecting therapies.

Objective.—To summarize the usefulness of currently available immunostains for the study of liver and gastrointestinal system neoplasms and to make recommendations for panels of immunostains that can be particularly helpful.

Data Sources.—Information has been collected from recent literature as well as from personal experience and practice.

Conclusions.—Many immunostains are now available for the practicing pathologist that allow for increasing accuracy in diagnosis of liver and gastrointestinal tract neoplasms. Panels of immunostains can be used to differentiate between various tumors and also to identify site of origin in the case of a metastatic neoplasm. Immunostains that allow for prognostic determinations and for guidance in the selection of chemotherapeutic agents can also be used by pathologists to assist in the management of patients with malignant tumors affecting the liver and gastrointestinal tract.
Shirt-Sleeve or Scanning Magnification as an Aid to the Diagnosis of Commonly Encountered Medical Lung Diseases
Authors: Mark Eugene J. , Ruangchira-Urai Ruchira , Kradin Richard L.
Published: February 2021

Shirt-sleeve magnification (holding a slide over a white sleeve) and low-power magnification serve as useful adjuncts in the general categorization of noninfectious medical lung disease. This article divides medical lung disease into chronic and acute, where the temporality is determined first by clinical circumstances and then confirmed by histopathology. The low-power patterns of various lung diseases overlap, sometimes greatly. Nevertheless, classic examples of chronic disease can be sorted as linear, lobular filling, nodular dispersed, nodular lymphangitic, or cystic patterns at shirt-sleeve or low-power magnification. Classic examples of acute disease generally produce a solidifying pattern at shirt-sleeve or low-power magnification, which can be followed by a determination as to whether alveolar filling is principally fibrotic or principally fluid or cells at higher magnification. This article gives a simple system for the categorization of medical lung disease by this approach, with an emphasis on the most common diseases to be encountered in a general surgical pathology practice. In our experience, this system also proves useful in arriving at some therapeutic decisions.
Reactive Versus Neoplastic Bone Marrow: Problems and Pitfalls
Authors: Hasserjian Robert P.
Published: February 2021

Examination of the bone marrow poses several unique challenges to the pathologist: it is a semisolid organ without helpful gross correlation, it exists in a dynamic state with the peripheral blood and other organs of the lymphohemopoietic system, and the diagnosis of diseases affecting bone marrow often depends heavily on ancillary special studies. The bone marrow examination ideally encompasses review of the bone marrow biopsy histology (with or without additional nondecalcified clot preparation material), bone marrow aspirate smear cytology, and the peripheral blood smear; optimal procurement and processing of these samples is critical in ensuring that a maximal level of diagnostic information can be extracted. The pathologist must be aware of the clinical context of the bone marrow and the results of ancillary tests, whether these are ordered by the pathologist or the clinician. A combination of excellent diagnostic samples, appropriate ancillary tests, and knowledge of the clinical context provides the best background to distinguish between the common reactive and neoplastic processes that involve the bone marrow and to avoid diagnostic pitfalls in making these distinctions.
Coronary Artery Aneurysm: A Review and Hypothesis Regarding Etiology
Authors: Nichols Larry , Lagana Stephen , Parwani Anil
Published: February 2021

Context.—Coronary artery aneurysm is an uncommon condition that can be a cause of death when it thromboses or ruptures. It is always associated with destruction of the tunica media, usually associated with atherosclerosis, and commonly associated with chronic inflammation.

Objective.—To review the pathology, epidemiologic and clinical features, and pathophysiology of coronary artery aneurysm, particularly new research results, drawing out implications for the understanding, diagnosis, and treatment of this condition.

Data Sources.—Pertinent literature and illustrative cases at our institution.

Conclusions.—Inflammation spilling over into the tunica media from the tunica intima may link atherosclerosis to aneurysm formation, but vasculitis without atherosclerosis causes coronary artery aneurysms in young children with Kawasaki disease. Increased proteolysis of extracellular matrix proteins is probably one mechanism of coronary artery aneurysm formation, either due to overactive matrix metalloproteinases or underactive inhibition of these proteinases, and an excess of transforming growth factor β may be another mechanism in the pathogenesis. Coronary atherosclerosis is a universal disease of adults, but only 1.5% of them have coronary aneurysms; this small group may be those with a second coronary artery disease, such as vasculitis.
Glial Choristoma in the Oral and Maxillofacial Region: A Clinicopathologic Study of 6 Cases
Authors: Sun Li-Sha , Sun Zhi-Peng , Ma Xu-Chen , Li Tie-Jun
Published: February 2021

Context.—Glial choristoma is an uncommon developmental abnormality typically presenting at birth or in early childhood. The nasal region is most frequently affected. Palate, tongue, cheek, scalp, and orbit can also be affected but these occurrences are relatively rare.

