In-Transit Metastasis From Squamous Cell Carcinoma.

BACKGROUND: In-transit metastasis from cutaneous squamous cell carcinoma (SCC) is an uncommon form of metastasis through lymphatics and occurs more commonly in immunosuppressed patients. OBJECTIVE: To identify cases of in-transit SCC and determine patient characteristics, tumor features, management, and prognosis. METHODS AND MATERIALS: A multicenter case series treated by Australian and New Zealand clinicians. RESULTS: In 31 patients, median age was 72 years (range 52-99) and 68% were immunocompetent. Tumors occurred on the head and neck in 94% of cases, with 71% of all tumors occurring on the scalp, forehead, or temple. The median time to presentation with in-transit SCC from treatment of the initial tumor was 5 months. Management included surgery (94%), radiotherapy (77%), chemotherapy (10%), and reduction of immunosuppression (3%). Median follow-up was 12 months. Overall survival at 3 and 5 years were 27% and 13%, respectively. CONCLUSION: In-transit metastases are described in 31 patients, of whom the majority was immunocompetent. The scalp, forehead, and temple were the most common sites. New clinical and histological diagnostic criteria are proposed. Prognosis was poor with 5-year survival of 13%. Recommended management is a combination of surgery and adjuvant radiotherapy. Reduction of any iatrogenic immunosuppression should be considered.

Double island pedicle or V-Y flap repair for partial-thickness combined defects of the cutaneous and mucosal lip.

BACKGROUND: Removal of skin cancer at or near the vermilion border may result in a partial-thickness combined cutaneous and mucosal lip defect for which repair has potential for poor cosmetic and functional outcomes. OBJECTIVE: We sought to describe the closure and results from repair of combined lip defects using 2 island pedicle or V-Y flaps, 1 for the cutaneous lip and 1 for the mucosa. METHODS: A retrospective review of all patients with combined defects of the lip who underwent double island pedicle or V-Y flap repair from June 2008 to December 2013 was performed. RESULTS: Ten patients (6 female, 4 male; ages 35-89 years, mean age 60 years) had defects on the upper lip in 8 cases and on the lower lip in 2 cases. Follow-up was for 3 months or longer with good or excellent outcomes in all cases. LIMITATIONS: This was a nonrandomized, unblinded clinical case series with a limited sample size. CONCLUSION: Double island pedicle or V-Y flap repair is an elegant closure with good to excellent results and may avoid potential problems inherent in other repair options.

Deletion of astroglial CXCL10 delays clinical onset but does not affect progressive axon loss in a murine autoimmune multiple sclerosis model.

Multiple sclerosis (MS) is characterized by central nervous system (CNS) inflammation, demyelination, and axonal degeneration. CXCL10 (IP-10), a chemokine for CXCR3+ T cells, is known to regulate T cell differentiation and migration in the periphery, but effects of CXCL10 produced endogenously in the CNS on immune cell trafficking are unknown. We created floxed cxcl10 mice and crossed them with mice carrying an astrocyte-specific Cre transgene (mGFAPcre) to ablate astroglial CXCL10 synthesis. These mice, and littermate controls, were immunized with myelin oligodendrocyte glycoprotein peptide 35-55 (MOG peptide) to induce experimental autoimmune encephalomyelitis (EAE). In comparison to the control mice, spinal cord CXCL10 mRNA and protein were sharply diminished in the mGFAPcre/CXCL10fl/fl EAE mice, confirming that astroglia are chiefly responsible for EAE-induced CNS CXCL10 synthesis. Astroglial CXCL10 deletion did not significantly alter the overall composition of CD4+ lymphocytes and CD11b+ cells in the acutely inflamed CNS, but did diminish accumulation of CD4+ lymphocytes in the spinal cord perivascular spaces. Furthermore, IBA1+ microglia/macrophage accumulation within the lesions was not affected by CXCL10 deletion. Clinical deficits were milder and acute demyelination was substantially reduced in the astroglial CXCL10-deleted EAE mice, but long-term axon loss was equally severe in the two groups. We concluded that astroglial CXCL10 enhances spinal cord perivascular CD4+ lymphocyte accumulation and acute spinal cord demyelination in MOG peptide EAE, but does not play an important role in progressive axon loss in this MS model.

Organotypic distribution of stem cell markers in formalin-fixed brain harboring glioblastoma multiforme.

The role of stem cells in the origin, growth patterns, and infiltration of glioblastoma multiforme is a subject of intense investigation. One possibility is that glioblastoma may arise from transformed stem cells in the ventricular zone. To explore this hypothesis, we examined the distribution of two stem cell markers, activating transcription factor 5 (ATF5) and CD133, in an autopsy brain specimen from an individual with glioblastoma multiforme. A 41-year-old male with a right posterior temporal glioblastoma had undergone surgery, radiation, and chemotherapy. The brain was harvested within several hours after death. After formalin fixation, sectioning, and mapping of tumor location in the gross specimen, histologic specimens were prepared from tumor-bearing and grossly normal hemispheres. Fluorescence immunohistochemistry and colorimetric staining were performed for ATF5 and CD133. Both markers co-localized to the ependymal and subependymal zones on the side of the tumor, but not in the normal hemisphere or more rostrally in the affected hemisphere. ATF5 staining was especially robust within the diseased hemisphere in histologically normal ependyma. To our knowledge, this is the first in situ demonstration of stem cell markers in whole human brain. These preliminary results support the hypothesis that some glioblastomas may arise from the neurogenic zone of the lateral ventricle. The robust staining for ATF5 and CD133 in histologically normal ventricular zone suggests that an increase in periventricular stem cell activity occurred in this patient on the side of the tumor, either as a localized response to brain injury or as an integral component of oncogenesis and tumor recurrence.

Overexpression of copper/zinc superoxide dismutase decreases ischemia-like astrocyte injury.

Overexpression of copper/zinc superoxide dismutase (SOD1) in transgenic mice protects from transient focal cerebral ischemia in adult animals, but increases oxidative injury in perinatal mice. The effect of SOD1 overexpression on astrocytes subjected to ischemia-like insults has not yet been determined. Overexpression of human SOD1 in astrocytes resulted in a 3-fold increase in SOD1 activity without coupled up-regulation of catalase or glutathione peroxidase activities. Cells subjected to oxygen-glucose deprivation (OGD) or glucose deprivation to mimic ischemic injury were protected by SOD1 overexpression. OGD injury was reduced 47.6+/-9.3%, assessed by release of lactate dehydrogenase. OGD also caused a significant increase in catalase activity which was moderated by SOD1 overexpression. The level of glutathione in astrocytes overexpressing SOD1 was maintained at higher levels following 5 h OGD compared to control cultures under the same conditions. Reduction of glutathione prior to OGD significantly increased cell death of SOD1-overexpressing astrocytes as well as controls, but SOD1 still provided significant protection, suggesting that both GSH-dependent scavenging and GSH-independent scavenging are relevant to SOD1 protection in astrocytes.