Search

Metastatic malignant melanoma (MM) represents a highly aggressive cancer associated with overall poor prognosis. Various anatomic sites can be affected, including the oral cavity and the oropharynx. It may mimic other entities by assuming a variety of clinical appearances and exhibiting a plethora of microscopic variations. Herein, we present a case of a 63-year-old male with a MM metastasizing to the base of tongue, which developed 5 years after the original diagnosis and treatment of cutaneous MM of the chest and heralded its relapse; subsequently, neurological symptoms developed as a result of metastasis to the brain. Diagnostic challenges were encountered, as the tongue lesion clinically masqueraded as a pedunculated reactive lesion and microscopically displayed unusual rhabdoid and neuroendocrine features. Tumor cells expressed S-100, HMB-45, Melan-A, and SOX-10, while most cells with rhabdoid morphology were also positive for myogenin and Myo-D1. Chromogranin and synaptophysin positivity was further noticed in a subset of cells, suggestive of focal neuroendocrine differentiation. Molecular investigation revealed mutations for the BRAF V600E gene. Divergent differentiation of tumor cells may cause diagnostic pitfalls necessitating thorough immunohistochemical analysis. The presence of rhabdoid features and neuroendocrine differentiation are very uncommon, while their co-existence is extremely rare. Better characterization of such microscopic variations in MMs with evaluation of their potential biologic significance is warranted.

Cheilitis Glandularis (CG) is an uncommon entity of obscure etiology. A cases series is presented with emphasis on etiopathogenesis.Fourteen CG cases were analyzed according to their demographic and clinicopathologic characteristics.The mean age of the patients with CG was 68.1 years, while a male-to-female ratio of 1.8:1 was observed. One or more potential causative factors were identified for each patient, including long-term smoking (9 cases), xerostomia (4 cases), cosmetic filler injections (2 cases), and actinic cheilitis (1 case). The lesions were located on the lips, buccal mucosa, or both in 7, 2, and 5 cases, respectively. Multiple submucosal nodules with dilated ductal orifices and mucous or purulent discharge were observed in all cases. Histopathologically, ductal ectasia with metaplasia, intraductal mucin, and chronic or mixed inflammation were noted, as well as pools of hyaluronic acid in 2 cases with a history of cosmetic filler injections.CG etiopathogenesis is probably multifactorial. Reduced salivary flow rate and increased viscosity of saliva, potentially caused by long-term smoking, diabetes mellitus, and drug-induced xerostomia, may participate in the initial pathogenesis, while local irritants, for example, poor oral hygiene and local trauma, may further contribute to the development and aggravation of the condition.

Background Osteomyelitis with proliferative periostitis is a relatively uncommon inflammatory condition of the jaws, mainly characterized by periosteal formation of reactive bone. It primarily affects children and adolescences, also referred to as Garre's osteomyelitis, more frequently involving the molar region of the mandible. Cases lacking an obvious source of infection may have an immunologically mediated etiopathogenesis, falling under the spectrum of primary chronic osteomyelitis or chronic recurrent multifocal osteomyelitis (CRMO). Case report Herein, we present a case of chronic osteomyelitis in a 6.5-year-old girl, who suffered from recurrent painful episodes of swelling of the mandible for the last 2 years, previously requiring hospitalization and administration of intravenous (IV) antibiotics and NSAIDs with limited responsiveness. The biopsy showed features consistent with osteomyelitis with proliferative periostitis. The patient was initially managed with an IV combination antibiotic regimen with only partial improvement. The possibility of an autoimmune mechanism in the context of primary chronic osteomyelitis or CRMO was considered, and immunosuppressive therapy (TNF inhibitor etanercept along with corticosteroids and methotrexate) was administered, resulting in clinical resolution. Conclusions Osteomyelitis and its childhood variants are relatively rare and their management presents several challenges. Although typically treated with administration of antibiotics, possibly along with surgical intervention, other treatment modalities may be necessary for resilient and persistent cases. In a subset of cases, especially in the absence of local infectious factors, immunologically mediated mechanisms may play an important role and appropriate immunosuppressive therapy may be effective.

An intact and fully functional immune system plays a crucial role in the prevention of several infectious diseases. Interleukin (IL)17 is significantly involved in oral mucosa immunity against several antigens and microorganisms, including Candida albicans (CA). Herein, we present three cases of oral candidiasis (OC) related to the use of an IL17A inhibitor for psoriasis. Three psoriatic individuals presented for evaluation of widespread symptomatic oral lesions temporally correlated with the onset of IL17A inhibitors (secukinumab in two patients and brodalumab in one patient). Clinical examination revealed either partially removable white plaques in an erythematous background (case #1) or diffuse erythematous lesions (cases #2 and 3) involving several areas of the oral mucosa. Cytology smear, accompanied by histopathologic examination in case #1, confirmed the clinical impression of OC in all three cases. All patients received antifungal therapy with satisfactory clinical response. No discontinuation of the antipsoriatic regimen was recommended, but all patients were advised to remain under monitoring for possible OC relapses. During the last few years, new systemic biologic agents targeting IL17 have been used for the management of variable immune-mediated diseases. Few clinical trials and scarce case reports have shown that these medications place individuals at high risk of developing candidiasis. We propose that patients treated with these medications should be at close monitoring for the development of OC and, if it occurs, receive appropriate management.

