Chronic Lymphocytic Leukemia Presenting as Bilateral Periorbital Edema Treated With Low-dose Radiation Therapy.

Ocular manifestations in chronic lymphocytic leukemia (CLL) have been reported in 30% to 40% of patients and may be a result of direct tissue infiltration, concomitant blood dyscrasias, or a result of therapeutic intervention. Leukemia cutis, defined as infiltration of the epidermis or dermis by neoplastic lymphocytes, is rare. Herein, we present a case report of a patient with leukemia who presented with periorbital edema and ecchymosis. This is the first known case to date of periorbital CLL successfully treated with low-dose radiation therapy (4 Gy in 2 fractions). Clinicians should be aware of the possibility of ocular involvement from CLL, given the importance of prompt diagnosis and treatment.

Computational pathology in 2030: a Delphi study forecasting the role of AI in pathology within the next decade.

BACKGROUND: Artificial intelligence (AI) is rapidly fuelling a fundamental transformation in the practice of pathology. However, clinical integration remains challenging, with no AI algorithms to date in routine adoption within typical anatomic pathology (AP) laboratories. This survey gathered current expert perspectives and expectations regarding the role of AI in AP from those with first-hand computational pathology and AI experience. METHODS: Perspectives were solicited using the Delphi method from 24 subject matter experts between December 2020 and February 2021 regarding the anticipated role of AI in pathology by the year 2030. The study consisted of three consecutive rounds: 1) an open-ended, free response questionnaire generating a list of survey items; 2) a Likert-scale survey scored by experts and analysed for consensus; and 3) a repeat survey of items not reaching consensus to obtain further expert consensus. FINDINGS: Consensus opinions were reached on 141 of 180 survey items (78.3%). Experts agreed that AI would be routinely and impactfully used within AP laboratory and pathologist clinical workflows by 2030. High consensus was reached on 100 items across nine categories encompassing the impact of AI on (1) pathology key performance indicators (KPIs) and (2) the pathology workforce and specific tasks performed by (3) pathologists and (4) AP lab technicians, as well as (5) specific AI applications and their likelihood of routine use by 2030, (6) AI's role in integrated diagnostics, (7) pathology tasks likely to be fully automated using AI, and (8) regulatory/legal and (9) ethical aspects of AI integration in pathology. INTERPRETATION: This systematic consensus study details the expected short-to-mid-term impact of AI on pathology practice. These findings provide timely and relevant information regarding future care delivery in pathology and raise key practical, ethical, and legal challenges that must be addressed prior to AI's successful clinical implementation. FUNDING: No specific funding was provided for this study.

NK/T-cell Lymphoma With Orbital Involvement: A Case Report and Systematic Review of the Literature.

PURPOSE: To present the clinical course of a patient with recurrent NK/T-cell lymphoma (NKTL) involving the orbit and to review the literature on patients with NKTL involving the orbit. METHODS: The PubMed database was searched for all cases of NKTL involving orbital, intraocular, or adnexal ocular structures. RESULTS: Ninety-six patients were included in the final analysis. The mean age of diagnosis was 48.1 ± 16.8 years. The patients were 53/96 (55.2%) male and 43/96 (44.8%) female. Tumor location varied and included the orbit in 80/96 (83.3%), nasosinus in 56/96 (58.3%), uvea in 11/96 (11.5%), lacrimal gland in 9/96 (9.4%), lacrimal drainage system in 11/96 (11.5%), and conjunctiva in 7/96 (7.3%) cases. Management included surgical debulking in 29/96 (30.2%) cases, radiotherapy in 52/96 (54.2%) cases, and chemotherapy in 82/96 (85.4%) cases. Median survival was 6 months (95% CI: 5-9). Chemotherapy (hazard ratio = 0.80, 95% CI: 0.67-0.95, p = 0.013), radiotherapy (hazard ratio = 0.75, 95% CI: 0.64-0.87, p < 0.001), and orbital involvement being a recurrence of disease (hazard ratio = 0.79, 95% CI: 0.67-0.95, p = 0.009) were associated with improved survival. Advanced Ann Arbor stage (III-IV) at diagnosis (hazard ratio = 1.22, 95% CI: 1.08-1.38, p = 0.001), vision loss (hazard ratio = 1.18, 95% CI: 1.04-1.34, p = 0.009), proptosis (hazard ratio = 1.15, 95% CI: 1.01-1.30, p = 0.035) and periorbital swelling (hazard ratio = 1.15, 95% CI: 1.00-1.33, p = 0.048) were associated with poor survival. CONCLUSIONS: NK/T-cell lymphoma involving the orbit, globe, or ocular adnexa heralds a poor prognosis where early diagnosis and therapy are critical. The use of radiotherapy and chemotherapy is associated with improved survival.

