Severe Drug-Induced Liver Injury Due to Self-administration of the Veterinary Anthelmintic Medication, Fenbendazole.

Fenbendazole is an anthelmintic agent approved for veterinary applications. Even though it is not approved by the US Food and Drug Administration for human use, such use appears to be increasing due to the popularization of fenbendazole's potential anticancer effects by social media. We describe the first case of histologically confirmed severe drug-induced liver injury, hepatocellular pattern, associated with the self-administration of fenbendazole in a 67-year-old woman who presented with 2 weeks of jaundice. Liver function tests normalized in 3 months after the cessation of fenbendazole.

Estrogen Receptor, Progesterone Receptor, and Human Epidermal Growth Factor Receptor 2 Expression Rates in Invasive Breast Carcinoma: A Study of 21 Institutions.

CONTEXT.­: Laboratories performing predictive marker testing for breast carcinoma are encouraged to compare patient results to published benchmarks. OBJECTIVE.­: To collect expression rates for estrogen receptor (ER), progesterone receptor (PgR), and human epidermal growth factor receptor 2 (HER2) in invasive breast carcinoma from multiple laboratories. DESIGN.­: Participants submitted data from up to 50 primary cases during the study period. Participants reported ER, PgR, and HER2 results in addition to demographic and histologic information. Participants also provided annual institution-level expression rates. RESULTS.­: A total of 21 institutions submitted data for 687 cases. Aggregate positivity rates for ER and PgR were 85.6% and 75.1%, respectively. Receptor positivity rates were higher in well-differentiated (grade 1) tumors (ER, 97.4%; PgR, 88.0%) compared with moderately differentiated (grade 2) tumors (ER, 92.4%; PgR, 84.0%) and poorly differentiated (grade 3) tumors (ER, 61.8%; PgR, 48.0%). Expression rates were higher in postmenopausal women (ER, 87.2%) than premenopausal women (ER, 79.6%) and higher in lobular carcinomas (ER, 98.7%; PgR, 85.3%) than ductal carcinomas (ER, 84.1%; PgR, 74.5%). The aggregate HER2 positivity (score 3+) rate was 9.0%. The aggregate HER2 equivocal (score 2+) rate was 14.5%. Of 81 equivocal (score 2+) cases, 70 (86.4%) were nonamplified. CONCLUSIONS.­: The data from this study provide multi-institutional benchmark data to assist laboratories performing periodic comparisons as part of a quality management program. Overall expression rates were generally similar to those of other published reports, with the exception of the ER-negative and HER2-positive rates, both of which were somewhat lower.

Sensitivity and Specificity of a Novel Colony Characteristic for Determination of Methicillin-Resistant Staphylococcus aureus.

PURPOSE: To assess colony morphology of Staphylococcus aureus isolates for target shape (T1) and its utility in the identification of methicillin-resistant S. aureus (MRSA). METHODS: Staphylococcus species isolated from blood cultures were studied for colony morphology characteristics. A polymerase chain reaction (PCR) test was performed on positive blood culture bottles for the detection of S. aureus and methicillin resistance. Colony morphology was read at 24 and 48 hours and defined as follows: target shaped (T1) - an elevated colony center encircled by a pale zone, which is surrounded by a single ring of peripheral enhancement giving a 'target' appearance; dome-shaped (T2) with an elevated center lacking the 'target' appearance. RESULTS: At 48 hours, 73.7% of MRSA and 59.5% of coagulase-negative staphylococci (CoNS) showed T1 morphology. T1 morphology has a sensitivity of 73.68% and specificity of 93.55% amongst S. aureus for identification of methicillin resistance and a high positive predictive value (95.45%) at 48 hours. CONCLUSION: T1 morphology has a modest sensitivity with specificity and positive predictive value amongst S. aureus for identification of methicillin resistance at 48 hours. It can be potentially used for the identification of MRSA, especially in resource-limited settings and wherein a molecular test is not repeated if PCR testing has already identified methicillin-sensitive S. aureus (MSSA) on a recent specimen on the same patient.