Objectives Localized juvenile spongiotic gingival hyperplasia (LJSGH) is a recently described entity with distinct manifestations. Herein we report a comprehensive histopathologic study of 21 lesions and a literature review. Additionally, we propose a new term that we consider more appropriate. Study Design LJSGH cases were retrieved and their clinicopathologic characteristics were assessed. A review of all pertinent literature was also conducted. Results Eighteen patients with LJSGH (21 biopsied lesions) were identified. Microscopically, surface morphology was classified into exophytic/papillary, flat, and micropapillary (8, 7, and 6 lesions, respectively). Cases with parakeratinization (n = 9), no prominent spongiosis (n = 5), or epithelial atrophy (n = 4) were recorded. Increased vascularity, mixed inflammation with exocytosis, and cytokeratin-19 positivity were uniformly observed. Less frequent findings included pseudoepitheliomatous hyperplasia (n = 8), bacterial colonies (n = 5), acantholysis (n = 3), and dystrophic calcifications (n = 2). The literature review disclosed 201 patients with a mean age of 14.8 years (range, 3-72; 13.6% affecting adults), similar sex distribution (103:98, female:male), and predominance of the anterior maxilla (≈ 80%). Eighteen cases were multifocal (≈ 10%). Conclusions Our data suggest that the terminology could be modified, because LJSGH may be multifocal, affect older individuals, or exhibit epithelial atrophy, and the entity's odontogenic origin (as highlighted by the histopathologic and immunohistochemical findings) needs to be emphasized.

Background Canalicular adenoma (CA) is a benign salivary gland tumor (SGT) almost exclusively affecting the minor salivary glands, predominantly of the upper lip, and exhibiting characteristic histopathologic features. As observed in several other SGTs, a commonly encountered finding is the presence of prominent cystic morphology. Even though a multicystic appearance is usually noticed, solitary cystic CAs may rarely occur. Case report Two female patients (74 and 78 years old respectively) presented for the evaluation of submucosal asymptomatic masses of the oral cavity. In the 1st case a solitary nodule was noticed in the upper lip, while the 2nd patient exhibited two symmetrical lesions of the buccal mucosae. All three excised specimens displayed cystic morphology upon gross examination. Histopathologically, a solitary cystic formation lined by monomorphic cuboidal or basaloid cells arranged in solid or trabecular patterns was observed in the 1st case. With a differential diagnosis of CA vs basal cell adenoma immunohistochemical examination was performed. Positivity for S-100, CK7 and CD117 (c-kit) and negative reaction for GFAP, p63 and SMA rendered the diagnosis of CA. In the 2nd case both lesions displayed well-circumscribed proliferations by monotonous cuboidal or columnar cells arranged in single cords and occasionally forming beading patterns, while central solitary areas of marked cystic degeneration were noticed. Diagnosis of multifocal unicystic CA was disclosed. Discussion To our knowledge, only 11 additional cases of unicystic CA have been reported in the English-language literature. Although the exact clinical significance of unicystic morphology in CA is unknown, a tendency for occurrence within the context of multifocal tumors has been detected. Key words:Canalicular adenoma, monomorphic adenoma, unicystic morphology, multifocal tumors, minor salivary glands.

The aim of this study was to investigate the effect of the application of orthodontic tooth forces on the alveolar bone distal to the loaded teeth, in ovariectomized female rats.Twenty-four eight-month-old Wistar rats were divided into one group ovariectomized at the age of six months and one control. An orthodontic appliance delivering a mesial traction force of 60 gr* was placed on the right maxillary 1In the non-ovariectomized rats, extensive resorption was noticed in the direction of the orthodontic movement in the 2In conclusion, orthodontic forces applied to the dentoalveolar complex of ovariectomized rats affect bone remodeling, even in areas distal to the site of force application. This finding should be taken into account during orthodontic treatment of women during menopause.

OBJECTIVES: The aim of this study was to investigate the relationship between M1 and M2 macrophage polarization and clinical stage in patients with medication-related osteonecrosis of the jaw (MRONJ) who underwent treatment with bisphosphonates or denosumab. MATERIALS AND METHODS: M1 and M2 macrophage density and expression of interleukin (IL)-6 and IL-10 were assessed on biopsies of mucosal tissues surrounding necrotic bone in 30 MRONJ patients with stages 1–3 and controls. For identification of M1 and M2 macrophages, double CD68/iNOS and CD68/CD206 immunofluorescence staining was conducted, respectively. Computer-assisted immunofluorescence quantification of markers was performed. RESULTS: Early stage 1 MRONJ patients showed a switch toward the M2 phenotype, as indicated by the higher density of M2 macrophages, the decreased M1/M2 ratio and the upregulation of IL-10. MRONJ patients with advanced stages 2 and 3 showed a shift toward M1-polarized macrophages, as suggested by the higher density of M1 macrophages, the increased M1/M2 ratio and the overexpression of IL-6. The macrophage density of both M1 and M2 subsets was significantly enhanced in patients receiving bisphosphonates compared to those receiving denosumab. CONCLUSIONS: The M1–M2 macrophage polarization status in mucosal tissues bordering necrotic bone correlates with clinical stage of MRONJ. Patients with early stage MRONJ show a switch toward M2-polarized macrophages, while MRONJ patients with advanced stage demonstrate a shift toward the M1 phenotype. CLINICAL RELEVANCE: Therapeutic molecules targeting the inflammatory microenvironment via the regulation of either M1 or M2 macrophage polarization may represent a novel strategy for treatment of MRONJ.

