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.

The role of oral microbiome in pemphigus vulgaris.

While the impact of oral microbiome dysbiosis on autoimmune diseases has been partially investigated, its role on bullous diseases like Pemphigus Vulgaris (PV) is a totally unexplored field. This study aims to present the composition and relative abundance of microbial communities in both healthy individuals and patients with oral PV lesions. Ion Torrent was used to apply deep sequencing of the bacterial 16S rRNA gene to oral smear samples of 15 healthy subjects and 15 patients. The results showed that the most dominant phyla were Firmicutes (55.88% controls-c vs 61.27% patients-p, p value = 0.002), Proteobacteria (9.17%c vs 12.33%p, p value = 0.007) and Fusobacteria (3.39%c vs 4.09%p, p value = 0.03). Alpha diversity showed a significant difference in the number of genera between patients and controls (p value = 0.04). Beta diversity showed statistical differences in the microbial community composition between two groups. Fusobacterium nucleatum, Gemella haemolysans and Parvimonas micra were statistically abundant in patients. We noticed the characteristic fetor coming out of oral PV lesions. Most of anaerobic bacteria responsible for oral halitosis are periopathogenic. Though, only F. nucleatum and P. micra were differentially abundant in our patients. Especially, F. nucleatum has been reported many times as responsible for bad breath. Furthermore, Streptococcus salivarius and Rothia mucilaginosa, species mostly associated with clean breath, were found in relative abundance in the healthy group. Consequently, the distinct malodor observed in PV patients might be attributed either to the abundance of F. nucleatum and P. micra and/or to the lower levels of S. salivarius and R. mucilanginosa in oral lesions.

Daylight photodynamic therapy for the management of actinic cheilitis.

Early identification and adequate treatment of actinic cheilitis (AC), which affects the lower lip vermillion and is considered a precursor of squamous cell carcinoma, is mandatory. Photodynamic therapy (PDT) has been successfully used in AC. PDT with the use of daylight (DLPDT) is equally effective and more convenient than the conventional PDT. Data on short and long-term efficacy of DLPDT in AC are limited. Our primary purpose was to assess efficacy of DLPDT in AC as well as safety and tolerance. Twenty-two individuals with histologically confirmed AC received 2 MAL (5-aminolevulinic acid)-DLPDT sessions 1 week apart. Patients were evaluated clinically 3, 6, and 12 months after treatment. Non-complete responders were biopsied and excluded from the study if histological alterations were indicative of AC. Adverse events were recorded from baseline to the end of the 12-month follow-up period. Twenty patients completed the study. Overall, complete clinical response 12 months after treatment was 80% (16/20), while an association between treatment response and grade of dysplasia was observed (p = 0.016). With respect to response by grade, complete clinical response achieved in grade I AC was 100% (12/12) and 50% (4/8) in grade II AC. Main adverse events included mild erythema, oedema, and scaling, with no pain associated with DLPDT. According to our results, DLPDT seems to be of significant benefit for the treatment of grade I AC. Combination with the other treatment modalities could improve the efficacy in grade II AC. Further studies are needed for the assessment of late recurrences.

The possible role of oral microbiome in autoimmunity.

OBJECTIVE: The human microbiome refers to the entire habitat, including microorganisms, their genomes and the surrounding environmental conditions of the microbial ecosystem. When the equilibrium between microbial habitats and host is disturbed, dysbiosis is caused. The oral microbiome (OMB) has been implicated in the manifestation of many intra- and extraoral diseases. Lately, there has been an intense effort to investigate and specify the relationship between microbial complexes, especially that of the oral cavity and intestine and autoimmunity. This study aimed to review the current literature about the possible role of the OMB in the pathogenesis of autoimmune diseases. METHODS: We searched for published articles in English indexed in PubMed, Medline, Research Gate and Google Scholar using a search strategy that included terms for oral microbiome, autoimmune diseases, dysbiosis and next-generation sequencing. RESULTS: An important number of articles were gathered and used for the description of the possible impact of dysbiosis of OMB in the pathogenesis of Sjögren's syndrome, systemic lupus erythematosus, rheumatoid arthritis, Behcet's disease, Crohn's disease and psoriasis. CONCLUSION: This review article draws attention to the relationship between OMB and the triggering of a number of autoimmune diseases. Although this specific topic has been previously reviewed, herein, the authors review recent literature regarding the full list of nosological entities related to the OMB, point out the interaction between the microbiome and sex hormones with regard to their role in autoimmunity and discuss novel and promising therapeutic approaches for systemic autoimmune diseases. Furthermore, the question arises of whether the OMB is associated with oral bullous autoimmune diseases.

