IL-27 maintains cytotoxic Ly6C+ γδ T cells that arise from immature precursors.

In mice, γδ-T lymphocytes that express the co-stimulatory molecule, CD27, are committed to the IFNγ-producing lineage during thymic development. In the periphery, these cells play a critical role in host defense and anti-tumor immunity. Unlike αß-T cells that rely on MHC-presented peptides to drive their terminal differentiation, it is unclear whether MHC-unrestricted γδ-T cells undergo further functional maturation after exiting the thymus. Here, we provide evidence of phenotypic and functional diversity within peripheral IFNγ-producing γδ T cells. We found that CD27+ Ly6C- cells convert into CD27+Ly6C+ cells, and these CD27+Ly6C+ cells control cancer progression in mice, while the CD27+Ly6C- cells cannot. The gene signatures of these two subsets were highly analogous to human immature and mature γδ-T cells, indicative of conservation across species. We show that IL-27 supports the cytotoxic phenotype and function of mouse CD27+Ly6C+ cells and human Vδ2+ cells, while IL-27 is dispensable for mouse CD27+Ly6C- cell and human Vδ1+ cell functions. These data reveal increased complexity within IFNγ-producing γδ-T cells, comprising immature and terminally differentiated subsets, that offer new insights into unconventional T-cell biology.

Mixed Reality Surgical Navigation System; Positional Accuracy Based on Food and Drug Administration Standard.

BACKGROUND: Computer assisted surgical navigation systems are designed to improve outcomes by providing clinicians with procedural guidance information. The use of new technologies, such as mixed reality, offers the potential for more intuitive, efficient, and accurate procedural guidance. The goal of this study is to assess the positional accuracy and consistency of a clinical mixed reality system that utilizes commercially available wireless head-mounted displays (HMDs), custom software, and localization instruments. METHODS: Independent teams using the second-generation Microsoft HoloLens© hardware, Medivis SurgicalAR© software, and localization instruments, tested the accuracy of the combined system at different institutions, times, and locations. The ASTM F2554-18 consensus standard for computer-assisted surgical systems, as recognized by the U.S. FDA, was utilized to measure the performance. 288 tests were performed. RESULTS: The system demonstrated consistent results, with an average accuracy performance that was better than one millimeter (.75 ± SD .37 mm). CONCLUSION: Independently acquired positional tracking accuracies exceed conventional in-market surgical navigation tracking systems and FDA standards. Importantly, the performance was achieved at two different institutions, using an international testing standard, and with a system that included a commercially available off-the-shelf wireless head mounted display and software.

Subacute Cutaneous Lupus as a Paraneoplastic Manifestation of Non-Hodgkin Lymphoma.

Malignancies have been associated with paraneoplastic syndromes, such as dermatomyositis. Subacute cutaneous lupus erythematosus (SCLE) can occur due to a wide array of cancers. Paraneoplastic SCLE obeys McLean's criteria and often regresses after the underlying malignancy has been treated appropriately. Anti-Ro/SSA antibodies are often present in patients with paraneoplastic SCLE; however, there have been many instances where anti-Ro may not be present. We report a case of non-Hodgkin lymphoma causing SCLE, a malignancy not previously known to be associated with paraneoplastic SCLE. We also highlight the importance of perhaps prompt chemotherapy to treat the underlying malignancy, as a failure to do so may lead to worse patient outcomes.

Scoping Review on Menstrual Suppression Among U.S. Military Service Members.

INTRODUCTION: The purpose of this scoping review was to systematically evaluate literature addressing menstrual suppression in the military population and to identify gaps in the literature. MATERIALS AND METHODS: A scoping review of the literature using Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) guidelines was completed. Quality appraisal was conducted using the Johns Hopkins Evidence-Based Practice (EBP) Evidence Level and Quality Guide. RESULTS: Thirteen research articles and nine non-research articles were included. The themes identified were methods for menstrual suppression, barriers to menstrual suppression, and educational recommendations. CONCLUSIONS: Six gaps were identified: (1) readiness, (2) single branch of service, (3) options for suppression, (4) hesitance to suppress, (5) provider practices, and (6) stagnant research. Recommendations for future research, practice, and military health policy are provided. Expanding research on menstrual suppression in U.S. military service members will enhance the health of military service members, provider practices, and military health policy to promote military readiness.