Fungi, a diverse group of eukaryotic organisms, play distinct roles in health and disease. Recent advances in the field of mycobiology have enabled the characterization of the "human mycobiome." The human mycobiome has extensively been studied in various disease models. However, to date, the role of the oral mycobiome in oral carcinogenesis has yet to be elucidated. Candida albicans, the most common oral colonizer, has been speculated to display tumorigenic effects; however, the literature lacks consistent documentation from mechanistic studies on whether oral mycobiota act as drivers, facilitators, or passive colonizers of oral premalignancy and cancer. This review article provides an overview of existing hypothesis-driven mechanistic models that outline the complex interplay between the oral mycobiome and oral epithelial dysplasia as well as their potential clinical implications.

This study aimed to evaluate prognostic outcomes of PVL-derived oral squamous cell carcinomas (P-OSCC) based on recurrence, new primary tumour, metastasis and survival information.Five databases and grey literature were searched electronically with the following main keywords (proliferative verrucous leukoplakia, squamous cell carcinoma and malignant transformation) to answer the following review question: 'Are survival outcomes for P-OSCC worse?' based on the PECOS principle. The Joanna Briggs Institute Critical Appraisal tool was used to identify possible biases and assess the quality of each of the primary studies.A total of 21 articles met the inclusion criteria, and the results of this systematic review suggest that P-OSCC can recur and generate new primary tumours; however, metastases are rare. Thus, most patients remain alive for an average period of 5 years.Apparently, P-OSCC has better clinical prognostic characteristics than conventional OSCC. There is a lack of information on the main prognostic outcomes of P-OSCC; therefore, specific studies must be performed to achieve a better comparison between P-OSCC and conventional OSCC progression.

BACKGROUND Oral lichen planus (OLP) is a common, frequently symptomatic, immune-mediated disease. Various treatments have been used for symptomatic OLP, including corticosteroids and immunosuppressants administered topically or systemically. The aim of this study was to compare the effectiveness of topical dexamethasone vs. topical cyclosporine in treatment of symptomatic OLP. MATERIAL AND METHODS Thirty-two patients with biopsy-proven symptomatic OLP were randomly assigned to two therapeutic groups: dexamethasone 2mg/5ml or cyclosporine 100mg/ml, both administered topically in a swish and spit method three times a day for 4 weeks. The patients were followed up for a total of 6 months. Assessed parameters included clinical scoring (according to Thongprasom's scale, 0-5), pain (VAS scale, 0-10), dysphagia and speech difficulties (none, mild or severe). Possible side effects, including fungal overgrowth, were also recorded. RESULTS At the end of the 4-week treatment period, both dexamethasone and cyclosporine showed a statistically significant improvement in clinical scoring (p

Mantle cell lymphoma (MCL) is a well-defined, non-Hodgkin lymphoma of B-cell origin displaying diverse morphological phenotypes and variable disease course. The World Health Organization recognizes two aggressive histopathologic variants of this type of lymphoma: pleomorphic and blastoid MCL. To date, only few cases of MCL affecting the oral cavity have been reported. Additionally, the involvement of the oral and maxillofacial area by aggressive MCL subsets is considered extremely rare with only two patients reported in the English language literature to the best of our knowledge. Herein, we describe a 69 year-old male with a prior history of MCL of the right lateral pharyngeal wall developing a recurrent lesion extending to the palatal mucosa as diffuse ulceration and exhibiting histomorphological features of blastoid MCL. We also review the pertinent literature with emphasis on the diagnostic challenges and distinction between the different MCL variants.

Oral leukoplakia (OL) has a propensity for recurrence and malignant transformation (MT). Herein, we evaluate sociodemographic, clinical, microscopic and immunohistochemical parameters as predictive factors for OL recurrence, also comparing primary lesions (PLs) with recurrences. Thirty-three patients with OL, completely removed either by excisional biopsy or by laser ablation following incisional biopsy, were studied. Selected molecules associated with the STAT3 oncogenic pathway, including pSTAT3, Bcl-xL, survivin, cyclin D1 and Ki-67, were further analyzed. A total of 135 OL lesions, including 97 PLs and 38 recurrences, were included. Out of 97 PLs, 31 recurred at least once and none of them underwent MT, during a mean follow-up time of 48.3 months. There was no statistically significant difference among the various parameters in recurrent vs. non-recurrent PLs, although recurrence was most frequent in non-homogeneous lesions (p = 0.087) and dysplastic lesions recurred at a higher percentage compared to hyperplastic lesions (34.5% vs. 15.4%). Lower levels of Bcl-xL and survivin were identified as significant risk factors for OL recurrence. Recurrences, although smaller and more frequently homogeneous and non-dysplastic compared to their corresponding PLs, exhibited increased immunohistochemical expression of oncogenic molecules, especially pSTAT3 and Bcl-xL. Our results suggest that parameters associated with recurrence may differ from those that affect the risk of progression to malignancy and support OL management protocols favoring excision and close monitoring of all lesions.

