Indurated purple plaques on the scalp.

Cutaneous epithelioid angiosarcoma is a rare neoplasm of vascular endothelial cell origin that can mimic a cutaneous lymphoma, metastatic carcinoma, or Kaposi sarcoma. It is one of the most malignant cutaneous tumors and early diagnosis is essential, as the tumor metastasizes quickly. We describe a 75-year-old man who presented with three tender, indurated violaceous plaques on his scalp. Biopsy revealed a poorly circumscribed infiltrate extending into the subcutaneous fat, composed of atypical epithelioid cells lining vascular spaces. We provide a brief review of the clinical presentation, histopathologic features, differential diagnosis, and management of this rare tumor.

Aleukemic cutaneous myeloid sarcoma.

BACKGROUND: Aleukemic cutaneous myeloid sarcoma (CMS) represents an important yet rare entity denoting the presence of a cutaneous myeloid leukemic infiltrate without concurrent peripheral blood or bone marrow disease. The clinicopathologic diagnosis remains elusive due to isolated skin findings and variable immunostaining. Cytogenetic and molecular findings have infrequently been reported. METHODS: Twenty-five patients with CMS were identified in the Massachusetts General Hospital pathology database between 2004 and 2012. Patients were excluded if concurrent blood or marrow acute myeloid leukemia (AML), myelodysplastic syndrome or lymphoproliferative disorder were diagnosed. RESULTS: Three patients were identified: a neonate with recurrent CMS and marrow disease that never met diagnostic criteria for AML and two patients relapsing as CMS without concurrent blood or marrow disease following chemotherapy-induced complete remission. Histology showed atypical mononuclear cell interstitial dermal infiltrates. All cases were CD68+, lysozyme+ and CD117-; one of two were CD34+; two of three were myeloperoxidase negative. 11q23 rearrangement, t(1;14), NPM1 (nucleophosmin I), FLT3-ITD (Fms-like tyrosine kinase 3-internal tandem duplication), and novel FLT3-D835 mutations were identified. CONCLUSION: An isolated atypical cutaneous infiltrate may represent aleukemic CMS and should prompt a search for other extramedullary sites of involvement. Immunohistochemistry, molecular and cytogenetic studies can help differentiate aleukemic CMS from benign and malignant, monocytic and histiocytic mimickers, and may potentially indicate therapy and prognosis.

Analysis of botulinum toxin products and litigation in the United States.

BACKGROUND: Botulinum neurotoxin (BoNT) has diverse cosmetic and therapeutic applications, spanning multiple medical specialties. Recent lawsuits alleging complications from its clinical use have raised significant questions about medicolegal risk. OBJECTIVE: To identify and assess legal cases related to clinical complications of BoNT products. METHODS AND MATERIALS: Using the LexisNexis Academic online database, a search of U.S. federal and state cases between 1985 and 2012 was performed. A second search of U.S. newspapers and wires was also completed. In all but one case, the plaintiffs' legal complaints were obtained for review. RESULTS: Twenty-four relevant legal cases were found, mostly in state courts. All cases alleged adverse effects from onabotulinumtoxinA, and each named its manufacturer, Allergan, Inc., as a defendant. Most lawsuits against Allergan, Inc. were dismissed or settled. In three cases, physicians were codefendants, including one dermatologist. In two cases, jury verdicts resulted in multimillion-dollar judgments in favor of the plaintiffs. None of the lawsuits named a dermatologist when the complication arose from on-label indications and cosmetic use. CONCLUSION: Lawsuits related to complications from BoNT products are uncommon, are more likely to result from therapeutic than cosmetic applications, and typically involve product liability claims against the manufacturer.

Developing melanoma therapeutics: overview and update.

Melanoma is a common, often deadly malignancy, historically associated with limited treatment options for advanced disease. In recent years, systems-based research has resulted in significant clinical advancements. Strategic inhibition of mutated oncoproteins and targeting of immune checkpoints have emerged as very promising approaches. Vemurafenib, which received US Food and Drug Administration (FDA) approval in 2011, selectively inhibits BRAF(V600E) , a hyperactivated mutant signaling kinase in the mitogen-activated protein kinase (MAPK) pathway. Another recently FDA-approved drug, ipilimumab, blocks the cytotoxic T-lymphocyte antigen-4 (CTLA-4) pathway from inhibiting T cell activation. Despite this apparent progress, compelling challenges remain for both researchers and clinicians. Responses to therapy remain unacceptably incomplete and, in most cases, resistance mechanisms quickly develop that lead to relapse and subsequent patient mortality. Combining therapeutic modalities may increase the percentage of responding patients as well as the magnitude and durability of response. Notably, combined therapies involving selective BRAF inhibitors (SBIs) and other inhibitors of MAPK-dependent or MAPK-independent resistance pathways appear particularly promising. Preclinical and clinical studies are needed to comprehensively evaluate the optimal combinations of therapies, to identify melanoma subtypes that will be most responsive, and to determine optimal dosing, timing, and route of delivery.

Molecular targeting of acid ceramidase: implications to cancer therapy.

Increasingly recognized as bioactive molecules, sphingolipids have been studied in a variety of disease models. The impact of sphingolipids on cancer research facilitated the entry of sphingolipid analogues and enzyme modulators into clinical trials. Owing to its ability to regulate two bioactive sphingolipids, ceramide and sphingosine-1-phosphate, acid ceramidase (AC) emerges as an attractive target for drug development within the sphingolipid metabolic pathway. Indeed, there is extensive evidence supporting a pivotal role for AC in lipid metabolism and cancer biology. In this article, we review the current knowledge of the biochemical properties of AC, its relevance to tumor promotion, and its molecular targeting approaches.