This is Jeopardy! A flexible coverage-based schedule model to address wellness for pathology training programs.

Scheduling rotations for a pathology training program involves balancing educational requirements, service coverage, and paid time off (PTO). Absences can affect training as residents cross-cover, managing multiple services at once. Other specialties utilize a "Jeopardy" based system for covering absences. In this system, residents on outpatient services are "jeopardized" to cover inpatient services for trainee absences. Borrowing this concept, we created a schedule model with a "Jeopardy-Elective" (JE) rotation to support resident absences. Prior to 2018-19, our residency program consisted of a 12 month-long rotation schedule. We adopted a 13 four-week block rotation model system, adding four JE rotations per resident over the course of training. The JE resident covered services during trainee absences and spent the remaining rotation on elective. We then conducted a pre- and post-intervention survey of all residents who trained in both systems. Following the change in schedule model, our results showed a statistically significant increase in resident satisfaction with taking PTO (p = 0.0014), finding coverage (p = 0.0006), and taking a sick day (p = 0.03). The mean number of days covered by the JE resident was 8.5 ± 2.7 workdays (out of 20). PTO usage increased from 16 to 20 days/resident while mean number of sick days decreased from 1.7 to 1.3 days per resident. There was overwhelming support with 82% of residents wanting to retain the new system going forward. Through use of the JE rotation, our program improved service coverage issues and resident satisfaction, with the long-term goal of enhanced resident well-being and enriched resident learning experiences.

PRAME immunohistochemistry of spitzoid neoplasms.

BACKGROUND: Spitzoid melanocytic neoplasms are well known to be diagnostically challenging. Immunohistochemistry (IHC) and molecular approaches have been used as ancillary diagnostic tests. Herein, we investigate the use of PRAME IHC for the assessment of spitzoid melanocytic neoplasms. METHODS: Ten Spitz nevi, 14 atypical Spitz tumors, and 11 spitzoid melanomas were retrieved, and PRAME IHC was scored on a scale of 1-4 (in % quartiles). Intensity of staining was categorized as weak or strong. Cases with no staining received a score of 0. Positive lymph nodes from three spitzoid melanomas were also analyzed. RESULTS: Spitz nevi, atypical Spitz tumors, and spitzoid melanomas had mean PRAME IHC scores of 1.20, 0.93, and 3.36, respectively. The percentage of cases with a score 3 or higher for each category of spitzoid neoplasms are as follows: Spitz nevus (20%), atypical Spitz tumor (0%), and spitzoid melanoma (82%). Among the spitzoid melanomas, three cases had positive sentinel lymph nodes, which showed PRAME score of 2, 4, and 4 in the metastatic deposits. CONCLUSIONS: Previous reports revealed PRAME IHC as useful tool to distinguish benign from malignant melanocytic lesions. The results presented here are concordant with the prior studies, but expand the application of this marker to Spitz nevi/tumors and spitzoid melanomas. The present findings suggest the potential diagnostic utility of PRAME IHC in the assessment of spitzoid melanocytic lesions, particularly in distinguishing spitzoid melanomas from Spitz nevi and atypical Spitz tumors.

Operational tolerance is not always permanent: A 10-year prospective study in pediatric liver transplantation recipients.

Immunosuppression withdrawal can be safely performed in select liver transplantation recipients, but the long-term outcomes and sustainability of tolerance have not been well studied. We completed a 10-year prospective, observational study of 18 pediatric liver transplantation recipients with operational tolerance to (1) assess the sustainability of tolerance over time, (2) compare the clinical characteristics of patients who maintained versus lost tolerance, (3) characterize liver histopathology findings in surveillance liver biopsies; and (4) describe immunologic markers in patients with tolerance. Comparator patients from two clinical phenotype groups termed "stable" and "nontolerant" patients were used as controls. Of the 18 patients with operational tolerance, the majority of patients were males (n = 14, 78%) who were transplanted for cholestatic liver disease (n = 12, 67%). Median age at transplantation was 1.9 (range, 0.6-8) years. Median time after transplantation that immunosuppression had been discontinued was 13.1 (range, 2.9-22.1) years. As many as 11 (61%) maintained tolerance for a median of 10.4 (range, 1.9-22.1) years, whereas 7 (39%) lost tolerance after a median of 3.2 (range, 1.5-18.6) years. Populations of T regulatory cells (%CD4+ CD25hi CD127lo ) were significantly higher in patients with tolerance (p = 0.02). Our results emphasize that spontaneous operational tolerance is a dynamic and nonpermanent state. It is therefore essential for patients who are clinically stable off immunosuppression to undergo regular follow-up and laboratory monitoring, as well as surveillance biopsies to rule out subclinical rejection.