Objective.—To report 6 cases of glial choristoma arising in the oral and maxillofacial region and to document the clinical and pathologic features of these lesions.

Design.—Histologic and immunocytochemical examinations were performed on 6 cases of glial choristoma. Biologic behavior, prognosis, and pathogenesis were discussed together with a review of the literature.

Result.—The patients included 5 boys and 1 girl. They all presented with the lesions at birth or soon after birth. Four lesions occurred on the dorsal side of the tongue, near the foramen caecum. One lesion was present in the infratemporal fossa and parapharyngeal space, and the other one was in the submandibular region. All patients received surgical excision, and follow-up data revealed no recurrence for a period of 10 months to 5 years after surgery. Histologically, the lesions showed mature glial cells intermixed with connective tissue. The glial tissue was strongly positive for glial fibrillary acidic protein and S100 but negative for neurofilament.

Conclusion.—Glial choristoma should be classified as a developmental malformation that occurs in many sites of the head and neck. In oral cavity, the tongue is the most frequently affected site. Although these lesions are rare, they should be included in the differential diagnosis of congenital masses in the oral and maxillofacial region.
Characterization of CXCR4 Expression in Chondrosarcoma of Bone
Authors: Bai Shuting , Wang Dezhi , Klein Michael J. , Siegal Gene P.
Published: February 2021

Context.—Alterations in molecular elements derived from the CXC chemokine receptor 4 (CXCR4)/stromal-derived factor 1 (SDF-1) cytokine system have been found to strongly correlate with neoplastic progression leading to metastasis in a number of tumors, including osteosarcoma. Excluding hematologic malignancies, chondrosarcoma of bone is the most common primary malignant tumor of bone in adults in the United States. Like osteosarcoma, chondrosarcoma preferentially metastasizes to lung, bone, and very rarely to regional lymph nodes. However, the role of the signal pathway(s) driving neoplastic progression in chondrosarcoma has not yet been clearly elucidated.

Objective.—To test whether CXCR4 was detectable in chondrosarcoma and whether CXCR4 expression levels correlated with chondrosarcoma grade.

Design.—Twenty-two chondrosarcoma samples banked at our institution between 2001 and 2006 were retrieved for study. By using invasive ductal carcinoma of the breast and osteosarcoma as the positive controls, immunohistochemistry was performed on paraffin-embedded tissue sections and the intensity of the tumor cells was analyzed by morphometric techniques.

Results.—All chondrosarcoma cases (22 of 22) were immunoreactive for CXCR4. However, the staining intensity of the CXCR4 between the low- and high-grade groups was significantly different. There was a higher staining intensity in high-grade chondrosarcoma cells (P < .001).

Conclusion.—CXCR4 is expressed in chondrosarcomas. CXCR4 expression levels were higher in high-grade chondrosarcoma cells than in low-grade specimens. A larger number of cases will be required to confirm these results and expand the observation, but preliminary data would argue for CXCR4 immunohistochemistry as a potential marker for biologic aggressiveness in chondrosarcoma of bone.
Diagnostic Utility of P504S/p63 Cocktail, Prostate-Specific Antigen, and Prostatic Acid Phosphatase in Verifying Prostatic Carcinoma Involvement in Seminal Vesicles: A Study of 57 Cases of Radical Prostatectomy Specimens of Pathologic Stage pT3b
Authors: Harvey Aaron M. , Grice Beverly , Hamilton Candice , Truong Luan D. , Ro Jae Y. , Ayala Alberto G. , Zhai Qihui “Jim”
Published: February 2021

Context.—Seminal vesicle invasion by prostatic carcinoma is directly associated with tumor staging; verification is challenging when the tumor demonstrates cribriform or papillary growth patterns or there are back-to-back small-gland proliferations. P504S is overexpressed in prostatic carcinoma and high-grade prostatic intraepithelial neoplasia with cytoplasmic immunoreactivity. p63 has positive immunoreactivity in basal cell nuclei of benign prostatic glands. Many researchers use a combination of these antibodies and their different colors.

Objective.—To evaluate the usefulness of a single-color P504S/p63 cocktail immunostain in verifying prostatic carcinoma within the seminal vesicle.