Impact of Liver Biopsy Size on Histopathologic Evaluation of Liver Allograft Rejection.

CONTEXT.­: Allograft liver biopsy is the gold standard in assessing transplant recipients for graft dysfunction. The impact of biopsy sample size on the diagnosis of acute cellular rejection (ACR) has not been studied. OBJECTIVE.­: To assess the relationship of biopsy sample length with the diagnosis and determine optimal biopsy sample size in the transplant setting. DESIGN.­: We retrospectively reviewed 68 core biopsies from patients with a history of liver transplant. Each biopsy sample was read, on 5 different occasions with differing lengths, to assess for ACR per Banff criteria. Categorical agreement was calculated from rejection severity. RESULTS.­: The length of biopsy sample strongly correlated with the number of portal tracts. ACR rates increased from 73.5% to 79.4% with increase in length from 1 cm to 2 cm, and moderate rejection increased from 27.9% to 33.82%. At 1.0 and 1.5 cm, no cases of severe rejection were detected; at 2.0 cm, 1 case was detected; and at 3.0 cm, 2 cases were detected. The major error rate was reduced to less than 10% with a length of 2.0 cm, at which length the average number of complete and partial portal triads was 10 and 13, respectively. CONCLUSIONS.­: The likelihood of diagnosing ACR and rejection grade increased substantially with increase in biopsy sample length. This study suggests that a minimum length of 2 cm, 10 complete portal triads, or 13 partial/complete portal triads should be obtained for confident exclusion and grading of ACR.

Detection of Corynebacterium kroppenstedtii in Granulomatous Lobular Mastitis Using Real-Time Polymerase Chain Reaction and Sanger Sequencing on Formalin-Fixed, Paraffin-Embedded Tissues.

CONTEXT.­: Associations between granulomatous lobular mastitis (GLM) and Corynebacterium kroppenstedtii have been reported since 2002, but large-scale studies to assess the actual prevalence of this bacterium in GLM have not been performed. OBJECTIVE.­: To assess the prevalence of C kroppenstedtii in GLM using real-time polymerase chain reaction and Sanger sequencing. DESIGN.­: We analyzed formalin-fixed, paraffin-embedded tissues from 67 cases of GLM by sequential DNA amplification and sequencing to assess the rate of C kroppenstedtii detection in GLM. A retrospective analysis including patient demographics, history of pregnancy and lactation, clinical signs and symptoms, radiographic findings, histologic pattern, Gram stain results, and microbial cultures was performed on 67 cases of GLM. In addition, 10 cases of nongranulomatous breast abscess were included as controls. RESULTS.­: C kroppenstedtii 16S rRNA SYBR real-time polymerase chain reaction was positive on formalin-fixed, paraffin-embedded tissues from 46 of 67 (68.7%) GLM cases, while all control cases were negative. Among the positive cases, the majority showed features of cystic neutrophilic granulomatous mastitis. CONCLUSIONS.­: C kroppenstedtii was highly prevalent in GLM cases and was not found to be associated with nongranulomatous breast abscess in our study (P < .001).

Correlation of cerebellar granular layer autolysis with ante-mortem systemic acid-base status.

