Alexandra Sklavounou-Andrikopoulou

Acantholytic squamous cell carcinoma of the gingiva: report of a case and review of the literature.

Adenoid squamous cell carcinoma differs from common squamous cell carcinoma in histologic features and its aggressive nature. Microscopically, the tumor shows cystic degeneration of the neoplastic epithelium, producing a prominent alveolar pattern and pseudoglandular structures with acantholytic cells. It occurs most commonly on the lips, rarely intraorally, and it is associated with a poor prognosis. This case concerns a 72-year-old woman who presented with the chief complaint of burning tongue and soreness of the lips. Clinical examination revealed an ulcerated and elevated mass on the edentulous left maxillary ridge, beneath the base of a partial denture. An incisional biopsy rendered the diagnosis of adenoid squamous cell carcinoma. The patient was referred to a specialized maxillofacial surgery center for diagnostic work-up and treatment. She underwent partial maxillectomy and radiotherapy, and 17 months after treatment, she died of uncontrollable recurrence.

Frequency of pain and correlation with clinical and histologic parameters in T1 squamous cell carcinoma of the tongue: a retrospective pilot study.

AIMS To conduct a pilot retrospective study to investigate the frequency of pain among patients with early-stage oral squamous cell carcinoma (OSCC) of the tongue and to correlate the pain with clinical and histopathologic parameters. METHODS Twenty-four archival cases of T1 OSCC of the tongue were reviewed. No power analysis was conducted due to the pilot nature of the study. Tumors were classified into two groups according to the presence or not of pain (P+ and P- groups). Clinical and histopathologic parameters, such as grade of differentiation, depth of invasion, and presence of vascular, muscular, and perineural invasion were recorded. Statistical analyses included parametric (Student t) and nonparametric (chi-square) tests. RESULTS Pain was reported by 13 of the 24 patients. In the P+ group, 11 of the 13 had moderately differentiated and 2 well-differentiated tumors; in contrast, P- patients had moderately differentiated tumors in 5 of the cases and well-differentiated tumors in 6 cases (P = .082). Vascular invasion was observed in 5 of the 13 P+ and 5 of the 11 P- patients, muscular invasion in 5 P+ and 2 P- patients, and perineural invasion in 4 P+ and 1 P- patients, respectively. The mean depth of invasion was 1.51 mm for P+ patients and 1.25 mm for P- patients. Only lymphoplasmocytic infiltration differed significantly, with P+ tumors exhibiting more intense inflammation (P = .041). CONCLUSION Despite the limited number of cases, the results of this study suggest that painful OSCCs of the tongue may be associated with more intense inflammation.

Oral lymphoepithelial cyst: a clinicopathological study of 26 cases and review of the literature

Introduction Τo describe the clinicopathological features of 26 oral lymphoepithelial cysts (LECs) and review the literature. Material and Methods Twenty-six cases of oral LECs diagnosed during a 37-year period were retrospectively collected. The patients’ gender and age, as well as the main clinical features of the cysts were retrieved from the requisition forms. The main microscopic features were recorded after reevaluation of all cases. Pubmed and Google Scholar electronic databases were searched with the key word “oral LEC”. Inclusion criteria were the microscopic confirmation of LEC diagnosis and the report at least two of three main clinical features (gender, age and cyst’s location). Results The 26 oral LECs represented 0.08% of 31,564 biopsies accessioned during the study period. They affected 25 patients, 14 females and 11 males with a mean age of 33.04±9.81 years. They appeared as smooth (92%) nodules, with soft (24%) or firm (76%) consistency and normal (28%), yellow to normal (20%), yellow (32%) or white (20%) hue, in the tongue (69.23%) or the floor of mouth (30.77%). They were covered by parakeratinized squamous (92.31%) or non-keratinized (7.69%) epithelium and contained desquamated epithelial cells, amorphous eosinophilic material and/or inflammatory cells (100%). The lymphoid tissue surrounded the cystic cavity partially (34.62%) or completely (65.38%), often in a follicular pattern with prominent germinal centers (53.85%). Literature review yielded 316 cases of oral LECs derived from 25 case reports, 3 case studies/retrospective studies with detailed information for each case and 7 studies with summarized data. Conclusions Oral LEC is a pathologic entity with discrete clinical presentation that is, however, commonly misdiagnosed in clinical practice as other, mostly benign, entities. Its pathogenesis remains obscure, as its clinicopathologic features are consistent with both theories suggested up to date. Key words:Oral lymphoepithelial cyst; developmental cyst; non odontogenic cyst; lymphoid tissue; oral tonsil.

