Composite hemangioendothelioma: An unusual presentation of a rare vascular tumor.

OBJECTIVES: Composite hemangioendothelioma (CHE) has been recently recognized as a low- to intermediate-grade vascular tumor. CHEs are rare vascular tumors that are clinically similar to more common vascular tumors but histologically exhibit a composite of hemangioendothelioma variants. We report the first case of a CHE on the scalp and the fifth case to show findings supportive of regional metastasis. METHODS: Our patient had a multilobulated, violaceous scalp nodule, which on histologic examination revealed epithelioid, retiform, and spindle-cell components and rare foci of intermediate-grade mitotic activity consistent with CHE. RESULTS: Imaging studies were performed and revealed an abnormal uptake of contrast media in a posterior neck nodule that, when examined via fine-needle aspiration, revealed clumps of atypical cells. CONCLUSIONS: This unique case presentation is representative of the variability seen in the presentation of CHE and highlights the importance of considering CHE on the clinical and histologic differential of vascular tumors.

Immunomodulation by imiquimod in patients with high-risk primary melanoma.

Imiquimod is a synthetic Toll-like receptor 7 (TLR7) agonist approved for the topical treatment of actinic keratoses, superficial basal cell carcinoma, and genital warts. Imiquimod leads to an 80-100% cure rate of lentigo maligna; however, studies of invasive melanoma are lacking. We conducted a pilot study to characterize the local, regional, and systemic immune responses induced by imiquimod in patients with high-risk melanoma. After treatment of the primary melanoma biopsy site with placebo or imiquimod cream, we measured immune responses in the treated skin, sentinel lymph nodes (SLNs), and peripheral blood. Treatment of primary melanomas with 5% imiquimod cream was associated with an increase in both CD4+ and CD8+ T cells in the skin, and CD4+ T cells in the SLN. Most of the CD8+ T cells in the skin were CD25 negative. We could not detect any increases in CD8+ T cells specifically recognizing HLA-A(*)0201-restricted melanoma epitopes in the peripheral blood. The findings from this small pilot study demonstrate that topical imiquimod treatment results in enhanced local and regional T-cell numbers in both the skin and SLN. Further research into TLR7 immunomodulating pathways as a basis for effective immunotherapy against melanoma in conjunction with surgery is warranted.

Tissue-selective effects of injected deoxycholate.

BACKGROUND: Recent studies suggest that the principal active ingredient in phosphatidylcholine-containing injectable fat-reduction formulations is actually deoxycholate (DC). This bile acid acts as a detergent to rapidly disrupt cell membranes. Thus, it is not obvious why DC would preferentially target fat. OBJECTIVE: To investigate possible mechanisms for the selectivity of DC for fat tissue using in vivo and in vitro models. METHODS AND MATERIALS: Histology, drug distribution studies, and cell viability assays were used to examine possible mechanisms contributing to DC selectivity. RESULTS: In vitro, DC caused the lysis of all cell types tested within the tested concentration range. DC injected into fat tissue caused adipocyte death, whereas other cell types appeared less affected. Physiological concentrations of albumin or protein-rich tissues decrease the ability of DC to lyse cells. Furthermore, DC relocated to the gastrointestinal tract in animals within hours of injection. This suggests that similar mechanisms may be present in humans. CONCLUSION: We report observations that provide a possible explanation for the in vivo preferential fat targeting by DC. Fat tissue, being deficient in cell-associated proteins and interstitial albumin, may be unable to sufficiently neutralize the detergent activity of DC, possibly making fat uniquely sensitive to DC.

A light-emitting mouse to image skin inflammation.

BACKGROUND: The mouse ear swelling test is a well-accepted method for quantitating the inflammatory response to contact irritants and sensitizing agents. However, this assay measures edema rather than the cellular component of skin inflammation. OBJECTIVE: To develop a quantitative and noninvasive assay of inflammatory cell infiltration in contact dermatitis. METHODS: We bred a transgenic bioluminescent mouse that emits light proportional to cutaneous infiltration of inflammatory cells. We characterized this model by correlating luminescence with edema and histologic analysis of affected skin. A mouse strain expressing cyclization recombinase enzyme (cre) recombinase exclusively in myeloid cells was crossed with a reporter strain containing an inactivated form of the luciferase gene. In progeny mice, cre-mediated recombination repaired the luciferase gene, causing light emission from myeloid cells. Light emission and swelling from the inflamed ear was quantitated and compared to the contralateral ear. RESULTS: Light intensity correlated with the inflammatory cell infiltration in the dermis. In sensitized mice challenged with squaric acid, luminescence increased about 2.2-fold while swelling increased about 1.5-fold. CONCLUSION: Our model may serve as a useful screening assay for topical antiinflammatory molecules. Moreover, this approach allows real-time imaging of skin infiltration by specific inflammatory cell lineages in living animals.