Local recurrence of uveal melanoma and concomitant brain metastases associated with an activating telomerase promoter mutation seven years after secondary enucleation.

Purpose: To describe a case of local recurrence of uveal melanoma with concomitant brain metastases after secondary enucleation. Observations: A 73 year-old patient presented with dizziness and gait instability. MRI of the orbits and brain showed an anophthalmic socket with an orbital implant and an associated optic nerve mass as well as multiple mass lesions in the brain. The patient's history was significant for secondary enucleation for uveal melanoma recurrence seven years prior to presentation. Histopathology of the enucleated eye revealed no signs of extrascleral extension or optic nerve invasion. Biopsy of the optic nerve mass confirmed recurrent uveal melanoma with somatic mutations in GNAQ (Q209L) and the telomerase (TERT) promoter (c.1-124C > T) found on targeted next-generation sequencing (NGS). The same mutations were found in the primary tumor in the patient's archived enucleation samples. Conclusions: Local recurrence of uveal melanoma can occur after enucleation and is associated with an increased risk of systemic metastases. It is important for clinicians to monitor patients for local recurrence and systemic metastases even after enucleation. Genetic biomarkers may play an important role in identifying tumors at highest risk of local recurrence and metastasis. To our knowledge, this is the first case study to describe the TERT promoter mutation c.1-124C > T in the setting of recurrent uveal melanoma.

Primary Mesenchymal Tumors of the Thyroid Gland: A Modern Retrospective Cohort Including the First Case of TFE3-Translocated Malignant Perivascular Epithelioid Cell Tumor (PEComa).

Primary mesenchymal tumors of the thyroid gland are extremely rare, with only case reports and small case series documented in the English literature, many of which were published prior to the era of molecular pathology. In the current study, we aim to present a contemporary multi-centric cohort of thyroid mesenchymal tumors. Nineteen primary thyroid mesenchymal tumors were collected from three tertiary centers. Their clinicopathologic features, immunoprofile, molecular alterations, and outcome were described. Eight cases were classified as benign or intermediate with solitary fibrous tumor being the most common histotype (n = 3). The remaining 11 cases were malignant, including three angiosarcomas, one epithelioid hemangioendothelioma, one adamantinoma-like Ewing sarcoma, one biphasic synovial sarcoma, one malignant melanocytic peripheral nerve sheath tumor (melanotic schwannoma), one myxofibrosarcoma, and two undifferentiated pleomorphic/spindle sarcomas (one of which was radiation-induced). Six tumors showed characteristic diagnostic translocations. We herein also described the first case of thyroid malignant perivascular epithelioid cell tumor (PEComa) with RBM10-TFE3 fusion in a 35-year-old female patient. Thyroid mesenchymal tumors, benign or malignant, are rare with a broad spectrum of possible diagnoses. A comprehensive examination to include histology, immunohistochemistry, and molecular testing is essential for the correct diagnosis and to distinguish them from anaplastic thyroid carcinoma. PEComa may occur as a primary tumor of the thyroid gland, expanding the histologic spectrum of thyroid mesenchymal tumors.

Cilioretinal Artery Occlusion as the Presenting Manifestation of Left Atrial Myxoma.