Research in neuroscience relies heavily upon postmortem human brain tissue. Cerebellar granular layer autolysis (GLA) is a surrogate marker for the quality of such tissue and suitability for molecular analysis. GLA is associated with reduced brain tissue pH. The aim of this study was to assess correlation of GLA with premortem systemic acid-base status. This is a retrospective study in which 62 consecutive adult autopsy cases were included. Sections of cerebellum were reviewed microscopically for presence of GLA. Autolysis was graded as negative, grade 1, grade 2, and grade 3. Medical records were reviewed for arterial blood gas analysis. Postmortem interval was recorded. 23 of 62 cases showed GLA. Of the 23 patients with autolysis, 22 were acidotic and 1 was alkalotic. Of these 23 cases, 15 had metabolic acidosis, 4 had respiratory acidosis, 3 had combined acidosis and 1 had respiratory alkalosis. There was no statistically significant difference in postmortem interval between the two groups. 10 cases with grade 3 autolysis had mean pH of 7.13, 7 cases with grade 2 autolysis had mean pH of 7.23 and in 6 cases with grade 1 autolysis the mean pH was 7.2. Overall, the mean pH in patients with GLA was 7.19, and in the non-autolytic cases the mean pH was 7.28 (P < 0.05). There was no correlation between the degree of acidosis and severity of autolysis. GLA is associated with premortem systemic acidosis, and premortem systemic alkalosis is associated with the absence of GLA. Premortem acid-base status may serve as an additional quality indicator for assessment of tissue for research.

Accuracy of Intraoperative Frozen Section in Detection of Acute Invasive Fungal Rhinosinusitis.

CONTEXT.­: Acute invasive fungal rhinosinusitis (AIFRS) is an aggressive form of fungal sinusitis, which remains a significant cause of morbidity and mortality. Early diagnosis and intervention are keys to improving patient outcomes. Intraoperative consultation has shown promise in facilitating early surgical intervention, but the accuracy of frozen section has not been clarified in this setting. OBJECTIVES.­: To assess the accuracy of frozen-section diagnosis in patients with clinically suspected AIFRS. DESIGN.­: All cases of clinically suspected AIFRS during a 10-year period (2009-2019) were retrospectively reviewed. The frozen-section results were compared with the final permanent sections as well as the tissue fungal culture results, following which the accuracy of frozen section was determined. RESULTS.­: Forty-eight patients with 133 frozen-section evaluations for AIFRS were included in the study. Thirty of 48 patients and 61 of 133 specimens were positive for AIFRS on final pathology. Of 30 positive patients, 27 (90%) had at least 1 specimen diagnosed as positive during intraoperative consultation; among the 61 positive specimens, 54 (88.5%) were diagnosed as positive during intraoperative consultation. Of 72 negative specimens, all were interpreted as negative on frozen section. Thus, frozen sections had a sensitivity of 88.5% (95% CI, 0.78-0.97), specificity of 100% (95% CI, 0.94-1), positive predictive value of 100% (95% CI, 0.92-1), and negative predictive value of 90.6% (95% CI, 0.82-0.97). CONCLUSIONS.­: This study represents the largest series assessing the diagnostic accuracy of frozen section analysis in AIFRS. These findings are useful in frozen section-informed intraoperative decision making.

Histopathologic findings in culture-positive secondary osteomyelitis.

As peripheral vascular disease and diabetes mellitus are increasingly common, chronic wounds are often seen. Bone biopsies, with imaging and microbial cultures, are often obtained to evaluate for osteomyelitis. Because much of the historical literature describing the histology of osteomyelitis pertains to primary osteomyelitis, this study characterizes the histologic findings and provides correlation with culture results in secondary osteomyelitis. The histologic features of bone biopsies were assessed over a 5 year period. Concurrent laboratory and radiographic data were obtained and these data were compared with culture results. This study included 163 cases, of which 104 were culture-positive osteomyelitis. All culture-positive cases had been present longer than 28 days and had at least one of the following histologic features: neutrophilic inflammation, plasmacytic inflammation, or eosinophilic fibrosis. However, none of these findings were restricted to culture-positive cases. Overall, plasmacytic and neutrophilic inflammation provided similar specificity, and positive predictive values for osteomyelitis. Medullary fibrosis gave a sensitivity of 95%, the highest for any single feature, and the combination of fibrosis and neutrophilic inflammation had the greatest specificity of 96%. Additionally, neutrophilic inflammation correlated often with isolation of Staphylococcus aureus, while plasma cell predominance was found more frequently with other infectious agents. This study describes histologic features in secondary osteomyelitis, which may challenge the widespread inclination to equate a neutrophilic inflammation with 'acute osteomyelitis' and 'chronic osteomyelitis' with one rich in plasma cells. We report an early correlation between common histopathologic findings and specific culture isolates, which can be further refined with additional research.