ERK1/2, JNK and STAT3 activation and correlation with tumor differentiation in oral SCC

Signal transducer and activator of transcription 3 (STAT3) and mitogen activated protein kinases (MAPKs), including ERK and JNK, have been implicated in oral squamous cell carcinoma (OSCC) development and progression. Our purpose was to evaluate the levels of activated STAT3, ERK1/2 and JNK by immunohistochemistry in OSCC and to investigate possible correlations of these molecules with each other as well as with the degree of tumor differentiation. Immunohistochemical assessment of the phosphorylated levels of STAT3(tyrosine/ serine), ERK1/2 and JNK was performed in 60 OSCC, including well, moderately and poorly differentiated tumors. Semiquantitative scoring system was used, by calculating intensity of immunostaining, percentage of positive cells and combined scores. Statistics included Fishers test, Students T-Test and Kruskal-Wallis analysis, Spearmans correlation coefficient and multivariate logistic regression analyses. Immunohistochemical levels of both pSTAT3(tyr) and pERK1/2 showed statistically significant differences between well and poorly differentiated tumors with the latter receiving higher mean percentage, intensity and total scores. On the other hand, pJNK showed statistically significantly higher intensity levels in moderately compared to poorly differentiated tumors. pSTAT3(ser) immunoexpression did not appear to correlate with tumor differentiation. Between different molecules, more pronounced, pERK1/2 levels exhibited statistically significant positive correlation with pSTAT3(ser), pSTAT3(tyr) and pJNK expression. ERK1/2 and STAT3 activation (as assessed by tyrosine but not serine phosphorylation) could contribute to a less differentiated phenotype in OSCC, while JNK activation may have an opposite, although possibly less pronounced, effect. Positive correlations between MAPK and STAT3 levels may indicate a direct crosstalk and/or regulation by common upstream pathways.

Expression of NF-κB and IL-6 in oral precancerous and cancerous lesions: An immunohistochemical study.

Background The purpose of this study was to evaluate the immunohistochemical expression of NF-κB and IL-6 in oral premalignant and malignant lesions and to investigate their possible correlation with the presence of subepithelial inflammation. Material and Methods Thirty two oral premalignant lesions, clinically compatible with leukoplakia or erythroplakia, were investigated. Microscopically, 11 of them showed hyperkeratosis and acanthosis (epithelial hyperplasia) and 21 showed dysplasia of varying degrees. Nine cases of OSCC and four control cases of normal oral mucosa were also included in the study. Immunohistochemical staining with NF-κB (p65) and IL-6 was performed. IL-6 and nuclear NF-κB staining were assessed as positive or negative. For cytoplasmic localization of NF-κB, a total score combining intensity and percentage of positive epithelial cells was additionally calculated. The presence of inflammation was also recorded. Results Intensity and total scores for NF-κΒ cytoplasmic immunostaining showed a statistically significant gradual increase from normal mucosa to OSCC (p=0.012 and p=0.026 respectively). Non-statistically significant increased NF-κΒ nuclear localization was detected in dysplasias and OSCCs. Positive statistical correlation was detected between the presence of inflammation and IL-6 expression (p=0.015). No correlation between NF-κΒ and IL-6 was detected. Conclusions NF-κΒ is activated in the early stages of oral carcinogenesis. IL-6 may have an NF-κΒ-independent role, possibly through regulation of the inflammatory response. Key words:NF-κB, IL-6, immunohistochemistry, oral squamous cell carcinoma, oral precancerous lesion.

Oral acanthosis nigricans in chronic hepatitis B with a 21-year follow up.

Acanthosis nigricans is a rare mucocutaneous disorder of unknown etiology that manifests as hyperpigmented velvety plaques, most often on intertriginous areas such as the neck and axillae as well as on mucosal sites such as the oral cavity. The disorder presents either as a paraneoplastic manifestation of an underlying malignancy, especially gastrointestinal adenocarcinomas or in association with obesity, administration of drugs or endocrinopathies, most commonly insulin‐resistant diabetes mellitus. In the present article, a case of acanthosis nigricans with oral and cutaneous manifestations in a male patient with chronic hepatitis B infection is described. To the best of our knowledge, this is the first case of benign oral acanthosis nigricans associated with chronic hepatitis B.

Non-healing tongue ulcer in a rheumatoid arthritis patient medicated with leflunomide. An adverse drug event?