Purpose: This work reports a case of left atrial myxoma presenting with cilioretinal artery occlusion. Methods: A case report is discussed. Results: A 57-year-old man was referred for acute vision loss in the left eye after a workup including electrocardiogram, magnetic resonance imaging of the brain without contrast, computed tomography angiography of the head and neck, erythrocyte sedimentation rate, and C-reactive protein had negative results. Examination revealed cilioretinal artery occlusion with visible emboli. Because an echocardiogram was not performed, the patient was referred to the emergency department. Echocardiogram revealed a large left atrial mass prolapsing into the left ventricle. The mass was excised, and pathology showed myxoma. Conclusions: This is the first case to our knowledge of isolated cilioretinal artery occlusion as the initial presentation of an atrial myxoma. Thorough and complete workup was crucial to averting further morbidity and mortality.

An Analysis of the Effect of the COVID-19 Pandemic on Case Volumes in an Academic Subspecialty-Based Anatomic Pathology Practice.

The recent COVID pandemic has had a major effect on anatomic pathology specimen volumes across the country. The effect of this pandemic on a subspecialty academic practice is presented. We used a data-driven approach to monitor the changing workloads in a granular fashion and dynamically adjust the scheduling of faculty and histology staff accordingly to minimize the number of people present on-site. At the peak of the pandemic locally, the main hospital in our health system had 450 COVID-positive inpatients. The surgical pathology specimen volume dropped to 13% of the pre-pandemic levels, and this occurred about 2 weeks before the peak of the inpatient census; cytology specimens (the majority of which are outreach gynecological) dropped to approximately 5% of the pre-pandemic volume, 4 weeks before the peak inpatient census. All of the surgical subspecialty services showed a significant decrease in volume, with hematopathology being the least affected (dropped to 30% of the pre-pandemic level). The genitourinary surgical subspecialty service (predominantly prostate and bladder biopsies) was the most affected (dropped to 1% of the pre-pandemic level) but was fastest to return as clinical operations began to return to normal. The only specimen type which showed a significant increase in turnaround time during the pandemic was our gynecologic cytology specimens and that occurred as the specimen volume returned. This was due to stay-at-home directives for the cytotechnologists and the fact that some of them were retasked to participate in our SARS-CoV-2 testing.

Dabrafenib and Trametinib for BRAF-Mutated Conjunctival Melanoma.

BACKGROUND: Conjunctival melanoma is a potentially lethal malignancy of the ocular surface. There have been no therapeutic advancements made in the past several decades despite increasing prevalence of the disease. METHODS: The authors report the case of a 52-year-old Caucasian male with unresectable, recurrent conjunctival melanoma with V600 BRAF mutation who was treated with systemic BRAF/MEK inhibition. RESULTS: There was complete regression of local disease within the first 9 months. The patient remains without local recurrence or systemic metastasis at 1 year. CONCLUSION: This is the first reported case of conjunctival melanoma with complete response to BRAF/MEK inhibition. As long as targeted therapy remains an option, patients with conjunctival melanoma should undergo mutational profiling of their tumor.

A Semiquantitative Scoring System May Allow Biopsy Diagnosis of Pulmonary Large Cell Neuroendocrine Carcinoma.

OBJECTIVES: The aim of this study was to devise reproducible biopsy criteria for distinguishing pulmonary large cell neuroendocrine carcinoma (LCNEC) from non-small cell lung carcinoma (NSCLC). METHODS: Tissue microarrays of LCNEC and NSCLC were generated from resection specimens and used as biopsy surrogates. They were stained for neuroendocrine markers, Ki-67, napsin-A, and p40, and independently analyzed by standardized morphologic criteria by four pathologists. Tumors were scored based on morphology, neuroendocrine marker expression, and Ki-67 proliferative index. RESULTS: The average total score for LCNEC was significantly higher than for NSCLC (5.65 vs 0.51, P < .0001). Utilizing a cutoff score of 4 or higher showed 100% sensitivity and 99% specificity for LCNEC diagnosis, with an excellent agreement among four pathologists (98%). CONCLUSIONS: The proposed semiquantitative approach based on a combination of specific morphologic and immunophenotypic features may be a useful tool for biopsy diagnosis of LCNEC.

A Survey of LOINC Code Selection Practices Among Participants of the College of American Pathologists Coagulation (CGL) and Cardiac Markers (CRT) Proficiency Testing Programs.