Peripheral Blood Examination Findings in SARS-CoV-2 Infection.

OBJECTIVES: Peripheral blood abnormalities in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have not been fully elucidated. We report qualitative and quantitative peripheral blood findings in coronavirus disease 2019 (COVID-19) patients and compare them with a control group. METHODS: We reviewed electronic medical records, complete blood counts, peripheral blood smears, and flow cytometry data in 12 patients with SARS-CoV-2. These were compared with 10 control patients with symptoms suspicious for SARS-CoV-2 but who tested negative. RESULTS: No significant differences were noted in blood counts, except that absolute lymphopenia was present frequently in the control group (P < .05). Acquired Pelger-Huët anomaly (APHA) was noted in all COVID-19 cases, in most cases affecting over 5% of granulocytes. This contrasted with APHA in only 50% of control cases, affecting fewer than 5% of granulocytes in all cases (P < .05). Monolobate neutrophils were exclusive to COVID-19 cases. COVID-19 patients had greater frequency of plasmacytoid lymphocytes (P < .05). Flow cytometry data revealed absolute CD3+ T-cell count reduction in 6 of 7 patients; all of them required mechanical ventilation. CONCLUSIONS: Lymphopenia was infrequent in our COVID-19 cohort; however, flow cytometric analysis revealed absolute T-cell count reduction in most cases. COVID-19 cases had significant APHA with monolobate neutrophils and plasmacytoid lymphocytes as compared to controls.

The impact of C4d testing on tissue adequacy in lung transplant surveillance.

BACKGROUND: Surveillance transbronchial biopsies are routinely used to assess lung allograft rejection. While the criteria for diagnosing acute cellular rejection have been well-established, the morphological findings associated with antibody mediated rejection are variable. To increase the sensitivity for antibody mediated rejection, a portion of a biopsy can be used for C4d immunofluorescence testing, along with histologic findings and donor specific antibodies. When the number of alveolar pieces in a biopsy is small, the relative utility of sending one piece for C4d testing is unclear. METHODS: Pathology reports of 1400 surveillance transbronchial lung biopsies from 2008 to 2017 were reviewed to obtain the number of pieces of alveolar parenchyma in each case. Based on a standard definition of adequacy as five pieces of well-expanded alveolar parenchyma, reports with five fragments were grouped as "adequate", four pieces as a "marginal" sample, and three or less were considered an "inadequate" sample. RESULTS: Of the 1400 biopsies, 653 specimens had 5 or more pieces of alveolar parenchyma.747 specimens were submitted with less than 5 pieces and 290 of those were considered marginal. In all marginal cases, a piece was withheld for C4d immunofluorescence testing. CONCLUSIONS: About 21% of specimens would have the recommended 5 pieces of alveolar parenchyma if not for the withholding of pieces for C4d IF testing. Over the span of 10 years, 290 such cases were recorded at our institution. Given this nontrivial impact, it is unclear if C4d immunofluorescence testing should be performed on surveillance transbronchial biopsies when the number of pieces in the specimen is marginal.

Histopathologic Patterns of Colitis in Patients With Impaired Renal Function.