An Unusual Presentation of Blastomycosis-Like Pyoderma Gangrenosum.

INTRODUCTION: Pyoderma gangrenosum (PG) is a complex disease that has the potential to mimic a wide variety of diseases and disorders. Pyoderma is a disease of exclusion, but it has many variants, including ulcerative, bullous, and pustular forms. Owing to the complexity of the disease, careful diagnosis is important because inappropriate treatment can result in wound recurrence. CASE REPORT: A 74-year-old female presented to the clinic with a presumed diagnosis of squamous cell carcinoma on biopsy but with an abnormal presentation mimicking a blastomycosis lesion. After surgical excision of the lesion in the operating room, the final pathology report confirmed the diagnosis of blastomycosis-like pyoderma gangrenosum. The patient was treated with high-dose prednisone and skin grafts, which resulted in resolution of the wound. CONCLUSIONS: This case report highlights the need to involve a wide array of health care providers in the management of complex and recurring wounds as well as the need to consider a wide and diverse differential diagnosis when determining the final diagnosis of complex wounds.

Endometriosis-associated colorectal carcinosarcoma: A case report and review of the literature.

•Endometriosis associated intestinal tumors are rare, with 5 cases documented.•Endometriosis associated intestinal tumors might present like colorectal carcinoma.•Endometriosis associated intestinal Carcinoma is associated with poor prognosis.

Extensive Circumferential Heterotopic Ossification Discovered at the Base of a Loop Ileostomy.

Heterotopic ossification is a rare phenomenon defined by the formation of bone within nonossifying soft tissues. A rare variant of heterotopic ossification is heterotopic mesenteric ossification (HMO), in which there is involvement of the mesentery and surrounding intra-abdominal structures. There are only four previously reported cases of HMO involving an ileostomy. We present a case of HMO affecting an ileostomy which was discovered during elective stoma reversal in a 52-year-old male who required fecal diversion following perineal necrotizing fasciitis.

LOCALLY INVASIVE PHEOCHROMOCYTOMA COMBINED WITH PRIMARY MALIGNANT ADRENAL LYMPHOMA.

OBJECTIVE: Pheochromocytoma (PHEO) combined with primary adrenal lymphoma is extremely rare. We describe a case of locally invasive PHEO combined with primary malignant lymphoma. METHODS: We provide a case description with biochemical analyses, imaging, and pathologic findings. RESULTS: A 79-year-old male presented with a 17-cm, complex mass in the left adrenal gland with non-contrast Hounsfield units of 100 and left para-aortic enlarged lymph nodes imaged by computed tomography. Biochemical evaluation showed plasma and 24-hour urinary normetanephrine significantly elevated about 22 times (about 13.5 times above the normal upper limit) while metanephrine levels were normal. With adequate perioperative preparation, en bloc resection of the left adrenal gland was performed. The pathology revealed a tumor consisting of B-cell lymphoma, a PHEO forming a large adrenal mass with soft tissue invasion with extensive sclerosis and a separate nodule with PHEO without sclerosis. Immunohistochemistry and in situ hybridization of the lymphoma were consistent with Epstein-Barr virus-positive, diffuse large B-cell lymphoma. Immunohistochemistry of the PHEO was positive for chromogranin, synaptophysin, and S100. The Ki67 index was 8.7% and PHEO of the adrenal gland scaled score was 8 (≥4 is considered potentially malignant). CONCLUSION: To the best of our knowledge this is the first case demonstrating locally invasive and potentially malignant PHEO combined with primary malignant lymphoma in the same adrenal gland.

