National pilot of entrustable professional activities in pathology residency training.

Entrustable professional activities (EPAs) are observable clinical skills and/or procedures that have been introduced into medical education at the student and resident levels in most specialties to determine readiness to advance into residency or independent practice, respectively. This publication describes the process and outcomes of a pilot study looking at the feasibility of using two anatomic pathology and two clinical pathology EPAs in pathology residency in 6 pathology residency programs that volunteered for the study. Faculty development on EPAs and their assessment was provided to pilot program faculty, and EPA assessment tools were developed and used by the pilot programs. Pre- and post-study surveys were given to participating residents, faculty, and program directors to gauge baseline practices and to gather feedback on the EPA implementation experience. Results demonstrated overall good feasibility in implementing EPAs. Faculty acceptance of EPAs varied and was less than that of program directors. Residents reported a significant increase in the frequency with which faculty provided formative assessments that included specific examples of performance and specific ways to improve, as well as increased frequency with which faculty provided summative assessments that included specific ways to improve. EPAs offered the most benefit in setting clear expectations for performance of each task, for providing more specific feedback to residents, and in increasing Program director's understanding of resident strengths abilities and weaknesses.

Melanocytic Nevus of the Superior Conjunctival Fornix: A Case Report.

Introduction: Conjunctival nevi are benign tumors that are commonly located at the nasal or temporal limbus and rarely in the fornix or tarsus. We report a case of a patient presenting with a solitary compound cystic nevus of the conjunctival fornix in the background of bilateral complexion-associated melanosis. Case Presentation: A 71-year-old African-American female was referred for evaluation of an incidentally noted melanocytic lesion of the right conjunctival fornix. The patient underwent an excisional biopsy, revealing histological features consistent with a compound cystic nevus. Conclusion: This finding is noteworthy due to the rarity of conjunctival nevi originating in the fornix. The case underscores the importance of excisional biopsy in evaluating conjunctival forniceal melanocytic lesions to exclude malignant melanoma, a critical consideration for prognosis.

Multisite Quality Improvement Study of a Patient-Pathologist Consultation Program.

OBJECTIVES: The aim of this multisite quality improvement study was to evaluate patients' experiences with the patient-centered pathology (PCP) consultation program and to determine whether PCP enhanced their care experience. METHODS: Patients were invited to attend PCP consultations to review their pathology report and slides and have their questions answered by the pathologist privately, with the option to attend the appointment with family members or friends for support. A patient experience questionnaire (PEQ) was administered to patients, who participated voluntarily in the PCP, and survey data were collected and stored in REDCap. Statistical analysis was performed using SAS 9.4 (SAS Institute). RESULTS: Sixty-seven patients (95.5% female) aged 18 to 84 years across 4 institutions completed the PEQ. Overall, 58% and 15.8% of patients had breast and brain tumors, respectively, and 59.7% of tumors were newly diagnosed. Most patients thought it was important for them to learn as much as they could about their health condition. However, the majority of patients reported some degree of difficulty learning about their health condition based on written information, despite 97% having completed high school and/or further education. The majority of patients rated their pathologist as "excellent" across communication metrics. Ultimately, 100% of respondents were satisfied, found their visits to be useful, and would recommend the PCP to other patients. CONCLUSIONS: Patients found that personalized clinical encounters with pathologists improved their understanding of their health condition and their satisfaction with their care experience. Patients thought pathologists communicated respectfully, effectively, and empathetically.

Eosinophilic globules in a classic ependymoma: evidence of a possible secretory role.

A number of neoplasms of the central nervous system can demonstrate diffuse eosinophilic globules, known to be secretory products of the corresponding cell type, but they have not been a salient feature in descriptions of classic ependymoma. Here, we present a case of a posterior fossa ependymoma demonstrating glassy PAS-positive, diastase-resistant, eosinophilic globules with light microscopic and ultrastructural features resembling Reissner fiber, the secretory product of the subcommissural organ. While there has been a single published description of an ependymoma with intra- and extracellular granulofibrillary material suggested to be evidence of secretory differentiation, ours is the first case to demonstrate diffuse eosinophilic globules in an ependymoma. The extent of globules allowed full study by electron microscopy to provide new insight into the secretory material and the surrounding structures. Our findings suggest that neoplastic ependymal cells can recapitulate the secretory capacity of the subcommissural organ.

