GNAQ and GNA11 mutations and downstream YAP activation in choroidal nevi

Background: Mutations in GNAQ/11 genes are considered an early event in the development of uveal melanoma that may derive from a pre-existing nevus. The Hippo pathway, by way of YAP activation, rather than MAP kinase, has a role in the oncogenic capacity of GNAQ/11 mutations.Methods: We investigated 16 nevi from 13 human eyes for driver GNAQ/11 mutations using droplet digital PCR and determined whether nevi are clonal by quantifying mutant nevus cell fractions. Immunohistochemistry was performed on 15 nevi to analyse YAP activation.Results: For 15 out of 16 nevi, a GNAQ/11 mutation was detected in the nevus cells albeit at a low frequency with a median of 13%. Nuclear YAP, a transcriptional co-activator in the Hippo tumour-suppressor pathway, was detected in 14/15 nevi.Conclusions: Our analysis suggests that a mutation in GNAQ/11 occurs in a subset of choroidal nevus cells. We hypothesise that GNAQ/11 mutant-driven extracellular mitogenic signalling involving YAP activation leads to accumulation of wild-type nevus cells

Mucosal melanomas in the elderly: challenging cases and review of the literature

Flavia Baderca,1,2 Dana Vincze,3 Nicolae Balica,4 Caius Solovan5,61Department of Microscopic Morphology, Victor Babes University of Medicine and Pharmacy, Timisoara, Romania; 2Service of Pathology, Emergency City Hospital, Timisoara, Romania; 3Victor Babes University of Medicine and Pharmacy, Timisoara, Romania; 4Otolaryngology Department, 5Department of Dermatology, Victor Babes University of Medicine and Pharmacy, Timisoara, Romania; 6Department of Dermatology, Emergency City Hospital, Timisoara, RomaniaAbstract: Melanomas are malignant tumors that originate from melanocytes. They are most frequently localized in the skin, but 5% of all melanomas interest also extracutaneous sites as mucosal surfaces, parenchymatous organs, the retroperitoneum area, and the ocular ball. The purpose of this study was to investigate the epidemiologic and morphologic data of mucosal melanomas diagnosed at Emergency City Hospital (Timisoara, Romania) during a period of 12 years. The study included 17 cases of extracutaneous, extraocular melanomas, with 16 primary melanomas and one secondary melanoma. All our patients were older than 53 years and were mostly men. Most of the patients presented with localized disease; only one case had regional lymph node metastases, and another one had systemic metastases at the time of diagnosis. Regarding localization, nine of 16 melanomas were in the head and neck region, six were diagnosed in the gastrointestinal and urogenital tracts (three cases each), and one case had a rare localization (retroperitoneum). The most common histologic type was represented by epithelioid cells, and the majority of the tumors were achromic. Mucosal melanoma is a tumor associated with aging, all our patients being older than 53 years. Because of unspecific symptoms and low incidence, the diagnosis is often delayed and requires teamwork among the clinician, pathologist, radiologist, and oncologist. Different genetic fingerprints impose a correct diagnosis to offer the patient the best novel, personalized therapy.Keywords: mucosal melanoma, melanocytes, molecular classification, kit gene mutations, immunohistochemistr

Age as an independent factor for the development of neuropathy in diabetic patients