A histological and functional description of the tissue causing chronic postthrombotic venous obstruction.

BACKGROUND: Postthrombotic intraluminal tissue causing postthrombotic syndrome (PTS) has not been well described. This study defines its histological characteristics and assess whether tissue function evolves over time. METHODS: Specimens from 18 common femoral veins (CFV) from 16 patients obtained during CFV endovenectomy and iliocaval recanalization were examined. Phase 1 used hematoxylin and eosin and Masson's trichrome stains for collagen, immunohistochemical, and Von Kossa stains. Phase 2 examined young (≤ one year) and mature (≥10years from acute DVT) specimens to evaluate evolution of endothelial function. Antibodies to four biomarkers were used to examine specific functions of endothelial cells lining neovessels and recanalization channels (RC). RESULTS: Phase 1: Specimens demonstrated 80-90% of collagen type I, 10-20% of collagen type III, and dystrophic calcification. Neovessels and RC were in close proximity to each other. Thrombus and smooth muscle cells were absent, but white blood cells were present. Phase 2: VEGFR2 receptor uptake was more abundant in neovessels than RC and more prominent in younger specimens. Neovascular, nonchannel cells were observed more frequently in young specimens. CD-31 was similar in young and mature specimens. TIE-2 and von Willebrand factor antibodies had greater uptake in mature specimens. CONCLUSION: Tissue causing chronic postthrombotic venous obstruction is predominantly type I collagen. Neovascularization and recanalization occur in close proximity. The biomarker for neovascularization and angiogenesis (VEGFR2) was more prominent in young specimens whereas TIE-2, a stabilizing biomarker and vWF were more frequently observed in mature specimens.

A panel of DNA methylation markers reveals extensive methylation in histologically benign prostate biopsy cores from cancer patients.

BACKGROUND: Men with a negative first prostate biopsy will undergo one or more additional biopsies if they remain at high suspicion of prostate cancer. To date, there are no diagnostic tests capable of identifying patients at risk for a positive diagnosis with the predictive power needed to eliminate unnecessary repeat biopsies. Efforts to develop clinical tests using the epigenetic signature of cores recovered from first biopsies have been limited to a few markers and lack the sensitivity and specificity needed for widespread clinical adoption. METHODS: We developed methylation-specific quantitative polymerase chain reaction assays for a panel of 24 markers that are preferentially methylated in prostate cancer. We modified the bisulfite conversion conditions to allow the integration of the methylation information from multiple markers. We determined the methylation status of the 24 markers in 213 prostate biopsy cores from 104 patients, 37 prostate cancer patients and 67 controls. We performed logistic regression on combinations of markers as well as the entire panel of 24 markers to identify the best candidates for a diagnostic test. RESULTS: The marker panel differentiated between cancer cores and benign cores from non-cancer patients with 100% sensitivity and 97% specificity. Furthermore, the panel detected significant methylation in benign cores from prostate cancer patients that was not present in controls. Using methylation of 5 out of 24 to define a cancer case, the analysis of a single benign biopsy core identified 62% of prostate cancer patients undergoing repeat biopsies. ROC curve analysis showed that markers commonly methylated in benign cores from cancer patients are the best candidates for a diagnostic test. The results suggest that 5 to 10 markers will be needed to achieve optimal predictive power. CONCLUSIONS: This study shows that epigenetic field effects differ significantly between cancer patients and controls. Their detection in benign biopsy cores can form the basis of diagnostic tests to identify patients in need of repeat biopsies, reducing the cost of continued PCA screening by up to 40%. They could also be used to identify prostate cancer patients with low grade disease who are likely candidates for active surveillance or focal therapy.

Consensus statement on effective communication of urgent diagnoses and significant, unexpected diagnoses in surgical pathology and cytopathology from the College of American Pathologists and Association of Directors of Anatomic and Surgical Pathology.