Essential mixed cryoglobulinemia manifesting as recurrent perioral edema: report of a case.

Cryoglobulins are immunoglobulins that precipitate in vitro at temperatures <37°C but that redissolve if heated; they are broadly divided into 3 classes. Cryoglobulinemia has a plethora of clinical manifestations, but it typically presents a vasculitic syndrome, most notably a triad of purpura, arthralgia, and weakness secondary to cryoglobulin deposition in small or medium-sized blood vessels. The highly variable clinical presentation and inconsistent laboratory isolation of cryoglobulins mean that the diagnosis may be one of exclusion or of retrospective review. We describe a case of a 67-year-old woman whose principal symptom was recurrent perioral edema, which was characteristically induced by cold. Raised cryoglobulins combined with a positive autoantibody screen suggested mixed cryoglobulinemia secondary to Sjögren syndrome. However, in the subsequent 6 years, she has remained generally well, having developed no autoimmune, neoplastic, or other disease, suggesting the diagnosis is one of "essential" mixed cryoglobulinemia. No treatment other than symptomatic analgesia has been required.

Plasmablastic lymphoma of the oral cavity, a B cell-derived lymphoma associated with HIV infection: a case series.

OBJECTIVES: Plasmablastic lymphoma (PBL) of the oral cavity is a rare form of non-Hodgkin lymphoma that is most frequently met in human immunodeficiency (HIV) positive patients. Only a few cases have been reported worldwide since 1997. This clinical entity may escape detection due to its unusual immunophenotype and rare occurrence. Our aim is to present two cases with this rare condition that were diagnosed and treated in our department. MATERIALS AND METHODS: We describe two cases of PBLs in HIV-infected patients, who presented with an expanding painless oral lesion and summarize the literature in order to elucidate the nature of this malignancy. RESULTS: The first patient received chemotherapy with additional radiotherapy that led to complete remission of the disease, while the second experienced a relapse 6 months after treatment with chemotherapy, that caused his death after refusal of further treatment. CONCLUSION: Because of the consistent epidemiological association of PBL with immunosuppression, any patient diagnosed with PBL should be tested for HIV. The clinical picture of PBL, including its affinity with HIV-infection, male sex, and its predilection for the oral cavity, may contribute to the differential diagnosis. Any oral mass occurring in an immunosuppressed patient should be referred for biopsy, since the early diagnosis of these tumors leads to better prognosis of the patients.

Plasmacytoid myoepithelioma of the palate: case report.

Myoepitheliomas are extremely rare benign neoplasms of salivary glands. They represent 1-1.5% of all salivary gland tumors. They occur, principally, in the parotid gland and infrequently in minor salivary glands. There are distinct histological and immunohistochemical characteristics of the tumor which aid in the diagnosis. Myoepithelioma of the palate is uncommon and only a limited number of cases has been reported in the English literature. Herein, a case of plasmacytoid type of myoepithelioma of the palate in an adult female is presented along with review of the literature.

Acute myeloid leukaemia diagnosed by intra-oral myeloid sarcoma. A case report.

Myeloid sarcoma (MS) is a rare extramedullary malignant tumor composed of immature myeloid cells. It is strongly associated with a well known or covert acute myeloid leukaemia, chronic myeloproliferative diseases or myelodysplastic syndromes. Intraoral MS scarcely occurs. An unusual case of acute myeloid leukaemia, which was diagnosed by mandibular MS that was developed in the alveolar socket after a dental extraction, is reported. The histological examination (including immunohistochemical analysis) of a subsequent biopsy showed infiltration of the oral mucosa by neoplastic cells. This lesion was therefore classified as acute myeloid leukaemia. The patient was referred to oncologists that confirmed the initial diagnosis. The patient underwent chemotherapy and the mandibular tumor disappeared. Forty days later, a relapse of the disease, which appeared as a great-ulcerated lesion, was developed in the hard palate. Thirty days after the second chemotherapy had finished, a new intraoral tumor was developed in the vestibular maxillary gingiva. Review of the literature shows no report of intraoral relapse and particularly multiple relapse of a MS that involves the oral cavity. Even though MS is encountered infrequently in the oral cavity, it should be considered in the differential diagnosis of conditions (especially tumors) with a similar clinical appearance.

Angiofibrolipoma of the oral cavity.

We describe an unusual and rare case of a lipoma variant known as angiofibrolipoma. A literature search revealed only a few cases of angiofibrolipoma which were located in different anatomical sites; no case of angiofibrolipoma in the oral cavity has been previously reported. We present and discuss the histopatholological-immunohistological findings and features. Angiofibrolipoma histologically consists of mature adipocytes, blood vessels, and bundles of collagenous connective tissue with low to moderate cellularity. It is not encapsulated, but is histologically distinct from surrounding tissue. Positive immunohistological staining with CD-34 presented a large number of blood vessels of different sizes located between collagen fibers and adipocytes. The treatment of choice for a patient with angiofibrolipoma is surgical excision, which is expected to be curative.