CONTEXT.­: Biomedical terminologies such as Logical Observation Identifiers, Names, and Codes (LOINC) were developed to enable interoperability of health care data between disparate health information systems to improve patient outcomes, public health, and research activities. OBJECTIVE.­: To ascertain the utilization rate and accuracy of LOINC terminology mapping to 10 commonly ordered tests by participants of the College of American Pathologists (CAP) Proficiency Testing program. DESIGN.­: Questionnaires were sent to 1916 US and Canadian laboratories participating in the 2018 CAP coagulation (CGL) and/or cardiac markers (CRT) surveys requesting information on practice setting, instrument(s) and test method(s), and LOINC code selection and usage in the laboratory and electronic health records. RESULTS.­: Ninety of 1916 CGL and/or CRT participants (4.7%) responded to the questionnaire. Of the 275 LOINC codes reported, 54 (19.6%) were incorrect: 2 codes (5934-2 and 12345-1) (0.7%) did not exist in the LOINC database and the highest error rates were observed in the property (27 of 275, 9.8%), system (27 of 275, 9.8%), and component (22 of 275, 8.0%) LOINC axes. Errors in LOINC code selection included selection of the incorrect component (eg, activated clotting time instead of activated partial thromboplastin time); selection of panels that can never be used to obtain an individual analyte (eg, prothrombin time panel instead of international normalized ratio); and selection of an incorrect specimen type. CONCLUSIONS.­: These findings of real-world LOINC code implementation across a spectrum of laboratory settings should raise concern about the reliability and utility of using LOINC for clinical research or to aggregate data.

Immune Checkpoint Inhibitor-Associated Pericarditis.

Side effects of immune checkpoint inhibitors, termed immune-related adverse events, are relatively common, but immune checkpoint inhibitor-mediated cardiotoxicities are rare; however, they can be serious and potentially fatal. Pericarditis is an infrequent cardiac toxicity of immunotherapy and predisposing factors remain unknown. Here we report three patients with NSCLC who developed pericarditis during therapy with programmed death 1/programmed death ligand 1+/- CTLA-4 inhibitors. We review the clinical presentation of these three cases and histopathologic findings from autopsies from the first two patients and a pericardial sampling that has been obtained from a pericardial window procedure in the third patient who recovered from the pericarditis episode. We also discuss the potential mechanisms, as well as what is known about pericarditis secondary to immune-related adverse events.

Asymmetric Deep Stromal Keratopathy in a Patient With Multiple Myeloma.

PURPOSE: To report a case of asymmetric deep stromal keratopathy in a patient with multiple myeloma. METHODS: Case report and literature review. RESULTS: An 85-year-old woman was found to have progressive visually significant left-sided deep stromal opacity in the setting of monoclonal gammopathy. Hematologic workup resulted in a diagnosis of IgG kappa multiple myeloma. Histopathology was significant for semicrystalline deposits in the posterior stroma. The patient's visual acuity improved to 20/50 7 months after penetrating keratoplasty. A similar deep stromal lesion appeared in the right eye 2 years after initial presentation. CONCLUSIONS: We present an unusual case of paraproteinemic keratopathy with a uniquely asymmetric presentation that resulted in a diagnosis of multiple myeloma.

Acute Presentation of Mesectodermal Leiomyoma of the Ciliary Body.

PURPOSE: We report a case of acutely presenting mesectodermal leiomyoma of the ciliary body in a 29-year-old female who reported waking up with swollen eyelids of the right eye and light-perception vision. The affected eye had elevated intraocular pressure, a flat anterior chamber, and a pale, round mass arising from the nasal ciliary body, invading the angle and protruding into the visual axis posterior to the lens. Within days, the visual acuity decreased to no light perception. The eye was enucleated. METHODS: The enucleated eye harbored a tumor arising from the ciliary body, measuring 18 mm in the greatest dimension. Spindled cells with fibrillary cytoplasmic processes suggested a neural origin though negative for S-100, Melan-A, and HMB-45. The cells stained strongly positive for smooth muscle actin and vimentin, leading to the diagnosis of mesectodermal leiomyoma of the ciliary body. RESULTS: We review the literature to expand upon the clinical findings, diagnostic methods, and histopathologic and immunohistochemistry characteristics of mesectodermal leiomyoma. CONCLUSION: Leiomyoma must be in the differential diagnosis for ciliary body mass, especially in women of reproductive age. Diagnosis relies on histopathology and immunohistochemistry. The mechanism of acute symptom onset may be multifactorial. This case emphasizes the possibility of acute presentation of a rare, benign intraocular tumor.