Prognostic Value of Tumor Staging: Predicting Nodal Metastases in Cutaneous Squamous Cell Carcinoma.

OBJECTIVES: Determine the ability of three staging systems to stratify the risk of nodal metastases in cases of cutaneous squamous cell carcinoma (cSCC). Examine differential staging of tumors across the three systems and the resulting implications for clinical decision making. STUDY DESIGN: Retrospective chart review. METHODS: This study included 118 patients who underwent excision of primary cSCC of the head and neck as well as elective neck dissection for the same tumor between 2006 and 2017. Tumors were staged using the 2010 7th edition American Joint Committee on Cancer (AJCC 7) staging system, the 2016 8th edition AJCC staging system (AJCC 8), and the Brigham and Women's Hospital (BWH) alternative tumor staging system published in 2013. RESULTS: There were 28 patients (23.7%) with positive nodal metastases at the time of tumor excision. Almost all tumors staged as tumor (T)2 using AJCC 7 were upstaged to T3 or T4 using the new AJCC 8, and these two groups accounted for the majority of the nodal metastases. Similarly, the BWH-staged T3 group contained the highest number of tumors with nodal metastases. None of the three staging systems significantly stratified tumors in a manner that predicted the presence of nodal metastases. CONCLUSION: Individuals with cSCC tumors staged T3 or higher in the AJCC 8 and BWH staging systems should undergo neck dissection, whereas those with lower staging should be discussed with the patient on a case-by-case basis. LEVEL OF EVIDENCE: 4.

DDIT3 Immunohistochemistry Is a Useful Tool for the Diagnosis of Myxoid Liposarcoma.

Myxoid liposarcoma is a malignant adipogenic neoplasm characterized by prominent arborizing capillaries, occasional lipoblasts, and primitive-appearing spindle cells in a myxoid background. A recurrent translocation in myxoid liposarcoma results in an oncoprotein consisting of full-length DDIT3 (CHOP) fused to an N-terminal segment of either FUS (TLS) or, less often, EWSR1. Here, we explore the diagnostic significance of DDIT3 expression in myxoid liposarcoma using a mouse monoclonal antibody recognizing an epitope in the N-terminal region. Studying a total of 300 tumors, we find diffuse, moderate-to-strong nuclear-localized anti-DDIT3 immunoreactivity in all 46 cases of myxoid liposarcoma representing 36 unique tumors, including 6 cases with high-grade (round cell) morphology. DDIT3 immunohistochemistry also highlighted a distinctive vasculocentric growth pattern in 7 myxoid liposarcomas treated with neoadjuvant radiation. In contrast, the vast majority of other examined lipomatous and myxoid neoplasms exhibited no DDIT3 expression; limited, weak immunoreactivity in <10% of cells was infrequently observed in dedifferentiated liposarcoma (6/39, 15%), solitary fibrous tumor (3/12, 25%), pleomorphic liposarcoma (1/15, 7%), and high-grade myxofibrosarcoma (2/17, 12%). Although this minimal DDIT3 expression did not correlate with DDIT3 amplification or myxoid liposarcoma-like morphology in dedifferentiated liposarcoma, there was evidence among sarcomas (excluding myxoid liposarcoma) of a relationship between expression and exposure to neoadjuvant radiation or cytotoxic chemotherapy. The constellation of findings indicates that DDIT3 immunohistochemistry may have utility in the evaluation of myxoid and lipomatous neoplasms to support the diagnosis of myxoid liposarcoma.

Drug-Induced Autoimmune Hepatitis From Hydralazine Leading to Acute Liver Failure and Liver Transplantation.

We describe a woman with no previous liver disease who developed drug-induced autoimmune hepatitis from hydralazine prescribed to her for hypertension. Despite the discontinuation of the medication, she developed acute liver failure and subsequently underwent successful liver transplantation. She survived and had a good clinical outcome.

Diffuse Alveolar Hemorrhage and Pulmonary Vasculitides: Histopathologic Findings.