The pathogenesis of oral cancer is a complex and multifactorial process that requires a deep understanding of the underlying mechanisms involved in the development and progress of malignancy. The ever-improving comprehension of the diverse molecular characteristics of cancer, the genetic and epigenetic alterations of tumor cells, and the complex signaling pathways that are activated and frequently cross talk open up promising horizons for the discovery and application of diagnostic molecular markers and set the basis for an era of individualized management of the molecular defects underlying and governing oral premalignancy and cancer. The purpose of this article is to review the key molecular concepts that are implicated in oral carcinogenesis, especially focusing on oral squamous cell carcinoma, and to review selected biomarkers that play a substantial role in controlling the so-called "hallmarks of cancer," with special reference to recent advances that shed light on their deregulation during the different steps of oral cancer development and progression.

ΕΙΣΑΓΩΓΗ: Ο καρκίνος του στόματος αποτελεί μία από τις συχνότερες μορφές καρκίνου παγκοσμίως, αντιστοιχώντας σε 380.000 νέες περιπτώσεις ετησίως, μεταξύ των οποίων το ακανθοκυτταρικό καρκίνωμα του στόματος (ΑΚΣ) αντιπροσωπεύει τη συντριπτική πλειοψηφία. Παρά τις εξελίξεις στις μεθόδους θεραπευτικής αντιμετώπισης, το ΑΚΣ εξακολουθεί να εμφανίζει σημαντική νοσηρότητα και θνησιμότητα με ποσοστά 5ετούς επιβίωσης που δεν υπερβαίνουν το 50%. Είναι γνωστό ότι ένα σημαντικό ποσοστό των ΑΚΣ αναπτύσσεται στο έδαφος μίας προκαρκινικής βλάβης ή κατάστασης με πιο συχνή τη λευκοπλακία. Σύμφωνα με τον Παγκόσμιο Οργανισμό Υγείας, ο κλινικός όρος λευκοπλακία αναφέρεται σε μία "λευκή πλάκα στον βλεννογόνο του στόματος που δεν αποκολλάται από το επιθήλιο στο οποίο αναπτύσσεται, αμφιβόλου κινδύνου κακοήθους εξαλλαγής, αφού αποκλειστούν άλλα γνωστά νοσήματα ή διαταραχές που δεν σχετίζονται με αυξημένο κίνδυνο καρκίνου". Η λευκοπλακία του στόματος εμφανίζει επιπολασμό 4,11% παγκοσμίως, ενώ το ποσοστό κακοήθους εξαλλαγής κυμαίνεται μεταξύ 0,13% και 34%, με ετήσια επίπτωση 1-3%. Συνεπώς, η έγκαιρη διάγνωση και αντιμετώπιση των προκαρκινικών βλαβών μπορεί να αναχαιτίσει την εξέλιξη των βλαβών και να συμβάλλει στην αποφυγή της κακοήθους εξαλλαγής. Μέχρι σήμερα, διάφορες μελέτες έχουν επιχειρήσει να προσδιορίσουν μία σειρά κλινικών, ιστολογικών και μοριακών χαρακτηριστικών που θα επιτρέψουν τον αδρό προσδιορισμό βλαβών με υψηλό κίνδυνο κακοήθους εξαλλαγής. Διάφοροι κοινωνικο-δημογραφικοί παράγοντες (μεγαλύτερη ηλικία, γυναικείο φύλο, μη καπνιστές), κλινικά χαρακτηριστικά (μεγαλύτερο μέγεθος, μη ομοιογενής εμφάνιση και εντόπιση σε περιοχές υψηλού κινδύνου, όπως τα πλάγια χείλη της γλώσσας και το έδαφος του στόματος), καθώς και ιστοπαθολογικά χαρακτηριστικά (υψηλότερος βαθμός δυσπλασίας) έχουν δειχθεί να σχετίζονται με τον κίνδυνο κακοήθους εξαλλαγής. Επιπλέον, ιδιαίτερη έμφαση έχει δοθεί στη χρησιμότητα μοριακών δεικτών για την πρόβλεψη κακοήθους εξαλλαγής μιας προκαρκινικής βλάβης. Εντούτοις, δεν έχουν ακόμα διευκρινιστεί ακριβείς παράμετροι και μέθοδοι προσδιορισμού τους που επιτρέπουν με αξιοπιστία τον ακριβή καθορισμό του δυναμικού εξαλλαγής μιας βλάβης σε κακοήθεια, γεγονός που καθιστά απαραίτητη την περαιτέρω μελέτη των λευκοπλακιών, κυρίως σε μοριακό και βιολογικό επίπεδο. Οι περισσότερες μελέτες, βέβαια, έχουν συσχετίσει τα χαρακτηριστικά εκείνα που προβλέπουν την κακοήθη εξαλλαγή των βλαβών, ενώ είναι πολύ λίγες εκείνες που έχουν επικεντρωθεί στον προσδιορισμό των παραμέτρων που θα μπορούσαν να προσδιορίσουν τον κίνδυνο υποτροπής, μετά την αφαίρεση της αρχικής βλάβης. Εντούτοις, οι υποτροπές των λευκοπλακιών, οι οποίες μερικές φορές μπορεί να είναι και περισσότερες της μίας στην ίδια θέση, θεωρούνται συχνές με συχνότητα 5ετούς εμφάνισης σε ποσοστό σχεδόν 50% και υποδηλώνουν επιμονή των βλαβών με συνακόλουθη αυξημένη τάση εξαλλαγής τους. Στη διεθνή βιβλιογραφία υπάρχουν διιστάμενες απόψεις ως προς το αν η αντιμετώπιση της λευκοπλακίας θα πρέπει να επικεντρώνεται στην επεμβατική θεραπεία ή στη συστηματική και μακροχρόνια παρακολούθηση