Squamous cell carcinoma of the umbilicus: management of an unusual localization

We describe the case of a squamous cell carcinoma spreading to the skin and regional lymph nodes from the umbilicus. Bilateral inguinal lymphadenectomy and a session of electrochemotherapy with bleomycin 15 mg/m2 were performed. However, because of the development of new cutaneous nodules in the abdominopelvic region, we performed targeted palliative therapy with erlotinib 150 mg/day. Targeted adjuvant therapy was preferred to the use of a major cytotoxic agent because of the high risk of superinfection and heart failure. Erlotinib produced a partial clinical response with reduction of the number and size of the skin nodules. CT scan performed after 60 days of treatment did not show any new lesions. To our knowledge, this is the first report of an umbilical metastatic squamous cell carcinoma treated with modern targeted therapy. This therapeutic strategy can be considered a valid palliative option in the management of metastatic cutaneous nodules of this rare primary site.     

N-valproyl-L-tryptophan for CNS-targeting: synthesis, characterization and efficacy in vitro studies of a new potential antiepileptic drug

A new aminoacidic derivative of valproic acid (VPA) has been synthesized and characterized by analytical and spectral data. The rationale for the preparation of such potential antiepileptic agent is based on the observation that chemical combination of the anticonvulsant pharmacophore, VPA with essential aminoacids could afford more effective and less toxic actives. The synthesis, characterization, physico-chemical parameters functional for crossing Blood Brain Barrier of N-valproyl-L-tryptophan (4) are reported. The Log D (pH7.4) (0.3) indicates that (4) is adequate to cross biological membranes. Its chemical and enzymatic stability were assessed. The experiments indicate high stability of compound (4) at pH conditions of physiological fluids. Moreover, both in plasma and in cerebral enzymatic environments compound (4) doesn't undergo cleavage after 24 h. The anticonvulsant activity of the new compound was assessed against epileptic burst discharges evoked in vitro in rat hippocampal slices (Seizure like events - SLEs) and compared with that of the widely used VPA. Compound (4), even at the lower tested concentration, when compared to VPA, showed an improved protective effect against hippocampal seizures. The collected data suggest that compound (4) could be considered a very valuable candidate for subsequent in vivo evaluation as new potential antiepileptic drug.     

Management of Aromatase Inhibitor-Resistant Disease with Estrogen,Selective Estrogen Receptor Down-Regulators,and Other Agents

With increased use of aromatase inhibitors (AIs) in the adjuvant and first-line metastatic settings for postmenopausal women with estrogen receptor (ER)-positive breast cancer, systemic relapse or progressive metastatic disease on AIs is an increasingly encountered clinical scenario. Overcoming resistance is a priority. Patients with AI-resistant disease represent a heterogeneous population, with diverse mechanisms of resistance dictating varied sensitivity to subsequent treatment. Cells with persistent dependence on ER signaling may be inhibited by fulvestrant, in which case dose-dependent ER downregulation and activity favor high-dose, loading schedule fulvestrant. In direct contrast, cells with long-term estrogen deprivation with adaptive estrogen hypersensitivity may be inhibited by exposure to estrogen. Cell survival by alternate growth signaling pathways may be inhibited by targeted agents. Currently missing, however, are predictive biomarkers to identify underlying resistance mechanisms and guide effective post-AI therapy for individual patients.     

Absence of KIAA1549-BRAF fusion in rosette-forming glioneuronal tumors of the fourth ventricle (RGNT)

Rosette-forming glioneuronal tumors (RGNT) of the fourth ventricle are rare mixed glioneuronal tumors included in the revised WHO classification of central nervous system tumors, showing partial histological similarities to pilocytic astrocytomas. To evaluate potential similarities at the molecular level between these tumors, we analysed a series of 10 RGNT for the presence of KIAA1549-BRAF fusions using interphase fluorescence in situ hybridisation. However, we found no cases showing KIAA1549-BRAF gene fusion or BRAF (V600E) mutation. Our data support the hypothesis that RGNT may represent a distinct entity among the glioneuronal tumors of the central nervous system, with molecular features different from pilocytic astrocytomas.     