Hereditary angioedema: three cases report, members of the same family.

BACKGROUND: This current clinical case report highlights three cases of Hereditary angioedema (HAE) patients who are all members of the same family (father and his two daughters). The father has C1-INH deficiency, while his daughters have low C1-INH levels: the first possesses only 10% function and the second has low C1-INH level with 0% function. Of note, the second daughter was discovered to have HAE at the age of 2, thus making her the youngest known HAE case report in the English literature. METHODS: Assess the efficacy of administration of C1-INH before dental operation as regards the prevention of HAE episode, when total or partial C1-INH deficiency exist. RESULTS: Acute angioedema leading to laryngeal oedema is a possibly fatal complication for HAE patients undergoing dental procedures. Use of both short-term and long-term HAE prophylaxis prior to dental operations might be life saving for those patients. CONCLUSIONS: Prevention and early recognition of potential laryngeal oedema that can occur as a complication of dental procedures may be lifesaving for HAE patients.

Oral lesions leading to the diagnosis of Crohn disease: report on 5 patients.

Crohn disease is a chronic granulomatous inflammatory disease of the gastrointestinal tract of unknown etiology. Oral lesions are significant, as they may occasionally precede intestinal and systemic manifestations. In this retrospective study, clinical and histopathologic data were reviewed from the files of 5 patients with Crohn disease diagnosed at the Department of Oral Medicine and Maxillofacial Pathology School of Dentistry, Aristotle University, Thessaloniki, Greece, and Division of Stomatology and Oral Surgery, Faculty of Medicine, University of Geneva, Switzerland. In the 5 patients, clinical signs included erosions, deep ulcers, cobblestoning of the buccal mucosa, mucosal tags, and lip swelling. Histopathologic examination revealed a granulomatous inflammation with noncaseating granulomas and deep fissuring of the oral mucosa. In all 5 patients, oral lesions were the early signs of the disease. The diagnosis of Crohn disease was confirmed by a colonoscopy and a biopsy of colonic lesions. Oral lesions may be significant and/or initial signs of Crohn disease. Recognition of the lesions may provide an early diagnosis.

Solitary superficial microcystic lymphatic malformation (lymphangioma circumscriptum) of the gingiva.

BACKGROUND: Lymphatic malformations are uncommon, hamartomatous, developmental aberrations of the lymphatic system. The case presented in this report is a rare solitary gingival involvement of a microcystic-type lymphatic malformation. METHODS: The lesion presented clinically as a small vesicular swelling of a buccal interdental papilla in a 16-year-old girl. Involved tissues were excised and submitted for routine histologic examination. The expression of the endothelial marker CD34 was investigated using immunohistochemical staining. RESULTS: A physical examination failed to reveal similar or other abnormalities elsewhere in the body of the patient, including the oral cavity. Histopathologic analysis of the specimen demonstrated the presence of subepithelial, thin-walled, distended vascular cavities forming confluent vesicles containing lymph. The dilated lymphatic formations were lined by flattened CD34-negative endothelial cells. These features were consistent with a microcystic gingival lymphatic malformation. To the best of our knowledge, only two additional reports of this malformation have been published to date, but both presented with bilateral gingival involvement. CONCLUSION: Even though lymphatic malformations are encountered very infrequently on gingiva, they should be considered in the differential diagnosis of related conditions with a vesicular clinical appearance.

Gingival involvement in a case series of patients with acquired immunodeficiency syndrome-related Kaposi sarcoma.

BACKGROUND: This case series presents the polymorphic clinical characteristics of gingival acquired immunodeficieny syndrome (AIDS)-related Kaposi sarcoma (KS), a malignancy that is gradually becoming uncommon in developed nations. An up-to-date overview of the related epidemiology, etiopathogenesis, histopathology, and treatment is provided, along with a pictorial guide to ease clinical diagnosis. METHODS: The oral/maxillofacial pathology records at Aristotle University and the University of Geneva were retrospectively reviewed. Thirty-two cases diagnosed with oral AIDS-related KS were retrieved between 1991 and 2004. KS diagnosis was established histologically by incisional biopsies from intraoral lesions. All charts contained clinical oral examination data, radiological images, and detailed photographic records. RESULTS: Thirteen patients (12 males and one female) presented with KS gingival involvement (40.6%). Eleven of the male patients were homosexual/bisexual men. The mean age of the patients at the time of intraoral KS diagnosis was 42.1 years, and the mean CD4 cell count was 103 (0 to 481). Gingival epidemic KS presented with various degrees of pigmentation and a wide range of clinical patterns, from relatively flat macules (early stage) to tumors with variable nodular morphology (advanced disease). Solitary or multiple gingival involvement may appear concomitantly with palatal and/or cutaneous lesions. CONCLUSIONS: Even though the incidence of intraoral KS had fallen precipitously in developed countries after the mid-1990s, gingival KS should be considered in the differential diagnosis of every pigmented gingival lesion. Periodontists are in a unique position to identify gingival involvement of intraoral KS and facilitate early diagnosis.