OBJECTIVES: To characterize the histopathologic features of colitis in patients with impaired renal function. METHODS: We retrospectively identified 413 patients who underwent colonoscopic evaluation for colitis between 2011 and 2015. Patients were divided into four groups based on estimated glomerular filtrate rates. Patients with impaired renal function were compared to overall and age-matched patients with normal renal function. RESULTS: Compared to a preponderance of inflammatory bowel disease (33%) and lymphocytic colitis (9.6%) in patients with normal renal function, ischemic colitis (58%) was the predominant histopathologic pattern in the patients with impaired renal function. Infectious colitis was the second most common pattern (20.8%), with Clostridium difficile and cytomegalovirus infections being more frequent. Medication-induced injury was the third most common pattern, with crystal-associated injury being the exclusive pattern found in this study. CONCLUSIONS: Colitis in patients with impaired renal function is etiologically distinct from that seen in patients with normal renal function.

Diagnosis of Papillary Breast Lesions on Core Needle Biopsy: Upgrade Rates and Interobserver Variability.

The histologic distinction between papillary breast lesions remains challenging, especially with core biopsy (CB) specimens. A retrospective review of the clinical, imaging, and histologic findings was performed for patients with papillary breast lesions on CB from 2013 to 2017. The interpretation accuracy was expressed as upgrade rate relative to the excision diagnosis. Diagnostic reproducibility with and without immunohistochemistry was analyzed as interobserver variability among 3 board-certified pathologists. Among 57 papillary lesions with biopsies and excisions available for review, the upgrade rates were 0% for benign papilloma, 30% for papilloma with atypical ductal hyperplasia, and 25% for papilloma with ductal carcinoma in situ, resulting in an overall upgrade rate of 11.1%. There were no statistical differences between patients in an upgrade group and others, when comparing the patient age, clinical presentation, BI-RADS (Breast Imaging Reporting and Database System) category, location, and histologic grade. The overall interobserver variability of the 60 consecutive core biopsies of papillary breast lesions by morphology alone was in the "substantial" agreement range (κ = 0.79, 86% agreement), with an excellent κ score of 0.88 for papilloma (92% agreement). "Substantial" and "fair" κ values were seen for papilloma with atypical ductal hyperplasia/ductal carcinoma in situ (0.74, 84% agreement) and invasive carcinoma (0.40, 60% agreement). Use of immunohistochemical stains improved the κ values into "excellent" range (0.92, 94% agreement). Our study favors a conservative approach in the management of benign papillomas, at least in cases of good radiologic-pathologic concordance. Papillary breast lesions with atypia/malignancy show lower diagnostic reproducibility on CB, and utility of immunohistochemistry is recommended in challenging cases.

Trends in Thyroid Fine-Needle Aspiration Cytology Practices: Results From a College of American Pathologists 2016 Practice Survey.

CONTEXT.­: The College of American Pathologists periodically surveys laboratories to determine changes in cytopathology practices. We report the results of a 2016 survey concerning thyroid fine-needle aspiration (FNA). OBJECTIVE.­: To provide a cross-sectional survey of thyroid cytology practices in 2016. DESIGN.­: In 2016, a survey was sent to 2013 laboratories participating in the College of American Pathologists Non-Gynecologic Cytology Education Program (NGC-A) requesting data from 2015-2016 on several topics relating to thyroid FNA. RESULTS.­: A total of 878 laboratories (43.6% of 2013) replied to the survey. Radiologists performed the most thyroid FNA procedures in most laboratories (70%; 529 of 756), followed by endocrinologists (18.7%; 141 of 756), and most of these were performed under ultrasound guidance (92.1%; 699 of 759). A total of 32.6% of respondents (251 of 769) provided feedback on unsatisfactory rates for nonpathology providers who performed FNA. Intraprocedural adequacy assessment was primarily performed by attending pathologists (77.4%; 490 of 633) or cytotechnologists (28.4%; 180 of 633). Most laboratories used the Bethesda System for Reporting Thyroid Cytopathology (89.8%; 701 of 781) and performed molecular testing based on clinician request (68.1%; 184 of 270) rather than FNA diagnosis. Correlation of thyroid excisions with prior cytology results most often occurred retrospectively (38.4%; 283 of 737) and was used for pathologist interpretive quality assurance purposes. CONCLUSIONS.­: These survey results offer a snapshot of national thyroid FNA cytology practices in 2016 and indicate that standardized cytology terminology is commonly used; pathologists perform most immediate adequacy assessments for thyroid FNA; laboratories use correlation statistics to evaluate pathologists' performance; and molecular tests are increasingly requested for indeterminate interpretations, but reflex molecular testing is rare.

