Co-existence of Congenital Epidermoid Cyst and Ranula in a Newborn. Report of a Unique Case.

Background: Congenital cystic swellings involving the floor of the mouth include various lesions such as developmental cysts (e.g., dermoid and epidermoid cysts), ranulas, vascular malformations etc. However, coexistence of such conditions, possibly with a cause-and-effect- relationship, is rare. The purpose of this case report is to present a rare case of a congenital epidermoid cyst associated with a mucous retention cyst in a newborn. Methods: A 6-month-old female infant was referred to an Oral Medicine Clinic in Athens, Greece on October 2019 for evaluation of a swelling at the floor of the mouth, first noticed by her paediatrician just after birth. Clinically, a yellowish "pearly" nodule in close association with the orifice of the left submandibular duct, posteriorly transitioning to a diffuse bluish cystic swelling of the left floor of the mouth was observed. With a provisional diagnosis of a dermoid cyst and/or ranula, a surgical excision was performed under general anaesthesia. Results: Histopathologically, a well-defined, keratin-filled, cystic cavity lined by orthokeratinized stratified squamous epithelium was observed in the anterior aspect while posteriorly and in close proximity, a dilated salivary duct lined by cylindrical, cuboidal or pseudostratified epithelium was noted. A final diagnosis of an epidermoid cyst intimately associated with a mucus retention cyst (ranula) of the submandibular duct was rendered. Conclusions: The coexistence of two cystic lesions in the floor of the mouth with features of epidermoid and mucous retention cyst, respectively, is rare and its pathogenesis intriguing, especially in a newborn.

Cheilitis Glandularis: A clinicopathologic study with emphasis on etiopathogenesis.

OBJECTIVES: Cheilitis Glandularis (CG) is an uncommon entity of obscure etiology. A cases series is presented with emphasis on etiopathogenesis. MATERIALS AND METHODS: Fourteen CG cases were analyzed according to their demographic and clinicopathologic characteristics. RESULTS: 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. CONCLUSIONS: 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.

Lymphoepithelial Subtype of Oral Squamous Cell Carcinoma: Report of an EBV-Negative Case and Literature Review.

Lymphoepithelial carcinoma (LEC) of the oral mucosa is a rare histopathologic subtype of squamous cell carcinoma (SCC), which shares morphologic similarities with nasopharyngeal carcinoma (NPC), non-keratinizing undifferentiated subtype. The admixture of neoplastic epithelial tumor cells and a dense lymphoplasmacytic infiltrate makes microscopic diagnosis challenging. LEC etiopathogenesis has been variably associated with Epstein-Barr virus (EBV) infection, depending on the specific anatomic location and racial predilection, with a higher incidence in endemic populations. Although described in several subsites of the head and neck region, including the major salivary glands, the oral mucosa is considered an infrequent location for LEC development, deriving either from minor salivary glands (MSGs) or the surface epithelium. Herein, we report a rare case of an EBV-negative LEC arising from the oral surface epithelium, presenting as gingival swelling, and review the pertinent English-language literature, which revealed only 26 previously reported oral LECs. Our case is only the fourth oral LEC originating from the surface epithelium and the first one to affect the gingiva.

Base of tongue metastasis of cutaneous malignant melanoma with rhabdoid and neuroendocrine features: Report of a rare case and review of the literature.

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.

Acquired Compound Melanocytic Nevus on the Palate of a Child: Report of a Case.