των βλαβών. Κατά κύριο λόγο όμως προτείνεται η αφαίρεση/εξάλειψη της βλάβης, ενώ οι πιο συχνά χρησιμοποιούμενες μέθοδοι περιλαμβάνουν τη χειρουργική αφαίρεση με νυστέρι ή την εξαίρεση ή εξάχνωση με laser. ΣΚΟΠΟΣ: Σκοπός της παρούσας διδακτορικής διατριβής ήταν: • Η συγκριτική αξιολόγηση των επιδημιολογικών, κλινικών και ιστοπαθολογικών χαρακτηριστικών των λευκοπλακιών με στόχο την ανίχνευση προβλεπτικών δεικτών υποτροπής. • Η ανοσοϊστοχημική διερεύνηση επιλεγμένων μοριακών δεικτών (pSΤΑΤ3, Bcl-xL, survivin, κυκλίνη D1 και Ki-67) που σχετίζονται με την ογκογόνο σηματοδοτική οδό του επαγωγέα σήματος και ενεργοποιητή της μεταγραφάσης 3 (SΤΑΤ3) και εμπλέκονται στη διαδικασία της καρκινογένεσης. Επίσης, η συσχέτιση της έκφρασής τους με τα ιστοπαθολογικά χαρακτηριστικά των βλαβών και η εκτίμηση της προβλεπτικής αξίας τους όσον αφορά τον κίνδυνο υποτροπής των βλαβών • Η σύγκριση των προαναφερθέντων κλινικών, μικροσκοπικών και ανοσοϊστοχημικών χαρακτηριστικών μεταξύ των αρχικών βλαβών και των αντίστοιχων υποτροπών τους. ΥΛΙΚΑ-ΜΕΘΟΔΟΣ: Υλικό της μελέτης αποτέλεσαν 33 ασθενείς με κλινική διάγνωση λευκοπλακίας από το Αρχείο της Κλινικής Στοματολογίας και Νοσοκομειακής Οδοντιατρικής της Οδοντιατρικής Σχολής Αθηνών, κατά το χρονικό διάστημα Ιανουάριος 2010 – Μάρτιος 2020. Όλοι οι ασθενείς είχαν υποβληθεί είτε σε ολική βιοψία-εξαίρεση με νυστέρι (βλάβες < 1 εκ.) ή σε αρχική μερική βιοψία (βλάβες > 1 εκ.) και στη συνέχεια εξάχνωση της υπολειμματικής βλάβης με CO2 laser. Το βιοπτικό υλικό είχε αποσταλεί για ιστοπαθολογική εξέταση με διάγνωση επιθηλιακής υπερπλασίας ή επιθηλιακής δυσπλασίας ήπιου, μέτριου ή έντονου βαθμού. Τα κριτήρια ένταξης στη μελέτη περιελάμβαναν τη διαθεσιμότητα δημογραφικών δεδομένων, όπως ηλικία, φύλο, συνήθειες καπνίσματος και κατανάλωσης αλκοόλ και πλήρες ιατρικό ιστορικό, λεπτομερείς κλινικές πληροφορίες, συμπεριλαμβανομένου του αριθμού, της θέσης, του μεγέθους και της κλινικής εμφάνισης (ομοιογενείς έναντι μη-ομοιογενείς βλάβες), βιοψία (ολική ή μερική) και ιστοπαθολογική διάγνωση με διαθεσιμότητα ιστών για περαιτέρω διερεύνηση και παρακολούθηση των ασθενών για τουλάχιστον 1 έτος. Κριτήρια αποκλεισμού αποτέλεσαν η διάγνωση ΑΚ κεφαλής και τραχήλου σε χρονικό διάστημα μικρότερο των 18 μηνών πριν από την πρώτη επίσκεψη και το ιστορικό προηγούμενης χημειοθεραπείας ή ακτινοθεραπείας. Λευκές μη αποκολλώμενες βλάβες συμβατές με υπερκερατίνωση λόγω τριβής ή άλλες διαγνώσεις (διαφορετικές από τη λευκοπλακία) αποκλείστηκαν επίσης από τη μελέτη. Από τα ιστορικά των ασθενών και τα παραπεμπτικά των ιστολογικών εξετάσεων αξιολογήθηκαν τα επιδημιολογικά χαρακτηριστικά, οι καπνιστικές συνήθειες και η κατανάλωση αλκοόλ, η κλινική εικόνα, η εντόπιση των βλαβών, καθώς και το μέγεθος. Οι ιστολογικές τομές όλων των βλαβών επαναξιολογήθηκαν από δύο ιστοπαθολόγους για την επιβεβαίωση της ιστολογικής διάγνωσης και τον καθορισμό της θετικότητας ή μη των ορίων. Η καταγραφή των κλινικών και ιστολογικών χαρακτηριστικών αφορούσε τόσο στις αρχικές βλάβες κατά την πρώτη επίσκεψη ή κατά τη διάρκεια της παρακολούθησης όσο και στις υποτροπές. Εφαρμόστηκε η ανοσοϊστοχημική μέθοδος της σημασμένης στρεπταβιδίνης-βιοτίνης υπεροξειδάσης σε 3 στάδια με τη χρήση μονοκλωνικών αντισωμάτων έναντι των μορίων: phospho-STAT3 (rabbit monoclonal Tyr705) (CST, D3A7, #9145) (1:200), Survivin (CST, 71G4B7, #2808) (1:300), Cyclin D1 (CST, E3P5S, #55506) (1:300), Ki-67 (CST, D2H10, #9027)(1:250) και Bcl-xL (CST, 54H6, #2764) (1:200) (Cell Signaling Technology, Leiden, The Netherlands). Η ανοσοϊστοχημική χρώση αξιολογήθηκε σε 5 επιλεγμένα πεδία (μεγέθυνση x400), κάθε ένα από τα οποία περιελάμβανε τουλάχιστον 100 κύτταρα. Η χρώση θεωρήθηκε θετική όταν τα κύτταρα εμφάνιζαν πυρηνική χρώση και καταγράφηκε η εντόπισή τους στη βασική, στις υπερβασικές και στην ακανθωτή στιβάδα. Η ανοσοϊστοχημική χρώση βαθμολογήθηκε ημιποσοτικά με κριτήριο την ένταση της χρώσης ως: (0) απουσία χρώσης, (1) ήπια, (2) μέτρια, ή (3) έντονη και την εντόπιση των θετικών κυττάρων ως: (0) < 1%; (1) 1-25%; (2) 26-50%; (3) >50%. Το τελικό σκορ προέκυψε από το άθροισμα των επιμέρους σκορ έντασης (0-3) και ποσοστού θετικότητας των κυττάρων (0-3) για κάθε περίπτωση. Όλες οι περιπτώσεις φωτογραφήθηκαν με τη χρήση του WSI software program (Microvisioneer, Germany) σε μικροσκόπιο Olympus CX 23 microscope. Η συγκριτική αξιολόγηση πραγματοποιήθηκε ως εξής: • Οι αρχικές βλάβες που υποτροπίασαν συγκρίθηκαν με εκείνες που δεν υποτροπίασαν με βάση τα δημογραφικά δεδομένα και τις συνήθειες των ασθενών (ηλικία, φύλο, κάπνισμα και χρήση αλκοόλ), τα κλινικά χαρακτηριστικά (εντόπιση, μέγεθος, ομοιογένεια ή όχι) και τα ιστοπαθολογικά χαρακτηριστικά (επιθηλιακή υπερπλασία έναντι διαφόρων βαθμών δυσπλασίας). • Τα ανοσοϊστοχημικά σκορ των πέντε μορίων που διερευνήθηκαν συγκρίθηκαν μεταξύ των αρχικών βλαβών που υποτροπίασαν και εκείνων που δεν υποτροπίασαν, ενώ επίσης συσχετίστηκαν με την παρουσία ή τον βαθμό δυσπλασίας των διαφόρων βλαβών • Για βλάβες που εμφάνισαν υποτροπή, όλες οι παραπάνω παράμετροι συγκρίθηκαν επίσης μεταξύ των αρχικών βλαβών και των αντίστοιχων υποτροπών τους. Η στατιστική ανάλυση πραγματοποιήθηκε για τις διάφορες παρατηρήσεις/μετρήσεις με όριο στατιστικής σημαντικότητας τιμή P < 0.05 και τη χρήση του στατιστικού προγράμματος SPSS software application (version 21.0: SPSS, Chicago, IL, U.S.A.). Τα αρχικά χαρακτηριστικά εκφράστηκαν ως απόλυτη (n) και σχετική συχνότητα (%) και τα στοιχεία συγκρίθηκαν με το two tailed Fisher’s exact test. Η στατιστική σύγκριση των ανοσοϊστοχημικών τιμών πραγματοποιήθηκε με τη στατιστική δοκιμασία Mann-Whitney U test, ενώ για τις καμπύλες ελεύθερης νόσου επιβίωσης εφαρμόστηκε η μέθοδος Kaplan and Meier. Η προγνωστική σημασία όλων των παραμέτρων αναλύθηκε με το προγνωστικό μοντέλο Cox proportional hazards model. ΑΠΟΤΕΛΕΣΜΑΤΑ: Σε σύνολο 33 ασθενών καταγράφηκαν συνολικά 135 βλάβες με ιστοπαθολογική διάγνωση επιθηλιακής υπερπλασίας ή δυσπλασίας. Από αυτές 97 καταγράφηκαν ως αρχικές βλάβες (63 κατά την πρώτη επίσκεψη και 34 κατά την παρακολούθηση) και 38 ως υποτροπές (24 κατά την πρώτη επίσκεψη και 14 κατά την παρακολούθηση). Ως υποτροπές, θεωρήθηκαν οι βλάβες που αναπτύχθηκαν στην ίδια εντόπιση και θέση με την αρχική βλάβη. Όσον αφορά τις αρχικές βλάβες (97) των ασθενών, η πιο συχνή εντόπιση ήταν ο παρειακός βλεννογόνος (33%), το μέσος μέγεθος των βλαβών ήταν 1.4 (± 0,7), από αυτές το 73.2% ήταν ομοιογενείς και το 62.9% ιστολογικά διαγνώστηκαν ως ήπιου βαθμού δυσπλασία. Από τις 97 αρχικές βλάβες 31 (32%) υποτροπίασαν τουλάχιστον μία φορά, ενώ καμία από αυτές δεν υπέστη κακοήθη εξαλλαγή. Εντούτοις, μία μόνο περίπτωση ανάπτυξης ΑΚΣ καταγράφηκε κατά την περίοδο παρακολούθησης των ασθενών, σε διαφορετική όμως εντόπιση (έδαφος στόματος) από την αρχική βλάβη (αριστερή παρειά) του ασθενούς. Η πιο συχνή εντόπιση των υποτροπών (38 βλάβες) ήταν ο παρειακός βλεννογόνος (31.6%), το μέσο μέγεθος των βλαβών ήταν 0.9 (± 0.4), 84.2% ήταν ομοιογενείς, ενώ 50% εξ αυτών διαγνώστηκαν ιστολογικά ως ήπιου βαθμού δυσπλασία και 28.9% ως υπερπλασία. Δεν παρατηρήθηκε στατιστικά σημαντική διαφορά ανάμεσα στις αρχικές βλάβες που υποτροπίασαν και εκείνες που δεν υποτροπίασαν όσον αφορά τις διάφορες επιδημιολογικές παραμέτρους (φύλο, ηλικία), τις συνήθειες καπνίσματος και αλκοόλ, τα κλινικά (εντόπιση, μέγεθος, ομοιογένεια) και ιστολογικά χαρακτηριστικά (παρουσία και βαθμός δυσπλασίας). Ωστόσο, περισσότερες υποτροπές παρατηρήθηκαν μεταξύ των μη ομοιογενών βλαβών (p=0.087) και μεταξύ των δυσπλασιών σε σχέση με τις υπερπλασίες (34.5% vs. 15.4%). Όσον αφορά την έκφραση των ανοσοϊστοχημικών δεικτών, ανάμεσα στις αρχικές βλάβες (97) που υποτροπίασαν και εκείνες που δεν υποτροπίασαν, τα μόρια Bcl-xL και survivin παρουσίασαν χαμηλότερα επίπεδα έκφρασης στις βλάβες που υποτροπίασαν σε σύγκριση με αυτές που δεν υποτροπίασαν και προσδιορίστηκαν ως σημαντικοί παράγοντες κινδύνου για υποτροπή της λευκοπλακίας, σύμφωνα με τη μονοπαραγοντική ανάλυση. Η πολυπαραγοντική ανάλυση ανέδειξε μόνο την έκφραση του μορίου Bcl-xL ως παράγοντα κινδύνου υποτροπής. Επίσης, στη σύγκριση των 31 αρχικών βλαβών και των αντίστοιχων υποτροπών τους, φάνηκε ότι οι υποτροπές ήταν όλες μικρού μεγέθους (έναντι 64,5% των αρχικών βλαβών) και στη πλειοψηφία τους ομοιογενείς (87,1%, έναντι 61,3% των αρχικών βλαβών), με στατιστική σημαντικότητα p