Autograft-derived spinal cord mass in the cervical spine following transplantation with olfactory mucosa cells for traumatic spinal cord injury: case report.

This study describes a patient with an autograft-derived spinal cord mass following transplantation of olfactory mucosa for treatment of cervical spine injury. The authors report the case of a 35-year-old man who suffered a complete spinal cord injury (SCI) at C5-6 in 2001. The patient underwent an olfactory mucosal cell implantation at the location of injury 4 years following initial trauma. Twelve years later, the patient presented with rapidly progressive decline in upper-extremity function as well as neuropathic pain. Imaging revealed a heterogeneously enhancing intramedullary mass from C3 to C7. At surgery, the patient was found to have a posttransplant mucinous mass. Each mucinous cyst was drained and a portion of the cyst wall was removed. Histological examination demonstrated ciliated epithelium-lined fibrous tissue, submucosal glands, and mucoid material, consistent with a transplant-derived tumor. This case report both documents a rare long-term complication of olfactory mucosal cell transplantation and serves as a cautionary tale encouraging prudent use of novel treatments in a vulnerable population of patients with severe SCI.

Genomic Profiling of Circulating Tumor DNA From Cerebrospinal Fluid to Guide Clinical Decision Making for Patients With Primary and Metastatic Brain Tumors.

Despite advances in systemic therapies for solid tumors, the development of brain metastases remains a significant contributor to overall cancer mortality and requires improved methods for diagnosing and treating these lesions. Similarly, the prognosis for malignant primary brain tumors remains poor with little improvement in overall survival over the last several decades. In both primary and metastatic central nervous system (CNS) tumors, the challenge from a clinical perspective centers on detecting CNS dissemination early and understanding how CNS lesions differ from the primary tumor, in order to determine potential treatment strategies. Acquiring tissue from CNS tumors has historically been accomplished through invasive neurosurgical procedures, which restricts the number of patients to those who can safely undergo a surgical procedure, and for which such interventions will add meaningful value to the care of the patient. In this review we discuss the potential of analyzing cell free DNA shed from tumor cells that is contained within the cerebrospinal fluid (CSF) as a sensitive and minimally invasive method to detect and characterize primary and metastatic tumors in the CNS.

Post-traumatic superior oblique tendon nodule associated with acquired Brown syndrome.

A 67-year-old woman presented with a left hypotropia and eye pain after a traumatic fall. She had multiple left orbital wall fractures and an acquired limitation to elevation in all gazes, worse in adduction, suggestive of Brown syndrome. During strabismus surgery, a white nodule on the superior oblique tendon was identified and excised. Histopathology of the nodule revealed densely aggregated inflamed fibrovascular and fibrocollagenous scar tissue. Superior oblique rupture with spontaneous reparative reapproximation resulting in nodular formation is uncommon. We speculate that resulting tendon shortening may have contributed to the apparent Brown syndrome in this patient.

Heritable spina bifida in sheep: A potential model for fetal repair of myelomeningocele.

BACKGROUND/PURPOSE: In 2004, a heritable occurrence of spina bifida was reported in sheep on a farm in the United States. We maintained and characterized the spina bifida phenotype in this flock to assess its potential as an alternative surgical model. METHODS: A breeding strategy was developed in which the sheep were crossed to maintain or increase the occurrence of spina bifida. Measurements and observations were recorded regarding lesion size, birthweight, ambulatory capacity, or urological function, and necropsies were performed on spina bifida afflicted lambs in conjunction with magnetic resonance imaging to determine the character of the spina bifida defects and assess the presence of Chiari-like malformations or hydrocephalus. RESULTS: The defects were observed to be more prevalent in ram lambs, and the rate of spina bifida per litter could be increased through backcrossing or by selection of a productive ewe breed. The lambs displayed a range of ambulatory and urological deficits which could be used to evaluate new fetal repair methodologies. Finally, affected lambs were shown to demonstrate severe Chiari malformations and hydrocephalus. CONCLUSIONS: We have determined that use of these sheep as a natural source for spina bifida fetuses is feasible and could supplement the deficits of current sheep models for myelomeningocele repair. LEVEL OF EVIDENCE: Level IV.