Design.—Sections from 57 radical prostatectomy specimens of pathologic stage pT3b that contain seminal vesicle with prostatic carcinoma involvement were immunostained with primary antibodies against prostate-specific antigen (PSA) and prostatic acid phosphatase (PAP) and a cocktail of antibodies against P504S and p63.

Results.—Prostatic carcinoma cells from all 57 cases were diffusely positive for P504S, PSA, and PAP with cytoplasmic staining and no p63 nuclear staining. Seminal vesicle epithelium from all 57 cases was negative for all 3 markers with distinct p63 nuclear staining of the basal cells. Benign prostatic tissue was positive for PSA and PAP, as well as for p63, but negative for P504S.

Conclusions.—The P504S/p63 one-color cocktail is a practical and cost-effective stain to differentiate prostatic carcinoma that involves the seminal vesicle from seminal vesicle epithelium. It is superior to PSA or PAP when sections contain both seminal vesicle and benign glands because PSA and PAP cannot distinguish benign from malignant glands.
Lobular Carcinoma In Situ Variants in Breast Cores: Potential for Misdiagnosis, Upgrade Rates at Surgical Excision, and Practical Implications
Authors: Sullivan Megan E. , Khan Seema A. , Sullu Yurdanur , Schiller Carol , Susnik Barbara
Published: February 2021

Context.—Differentiating ductal carcinoma in situ (DCIS) from lobular carcinoma in situ (LCIS) on core biopsy has important clinical implications. Lobular carcinoma in situ variants, including LCIS with necrosis and pleomorphic LCIS, share morphologic features with solid DCIS that may lead to misclassification.

Objectives.—(1) To review all LCIS variants diagnosed in core biopsies at Northwestern University, Feinberg School of Medicine, and determine the frequency of misinterpretation of variant LCIS as solid DCIS in archival core biopsies, and (2) to determine the frequency of upgrade to invasive carcinoma or DCIS in the surgical excision.

Design.—Consecutive core biopsies with original diagnoses of predominantly solid DCIS without invasion that were performed between January 2001 and December 2005 at Northwestern University, Feinberg School of Medicine, were selected for E-cadherin staining. The revised diagnosis of LCIS was based on E-cadherin negativity and morphology. The frequency of LCIS variants upgraded was then estimated from all core biopsies with original or revised diagnoses of pleomorphic LCIS or LCIS with necrosis.

Results.—Among 75 cases of solid DCIS, 10 (13.3%) were reclassified as LCIS, including 9 variants (5 pleomorphic LCIS, 4 LCIS with necrosis) and 1 classic LCIS. Twenty-eight patients comprised the entire group of LCIS variant cases (both reclassified and originally diagnosed cases). Seven patients with LCIS variants (25%) were upgraded to invasive lobular carcinoma in surgical excision (4 of 11 cases of LCIS with necrosis [36%] versus 3 of 17 cases of pleomorphic LCIS [18%]).

Conclusions.—About one-tenth of solid DCIS diagnosed in core biopsies in the past may represent LCIS variants. These show a 25% upgrade to invasive lobular carcinoma in surgical excision. The distinction of an LCIS variant from DCIS is important because of its implications for radiation therapy, although it may not affect surgical management.
Diagnostic Concordance of Histologic Lung Cancer Type Between Bronchial Biopsy and Cytology Specimens Taken During the Same Bronchoscopic Procedure
Authors: Sackett Melanie K. , Salomão Diva R. , Donovan Janis L. , Yi Eunhee S. , Aubry Marie Christine
Published: February 2021

Context.—The diagnosis of lung cancer is often confirmed by cytology and biopsy specimens obtained during a bronchoscopic procedure. At our institution, these specimens are read by different pathologists, and the rate of concordance was not known.

Objectives.—To evaluate the concordance rate in the diagnosis of lung cancer types between cytology and biopsy specimens and to correlate discordance with patient outcome.

Design.—Specimens obtained during the same procedure, between January 1, 2000, and December 31, 2005, were identified. Cases with cytology and biopsy specimens positive for cancer were evaluated for concordance of histologic type, small cell versus non–small cell lung carcinoma. Cases with different types were considered discordant, and slides were reviewed.

Results.—Of 231 cases, 225 (97.4%) had concordant diagnoses. Discordance was the result of misinterpretation of undifferentiated carcinoma, overinterpretation of squamous dysplasia, interpretation of suboptimal specimens with necrosis and crush artifact, and sampling error.