Pathology Informatics Essentials for Residents: A Flexible Informatics Curriculum Linked to Accreditation Council for Graduate Medical Education Milestones.

CONTEXT: -Recognition of the importance of informatics to the practice of pathology has surged. Training residents in pathology informatics has been a daunting task for most residency programs in the United States because faculty often lacks experience and training resources. Nevertheless, developing resident competence in informatics is essential for the future of pathology as a specialty. OBJECTIVE: -To develop and deliver a pathology informatics curriculum and instructional framework that guides pathology residency programs in training residents in critical pathology informatics knowledge and skills, and meets Accreditation Council for Graduate Medical Education Informatics Milestones. DESIGN: -The College of American Pathologists, Association of Pathology Chairs, and Association for Pathology Informatics formed a partnership and expert work group to identify critical pathology informatics training outcomes and to create a highly adaptable curriculum and instructional approach, supported by a multiyear change management strategy. RESULTS: -Pathology Informatics Essentials for Residents (PIER) is a rigorous approach for educating all pathology residents in important pathology informatics knowledge and skills. PIER includes an instructional resource guide and toolkit for incorporating informatics training into residency programs that vary in needs, size, settings, and resources. PIER is available at http://www.apcprods.org/PIER (accessed April 6, 2016). CONCLUSIONS: -PIER is an important contribution to informatics training in pathology residency programs. PIER introduces pathology trainees to broadly useful informatics concepts and tools that are relevant to practice. PIER provides residency program directors with a means to implement a standardized informatics training curriculum, to adapt the approach to local program needs, and to evaluate resident performance and progress over time.

Pathology Informatics Essentials for Residents: A flexible informatics curriculum linked to Accreditation Council for Graduate Medical Education milestones.

CONTEXT: Recognition of the importance of informatics to the practice of pathology has surged. Training residents in pathology informatics have been a daunting task for most residency programs in the United States because faculty often lacks experience and training resources. Nevertheless, developing resident competence in informatics is essential for the future of pathology as a specialty. OBJECTIVE: The objective of the study is to develop and deliver a pathology informatics curriculum and instructional framework that guides pathology residency programs in training residents in critical pathology informatics knowledge and skills and meets Accreditation Council for Graduate Medical Education Informatics Milestones. DESIGN: The College of American Pathologists, Association of Pathology Chairs, and Association for Pathology Informatics formed a partnership and expert work group to identify critical pathology informatics training outcomes and to create a highly adaptable curriculum and instructional approach, supported by a multiyear change management strategy. RESULTS: Pathology Informatics Essentials for Residents (PIER) is a rigorous approach for educating all pathology residents in important pathology informatics knowledge and skills. PIER includes an instructional resource guide and toolkit for incorporating informatics training into residency programs that vary in needs, size, settings, and resources. PIER is available at http://www.apcprods.org/PIER (accessed April 6, 2016). CONCLUSIONS: PIER is an important contribution to informatics training in pathology residency programs. PIER introduces pathology trainees to broadly useful informatics concepts and tools that are relevant to practice. PIER provides residency program directors with a means to implement a standardized informatics training curriculum, to adapt the approach to local program needs, and to evaluate resident performance and progress over time.

Computational Pathology: A Path Ahead.

CONTEXT: We define the scope and needs within the new discipline of computational pathology, a discipline critical to the future of both the practice of pathology and, more broadly, medical practice in general. OBJECTIVE: To define the scope and needs of computational pathology. DATA SOURCES: A meeting was convened in Boston, Massachusetts, in July 2014 prior to the annual Association of Pathology Chairs meeting, and it was attended by a variety of pathologists, including individuals highly invested in pathology informatics as well as chairs of pathology departments. CONCLUSIONS: The meeting made recommendations to promote computational pathology, including clearly defining the field and articulating its value propositions; asserting that the value propositions for health care systems must include means to incorporate robust computational approaches to implement data-driven methods that aid in guiding individual and population health care; leveraging computational pathology as a center for data interpretation in modern health care systems; stating that realizing the value proposition will require working with institutional administrations, other departments, and pathology colleagues; declaring that a robust pipeline should be fostered that trains and develops future computational pathologists, for those with both pathology and nonpathology backgrounds; and deciding that computational pathology should serve as a hub for data-related research in health care systems. The dissemination of these recommendations to pathology and bioinformatics departments should help facilitate the development of computational pathology.