The chapter discusses notions of value, focusing on the plastics found in the Camberwell Inner London Education Authority (ILEA) Collection, an educational collection of objects circulating in London schools from the mid-1950s to the mid-1970s. Making reference to prominent design platforms such as the Council of Industrial Design and the 1951 Festival of Britain, the discussion explains how the implementation of the tenets of ‘good design’ aligned plastics in the Collection with modernism, and aimed at cultivating taste in post-war school children. Using the case study of the EKCO Nova range of products, the chapter questions the design of high-end products in plastic, and makes the case of how the aesthetic canon lost its relevance outside the guarded spaces of modernist influence.

Apart from genetics, environmental factors, such as food consistency, may affect craniofacial morphology and development. The present systematic review aims to systematically investigate and appraise the available evidence regarding the effect of diet consistency on the anatomical structures of the basal bone of the rat mandible. The search was performed without restrictions in five databases (PubMed, Scopus, Web of Science, ProQuest Dissertations and Theses Global, including grey literature) and hand searching through January 2022. A total of 14,904 references were initially identified, and 16 articles were finally included in the systematic review. Rats that consumed hard diets were found to exhibit an increase inbigonial width, corpus height, condylar depth, condylar base inclination, condylar process inclination, mandibular plane inclination, height and length of angular process, mandibular body height, depth of antegonial notch, growth rate in the gonial angle, angular process convexity and height of condylar process. It was also noted that mandibular depth, mandibular height, ramus angle and angle between the angular process and mandibular plane were decreased in rats that were fed with a hard diet. On the other hand, there were conflicting results about the growth of mandibular length and width, corpus length, mandibular body length, ramus height, condylar length and width, gonial angle and height of coronoid process. From the abovementioned results, it can be concluded that food consistency may affect the morphology of anatomical structures and the overall growth and development of rat mandibles in various ways.