Conclusions.—Even though the cytology and biopsy specimens were reviewed by different pathologists, the concordance rate for histologic type at our institution was high, emphasizing that this is a safe practice. The few discordant cases did not affect the patient's outcome.
PAX-2 Is a Helpful Marker for Diagnosing Metastatic Renal Cell Carcinoma: Comparison With the Renal Cell Carcinoma Marker Antigen and Kidney-Specific Cadherin
Authors: Ozcan Ayhan , Zhai Qihui , Javed Rehana , Shen Steven S. , Coffey Donna , Krishnan Bhuvaneswari , Truong Luan D.
Published: February 2021

Context.—The diagnosis of metastatic renal cell carcinoma (RCC) remains problematic.

Objective.—To evaluate the role of PAX-2, a renal tubular cell transcription factor, in the diagnosis of metastatic RCC. PAX-2 expression in metastatic RCC was compared with that of the renal cell carcinoma marker antigen (RCCM) and kidney-specific cadherin (KSC), which are 2 known markers for RCC.

Design.—Immunostaining for PAX-2, RCCM, and KSC was performed on consecutive tissue sections of 95 metastatic RCCs (77 clear cell, 8 papillary, 5 sarcomatoid, and 5 collecting duct) and 183 metastatic tumors other than RCC.

Results.—For PAX-2, positive immunoreactivity was detected in 77% clear cell, 75% papillary, 100% collecting duct, and 0% sarcomatoid metastatic RCCs. For RCCM, positive immunoreactivity was detected in 49% clear cell, 75% papillary, 0% collecting duct, and 0% sarcomatoid metastatic RCCs. For KSC, only 2 metastatic clear cell RCCs (3%) were positive. In combination, all markers were positive in 0% of cases; all markers were negative in 23% of cases (17 clear cell, 1 papillary, and for all 5 sarcomatoid); and at least 1 marker was positive in 76% of cases (PAX-2 only in 28% of cases [21 clear cell, 1 papillary, and 5 collecting duct] and RCCM only in 3% of cases [2 clear, 1 papillary]). Of 183 metastatic tumors other than RCC, 14 were positive for PAX-2 (nodal metastasis of carcinoma of colon [1], breast [1], endometrium [1], and ovary [1]; and omental metastasis of carcinoma of uterus or ovary [10]).

Conclusions.—PAX-2 is a sensitive and specific marker for metastatic RCC. The diagnostic yield would be marginally increased by adding RCCM, but not KSC, as an immunomarker.
International Normalized Ratio Versus Plasma Levels of Coagulation Factors in Patients on Vitamin K Antagonist Therapy
Authors: Gulati Gene , Hevelow Megan , George Melissa , Behling Eric , Siegel Jamie
Published: February 2021

Context.—The key question when managing patients on warfarin therapy who present with life-threatening bleeding is how to use the international normalized ratio (INR) to best direct corrective therapy. The corollary question for the clinical laboratory is at what level will the INR reflect a critical value that requires notifying the clinician.

Objective.—To determine the levels of vitamin K–dependent factors over a range of INR values.

Design.—Evaluation of the vitamin K–dependent coagulation factor levels on plasma remnants from patients in whom a prothrombin time and INR was ordered to monitor warfarin therapy. There were a total of 83 specimens evaluated with an INR range from 1.0 to 8.26.

Results.—The mean activity levels of all 4 factors remained near or above 50% when the INR was less than 1.5. The average factor X level was 23% when the INR range was 1.6 to 2.5, but levels of factors II, VII, and IX did not drop below the hemostatic range until the INR was greater than 2.5. At an INR of 3.6 or more, the activity levels of all 4 factors were less than 30% in more than 90% of the specimens.

Conclusion.—Levels of factors II, VII, IX, and X declined with increasing INR but not at the same rate and not to the same level at a given INR. However, most of the values were below the hemostatic value once the INR was 3.6 or more, the level that was also considered critical for physician notification.
Granulomatous Inflammation—An Underestimated Cause of False-Positive Diagnoses in Lung Fine-Needle Aspirates: Observations From the College of American Pathologists Nongynecologic Cytopathology Interlaboratory Comparison Program
Authors: Auger Manon , Moriarty Ann T. , Laucirica Rodolfo , Souers Rhona , Chmara Beth Anne , Fatheree Lisa A. , Wilbur David C.
Published: February 2021

Context—The false-positive rate for fine-needle aspirates of the lung has been cited as less than 1% for granulomatous inflammation, comprising one of the known causes of false-positive diagnoses.

