PURPOSE: We wished to determine whether virally- induced endothelial tumors are rejected by CD4 and CD8 lymphocytes, and whether there are differences in requirements for costimulation in the rejection of these tumors by lymphocyte subsets. EXPERIMENTAL DESIGN: We have developed a model of endothelial tumorigenesis through the sequential introduction of SV40 large T antigen and oncogenic H-ras into endothelial cells. These cells (SVR cells) form highly aggressive angiosarcomas in immunocompromised mice, but do not grow in syngeneic C57BL/6 mice. Using both acute blockade with systemic administration of antibodies and mice genetically deficient in the costimulatory molecules CD28, CD40, and CD40L, we have delineated the requirements of costimulation required to reject this virally-induced endothelial tumor. RESULTS: Control of SVR angiosarcoma is mediated through T lymphocytes, and both CD4 and CD8 lymphocytes are capable of controlling SVR angiosarcoma growth in vivo. Mice genetically deficient in CD28, CD40, and CD40L were able to reject SVR tumors, but depletion of these mice of CD8, but not CD4 cells led to rapid tumor growth. This data suggests that CD4 mediated rejection has a greater dependence of costimulation than CD8 mediated rejection. Surprisingly, acute depletion of costimulatory molecules in immunocompetent C57BL/6 mice led to rapid tumor growth. CONCLUSIONS: Significant differences exist in the immune status of mice acutely depleted of costimulatory molecules versus genetically deficient mice. Our results suggest that acute depletion is more immunosuppressive than genetic depletion. Humans who undergo costimulatory blockade may require periodic surveillance for virally-induced tumors.

Background/Purpose: Synoptic, or standardized, reporting of surgery and pathology reports has been widely adopted in surgical oncology. Patients with Hirschsprung disease may experience morbidity related to surgical factors or underlying pathology and often undergo multiple operations. Our aim is to improve the postoperative outcome and care of patients with Hirschsprung disease by proposing a standardized set of data that should be included in every surgery and pathology report. Methods: Members of the American Pediatric Surgical Association Hirschsprung Disease Interest Group and experts in pediatric pathology of Hirschsprung disease participated in group discussions, performed literature review and arrived at expert consensus guidelines for surgery and pathology reporting. Results: The importance of accurate operative and pathologic reports and the implications of inadequate documentation in patients with Hirschsprung disease are discussed and guidelines for standardizing these reports are provided. Conclusions: Adherence to the principles of reporting for operations and surgical pathology may improve outcomes for Hirschsprung disease patients and will facilitate identification of correlations among morphology, function, genetics and outcomes, which are required to improve the overall management of these patients. Level of Evidence: V.

Background Previously, using imaging mass spectrometry (IMS), we discovered proteomic differences between Spitz nevi and Spitzoid melanomas. Objective We sought to determine whether IMS can assist in the classification of diagnostically challenging atypical Spitzoid neoplasms (ASN), to compare and correlate the IMS and histopathological diagnoses with clinical behavior. Methods We conducted a retrospective collaborative study involving centers from 11 countries and 11 US institutions analyzing 102 ASNs by IMS. Patients were divided into clinical groups 1 to 4 representing best to worst clinical behavior. The association among IMS findings, histopathological diagnoses, and clinical groups was assessed. Results There was a strong association between a diagnosis of Spitzoid melanoma by IMS and lesions categorized as clinical groups 2, 3, and 4 (recurrence of disease, metastases, or death) compared with clinical group 1 (no recurrence or metastasis beyond a sentinel node) (P  <  .0001). Older age and greater tumor thickness were strongly associated with poorer outcome (P = .01). Conclusions IMS diagnosis of ASN better predicted clinical outcome than histopathology. Diagnosis of Spitzoid melanoma by IMS was strongly associated with aggressive clinical behavior. IMS analysis using a proteomic signature may improve the diagnosis and prediction of outcome/risk stratification for patients with ASN.