Periocular Histiocytoid Carcinoma: Potential Diagnostic Challenges.

Cutaneous histiocytoid carcinoma can occur as a primary tumor of the periocular region. Morphologically similar histiocytoid carcinomas arising as primary tumors of the breast have a predilection for orbital metastases. They can occasionally contain regions with prominent vacuolated cytoplasm and minimal nuclear atypia, which mimic benign histiocytic lesions. Differentiating nonneoplastic, primary neoplastic, and metastatic histiocytoid lesions involving the periorbita can be challenging for both the clinician and the pathologist, and this distinction has management implications. Herein, we present 3 cases to illustrate the challenges of diagnosing periocular histiocytoid carcinoma.

Ectopic Ocular Surface Calcification in Patients With Hypophosphatasia Treated With Asfotase Alfa.

PURPOSE: To assess for ectopic ocular calcification in a series of patients with hypophosphatasia (HPP) treated with asfotase alfa, a recombinant tissue-nonspecific alkaline phosphatase. METHODS: This is a retrospective analysis of subjects enrolled at Duke University Medical Center in ENB-009-10 (ClinicalTrials.gov: NCT01163149), a randomized controlled trial of asfotase alfa in adolescents and adults with HPP. Seven patients between the ages of 45 and 66 years diagnosed with HPP based on clinical features and low serum alkaline phosphatase levels were enrolled at our site. Subjects were randomized to receive either daily subcutaneous injections of asfotase alfa or no treatment. After 24 weeks, during the open-label extension phase, all subjects received treatment for at least 4 years. All subjects underwent comprehensive eye examinations at baseline and at 24-week intervals throughout the study to assess for development of ocular calcifications. RESULTS: By week 120, all 7 subjects developed asymptomatic white refractile deposits in the interpalpebral perilimbal conjunctiva. Biopsy of the conjunctival lesions in 2 subjects revealed elastosis with subepithelial calcification. The lesions were nonprogressive and in 5 subjects exhibited some degree of regression. CONCLUSIONS: Asfotase alfa was invariably associated with development of mild focal conjunctival calcification, likely through disinhibition of hydroxyapatite crystal propagation. The calcifications were not symptomatic or vision-threatening and should not preclude enzyme replacement therapy for patients with this rare and often debilitating disease.

Comparison of Optical Coherence Tomography With Fundus Photographs, Fluorescein Angiography, and Histopathologic Analysis in Assessing Coats Disease.

Importance: Coats disease is a rare pediatric vitreoretinopathy that can cause devastating visual and anatomic outcomes. Objective: To compare optical coherence tomography (OCT) with fundus photographs, fluorescein angiography (FA), and histopathologic findings in Coats disease. Design, Setting, and Participants: This retrospective cohort study was conducted in a single tertiary institution (Duke Eye Center) and identified 28 children with Coats disease through a review of medical records from December 2002 to January 2018. Four eyes were obtained from a biorepository for histopathologic analysis. Main Outcomes and Measures: Macular OCT, fundus photographs, and FA results were reviewed and compared for morphological changes. These were compared with retinal histopathological findings. Results: The mean (SD) age was 9.5 (5.5) years for the 28 children (and 29 eyes) with clinical imaging results, and 24 (86%) were boys. A comparison between imaging modalities revealed OCT features that were not visible in photographs or FA, including exudates in multiple retinal layers (23 [82.1%]), small pockets of subretinal fluid (4 [14.3%]), an outer retinal atrophy overlying fibrotic nodules (7 [25.0%]), and small preretinal hyperreflective OCT dots (25 [89.3%]). Next, a comparison with light micrographs introduced an association of OCT findings with possible pathological features, including hyperreflective linear structures on OCT that appeared consistent with cholesterol crystals, small hyperreflective dots with macrophages, outer retinal tubulations with rosettes, and analogous OCT histopathology features such as intraretinal vessels entering fibrotic nodules and retinal pigment epithelium excrescences under the subretinal fluid. An OCT analysis revealed intraretinal cystoid spaces in 19 eyes, but in 9 of 19 (47.4) this was not associated with cystoid macular leakage; rather, fluorescein leakage was observed from peripheral telangiectatic vessels. Additionally, exudates were intraretinal only (6 [21.4%]) or both intraretinal and subretinal (17 [60.7%]); none were subretinal only. In eyes with follow-up results, new fibrosis developed in 8 of 17 eyes (47.1%). Fibrosis developed in 5 of 5 eyes (100%) with baseline subretinal fluid vs 3 of 12 without (25%; 95% CI, 22%-92%) and in 7 of 9 eyes (77.8%) with subretinal exudates vs 1 of 8 (12.5%) without (95% CI, 16%-89%). Conclusions and Relevance: Optical coherence tomography may show the transient and permanent effects of Coats disease on the retina. These results suggest that exudates and fluid in the macular subretinal space appear later in the disease and may result in fibrosis formation. Further studies are needed to confirm if early treatment could prevent vision-threatening macular fibrosis.