Radiotherapy is generally used as an adjuvant treatment in malignant head and neck tumors, which can cause a series of toxicities to tissues involved in the radiation field. Hard tissue necrosis surrounding the tumor is widely debated and recognized; however, oral mucosa necrosis as a late effect of head and neck radiotherapy is a toxicity that has been little explored and understood in the literature. The present report describes a 53-year-old Caucasian, diabetic man with a painful yellowish mass in the buccal mucosa, remaining oral mucositis with history of radiotherapy completed 90 days ago as adjuvant treatment for a polymorphic adenocarcinoma in the palate. Photobiomodulation was used as therapy for tissue necrosis with good therapeutic response despite discontinuation of treatment by the patient. Since there are few descriptions and illustrations of radiotherapy-related soft tissue necrosis, the current case may bring some new experience with this important topic, which directly impacts on the patient's quality of life.

Identification and management of potentially premalignant oral epithelial lesions (PPOELs) at highest risk of malignant transformation holds great promise for successful secondary prevention of oral squamous cell carcinoma, potentially reducing oral cancer morbidity and mortality. However, to date, neither clinical nor histopathologic validated risk predictors that can reliably predict which PPOELs will definitively progress to malignancy have been identified. In addition, the management of PPOELs remains a major challenge. Arguably, progress in the prevention and treatment of oral premalignancy and cancer will require improved understanding of the underlying molecular mechanisms, facilitating the discovery of diagnostic, prognostic, and predictive markers, as well as the identification of novel targeted therapeutics. This review provides a synopsis of the molecular biomarkers that have been studied in PPOELs and have been correlated with the presence and grade of dysplasia and/or their propensity to undergo malignant transformation to oral squamous cell carcinoma. The emphasis is on highlighting new emerging research fields, particularly epigenetic events, including methylation and micro-RNA regulation. Several promising biomarkers are highlighted. Current limitations and challenges are discussed. Recommendations for future focused research areas, to validate and promote clinically useful applications, are offered.

Squamous cell carcinoma (SCC) developing in lesions of discoid lupus erythematosus (DLE) is rare, most frequently arising on sun-exposed skin and very rarely affecting the lips. A review of the English language literature revealed only 21 published cases of labial SCC in patients with DLE. Here, an unusual case of a patient with DLE who developed 3 primary SCCs of the oral and perioral region is presented. A 40-year-old female with a 24-year history of DLE with peri- and intraoral involvement initially developed SCC of the vermillion border of the right lower lip; the lesion was surgically removed and did not recur within 6 months. In spite of strong recommendation for regular follow-up, the patient failed to keep her appointments but returned 7 years later. No signs of recurrence of the original lower lip cancer were noticed, but a new SCC of the left lateral border of the tongue with cervical lymph node metastasis was diagnosed; despite aggressive combined treatment, locoregional recurrence and distant metastatic disease developed within a few months; in addition, a new primary SCC of the vermillion border of the left lower lip developed. This rare case and a thorough review of the pertinent literature underscore the possibility of development of even multiple intraoral and perioral SCCs in the context of longstanding DLE, which necessitates close long term follow-up for early diagnosis and management.

Introduction: Deletions of the INK4 locus (on chromosomal region 9p21) are common in chALL. p16/14 and p15 genes lost with INK4 deletion are tumor suppressors, with a well-documented role in regulating cell cycle and chemosensitivity and in promoting apoptosis in vitro. However, the clinical significance of INK4 deletions remains unclear. Patients & Methods: The study included 78 children (49 boys and 29 girls) with ALL (medium age: 3,12, range:0,7 to 16,5 ). The disease was of B- and T-cell origin in 70 and 8 cases, respectively. INK4 deletion was investigated by interphase FISH on the diagnostic bone marrow samples and the result was correlated with the patients’ demographic data, biological and clinical parameters, and disease outcome. All patients were treated according to the ALL-BFM-95 protocol and followed-up for 11–105 (medium 41) months. Results: INK4 locus deletion was found in 24 cases (30.8%). The loss was hemizygous in 15 (19.2%) and homozygous in 9 cases (11.5%). A positive finding was strongly associated with disease of T-cell origin (p=0.008). Apart from a weak correlation between INK4 deletion and advanced age (p=0.068), there was no association with sex, initial leucocytosis level, cytogenetic category, risk group grade according to the ALL-BFM- 95 criteria or the presence of residual disease at days 15 and 33. Nevertheless, INK4 homozygous deletion was significantly associated with disease-free (p=0.004) and overall survival (p=0.002), while the respective associations for an hemizygous deletions were found insignificant (p=0.137 and p=0.131). Conclusions: The findings from this cohort of children suggest that INK4 homozygous deletion is an unfavorable prognostic factor in chALL, even for cases in which an aggressive course cannot be predicted by the conventional risk estimating criteria. Unclear results with regard to hemizygous deletion may be attributed to the functional state of remaining p16/p14 and p15 genes on the non-deleted chromosome 9. The study of a greater group of patients and the extension of the follow-up period will hopefully clarify whether INK4 deletion is an independent prognostic factor and whether it could be incorporated in risk evaluation guidelines, especially for cases which would otherwise be treated as chALL of standard or medium risk.