Background: Oral melanocytic nevi are relatively rare in comparison to their cutaneous counterparts. The aim of this manuscript is to present a case of acquired compound oral melanocytic nevi on the hard palatal mucosa of a child. Methods: A 5-year-old female girl was referred for evaluation of a pigmented lesion on the hard palate. The lesion was asymptomatic and present for approximately 2 months. Oral clinical examination revealed a well-circumscribed brownish macule on the hard palatal mucosa, adjacent to the left first primary upper molar. Considering the recent onset of the lesion, biopsy was recommended, but the patient returned 3 years later, when increase in size with slight asymmetry and colour variation were noticed. An excisional biopsy was performed. Results: Microscopic examination revealed nevus cells randomly distributed along the basal cell layer and organized into nests along the junctional area and within the papillary layer of lamina propria, while immunohistochemical evaluation showed positivity of nevus cells for SOX-10 and Melan-A. A final diagnosis of compound melanocytic nevi was rendered, and the patient was advised to attend regular follow-up appointments. Conclusions: Although oral melanocytic nevi are rare in childhood, their potential development should not be overlooked. Acquired oral melanocytic nevi need to be differentiated from several other common (e.g. amalgam tattoo) and uncommon (e.g. melanoma) oral pigmented lesions, as well as from the more rare congenital oral melanocytic nevi. Oral melanocytic nevi with junctional activity (i.e. junctional, compound subtypes) appear to be more common in children, possibly reflecting an earlier developmental stage.

The oral mycobiome: Oral epithelial dysplasia and oral squamous cell carcinoma.

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.

A randomized clinical trial of topical dexamethasone vs. cyclosporine treatment for oral lichen planus

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<0.025 and p=0.034, respectively), which was better with dexamethasone (p=0.001). In addition, both dexamethasone and cyclosporine induced statistical significant improvement in pain and dysphagia (and speech difficulties for dexamethasone), without significant differences between the two groups. Regarding side effects, patients in the dexamethasone group developed candidiasis more frequently compared to cyclosporine (p=0.031). At the end of the 6-month follow-up period, the difference in response between the two groups was not statistically significant. Interestingly, a trend for further improvement compared with the end of the 4-week treatment period was noticed only for patients treated with cyclosporine. Conclusions: Despite the small number of enrolled patients, topical cyclosporine treatment induces a significant clinical improvement in symptomatic OLP patients, which, compared to topical dexamethasone, appears to be less pronounced during initial administration, but capable to induce further improvement after discontinuation with a satisfactory long-term remission in the absence of significant side effects. This study may contribute to a better understanding of the differences in effectiveness of OLP topical treatments and guide future larger scale clinical trials.(AU)

Blastoid Mantle Cell Lymphoma of the Palate: Report of a Rare Aggressive Entity and Review of the Literature.

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.

Understanding the complex pathogenesis of oral cancer: A comprehensive review.

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.

Recurrence in Oral Premalignancy: Clinicopathologic and Immunohistochemical Analysis.

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.

Canalicular adenoma with unicystic morphology. A rare entity.

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.

Oral Candida Infection in Psoriatic Patients Treated with IL17A Inhibitors: Report of 3 Cases and a Comprehensive Review of the Literature.

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.

"Ring-Like Mass" Surrounding the Cervix of a Primary Incisor. Report of a Challenging Case.

BACKGROUND: Several lesions of diverse origin may be detected in the oral cavity of children, affecting the oral mucosa, jaws, or teeth. In equivocal cases, their clinicopathologic features may show considerable overlap with various entities. We present a case of a "ring-like" hard mass around the cervical area of a primary tooth in a child and discuss the diagnostic challenges. METHODS: A 2.5 year-old girl was presented by her mother for evaluation of a painless left first primary lower incisor lesion, first noticed 5 months ago. Medical history was unremarkable, while previous injury or other incident could not be recalled by the patient's mother. Clinical examination and a periapical radiograph were performed. RESULTS: The clinical examination revealed a yellowish, non-removable, hard in consistency, cylindrical mass, completely surrounding the cervical area of the left first primary lower incisor. A periapical radiograph was performed, revealing a cylindrical radiopacity of mild intensity encasing the tooth cervix and a diagnosis of a foreign body inserted around the tooth was made. Regular follow-up appointments were attended for the next 4 years in which mild but progressive gingival recession, revealing a larger part of the ring-like structure was observed. At age of 6, the tooth was extracted and a cylindrical structure was detached from the tooth, confirming its nature as a foreign body. CONCLUSIONS: A foreign body surrounding the cervix of a tooth eventually becoming inseparable may cause a peculiar clinical and radiographic appearance and provoke diagnostic difficulties, especially in the lack of a relevant history.

Localized juvenile spongiotic gingival hyperplasia: Microscopic variations and proposed change to nomenclature.

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.