Leflunomide is a member of the disease modifying anti-rheumatic drugs group used as a treatment modality in active rheumatoid and psoriatic arthritis. “Oral ulcers” are reported in 3-5% of leflunomide medicated rheumatoid arthritis patients with adverse events, but they are not described in detail in the literature. We present a case of an ulcer in the tongue of a rheumatoid arthritis patient managed with leflunomide and contemplate on its pathogenesis. Key words:Leflunomide, oral ulcer, DHODH.

Atypical methotrexate ulcerative stomatitis with features of lymphoproliferative like disorder: report of a rare ciprofloxacin-induced case and review of the literature

Methotrexate (MTX) is an established immunomodulating agent used in low doses (LDMTX) to treat several autoimmune diseases. Ulcerative stomatitis (US) may be observed as a long-term LDMTX adverse effect showing a wide histopathologic spectrum. A 73-year old female presented with painful oral ulcers of 5 days duration. The patient had been under treatment for rheumatoid arthritis with LDMTX, while one week before presentation she was prescribed ciprofloxacin for a urinary infection. Histopathologic examination of a lingual ulcer revealed a polymorphous lymphohistiocytic proliferation with scattered binucleated atypical lymphocytes. Immunohistochemically, most cells were of T-cell lineage while the EBER test was negative and a diagnosis of MTX-induced reactive ulceration was rendered. MTX cessation resulted in complete resolution of the ulcers with no recurrences reported so far. The clinical and histopathologic features of MTX-induced oral ulcers are not always diagnostic and a detailed history and an extensive clinicopathologic investigation may be needed to exclude a lymphoproliferative disorder. Key words:Atypical oral ulcers, ciprofloxacin, lymphoproliferative disorders, methotrexate.

Localized gingival enlargements. A clinicopathological study of 1187 cases

Background To describe the incidence, demographic and clinical features of 1187 localized gingival enlargements. Material and Methods 1187 cases of localized gingival enlargements diagnosed during a 20-year period were retrospectively collected. The patients’ gender and age, as well as the main clinical features of the tumors were retrieved from the biopsy report forms. Results The 1187 localized gingival enlargements represented 6.23% of 19.044 biopsies performed during the study period. 756 females and 427 males were affected with a mean age of 41.92±19.68 years. The lesions appeared as smooth (52.4%), granular (17.9%) or rough (13.16%) tumors, elastic (50.73%) or soft (29.56%) in consistency and red (60.8%), normal (28.58%) or white (8.17%) in color. The majority of the lesions (85.17%) were reactive in origin with pyogenic granuloma being the most common. In 1.1% of the cases a diagnosis of malignant lesion was rendered. Conclusions All localized gingival enlargements should be submitted for microscopic examination because in approximately 1% of cases they are malignant. Key words:Localized gingival enlargements, gingival mass, gingival lesions, gingival reactive lesions, gingival malignant lesions.

Oral verruciform xanthoma: report of 13 new cases and review of the literature

Background Oral verruciform xanthoma (OVX) is a rare lesion. The purpose of the present study is to describe the clinical features of 13 OVXs and review all cases reported in the English literature. Material and Methods Thirteen cases of OVX diagnosed during a 47-year period were retrospectively collected. The patients’ gender and age, as well as the main clinical features of the lesions were retrieved from the biopsy request forms. Pubmed®, Scopus® and Google ScholarTM electronic databases were searched with the key word “verruciform xanthoma”. Only cases of histologically confirmed OVX were included in the study. Results The 13 OVXs represented approximately 0.04% of 35,617 biopsies accessioned during the study period. They affected 13 patients, 8 males and 5 females with a mean age of 48.8±14 years. They mainly appeared as asymptomatic granular nodules or plaques, with elastic or normal consistency and white color, in the gingiva or hard palate. Literature review yielded 416 cases of OVX. With the addition of cases of the present study, 429 cases of OVX have been presented in the English literature. OVX has a slight male predominance with a male to female ratio of 1.4:1 and the majority of patients are in the 5th to 7th decade of life. Clinically, OVX mainly presents as an asymptomatic, single, papillary or granular plaque or nodule, with elastic or soft consistency and white, red or pink color. It measures approximately 1cm and is most commonly located on the gingiva, tongue, hard palate or buccal mucosa. The treatment of choice is surgical excision with little rates of recurrence. Conclusions Verruciform xanthoma is a rare lesion most often encountered on the ginigival mucosa. As its clinical presentation is not pathognomonic, it should be included in the differential diagnosis of verrucous or papillary lesions. Key words:Oral verruciform xanthoma, oral tumors.