Histologic and molecular analyses of colonic perineurial-like proliferations in serrated polyps: perineurial-like stromal proliferations are seen in sessile serrated adenomas

Colonic perineuriomas are recently described benign mucosal polyps that are composed of a bland spindle cell proliferation surrounding crypts that often demonstrate hyperplastic/serrated epithelial changes. However, the origin of this unique stromal proliferation is still unclear, and the association with serrated polyps, including sessile serrated adenomas, has not been fully described. We evaluated the pathologic and molecular features of colonic polyps associated with perineurial-like proliferations in 2 retrospective cohorts: (1) a series of 198 consecutive sessile serrated adenomas and (2) 20 colonic polyps diagnosed as a perineurioma irrespective of the presence of serrated colonic crypts. Thirteen of 198 (6.5%) sessile serrated adenomas demonstrated a perineurial-like stromal proliferation, with most (12 of 13, 92%) involving the right (9 cases) and transverse colon (3 cases). In all 13 cases, the perineurial-like proliferation surrounded serrated colonic crypts and typically involved only a small area of the sessile serrated adenoma (average 9% of polyp size; range, 2% to 19%). All 11 polyps evaluated for epithelial membrane antigen (EMA) expression demonstrated stromal EMA staining limited to the perineurial-like proliferation. Twelve of 13 (92%) sessile serrated adenomas with perineurial-like proliferations demonstrated a pV600E BRAF mutation. Of the 20 colonic polyps diagnosed as a perineurioma, 18 (90%) demonstrated serrated crypts intimately associated with the perineurial-like proliferation. In 13 of 18 polyps with associated serrated crypts, all serrated crypts were invested with the perineurial proliferation. In 5 cases, serrated crypts were seen away from the perineurial proliferation. Of these 18 polyps, the majority (16 of 18, 89%) were microvesicular hyperplastic polyps involving the left colon. However, 2 (11%) polyps in the right colon demonstrated histologic features diagnostic of sessile serrated adenoma. All 18 polyps with serrated crypts demonstrated a pV600E BRAF mutation. In contrast, the 2 polyps not associated with serrated crypts were negative for a BRAF mutation. Our results show for the first time that perineurial-like stromal proliferations frequently occur in sessile serrated adenomas. The presence of focal perineurial-like stromal proliferations in sessile serrated adenomas and the common finding of serrated crypts in colonic perineuriomas are likely indicative of an epithelial-stromal interaction, possibly related to some factor elaborated by the serrated epithelium.     

Opportunities to intervene? “Warning signs” for suicide in the days before dying

To validate warning signs for suicide, researchers interviewed 20 respondents, representing 17 suicides in Orleans Parish, Louisiana, about characteristics of the decedent in the year, month, and days preceding the death. Decedents did exhibit behaviors consistent with existing warning signs, but these were rarely new behaviors present 7 days prior to the suicide but not previously. Research is needed to continue to test warning signs for suicide, and education campaigns that teach warning signs may not be relevant for preventing suicide among those in mental health treatment or involved in the criminal justice system.     

Cell-mediated immunity to herpes simplex virus: recognition of type-specific and type-common surface antigens by cytotoxic T cell populations.

In this communication, we examine the specificity of anti-herpes simplex virus (HSV) cytotoxic T lymphocytes (CTL). Serological studies of the two related HSV serotypes (HSV-1 and HSV-2) have revealed both type-specific and cross-reactive antigenic determinants in the viral envelope and on the surface of infected cells. By analysis of cytotoxicity of CTL, generated in vitro by restimulation of splenocytes from mice primed with one or the other HSV serotype, the recognition of both type-specific and cross-reactive determinants on infected target cells by anti-HSV CTL was detectable. Thus, effector cells generated by priming and restimulating with the same virus recognized both type-specific and cross-reactive determinants on target cells infected with the homologous virus, but only cross-reactive determinants on target cells infected with the heterologous HSV serotype. CTL generated by restimulation with the heterologous virus were capable of recognizing only the cross-reactive determinants on either HSV-1- or HSV-2-infected target cells. These results indicate that two subpopulations of CTL exist in a population of anti-HSV immune spleen cells--those which recognize type-specific determinants and those specific for cross-reactive antigenic determinants present on the surface of HSV infected cells. The type-specific subset of anti-HSV CTL was shown to recognize the gC glycoprotein of HSV-1 infected target cells. In addition to the gC glycoprotein, at least one other type-specific surface antigen was also recognized by anti-HSV CTL in addition to the cross-reactive determinants recognized by anti-HSV CTL.