Oral tuberculosis associated with a treatment with anti-rheumatic drugs.

BACKGROUND: The use of immunosuppressive medication is a dominant risk factor for infection in patients with rheumatoid arthritis (RA). Methotrexate (MTX) is one of the traditional disease-modifying antirheumatic drugs. Adalimumab [a human anti-tumor necrosis factor-alpha (anti-TNF-alpha) monoclonal antibody] represent an important advance in the treatment of RA and has been recently come in use. TNF-alpha plays a role in the host defense against Mycobacterium tuberculosis and notably in granuloma formation. Infections occur at a high rate among those who use one or the combination of the two medications. METHOD: We examined a female patient that was referred to our department for evaluation and treatment of a granular lesion on the soft palate and uvula, complaining of mild dysphagia. The patient was treated for 4 months with MTX and adalimumab for RA before the oral lesion appeared. RESULTS: The histopathological examination of a specimen of the oral lesion, taken by biopsy, showed a chronic inflammation characterized by tuberculous granulomas. Polymerase chain reaction test and culture of a new specimen was positive for M. tuberculosis. CONCLUSIONS: The therapeutic use of MTX or/and adalimumab for the treatment of RA or few others diseases, can cause oral tuberculosis.

Facial and perioral primary impetigo: a clinical study.

Impetigo is the most common skin infection in children. The face, especially the perioral region, is one of the most frequently involved areas. Impetigo is a disease that interests the pediatric dentist, as it poses significant problems in its differential diagnosis from other conditions. Sixteen otherwise healthy children were examined suffering from facial and perioral impetigo. The typical clinical appearance was scattered, painless, slightly pruritic erosions covered by "honey-colored" crusts. In 4 children impetigo was localized in the facial and perioral area, whereas in all other cases lesions were diffused in perioral area and several regions throughout the body. Four children exhibited neck lymphadenopathy and one had mild fever. The treatment of impetigo included the application of topical measures with the systemic antibiotic chemotherapy.

Localized B-cell non-Hodgkin's lymphoma of oral cavity and maxillofacial region: a clinical study.

OBJECTIVE: Non-Hodgkin's lymphomas (NHL) are the third most common group of malignant lesions in the oral cavity and maxillofacial region. Most such lymphomas have been shown to be predominantly of B-lineage. The purpose of the present study is to analyze the clinical signs and symptoms and the clinical staging of B-cell NHL of this region. STUDY DESIGN: Eighteen adults, with B-cell NHL manifestations of the oral cavity and maxillofacial region, were available for this study. The clinical stage according to the Ann Arbor system was assessed by history, physical, and laboratory examination. Hematoxylin and eosin--stained slides and paraffin blocks were available for all cases. Histologic diagnosis was based on the WHO classification of tumors. RESULTS: The mean age of patients at the time of biopsy was 64 years. At the time of the disease presentation, according to the Ann Arbor system, 11 patients were in stage IE, 2 patients in stage IIE, 2 patients in stage IIIE, 1 patient in stage IVE, and 2 patients in stage IV. The typical clinical appearance was a painless local mass lateral or bilateral. Often there is a superficial ulceration of the tumor mass. Tonsillar NHL was the most frequent site occurring in 8 patients followed by NHL of the oral cavity, of the salivary glands, and of the mandible. Grading revealed that most cases were high grade (11 cases), followed by the cases of low grade (5 cases) and intermediate grade (2 cases). All the different histologic types may be observed, but the most frequently encountered is the diffuse large type. CONCLUSIONS: The B-cell NHL may involve both osseous and soft tissues of the oral cavity and maxillofacial region. The favored sites are tonsils, palatal mucosa and parotid glands. The typical clinical appearance is a painless local mass lateral or bilateral. Often there is a superficial ulceration of the tumor mass. According to the Ann Arbor system, the majority of the cases at the time of diagnosis are in stage I or II. Most patients have high grade disease. All the different histologic types may be observed, but the most frequently encountered is the diffuse large type.