The April Case of the Month (COM). The contributors report a case of a 70 year-old woman with recurrent meningiomas, one of which showed rhabdoid and lipomatous differentiation. Histopathological ...study of the first and second previous resections showed only typical meningothelial meningioma. On the third craniotomy, a new tumor specimen showed an admixture of classic meningothelial meningioma with lipomatous and rhabdoid foci. Immunohistochemical studies showed diffuse reactivity for epithelial membrane antigen and vimentin, as well as focal positivity for desmin and smooth muscle actin in the areas with rhabdoid features and S100 protein in the lipomatous foci. The presence of these three different and concomitant histological patterns only in the third surgical resection might support a metaplastic origin and, also, corroborates the concept that rhabdoid features are suggestive of an aggressive behavior.
Abstract
Background: Personalized healthcare tailors treatments to patients and their disease characteristics through the use of genetics and other biomarkers. Genetic differences among individuals ...may explain variations in drug treatment response, including side effects. With such information physicians could make more informed decisions about drugs and dosing for a given individual, thereby improving patient care. Although there has been some success, to a large extent genetic variation related to drug response remains unexplained.
Bevacizumab, a humanized monoclonal antibody against the angiogenic factor VEGF, has demonstrated activity in patients with metastatic breast cancer (MBC). The InVite study will evaluate the feasibility of performing genomewide association studies using self-reported information collected via an online platform from patients with MBC who have been treated with bevacizumab. Using novel methodology in a convenient, user-friendly, and scientifically rigorous format, InVite ultimately aims to identify potential pharmacogenetic associations in this patient population.
Trial design: InVite is a pilot, non-interventional, observational, web-based, prospective cohort study designed to collect patient-reported safety, efficacy, and genetic data from patients with MBC treated with bevacizumab. Data on demographics, breast cancer disease status, cancer treatment history, bevacizumab-related outcomes, and certain safety events will be collected directly from patients entirely via online surveys. Patients will be asked to complete surveys at the time of enrollment and then every 3 months for 1 year after enrollment. A saliva sample for DNA collection will be gathered using an at-home kit. Evaluations of data quality and collection feasibility will be conducted intermittently. There will be an optional substudy to allow for blood sample collection for DNA analysis.
Eligibility criteria: ≥18 years of age, residing in the US, locally recurrent breast cancer or MBC, currently being or having been treated with bevacizumab starting on or before Dec 31, 2011, fluent in English, and access to a computer with an internet connection.
Specific aims: The primary objective is to assess the feasibility of recruiting subjects and collecting biospecimens and self-reported data online. The secondary objective is to characterize the patient population. Exploratory objectives include analyzing potential associations between genetic polymorphisms and 1) bevacizumab-induced hypertension, the most common bevacizumab-related adverse event, and 2) patient-reported time-to-progression.
Statistical methods: Baseline demographics, clinical and treatment characteristics of enrolled patients will be summarized. Each polymorphism genotyped will be tested for association with the defined endpoint using appropriate statistical modeling.
Present and target accrual: Accrual as of May 23, 2012 is 82 patients. Target accrual is 1000 patients.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr OT3-4-04.
: Invasive zygomycosis is a devastating fungal infection occurring as an opportunistic infection after bone marrow transplantation (BMT). Sinusitis can lead to fungal infection in immunosuppressed ...patients, and cavernous sinus thrombosis, an uncommon condition in immunocompetent patients, typically follows an infection involving the medial third of the face, nose, or paranasal sinuses. Patients undergoing unrelated‐donor BMT (UD‐BMT) are prone to develop life‐threatening infections because of poor recovery of cellular immunity. Despite adequate clinical evaluation and treatment, the prognosis of patients with invasive fungal infections is dismal, especially when intracerebral structures are affected. We describe a case of a patient who underwent an UD‐BMT and developed cavernous sinus thrombosis after sinusitis due to zygomycosis. Moreover, he also had disseminated fungal (Zygomycetes and Aspergillus) and viral (cytomegalovirus and adenovirus) infections.
CASES OF THE MONTH: April 2001 – June 2001 Hamilton, Ronald L.; Bleggi‐Torres, L.F.; Reis‐Filho, J. S. ...
Brain pathology (Zurich, Switzerland),
04/2011, Letnik:
11, Številka:
4
Journal Article
Myofibroblastoma of the breast is a rare benign neoplasm, which has rarely been reported in association with gynecomastia. We report a case of a 25-year-old male patient with an epithelioid ...myofibroblastoma arising in a context of bilateral gynecomastia. The lesion was composed of nests and cords of epithelioid cells, with round to oval nuclei, granular chrornatin, and distinct nucleoli dispersed in a myxoid to collagenous stroma with marked vascular proliferation. Immunohistocrhemical profile showed diffuse positivity for vimentin and focal immunoreactivity for desmin, whereas cytokeratins (CAM5.2 and AE1/AE3), EMA, alph-a smooth muscle actin, actin HHF35, CEA, S1OO, factor VIII, neuron-specific enolase, CD31, and CD34 were all negative. We emphasize that this diagnosis is difficult to establish, owing to the rarity of this variant and clinical presentation.
Abstract only
7656
Background: The protein kinase C (PKC) family of serine-threonine protein kinases has been shown to be involved in tumor cell growth, survival, and progression. Tumor-induced ...angiogenesis requires activation of PKCs, particularly PKCβ, through vascular endothelial growth factor (VEGF) pathways. PKCβ-2 appears to be a major down-stream signaling protein for the VEGFR. This makes PKCβ an attractive target in treatment of malignancies, including lung cancer. Methods: 135 tumor samples (111 Non-small cell lung cancer tissues (52 adenocarcinomas (AC), 34 large cell (LC), 25 squamous cell carcinoma (SCC)) and 24 mesotheliomas (MT)) arranged in tumor microarrays (TMAs) were subject to immunohistochemical staining of PKCβ-1 and PKCβ-2. Results were analyzed manually and scored for intensity (1+, 2+, 3+). Clinical information was available for the AC, LC, and SCC group. Survival curves were generated and median survival between groups was compared utilizing the Log-rank methodology. Results: In NSCLC the expression of PKCβ1 was negative in 1% (1/107), 1+ in 14% (15/107), 2+ in 43% (46/107), 3+ in 42% (45/107); PKCβ2 immunostaining was negative in 28.4% (29/102), 1+ in 12.7% (13/102), 3+ in 23.6% (24/102) and 3+ in 35.3% (36/102). Median survival was superior for patients who expressed PKCβ1 (2+ or 3+) as compared to non-expressors (median survival 1258 days versus 124 days, p<0.001). There was no difference in median survival in patients whose tumors expressed PKCβ2 and those that did not express it. In mesothelioma, staining for PKCβ1 was negative in 0, 1+ in 0, 2+ in 8.3% (2/24) and 3+ in 91.7% (22/24). For PKCβ2, tissues stained negative in 56.5% (13/23), 1+ in 21.8% (5/23), 2+ in 8.7% (2/23), 3+ in 13% (3/23). Median survival was superior for patients whose tumors did not express PKC-beta 2 (0 or 1+) as compared to expressors (median survival 604 days versus 103 days, p<0.001). Conclusions: PKCβ is expressed in NSCLC and mesothelioma. PKCβ1 expression is a favorable prognostic factor in NSCLC, whereas expression of PKCβ2 is an adverse prognostic factor in mesothelioma. Therapeutic targeting of this molecule would be useful for the future.
No significant financial relationships to disclose.
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