Objective—To determine the rate of false-positive diagnoses of granulomatous inflammation for lung fine-needle aspirates by assessing the false-positive response rate in the context of the College of American Pathologists Nongynecologic Cytopathology Interlaboratory Comparison Program.

Design—We performed a retrospective review of 1092 participant responses for lung fine-needle aspirate challenges with the reference diagnosis of specific infections/granulomatous inflammation from 1998 to 2008 from the College of American Pathologists Nongynecologic Cytopathology Interlaboratory Comparison Program. False-positive rates by participant type (pathologist versus cytotechnologist), general diagnosis category, reference diagnosis, and preparation type were analyzed for the pathologists' responses.

Results—Of the 502 general category responses for pathologists, 428 (85.3%) were benign, 55 (11%) were malignant, and 19 (3.8%) were suspicious. There was no difference in the false-positive rate between preparations (P  =  .76) or participants (P  =  .39). Of those responses by pathologists that were benign, only 68.7% (292 of 425) were an exact match to granulomatous inflammation. Non–small cell carcinoma, adenocarcinoma, and squamous carcinoma represented 64% of false-positive/suspicious responses, while small cell carcinoma and carcinoid comprised 13%.

Conclusion—In an interlaboratory comparison program, granulomatous inflammation represents an important cause of false-positive/suspicious responses in lung fine-needle aspirates (14.8%) and is much higher than false-positive rates reported historically in clinical studies. These results highlight the importance of granulomatous inflammation as a mimic of carcinoma.
Reliability and Reproducibility of the Edmondson Grading of Hepatocellular Carcinoma Using Paired Core Biopsy and Surgical Resection Specimens
Authors: Pirisi Mario , Leutner Monica , Pinato David J. , Avellini Claudio , Carsana Luca , Toniutto Pierluigi , Fabris Carlo , Boldorini Renzo
Published: February 2021

Context—It has been claimed that the Edmondson and Steiner grading system (EGS) values should be obtained preoperatively to select patients with hepatocellular carcinoma for liver transplantation. However, EGS reliability in biopsy specimens has been questioned.

Objective—To verify the reliability of the EGS using core biopsy specimens and its reproducibility among pathologists.

Design—Paired biopsy and surgical specimens obtained from 40 patients (subset 1) were retrieved by means of computer-aided search of the pathology records and blindly and independently reviewed. The EGS interrater agreement was measured using κ statistics. After having held a consensus meeting, pathologists graded an additional 21 paired hepatocellular carcinoma specimens (subset 2).

Results—Analyzing subset 1, pathologists gave significantly lower EGS grades to the biopsy specimens (P < .001), for which the observed agreement was 32.5% (κ  =  0.021), which increased to 82.5% (κ  =  0.186) if only 2 categories were considered (low grade, EGS I–II; high grade, EGS III–IV). The observed agreement in the case of the surgical specimens was 52.5% (κ  =  0.199), which increased to 62.5% (κ  =  0.275) when the low- and high-grade scores were merged. The observed agreement between the assessments of paired biopsy and surgical specimens was 50.0% for pathologist 1 (κ  =  0.057) and 35.0% for pathologist 2 (κ  =  0.078). Merging the EGS grades did not improve the strength of the agreement. Analyzing subset 2 (after the consensus meeting), the observed agreement between pathologists improved more on biopsies (76.2%, κ  =  0.614) than on surgical specimens (61.9%, κ  =  0.434).

Conclusions—The EGS is easily underestimated in core biopsy specimens, and interrater disagreement between pathologists can be significant unless consensus meetings are held.
Sarcomatoid Carcinoma of Esophagus
Authors: Raza Muhammad Adeel , Mazzara Paul F.
Published: February 2021

Sarcomatoid carcinoma of the esophagus is an uncommon malignancy, representing approximately 2% of esophageal carcinomas. It has also been referred to as carcinosarcoma, pseudosarcoma, pseudosarcomatous squamous cell carcinoma, spindle cell carcinoma, and polypoid carcinoma, reflecting the uncertainty of its pathogenesis. Histologically, carcinomatous and sarcomatous components coexist. The clinical and radiologic findings resemble other esophageal neoplasms. Sarcomatoid carcinoma often presents as a large, intraluminal, polypoid mass on barium esophagram. Despite its size, however, sarcomatoid carcinoma has a more favorable prognosis than other malignant esophageal neoplasms, likely because of its exophytic growth into the lumen, rather than deep invasion. This article provides a brief overview of the clinicopathologic features and possible pathogenesis of this uncommon tumor.