Metastatic cutaneous melanoma has poor prognosis with 2-year survival rate of 10–20%. Melanoma cells express various antigens including gp100, melanoma antigen recognized by T cells 1 (MART-1), and tyrosinase, which can induce immune-mediated anticancer response via T cell activation. Cytotoxic T-lymphocyte associated antigen-4 (CTLA-4) is an immune check point molecule that negatively regulates T cell activation and proliferation. Accordingly, recent phase III clinical trials demonstrated significant survival benefit with ipilimumab, a human monoclonal antibody (IgG1) that blocks the interaction of CTLA-4 with its ligands. Since the efficacy of ipilimumab depends on T cell activation, it is associated with substantial risk of immune mediated adverse reactions such as colitis, hepatitis, thyroiditis, and hypophysitis. We report the first case of late onset pericarditis and cardiac tamponade associated with ipilimumab treatment in patient with metastatic cutaneous melanoma.

Vascular endothelial growth factor B (VEGF-B) has recently been shown to be a promising novel neuroprotective agent for several neurodegenerative conditions. In the current study we extended previous work on neuroprotective potential for Parkinson’s disease (PD) by testing an expanded dose range of VEGF-B (1 μg and 10 μg) and directly comparing both neuroprotective and neurorestorative effects of VEGF-B in progressive unilateral 6-hydroxydopamine (6-OHDA) PD models to a single dose of glial cell line-derived neurotrophic factor (GDNF, 10 μg), that has been established by several groups as a standard in both preclinical PD models. In the amphetamine-induced rotational tests the treatment with 1 and 10 μg VEGF-B resulted in significantly improved motor function of 6-OHDA-lesioned rats compared to vehicle-treated 6-OHDA-lesioned rats in the neuroprotection paradigm. Both doses of VEGF-B caused an increase in tyrosine hydroxylase (TH)-positive cell and fiber count in the substantia nigra (SN) and striatum in the neuroprotective experiment. The effect size was comparable to the effects seen with GDNF. In the neurorestoration paradigm, VEGF-B injection had no significant effect in either the behavioral or the immunohistochemical analyses, whereas GDNF injection significantly improved the amphetamine-induced rotational behavior and reduced TH-positive neuronal cell loss in the SN. We also present a strong positive correlation (p = 1.9 e-50) of the expression of VEGF-B with nuclear-encoded mitochondrial genes involved in fatty acid metabolism in rat midbrain, pointing to the mitochondria as a site of action of VEGF-B. GDNF showed a positive correlation with nuclear-encoded mitochondrial genes that was not nearly as strong (p = 0.018). VEGF-B counteracted rotenone-induced reduction of (a) fatty acid transport protein 1 and 4 levels and (b) both Akt protein and phosphorylation levels in SH-SY5Y cells. We further verified VEGF-B expression in the human SN pars compacta of healthy controls and Parkinson’s disease patients, in neuronal cells that show co-expression with neuromelanin. These results have demonstrated that VEGF-B has potential as a neuroprotective agent for PD therapy and should be further investigated.

Pleomorphic liposarcoma is the least common subtype of liposarcoma, accounting for less than 5% of cases, but is important to distinguish from other liposarcoma subtypes due to a significantly worse prognosis closer to that of a high-grade sarcoma. A substantial proportion of cases demonstrate histologic features overlapping with myxofibrosarcoma, except for the presence of diagnostic pleomorphic lipoblasts. These lipoblasts are essential to the diagnosis of pleomorphic liposarcoma, in contrast to the other subtypes of liposarcoma, but can be highly focal/variable in extent, mandating extensive gross sampling and thorough histologic examination and representing a pitfall in diagnosis particularly in small biopsies. Awareness of the less common histologic patterns of this uncommon entity will hopefully facilitate correct diagnosis.

Transcription factor E3 (TFE3) represents a useful target for immunohistochemistry assays in routine surgical pathology practice. This protein has shown nuclear expression in a variety of normal tissues; however, this expression is usually at very low levels, while strong nuclear immunoreactivity of TFE3 has been seen almost exclusively in tumors. We present the case of a 30-year-old female on oral contraceptive pill (drospirenone/ethinylestradiol) and with complaints of dysmenorrhea and menorrhagia. She was found to have a cervical mass on pelvic ultrasound, and the biopsy showed fragments of benign squamous epithelium and polypoid endometrial tissue with stromal pseudodecidualization and abundant mixed inflammation. The pseudodecidualized stromal component showed moderate to strong nuclear staining in ~85% of stromal cells for TFE3. We discuss the intracellular role of TFE3 during inflammatory states and hypothesize that TFE3 expression can be associated with ongoing inflammation. Our case shed light upon the possibility that nonneoplastic environments with an inflammatory background could lead to increased nuclear expression of TFE3. Pathologists should be aware of the possibility of strong nuclear expression of TFE3 in nonneoplastic endometrium to avoid potential misdiagnosis.