CONTEXT: Recognizing the difficulty in applying the concept of critical values to anatomic pathology diagnoses, the College of American Pathologists and the Association of Directors of Anatomic and Surgical Pathology have chosen to reevaluate the concept of critical diagnoses. OBJECTIVE: To promote effective communication of urgent and significant, unexpected diagnoses in surgical pathology and cytology. DESIGN: A comprehensive literature search was conducted and reviewed by an expert panel. RESULTS: A policy of effective communication of important results in surgical pathology and cytology is desirable to enhance patient safety and to address multiple regulatory requirements. CONCLUSIONS: Each institution should create its own policy regarding urgent diagnoses and significant, unexpected diagnoses in anatomic pathology. This policy should be separate from critical results or panic-value policies in clinical pathology, with the expectation of a different time frame for communication. Urgent diagnosis is defined as a medical condition that, in most cases, should be addressed as soon as possible. Significant, unexpected diagnosis is defined as a medical condition that is clinically unusual or unforeseen and should be addressed at some point in the patient's course. Further details of this statement are provided.

Cats are not small dogs: the emergence of feline medicine.

Cats have finally garnered the attention they deserve in veterinary medicine, however, there is still much to learn about this unique species and new challenges surface daily. For example, at the time of writing, avian influenza in cats is being closely monitored by world veterinary and health officials. Controversial topics, such as how to manage the homeless cat population, declawing, and cloning will continue to spark active debate. However, the future appears promising for cats as more veterinarians, researchers, and organizations increase their focus on felines.

Lepromatous phlebitis of the external jugular vein.

Mycobacterium leprae (M leprae), the causative agent of Hansen's disease, is endemic in many areas of Asia, sub-Saharan Africa, South and Central America, the Pacific Islands, and the Philippines. The spectrum of clinical disease is dependent on the patient's cell-mediated immunity and might range from localized anesthetic patches or plaques to disseminated disease. If undiagnosed, progression with damage to the involved sensory and motor nerves might occur. Lepromatous vasculitis occurs most commonly in patients with severe disseminated disease. Vascular disease, as the initial presenting sign of tuberculoid leprosy, is, however, rare. We present one patient in whom the development of Hansen's disease was associated with involvement of the external jugular vein and was initially seen as external jugular vein fibrosis.

Histologic features of surgically removed fallopian tubes.

CONTEXT: The fallopian tube is a common specimen in a pathology laboratory. It may be examined either alone as a salpingectomy or tubal ligation specimen, or as part of a more complex specimen from a hysterectomy and/or oophorectomy operation. Although the common histologic findings in the fallopian tube have been described previously, to our knowledge no study has documented the frequency of histologic changes in fallopian tubes removed for all reasons or associations with clinical history. DESIGN: Hematoxylin-eosin-stained slides from 287 fallopian tube specimens were reviewed without knowledge of the clinical history. Three categories and associated subcategories of histologic findings were identified (listed in descending order of frequency): stromal and architectural alterations (fibrosis, intramuscular edema, cellular luminal contents, inclusion cysts, Walthard nests, pigmentosis tubae, Wolffian duct remnants, decidualized stroma, endosalpingiosis, and metastatic carcinoma), epithelial characteristics (cytologic atypia, vacuolization, metaplasia, and tufting), and inflammatory changes (intramuscular mast cells, plasma cells, neutrophils, and lymphoid follicles). Histologic findings were correlated with clinical history, surgery type, and age. RESULTS: Intramuscular edema was identified in 12.5% of specimens, most frequently in postpartum women. Plical fibrosis (35.5% of specimens), epithelial atypia (7.3%), epithelial vacuolization (6.6%), and epithelial tufting/stratification (3.5%) correlated with increased patient age. Inflammatory cells were relatively common; 69% of specimens contained intramuscular mast cells, 19.9% had stromal plasma cells, 10.5% had neutrophils, and 2.1% had lymphoid follicles. CONCLUSIONS: This study provides data that may be valuable for surgical pathologists involved in identifying and characterizing common histologic changes in surgically removed fallopian tubes.