Pathology Informatics Essentials for Residents: A Flexible Informatics Curriculum Linked to Accreditation Council for Graduate Medical Education Milestones (a secondary publication).

CONTEXT: Recognition of the importance of informatics to the practice of pathology has surged. Training residents in pathology informatics has been a daunting task for most residency programs in the United States because faculty often lacks experience and training resources. Nevertheless, developing resident competence in informatics is essential for the future of pathology as a specialty. OBJECTIVE: To develop and deliver a pathology informatics curriculum and instructional framework that guides pathology residency programs in training residents in critical pathology informatics knowledge and skills, and meets Accreditation Council for Graduate Medical Education Informatics Milestones. DESIGN: The College of American Pathologists, Association of Pathology Chairs, and Association for Pathology Informatics formed a partnership and expert work group to identify critical pathology informatics training outcomes and to create a highly adaptable curriculum and instructional approach, supported by a multiyear change management strategy. RESULTS: Pathology Informatics Essentials for Residents (PIER) is a rigorous approach for educating all pathology residents in important pathology informatics knowledge and skills. PIER includes an instructional resource guide and toolkit for incorporating informatics training into residency programs that vary in needs, size, settings, and resources. PIER is available at http://www.apcprods.org/PIER (accessed April 6, 2016). CONCLUSIONS: PIER is an important contribution to informatics training in pathology residency programs. PIER introduces pathology trainees to broadly useful informatics concepts and tools that are relevant to practice. PIER provides residency program directors with a means to implement a standardized informatics training curriculum, to adapt the approach to local program needs, and to evaluate resident performance and progress over time.

Customizing Laboratory Information Systems: Closing the Functionality Gap.

Highly customizable laboratory information systems help to address great variations in laboratory workflows, typical in Pathology. Often, however, built-in customization tools are not sufficient to add all of the desired functionality and improve systems interoperability. Emerging technologies and advances in medicine often create a void in functionality that we call a functionality gap. These gaps have distinct characteristics­a persuasive need to change the way a pathology group operates, the general availability of technology to address the missing functionality, the absence of this technology from your laboratory information system, and inability of built-in customization tools to address it. We emphasize the pervasive nature of these gaps, the role of pathology informatics in closing them, and suggest methods on how to achieve that. We found that a large number of the papers in the Journal of Pathology Informatics are concerned with these functionality gaps, and an even larger proportion of electronic posters and abstracts presented at the Pathology Informatics Summit conference each year deal directly with these unmet needs in pathology practice. A rapid, continuous, and sustainable approach to closing these gaps is critical for Pathology to provide the highest quality of care, adopt new technologies, and meet regulatory and financial challenges. The key element of successfully addressing functionality gaps is gap ownership­the ability to control the entire pathology information infrastructure with access to complementary systems and components. In addition, software developers with detailed domain expertise, equipped with right tools and methodology can effectively address these needs as they emerge.

Pathologists' place in the electronic health record landscape.

With growth spurred by recent federal efforts, electronic health records (EHRs) are transforming the practice of medicine and have important implications for pathologists, their laboratories, and the patients they serve. Beyond new EHR-related regulatory requirements, EHRs fundamentally alter the way clinicians interact with laboratory information, including test order entry and result reviewing. This article is the first in a series of 5 related articles whose goal is to provide a "framework" for empowering pathologists to adapt to, and to succeed in, the era of expanding EHR use. This series aims to describe the environment for EHR uptake, to raise awareness of EHR-related issues that pathologists and laboratories face, and to explore new professional roles for pathologists as stewards of patients' laboratory information in EHRs.