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

Biopsying parapsoriasis: quo vadis? Are morphological stains enough or are ancillary tests needed?

BACKGROUND: Parapsoriasis represents a group of cutaneous disorders that shows variable clinical aspects somehow resembling to psoriasis, how is reflecting by its name. It was first named by Brocq, in 1902, as an entity with three components: pityriasis lichenoides, small plaque parapsoriasis and large plaque parapsoriasis. Nowadays, under the name of parapsoriasis are included only the last two categories, that are considered disorders characterized by the presence of a mononuclear infiltrate in the dermis, composed of T-cells. Until now, there were not established pathognomonic histopathological features to diagnose parapsoriasis. AIM: The aim of the study was to investigate the epidemiological and morphological data of parapsoriasis cases diagnosed at Emergency City Hospital, Timisoara, Romania for a period of 12 years. MATERIALS AND METHODS: The study had two parts; one was retrospective and another one prospective. For the retrospective part, we searched 210111 patient files recorded in our Pathology Service for a period of 11 years, from January 2002 to December 2012. The slides were searched from the archive and re-read by two individual pathologists. For prospective part of the study, we reviewed 11815 histological slides read between January and June 2013. After inspection of the recorded files, the pathologists noted, were available, the localization and number of the lesions, together with symptoms. The biopsied specimens were initially processed with routine histological technique, the archive slides being stained with Hematoxylin and Eosin. While reading the slides, the pathologists paid attention to the architecture of the epidermis, the presence of epidermotropism and interface dermatitis, type of the dermal infiltrate and its distributions. CONCLUSIONS: In the present study, we emphasized the histopathological aspects of parapsoriasis in order to create a basic line that could help in the establishment of a uniformly accepted definition of parapsoriasis on histopathological grounds

A rare case of plexiform schwannoma of the lower lip: Treatment and management

An 18-year-old female presented with a swelling on the lower lip, which was insidious in onset and gradually progressive. The mass was completely excised under local anaesthesia. Complete histopathologic and immunohistochemical studies were conducted. The Antoni A areas were found along with typical verocay bodies composed of palisading nuclei and surrounding spaces filled with eosinophilic filaments. No necrosis was noted and there were no atypical mitotic figures. In the Antoni B region, a closely textured matrix with areas of edema, myxomatous changes, cystic degeneration and dilated vessels were noted. On the basis of the histopathologic and immunohistochemical staining with S-100 protein, a diagnosis of plexiform schwannoma was made and has been reported in this study. The post-operative view confirmed complete recovery after 6 weeks of surgery. This is a rare case with the tumour located in the lower lip, as very few cases have been reported in literature and it may be the first one reported from India