Sensitivity and Specificity of Alzheimer Type II Astrocytes in Hepatic Encephalopathy.

CONTEXT.­: Hepatic encephalopathy (HE) is associated with presence of type II astrocytes in the brain on the basis of observations made in single uncontrolled cases. This finding was subsequently demonstrated by in vitro studies with replication of microenvironment of HE by increase in ammonia levels. However, no human studies have been done correlating HE with type II astrocytes. OBJECTIVE.­: To determine the sensitivity and specificity of type II astrocytes in HE. DESIGN.­: This is a retrospective cohort study in which cases and controls were included. A database search was conducted to identify potential cases of hepatic encephalopathy during a 3-year period, as well as concomitant cases with altered mental status from other causes, liver disease, both, and neither. The presence of HE was determined according to standard clinical criteria, and a coronal section of basal ganglia was selected for examination from each case. Type II astrocytes were enumerated over 20 random high-power fields (HPFs). RESULTS.­: Twenty-one patients with HE were identified, with 35 patient controls (18 females, 38 males). Among the patients with HE there was a mean of 19.8 type II astrocytes in 20 HPFs. Patients with altered mental status without HE had an average of 7.2 type II astrocytes per 20 HPFs, and for those without altered mental status, the average was 2.8. For patients with hepatic insufficiency without HE, the average was 11, while for patients with normal hepatic function, the average was 4.1. Overall, for those without HE, the average was 5.4 type II astrocytes per 20 HPFs. CONCLUSIONS.­: At a cutoff of 5 or more type II astrocytes per 20 HPFs, sensitivity for HE was 85.7% and specificity was 68.6%. Alzheimer type II astrocytes were present in all cases of HE but were also present in a wide variety of patients without HE.

Idiopathic Granulomatous Mastitis: Manifestations at Multimodality Imaging and Pitfalls.

Idiopathic granulomatous mastitis (IGM) is a rare benign inflammatory breast entity characterized by lobulocentric granulomas. IGM has a persistent or recurrent disease course and affects parous premenopausal women with a history of lactation. It has also been associated with hyperprolactinemia. The most common clinical sign is a palpable tender mass. However, the nonspecific manifestations and varied demographic features of this condition, as well as the other similar-appearing and superimposed breast entities, pose substantial diagnostic challenges. Entities with similar manifestations include inflammatory breast cancer (IBC), infective mastitis, foreign body injection granulomas, mammary duct ectasia, diabetic fibrous mastopathy, and systemic granulomatous processes. The strategy for imaging IGM depends on patient age, clinical manifestations, and risk factors. Targeted ultrasonography, mammography, and less commonly, magnetic resonance imaging have proven to be useful for imaging evaluation. Core-needle biopsy, with or without fine-needle aspiration for cytopathologic examination, and culture analysis are usually required to exclude IBC and other benign inflammatory breast processes. Patients with IGM have an excellent prognosis when they are appropriately treated with oral steroids or second-line immunosuppressive and prolactin-lowering medications. However, surgical excision may be an option for patients in whom medication therapy is unsuccessful. Imaging surveillance can be offered to patients with incidentally encountered IGM or mild symptoms. Clinical suspicion for this rare disease and the breast imager's prompt diagnosis can lead to an improved patient outcome. The purpose of this article is to review the imaging manifestations of IGM in a multimodality case-based format and to describe relevant clinical and imaging-based differential diagnoses. The associated pitfalls, epidemiologic and histopathologic factors, clinical manifestations, natural course, and management of IGM also are discussed. ©RSNA, 2018.