Subcutaneous malignant melanoma of the scalp surgical flap after brain irradiation for anaplastic astrocytoma

Journal of Neuro-Oncology -     

Prognostic significance and clinical relevance of the expression of the HER family of type I receptor tyrosine kinases in human laryngeal squamous cell carcinoma

IntroductionThe full clinical relevance of the expression pattern of HER family of type I receptor tyrosine kinases in laryngeal squamous cell carcinoma remains to be elucidated. We evaluated the clinical relevance of such parameter in our population.Patients and methodsThis study examined the expression pattern of HER family receptor members by quantitative immunohistochemistry and the amount of the EGF binding sites by a radioligand binding assay, in the same group of 67 LSCC patients, analysing the correlation between the expression of the four HER receptors and the clinical and prognostic parameters.ResultsHER1 levels inversely correlated with that of HER2–4, while HER2–4 directly correlated among them. Cox univariate analysis using HER1–4 values as continuous covariates indicated that HER1 expression was directly associated with the risk of death and relapse while that of HER2–4 was inversely associated with the risk of death. Among the patients with high HER1 expressing tumours, those with tumours co-expressing HER2–4 showed a lower risk of death and relapse (in particular regional relapse) than those with tumours displaying a negative HER2–4 status.ConclusionsThe evaluation of HER2–4 status adds more power to the prognostic role of HER1 detection. In the era of molecularly targeted therapy, the expression of HER family of receptor tyrosine kinases in LSCC may hold relevant clinical significance and turn out to be a key factor in prognostic assessment and in treatment planning.     

Targeting triple negative breast cancer: Is p53 the answer?

Triple negative breast cancers, which are defined by lack of expression of estrogen, progesterone, or HER2 receptors, represent approximately 15% of all breast cancers, although they account for a much higher proportional of breast cancer mortality. This is due both to their innate aggressive biological characteristics, but also to lack of effective therapies. Conventional chemotherapy is currently the only treatment option, thus there is a critical need to find new and effective targeted therapies in this disease. While investigation of agents such as poly (ADP-ribose) polymerase (PARP) inhibitors and EGFR inhibitors continues, results from recent clinical trials indicate that these therapies are not as active in sporadic triple negative breast cancers as initially hoped. It is important therefore to consider other emerging therapeutic agents. Mutation in p53 is found in the vast majority of triple negative breast cancers, and as such is a target of particular interest. Within this review, several agents with potential activity against aberrant p53 signaling have been considered, as a novel approach to finding an effective targeted therapy for this aggressive breast cancer subtype.     

A novel von Hippel-Lindau point mutation presents as apparently sporadic pheochromocytoma

Von Hippel Lindau disease is a common cause of apparently sporadic pheochromocytomas. Herein, we describe a 20-year-old man with an apparently sporadic pheochromocytoma associated with a novel, relatively conservative germline Gly104Val VHL gene mutation, which is localized within exon 1 of the VHL gene corresponding to the beta -domain of the VHL protein (pVHL). The nearly asymptomatic patient's father also carries the same mutation. Similar to other mutations localized in the same codon, the Gly104Val VHL mutation seems to have an attenuated disease phenotype.     

Unusual presentation of intradural endodermal cysts in young children under 2 years of age. Report of two cases

Introduction Spinal endodermal cysts are congenital maldevelopmental lesions usually presenting in early adulthood. Whereas the diagnosis is rare in newborns and it is usually led by cardiopulmonary distress or other associated malformations, no characteristic clinical findings associated with these entities have been described in older patients where spinal endodermal cysts usually behave as intraspinal space occupying lesions. Discussion The authors report on two children under 2 years of age affected by cervical endodermal cysts that presented with a history of acute motor deficit following a laryngitis. The hypothesis about the pathogenesis is that the upper respiratory tract infection might have stimulated the secretion of the cyst lining, inducing growth of the cyst and the sudden appearance of the motor deficit. Because of the apparent lack of relation between the benign laryngitis and the motor deficit, the occurrence of such an association might have been underestimated in some of the previously reported cases.