Flow cytometry immunophenotyping of vitreous specimens does not contribute to diagnosis of lymphoma without supporting morphologic features.

BACKGROUND: Diagnostic vitrectomy with flow cytometry immunophenotyping (FCI) is being increasingly used as part of screening for diagnostically challenging cases. We aim to evaluate the utility of combined cytopathology and FCI in diagnostic pars plana vitrectomy. We also aim to evaluate cytologic features that could potentially predict FCI outcomes. This study provides clearer indications for use of FCI in diagnostic vitrectomy. METHODS: A case series of diagnostic pars plana vitrectomy specimens from 2010 to 2016 from a single institution was retrospectively evaluated. Associations between cytologic features and FCI were analyzed statistically. RESULTS: Ninety-nine vitrectomy specimens (90 patients) were evaluated. Evaluation was diagnostic in 39 of 99 (39.4%) specimens. FCI was performed in 66 of 73 (90.4%) specimens collected for lymphoma indication, and 9 of those 66 FCIs (13.6%) demonstrated abnormal lymphocytes. FCI was performed in 10 of 26 (38.5%) specimens collected for non-lymphomatous indications; all 10 FCIs failed to demonstrate lymphocyte abnormality. The absence of large lymphocytes frequently demonstrated negative FCI (negative predictive value = 97.7%), and was the sole cytologic feature significantly associated with a negative FCI result [OR, 14.0; 95% CI, 1.65-635.6; P = .034]. CONCLUSIONS: Diagnostic vitrectomy with cytopathology evaluation is valuable, and concomitant FCI is useful to confirm intraocular lymphoma. However, the absence of large lymphocytes on cytologic examination is the single significant predictor of a negative FCI, and this finding should preclude the use of FCI.

Masson's tumor of the pineal region: case report.

Intracranial intravascular papillary endothelial hyperplasia (IPEH), also referred to as Masson's tumor, is a condition that rarely occurs in the nervous system. IPEH most frequently occurs extracranially in the skin of the face, skull, neck, and trunk and can easily be mistaken clinically, radiologically, and histologically for angiosarcoma, organizing hematoma, or other vascular malformations. IPEH accounts for roughly 2% of all vascular tumors and is extremely rare intracranially, with only 23 reported cases compared with more than 300 cases of IPEH occurring in the skin and subcutaneous tissue. To date, it has never been reported to occur in the pineal region. The authors report the case of a patient with an IPEH in the pineal region who underwent complex resection and experienced reversal of neurological symptoms.

Multifocal iris melanoma in a 2-year-old managed with I-125 plaque brachytherapy.

We report a 23-month-old patient presenting with multifocal iris melanoma who underwent plaque brachytherapy with full corneal coverage. The lesion demonstrated several high-risk clinical and histopathologic features associated with iris melanoma in adults, including growth and angle seeding. The patient has been subsequently followed for 3.5 years with no evidence of recurrence. This report demonstrates the importance of serial examination of suspected melanocytic iris lesions in very young children and the effective treatment option of globe-sparing radiation therapy.