Vasculitides are a heterogeneous group of disorders in which inflammation of blood vessel walls is present at least some time during the course of the disease. Vasculitides can affect any caliber or type of vessel in many anatomic sites; however, the disease can alter more than just vasculature. Given the diversity of vasculitides, in 2012, a revised classification system was proposed to categorize vasculitides by the type of vessel involved including size, function, and structural attributes. In the lung, vasculitis impacts both the pulmonary vessels and parenchyma. Extrapulmonary involvement, particularly with concomitant kidney involvement, is a frequent occurrence. Pulmonary vasculitides often present with hemoptysis, pathologically manifested as diffuse alveolar hemorrhage (DAH) with or without capillaritis and can be life threatening when diffuse throughout the lungs. Etiologies for DAH include both primary and secondary vasculitides, along with collagen-vascular diseases, infection, and drug toxicity. Therefore, diagnosing the specific vasculitic etiology often relies on comprehensive assessment of all clinical, laboratory/serological, imaging, and histopathologic features that may be present. The most common primary pulmonary vasculitides often affect small vessels and are associated with circulating antineutrophilic cytoplasmic antibodies (ANCAs). In the 2012 classification, these include granulomatosis with polyangiitis (formerly Wegener granulomatosis), eosinophilic granulomatosis with polyangiitis (formerly Churg-Strauss' syndrome), and microscopic polyangiitis. Other less frequent vasculitides that are non-ANCA associated or affect medium- to large-sized vessels can have pulmonary involvement. These entities are usually associated with extrapulmonary disease and include polyarteritis nodosa, Takayasu's arteritis, Behçet's disease, and antibasement membrane antibody disease (formerly Goodpasture's syndrome). Although all vasculitides have vessel wall inflammation at some phase in the disease process, their histopathologic findings are as diverse as the group of diseases themselves. The characteristic histologic findings of the pulmonary vasculitides will be reviewed here.

Obliterative portal venopathy: A histopathologic finding associated with chronic antibody-mediated rejection in pediatric liver allografts.

The significance of post-transplant HLA DSA and chronic AMR in LT is an emerging field of study. Although OPV has previously been described as a histopathologic finding in DSA-positive adult LT recipients, it was not included in the recent Banff criteria for chronic AMR. Our aim was to describe the association between OPV and chronic AMR in pediatric LT recipients. A retrospective review of 67 liver biopsies performed between November 2014 and April 2016 in 45 pediatric LT recipients identified four patients with OPV. Clinical status, liver biochemistry, the presence of DSA, and available non-HLA antibody testing, as well as histopathologic features of chronic AMR, were assessed. All four patients with OPV had class II DSA and histopathologic features of chronic AMR based on the Banff criteria. Two patients were noted to have non-HLA antibodies. Three patients are undergoing treatment with IVIG but have persistent DSA. Two patients have graft failure and are awaiting retransplantation. In conclusion, OPV is a histopathologic finding associated with chronic AMR in pediatric LT recipients. Further studies are needed to elucidate whether OPV is reversible and/or amenable to medical therapy.

ß1-integrin is essential for vasoregulation and smooth muscle survival in vivo.

OBJECTIVE: Integrins contribute to vascular morphogenesis through regulation of adhesion and assembly of the extracellular matrix. However, the role of ß1-integrin in the mature vascular wall is less clear. APPROACH AND RESULTS: We sought to determine the function of ß1-integrin in mature smooth muscle cells in vivo using a loss of function approach by crossing a tamoxifen-inducible sm22αCre line to a floxed ß1-integrin transgenic line. Adult mice lacking smooth muscle ß1-integrin survived only 10 weeks post induction. The deletion of ß1-integrin resulted in profound loss of vasomotor control. Histological analysis revealed progressive fibrosis in arteries with associated apoptosis of smooth muscle cells, which was not rescued by adventitial stem cells. Smooth muscle cell apoptosis was detected in arteries with dead cells replaced primarily by collagen. Despite the catastrophic effects on vascular smooth muscle, the deleted visceral smooth muscle remained viable with the exception of a short portion of the colon, indicating that vascular but not visceral smooth muscle is particularly sensitive to changes in ß1-integrin. CONCLUSIONS: This study reveals an essential function of ß1-integrin in the maintenance of vasomotor control and highlights a critical role for ß1-integrin in vascular, but not visceral, smooth muscle survival.