Intradural extramedullary spinal metastases from uterine carcinosarcoma: A case report.

BACKGROUND: In recent years, improvements in oncological care have led to an increased incidence of intradural extramedullary spinal metastases (IESMs) attributed to uterine carcinosarcoma (UCS). When such lesions occur, they typically carry a poor prognosis. Here, we have evaluated newer treatments, management strategies, and outcomes for IESM due to UCS. CASE DESCRIPTION: A 59-year-old female with a history of recurrent UCS presented with the new onset of the left lower extremity pain, numbness, and episodic urinary incontinence. When the MR revealed an enhancing intradural extramedullary mass posterior to the L1 vertebral body, she underwent a focal decompressive laminectomy. Although she improved neurologically postoperatively, she succumbed to the leptomeningeal spread of her disease within 2 postoperative months. CONCLUSION: Management of IESM due to UCS requires multifaceted, individualized treatment modalities, including neurosurgery, radiation therapy, and medical oncologic management to maximize outcomes.

Mechanism, Consequences, and Therapeutic Targeting of Abnormal IL15 Signaling in Cutaneous T-cell Lymphoma.

UNLABELLED: Cutaneous T-cell lymphoma (CTCL) is the most common type of primary cutaneous lymphoma. Here, we report that patients with CTCL show increased IL15 in a clinical stage-dependent manner. Mechanistically, we show that ZEB1 is a transcriptional repressor of IL15 in T cells and that hypermethylation of the ZEB1 binding region within the IL15 promoter, as seen in patients with CTCL, prevents ZEB1 binding and causes increased transcription of IL15 Using a transgenic mouse model of IL15, we provide evidence that overexpression of IL15 induces a spontaneous CTCL that mimics the human neoplasm. Excessive autocrine production of IL15 in T cells inhibits an HDAC1-mediated negative autoregulatory loop, resulting in the upregulation of HDAC1 and HDAC6 and transcriptional induction of the onco-miR-21. Interruption of IL15 downstream signaling with isotype-specific HDAC inhibitors halts (HDAC1) or significantly delays (HDAC6) the progression of CTCL in vivo and provides preclinical evidence supporting a hierarchical model of oncogenic signaling in CTCL. SIGNIFICANCE: To date, CTCL pathogenesis remains unknown, and there are no curative therapies. Our findings not only demonstrate a critical role for IL15-mediated inflammation in cutaneous T-cell lymphomagenesis, but also uncover a new oncogenic regulatory loop in CTCL involving IL15, HDAC1, HDAC6, and miR-21 that shows differential sensitivity to isotype-specific HDAC inhibitors. Cancer Discov; 6(9); 986-1005. ©2016 AACR.This article is highlighted in the In This Issue feature, p. 932.

Swelling among women who need education about leg lymphedema: a descriptive study of lymphedema in women undergoing surgery for endometrial cancer.

OBJECTIVES: In addition to hysterectomy and bilateral salpingo-oophorectomy, comprehensive surgical staging for endometrial cancer includes pelvic and para-aortic lymphadenectomy. Clarifying and addressing the morbidity from these surgical procedures is imperative. The goal of this study was to assess the prevalence of lower extremity swelling after surgery for endometrial cancer. MATERIALS AND METHODS: We performed a descriptive, cross-sectional survey study of women who underwent surgery for endometrial cancer at our institution from 2006 to 2008. Survey information included symptoms, management, and education regarding lymphedema. Demographic information such as race and education was collected in addition to clinical data such as body mass index and age. RESULTS: Of the 482 patients identified, 440 were determined eligible and 305 (69.3%) responded to the survey with information on lower limb swelling (LLS). Of the 108 (35%) responders who reported swelling, only 68 (22%) participants reported a diagnosis of lower limb lymphedema (LLL). The most commonly experienced symptoms among those who reported LLS were tightness, pain/tenderness, and heaviness. Among those with a diagnosis of LLL, most (60%) stated it affected their daily activities and noted exacerbating factors such as prolonged standing, heat, and walking. The most common therapies used to reduce symptoms included leg elevation (96%), compression stockings (65%), diuretics (46%), massage therapy (35%), and bandaging (25%). There was no association between LLS or LLL diagnosis and body mass index, age, race, and tobacco use. Only 8% of responders reported receiving preoperative education regarding risks for LLS and a desire for more comprehensive education was frequently noted. CONCLUSIONS: The patient-reported incidence of LLS occurred in approximately 35% of survey participants who underwent surgery for endometrial cancer. However, only 22% reported a diagnosis of LLL. Efforts to obtain the true incidence of LLL and to develop effective educational materials and programs to improve the management of lymphedema are warranted.

A novel mouse model for the aggressive variant of NK cell and T cell large granular lymphocyte leukemia.

Murine models of disease are vital to the understanding of pathogenesis and the development of novel therapeutics. We have previously established interleukin (IL)-15 transgenic (tg) mice that demonstrate rapid proliferation of natural killer (NK) and T cells, followed by spontaneous transformation to lethal leukemia. Herein, we have characterized this model, which has many features in common with the aggressive variants of NK and T large granular lymphocyte leukemia (LGLL) in humans. The LGLL blasts are cytolytic and produce IFN-gammaex vivo. Cytogenetic analysis revealed trisomy of chromosome 17 and/or 15. This model should provide opportunities to develop effective standard therapies for this fatal disease.