Simona Popescu,1,2 Bogdan Timar,2,3 Flavia Baderca,4,5 Mihaela Simu,6,7 Laura Diaconu,1,2 Iulian Velea,8,9 Romulus Timar1,2 12nd Department of Internal Medicine, “Victor Babes” University of Medicine and Pharmacy, 2Clinic of Diabetes, Nutrition and Metabolic Diseases, Emergency Clinical County Hospital, 3Department of Functional Sciences, 4Department of Microscopic Morphology, “Victor Babes” University of Medicine and Pharmacy, 5Service of Pathology, Emergency City Hospital, 6Department of Neurosciences, “Victor Babes” University of Medicine and Pharmacy, 7Clinic of Neurology, Emergency Clinical County Hospital, 8Department of Pediatrics, “Victor Babes” University of Medicine and Pharmacy, 9Clinic of Pediatrics, Emergency Clinical County Hospital, Timisoara, Romania Abstract: Population aging is unprecedented, without parallel in the history of humanity. As type 2 diabetes mellitus is predominantly more prevalent in aging populations, this creates a major public health burden. Older adults with diabetes have the highest rates of major lower-extremity amputation, myocardial infarction, visual impairment, and end-stage renal disease of any age group. The aims of our study were to assess whether age is an independent factor for the occurrence of diabetic neuropathy (DN), and to evaluate the relationship between the presence and the severity of DN and the diabetes duration and blood glucose level. In this study, we enrolled 198 patients, previously diagnosed with type 2 diabetes mellitus. For all patients, we measured hemoglobin A1c (HbA1c), lipid profile, and body mass index and we assessed the presence and severity of DN using the evaluation of clinical signs and symptoms. Patients had a median age of 62 years, with a median of diabetes duration of 7 years; 55.1% of the patients were men and the average HbA1c in the cohort was 8.2%. The prevalence of DN according to Michigan Neuropathy Screening Instrument was 28.8%, being significantly and positively correlated with higher age (65 vs 59 years; P=0.001) and HbA1c (8.6% vs 8.0%; P=0.027). No significant correlations were observed between the severity of DN and diabetes duration, body mass index (31.9 vs 29.9 kg/m2), or the number of centimeters exceeding the normal waist circumference (25.2 vs 17.3 cm; P=0.003). In conclusion, age influences the presence of DN, independent on other risk factors. This influence persists even after adjusting for other, very important risk factors, like blood glucose level or diabetes duration. Keywords: peripheral neuropathy, elderly patients, type 2 diabetes mellitus, body mass index, hemoglobin A1c, diabetic neuropath

Synchronic rhynopharyngeal and gingival carcinoma

We present a case of a 38-year-old male who presented recurrent otitis media, maxillary gingival ulceration and no lateral cervical lymph nodes. Admission signs and symptoms: right: mild conductive hearing loss, trigeminal V2 nerve anaesthesia, ear tinnitus, hypoglossal nerve paralysis, minor maxillary gingival ulceration, Claude Bernard Horner's syndrome. A non-homogenous mass of 4.5/5.3/5.6 cm from the level of the right rhinopharyngeal wall, extending in the right parapharyngeal space, invading the right middle cranial fossa was visible on cranial contrast enhanced CT scan. Contrast enhanced cranial MRI revealed a rhino- and parapharyngeal mass of 4.5/5.3/5.6 cm with intracerebral extension in the right cavernous sinus, right internal carotid artery engulfed by the tumor mass with partial compression. Lymph node masses of 0.7/1.2cm were also revealed.Rhinopharyngeal and gingival biopsy, right tympanotomy were performed.Routine histological technique was performed and subsequent immunohistochemical reactions for pan-cytokeratin AE1/AE3 and leucocytes common antigen were used, showing that malignant tumor cells had a syncytial pattern of growth in a background of small lymphocytes for the rhynopharyngeal biopsy. Cellular dysmorphias, well-differentiated stratified squamous epithelial cells with deep bulbous ridges and also parakeratin invaginations were visible on the gingival biopsy. The positivity of tumor cells for pan-cytokeratin established the final diagnosis of non-keratinizing undifferentiated carcinoma of the rhynopharinx and Keratins (10-16), MNP 2, 9; VEGF, KI67, P53 confirmed the verrucous cell carcinoma of the maxillary mucosa.The age of onset, the signs and symptoms and minimum lymph node involvement represent the particularities of this case.Der Erstautor gibt keinen Interessenkonflikt an

Vulvar cancer: a review for dermatologists.

Vulvar malignancies are important tumors of the female reproductive system. They represent a serious health issue with an incidence between 2 and 7 per 100,000 and year. We provide a review about most important cancer entities, i.e., melanoma, squamous cell carcinoma, basal cell carcinoma, neuroendocrine cancer, and skin adnexal malignancies.Squamous cell carcinoma is the most common vulvar malignancy that can develop from vulvar intraepithelial neoplasia or de novo. Basal cell carcinoma represents only 2 % of all vulvar cancers. Melanoma of the vulva exists in two major types-superficial spreading and acral lentiginous. A special feature is the occurrence of multiple vulvar melanomas. Of the adnexal cancer types Paget's disease and carcinoma are seen more frequently than other adnexal malignancies. The dermatologist should be aware of this problem, since he might be the first to be consulted by patients for vulvar disease. Treatment should be interdisciplinary in close association to gynecologists, oncologists, and radiologists